TITLE:

Authors: MG Parry, GPS Bawa, B Poulton, R Fernando

Affiliation: Department of Anesthesia, The Royal Free Hospital, Hampstead. London, UK

Keywords: Anesthetic Techniques: epidural, combined spinal epidural; Investigations: dorsal column function

Dorsal Column Function in Parturients receiving Epidural and Combined Spinal Epidural (CSE) for Labor and Elective Cesarean Section

INTRODUCTION Low dose mixturesof localanesthetic and opioid are being increasingly used for labor analgesia with epidural and CSE techniques (1). Reduced motor block, increased maternal satisfaction and the ability to ambulateoffer significant advantages. A recent study using low dose bupivacaine (0.1%) with fentanyl (0.0002%) for epidural labor analgesia, has questioned the safety of ambulation following such techniques, claiming dorsal column function (DCF) impairment in almost 70% of patients receiving low dose epidurals for labor (2). The methodology and conclusions of this study have been criticised (3). The aim of our study was to compare the effects of different regional anesthetic methods used for labor analgesia and cesarean section on DCF. METHOD After ethics committee approval 90 patients requesting either regional analgesiafor labor (Gpl & Gp2) or admitted for elective cesarean section (Gp3) were recruited into the study. Group 1 received 15ml of epidural topup solution containing 0.1% bupivacaine with 0.0002% fentanyl after a standard epidural was sited. Group 2 received a CSE using an intrathecal dose of 2.5mg bupivacaine with 25mcg fentanyl via a Becton Dickinson 27G,119mm Whitacre spinal needle. Group 3 received a CSE for elective cesarean section using 10mg bupivacaine with 25mcg fentanyl. Assessment of the block after 30 minutes included dermatomal height of block, joint position sense (JPS), vibrational sense (VS), and motor power (MRC scale). VS was tested using a purpose built electronic device capable of independently delivering a 128 Hz vibrational stimulus to 4 surface electrodes attached to the upper and lower limbs. Each patient acted astheir own control. Students t-test and Chi-squared tests were used for statistical analysis. P< 0.05 was regarded as statistically significant. RESULTS All three groups werecomparable in age, weight, height and parity. In the groups receiving low dose laboranalgesia(Gps1 & 2), only 6 patients (10%) exhibited abnormal dorsalcolumn signs. There were no significant differences in JPS, VS, upper sensory level and motor power between Groups 1 & 2. However 93% patients in the cesarean section group (Gp3) showed impaired DCF, this being significantly different from Groups 1 & 2 (pcO.05).

Upper Sensory Level (mean, range)

Gp 1 [n=30] Labor Epidural

Gp 2 [n=30] Labor CSE

Gp 3 [n=30] Cesarean Section I CSE

Ethyl Chloride Spray T8 (T12-T4) TlO (T12-T4) T3 (T4-Tl)

Pinprick (25G needle) T8 (Ll -T6) TlO (Ll -T5) T4 (T6 - C8)

Abnormal VS (n, %I 2 (7) 2 (7) 28 (93)

Abnormal JPS (n, %I 1 (3) 1 (3) 21 (70)

Abnormal Motor Power (n. %) 2 (7) 3 (10) 30 (100)

CONCLUSION Incontrast to Buggy et al’sstudy over 90% of patients receiving either low dose epidural or CSE for labor analgesia showed intact DCF, whereas increasing the dose of intrathecal bupivacaine for cesarean section under CSE resulted in significant DCFimpairment. We conclude that low dose mixturesof bupivacaine and fentanyl for labor analgesia using epidural or CSE result in minimal impairment of DCF and that providing each patient is adequately assessed, ambulation during labour remains a safe option. Extrapolating from the data in Gp3, the cesarean section group, we presume that if higher doses of local anesthetic are used for labor, DCF may be significantly impaired. REFERENCES 1. Norris MC, Grieco WM, Borkowski M, Leighton BL. Arkoosh VA, Huffnagle HJ, Huffnagle S. Complications of labor analgesia: epidural versus combined spinal epidural techniques. Anesth Analg 1994;79:529-537. 2. Buggy D, Hughes N, Gardiner J. Posterior column sensory impairment during ambulatory extradural analgesia in labour. Br J Anaesth 1994;73:540-542. 3. Fernando R, Price CM. Posterior column sensory impairment during ambulatory extradural analgesia in labour. Br J Anaesth 1994;73:540-542.

II

A COMPARISON OF EPIDURAL TEST DOSE SOLUTIONS AFTER COMBINED SPINAL-EPIDURAL ANESTHESIA FOR CESAREAN SECTION: EPINEPHRINE INCREASES INCIDENCE OF MOTOR BLOCKADE

JB Jr&e, M.D., LM Newman, Ph.D., M.D., AD Ivankovich, M.D.

Department of Anesthesiology, Rush Medical College at Rush-Presbyterian St. Lukes Medical Center, Chicago Illinois

Epidural test dose, lidocaine, epinephrine, Anesthesia: combined spinal epidural

lNTRODUCTlON: It is our practice to use the combined spinal/epidural technique for patients undergoing cesarean section. Bupivacaine 1 Img with dextrose and fentanyl25mcg are administered for spinal anesthesia and the epidural catheter is inserted. Prior to starting the epidural opiate infusion for postoperative analgesia, the catheter must be tested to rule out intrathecal placement.

METHODS: After IRB approval, cesarean section patients were monitored for return of lower extremity motor function as evidenced by complete knee flexion. The patients were randomized to receive one of four solutions via the epidural catheter: lidocaine 1% (4mL), lidocaine 1% w/epinephrine 1:200,000 (4mL), lidocaine 2% (2mL), lidocaine 2% w/epinephrine 1:200,000 (2mL). Return of motor block as indicated by loss of knee flexion, blood pressure, and heart rate were evaluated and recorded for fifteen mimrtes. Duration of motor block as evidenced by return of knee flexion was noted. Chi square and ANOVA were used to determine statistical significance with pi.05 considered statistically significant.

RESULTS: The table s ummarizes the results of the study. There were no intrathecal catheters discovered as evidenced by a rapid return (< 2 minutes) of bilateral motor block. There were no significant differences in blood pressure or heart rate al& injection of any of the four solutions (figure 1).

Haul Rab h SyWk Blood Pnwnc

I I I I Onset of I Durationof I ‘*I Occurrence Motor Motor Block

Volume of Block (min) (mm) Solution (ml) Number Motor Block Mean* SEM Mean f SEM

1% lido 4 9 0 1% lido wiepi 4 9 44.4%* 15**4.3 70.75*&6.9 ____.____________---I-----

2% lido 2 9 0 2% lido wlepi 2 8 SO%* 151k4.3 77.75**10.4 @

*PC.05 comparing plain lidocaine to lidocaine with epinephrine 6 1 1 ‘ 1, I* mck)

DISCUSSION In our study of post-cesarean section patients, epidurally administered lidocaine (40mg) when given as a 1% or 2% solution with Epinephrine 1:200,000, had a significantly higher incidence of return of motor blockade afler spinal anesthesia compared to the same solutions without Epinephrine. This is a clinically relevant fmding since patient discharge criteria lhnn post-anesmesia care tmits includes regression of motor blockade. Since intrathecal placement of an epidural catheter must be ruled out, lidocaine 1% and 2% solutions without epinephrine provide that information without restoring the motor blockade and delaying egress from the recovery room. For the purposes of the present study the occurrence of an intravascular catheter poses no threat to the patients well-being. If the catheter is intravascular the postoperative epidural analgesic bolus and inlusion will be intravascular and they are so small and dilute that the only effect would be inadequate analgesia. If the epidural catheter is going to be used for large doses of local anesthetic or if analgesia is inadequate, then intravenous placement must be ruled out by injection of epinephrine or air via the epidural catheter.

12

Acute Reversible Umbilical Cord Occlusion Increases Extracellular Glutamate Concentration in the Cerebral Cortex of the Immature Fetal Sheep.

RJ Goldsmith, M.D.; DH Penning, M.D.; J Henderson, M.D.; F Dexter, M.D., Ph.D.; B Atkins, B.S.; D Poduska, B.S.; JD Reynolds, Ph.D.

Obstetrical Anesthesia Research Laboratory, Department of Anesthesia University of Iowa Hospitals and Clinics, Iowa City, IA.

Cerebral Cortex, Cerebral Palsy, Fetal Hypoxia, Glutamate, Microdialysis

INTRODUCTION: An episode of fetal hypoxia, even early on in pregnancy, can produce severe neurologic and behavioral deficits in postnatal life and may be involved in the etiology of conditions such as cerebral palsy. L-Glutamate (Glu) is the major excitatory neurotransmitter in the CNS and plays an important neurotrophic role in developing brain. In adult brain, an hypoxia-induced increase in Glu release can result in neuronal damage. It is possible that hypoxia may have a similar effect on Glu release in the developing brain to produce neurologic injury. This laboratory has developed the novel technique of in utero microdialysis to investigate the effect of hypoxia on Glu release in the intact fetal brain at different, distinct stages of development. The purpose of the present study was to test the hypothesis that acute hypoxia increases Glu release in the intact cerebral cortex of the midterm ovine fetus.

METHODS: Five pregnant sheep at 88 days gestation (term=147 days) were catheterized, and an inflatable vascular occluder was placed around each umbilical cord. EEG electrodes were secured to the fetus and a microdialysis probe was stereotaxically placed in the fetal parasagittal cortex. The instrumented animals were studied 3 days after surgery. Consecutive dialysate samples were collected at 14 min intervals and Glu concentration determined by an HPLC method. On the day of experimentation, nine samples were collected before inducing an episode of fetal hypoxia at the start of the tenth sample. The clamp was inflated for 10 min and then released. Subsequent dialysate samples were continuously collected for the next 3 h.

RESULTS: Complete inflation of the umbilical occluder resulted in a rapid cessation of fetal brain wave activity. Normal brain electrical activity slowly resumed after the clamp was released. One of the five fetuses died approximately 45 min after the clamp was released. After the clamp was deflated, there was a paroxysmal increase in fetal cerebral cortical Glu release. This increase was variable in magnitude, time and frequency of occurrence, and it was observed in all four of the animals that survived the procedure. A representative fetal cerebral cortical glutamate concentration-time plot, and corresponding fetal arterial oxygen content-time curve, before, during and after inflation of the umbilical occluder, is presented in the Figure. In this animal, cord occlusion resulted in a rapid and reversible reduction in fetal arterial oxygen content (line), followed by an increase in cortical glutamate release (bars) 60 min after occluder deflation.

CONCLUSION: In utero microdialysis is a ”

powerful experimental technique which can be used to sample the extracellular environment of the intact fetal brain. In this study, a short reversible episode of acute hypoxia increased Glu release in the parasagittal cortex of the midterm fetal sheep. This hypoxia-induced paroxysmal increase in Glu concentration could damage developing neurons and disrupt normal cortical development. As such, alterations in Glu release may be important in the pathogenesis of developmental neurologic disorders such as cerebral palsy.

Supported by NIH grant NINDS lROlNS34457-01

13

HORMONAL EFFECTS OF INTRAVENOUS FLUID LOADING PRIOR TO EPIDURAL ANALGESIA

R Pitner, S Segal, X Zhang, D Carr, S Datta

Departments of Anesthesia, Brigham and Women’s Hospital, Harvard Medical School, and New England Medical Center, Tufts University School of Medicine, Boston, MA

Epidural analgesia, oxytocin, antidiuretic hormone, atria1 natriuretic peptide

Introduction: The effects of epidural analgesia on uterine activity and the progress of labor remain controversial, and the mechanisms of any such effects have been particularly elusive. One hypothesis to explain slowing of first stage labor progression holds that intravenous fluid loading prior to initiation of the block may cause decreased uterine activity [l]. It has been assumed that this reflects reduced antidiuretic hormone (ADH) release due to volume expansion, which may be accompanied by reduced oxytacin excretion since both hormones are produced simultaneously in the posterior pituitary [Z]. We tested this hypothesis by measuring hormone levels in laboring women receiving epidural analgesia.

Methods: With approval of the hospital Committee on Human Research, 15 consenting parturients have been studied to date. Healthy nulliparous patients in active labor with singleton, vertex, term gestations, and who had requested epidural analgesia were randomized to receive maintenance fluids only (1.5 ml/kg/hr of Lactated Ringer’s [LR]), a 7.5 ml/kg bolus of LR over 15 rnin prior to the block, or a 15 ml/kg bolus. A full bag of LR was hung after fluid administration in order to blind the patient, labor nurse, and obstetrician to the treatment group. All patients received standardized epidural analgesia in the lateral decubitus position. Blood was collected at four timepoints: prior to fluid administration, after fluid, and 10 min and 60 min after epidural placement. Samples were assayed in duplicate by commercial radioimmunoassay methods which were sensitive and specific for ADH, atria1 natriuretic peptide (ANT’), and oxytocin. Noninvasive maternal hemodynamic monitoring, fetal heart rate monitoring, and external tocodynamometer recordings were employed continuously during the study period. Uterine activity was calculated as contraction frequency @r-l) x mean contraction amplitude (arbitrary units). Analysis was by paired t-test and analysis of variance.

Results: Oxytocin levels varied by an order of magnitude

4 p=.59 between patients (range baseline levels 0.835-11.918 pg/ml),

b_ but interassay variation was less than 3%. Oxytocin and p=.Ol ADH levels were very tightly correlated (R2=0.85, pc.0001).

Oxytocin levels decreased significantly in all patients after fluid loading but returned to baseline after epidural analgesia (see Figure). Fluid volume administered before the block did not affect the changes in oxytocin observed.

B I

7 ANP levels also correlated with oxytocin levels, though not

4-

as closely as did ADH (R2=0.13, p=.OO5). Uterine activity

5 3. did not significantly differ between groups prior to the epidural but tended to decrease with increasing fluid loads

2. after the block (ANOVA, p=.O6).

1. Discussion: These results are consistent with those of Cheek

o- et al. [l] who found decreased uterine activity in patients

Baseline After fluid After epidural randomized to larger fluid loads. As hypothesized, ADH and oxytocin were well correlated, but oxytocin levels decreased in all fluid loading groups. This may reflect the

tremendous interpatient variability in oxytocin levels, or perhaps the influence of other more influential factors, such as the assumption of the supine position in all three groups upon initiation of fluid administration.

References: [l] Cheek TG et al. Anesthesiology 1989; 71:A884. [Z] Bieniarz J et al. Am J Obstet Gynecal 1971; 111: 874-85.

14

?BSTRi~FOR~ I

TITLE: PAINFULNESS AND DURATION OF LATENT PHASE LABOR: CORRELATES OR CAUSES OF DURATION OF ACTIVE PHASE LABOR?

.GrHoRs: A LOBO, MD, MPH; C TINNELL, MSPH; S PALMER, MD

AFFILIATIOS: UNIV OF COLORADO HEALTH SCIENCES CENTER, DEPARTMENT OF ANESTHESIOLOGY, DENVER COLORADO

KEYX’m: Human pregnancy, labor and delivery

INTRODUCTION: Many physical, social, pharmaceutical, medical, ethnic, and monetary factors have been statistically associated with the pain, length and outcome of labor. Research on the causes or effects of labor pa& have been far less frequent. This study was designed to determine whether patient-reported length and painfulness of latent phase labor is related to the length and outcome of active phase labor.

METHODS: This IRB-approved study consisted of a questionnaire and chart study of consenting volunteers. The study took place over eight months in five hospitals with all the interviews and chart studies accomplished by one investigator (AL). Patients at term pregnancy in latent phase labor (defined as regular painful contractions with cervix less than 4cm) committed to delivery by their obstetrician, who could understand and respond to the questionnaire were invited to participate. Subjects were questioned about their medical history, previous and current labor and other pain experiences. Pain was studied using the short form McGill Pain Questionnaire’, a visual analog scale and a pain ranking table. The interviewer was not a treating physician and had no part in labor management or delivery plans. Obstetric outcome, use and timing of any form of analgesia, and demographic data was obtained from the patients chart. Data were analyzed using step-wise multiple regression and analysis of variance to determine the statistical effects of multiple covariates. We report here on the initial statistical analysis of the effect of age, hgt, wt, parity, education, pain intensity during latent phase, use of epidural analgesia, and duration of latent phase (regular contractions to 4cm dilation = LLRG4) on the duration of active phase (4 to 1 Ocm = LL410). All results reported below are significant at ~~0.05 level.

RESULTS: Of the 203 patients who participated in the study, 191 reached 4cm dilation, and 176 reached IOcm dilation. In the entire sample of patients, the length of latent phase labor (LLRG4), the pain ranking of latent phase labor, parity and maternal weight were correlated with the time from 4 to IOcm dilation (LL410). In patients who received epidural analgesia (N=139) patient-reported pain ranking and length of latent phase labor oredicted whether thev received eoidural analaesia and correlated with the duration of subseauent active chase labor.

DISCUSSION: If we had not examined the painfulness and duration of latent phase, these results could have been reported as “the presence of epidural analgesia influenced the length of active phase labor.” Statistical correlations between proposed independent and dependent variables can suggest a relationship but never prove a causal relationship. The possibility of intervening and causally determining variables must be recognized. The findings of this study suggest that whatever causes painful and lengthy early labor may be the real determinant of overall duration of labo? or success of vaginal delive$. Until we understand the causes of Pain durina earlv labor and its effect on subseauent uterine efficiencv. anv comoarison of obstetric eoidural analaesia to non-eoidural oatients should be controlled or case-matched for oain and lenath of early labor.

REFERENCES: I. Melzack R. The short-form McGill Pain Questionnaire. Pain 1967;30:191-197. 2. Wuitchik M, Bakal D, Lipshitz J. The clinical significance of pain and cognitive activity in latent labor. Obstet Gynecol 1989;73:35-42. 3. Lederman R, Lederman E, Work B, McCann D. Anxiety and epinephrine in multiparous women in labor: relationship to duration of labor and fetal heart rate pattern. Am J Obstet Gynecol 1985;153:870-7.

__

Combined Spinal/Epidural vs. Epidural Analgesia: Effects on Progression and Outcome of Labor

Tsen L, Segal S, Datta S

Department of Anesthesia, Harvard Medical School, Brigham & Women’s Hospital, Boston, MA

Opioids, intraspinal; epidural; progress of labor

Introduction: Intrathecal sufentanil with bupivacaine has been shown to provide excellent analgesia with rapid onset and absence of significant motor block 111. Standard epidural analgesia has been suggested by some to prolong labor in nulliparas, especially if administered early in labor [Zl. Other work failed to verify this but was limited by poor analgesia in patients randomized to receive epidurals later in labor [31. We hypothesized that delaying dosage of an epidural for labor while still providing comparable analgesia with intrathecal sufentanil/bupivacaine as part of a combined spinal/epidural (CSE) would accelerate the progression of labor, compared to standard epidural analgesia (EN).

Methods: With approval of the hospital’s Human Research Committee, we have to date enrolled 45 consenting parturients, all nulliparous, ASA 1-2 , with spontaneous onset of labor, singleton, vertex, term gestations, and cervical dilatation <5 cm. The patients were randomized to receive intrathecal sufentanil (10 mcgl with bupivacaine 0.25% (1 cc) or epidural bupivacaine 0.25% (lo-12 cc, to achieve a T10 sensory level to pinprick) when in active labor and requesting analgesia. The EPI group received an infusion of 0.125% bupivacaine with 2 mcg/cc fentanyl following the initial bolus dose; those in the CSE group received no epidural drug until discomfort returned, at which time they received 6-12 cc 0.25% bupivacaine (to achieve a bilateral TlO sensory level) and the same infusion as the EPI group. The patient, labor nurse, and obstetrician were blinded to the group assignment. Management of pain, hypotension, nausea, and pruritus were standardized. VAS pain scores, sensory level to pinprick, and motor blockade were assessed by a blinded observer at entry, first analgesia, and regular intervals thereafter. Outcomes measured included cervical dilatation, use of oxytocin, length of first and second stages of labor, and mode of delivery. I

T 1 Results: The grouns were comparable with regard to baseline characteristics. VAS’ pain scores were comparablg throughout the study period, though there was a trend towards better analgesia in the CSE group in the first 10 minutes after analgesia (p=.OB. Initial cervical dilation rate following analgesia was significantly faster in the CSE group (4.4 +_ .8 [mean &SE] vs. 1.8k.69 cm/hr; p=.O2) and the first stage of labor tended to be shorter in this group as well (3.2 +.6 vs. 4.8+.5 hr, p=.O6). As seen in the Figure, there were a number of patients with very rapid cervical dilation in the CSE group (5-10 cm/hi+, but not in the EPI group. Second stage duration and mode of delivery did not differ between the groups

I I

CSE EPI Discussion: These preliminary results suggest that in healthy nulliparous patients, CSE may offer salutary effects on progress of labor. Our data confirms our clinical impression (but is at odds with

past work [4Jl that some patients given CSE progress very rapidly though the first stage of labor. Our small sample size to date does not permit us to assess whether these effects will be also reflected in fewer operative deliveries once this investigation is complete.

References: 111 Camann W et al. Anesthesiology 1992; 77: 884-7. J2J Thorp JA et al. Am 1 Obstet Gynecol 1993; 169: 851-8. J3J Chestnut DH et al. Anesthesiology 1994; 80: 1201-a. J4J Sarna MC et al. SOAP 27th Annual Meeting Abstracts 1995, p. 43.

16

‘4EslRAcI-FoRM ,” I

TITLE: The Analgesic Efficacy of Hyperbaric Subarachnoid Fentanyl in Parturients

AUIHORS: M. Kang, MD, S. Orebaugh, MD, S. Ramanathan, MD

AFFILIATION: The Department of Anesthesiology, Magee-Womens Hospital, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 152 13

KEYWORlx Subarachnoid, Fentanyl, Analgesia, Hyperbaric

Introduction: Intrathecal fentanyl is popular for providing labor analgesia. Most opioids including fentanyl have the same baricity as cerebrospinal fluid at room temperature (993.0 kg/n?) ‘. A local anesthetic solution made hyperbaric by the addition of glucose spreads rapidly and predictably in the spinal tluid with gravity. In this study, we evaluated if the analgesic &cacy of intrathecal fentanyl in laboring parhnients may be mcditied by making it hyperbaric. Methods: IRJ3 approval and informed consent were obtained from ASA I or II parturients in active labor. They were randomized to receive intrathecally either 25 pg of fentanyl + 0.5 ml of normal saline (group I) or 25 pg + 0.5 ml of 10% dextrose (group Il). Fentanyl was administered intrathecally in the sitting position, at L2-3 or L3-4 interspace using combined spinal-epidural technique, following which an epidural catheter was also inserted. The patients were then placed in the supine position with lateral tilt, with the head slightly elevated. No medications were admimstered through the epidural catheter until the patient requested additional analgesia. Ihe time to onset and complete analgesia as well as time to additional analgesia were noted. Pain scores (A 10 cm visual analogue scale, VAS), sensory levels to pinprick, motor block in the lower extremities (Bromage score), blood pressure, and side effects were recorded at baseline and once every 5 min for 45 min. Results expressed as mean f 1 SD and were analyzed using t- test and X2 analysis. Results: A total 22 patients (11 per group) were studied. Age, height, weight, gestational age, parity, baseline cervical dilation, baseline VA.8 scores were similar between groups. Compared to the isobaric group, the onset time was longer, duration of analgesia shorter, number ofpatients with complete analgesia smaller, the number with itching smaller and the lowest post- injection VAS score greater in the hyperbaric group (Table ).

prevents its spread to B fentanyl to the receptor, although such a phenomenon has not been reported to occur with morphine.

1. Nicole ME, et al: British Journal of Anaesthesiology 68:60-63, 1992 2. Abboud TK, et al: British Journal ofAnaesthesio1ogy 56:135-1359,1984

21

TITLE: Labor Analgesia

d Direction of Drug Injection on

AUTHORS: Fazeela Ferouz, M.D., Mark C. Norris, M.D., Valerie A. Arkoosh, M.D. Barbara L. Leighton, M.D., Louis M. Boxer, M.D., Robert J. Corba, D.O.

AFFILIATION: Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson

University, Philadelphia, Pennsylvania 19107

KEYWORDS: opioids, intrathecal, sufentanil, baricity

INTRODUCTION: Intrathecal sufentanil provides rapid relief of labor pain, but with associated pruritus and nausea (1). These side effects result from brainstem actions of intrathecal sufentanil(2). Baricity and the direc- tion of the lateral opening of a pencil point needle modify the spread of intrathecal local anesthetics (3,4). Here, we examined the effect of these variables on intrathecal sufentanil labor analgesia. METHODS: After IRB approval and written informed consent, 20 ASA 1 or 2, laboring, term parturi- ents, < 5 cm cervical dilation, requesting combined spinal epidural labor analgesia were enrolled in this ongoing study. They were randomly allocated to receive either hyperbaric (H) or isobaric (I) sufentanil with the Sprotte

needle opening facing cephalad (up=U) or caudad (down=D). Thus, there were four groups: down-hyperbaric (DH), down-isobaric (DI), up-hyperbaric (UH), and up-isobaric (UI). Sufentanil, supplied in a 50 ug/mL am- poule, was diluted with normal saline to a concentration of 10 yg/mL. Hyperbaric drug was made by adding 1 ml_ 10% dextrose to 1 mL sufentanil solution. Isobaric drug consisted of 1 ml_ normal saline and 1 mL sufentanil solution. Visual analogue scales (VAS) for pain, nausea, pruritus and pain relief as well as maternal blood pres- sure were obtained before (baseline) and at time 5, 10, 15, 30 and 45 minutes after drug injection. At the 30 minute time interval, patients requesting more pain medicine had their epidural activated. Time from intrathecal injection to epidural activation was recorded. Results were analyzed by analysis of variance, repeated measures analysis of variance and Kruskal-Wallis test, as appropriate. RESULTS: There were no statisticallysig- nificant differences among the groups in age, parity, height, weight and cervical dilation. Systolic blood pres- sure and severity of nausea did not change during the study period. Diastolic blood pressure fell slightly and pruritus VAS increased significantly with time. Patients in the DH group had more pain after intrathecal sufen- tanil (fig). Four of the 5 women in the DH group re- quested additional analgesia at 30 minutes. Only 2 of the remaining 15 women requested additional analge- sia (p < 0.04). DISCUSSION: *

tapI* tedhe- kwainsteq Injecting hyperbaric sufentanil with the Sprotte needle opening oriented cau- dally should limit cephalad spread of drug. We had

+ DH -A- UH

- + - DI --a - UI

0 5 10 15 20 25 30 35 40 45 Time (min)

hoped that this technique would provide spinally mediated analgesia without supraspinally mediated side effects. , the DH ~gmtap developed little * n #I%. In animal models, spinal and supraspinal opioid sites

ftwmggest that rmpwspinaf actions produce some of&e

REFERENCES: 1) Norris MC, et al. Anesth Analg 79:529, 1994. 2) Thomas DA, et al. Anesthesiology 79:548, 1993. 3) Urmey WP, et al. Reg Anesth 20: 11, 1995.4) James KS, et al. Int J Obstet Anesth 4: 183, 1995. 5) Yeung JC, Rudy TA. J Pharmacol Exp Ther 215:633,1980.

22

INCIDENCE OF FETAL HEART RATE CHANGES FOLLOWING EPIDURAL AND INTRATHECAL FENTANYL ANALGESIA FOR LABOR

K Gossler, MD*, CM Palmer, MD*, JE Maciulla, MD”, WM Nogami, MD*, RC Maquez, MD*, DM Alves, RN’

Department of Anesthesiology*, and Department of Obstetrics and GynecologV*, University of Arizona Health Sciences Center, Tucson, AZ, 857246114

Analgesia, labor. epidural, intrathecal. Fetal monitoring: Fetal heart rate.

WTRODUCTION: A recent report has raised concerns that intrathecal fentanyl 50 vg, when administered for labor analgesia, may be associated with a hiih incidence of fetal bradycardia (1). A subsequent report found a higher incidence of late decelerations associated with an intrathecal sufentanil technique than epidural analgesia (2). We undertook thii study to quantify the incidence of fetal heart rate (FHR) changes following intrathecal (l-T) fentanyl labor analgesia, and to compare lt to the incidence following epidural (Epid) labor analgesia. WHODS: IRB approvsl was not required for thii retrospective, chart review study. Complete medical records of patturients delivering at our Institution between June 1 and July 30,1995, were reviewed. During this time period, both Epid and I-T techniques were in routine use for labor analgesia. Epid analgesia was initiated with a loading dose of lidocaine 0.9%, fentanyl 50 pg, and epi 1:300,000 (volume lOcc), followed by a dilute infusion of bupivacaine, fentanyl, and epi. All I-T analgesics induded fentanyl25 pg; in some, thii was combined with up to 2.5 mg bupivacaine. Beginning on June 1.1995, and proceeding in chronological order, the first 100 patients receiving I-T analgesia, and who had FHR tracings for a minimum of 30 minutes before and after injection were identified. In like fashion, 99 parturients receiving Epid analgesia were identified. Parturients with abnormal presentation (i.e., breech), multiple gestation, or significant co-existing disease were excluded. A perinatologist, blinded to anesthetic technique, reviewed each FHR trace beginning 30 minutes prior to, and continuing for 30 minutes after injection, noting baseline FHR, variability, presence of decelerations, or other pertinent changes. Other data compared between groups included demographics, use of oxytocin augmentation, maternal blood pressures, dilation/station at placement, presentation, mode of delivery, and neonatal weight and Apgars. Data were analyzed with Fiih8r.S exact test and Chi -square, as appropriate. RESULTS A total of 199 patient records were reviewed (I-T, n = 100; Epid, n = 99). Significant changes were noted in 22 FHR tracings in the 30 minutes after injection, 4 of whiih were charactedzecl as positive or improved; negative changes were noted in 18 (I-T, 12; Epid, 8; p = NS, Chi-square). Negative FHR changes are summarized in Table One: all changes identified were transient, resolving within 30 minutes. and no parturient required urgent delivery due to FHR changes noted. Table Two summarizes d8liv8Iy route, oxytocin use, and complications between groups; in no subgroup were proportions significantly different from the sample as a whole. DISCUSSION: Clarke, et al, (1) reported a hiih incidence of fetal bradycardia (30%) and apparent uterine hyperactivity after the intrathecal injection of 50 pg fentanyl. While we did not assess-s uterine activity directly, we were unable to document any difference in FHR patterns between parturients receiving epidural analgesia, and those receiving 25 pg intrathecal fentanyl. Our data indicate that at this dose, any effect I-T fentanyl may have on FHR, either directly or indirectly via uterine activity, is transient and considerably less frequent.

Late I 2 I 2 Isolated Eradycardia(s) I 5 I 1

REFERENCES: 1. Anesthesiology 81:1083,1994; 2. Anesthesiology 83:A944,1995.

.

., /

-II.

TITLE: Fetal Bradycardia after Intrathecal Sufentanil Use during Labor

AUTHORS: D.R. Gambling MB.

AFFILIATION: Department of Anesthesiology, UCSD, San Diego, CA.

KEY WORDS : Sufentanil, Intrathecal, Spinal, Labor.

INTRODUCTION : Intratbecal sufentanil is used in some centers as a single shot analgesic or as the spinal component of a combined spinal epidural (CSE) analgesic technique’, 3 for labor pain. It produces rapid onset analgesia and a duration of 90-120 min. To date, side- effects that have been described include pruritus, maternal hypotension and fetal heart rate (FHR) changes, which in one study “did not adversely affect neonatal outcome 4r’. This abstract is to draw attention to some adverse neonatal outcomes associated with CSE observed during a large randomized comparison of CSE with intravenous analgesia.

METHODS : Following approval of the IRB, healthy parturients in established labor were randomly assigned to receive either 1Opg intrathecal sufentanil in 2ml preservative-free normal saline, as part of a CSE technique prior to epidural catheter insertion, or 50 mg iv meperidine qlh pm, Analgesia was provided at the patient’s first request for pain relief. This study was designed to assess the impact of the analgesic method on labor outcome in women admitted to Parkland Memorial Hospital in Dallas. After the first X0 women receiving CSE had been studied, a review of the incidence of severe fetal bradycardia was made, since this had been perceived as a clinical problem within. 6 weeks of starting the study. All patients in the CSE group had received a fluid preload of 5OOml normal saline prior to the sufentanil injection. All were followed by continuous electronic FHR monitoring and positioned with left uterine displacement. Ephedrine 1Omg iv was used as part of the therapy to treat fetal bradycardias, even in the absence of maternal hypotension. If fetal bradycardia was observed the patient was placed in a lateral postion and oxygen administered by face mask. The incidence of bradycardia was determined and its timing, treatment and impact on neonatal outcome documented.

RESULTS : 18% of all women receiving intrathecal sufentanil had a documented fetal bradycardia within 60 min of the injection. Most patients responded to positioning, iv fluid bolus and/or ephedrine, but 1.6% ( 8/499) of all patients required an emergency cesarean section for persistent, severe fetal bradycardia. Of these 8 cases, seven involved nulliparous women. All but one of the neonates had an umbilical artery pH 4.2 and a pC0, > 65 and three required resuscitation for a low 1 min Apgar score. However, 20% of all patients studied demonstrated a UA pH < 7.2 and 12% had a pC0, >65, regardless of the presence of intrapartum FHR abnormalities. In addition, 57% of those with a UA pH < 7.2 had no fetal bradycardia within 60 min of the sufentanil injection.

@iW&?titiGNS : Tk ind%ehc&f fetal Sk%ycadk f&bwifrg Q$Mhec@ Mentanil is 9 t@xxM~~~, &3t&mdl perfx9dge may require rirf+ru eesamaWS because of

w’drops i&m, resistent to conservative management. Whether these observations are clinically important and im a direct

s 1s a matter for conjecture. Ho or indirect effect of sufentanil upon

to be established before use of MlWeGal SUfeHad in th issues such as fetal

b&yuadia,Werine hypertonus and maternal resp&atMy depressions;aall rare, but potentklly reversable wmplications.

REFERENCES : 1. Lancet 1993; 341: 767-8; 2. Anesth Analg 1994; 79: 529-37; 3. Int J Obstet Anesth 1994; 3:75-81; 4. Anesth Analg 1993; 77: 1155-60 1994; 81: 511-2.

5. Anesthesiology

24

TITLE: Intrathecal Sufentanil versus Epidural Lidocaine for Labor Analgesia

AUTHORS: Louis M. Boxer, M.D., Valerie A. Arkoosh, M.D., Mark C. Norris, M.D., Barbara L. Leighton, M.D., Fazeela Ferouz, M.D.

AFFILIATION: Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

KEYWORDS: opioids, intrathecal, sufentanil; epidural analgesia, lidocaine

INTRODUCTION: Compared to intrathecal sufentanil (IT), epidural (BPI) analgesia with bupivacaine has a slower onset of pain relief and may be associated with more motor blockade (1). Epidural lidocaine has a faster analgesic onset than bupivacaine. We undertook this study to compare the labor analgesia produced by intrathecal sufentanil or epidural lidocaine. METHODS: Following IRB approval, 37 multigravidae with single vertex fetuses, receiving oxytocin and at <5 cmcervical dilation were randomly assigned toeither IT or EPI analgesia. Demographic information, baseline blood pressure, heart rate, and visual analog scores (VAS) for pain, nausea, and pruritus were obtained. The IT group received 10 pg of sufentanil via a 24g Sprotte needle at time 0. The EPI group received a bolus of 5 mL of 0.75% lidocaine with 1 .O pg/rnL of sufentanil at time 0. After 2 minutes, 2 mL of air was injected through the epidural needle with Doppler auscultation of the maternal right ventricle to rule out intravascular injection. An additional 5 mL of the lidocaine/sufentanil solution was given through the needle at time 0 plus 3 minutes. Both groups had epidural catheters inserted into the epidural space. At time 5, 10, 15,20,25 and 30 minutes, blood pressure, heart rate and the above VAS were obtained. Motor strength was assessed via the Bromage scale (2) and the rectus abdominal muscle (RAM) (3) tests at baseline, 15, and 30 minutes. If the assigned analgesic regimen failed to provide adequate analgesia in either group within 30 minutes, additional local anesthetic was administered through the epidural catheter. Time of additional drug injection was recorded as the study endpoint. Statistical analysis of ratio demographic data, duration of initial analgesia and VAS was performed using analysis of variance (ANOVA) or ANOVA for repeated measures. Ranked demographic data and motor strength data were analyzed using the Mann-Whitney U or the Friedman Rank test. A p<O.O5 was considered significant. Following initial analysis of the VAS data, a Bonferroni correction was applied, resulting in an acceptable pvalue of p10.007 for between group VAS comparisons. RESULTS: Groups were similar in age, height, weight, gra- vidity and parity. There were no differences between the groups in the incidence or severity of nausea, or loss of motor strength. Patients in the IT group had significantly lower pain scores (Fig). IT group patients reported more pruritus at all times after injection. No patient required treatment for pruri- tus. Request for additional analgesia in the IT group occurred at 103 f 3 1 min and in the EPI group at 85 f 52 min (p=ns).

rMaoll @Gaduces f@ta’%@l li&tq&-wi* $#3

QfMrc4w in Wernai mowstrengk This fqS4, intense pam relief following intrathecal sufentanil injection is consistent with a previous study comparing intrathecal sufen- tanil to epidural bupivacaine (1). ma1 opioid art&Is,* -ins the superior choice for swift and profound analgesia in

ngpatients. ’

lo1 -Q- Epidural -9- Intrathecal

29 2 8

E v7

%6

$5 .9 4 23 m2

$1

*p<O.O07 vs Intrathecal

0 ; I I I I I I 0 5 10 15 20 25 30

Time (min)

REFERENCES: 1) Anesthesiology 80:1209-15,1996.2) Acti Anaesthesiol Stand 16:55-69.1965.3) Anesth Analg 65:333-6,1986

25

ADDITION OF EF’INEPHRINE TO INTRATHECAL SUFENTANIL AND BUPIVACAINE FOR AMBULATORY LABOR ANALGESIA

Campbell DC, MD, Banner R, MD, Crone LA, MD, Gore-Hickman W, MD, Yip RW, MD

Department of Anaesthesia, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Analgesics, opioid: sufentanil. Anesthesia, obstetric. Anesthetic techniques: spinal, epidural, combined spinal-epidural. Obstetric, labor: outcome

INTRODUCTION: Combined spinalepidural (CSE) anesthesia, utking the combination of 10 mcg of sufentanil (S) and 2.5 mg of bupivacaine (B), was recently shown to provide rapid, profound labor aualgesia for 2-3 hours without demonstrable motor blockade.’ The addition of 0.2 mg of epinephrine (E) has been employed to prolong the action of local anesWkx2 Although 0.2 mg of E did not significantly increase the duration of labor analgesia provided by intrathecal S,’ the addition of E to the combination of intrathecal S and B for labor analgesia has not been evahrated. Therefore this prospective, randomized, double-blind study was designed to evahtate the efficacy of the addition of 0.2 mg of E to the combination of S and B for intrathecal labor analgesia using the CSE technique. The ability of the patient to ambulate and the progress of labor were ako examined.

METHODS: Following IRB and informed written consent, 39 nulliparous patients in active labor, with cervicaI dilatation between 2-5 cm, mquesbng epidural analgesia were randomized to receive one of two intrathecal study solutions consisting of a total volume of 2.2 ml: i) NS: 10 mcg S + 2.5 mg B + 0.2 ml 0.9% saline, or ii) EPI: 10 mcg S + 2.5 mg B + 0.2 mg E. Each study solution was injected intrathecally through a 25G Whitacre (4-11116”) spinal needle which was inserted through a 17G epidural needle. The spinal needle was then removed and an epidural catheter placed, but not tested. Patients were eval~ted at regular intervals using a VAS score for pain and also for hypotension, nausea, vomiting, pruritus, degree of somuolence. SpG2 and FHR abnormalities. Fifteen minutes following the admiuistration of the study solution, assessment of cep&d level of sensory loss to add ability to straight leg raise (SIB), stand and deep knee bend (DEB) were undertaken. Patients were permitted to ambulate only after successtkl demonstration of a DEB. The duration of analgesia was detIned as the time from the injection of the study solution to the patient’s request for additional analgesia via the epidural catheter.

RESULTS: There was no statistical difference between the two groups as to demographic data, ASA status, gestation, initial cervical dilatation (3 cm), Apgar scores, birth weight and iuitial VAS pain scores. All 39 patients reported no pain (VAS=O) within 5 minutes of injection of the study solutions. Seven patients (3 NS, 4 EPI) delivered vaginally and two (1 NS; 1 EPI) required C-delivery prior to requesting epidural aualgesia. of the remainin g 30 patients, the mean duration of analgesia (min +/- SD) was signiticautly longer in the group receiving E: NS(n=15): 145 +/- 23; EPI(n=15): 188 +/- 25 (P<O.OOOl). Ambulation occmred in 100% (19/19) NS and 80% (16/20) EPI. Gf the 4 EPI not ambulating, 2 demonstrated normal SLR but were unable to DKB and a third refused, due to fatigue. The mean times (min +/- SD) from injection of the study solution, at mean cervical dilatation of 3 cm, to the end of the first stage of labor, NS(n=17): 249 +/- 186; EPI(n=18): 299 +/- 196 (PM.OS), were much less thau conventionally predicted for nulliparous patients (i.e. 3 to 10 cm at 1 cm&r = 420 min).’ Six episodes (3 NS; 3 EPI) of transient FHR variable decelerations were noted afler CSE, none of which necessitated urgent C-delivery Five of these were associated with rapid cervical dilatation and a nuchal cord and the sixth, with a concealed prolapsed cord observed during eventual C-delivery. Four of 39 (10%) labors (2 NS; 2 EPI) culminated in C-delivery.

CONCLUSION: The results of this prospective, raudomikd, double-blind study indicate that the addition of 0.2 mg of E to the intrathecal combination of 10 mcg S and 2.5 mg B siguiflcantly prolongs labor analgesia; This study also demonstrates that CSE utilizing intrathecal S + B, witbor without E, not only provides rapid, profound labor analgesia, but also enables the majority of patients to ambulate an@educes the duration of the first stage of labor in nulliparous pmturients.

REFERENCES: l.Campbell DC, Camann WR, Datta S. Anesth Aualg 1995;81:305-9 2.AbouIeish EI. Anesth Analg 1987;66:395-400 3Camann WR, h4inzter BH, Denney RA, Datta S. Anesthesiology 1993;78:8704 4.Friedman EA. Obstet Gyuecol 1955;6:567

TITLE: Expression of Adenylyl Cyclase Isoforms in the Pregnant Rat Uterus

AUIHORS D Kumasaka, C Hirshman, C Emala and K Lindyan

AFFILIATION: The Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland

Adenylyl Cyclase, Myometrium, /3-adrenergic Receptor

INTRODUCTION: /3-adrenergic receptor @AR) agonists are the pharmacologic agents most frequently used for prevention of preterm labor and rapid treatment of uterine tetany. The BAR- mediated pathway is the major receptor signal transduction pathway that produces uterine relaxation. &AR agonists relax uterus by stimulating adenylyl cyclase and increasing intracellular concentrations of cyclic adenosine 3’, 5’ monophosphate. Recent reports have revealed the presence of at least nine distinct mammalian isoforms of adenylyl cyclase. The functional significance of these isoforms is not understood. Differences in tissue distribution, basal activities, and regulation by Ca*‘, by G protein, and by phosphorylation suggest that differences in expression of the isoforms may be important in determining biological activity of adenylyl cyclase. We questioned whether pregnant rat myometrium expresses mRNA for each of the nine adenylyl cyclase isoforms that have been identified in other tissues.

METHODS: Using reverse transcriptase (RT) and polymerase chain reaction (PCR), we sought to identify the adenylyl cyclase isoforms present in the rat myometrium. Total RNA was extracted from myometrial tissue of a late gestation (19-21 days) rat using phenol, guanidine isothiocyanate and chloroform. Following treatment with DNAse to remove residual genomic DNA, cDNA was prepared by RT using random hexamer primers. Forty cycles of PCR were performed with primers specific for adenylyl cyclase isoforms I through IK (based on published rat, mouse and cow sequences). PCR products were electrophoresed through polyacrylamide gel and stained with ethidium bromide.

RESULTS: PCR performed on DNAse-treated RNA, which was not exposed to RT, confirmed that PCR products were not generated from genomic DNA. Single PCR products were identified at the appropriate molecular weights for AC isoforms II-IX

CONCLUSIONS: The presence of multiple isoforms of adenylyl cyclase suggests complex interactions with multiple signal transduction pathways in uterine smooth muscle. This information will serve as a basis for understanding differences in uterine relaxation in response to &AR agonists.

Supported by The SOAP/Braun Fellowship Award.

1:OOpm - 2:30pm

BY NITROGLYCERIN

ulates the Stimulatory Signal Transduction 1 Cyclase in Cultured Rat Myometrium

KS Lindeman, D asaka, I Kuhl, C Hirshman, and C Emala

1:45pm-2:OOpm

EATING IN LABOR: NT OF THE RISKS AND

BENEFITS

Mark Scrutton, Clara

2:00pm-2:15pm

Timing of Postpartum St ion: Complications and Cost-savings of Early Tubal Ligations A.C.H. Barton, M.D., F man, M.D., R. Onder, R.N., DC. Mayer, M.D.

SHIP BETWEEN AREAN SECTION FOR

2:30pm - 3:OOpm

3:OOpm - 3:45pm w in Obstetrics? Lecture urice L. Druzin, M.D.

rofessor, Obstetrics and Gynecol

Stanford, CA

3:45pm - 4:45pm 7:OOpm -

OAP Business Meeting Dining with SOAP

33

PLACENTAL TISSUE MARKEDLY ENHANCES UTERINE RELAXATION BY NITROGLYCERIN

S. Segal, MD, $Datta, MD

Department of Anesthesia, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Nitroglycerin, uterine activity, placenta

Introductiom Recent case reports suggest nitroglycerin f’lNG) may be successfully employed in very small doses to achieve uterine relaxation in the management of obstetric emergencies such as retained placenta or entrapped fetus [l]. Laboratory efforts to characterize and quantitate this effect, however, have demonstrated marked resistance of the uterus to TNG, with doses 10,000 times higher than those used clinically required to achieve significant relaxation. We hypothesized that one important difference between the clinical and laboratory conditions that could explain this discrepancy could be the presence of the placenta in the uterus. We therefore tested this possibility in an in nitro gravid rat uterus model.

Methods: Transverse sections of uteri (uterine rings) harvested from timed pregnant rats at 19-20 days gestation were mounted ln tissue baths in Krebs-Henseleit buffer (KHB), aerated with 95%02/5%CO2, and pretensioned to 0.5 g. Spontaneous contractions occurred within 15 min and continued for at least 4 h. Alternatively, uterine rings placed in low Ca +2 KHB (.625 mM) showed no spontaneous contractions, but added acetylcholine (ACh; 10-100 @I) stimulated 5 min long sustained contractions. Placentas (2 per uterine ring studied) were finely minced, rinsed in 20 volumes KHB, placed into fine nylon mesh bags, and after a 60 min stabilization period, added to the tissue bath in close approximation to the contracting uterine ring. Cumulative dose-response curves for TNG, 1 nM-1 n-&I, were constructed, with uterine activity expressed as percent of control before drug addition. For comparison, 3 mm wide thoracic aortic rings from the same animals were placed in identical tissue baths, pretensioned to 4 g, and submaximally contracted with phenylephrine and then relaxed with TNG.

Results: As shown in the Figure, nitroglycerin alone did not relax the spontaneously contracting uterine rings until very high doses (ED50 = 10m4 MI were given. ACh-induced sustained contractions were no more sensitive to TNG. However, addition of placental tissue fragments to the tissue baths increased the sensitivity to TNG by approximately three orders of magnitude (ED50 = 10m7MI, approximately equal to the effect on aortic tissue.

Discussion: Doses of TNG found useful clinically in relaxing the uterus (50-100 ug IV) have been called “suspiciously small” (21. The expected plasma level from such doses is in the range of lO-g-lO-7 M, orders of magnitude lower than apparently required in in uitro studies [2] or postpartum in uioo animal studies [3] in the past. This data suggests that the reason for thii discrepancy may be the placenta, which is always present in the uterus in every clinical report of TNG’s effectiveness. The role of the placenta may be in facilitating the enzymatic release of nitric oxide from TNG, an activity

present in vascular smooth muscle but not in some other forms of smooth muscle, probably including the uterus.

References: [l] Altabef KM, Spencer JT, and Zinberg S. Am ] Obstet Gynecoll992; 166:1237-S. [2] Chen B et al., Anesthesiology 1993; 79: A995. [3] Langevin PB and James CF, Anesthesiology 1993; 79: A994.

35

Oxytocin Cross-Regulates the Stimulatory Signal Transduction Pathway of Adenylyl Cyclase in Cultured Rat Myometrium

KS Lindeman, D Kumasaka, J Kuhl, C Hirshman, and C Emala

The Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland

Oxytocin, Myometrium, Adenylyl Cyclase, Isoproterenol

INTRODUCTION: Intrathecal opioids are an increasingly popular alternative to epidural local anesthetics during labor. However, this technique is associated with uterine hyperactivity and fetal bradycardia in up to 10% of patients (VT Clarke et al., Anesthesiology 81: 1083, 1994), especially in those receiving oxytocin (OT). The proposed mechanism of uterine hypertonus involves sudden reductions in circulating catecholamines. It is unclear, however, how rapid decreases in catecholamine concentrations produce sudden increases in uterine tone and how OT enhances this problem. The physiologic mechanisms underlying normal changes in uterine contractility are not well understood. Although external modulating influences, such as neural, hormonal, or metabolic factors, are important, regulation of uterine activity ultimately depends on the contractile state of the myometrium. Smooth muscle responses to external influences are determined by cellular signal transducing pathways that produce either contraction or relaxation. Uterine hyperactivity can result from activation of a contractile pathway or inhibition of a pathway producing relaxation or a combination of both. The two most important of such pathways, the OT pathway and the /3 adrenergic receptor @AR) pathway, were thought to operate independently. We questioned whether OT crossregulates the stimulatory signal transduction pathway of @AR. We therefore studied effects of chronic pretreatment with the contractile agonist GT on adenylyl cyclase activity in cultured late gestation (day 20) rat myometrial cells.

METHODS: At confluence, cells were exposed to growth medium with or without oxytocin (10-M) for 24 hours. Adenylyl cyclase activity was measured in washed membranes at basal state and in response to isoproterenol (a BAR agonist); forskolin (a stimulator of adenylyl cyclase); GTP and NaF (which stimulate G proteins).

RESULTS: When compared to controls, oxytocin-pretreated tissues showed reduced basal adenylyl cyclase activity (95+44 vs. 54+29 pmol cAMP/mg protein/l0 mm, respectively, means&SE, n=2). This reduction was also reflected in adenylyl cyclase activity induced by GTP (10%) [147f82 vs. 91*57J, isoproterenol (lO-‘M) [207f109 vs. 112+62], forskolin (10%) [1277+606 vs. 995+671], and NaF [1044f616 vs. 804f5231.

CONCLUSIONS: These findings suggest that chronic pretreatment with OT inhibits adenylyl cyclase activity through a mechanism that is distal to the B adrenergic receptor. Decreased basal and forskolin-stimulated activity suggest that this effect occurs at the level of adenylyl cyclase. We conclude that chronic oxytocin exposure downregulates the stimulatory adenylyl cyclase pathway, possibly leading to uterine hypertonus during withdrawal of /JAR input.

Supported by The SOAPlBraun Fellowship Award.

36

EATING IN LABOR: AN ASSESSMENT OF THE RISKS AND BENEFITS

Mark Scrutton, Clara Lowy*, Geraldine O’Sullivan.

Departments of Anaesthesia and Endocrinology*, St Thomas’ Hospital, London SE1 7EH.

Labor, Metabolism, Nutrition, Aspiration.

INTRODUCTION: Eating in labor has been discouraged in most delivery units since the 1950s in order to reduce the morbidity and mortality caused by maternal aspiration of gastric contents. In the past decade deaths from maternal aspiration have become extremely rare, in part perhaps because of changes in anesthetic technique and the introduction of HZ receptor antagonists which may have obscured the importance of nil-by-mouth policies.’ As a result, many midwives and maternal pressure groups are demanding a more liberal approach to eating in labor. They argue that the physiological and psychological benefits of allowing mothers to eat in labor outweigh the potential risks2 METHODS: With Ethics Committee approval and following informed consent, women presenting in early labor (cervical dilatation < 5cm) were stratified by parity and induction and randomised to receive either a light standardised low fat diet (Groupl) or water only (Group 2) during the rest of labor and assessed as follows: 1. Plasma beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and glucose were measured in early labor (Tl) and at the end of the fast stage (T2). 2. Residual gastric volume was assessed 45 minutes after delivery using an ultrasound scanner (Aloka SSD 620) to measure gastric antral cross-sectional area.’ Incidence and volume of vomiting within an hour of delivery were recorded. RESULTS: 1. There were no differences between the groups in the time of entry into the trial or in the length of the first stage. By the end of the fast stage of labor (T2) plasma BHB (p<O.OOl) and NEFA (p<O.OOS) had increased and plasma glucose (pcO.01) had fallen significantly in the starved group (Gp 2) (Table 1).

Table 1: Mean plasma concentrations of BHB, NEFA and glucose (mmol/l):

BHB NEFA Glucose Tl n Tl T2 Tl T2

Group 1 (n=ZS) 0.32 0.16 0.92 0.81 4.65 5.47 Group 2 (n=28) 0.26 0.53 0.97 1.21 4.91 4.74

2. Gastric volumes: Group 1 had a significantly greater mean gastric antral cross-sectional area (p<O.O05) after delivery. Furthermore, the pregnant women who were allowed to eat were more likely to vomit, and vomited significantly greater volumes (pcO.01) (Table 2):

Table 2: Antral cross-sectional area (mean), percent of women vomiting and volume of vomit (median):

Group 1 (n=30) Group 2 (n=29)

Antral x-section area % Vomiting 7.10 cm’ 37% (1 l/30) 4.75 cm* 17% (5/29)

Volume of vomit 400ml 1 Oml

CONCLUSIONS: We have found evidence that allowing women in labor to eat reduces the plasma levels of ketones and non- esterified fatty acids which, it has been suggested, may be of physiological benefit to the progress of labor.4 However these same women have increased gastric volumes suggesting that liberal eating policies in labor should be approached with caution. REFERENCES: 1. Department of Health and others. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1988-1990.

London: HMSO, 1994. 2. Ludka L, Roberts CC. Journal ofNurse-Midwifery 1993; 38: 199-207. 3. Bolondi L, Bortolotti M, Santi V, Caletti T, Gaiani S, Labo G. Gastroenterology 1985; 89: 752-759. 4. Dumoulin J G & Foulkes J. Ketonuria during labour. Br J Obstet Gynaecol 1984; 91: 97-98.

37

AKlR AC-I-FORM

TITLE: Timing of Postpartum Sterilization: Complications and Cost-savings of Early Tubal Ligations

AUIHORS: A.C.H. Barton, M.D., F.J. Spielman, M.D., R. Onder, R.N., D.C. Mayer, M.D.

AFFILIATION: Department of Anesthesiology, University of North Carolina School of Medicine, Chapel Hill, N.C., 27599

Postpartum Sterilization, Timing

INTRODUCTION: The timing of performing postpartum sterilization is controversial. Many anesthesiologists and obstetricians require 8-12 hours after vaginal delivery prior to initiating an anesthetic. Their concerns include risk of aspiration, cardiovascular instability, unknown hemoglobin, and inability to obtain and document an informed consent. Other physicians wish to proceed without delay in order to discharge their patients quickly. The purpose of our investigation was to document the advantages and disadvantages of early and late tubal ligations. Since January 1, 1995 it has been the policy of the anesthesiology and obstetric and gynecology departments to perform postpartum sterilization as expeditiously as possible following vaginal delivery.

METHODS: After approval from the institutional review board, peripartum records of women undergoing postpartum sterilization for the period January 1, 1994, through September 1, 1995 were reviewed. Demographic data recorded included age, weight, ASA PS. Peripartum events recorded included anesthesia for delivery and tubal ligation, length of surgery,. interval from delivery to start of tubal ligation, incidence and treatment of hypotension, nausea, and vommng during surgery. PACU medications and problems were recorded as was the time interval from PACU discharge to leaving the hospital. Statistical analysis was accomplished using a Student’s t-test or chi-square test, as appropriate. A p value of less than 0.05 was considered significant.

RESULTS: 153 peripartum records were reviewed. 68 patients (45%) had their tubal ligations within 8 hours after delivery; the mean interval was 3 hours (range 0.4-7.8). 85 patients (55%) had their tubal ligations more than 8 hours after delivery; the mean interval was 18.8 hours (range 8.1-45.4). Demographic features of the two groups were similar. Table 1 summarizes some of the differences between the immediate group (< 8 hrs) and the delayed group (>8 hrs). No statistically significant difference existed between the two groups in the incidence of intraoperative and postoperative hypotension, nausea, vomiting, need for postoperative pain medications. Epidurals placed for labor and delivery failed to be adequate for tubal ligations in 20 and 37 percent of the patients undergoing surgery with short and long intervals respectively. Patients who were sterilized within 8 hours of vaginal delivery were more likely to spend less time in the hospital and be charged for fewer hospital days by the patient accounts office (p<O.O5). Tubal ligations were most commonly delayed because of a shortage of nursing personnel.

CONCLUSIONS: Postpartum sterilization performed within 8 hours of delivery is not associated with an increased frequency of peripartum complications. The significant advantage to early surgery is quicker discharge from the hospital with associated reduction in costs. The ability to perform tubal ligations 24 hours a day requires a strong commitment from the departments of anesthesiology, obstetrics and nursing that may not be possible in all hospitals.

38

THE PHYSICIAN FACTOR IN THE RELATIONSHIP BETWEEN EPIDURAL ANALGESIA AND CESAREAN SECTION FOR DYSTOCIA

S. Segal, MD, R. Blatman MD, M. Doble, BS; S. Datta, MD

Departments of Anesthesia and Information Systems, Brigham and Women’s Hospital, and Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Epidural, cesaxean section, dystocia

Introduction: The effects of epidural analgesia on the progress and outcome of labor, especially on the incidence of ce.wrean section (C/S) has become a matter of tremendous controversy in recent years. However, methodological difficulties have plagued both retrospective and the few prospective studies of this relationship. In particular. the inability to blind the obstetrician to the presence or absence of an epidural hopelessly complicates the interpretadon of any such study, since he cr she makes the decision regarding operative delivery. A “physician factor” in cesarean bii rates has been suggested in the past [l], but never in the context of the relationship between epidural use and C/S. We therefore undertook an analysis of epidural usage and C/S among obstetricians in a busy academic practice.

Methods: Patients and dura abstmction. We analyzed all records of admissions resulting in delivery between l/l/90 and 6/15/95 and identified a population of 18, 333 deliveries, sorted by practitioner, that met these criteria: admitted for an intended vaginal delivery, singleton vertex presentation, no prior C/s, and obstetrician with SO deliveries and a nonzem C/s rate. Deliveries were sorted by type of delivery (spontaneous vaginal, vacunm extraction, forceps, or C/S), within delivery mode by primary type of anesthesia (none, local, spinal, epidural, or general), and for C/S, by indication for operation (dystocia, fetal distress, nonreassuring fetal heart rate tracing, or other). For each practitioner, the total cpidural rate, the C/S rate for dystocia, and the C/S rate for all indications were calculated. For each practitioner and for the study population as a whole we also analyzed other factors that might explain variation in C/S rates observed betwcen obstetricians: maternal age, incidence of nullipatity. biiweight, incidence of induction of labor, and incidence of preterm or postdates infants. Data W&Sk Linear regression was used to assess the relationship between epidnral usage and C/S rate, where each data pair represented one provider’s experience. The relationships between C/s for dystocia and the other patient descriptors (all sorted by practitioner) were analyzed by linear regression. Finally, for the entire included patient population, not sorted by practitioner, we analyzed the associations between each of the above factors and C/S rates (total and for dystocia) by chi- squara

Results: There was no relationship between frequency of epidural analgesia and C/S for dystocia rate across practitioners (R2=0.019. p=.156; see Figure). There was also no relationship when the rate of C/S for all indications was analyzed (R2=0.026, p=.O93). Extremes of birthweight, extremes of gestational age, maternal age, nulliparity, and induction of labor were each associated with C/S for dystocia when analyzed on the entire patient population (p&O01 for each factor). When analyzed by the incidence of each of these factors within a given practitioner’s practice, only incidence of non-term gestation (R2=.157, p<.OOOl) and frequency of induction of labor (R2=.04, p=.O374) were significantly related to the practitioner’s C/S rate for dystocia. There was a highly siyifkant sssociation between practitioner identity and C/S for dystccia (X =464.1, pc.00001).

Discussion: These results suggest that the effect of epidural analgesia on the C/S rate for dystocia is at best very weak when compared to the influence of the practice style of the obstetrician. Our data is consistent with previous work demonstrating that variations in obstetrical practice may be associated with reduced C/S rates, despite increasing epidnral use rates [l-3]. Future research should investigate practitioners with low C/S rates despite high epidural rates, in order to identify practice patterns that foster this pattern.

References: [I] Goyert GL et al. New Engl J Med 1989; 320: 706-9. [2] Iglesias S et al. Can Med Assoc J 1991; 145: 145964. [3] Socol ML et al. Am J Obsrer Gynecol 1993; 168: 1748-1754.

39

Notes

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9621

TITLE: EFFECT OF pH ON TRANSFER OF NARCOTICS IN HUMAN PLACENTA DURING IN VITRO PERFUSION

AUTHORS: M.I. Zakowski MD, R. Krishna, PhD, G.J. Grant MD, H. Tumdorf MD

AFFILIATION:

Department of Anesthesiology, New York University Medical Center, New York NY 10016

drug clearance, meperidine, morphine, perfusion, placenta, sufentanil

INTRODUCTION: Narcotics are commonly used alone or in combination with local anesthetics for labor ’ analgesia and anesthesia for cesarean section. While maternal/fetal plasma ratios of most narcotics have been measured at delivery, no study has directly measured the effect of pH on placental transfer of liphophilic and hydrophilic narcotics in vitro. METHODS: After IRR approval, human placenta lobules were isolated and perfused with Media 199/Earle’s salts/dextran equilibrated with 02:CO2 9585%. The decidual plate (maternal side) was perfused at 12 ml/min using four blunt cannulae while the chorionic plate (fetal side) was perfused at 6ml/min via cannulae in the lobular artery and vein. Preliminary experiments showed that maternal to fetal placental transfer of sufentanil (SUP), meperidine (MEP) and morphine (MOR) remained unchanged when perfused singly or in combination. After 30 min stabilization. 50 nM of sufentanil (SUF), meperidine (MEP) and morphine (MOR) (with radiolabelled tracers) and 10 mg% of antipyrine (AP) and cieatinine (CR) were added to maternal (n=7) perfusate, pH 7.4. The fetal pH was adjusted every 30 min with HCl to obtain perfusate pH of 7.4, 7.2,7.0, 6.8,7.4 while maintaining a constant pC02. AP transfer is flow limited, and CR transfer is membrane limited,

thus both serve as reference compounds. 1 Narcotics were measured by scintillation counter and AP and CR by calorimetric assay. Clearance Index (CI =clearance drug/clearance AP) and Transfer Index (TI =clearance drug/clearance CR) were calculated. Results are mean f SE and analyzed using repeated measures ANOVA. RESULTS: Reduction in fetal pH significantly increased CI (pH 6.8-7.2. Figure) and TI (pH 6.8-7.0) ~0.05. At pH 6.8, CI and TI were 2-3x higher than at baseline pH 7.4 ~~0.05. DISCUSSION: The reduction in fetal pH increased maternal to fetal transfer of both liphophilic and hydrophilic narcotics up to 2-3 fold, a finding of potential clinical signficance. SUP, MEP and MOR have pKa of 7.9-8.5 and octanol:water coefficents at pH 7.4 of 1.4-1,527. The pKa, and thus percent ionization, may be of more significance to placental transfer than liphophilicity. REFERENCES: 1) Dancis J, Am J Obstet Gynecol 1988;159: 1435-9. This research was supported by the Foundation for Anesthesia Education and Research with a grant from Malinckrodt Anesthesiology.

pH= 2.0 1 * * *

sufentanil meph-idine morphine

Legend: Clearance index at pH 7.4-6.8. * - P 4.05 compared to baseline pH 7.4.

52

Chronic administration of the hormones of pregnancy renders female rats more sensitive to the hypotensive effect of intrathecal bupivacaine

A. Jayaram, H. Carp, D. Morrow

Department of Anesthesiology, Oregon Health Sciences University, Portland, OR 97201.

Hypotension, Intrathecal bupivacaine, Progesterone, Estrogen

INTRODUCTION: Spinal anesthesia produces more severe hypotension in pregnant women (1). Implicated in this as causative factors have been diminished venous return due to caval compression (2), exaggerated spread of blockade (3) and greater sensitivity to blockade (4). Quite apart from the role played by mechanical factors, progesterone in an in vitro study was shown to enhance bupivacaine induced nerve blockade (5). However no attempt has been made to investigate these putative causes coherently and systematically in an intact animal model. This preliminary study was designed to address the possible role of the hormones of pregnancy in the exaggerated hypotensive response to spinal anesthesia.

METHODS: Approval was obtained from the animal care committee at our instituition. Female Sprague-Dawley rats (240-290 g ) were studied. Under halothane anesthesia, chronically indwelling intmthecal (IT) and intraarterial (IA) (carotid) catheters were implanted. At least 5 days were allowed for recovery and only neurologically intact ammals were studied further. For the study, animals (n=7) were placed in restrainers and sufficient time given for blood pressure and heart rate to stabilize. Thereafter, a baseline period of 15 min was allowed for resting

nEVon~ nno(; , EST measurements. Then intrathecal bupivacaine 125 ug in 10 pl normal saline was given, followed by a period of 60 min during which blood pressure and heart rate were continuousiy monitored. Next, these animals were given daily subcutaneous injections of estradiol (lmgkg) and progesterone (50mgkg) for 5 days and then their hemodynamic response to IT bupivacaine 125 Pg was again studied. Data are expressed as mean *SD. Statistical differences were

APTEH PROG + tis~detected by repeated-measures analysis of variance.

RESULTS: IT bupivacaine 125 pg lowered mean blood pressure significantly more (~4.01) following hormonal treatment - 108f15 mm Hg to 67 f 17 mm Hg vs. 117 f 8.5 mm Hg to 98 *I6 mm Hg before such treatment. Though heart rate was lowered more by IT bupivacaine 125 pg following hormonal treatment - 405f33 bpm to 320 f 58 bpm vs. 434 lts8 bpm to 387k68 bpm before therapy - this was not statistically significant.

The administration of the hormones of pregnancy to non pregnant animals rendered them significantly more sensitive to the hypotensive effect of intrathecal bupivacaine. The results of this preliminary investigation indicate the importance of hormonal factors, independant of mechanical factors, in the exaggerated hypotensive reponse to intrathecal local anesthetics in pregnancy.

REFERFBCES : 1. J Clin Invest 1950 ; 29:1354.2. Physiology qf spinal unesthwia. Fourth edition.1993.3. Am J Obst Gynecol 101:792, 1968.4. Anesthesiology 721962, 1990.5. Anesthesiology 69: A676, 1988.

53

Many Dextrose-Free Intratbecal Anesthetics are Hypobaric Relative to Human Cerebrospinal Fluid

M.G.Richardson MD*, R. Wissler MD PhD*t

Departments of Anesthesiology* and Obstetics & Gynecologyt, University of Rochester Medical Center, Rochester NY 14642

Anesthesia: spinal; Local Anesthetics; Opioids: intraspinal

OBJECTIVES: The intrathecal (II) administration of dextrosefree local anesthetics and opioids continues to gain popularity in providing labor analgesia as well as surgical anesthesia for obstetric and non-obstetric procedures. Intratbecal solutions with densities less than 0.99940 (mean density of CSF - 3 SD) are considered hypobaric relative to CSF’. Hypobaricity of IT agents has been proposed as a mechanism to explain the high cephalad extent and great variability in sensory block produced by dextrose-free IT agents.2’3*4 Density differences as little as 0.00060 g I mL are thought to influence IT spread of local anesthetics.4 Several studies have reported the densities of dextrose-free local anesthetics’*’ and opioids’ measured at 37°C. However, the clinical applicability of these data are limited by the levels of accuracy5 and precision’ in the density measurements. In addition, neither report describes the accuracy or precision of temperature measurement, which is known to significantly influence density.4V5 We sought to accurately determine the density of preparations of dextrose-free local anesthetics, opioids, and combinations commonly used in the US. METHODS: Densities were determined directly using a density meter (DA-310, Mettler-Toledo, Inc., Hightstown, NJ) which employs a mechanical oscillation resonance frequency technique. Accuracy of density measurements was +/- O.tlOOO1 g/mL. Calibration using desiccated air and distilled water was performed prior to and after each measurement. Temperature was maintained with an electronically controlled thermostat at 37.00 +I- 0.01 “C. Density determinations were made on three samples from each lot evaluated. We tested multiple lots of 0.25% bupivacaine, 1.5% lidocaine with epinephrine (1:200,000), and 0.9% saline to evaluate inter-lot variation. As variation was negligible, a single lot was tested for the remainder of the solutions. Combinations of local anesthetics and opioids were prepared using the same syringes used in clinical situations. Three separate mixtures were prepared and tested once for each combination. Densities are expressed as mean (g/mL) +/- SD. RESULTS: Densities are tabulated below. Many dextrose-free solutions tested were found to be hypobaric.

Solution (Undiluted) Bupivacaine, 0.25% (Ash) Bupivacaine, 0.50% (Ash) Bupivacaine, 0.75% (Ash) Lidocaine (A&a)

1.5% with cpi 1:200,000 240, plain 2% with epi 1:200,000

Fentanyl, 0.005% (Abbott)

Sufentanil, 0.005% (Janssen) Morphine-PF, 0.1% (A&a)

0.9% saline (Abbott)

Density Solution (Combinations) Density 0.99912 +I- 0.00002 0.2mL 0.005% sufentanil + 1.8mL0.996 saline 0.99893 +/- 0.00004 0.99937 +/- 0.00001 OSmL 0.005% fentanyl + 0.5mL 0.9% saline 0.99635 +/- 0.00002 0.99964 +/- 0.00001 0.5mL 0.005% fentanyl + 1.5mL 0.9% saline 0.99775 +/- 0.00007

1mL 0.25% bupivacaine + 0.2mL 0.005% sufentanil 1.00019 +/- 0.00003 + 0.8mL 0.9% saline 0.99874 +/- 0.00005 0.99994 +I- 0.00000 1.00047 +/- 0.0ooo1

0.99333 +I- 0.00002 1mL 0.25% bupivacaine + 0.2mL 0.005% sufentanil 0.99822 +/- 0.00005 0.99332 +/- 0.00001 1mL 0.25% bupivacaine + 0.5mL 0.005% fentanyl 0.99722 +/- 0.00012 0.99983 +I- 0.00002 0.25mL (250 mcg) MS-PF + 0.5mL 0.005% F

+ 1.25mL 0.9% NS 0.99811+/- 0.00004

0.99951 +I- 0.00001 3mL 0.5% bupivacaine + 0.2mLO.l% MS-PF 0.99941 +/- 0.00001

DISCUSSION: We determined highly precise and accurate density values for many of the undiluted lT agents as well as combinations currently used in the US. Many of the solutions tested are hypobaric relative to CSF. These accurate density values should facilitate elucidation of the mechanisms underlying the behavior of some dextrose-free IT anesthetics. REFERENCES: 1. Horlocker IT, et al: Anesth Analg 76: 1015-1018, 1993; 2. Cohen S, et al: Anesth Analg 77:1155- 1160, 1993; 3. Blomqvist H, Nilsson A: Reg Anesth 14:195-198,1989; 4. Stienstra R et al: Reg Anesth 15:6-11, 1990; 5. Nicol ME et al.: Br J Anaesth 68:60-63, 1992

54

AB!3RACTFORM

TITLE: IS MATERNAL FEVER ASSOCIATED WITH THE ADMINISTRATION OF REGIONAL ANESTHESIA IN LABORING PATIENTS?

AUTHORS: J K Hartman, DJ Birnbach, B Shubin-Stein, DJ Stein, BI Danzer, A Grunebaum

I AFFILIATION: Department of Anesthesiology and Ob/Gyn, St. Luke’s_Roosevelt Hospital

Center, College of Physicians and Surgeons of Columbia University, New York

KlimwRm Fever, epidural analgesia, complications, combined spinal-epidural anesthesia

Introduction: It has been suggested that parturients receiving epidural analgesia for labor are at. increased risk of developing fever(l). In a recent article published in an Ob/Gyn newspaper, an obstetrician stated that 30% of his patients who received epidurals developed a fever of ~38°C and

that this effect of epidurals resulted in “interventions that may be expensive and unnecessary” (2). The aim of this study was to investigate the association between epidural anesthesia and maternal fever. Methods: Hospital records of all parturients who underwent vaginal deliveries between July 1, 1994-

June 30, 1995 at St. Luke’s_Roosevelt Hospital Center were evaluated. Patient records were divided into four groups: Those receiving labor epidurals (n= 411), those receiving combined spinal-epidural analgesia (CSE) with no use of the epidural catheter(n=285 ), those receiving CSE anesthesia with subsequent use of the epidural catheter (n=310) and those who did not receive a regional anesthetic for labor (n= 1090). The following information was collected: temperature at admission, maximum intrapartum temperature, type of analgesia administered, and duration of rupture of membranes. All temperatures were oral measurements. Temperatures were recorded on all patients every two hours

unless febrile( temperature of ~38°C). Any patient who had a fever prior to placement of the regional anesthetic was excluded from the study. Statistical analyses were performed using Yate’s corrected x2

analysis and Student’s t-tests, with a p value of ~0.05 considered significant. Results: TABLE I

1 lntrapartum Fever (238°C)

Regional Anesthesia No Regional Anesthesia p Value

87/1006 (8.6%) 82 / 1090 (7.5%) ns

TABLE II CSE / No CSE+ Epid. Epidural No Regional Epidural Infusion(285) Infusion(310) Infusion(411) Anesthesia(l090)

lntrapartum Fever(z38”C) 12 (4.2%) 37 (11.9%) 38 (9.2%) 82 (7.5%)

ROM to Delivery (hrs) 4.2 k 2.0 16.7 + 7.9 13.9 i 6.5 5.8 i 4.9

There was no difference in the proportion of patients who developed fever 238°C when those who received regional analgesia were compared with those who did not (p>O.O5). There was a significant difference in rupture of membranes (in hours) between the regional vs. no regional anesthesia groups(p<O.OOl).The proportion of fever in women who were given CSE without epidural infusion was lower than the proportion of fever in each of the other groups (pcO.01). Conclusions: Camann et al (3) reported that epidural anesthesia caused an increase in maternal temperature, but suggested that the increased temperatures were clinically insignificant. Our results confirm that regional anesthesia for labor does not cause clinically significant maternal fever. Possible explanations for our finding of a decreased incidence of maternal fever in patients receiving CSE without epidural infusion include: (1) The duration of labor in the CSE without epidural infusion group may have been SO short as to preclude the development of fever (2) epidural local anesthetics may alter thermoregulation to a greater degree than spinal opiates (3) spinal narcotics may be transiently protective against maternal non-infectious fever.

(1) Fusi Let al. Lancet 1989;1:1250 (2)ObGyn News, 1995 (3)Camann WR et al. Br J Anaesth 1991;67:565

55

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9626

THE EFFECT OF EPIDURAL OPIOIDS ON NEONATAL RESPIRATION

Jackie Porter MB BS, FRCA, Felicity Reynolds MB BS, MD, FRCA, FRCOG

Anaesthetic Department, St. Thomas’ Hospital, London, SE1 7EH, UK

Epidural Opioids, Neonatal Respiration

INTRODUCTION: The administration of systemic opioids to mothers in labor causes neonatal depression including respiratory depression’. Epidural analgesia using bupivacaine alone is associated with improved neurobehavioral scores’ and less respiratory depression3 in the neonate than systemic opioids. The addition of opioids to epidural infusions may reintroduce the problem of neonatal depression once more. We have therefore examined neonatal PC02 and PO2 and neurologic and adaptive capacity scores (NACS) to evaluate this.

METHODS: Following ethics committee approval 138 women requesting epidural analgesia in labor received a loading dose of plain bupivacaine. When pain free, women with a singleton fetus who had not received systemic opioids earlier in labor, if consenting, were randomized to receive an infusion of either bupivacaine 0.125% alone or bupivacaine 0.0625% with 2.5 ug.ml’ fentanyl. After delivery transcutaneous PO, (tcP0,) and PC02 (tcPC0,) were recorded every 10s until 90 min after delivery using a Novametrix Model 840-VFD Transcutaneous O,/CO, Monitor attached to the babies chest. Mean values for each minute were calculated and gradient and intercept were obtained from graphs of tcP0, and tcPC0, against time. Mean tcP02 and tcPC0, at 20 and 90 mins after delivery were also calculated. Ftmic acid-base status, Apgar score and NACS 2h and 24h after delivery were measured. Umbilical venous (UV) plasma fentanyl concentration was correlated with indices of neonatal respiration and welfare in the fentanyl group. RESULTS: 23 babies were delivered by cesarean section and were excluded from the study and one baby was withdrawn early in the study period. Neonatal weight and mode of delivery were similar in the two groups. There were no significant differences between the two groups for any of the indices of neonatal respiration (Table 1) or neonatal welfare. The mean (range) maternal dose of fentanyl was 184 (53-400) pg and the mean (range) UV fentanyl concentration was 0.075 (o-0.244) ng.ml’. Plasma fentanyl concentration did not correlate with any of the indices of neonatal respiration or welfare. Table 1: Neonatal respiratory gas status: Mean (SD).

tcpco, tcpo, Controls (n=60) Fentanyl(n=54) Controls (n=60) Fentanyl (n=54)

Intercept @Pa) 5.3 (11.0) 5.1 (8.2) 8.2 (15.7) 8.4 (19.3)

Gradient -0.07 (0.13) -0.03 (0.15) 0.14 (0.27) 0.08 (0.34)

20 min &Pa) 5.3 (8.7) 5.1 (8.6) 8.7 (14.6) 8.1 (14.4)

90 min @Pa) 5.1 (5.9) 5.2 (6.3) 9.3 (21.6) 8.7 (14.9)

CONCLUSIONS: The results suggest that fentanyl added to epidural bupivacaine infusions during labor does not depress neonatal respiration or adversely affect neurobehavioral scores and other indices of neonatal welfare. REFERENCES: 1. Brice JEH, Moreland TA, Walker CHM. Arch Dis Child 1979; 54: 356-361. 2. Corke BC. Anaesthesia 1977; 32: 539-543. 3. Thalme B, Belfrage P, Raabe N. Acta Obstet Gynec Stand 1974; 53: 27-35.

65

ABslRAcrFoRM

I 1 TITLE: Regional Anesthesia and External Cephalic Version: A QUALJTY ASSURANCE STUDY

AIJIHORS: R. Patel, MD., S. Ramenathan, M.D.

J

AFFILIATION:Department of Anesthesiology, Magee-Womens Hospital, University of Pittsburgh School of Medicine, 300 Halket St., Pittsburgh, PA 15213.

KEYQQUB External cephalic version, Regional anesthesia, Hypotension, Tocolysis

Introdwtlon: External cephalic version (ECV) when suxe&ul may decrease the need for cesarean se&ion (CS) in managing breech presentation (1). Although several articles have discussed the obstetrical management of ECV, only a few articles discuss the anesthetic management. (2). Methodr: The Quality Assurance department of our institution conducted a focused study of all ECV procedures performed between the years 1992-l 994. One hundrexl and twenty three records were identified and the following data were obtain& demographic data, ECV success rate, type of anesthesia, tocolytic therapy, incidence of complications, and CS rate. Patients were divided into two groups, those receiving regional anesthesia (RA; n=45), and those receiving no anesthesia for ECV (controls; n=78). F’re- block i.v. hydration and left uterine displacement were used. The use of tocolytics was left to the choice of the obstetrician. Results were expressed as mean f 1 SD a@ analyzed using X2 analysis and t-test at p < 0.05. Results: Results are summarized in the Table. The success rate in the regional anesthesia group was significantly greater than

that in the control group. despite more &equent use of tocolytics in the control group. The CS rate in the RA group was lower than that in the control group. Hypotension requiring ephedrine therapy occurred more &equcntly in the RA group. There was also an increased incidence of fetal bradycardia in the I& group but the number of CS performed for fetal distress was not signi6cantly different between the two groups. Parity, gestational age, and body weight did not significantly differ between the groups. Conclurion: Our data show that regional anesthesia is associated with higher success rate ofECV and decreased CS rate for breech presentation. However, it is associated with an increased incidence of hypotension and transient fetal bradycardia

Variable

Version successful

Fetal bradycrrdia

Regional Control p value

n=45 % ll=78 %

29 64 32 41 0.01

13 28 10 12 0.01

Hypotension 21 47 0 0 0.000

Ephedrine 12 27 0 0 0.000

cs 13 29 41 52 0.008

ToeOlyth 19 42 71 91 0.000

CS for fetal dbtresa 1 2 1 1.3 NS

Parity=0 23 51.1 37 47.4 NS

Parity >o 22 I 48.9 41 I 52.3 NS

Gestational age (Wks) 37.2H 37.4h1.6 NS

Weight (Kg) 77.2zt14.6 74.4*19.4 NS

Referencea: 1. Zhang ct al: Obstet and Gynecol82: 306-3 12,1993 2. Carlan S, et al: An&h halg 79: 525-528,1994

66

Sterility of Emergency Anesthetic and Resuscitative Drugs in the Obstetric Operating Room

R.P. Driver, Jr., M.D., I. Snyder, Ph.D., F.P. North, M.D., T.J. Fife, D.O.

Department of Anesthesiology, Department of Microbiology and Immunology, West Virginia University, Morgantown, WV.

Bacterial Contamination, Thiopental, Succinylcholine, Ephedrine, A&opine, Lidocaine, Oxytocin

INTRODUCTION Tbe constant threat of impending cesarean sections mandates that induction and resuscitative drugs be immediately available in the operating theater. However, recent guidelines promulgated by the Anesthesia Patient Safety Foundation (APSF) suggest that previously aliquoted drugs remain in syringes for no longer than 24 hours. The purpose of this study was to examine the potential for bacterial contamination and the duration of sterility of emergency drugs in a clinical environment.

METHODS: Each of the following 6 drugs, Sodium ThiopentaI, Succinylcholine Chloride, Ephedrine Sulfate, Atropine Sulfate, Lidocaine Hydrochloride, and Oxytocin Injection, USP, were drawn into 24 sterile syringes under normal clinical conditions (total 144 syringes). They were then covered with clean towels and stored on a table in the operating room. Then serially for 7 days, 3 different syringes were randomly selected from the pool of 24 syringes containing the same drug and 1Sml was decanted from each. This material was then plated onto 3 separate blood agar plates (0.5 ml/plate) for a total of 9 plates and 4.5mls cultured volume for each drug/day. All inoculations were performed inside a laminar flow hood and plates were incubated in a 5% CO* incubator at 35°C for 72 hours. Control plates were exposed in the obstetric OR and in the lruninar flow hood. The number of colony forming units (CRT’s) were quantified and identified for genus and/or species.

RESULTS: Each of the 6 drugs supported the growth of one or more of the following bacterial contaminants (staphylococus epidermidis, micrococci, alpha-hemolytic streptococci) or the fungal contaminant penicillium. These results are presented in Table 1. Colony counts did not increase with longer incubation periods.

Table 1: Colony Forming Units Isolated from Drug Solutions at Daily Intervals

SIP-sodium thiopental; Sch-succinylcholine; EPH-ephedrine; Atr-atropine; Lid-lidocaine; Oxy-Oxytocim (B)-bacteria, (F) Fungi

CONCLUSIONS: Drugs drawn into sterile syringes and stored at room temperature in an operating room environment for up to 7 days showed random growth of bacterial and fungal contaminants. Such growth was independent of the incubation period and consistent with previously published work.1*2 Our findings and those of Wong and Ohsuka with the drugs sodium tbiopental* and lidocaine2 support our contention that the guidelines promulgated by APSF to change syringes every 24 hours may be too stringent.

REFERENCES: *Wang et al 1992; 20hsuka et al 1994.

67

BRAIN CHANGES ON MRI IN PRE-ECLAMPSIA: EDEMA OR ATROPHY?

A. HOLDCROFT MD. FRCA., J.V HAJNAL PhD., A.OATRIDGE DCRR. MSc., G.M. BYDDER FRCR

DEPARTMENT OF ANAESTHESIA AND THE ROBERT STEINER MAGNETIC RESONANCE UNIT ROYAL POSTGRADUATE MEDICAL SCHOOL, LONDON W.12 OHS U.K

MAGNETIC RESONANCE IMAGING, PRE-ECLAMPSIA, BRAIN

INTRODUCTION: Central nervous system symptoms and signs accompany pre-eclampsia, especially when severe.These include reflex irritability and visual disturbances and may be premonitory to eclamptic convulsions. These features are widely believed to be due to cerebral edema and hemorrhage, which are frequently reported with Computed Tomography and Magnetic Resonance Imaging(MRI) ‘. We wished to study patients with pre-eclampsia before and after delivery to determine changes in brain size using accurately registered MRI.

METHODS: Four pregnant women with varying degrees of pre-eclampsia gave informed consent for MRI of their head and neck.They were scanned within two weeks of their delivery and then once or twice six weeks or more after delivery. Subvoxel registration of serial T,weighted images was used to detect changes to the brain and its surrounding tissues and fluids2 .The women were positioned with the head supine but with a comfortable tilt to the pelvis when pregnant.

RESULTS: On two separate occasions all four patients had recorded diastolic blood pressures of at least 1OOmmHg as well as proteinuria in the two weeks before delivery. Three patients also showed edema.The other patient (A) was being treated with diuretics for chronic renal failure and essential hypertension. Patient B had mild hypertension which settled with rest and no treatment, and was delivered at term. The other women were delivered between 30 and 33week’s gestation, two for central nervous system symptoms (patients A and C) and one (D) because of fetal distress. The serial MRI images were matched precisely and subtraction images were obtained. A significant increase in brain size was observed in the postpartum images in all four patientsThese findings were consistent with cerebral atrophy (reversible) and not edema, prior to delivery. A further small increase in brain size was seen on the repeat scan 5 to 10 months after delivery.

CONCLUSIONS: MRI subtraction images from serial scanning have detected significant reductions in brain size in the last trimester of pregnancy in women with mild to severe pre-eclampsia. These changes were not related to therapy and were partially reversible in the postpartum period. The primary change in pre-eclampsia may be ischemia due to hypovolemia and vasospasm with cerebral edema only appearing as a late secondary phenomenon.

REFERENCES: 1. Digre KB, Vamer MW, Osbom AC?, Crawford S. Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia. Arch Neurol 1993;50:399-406

7 _. Bydder G M. Detection of small changes to the brain with serial magnetic resonance imaging. Br J Radiology 1995;68:1271-1295

68

OBSTETRIC! ANESTHESIA: USA

Charles P. Gibbs, M.D. Denver, Colorado

ODUCTION.

In 1981 obstetricians and anesthesiologists were surveyed to determine personnel and methods used to provide obstetric anesthesia in this country, as well as their subjective opinions why anesthesiologists were not more involved in obstetric anesthesia.’ With support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists, the survey was expanded and practitioners were asked to respond using data from 1992. Preliminary results are presented here.

Comments from the A.S.A. Committee on Obstetrics and the A.C.O.G. Committee on Maternal-Fetal Medicine were incorporated into the original survey instrument to include newer issues and concerns while allowing comparison with data from 1981. The American Hospital Association registry of hospitals was used to provide demographic breakdown by number of births (Stratum I = > 1500 births, Stratum II = 500-1500 births, and Stratum III = < 500 births) and U.S. Census region. A stratified randomized sample of 1,400 hospitals was selected. Two copies of the survey were sent to the administrator of each hospital: one for the chief of obstetrics and one for the chief of anesthesiology.

RESULTS

Compared to 1981 data, there was an overall reduction in the number of hospitals providing obstetric care (from 4,163 to 3,545), and the decrease occurred in the smallest units (56% Stratum III hospitals in 1981 versus 45% in 1993). More regional anesthesia was provided in 1992 than 1981 resulting in a marked decrease in the use of general anesthesia for cesarean section. More women received some type of labor analgesia, and more epidural analgesia was used in all size hospitals. Interestingly, the new technique of spinal analgesia was used about equally in all hospitals surveyed. This involved approximately 4% of parturients.

Number of AIL4 Hospl@s by Nhnber of Deliveries

Size 2lx!Q 500-1499 1511Il Total 1981 573 (14%) 1249 (30%) 2341 (56%) 4163 1993 824 (23%) 1118 (32%) 1603 (45 X) 3595

. Anesthesia for C!esarw&&m

1981 vs. 1992

siz.c 2L5Ml 500-1499 a!JQ Total Epidural (%) 29156 16145 12132 21144 Spinal (%) 33133 35138 37148 34140 General( %) 35112 45118 46120 41117

69

esia foi Labor 1981 vs. 1992

Size > 500-1499 15M Total None (%) 27112 33115 45l38 32122 Parenteral (%) 52150 53163 37147 49154 Spinal (%) 4 5 3 4 Epidural (%) 22149 12127 9114 16129

. . Newborn Resuscltat o Vaginal Delivery - Perso;: (X)

1981 vs. 1992

Law Anesthesiologist 1817 CRNA 514 Obstetrician 37114 Pediatrician 36147 Family Practitioner 2 RN 22 Other 415

small All l/2 12114

1217 916 32116 37119 13l15 28129

37 17 13 17

43lll 1419

Newborn Resuscitation Cesarean Section - Personnel ( W)

1981 vs. 1992

Anesthesiologist CRNA Obstetrician Pediatrician Family Practitioner RN Other

l.eaEis small AA 2215 1214 1915

2/o Ill13 415

4/l 212 512

70172 46136 64l59

2 31 13

22 13 17

2/s 24111 719

CONCLUSIONS

Additional results from the survey will be presented at the meeting. From the initial data: (1) General anesthesia is being used much less for cesarean sections; (2) In smaller hospitals, up to 66 % of anesthetics for cesarean section are provided by nurse anesthetists supervised by an obstetrician or practicing independently, and (3) Anesthesiologists are less involved in newborn resuscitation, with nurse clinicians increasingly utilized at larger hospitals.

REFERENCE

1. Gibbs CP, et al: Obstetric Anesthesia: A national survey. Anesthesiology 65:298-306, 1986.

70

PROPHYLACTIC EPHEDRINE WITHOUT FLUID LOADING LEADS TO FETAL ACIDOSIS FOLLOWING SPINAL ANESTHESIA FOR CESAREAN SECTION.

CC Rout, DA Rocke, E Gouw.s.*

Department of Anaesthesia, University of Natal and *MRC, Institute for Biostatistics, Durban, South Africa.

Anesthesia spinal, hypotension, intravenous fluids, ephedrine.

INTRODUCTION. Intravenous fluid preload and ephedrine infusion are both used to prevent hypotension due to obstetric spinal anesthesia. Recently the value of volume preloading has been questionedoV2) and the current trend is towards the use of ephedrine infusion. However, studies of prophylactic ephedrine have invariably been in subjects who have also been volume preloaded and there is insufftcient information relating to the effects of ephedrine as the sole prophylactic method. The purpose of this study was to determine the relative efficacy of the two methods in preventing hypotension and whether a combination of methods is more effective than either method alone. METHODS. Following institutional ethical approval patients with uncomplicated term pregnancies scheduled for elective cesarean section under spinal anesthesia were randomly allocated to four Groups. Group A received no prophylaxis (controls), Group B received intravenous ephedrine administered by a syringe pump at a constant rate of 2.5 mg/min following spinal injection until delivery, Group C received intravenous modified Ringer’s lactate 20 ml/kg preload over lo-20 mins before spinal injection, Group D received both fluid preload and ephedrine infusion. Spinal anesthesia was administered in the sitting position using hyperbaric bupivacaine OS%, 2.2. ml, and fentanyl 15 mcg. Heart rate and blood pressure were automatically recorded at one minute intervals following spinal injection. Hypotension was defined as a decrease in systolic pressure to less than 100 mmHg and to less than 80% baseline value, and was immediately treated with intravenous ephedrine 5 mg every minute until reversed. In the event of hypertension in Groups B and D, the ephedrine infusion was discontinued if the systolic pressure increased to above 170 mmHg. RESULTS. Ephedrine infusions were stopped in 2 subjects in Group B (7%) and 3 subjects in Group D (9%) due to unacceptable hypertension. The incidence of hypotension tended to be lower in Group D compared to Groups A, B and C (p < 0.15) and the incidence of hypotension of three or more minutes duration was lower in Groups B and D (p = 0.08). Umbilical arterial pH was significantly @ = 0.03) lower in babies of Group B.

n

Hypotension (%, 95% CI) Ephedrine, mg (SD) Hypotension > 2 min(%, 95% CI) Umbilical Arterial pH (SD) UA base deficit, mmol/l (SD)

: p < 0.05.

Group A Group B 26 27

13(50,29.9 - 70.1) 13(48,28.7 - 68.1) 20.4(10.5) 13.1(7.0) 11(42,23.4-63.1) 6(22, 8.6 - 42.3) 7.26 (0.04) 7.20 (0.08)* 2.6 (1.54) 5.1 (3.6)*

Group C Group D 26 33 14(54, 33.4 - 73.4) 9(27, 13.3 - 45.2) 18.2(6.7) 15.0(7.9) 1 1(42,23.4 - 63.1) 6(18,7.0 - 35.5) 7.26 (0.06) 7.23 (0.09) 2.6 (2.35) 4.3 (3.4)

DISCUSSION. These preliminary results confirm the inadequacy of fluid preloading alone seen in other studies(” *) and suggest that ephedrine infusions are more effective in preventing hypotension. However the beneficial effects seen in previous studies of prophylactic ephedrinec3, 4, may have been in part due to combination with volume preload. Ephedrine infusions alone may cause fetal acidosis and the current recommendation should be to preload patients before their use. REFERENCES : 1. Rout CC et al. Anesthesiology. 1993; 79: 262-269.

2. Jackson R et al. Br J Anaesth. 1995; 75: 262-265. 3. Gutsche BB. Anesthesiology. 1976; 45: 462-5. 4. Kang YG et al. Anesth Analg. 1982; 61: 839-42.

133

AEsIR4cmcRM

TITLE: HAEMODILUTION FOR CAESAREAN SECTION

AUlHOR!3: C.S. Grange, MBBS, M.J. Douglas MD, T. J. Adams, MBBS, L.D. Wadsworth, MBBS

AFFILIATION: Departments of Anaesthesia and Hematopathology, The University of British Columbia and BC Women’s Hospital and Health Centre Society, Vancouver, B.C.

Haemodilution, Pregnancy

INTRODUCTION: Concern over transmissible disease has increased interest in ways to minimize homologous transfusion during elective surgery’. Although haemodilution (HD) has been reported previously ’ this technique has not been described in parturients. This study was designed to assess the safety and efficacy of preop HD in women with placental and uterine anomalies at risk for haemorrhage during caesarean section (c.s.). METHOD: Following institutional approval and informed consent, 15 women (ASA I-II, preop Hgb > lOOg/l), undergoing C.S. were studied. Using standard, aseptic donation technique, l-2 units of blood were removed preop and replaced with an equal volume of PentaspanO. ECG, SaO, NIBP and FHR were continuously monitored during HD. HGB was measured preHD, postHD, pretransfusion, post transfusion and 24 hrs postoperatively. Umbilical blood gases, Apgar scores were recorded. The blood collected was reinfused at the end of surgery or when required.

All were stable hemodynamically and had no FHR RESULTS: Table I includes patient details. abnormalities during I-ID. One patient received homologous blood (intraoperative blood loss 3L, no previously donated autologous blood (PAB) available) and only three required PAB. Umbilical blood gases were normal and all 5-min Apgar scores were >7. DISCUSSION: This study suggests that I-ID is well tolerated in parturients undergoing C.S. The combination of I-ID and PAB or only HD ( where PAB is prohibited due to time limitations), may reduce homologous transfusion, REFERENCES: 1. Can J Anaesth 1994;41:R52-R61 2. Anesth Analg 1994;78:932-7

Hemoglobin ‘601

I 13 140.

Weight kg (range) 80 2 ($7.5-162)

Estimated blood loss mls 1194 1x-

(range) (600-3000) 100~ T

# wth PAB 8 80.

I&=-

# given PAB 3 ‘I

U given homologous blood 1 6OJ

40. ~.~ Ll= L 11 Prek”L”tb” Pretrazlmm 24 h,S PoTtoperative

PoSthemOdll”tmn Pos”ra”sfusio”

134

AESIRACT FORM

I TITLE:

EPHEDRINE RESISTANCE IN THE COCAINE-POSITIVE PARTURIENT: PREVALENCE AND TREATMENT

AUIHORS: DJ Birnbach, DJ Stein, BI Danzer, JK Hartman, DM Thys

AFFILIATION: Department of Anesthesiology, St. Luke&Roosevelt Hospital Center College of Physicians and Surgeons of Columbia University, New York

KEywoRDs: Cocaine, hypotension, ephedrine, phenylephrine

Introduction: Previous data have suggested that regional anesthesia may be safely administered to the cocaine-using parturient (1). However, the effectiveness of ephedrine in treating the hypotension that may occur following initiation of epidural and spinal anesthesia in these patients has not been evaluated. The aim of this study was to determine if ephedrine was able to reverse regional anesthesia-induced hypotension in the cocaine-positive patient. In addition, we sought to determine if hypotension unresponsive to ephedrine could be successfully treated with phenylephrine.

The anesthesia records of 240 unregistered patients who underwent cesarean section Methods: under regional anesthesia at St. Luke’s_Roosevelt Hospital Center between 1988-1993 were retrospectively evaluated. When hypotension occurred after initiation of regional anesthesia, the amount of ephedrine administered and the results of the ephedrine administration were evaluated. Only hypotension that occurred prior to the start of surgery was evaluated, so that surgical factors, such as blood loss, would not be studied. Data were analyzed using Student’s t-test and Yates corrected x2 with ~~0.05 considered significant.

Results: Cocaine-positive urine toxicology results were found in 145 (80%) of the 240 anesthesia records evaluated. No cocaine-negative patient required more than 15 mg of intravenous ephedrine to restore systolic BP to >I00 mm Hg prior to the start of surgery. However, 20 mg of IV ephedrine was insufficient to raise the systolic BP to > IOOmm Hg in 32% of the cocaine-positive patients. Six cocaine-positive patients required phenylephrine administration to restore blood pressure when there was no response to 50 mg intravenous ephedrine. No cocaine-negative patient required

phenylephrine.

Maternal Parity Pts. receiving Patients not responding to 20

age ephedrine mg ephedrine Cocaine (+) 29.1 f 5.0 2.2 +/- 1.3 100 (68.9%) 32/I 00 (32%) n= 145

Cocaine (-) 25.2 + 1.3 1.3 +I- 1 30 (31.5%) o/30 (0%) n= 95

P <O.OOl ~0.001 <O.OOl <O.OOl

Conclusions: Our findings indicate that hypotension requiring pharmacologic treatment occurs more frequently in cocaine-using patients than in non cocaine-using patients receiving regional anesthesia for cesarean sections. In addition, our data demonstrate that ephedrine may be ineffective in restoring blood pressure among cocaine-positive patients who become hypotensive after initiation of regional anesthesia. Ephedrine-resistance may occur due to a depletion of norepinephrine in these patients. In all cases where the patient did not respond to a large dose of ephedrine, phenylephrine was effective in restoring blood pressure. Based on the findings of this study, phenylephrine may be useful when treating ephedrine-resistant hypotension in pregnant patients using cocaine.

I 1. Birnbach DJ et al. Anesthesiology 81, Al 183,1994

135

TITLE: Intrathecal Neostigmine for Post Cesarean Section Analgesia: Dose Response

AUTHORS: JA Krukowski, MD, DD Hood, MD, JC Eisenach, MD, KA Mallak, MD

AFFILIATION: Department of Anesthesia, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1009

KEYWORDS: Neostigmine, Morphine, Analgesia, Nausea, Spinal, Epidural, Cesarean section

INTRODUCTION: Intrathecally administered neostigmine produces analgesia, but also side effects, particularly nausea, in volunteers (1) and following minor surgery (2). However, the dose response for analgesia and side effects of intrathecal nmtigmine has not been determined for women having cesarean section. The purpose of this study was to define intratheeal neostigmine’s efficacy and side effects in patients following elective cesarean section. METHODS: Following Institutional Review Board approval and written informed consent, 24 ASA physical status 1 women scheduled for elective cesarean section under epidural anesthesia were studied using a placebocontrolled, open label, dose escalation design. Six patients in each group received intrathecal placebo, then neostigmine 10, 30, and 100 pug in 1 ml of D$IS. Fetal Heart Tracings (FHR) were recorded continuously from 15 mm before the procedure until transporting the patient to the operating room. FHR tracings were analyzed by an obstetrician blinded to drug treatment. Uterine displacement was assured at all times until delivery. The epidural space was located with the patient in a lateral decubitus position and a spinal needle placed through the epidural needle into the intrathecal space. The study drug was then injected intrathecally, and an epidural catheter passed for subsequent local anesthetic administration. Patients were then placed supine for 15 min, followed by epidural admin&ration of 2% lidocaine containing 3 @g/ml epinephrine and bicarbonate 1 mEq/ml. Intravenous morphine was administered in the operating room and the recovery room upon the patient’s request for pain relief. Postoperative analgesia was provided for with a Patient Controlled Analgesia (PCA) pump using morphine. Verbal pain, nausea, and sedation scores (O-10 point scale) were assessed at multiple time points. Nausea was treated in a standardized fashion as specified in the protocol. Data were analyzed with 2-way ANOVA for repeated measures and pairwise multiple comparisons for significant ANOVA tests. P < 0.05 was considered significant. RESULTS: Cumulative morphine use was significantly reduced following intrathecal neostigmine (P<O.O03, see Figure). All neostigmine doses associated with similar postoperative morphine requirements. Total morphine use (intraoperative and postoperative for 24 hours) was 82*7 mg for women receiving intrathecal placebo and averaged 50 f 8 mg for women receiving intrathecal neostigmine. Sixteen percent of women receiving intrathecal placebo or neostigmine 10 Fg required more than 1 intervention for nausea, while 50 % and 66 % of patients receiving either 30 or 100 pg of neostigmine respectively, required multiple pharmacologic treatments for nausea. APGAR scores are similar in all groups. FHR analysis will be presented. CONCLUSIONS: Studies in human volunteers demonstrated no I kag n f ‘ I ,* 1‘ 4, 2, 24 significant analgesia following intrathecal neostigmine in doses <50 pg Time (Intla-cQ, RewWy worn, o( Han Pcc&cemdly)

(1). In contrast, these data in patients receiving cesarean section, suggest that analgesia may occur at considerably lower doses, perhaps even 10 wg. This is in agreement with results in animals which demonstrate greater potency of intrathecal neostigmine in the acute postoperative period than in the absence of pain (3). This study suggests that intrathecal neostigmine 10 Qg may produce postoperative analgesia, reduce morphine requirements, and have associated risks for nausea which are similar to placebo. Neostigmine doses greater than 10 pg had increased associated nausea and did not improve analgesia when compared to neostigmine 10 pg. Larger prospective studies are,planned to confirm these preliminary findings. REFERENCES: 1. Hood DD, et al. Anesthesiology 82:331-343, 1995; 2. Lauretti GR, et al. Reg Anesth 20:60, 1995 (Abstract) 3. Bouaziz H, et al. Anesth Aualg 80: 1140-l 144, 1995 Funded in part by the 1995-96 IARS Clinical Scholar Grant.

136

Remifentanil: an Ultra-Short Acting Opioid in Obstetric Anesthesia

R Kan, S Hughes, M Rosen, C Kessin, P Preston, J Johnson, L Johnson

University of California, San Francisco, CA and Kaiser Hospital, San Francisco, CA

Opioid, remifentanil; placental transfer; drug metabolism; newborn outcome

Introduction: Remifentanil (R) is a new, ultra-short acting phenylpiperidine p specific opioid receptor agonist. It is metabolized by nonspecific blood and tissue esterases and has a short elimination half-life (t112 = 8-12 min.). The

context sensitive half-life (50% decrease in plasma level after stopping infusion) is 3 min vs. 47 min for alfentani1.l Animal studies suggest a limited placental transfer of R. The objective of this study was to evaluate placental transfer of R, newborn effects, and effectiveness of analgesia after IV infusion as an adjuvant to epidural anesthesia for cesarean section (C/S). Methods: Thirty-nine parturients presenting for non-emergent C/S were studied after informed consent. All patients received epidural anesthesia with 2% lidocaine with 1:200,000 epinephrine. The remifentanil group (RG, n=19) received 0.1 @kg/min IV and 2ml of saline added to the epidural anesthetic. The fentanyl group (FG, n=lO) received fentanyl 100 pg (2ml) added to the epidural anesthetic and D5W IV. The placebo group (PG, n=lO) received saline

2ml added to the epidural anesthetic and D5W IV. For additional analgesia, IV opioids were available: fentanyl 50 pg/ml (FG and PG) or R, 16.7 pg/ml (RG) in a syringe labeled “narcotic”. The patient’s anesthesiologist, blinded to the drugs would initiate the infusion and give additional IV drugs as needed.

Pain and sedation assessments were made at predetermined times: 15 min prior to initiation of infusion, skin incision, bladder retraction, delivery, uterine repair/exteriorization, and 5 and 10 min after infusion stopped. Cardiovascular parameters and respiratory rate were measured throughout as well as side-effects. At delivery, a maternal artery (MA) and umbilical artery (UA) and vein (UV) sample were drawn for drug levels and blood gas analyses. Apgar scores (1,5,10,20 min) and NACS (30 and 60 min) were performed. The parturient and neonate were observed for 24 hr or longer if necessary for side effects and requirement for subsequent therapy.

: l Remifenatanil . 2.0 _

. l

l 0.0 0.2 0.5 0.8 1.0 1.1

Wcxmcmdm(W)

Results: The figure represents the R cont. (UV vs. MA) at delivery with a UV/MA ratio of 0.98 and clearance of 101 + SD 79 ml/min/kg. Mean MA R was 1.19 ng/ml with a mean UV of 0.76 ng/ml and UA of 0.25 ng/ml. Metabolite data (GR90291) will be presented. All parturients received effective anesthesia and were satisfied. However, two parturients in the RG experienced respiratory depression (RR = 10-l 1 breathsimin) with changes in MA and UV blood gas values at delivery. The Apgars and NACS results were similar among the three groups but NACS were statistically lower at 60 min in the R group. Conclusion: R easily crosses the placenta but continues to be rapidly metabolized by the fetus with a UA/UV ratio of 0.3 1. Significant maternal analgesia and sedation with respiratory changes occur at 0.1 ng/kg/min dose but the newborns were similar in all groups. Further investigation of dose requirements is suggested as well as evaluation for potential use in labor or general anesthesia in obstetrics. This rapidly metabolized opioid may find a unique place in obstetric anesthesia. Reference: Kapila A, et al: Anesthesiology 83:968-975, 1995.

137

Maternal and Fetal Blood Gas Data

PH pa02 paco2

MA(rk9) 7.4EO3 166.4-127.6 uv (MO) 7.3-E&09 26.6M.4

30.&6.1 40.6zt6.6

Aemifenianil MA (rkl9) 7.37*.03* w (rid9) 7.26506

170.s39.9 35:?5:;* 30.6557 *

MA= maternal artery, W= umbilical vein. * P<.O5 one wav ANOVA with Bonferroni correchon aphsl the pkib group.

smithbe

9638

‘AmIRAcrFoRM I I

TITLE: Effects of Position During Induction of Combined Spinal Epidural Anesthesia for Cesarean Delivery

AUlHORS: E.M. Yun, M.D., A.C. Santos, M.D., G.F. Marx, M.D.

AFFILIATION: Departments of Anesthesiology, Obstetrics and Gynecology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461

Combined Spinal Epidural Technique, Position, Hypotension

INTRODUCTION: Combined spinal epidural (CSE) technique has become popular for cesarean delivery. Either the sitting or the lateral recumbent position may be used for induction. However, there has been concern that a delay in assuming the supine position (due to epidural catheter placement) may increase the incidence of hypotension after intrathecal injection of local anesthetic when CSE is performed in the sitting position. The current study was undertaken to compare the incidence and severity of side effects, such as hypotension, when CSE is induced in the sitting versus lateral recumbent position.

METHODS: Following 1P.B approval, healthy parturients having an elective cesarean delivery were randomly assigned to either the sitting or the lateral recumbent position for CSE placement. All received 1000 mL of lactated Ringer's solution in the 10 min preceding induction. The epidural space was identified using loss of resistance. Then, an intrathecal injection of hyperbaric bupivacaine (12 mg) and fentanyl (10 ,sg) was performed using a 5 inch 24 gauge Gertie Marx"' needle. Thereafter, an epidural catheter was inserted and taped. The mother was then placed in the supine position with left uterine displacement. At this point, another anesthesiologist blinded to the position used for CSE placement evaluated and recorded blood pressure, heart rate, and level of anesthesia (pin-prick). The incidence of hypotension (systolic blood pressure < 100 mm Hg or a 30% decrease from baseline), nausea/vomiting, as well as the use of ephedrine were compared in the two groups using Student's t or Chi Square test as appropriate l p c 0.05. Results = mean*SD.

RESULTS: Six parturients in each group have been studied thus far. The spread of anesthesia, the time to achieve the highest level of sensory block, and the incidence of nausea/vomiting did not differ between the two positions. Although all mothers had a drop in blood pressure, there was a tendency for hypotension to be more severe and of longer duration in the sitting as compared with the lateral recumbent group, thus requiring a significantly greater dose of ephedrine for reversal.

Sitting Lateral Recumbent

# of dermatomal segments blocked 21*2 22*2 Time to achieve highest sensory block (min) Sk3 6i2 Duration of hypotension (min) 6f4' 30 Ephedrine (mg) 42k22' 18*11

+p = 0.06 *p < 0.05

DISCUSSION: These preliminary data indicate that hypotension may be more severe and more difficult to treat when CSE is performed in the sitting versus lateral position. This may be related to a slow recovery from the effects of venous pooling in the lower extremities when the sitting position is employed for induction of CSE.

153

A COMPARATIVE STUDY OF CONTINUOUS EPIDURAL INFUSION OF 0.05 % BUPIVACAINE MIXED SOLUTION AND 0.175 %, LIGNOCAINE MIXED SOLUTION FOR PAIN RELtEF IN LABOUR

L. KILICKAN, M. TANYER, N. ASCI

Deparfment of Aneesfhesia, University of Kocaeli, IZMIT, TiiRKlYE

Introduction

Continuous infusion of low concentration of local anesthetic into the epidural space provides a continuous slable anaesthetic level , avoiding the fluctuations in pain relief often found with conventional intermitlen epidural injections during labour. The choice of drug for continuous infusion remains controversial. (12) We aimed to assess on the effects of these 0.05 % bupivacaine mixed solution with 0.175 % lignocaine mixed solution of continuous epidural infusion on the first and second stages of labour.

Methods

After Ethics Committee approval and informed consent had been obtained, we studied 26 women requesting pain relief in labour. Women were excluded from the study if they had gestation of less than 37 weeks, multiple pregnancy, preeclampsia, known coagulation defect, cardiovascular disease or were not in ASA classes I or II. The women were randomyl allocated to receive continuous epidural analgesia. All patients underwent epidural puncture with a 16 gauge Tuohy needle. Both groups were administered 2 ml of 2 % lignocaine solution as a test dose al 0 minute and 12 ml of 0.3 % lignocaine + 1 I 1 .OOO.OOO adrenalin as loading dose al 5 minutes. 0,175 % lignocaine + 0.00015 % fentanyl + 1 I800.000 adrenalin solution was administered through epidural catheter at a rate of 8-14 ml/h via an infusion pump in the Group L ( Lignocaine mixed solution group) , whereas in the Group B ( Bupivacaine mixed solution group ) 0.05 % bupivacaine + 0.00015 % fentanyl + 1 I 800.000 adrenalin solution was administered to the pregnants at 10 minutes. Statistical analysis used Student - t and Chi - square tests as appropriate.

Results

There was no statistically significant difference between group L and group B in respect of maternal characteristics such as age, weight, height, gestational week, cervical dilatation and VAS score prior to epidural analgesia. The quality of VAS and Chestnut’s ( 3 ) analgesia in the first and second stages of labour was significantly higher in the group with bupivaoaine than that in the group with lignocaine.

Conclusions

While continuous epidural infusion of a mixed solution of bupivacaine ( 0.05 % bupivacaine + 0.00015 % fentanyl + I I 800.000 adrenaline ) was providing adequate analgesia in the first and second stages of labour. However , continuous epidural infusion of a mixed solution of lignocaine ( 0.175 % tiinocaine + 0.00015 % fentanyl + 1 I800.000 adrenaline ) was provided effective analgesia during the firs! stage of labour, seemed lo be ineffective in the second stage.

References

1. Chestnut DH, Bales JN, Choi WW. Continuous infusion epidural analgesia with lidocaine : Efficacy and influence during the second stage of labor. Obsiel Gyneooll987 ; 69 : 323

2. Naulty JS. Continuous infusions of local anesthetics and narcotics for epidural analgesia in the management of labor. Int Anesthesiol Clin 1990 ; 28 : 17.

3. Chestnut DH, Owen CL, Bates JN, Ostman LG, Choi WW, Geiger MW. Continuous infusion epidural analgesia during labor : A randomized , double-blind comparison of 0.0625 96 bupivacaine , 0.0002 fentanyl versus 0.125 % bupivacaine. Anesthesiology 1991 ; 68 : 31-37.

1.54

TITLE: Does Dextrose Affect Analgesia or Side Effects of Intratbecal Sufentanil?

AUTHORS: JC Gage, MD, R D’Angelo, MD, R Miller, DO, JC Eisenach, MD

AFFILIATION: Department of Anesthesia, The Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009

KEYWORDS: Sufentanil, Dextrose, Baricity, Analgesia, Spinal, Intrathecal, Labor

INTRODUCTION: Intrathecal(IT) sufentanil provides rapid effective pain relief for Stage I labor, but also associates with undesirable side effects which may be related to cephalad spread.’ Hyperbaric preparations limit the cephalad spread of IT neostigmine.~ 3 Therefore, we tested whether dextrose prolonged analgesia or reduced side effects from IT sufentanil administration.

METHODS: Following IRB approval and informed consent, 36 healthy primipsrous parturients with uncomplicated pregnancies in early labor (2 2cm but s 5cm cerv did) requesting analgesia where

Table 1 Duration of Analgesia (min)

randomized to receive a 2ml IT injection of either sufentanil lOc(g + Solution Analgesia saline (15 patients), sufentanil lOc(g + 7.5% dextrose (15 patients), or 7.5% dextrose (6 patients). A combined spinal epidural technique SufentaniI/Saiine 108*49* was utilized with the patients in the lateral decubitus position. Pain (10cm visual analog scale (VAS)), nausea, pruritus, sedation, leg SufentanillDextrose 124f48*

weakness, sensory levels to pin prick and temperature, maternal 7.5% Dextrose 26&-24 blood pressure and heart rate were recorded at 0, 5, 15, 30, and every 30 min after IT injection until the patient requested additional * p<O.O5 compared to 7.5% Dextrose analgesia. Statistical analyses included Kruskal-Wallis One Way Analysis of Variance on Ranks, Chi Square, and Fisher’s Exact teats as appropriate (P < 0.05 significant).

RESULTS: Demographic variables were similar between groups. Sufentanil groups did Table 2 Side Effects (%) not differ in duration of analgesia; however, both groups had signilicantly longer analgesia Side Effect Suf/Saline* Suf/Dextrose

than the plain 7.5% dextrose group (Table 1). There was no di&rence in VAS pain, nausea,

Nausea 0 7

pruritus, sedation, leg weakness, sensory levels Pruritis 87 93 to pin prick or temperature, bradycardia, or hypotension between sufentanil groups (Table Leg Weakness 27 33

2). Sedation 47 27

CONCLUSIONS: Dextrose did not intluence Hypotension 13 13 the duration nor quality of analgesia from IT sufentanil. These data suggest that baricity > T, Sensory Block 40 47 does not influence cephalad spread of IT sufentanil; however, it is possible that more * No Significant Difference Between Groups

extreme positioning, such as sitting, could result in clinically significant effects.

REFERENCES: ‘D’Angelo R, et al. Anesthesiology 80: 1209, 1994. ‘Hood DD, et al Anesthesiology A928, 1994. ‘Hood DD, et al. Anesthesiology A883,1995.

155

Do Obstetric Outcomes differ between Early Combined Spinal-Epidural and Epidural Anesthesia in Nulliparous patients Receiving Intravenous Oxytocin ?

pan PH. hQ, Fragneto R, MD, Moore C, Phd, Ross V, MD, DiNunzio G, MD

Division of Gbstetrical Anesthesia, Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298

Anesthesia, obstetric; Anesthetic techniques: spinal, combined spinal-epidural; Analgesics, opioid: fentanyl, sufentanil.

I&~Dc~~ Some atudia mgg& tht utministration of epidural analgesia may result in longer 2nd stage labor and more instrument deliveries or ceaaman sections. Combined spinal epidural (CSE) has gained wide acceptance for labor analgesia with no motor blockade at least for the duration of intrathecal analgesia. The goal of this prospective randomizd study is to de&mine whether obstetric outcomes differ between early administration of CSE versus epidural aneetheaia (RA) alone in mtlliparous parturients while receiving intravenous oxytocin. &iethodaz After IRR approval, informed consent was obtained from 19 healthy nulliparous term parturients with singleton fetus in vertex presentation and cervix dilation less than 5 cm, who requested regional labor analgesia while receiving intravenous oxytocin. Raclt patient was randomized, via a randomimtion table, to receive either CSE or EA alone. CSE or EA was performed with patient in sitting position after receiving a preload of 1000 ml of lactated ringer solution. CSE group received 35 ug f&any1 intrathecally (via a 25 G Sprotte needle passed through a 17G Tuohy needle) before insertion of the epidural catheter, which was not tested or dosed until patient requested more analgesia when intmtheud analgesia wore off. In both EA and CSE groups, testing of epidural catheter consisted of 3 cc of 2% lidncaine with epmephrine and then dosed with 0.25 % bupivacaine to T-10 level. After initial epidural dosing, both groups received epidural PCA (EPCA) with 0.125 % bupivacaine and 2 ug/cc of fentanyl. EPCA basal rate was set at 4 ml/hr with demand dose of 3ml every 8 mitts. Additional bolus of 0.25 46 bupivacaine in 5 cc incren~&~~ were administered if patient was still uncomfortable after maximal use of the EPCA. Patients remained at bed rest in an upright 45 degree position and were evaluated every 10 minutes for the first 30 minutes, then every hour l ilewads. Pammkm assesd were: progress of labor, mode of delivery, duration of intrathecal analgesia, visual analog pain scale(VAPS), level of sensory block and motor block, vital signs (RP,HR,RR), fetal heart rate, side effects (nausea, vomit, sedation aud pruritus) and patients’ rating of satisfaction (excellent, good, fair or poor). Data analysis included Chi square, ANOVA and unpaired t-test as appropriate. &mtlta: 11 patients received CSE and 8 patients received EA alone. Demographics (age, weight, height, race, geatational age, newborn wt) are similar between groups. Preliminary results are summarized in the table below.

. . gurcnsslon; Despite the small sample sixe, preliminary data shows a statistical significant difference (P < 0.01) in the duration of 2nd stage labor between groups. Duration from initiation of CSE or EA to end of 1st stage labor were similar between groups, but the amount of local anesthetic administered by EPCA is higher for EA than CSE group (p <0.003). Incidence of spontaneous vaginal delivery is also higher for CSE than EA. but it has not reached statistical significance. A larger sample size will be obtained from this ongoing study to confirm the trend L&OWL CSE Group+= 11) Epidural Group(n= 8) p value

Cervix Dilation at randomi?ation(cm) 3.1 f 1.2 2.8 f 1.1 Intrathecal Analgesic Duratioo(min) 125 f 51* 0 f o* APS (10 mins after CSE or Epid dose) (O-10) 0.09 f 0.28* 2.7 f 1.7* Total EPCA volume used till delivery (ml) 35.6 f 17.5* 89.6 f 49.8” Duration of 1st Stage Labor(hours) 15.4 f 7.4 15.3 f 7.6 Duration of 2nd Stage Labor(mins) 43.7 f 25.3* 109.1 f 72.2* Duration of CSE or Epid to C/C Cervix(hours) 5.72 f 2.3 6.09 f 3.1 Duration of CSE or Epid to Delivery(hours) 6.5 f 2.5 9.2 f 4.4 APGARatlminISmin 0.7*0.4 l9fO 8.5*0.8 t9*0 Percent with Spontaneous Vaginal Delivery ( W) 72.7 % 37.5% Percent with Instrument Vaginal Delivery (%) 18.2 % 50 96 Percent with Cesarepn Section (96) 9.1 % 12.5 96 Percent with non occiput anterior presentation( %) 18 96 0%

Data are mean !c SD except for incidences in percent.

NS (p=O.6) p< 0.00001 p< 0.00002 p< 0.003 NS (p=O.9) p< 0.01 NS @=0.7) NS @=O.l) NS (p=O.S) NS @=O.l) NS @=O.l) NS @=0.8) NS @=0.2)

156

EPINEPHRINE AS AN ADJUNCT TO INTRATHECAL FENTANYL I BUPIVACAINE FOR LABOR ANALGESIA

CM Palmer, MD; RC Marquez, MD; WM Nogami, MD; G Van Maren, MD; DM Alves, RN

Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson, AZ, 05724

Epinephrine: intrathecal. Analgesia: labor. Fentanyl, bupivacaine: intrathecal.

PRODUCTION: lntrathecal techniques for labor analgesia, utilizing both opioids and local anesthetics, have become increasingly popular in recent years. The optimal agent or combination of agents for this purpose has yet to be defined. The purpose of this study was to determine the effect of the addition of epinephrine to intrathecal fentany125 pg and bupivacaine 2.5 mg on analgesic duration and side effects. MFTHODS: Thiriy-five ASA I and Ii nulliparous term parturients in active labor gave written, informed consent and parlicipated in this IRB-approved study. Following enrollment, patients were randomly assigned to one of two groups; Group Plain received an intrathecal fentany125 pg with isobaric bupivacaine 2.5 mg, while group Epi received 200 pg epinephrine in addition to the fentanyU bupivacaine combination. All injections were performed with patients in the sitting position as part of a combined spinaWepidural coaxial technique. Following completion of the procedure, patients were initially positioned supine with left uterine displacement, then permitted to position themselves “ad lib.” Visual Analog Scores (VAS) were recorded prior to injection, then at intervals until first request for additional analgesia. Maternal blood pressure was recorded prior to injection, and at 10, 20, and 30 minutes post- injection. Baseline fetal heart rate (FHR) was noted prior to and 30 minutes post-injection, as was maternal ability to perform a deep knee bend at bedside. VAS scores for “numbness” and side effects were recorded 20 minutes post-injection . Data was analyzed with student’s t-test, ANOVA, and Fisher’s exact tests as appropriate; a p value of < 0.05 was considered significant. RESULTS: There were no demographic differences between groups. The duration of analgesia (time to first request for additional analgesia) was 111.5 f 5.8 in Group Plain and 113.8 f 7.3 Group Epi (minutes, mean f SEM, p = NS). Maternal systolic blood pressures following injection did not change significantly in either group, while diastolic blood pressure declined moderately, but significantly in Group Epi (p e 0.01, ANOVA) (see Fig. Blood Pressure One). Fetal heart rates did not change in either group, and Post-Injection subjective VAS scores for lower extremity “numbness” were (Mean +/- SEh$

not significantly different. Patients in GroupEpi were significantly more likely to be either weak or unable (8 of 16) to complete a deep knee bend after injection than patients in Group Plain (2 of 16), (p c 0.05, Fisher’s exact test). pISCUSSlON: Epinephrine has been reported to prolong fentanyl analgesia following postpartum tubal ligation (1) and morphine analgesia following gynecologic surgery (2). Our series indicates that while epinephrine, 200 pg, added to fentanyl/bupivacaine for labor analgesia does not prolong analgesia, it does intensify motor blockade. This is of particular importance should use of intrathecal epinephrine be considered as part of an ambulatory labor analgesic technique. REFERENCES: 55 I I 1. Anesthesiology 73:381-385, 1990. 0 10 20 30

2. Anesth Analg 81:508-513, 1995. Mhifes Rkst-in~on

157

"Effects of Bupivacaine with and without Epinephrim added to Fentanyl for Intrathecal Labor"

Vitaly Soskin, M.D.; Aaron Betel, M.D.; Mxris Brawn, M.D.

Sinai Hospital and Wayne State University School of hkdicine; Detroit, MI

Intrathecal F'entanyl, Bupivacaine, Epinephrine, Analgesia, Labor

1NTRCDUCTION:lntrathecal narcotics provide rapid onset but limited duration of analgesia for labor. This study was designed

to determine if the addition of bupivacaine with and without epinephrine could significantly prolong labor analgesia without adverse maternal or fetal effects.

MBTHODS:Following Research Committee approval and informed consent 41 healthy nulliparous parturients at term in active labor were studied. All patients had achieved 3 - 5cm cervical dilation with normal fetal heart rate tracings. Patients were randomly assigned to the following groups for intrathecal injection: Croup I: Fentanyl 5Oug (F); Croup II: Fentanyl 5Oug with bupivacaine 2.5mg (FBI; Croup III: Fentanyl 5Oug with bupivacaine 2.5mg and epinephrine 200ug JFBE). Following intrathecal injection, maternal blood pressure, heart rate, and fetal heart rate were monitored. Linear visual analog scale for

pain IVASj, sensory level, and motor blockade were assessed. Side effects including somnoience, pruritis, nausea, and vomiting were recorded. Data are expressed as mean _f. standard deviation. Statistical analysis was performed using Student t-test with P L 0.05 considered significant.

RESULTS:There was a statistically significant prolongation of the duration of analgesia with FB and FBE (Table 1). Further, the addition of epinephrine (FBE) significantly increased the duration of analgesia compared to FB (P< 0.01). There were no significant differences between the groups in maternal blood pressure, heart rate, or in fetal heart rate changes. The VAS scores were comparable between the groups with all patients being pain free within 10 minutes of injection. The sensory loss ranged between Tg and Tit with FB and FBE and below T The was no motor blockade noted in any patients. %

in Group F. here were no

significant differences in side effects between the groups.

CONCLUSION:The addition of 2.5mg of bupivacaine and 2.5mg of bupivacaine with 2GOug of epinephrine to 5Oug of fentanyl administered intrathecally significantly prolongs labor analgesia without adverse maternal or fetal effects.

158

1

J FKXJ!? N,DUPATICNOFANAlCESIA F 13 56.6 + 11.8

FB 13 93.0 + 19.2*

E‘BE 15 113.9 + 20.3*

*p<o.o1

Determination of Dose Response for Intraspinal Bupivacaine and Fentanyl in Laboring Patients Using Combined Spinal Epidural Technique

S. Panchal, M.D., M.S. Suresh, M.D., C.P. Jayasinghe, M.D., B. Baker, M.D., D. Kennamer, M.D., S. Longmire, M.D., Q, Palacios, M.D., R. Vadhera, M.D., A. Waii, M.D., G. Townsend, M.D.

Department of Obstetric Anesthesiology, Baylor College of Medicine, Houston, TX

Intraspinal, Bupivacaine, Dose Response, Labor Analgesia

INTRODUCTION: Low doses of local anesthetics or opioids injected intraspinally provide immediate analgesia which is beneficial for laboring parturients requesting pain relief. Combined spinal epidural is a newly introduced technique for labor analgesia. To our knowledge different intraspinal doses of bupivacaine for labor analgesia have not been tested. The purpose of this study was to determine the ideal intraspinal dose of local anesthetic which would provide adequate sensory blockade with minimal or no motor blockade and without adversely affecting the mother, fetus, or progress of labor.

METHODS: Institutional approval was obtained and twenty one healthy, term parturients aged 19-35 years, who requested analgesia for labor, participated in the study after signing informed consent. All parturients received aspiration prophylaxis and 200 cc bolus of Ringer’s lactate solution. The parturients were randomized into four groups: Group A - bupivacaine 1 .Omg + fentanyl 15mcg (n=6), Group B - bupivacaine I Smg + fentanyl ISmcg (n=7), Group C - bupivacaine 2.0mg + fentanyl 15mcg (n=4), Group D - bupivacaine 2.5mg + fentanyl 15mcg (n=4). Using the double needle technique {Touhy I7 gauge and Whitacre 27 gauge (1 I .9cm)}, all parturients received the study drug followed by epidural catheter insertion. The epidural block was initiated with bupivacaine 0.0625% and fentanyl2mcg/cc infusion based on patient’s request for further analgesia. Visual analog scores (VAS) were assessed before and after intraspinal dose and initiation of epidural block, respectively. Sensory and motor blockade were assessed by pinprick and modified Bromage scale, respectively. Duration of the first and second stages of labor were recorded. Umbilical cord gases were obtained post delivery. Hemodynamics, blood pressure, heart rate, and oxygen saturation were assessed before and after intraspinal injection. Parturients were assessed twenty- four hours postpartum for satisfaction with analgesia, and for side effects (headache and urinary retention).

RESULTS: There were no demographic differences in the four study groups. Five parturients from the various groups {group A (n=l), group B (n=3), group C (n=l)) required cesarean section for cephalopelvic disproportion. Onset of analgesia in all parturients was 30-60 seconds after intraspinal injection. Average duration of analgesia from intraspinal injection to initiation of epidural block was 134 minutes. Average duration of the first and second stages of labor were 10.6 hours and 95 minutes, respectively. The dose of bupivacaine that produced 50% sensory loss (ED50) and 95% sensory loss(ED95) were not significantly different between the four groups. The VAS pain scores were not significantly different between the four groups before and after intraspinal bupivacaine and fentanyl injection (statistical analysis by Kruskal- Wallis test). Furthermore, there was no association between sensory blockade and intraspinal dosage. Motor blockade (detectable weakness of hip flexion) was greater in some parturients in group D (statistical analysis by Kruskal-Wallis test). Hemodynamic parameters were not significantly different between the four groups. There were no differences in umbilical cord gases or Apgar scores. None of the parturients experienced postpartum headache or urinary retention.

CONCLUSION: In this ongoing study, our findings suggest that intraspinal bupivacaine dose ranging 1 .O-2.5mg with fentanyl for laboring parturients provides instantaneous analgesia (a clinically desirable feature). Although at this time inferences cannot be made with regard to the optimal intraspinal dose which would provide adequate sensory blockade with minimal or no motor blockade, our preliminary data statistically and clinically suggest bupivacaine at a higher dose (2.5mg) produces greater motor blockade, compared to lower doses.

REFERENCES: Collis R.E. et al: Combined spinal epidural (CSE) analgesia: technique, management, and outcome of 300 mothers. International Journal of Obstetric Anesthesia. Volume 3, Number 2:75-81, 1994.

159

Effects of Bupivacaine on Intrathecal Fentanyl for Labor Analgesia

Pan PH. MD, Fragneto R, MD, Moore C, Phd, Ross V, MD, DiNunzio G, MD

Division of Obstetrical Anesthesia, Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298

Anesthesia, obstetric; Anesthetic techniques: spinal, combined spinal-epidural; Analgesics, opioid: fentanyl, sufentanil.

&ttmduction: Bupivacaine has been shown to prolong labor analgesia duration of intrathecal sufentanil, but intrathecat sufentanil has been reported to have a higher incidence and severity of pruritus and nausea; and cost more than intrathecal fentanyl. Whether bupivacaine can prolong labor analgesia duration of intrathecal fentanyl as with sufentanil has not been reported. The aim of this randomized, double-blinded study is to evaluate the effect of bupivacaine on intrathecal fentanyl for labor analgesia. J&tbod; After IBB approval and written informed consent, 45 ASA I or II parturients at term in active labor with cervical dilation between 2 to 5 cm and requesting regional labor analgesia were studied. Each patient was randomized, using a computer-generated randomization table, to receive one of three intratbecal study solutions: fentanyl35 micrograms (F) or 2.5 mg bupivacaine with 35 micrograms of fentanyl (BF) or bupivacaine 2.5 mg (B). All study solutions were diluted to a 2 cc volume with normal saline. Combined spinal-epidural(CSE) anesthetic was performed with patient in sitting position atIer receiving a preload of 1000 ml of lactated ringer solution. A 17 G Tuohy needle was inserted between L2-4 levels with loss of resistance technique, and a 25G Sprotte needle was passed through the Tuohy needle until clear cerebral spinal fluid (CSF) returned. A study solution was administered and an epidural catheter was placed without prior injection of saline to dilate the epidural space. The epidural catheter was aspirated to confirm no CSF return but the catheter was not tested. Patients remained at bed rest in an upright 45 degree position and were evaluated every 5 minutes for the first 15 minutes, then every 15 minutes until they requested further analgesia. Parameters assessed were: duration of intrathecal analgesia (defined as time from intrathecaf injection until patient request additional analgesia via epidural catheter), visual analog pain scale(VAPS), level of sensory block and motor block, vital signs (BP,HB, RR), fetal heart mte monitor, side effects (nausea, vomit, sedation and pmritus by VAS) and patients’ rating of satisfaction (excellent, good, fair or poor). Data analysis included Chi square, ANOVA and unpaired t-test where appropriate. &p&z Of the 45 patients enrolled in the study, 3 patients were excluded because no CSF was obtained through the Sprotte needle even though epidural catheter was subsequently placed and dose with success. Of the remaining 42 patients. 17 were in the fentanyl group (F). 14 in the bupivacaine and fentanyl group (BF) and 11 in the bupivacaine group (B). The demographics (weight, height, age. parity, childbirth education, fetal weight, cervical dilation before CSE) of the three groups were similar without statistical differences. The comparative results of the three groups are summari xed in the table below. BF and F provided quick onset of profound complete analgesia (VAPS = 0) while B alone frequently resulted in incomplete analgesia (VAPS > 0). BF provided the longest duration of analgesia without additional side effects. There was no postdural puncture headache, excessive somnolence or clinically significant motor block in any of the groups. Discussion: The analgesic duration(AD) of BF reported from this study is about 14% less than bupivacaine/sufentanil(BS) as reported by Campbell et al, but the incidence of nausea is 3 times less with fentanyl in this study than with sufentanil as compared to previous reports. Preliminary data from this ongoing study has not reached statistically significant difference in AD between F and BF group because of small sample size, but it shows a strong trend that bupivacaine prolongs the AD of intrathecal fentanyl by about 20%. Intrathecal bupivacaine and fentanyl combination is a good alternative to sufentanil with lower cost and lower incidence and severity of pruritus and nausea. Bupivacaine +

Fentanyl Group (F) Fentanyl Group (BF) Bupivacaine (B) (N= 17) (N= 14) (N=ll)

Duration of Intrathecal Analgesia (mins) 104.2 f 42.2’ 126.7 f 33.1’ 53.2 f 30.1’ VAPS before intrathecal drug (O-10) 8.3 f 1.6 7.4 f 1.9 7.9 f 1.7 Loweat VAPS achieved (O-10) 0 f o= 0 f o* 2.0 f 2.7’ VAPS before dosing epidural catheter@-10) 5.3 f 1.2 5.8 f 1.8 6.8 f 1.6 Worst Pruritus Visual Analog Score (O-10) 3.9 f 2.4’ 6.2 f 2.9’ 0.1 l 0.3’ Incidence of Nausea (96) 11 % 14.3 % 27 % Patient rated Satisfaction as Excellent(%) 88 96’ 100 46’ 45 %’

Data are mean f SD except for incidence of nausea and patient satisfaction rating. l P < 0.05 when comparing B group to F group or B group to BF group.

160

BUPIVACAINE AUGMENTS INTRATHECAL FENTANYL FOR LABOR ANALGESIA

CM Palmer, MD; BJ Csmmarats, MD; G Van Maren, MD; WM Nogami, MD; RC Marquez, MD; DM Alves, RN

Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson, AZ, 85724

Analgesia, labor: bupivacaine, fentanyl. Analgesia, intrathecsl: bupivacaine, fentanyi

-: ml fentanyl is an eKedive analga when administered intrathecally for labor (1). One drawback of the technktue is the ltmited duration of analgesia. The purpose of this study was to Investigate whether the addiin of low dose tsobarlc bupivacaine would prolong analgesia, and to document any changes in the quality of analgesia. m: Ninety ASA Class I and II nulliparoua term paiturienta with a cervical dilation of less than 5 cm requesting labor analgesia gave wrKten informed consent and completed the protocol of tNs double-blind, IRB-approved study. Upon request for labor analgesia, patients were randomized to one of three groups to receive a single intrathecal injection of either fentany125 pg (FTL), fentanyl25 ug wtth bupivacaine 1.25 mg (BUP1.25), or fentanyl25 pg with bupivacaine 2.5 mg (BUP2.5) vie the coaxial technique at time of placement of an epidural catheter. All injections were diluted to a total volume of 1.5 ml wtlh sterile saline as necessary, and administered in the sitttng positkrn. Visual analog scales (VAS) for pain were recorded q 2.5 minutea for 10 minutes, then q 30 minutes unfl first request for additional analgesia, when a final VAS score WBS recorded. VAS scorea for side effects (pruritus, nausea) were recorded at 15 minutes post-injection, as was sensory level to cokl. K a patient reached complete cervical dilation prior to requesting additional analgesia, they were dropped from the study and their group assignment m-randomized. Patients were questioned the day after delivery regarding headache, recollecKon of side eKeda, and satisfaction. Data was analyzed with ANOVA, and a posterion’tests as indicated; a p value 0.05 or leas was considered significant. w: Thirty parturlents were enrolled and completed the protocol in each group. Group BUP2.5 was significantly youngerthan the other groups, but groups were otherwise demographically similar. Duration of analgesia was s@rKicantty longer in the BUP2.5 group (108 f 3.7) compared to the other two groups, which were not s&riticantly different (FTL: 92 f 4.1; BUP125: 93.8 f 4.6) (mean f SEM). Onset of analgesia was faster in both BUP groups compared to plain fentanyl (FB. 1). There was no difference between groups with regard to the incidence or severity of prudtus; nausea was uncommon and not related to group. Sensory level to cold was noted in 21 of 30 patients in the FTL group, as well as all patients in the BUP groups. Overall C/S rate was 5.6% (5 of 90); there was no difference between groups. One patient complained of a mild headache the dav after delivery which responded to consecrative treatment; no patients required epidural blood patch. DlSCUSSION: lntrath&l fentanyl;25 pg, provides intense labor analgesia of approximately 90 min duration without detectable motor block (1). The addiion of 2.5 mg isobaric bupivacaine increases duration to 108 minutes: further, the speed of onset is significantly shortened.

VAS Pain Scores vs. Time (Mean +/- .%I%$

The finding that plain intrathecal fentanyl may produce anesthesia to temperature has not been reported before. While no motor block which would prevent ambulation was detected in this series, the sensory levels noted indicate that ambulation may be hindered due to altered proprkrceptton. The mild side effects and low headache rate reflect a low incidence of complications, and the low C/S rate would indicate this coaxfal technique has lie effect on the normal course of labor.

77me Post-injection (minutes)

REFERENCES: 1. Anesthesiology 81 Al 149,1994.

161

TITLE: Intrathed fentanyl versus fentanyl + bupivacaine for labor analgesia

AUTHORS D. Karambelkar MD, S. Kamanathan MD.

AFFILIATION: Department of Anesthesiology, Magee-Womens Hospital, University of Pittsburgh School of Medicine, 300 Halket St, Pittsburgh PA 152 13.

Labor analgesia, Intrathecal, Fentanyl, Bupivacaine, Combined technique

Introduction: Fentanyl administered via a combined Spinal-Epidural (CSE ) technique has recently become popular for labor analgesia. However, subsequent reactivation of the epidural catheter with local anesthetics may be needed. We reviewed 239 Quality Assurance records from our obstetric anesthesia service to determine, if addition of bupivacaine to fentanyl will decrease the number of reactivations. Methods: Data from 239 patients receiving CSE were collected. A needle through needle technique was used for CSE. Fentanyl (F) 25 ug or fentanyl + bupivacaine 2.5 mg (F+B) was injected into the subarachnoid space. The epidural catheter was reactivated as necessary during first stage with 0.25% bupivacaine. Demographic data, parity, cervical dilatation, and the number of epidural reactivations were recorded. Data were analyzed using X2 analysis and t-test at p CO.05 Results: A total of 47 primiparous (22 and 25 in the F and F+B groups respectively) and 192 multiparous (73 and 119 in the F and F+B groups respectively) women were included. The number of patients at cervical dilatation <=5 did not significantly differ between F and F+B groups in both parity subsets. In both subsets, the number of people requiring no further reactivation was significantly lower in the F+B group than in the F group (Tables land 2). Conclusion: The addition of a small amount of bupivacaine to fentanyl during CSE decreases the number of additional reactivations during first stage, especially in multiparous women. The decreased need for intervention by anesthesia staff may be particularly beneficial in the current climate of dwindling resources in busy obstetrical anesthesia services.

Table 1 : Primiparous subset

Drug No additional Additional P Age (yrs. ) Ht. (cm. ) Wt. (kg ) reactivations reactivations

F 6 16 26.5+6 164.1k6.2 78.2213 co.05

F+B 15 10 25.4k5.7 163.7t5.7 75.2+13 -

Table 2 : Multiparous subset

Drug No additional Additional P Age (yrs. ) Ht. (cm. ) Wt. (kg. ) reactivations reactivations

F 38 35 29.7k5.6 165.Ok5.9 77.5212

F+B 85 34 co.007

29.725.2 163.e66.1 78.8+17

162

Selective sensory blockade with low-dose combined spinal/epidural

(CSE)allows safe ambulation in labour: A pilot study.

Sinsh R', Plaat F*, Alsoad SW', Crowhurst JA'.

Department of Anaesthesia, Queen Charlotte's and Chelsea Hospital, London W6 OXG, United Kingdom.

Anaesthesia - regional; combined spinal-epiduralj obstetric; labour: sensory, motor; blockade; ambulation; walking.

INTRODUCTION: Although low-dose epidural analgesia in labour preserves motor function, widespread controversy exists about the safety of allowing ambulation with varying degrees of sensory blockade. Significant loss of proprioception has been demonstrated in women receiving low-dose conventional epidural analgesia using a bupivacaine/fentanyl mixture. Buggy et all were so concerned by these findings they suggested that allowing such women to walk was unsafe.

AIM: The aim of this preliminary study was to investigate the spectrum of sensory blockade in women receiving low-dose CSE analgesia in labour and its effect, if any, on their ability to walk.

PATIENTS AND MRTI-IOD: Forty parturients who had received CSEs in labour were studied. Following routine practice in this unit*, analgesia was induced with a 1.5ml

intrathecal dose of bupivacaine 2.5mg and fentanyl 25pg. Top-up doses of 10 ml of

0.1% bupivacaine with fentanyl 2 ug/ml were given via the epidural catheter on request. 30 minutes after the intrathecal dose and the first epidural top-up, sensory and motor functions were examined. Posterior column modalities (vibration sense, distal-joint position sense and Romberg's sign), and spino-thalamic modalities (temperature and pain) were assessed using standard clinical tests. Motor function, in lumbar-plexus muscle groups, was graded according to the Medical Research Council (MRC) scale3. Patients were asked if they felt confident to walk, and if so they were permitted to do so, provided that motor function was intact. Pain was assessed using a linear scoring system (0 = no pain; 10 = worst pain imaginable) immediately before the block and 10 mins later.

RESULTS: 89% of patients following their intrathecal dose, and 97% following the first epidural top-up, had minimal motor blockade (grade 4 or 5 on MRC Scale) and no loss of posterior column functions. All of these patients felt confident to walk, and did so normally.

DISCUSSION: It is apparent that the spectrum of sensory blockade achieved with this technique of CSE is very different from that seen with conventional low-dose epidural block. Subtle differences between subarachnoid and epidural sensory blockade are suggested as the reason for these differences. A more detailed controlled study of all sympathetic, sensory and motor functions is in progress.

CONCLUSION: With low-dose CSE analgesia, selective, minimal motor and sensory blockade are readily achievable to a degree where safe ambulation is possible.

REFERENCES: l.Buggy D et al. Posterior column sensory impairment during ambulatory extradural

analgesia in labour. Br J Anaesth 1994; 73: 540-542. 2.Collis RE et al. Combined spinal epidural analgesia with ability to walk

throughout labour. Lancet 1993; 341: 767.

163

POSTERIOR COLUMN SENSATIONS DURING NEUROAXIAL LABOR ANALGESIA

A. K. Soni MD, M. C. Santa MD, P. A. Groves MD and N. E. Griol MD

Dept. of Anesthesia and Critical Care, Beth Israel Hospital, Harvard Medical School, Boston MA

Tetracaine, Ambulation, Posterior Column Sensation, Spinal analgesia, Epidural analgesia

Introduction: Walking or ambulatory epidural analgesia for labor has recently become popular. Preservation of motor function and possibly posterior column sensation could lead to increased maternal satisfaction and reduced side effects. Impairment of posterior column sensation was detected in an earlier study [l] in epidural analgesia (0.1% bupivacaine) but it has not been reported following intrathecal sufentanil or tetracaine. Reported concentrations of bupivacaine used (O.l%-0.0625%) are still higher than what we use at our center (0.04%) for ambulatory epidural analgesia [1,2,3]. This study was conducted to observe any loss of posterior column sensations with the ultra low dose epidural bupivacaine, intrathecal sufentanil and ultra low dose intrathecal tetracaine. Methods: After obtaining IRB approval and informed consent we studied 29 healthy term parturients who requested labor analgesia. They were randomly assigned to one of seven groups using lumbar combined spinal epidural technique (CSE). Group l- received 1 mg intrathecal tetracaine; Group 2- 1 mg intrathecal tetracaine and 10 pg of sufentanil; Group 3- 1 mg tetracaine + 2 ug of epinephrine; Group 4- 1 mg tetracaine + 10 pg of sufentanil + 2 pg of epinephrine; Group 5- 10 ug of sufentanil; Group 6- 10 pg of sufentanil + 2 pg of epinephrine and Group 7- lumbar epidural analgesia with 0.04% bupivacaine + 1.66 pg of fentanyl + 1:600,000 of epinephrine, 15 cc bolus and continue with 15 c&r of infusion. Intrathecal volume was kept constant (1.5 ml) in all groups by adding preservative free 0.9% saline. All patients were assessed for any preoperative neurological deficit including posterior column sensations, linear analogue score for labor pain, motor power in the lower limbs using modified Bromage scale (Modified Bromage scale: grade l- complete block; grade 2- moves feet only; grade 3- moves feet and knees; grade 4- weakness of hip flexion; grade 5- no weakness of hip flexion when supine; grade 6- partial knee bend on standing), coordination (heel to shin test), deep tendon reflex of the knee, distal joint proprioception (great toe), vibration sense over tibia1 tuborosity and medial malleolus using 128 Hz tuning fork, and Romberg’s sign. These signs were noted after 5 and 30 minutes of providing analgesia. In addition sensation to cold and pin prick were also recorded. Next day all patients were assessed for any neurological deficit. Statistical analysis was performed using ANOVA for parametric data and Chi square test for frequencies. Results: There was no difference among the groups who received tetracaine and sufentanil, hence the data from the groups 1 to 4 was pooled and from group 5 and 6 was pooled (TC- tetracaine group; S- sufentanil; BEF- epidural) for further analysis. All the groups matched evenly in terms of age, height, weight, gravida and para. Patient in all groups had satisfactory analgesia. Data for neurological examination is presented in table 1. Sensory level could be elicited in all groups with cold as well with pinprick. All patients in TC group had a level ranging from tboracic (T) 10 to T5. One patient in S group had Tl 1 level to cold and Ll to pin prick but demonstrated adequate analgesia. Sensory level to pin prick was consistently 2 segments lower than that with cold sensation. There were no long term neurological complications in any of the patients. Table 1.

mfsem mfsem impairment absent impairment impairment 4 5 6 4 5 6

Tetracaine (15) 86i2.2 6.5i3.7 12**(80%) 7 (46%) none 1 (6.6%) 6 5 4 7 4 4

Sufentanil(8) 9Ok2.1 lOi3.9 2* (25%) none none none 0 2* 6 0 2* 6 BEF (6) 66.758.1 3.3s2.1 lf (16%) none none none 006015

* - Patients did not want to stand in spite of no motor weakness. ** - not elicited because of motor weakness. Conclusions: Vibration sense and joint proprioception were not impaired with 1 mg of intrathecal tetracaine. Romberg’s sign could not be performed due to motor impairment in this group. Intrathecal sufentanil and ultra low dose epidural bupivacaine (BEF) may not impair posterior column sensation and motor function. Ambulation during neuroaxial analgesia may be allowed after careful assessment of motor function (Bromage grade 6), posterior column sensation and individual patient preference. References: 1. Buggy D, Hughes N, Gardiner J, Br J Anaesth 1994;73:540-2

2. Collis KB, Baxandall ML, Srikanthirajah ID et al, Lancet 1993;341:767 3. Breen TW, Shapiro T, Glass B, Foster-Payne D, Oriol NE, Anesth Analg, 1993;77(5):919-24

164

STERNOMENTAL DISTANCE AS THE SOLE PREDICTOR OF DIFFICULT LARYNGOSCOPY IN OBSTETRIC ANESTHESIA

DA Rocke* , SAL Ramadhani+, LA Mahomed+, E Gouws+t

Departments of Anaesthesia, Al Corniche Hospital+, Abu Dhabi, United Arab Emirates; University of Natal*, Durban, South Africa and Institute of Biostatisticstt, Medical Research Council, Durban, South Africa.

Preoperative assessment, laryngoscopy, tracheal intubation

Introduction: Difficult intubation continues to be of serious concern following induction of general anesthesia for cesarean section. Preoperative assessment of the airway, which atempts to predict the difftcult case, should include examination of head and neck mobility, a measure of atlanto-occipital extension. Previous studies have ,only subjectively assessed head and neck mobility[ 1,2]. Recently, in a largely non-obstetric population it has been suggested that sternomental distance would be a useful and objective measure of neck extension[3]. The present study reports the use of sternomental distance in predicting difficult laryngoscopy in an obstetric population.

Methods: Sternomental distance and subsequent direct laryngoscopy were recorded on a group of patients presenting for elective or emergency cesarean section. Sternomental distance was measured as the straight distance between the upper border of the manubrium stemi and the bony point of the mentum with the head in full extension and the mouth closed. The distance measured was approximated to the nearest 0.5cm. The intubating anesthesiologist was unaware of the sternomental distance. Immediately following the rapid sequence induction an assessment was made of the view at laryngoscopy and categorised into 4 grades[4]. Grades 1 and 2, were combined and grouped as ‘easy’ whilst Grades 3 and 4 were combined and categorised as ‘difftcult’.

Results: 523 parturients, representing 85% of the obstetric case load over an 8 month period were studied. Eighteen (3.5%) had a Grade 3 or 4 laryngoscopy. Using discriminant analysis, a sternomental distance of 13.5cms or less was calculated as the most accurate cutoff point for discriminating between a ‘difficult’ laryngoscopy and an ‘easy’ laryngoscopy. There was a significant difference (p = 0.0013) between the sternomental distance for the easy (14.3 * 1.49 ems) group compared to the difficult group (13.17 + 1.54). At 13.5cms the sensitivity, specificity, positive and negative predictive values were 66.7%, 71.1%, 7.6% and 98.4% respectively. A receiver operator characteristic curve was used to assess the predictive value of various cutoff points in the prediction of laryngoscopic grade. At a stemomental distance of 12cms the likelihood of experiencing a grade 3 or 4 laryngoscopy was 5.6 (95% CI 2 - 14) times more than an easy grade. Whilst there was no association between sternomental distance and age, weight, height or body mass index there was a significant association between grade of laryngoscopy (3 and 4) and older (p = 0.004) and heavier (p = 0.0495) mothers.

Discussion: Compared with the previous study of Sawa[3] who found a stemomental distance of 12Scms to be the best predictor the present study has a lower sensitivity and specificity. The results of this study do however show that sternomental distance can be used to assist in the prediction of subsequent difficult laryngoscopy. However, because sternomental distance only looks at one aspect of airway assessment it cannot be used in isolation and should be combined with other simple tests.

Reference: 1. Bellhouse CP, DorC C. Anaesthesia and Intensive Care 1988; 16: 329-337. 2. Rocke DA et al. Anesthesiology 1992; 77: 67-73. 3. Sawa D. Br J Anaesth 1994; 73: 149-153. 4. Cormack RS, Lehane J. Anaesthesia 1984; 39: 1105-l 111.

165

ru33 1 nnL 1 rcnuv1

TITLE: EFFECT OF CISAPRIDE ON GASTRIC EMPTYING FOLLOWING CAESAREAN SECTION

4ulHm: C.S. Grange, MBBS, T. J. Adams, MBBS, A.P. KlifXer, MD, M.. J. Douglas MD,

4FFILIATION: Departments of Anaesthesia, The University of British Columbia and BC Women’s Hospital and Health Centre Society, Vancouver, B.C.

KRwcRlX Cisapride, Gastric Emptying, Aspiration Pneumonitis, Caesarean Section

INTRODUCTION: Delayed gastric emptying may increase the risk of aspiration of gastric contents during general anaesthesia Effects of Caesarean section (CS) and opioids’ have been shown to decrease gastric emptying Studies have indicated Cisapride may overcome morphine induced delays in gastric emptying’ However, little is known of the effects of spinal anaesthesia, intrathecal opioids or cisapride in parturients undergoing a CS. METHODS: Following ethics approval and informed consent, 37 women undergoing a term C. S. with spinal anaesthesia, were randomly allocated to receive either Group 2 cisapride ( 1 Omg orally), or Group 1 placebo at delivery. All patients were healthy and not on any medication likely to affect gastric emptying. A standard spinal anaesthetic consisting of 1.4 mls, 0.75% heavy bupivacaine, 250mcg morphine and 1Omcg fentanyl was given. One hour post delivery, 1.3g of acetaminophen was given with 5Omls of water. Blood samples were taken at 15,30,45,60,75,90, 120 and 150 mins after the acetaminophen. Twenty-four hours post op symptoms were also documented. Analysis was performed using T tests, Mann Whitney U, Chi 2 , and Fishers exact tests and p <0.05 was considered significant, RESULTS: Absorption of acetominophen The demographics of the two groups were similar. (gastric emptying) was markedly delayed in both groups. Group 2 appeared to have an increased absorption (Figure) This group also had a significant reduction in nausea and gut transit time. DISCUSSION: Opioid spinal anaesthesia fbr CS causes considerable delay in gastric emptying.

Cisapride may reduce this delay, reduce nausea and promote gut motility. REFERENCES: 1. Anaesthesia 1991,46:1016-18 2, Br J Anaesth 1987,59:536-39

Acetamlnophen Conc'n Mean+/-SEM

80 I=!

67 2=2

53

; \ u, 40 ,

27

13

0 0 30 60 120

15 45 90 150

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166

AEcsIRAaFoRM

I TITLE:

TRANSFER OF SUFENTANIL BY THE PERFUSED HUMAN PLACENTA: THE EFFECT OF PROTEIN BINDING.

AUIHORS:

A. Hussain, MD, M.I. Zakowski, MD, R. Krishna, PhD, G.J. Grant, MD, H. Tumdorf MD.

AFFILIATION:

Department of Anesthesiology, New York University Medical Center, New York NY 10016.

placenta, perfusion, sufentanil, clearance, protein binding.

Introduction: Sufentanil is commonly used to supplement local anesthetics for labor analgesia and cesarean delivery. This study investigates the effect of protein binding on placental transfer of sufentanil. Methods: Maternal to fetal transfer of sufentanil was studied utilizing a recirculating dually perfused human placental model. After IRB approval, human placental lobules were isolated and a tributary fetal artery and vein pair were cannulated and perfused, Four blunt cannulas were inserted through the decidual plate to establish an independent maternal circulation, Maternal and fetal flow rates were 12 ml/min and 6 ml/min respectively. The fetal perfltsate was Media 199 with dextran equilibrated with O,:CO, 95 % :5 % . Following a 45 minute stabilization both sides were recirculated and experiments were performed in three sequential 45 min phases: maternal perfusate consisting of M199, fresh human plasma and Ml99 containing 4% albumin, the order of each perfusate being rotated. A 45 minute washout was allowed between phases. Antipyrine, creatinine (10 mg%) and 3H sufentanil (50 nM) were added to all maternal perfusates. Sufentanil was measured using a scintillation counter and antipyrine and creatinine by calorimetric assay. Protein binding was measured by ultrafiltration. Preliminary studies showed higher binding of sufentanil to fresh human plasma compared to frozen human plasma. Results: Binding of sufentanil to fresh human plasma and to 4% albumin was 97% and 74 % respectively. Sufentanil was rapidly transferred across the placenta reaching equilibrium within 35 minutes. The clearance, clearance index (C.I:clearance of drug/clearance of antipyrine) and transfer index (T.I:clearance of drug/cIearance of creatinine) of sufentanil was calculated and analyzed by repeated measures (ANOVA). Data are mean+S.D (n=lO):

Clearance c.1

Ml99 1.41kO.42 0.42&O. 13

Plasma 0.58+p.24* 0.17+0.06’

Albumin 1.41kO.47 0.4&O. 15 * Significantly different to Ml99 and albumin (pCO.01)

T.1

3.48kl.34

1.46+p.77*

3.76kl.43

Discussion: The results of this study show that matemo-fetal transfer of sufentanil is rapid and is unaffected by albumin, thus suggesting that placental transfer of sufentanil may be unaffected in certain hypoalbuminemic states such as preeclampsia. Sufentanil is highly bound to human plasma (presumably to AAG) thereby reducing transfer to the fetal circulation. Conditions affecting plasma AAG concentrations, may reflect directly on the degree of placental transfer of sufentanil.

This research was supported by the Foundation for Anesthesia Education and Research with a grant from Malinckrodt Anesthesiology.

167

THE EFFECT OF FETAL pH AND MATERNAL PROTEIN BINDING ON LOCAL ANESTHETIC TRANSFER ACROSS THE HUMAN TERM PLACENTA.

RF. Johnson, B.S., H.V. Johnson, M.D., T.L. Arney, M.D., R.L. Paschall, M.D., N. Herman, M.D., and J.W. Downing, M.D.

Departments of Anesthesiology, Vanderbilt University, Nashville,TN. 37232 and Cornell Medical Center, New York, NY. 10021.

Lidocaine, Bupivacaine, Placental Transfer, Placental Perfusion, pH

Introductiln a previous investigation lidocaine and bupivacaine placental drug transfer was shown to be increased as the pH of the fetal circuit was acidified’. These experiments were performed using the dual perfused human placental model with perfusates of low drug protein binding potential in both the maternal and fetal circuits. We have conducted a similar investigation substituting perfusates that provide maternal and fetal protein binding potentials similar to those observed in vivo. Methods; All experiments were performed using the open (single pass) model. Placentas were collected from three healthy women with their written informed consent and IRB approval. Single cotyledons were perfused with fresh frozen plasma (FFP) in the maternal circuit and with Krebs-Ringer buffer supplemented with human albumin (4.0 gm/lOO ml) in the fetal circuit. Temperature and maternal pH were maintained at 37” and 7.4. The fetal pH equilibrated over 45 minutes to 7.4, was then reduced to 6.8 using dilute HCL. Sixty minutes later baseline pH (7.4) was reestablished with sodium bicarbonate. Fetal and maternal flow rates were 1.5-2.5 and 12-l 5 ml/min, respectively. Perfusate lidocaine, bupivacaine and antipyrine concentrations were determined using high performance liquid chromatography. Maternal to fetal clearances were calculated at 15 minute intervals. Local anesthetic transfer was expressed as a ratio of antipyrine transfer (transfer ratio). Results: Lidocaine and bupivacaine maternal to fetal transfer ratios increased significantly from baseline values of 0.80 iO.07 and 0.29 kO.06 to 1 .Ol +0.09 and 0.35 kO.06 (~~0.05) respectively during the period of acidemia. The transfer ratios returned to baseline values (0.81 +0.05 and 0.28+0.05) when the fetal pH was restored to 7.4. Protein binding of lidocaine and bupivacaine to the maternal perfusate (FFP) was shown to be within normal expected in viva parameters (48.0% and 79.5% respectively). Conclusions: As the pH related changes in local anesthetic placental transfer noted in the current study are less than those reported earlier’, we have demonstrated that enhanced maternal protein binding limits but does not abolish the phenomenon of enhanced local anesthetic transfer during fetal acidemia. These pH associated changes may more accurately represent those anticipated to occur in vivo where the natural forces of maternal protein binding are at work.

Supported by the Study Center for Anesthesia Toxicology of Vanderbilt University.

Referencesr 1. Johnson RF, et al: Placenta 15:A35, 1994 .

168

THE EFFECTS OF EPHEDRINE, PHENYLEPHRINE AND METHOXAMINE ON FETAL INTRAVILLOUS VASCULAR PRESSURE DURING I/V WTRO PLACENTAL PERFUSION.

J.W. Downing, M.D., H.V. Johnson, M.D., T.L. Arney, M.D., R.L. Paschall, M.D., N. Herman, M.D. and R.F. Johnson, B.S.

Departments of Anesthesiology, Vanderbilt University Medical Center, Nashville,TN. 37232 and Cornell Medical Center, New York, NY. 10021

Ephedrine, Phenylephrine, Methoxamine, placental perfusion, fetal pressure

htroduction; Previous investigations have demonstrated that some sympathomimetics constrict the fetal intravillous vasculature of the human placenta’,‘. Therefore we studied the effects of three vasoactive agents (ephedrine, phenylephrine and methoxamine) on fetal intravillous vasculature following there direct introduction into the maternal perfusate. Method: The study was performed using the closed (recirculating) dual perfused human placental mode13. Fresh placentae were obtained from thirteen healthy women with informed consent and IRB approval. Single cotyledons were perfused with Krebs- Ringer buffer supplemented with human albumin. Fetal and maternal flow rates ranged between 1.5-2.5 and 12-l 5 ml/min, respectively. Maternal and fetal pH were held constant at 7.4kO.05 and 7.35 kO.05, respectively. Perfusion pressures for both circuits were measured using mercury manometers and by in line pressure transducers linked to a Hewlett Packard monitor (module 78342A). Ephedrine 100 mg (n =4), phenylephrine 40 mg (n = 5), or methoxamine 40 mg (n =4) were added individually to the maternal circuit . Maternal and fetal pressures were recorded electronically every minute for three hours.

Fetal perfusion pressures increased linearly as ephedrine or phenylephrine Results equilibrated between the maternal and fetal circuits. Ephedrine administration was associated with an increase in fetal perfusion pressure from a baseline mean value of 64 f 5.5 mmHg to a maximum mean value of 172 + 37.5 at the end of the perfusion period (p< 0.05). Similarly, maternal administration of phenylephrine resulted in an increase from a baseline mean of 81mmHg to a maximum mean of 132 mmHg (~~0.05). In contrast, methoxamine administration caused no such increase in fetal perfusion pressures. Maternal perfusion pressures were constant throughout. Conclusions: This investigation shows that both ephedrine and phenylephrine cross the human placenta and cause vasoconstriction of the fetal intravillous vasculature resulting in increasing fetal perfusate pressures. No pressure changes were noted when methoxamine was added to the maternal circuit.

Supported by the Study Center for Anesthesia Toxicology of Vanderbilt University.

‘Br J obstet Gynaecol 1994;101:871. 2Trophoblast Research 1987;2:289. 3Anesthesiology 1995;82:459.

169

Changes In Uterine Artery Blood Plow Associated With Labor Analgesia Via Intrathecal Administration Of Sufentanil

L.J. Epstein, M.D., A, Lysikiewicz, D. Garry, M.D. M.D, J. Chhipa,M.D.

Departments of Anesthesia and Perinatal Medicine, The New York Medical College, Valhalla, New York 10595

Intrathecal Opioids, Uterine Artery Blood Plow, Doppler, Analgesia

. Introduction: The hrtroductlon of hnnbar epidural analgesia with local anesthetic agents is associated with an

increase in uterine blood flow in both normal1 and pmeclamptic patients2 However, this is only true if volume is aggressively replaced and blood pressure remains stable. The mechanism of this change is not clear, although changes in sympathetic tone or circulating catecholamines are the two most likely explanations.

Recently, analgesia~via intrathecal adminisazltion of narcotics has become popular.3 p4 Advantages of this technique include easy -on, single dosing and less profound sympathetic blockade. We examined the relationship of analgesia provided by this technique and uterine blood flow as indicated by changes in uterine’ artery Doppler veloclmetry with the hypothesis that there is no diierence in uterine blood flow after intrathecal admiktration.

. patients in labor, requesting analgesia and consenting to participation in the study and

. . mtion of intrathecal narcotics am included. Patients with diabetes, P.I.H. or known compromise in uterine blood flow were not included in the study. All patients were pre-hydrated with S-1.0 liters of lactakd Ringer’s solution. Baseline MAP, HR, Doppler measurements of systolic/diastolic ratio (S/D) and Resktance Index (RI.) will be obtained with the patient in supine position with left uterine displacement. Upon a request for labor analgesia, in all patients a 16ga Tuohy needle was placed in the epidural space using the “loss of resistance technique”. A 25 or 27ga Whitacre@ spinal needle was passed through the Tuohy needle and patients received sufentanil l$.tg mtrathecally. An epidural catheter was placed in all patients. Three? patient who reported no pain relief in 15minutes or inadequate analgesia (patient’s assessment) after 30 minutes received local anesthetic via the epidural catheter and their data was excluded Tom the analysis. All flow measurements were be made by a single investigator Uterine artery Doppler velocimetry measurements were obtained immediately prior to the administration of analgesia and at 30,60 and minutes post introduction. Results:_To date, a total of 8 patients have participated in the study. At the time of intrathecal injection, the mean cervical dilatadon was 4.75 cm with a range of l-7 cm. The means for R.1, S/D ratio & M.A.P. am presented in

Initial Doppler velocimetry revealed a higher R.I. on the left than the right (pc.OOl).. The R.I. on the right and left following the intrathecal administration of sufentanll were similar to each other and the preanesthetic values. The letI uterhre displacement in combination with labor pain is a possible explanation for this difference which resolved with analgesia. Gverall, no difference was observed between initial and post-anesthetic values for uterine artery Doppler velocimetry. We conclude that intrathecal sufentanil does not alter uterine artery blood flow in this group of patients.

1 Holhnen ALJouppila R Jouppila P, et al. Effects of extradural analgesia using bupivacaine and 2-chloroprocahre in mtervillous blood flow during normal labor. Br J Aneaesth 54:837-842.1982 2Jouppila P, Jouppila R, et al. Lumbar epidural analgesia to improve intervillous blood flow during labor in severe ~meclampsia. Obstet Gynecol59:158-161 1982 Abboud TK, Shmder SM, et al. Intrathecal administration of hyperbaric morphine for the relief of pain in labor. Br J

Anaesth 56:1351-1360,1984 %eighton BL, DeSimone CA, et al. Intrathecal narcotics for labor revisited: The combination of fentanyl and morphine intrathecally provides rapid onset of profound, prolonged analgesia. Anesth Analg 69:122-125,1989

170

TITLE: The Effects of Levobupivacaine, Bupivacaine, and Ropivacaine on Uterine Blood Flow

A- B. Karpel, D.O., E. Yun, M.D., G. Noble, M.D., A. Santos, M.D., M. Finster, M.D.

AFFILIATION: Departments of Obs/Gyn and Surgery, SUNY-Stony Brook, NY, Depts. of Anesthesiology, OBS/Gyn, Albert Einstein College of Medicine, Bronx, NY and Columbia University, New York, NY

Local Anesthetics, Uterine Blood Flow, Placental Transfer

INTRODUCTION: The purpose of this study was to compare the effects on uterine blood flow (UBF) of two new amide local anesthetics, levobupivacaine (LB) and ropivacaine (R), with those of racemic bupivacaine (B), currently the most commonly used local anesthetic (LA) in obstetric anesthesia.

METHODS: Thirty chronically instrumented ewes, near term of pregnancy, were studied under an approved protocol. Animals were randomized to receive a two-step IV infusion of LB, R, or B at a rate of 0.07 mg/kg/min for 15 min followed by 0.035 mg/kg/min for 45 min. The rate of infusion was chosen to achieve serum concentrations of drug similar to those expected to occur during uneventful epidural anesthesia for c/s. The investigators were blinded to the identity of the drug. UBF was measured using a pulse transit-time Doppler flow probe. Measurements were made prior to (time 0) and at 30 and 60 min of infusion. Intraamniotic (IA) pressure was monitored continuously through an indwelling catheter. Serum drug concentrations ,were determined by gas chromatography in maternal and fetal arterial blood samples obtained at the end of infusion. Repeated measures ANOVA was used to detect statistically significant differences. *p < 0.05. Results = mean&SD.

RESULTS: Ten ewes were studied in each drug group. There were no significant differences among groups in the maternal or fetal serum concentration of LB, R or B at the end of drug infusion. These were 1.33kO.65, 1.17+0.41, and 1.56kO.61 pg.ml-', respectively, in the mother and 0.20*0.15, 0.51iO.5 and 0.61iO.71, pg.ml-', in the fetus. The corresponding F/M ratios of serum concentrations were 0.2OkO.3, 0.41kO.35 and 0.51&0.60. No drug resulted in a significant change in UBF or intraamniotic pressure (IA).

UBF (ml/min)

Time LB R B

0 457+139 451*118 466*121 30 453+127 453*119 472&113 60 45Ok136 4672119 469*127

CONCLUSIONS: There were no untoward effects on UBF or IA with all three LA tested. This may not apply to higher serum concentrations associated with maternal systemic toxicity.

Supported by Chiroscience, Ltd.

171

TREATMENT OF INCOMPLETE ANALGESIA AFTER PLACEMENT OF AN EPIDURAL ANESTHETIC FOR THE WOMAN IN LABOR.

Y. Beilin MD, H.H. Bernstein MD, B. Zucker-Pinchoff MD, J. Zahn MD, W.J. Zenzen BS

Departments of Anesthesiology, Obstetrics, Gynecology and Reproductive Sciences, Mount Sinai School of Medicine, New York, NY 100296574

Epidural anesthesia, unilateral block, complications,

INTRODUCTION: Epidural analgesia is a popular and effective method of pain relief during labor, but as many as 15% of all epidurals fail with resultant unsatisfactory analgesia that is frequently unilateral in nature. No previous study has sought to determine the most efficacious way to treat unilateral pain although three approaches have been recommended: 1) withdraw the catheter 1 cm and redose;’ 2) turn the patient to the opposite side and redose without any catheter manipulation;’ or 3) immediately replace the epidural.3 This study was undertaken to determine the best way to treat the woman who continues to have unilateral labor pain after the placement of an epidural anesthetic. METHODS: After IRB approval and informed consent, women in labor were enrolled in this prospective, randomized and double-blind study. After placement of a multi-orifice epidural catheter to a depth of 5 cm, all patients received a test dose of 3 ml 0.25% bupivacaine followed by an additional 10 ml 0.25% bupivacaine in 2 divided doses. Fifteen minutes later, the adequacy of analgesia was assessed by asking the woman if she still has pain. All women who still complained of unilateral pain were placed with the painful side down. They were then randomized to (first intervention) either receive an additional 5 ml 0.25% bupivacaine (group 1) or to receive 5 ml 0.25% bupivacaine after first withdrawing the catheter 1 cm from the epidural space (group 2). Success was assessed 15 minutes later by asking the woman if she still had pain. If the patients in group 1 still had pain the catheter was withdrawn 1 cm and an additional 5 ml 0.25% bupivacaine was given. If the patients in group 2 still had pain they were given 5 ml 0.25% bupivacaine without further catheter manipulation. Success was again assessed 15 minutes later by asking the woman if she still had pain. If patients were still in pain after the second intervention the epidural catheter was replaced. Results were analyzed using the chi square test. P < 0.05 was considered significant.

RESULTS: Two hundred women were enrolled and 31 with unilateral blocks were studied.

TABLE

Initial intervention Number of patients Success after initial intervention Success after 2nd intervention Replaced catheters

Group 1 Group 2 Medications only Catheter manipulation 15 16 10 (67%) 13 (81%) 5 (100%) 2 (94%) 0 1

CONCLUSIONS: We were not able to detect a significant difference in the success rate between the two groups either after the first or second intervention. There is a high success rate in both groups when treating a woman with a unilateral block. Based on our results, we do not feel the epidural catheter should be replaced without first trying one of the above techniques. REFERENCES: 1. Brown DL. In Chestnut DH (ed). Obstetric Anesthesia; Principles and Practice, 1994, 195-6. 2. Shnider SM. In Shnider SM , Levinson G (eds). Anesthesia for Obstetrics 3rd edn., 1993, 143. 3. Gutsche BB. Annual refresher course lectures of the ASA, 1994, Lecture 411.

172

Tuohy Needle Bevel Orientation During Epidural Catheter Placement: Effect on Analgesic Success During Labor

M.G.Richardson MD*. R. Wissler MD PhD*t

Departments of Anesthesiology* and Obstetrics & Gynecology+, University of Rochester School of Medicine and Dentistry, Rochester NY 14642

Analgesia: epidural

OBJECTIVES: Techniques designed to reduce the incidence of postduraI puncture headache (PDPH) while reliably producing effective analgesia are highly desirable. Dural puncture with a spinal or epiduml needle bevel oriented parallel to the longitudinal axis of the spine results in reduced incidence of PDPH as compared to the perpendicular orientation.(l,2) Some recommend the epidurrd needle be inserted with bevel oriented laterally, followed by 90” rotation to cephalad after obtaining loss of resistance.(2) Recommendations to rotate the needle prior to catheter insertion continue to prompt debate regarding the safety of needle rotation within the epidural space, with concern about potential “coring” of the dura during needle rotation.0) Ninety-degree rotation of a laterally-oriented bevel to cephalad prior to epidural catheter insertion has been assumed to be necessary without supporting evidence. If catheter placement is equally satisfactory when inserted through the lateral-oriented bevel, then the rotation technique is unnecessary. We compared the effects of catheter insertion through lateral- and cephalad-oriented Tuohy needles in laboring parturients. METHODS: This prospective study received IRB approval. Informed consent for epidurai analgesia was obtained. 18G Tuohy needles and 2OG ouen-ended, non-style&d , singleorifice catheters were used (B.Braun Medical, Inc., Bethlehem PA). Lidocaine with epinephrine was used to rule out IV and inunthecal catheter placement. OB anesthesia service residents were randomized to identify the epidural space with the needle bevel oriented either cephalad (C) or lateral Q for the first half of the month, and vice versa during the second half. After loss of resistance, catheters were inserted without needle rotation and were managed per routine. Demographic data and details of anesthetic management were recorded. Pain VAS scores were obtained prior to and 20 minutes after administration of epidural analgesics. Outcomes compared included ease of catheter insertion, presence and location of paresthesias, presence and extent of sensory block bilaterally at 20 minutes, need for catheter redosing owing to inadequate analgesia at 20 minutes, need for catheter replacement, and occurrence of intravenous cannulation or durai puncture. Asymmetric sensory block was defined as at least a 2-segment greater extent on either side. All parturients were evaluated for PDPH. Data were analyzed with the chi square or Fisher’s exact test as appropriate, with p < 0.05 considered significant. RESULTS: We studied 500 parturients undergoing 534 catheter placements. Incidence of impossible catheter insertion beyond the needle orifice was greater in the lateral group @ c 0.001) (Table). However, subsequent successful catheter insertion was achieved in each of these cases by needle withdrawaI and reestablishment of loss of resistance. The incidence of paresthesias was greater in the lateral group (31% L vs 23% C, p=O.O35). When paresthesias occurred during catheter insertion, there was a greater incidence of asymmetric block than when psresthesias were absent (35% vs 24%. p=O.O29). In parturients who experienced both paresthesias and asymmetric block, the greater extent of block was more often on the same side as the paresthesia (81%) than on the contralateraI side (19%) @ c. 0.001). There were no significant differences in the incidence of dural puncture (2.0% C, 3.8% L), or the incidence of PDPH following known durai puncture (33% C vs 11% L, p=O.525).

Successful catheter placement with initial attempt; satisfactory analgesia Successful catheter placement with initial attempn catheter replaced owing to IV cannulation, absent or inadequate sensory block

Cephahd (n = 294) Lateral (n = 240) 264 (89.8%) 185 (77.1%)

19 (6.5%) 18 (7.5%)

Initial catheter insertion impossible; subsequent insertion successful 5 (1.7%) 28 (11.7%) Dural puncture 6 (2.0%) 9 (3.7%)

DISCUSSION: Epidural catheter insertion through a laterally-oriented Tuohy needle results in comparable rate of success in providing satisfactory analgesia for labor. However, the technique is associated with a greater incidence of difficulty passing the catheter beyond the needle orifice, as well as a greater incidence of paresthesias. For those anesthesiologists concerned about the safety of epidural needle rotation, lateral bevel orientation may be an acceptable alternative technique despite these limitations. REFERENCES: 1. Mihic D: Reg Anesth 10:76,1985. 2. Norris M: Anesthesiology 70:729,1989. 3. Bromage P: Anesth Amdg 81:204,1995

173

COMPARISON OF FLEXOMETALLIC AND NYLON CATHETERS FOR EPIDURAL LABOR ANALGESIA IN PARTURIENTS USING MIDLINE AND PARAMEDIAN APPROACH

M. C. Sama MD, A. K. Soni MD and N. E. Oriol MD.

Dept. of Anesthesia and Critical Care, Beth Israel Hospital, Harvard Medical School, Boston MA.

Epidural, Paramedian, Midline, Flexometallic, Nylon, Paresthesia

Introduction: Two approaches to the epidural space are commonly employed- midline (ML) and paramedian (PM). Recently a flexometallic catheter, Arrows catheter has been introduced into clinical practice. The proposed advantages of this catheter are a decreased incidence of paresthesia, lower incidence of vessel puncture and accidental dural penetration. The PM approach may offer these advantages.(l) To our knowledge no study has compared these techniques and two different catheters in a fashion that controls for inter-operator experience, position of patient during placement and fluid used for loss of resistance. The aim of this study is to evaluate the end-hole flexometallic catheter (19G) in comparison to the multi-orifice nylon Portex@ catheter (20G) via the two approaches. Methods: Following IRB approval a prospective randomized study was initiated. To date 54 women requesting labor analgesia have been enrolled. Two anesthesiologists, AKS and MCS with more than ten years’ experience each undertake all procedures. AKS routinely employs the PM approach while MCS routinely practices the ML approach. However, for the purposes of this study subjects are randomized to either operator who is then randomized to the midline or paramedian technique with either the Portex or Arrow catheter. Patients are sat up for the procedure using loss of resistance to saline to identify the epidural space with a 17 G Touhy needle. Catheters are advanced 5 cm into the epidural space. An independent observer notes- pain experienced by the parturient during epidural placement on a visual analogue score (VAS), ease of catheter insertion (scale l- easy, 2- obstruction overcome by mild force, 3- obstruction requiring moderate force and 4- complete obstruction requiring needle reinsertion), paresthesia and presence of blood or cerebrospinal fluid in the catheter. Following a negative test dose of 3 cc of 1% lidocaine & 15pg of epinephrine, 15 cc of a mixture of bupivacaine 0.04% + fentanyl 1.66pg/cc + epinephrine 1:600,000 is bolused via the epidural catheter. 15 minutes later the height of block to cold is recorded along with degree of pain relief. Mode of delivery, duration of labor, replacement of catheter, use of rescue analgesia (bolus needed), adequacy of analgesia/anesthesia and ease of removal (I- easy; 2- force applied to pull; 3- stretching of catheter) are also noted. Parametric data are analyzed by ANOVA and non parametric by Kruskal Wallis and chi square test. Results: No difference was found in the demographics among parturients managed by the two operators. No CSF was observed in any catheter. Data are displayed according to the catheters used (table 1) and approach to the epidural space (table 2). VAS scores of discomfort during epidural placement were similar in the two approaches (p=O.44). Incidence of paresthesia upon catheter insertion was significantly greater with the nylon catheter (;1* =4.96, ~~0.05 ), as well as with ML approach (x2 =4.96, p<O.OS). Both catheters were easier to thread via paramedian approach (x2 =6.59, p<O.O25). No catheter needed to be replaced for inadequate block. Depth of space via paramedian approach was greater than via midline (p==O.O05). Two catheters that required moderate force during removal were flexometallic and had been placed via ML approach. Table 1.

Catheters (n) Operator Approach Paresthesia Ease of insertioe Blood in u w ti -removal

mcs aks ML PM mild mod severe 1 2 3 4 I 2 3 Flexometallic(26) 16 10 13 13 1 1 1 ) 0 0 15 8 1 0 3 20 4 2

Nvlnn128~ 16 17 15 l? f; I 3 I 1 3 33 6 7 n A 95 7 n

Taole L. Approach (n) Ooerator Paresthesia Ewl Ease of insertioq Wf BQl.w Death

b removalJ.uzd&@wz mcs aks mild mod severe & 1 2 3 4 1 2 3 m m

Midline(28) 20 8 5 1 3 1 1 1 16191310 2313121 4 5.04*0.13 Paramedian(26) 12 14 2 I 0 ( 0 1 23(3jOlO 2214101 3 5.8i0.25 Conclusiow Flexometallic catheter may have certain advantages. There was a lower incidence of paresthesia and vessel puncture. However its removal may require mild to moderate force resulting in stretch that may be harmless but nonetheless disconcerting. PM approach was associated with lower incidence of paresthesia and greater ease of insertion of both catheters. Pain scores during placement were similar with both approaches. References: 1. Blomberg RG, Jaanivald A, Walther S, Anesthesia 1989;44:742-46

174

TITLE: A Comparison of Uniport and Multiport Epidural Catheters

AUTHORS: R D’ Angelo, MD, ML Foss, MD, CH Livesay, MD

AFFILIA-fION: Department of Anesthesia, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1009

KEYWORDS: Epidural, Catheter, Analgesia, Anesthetic Techniques, Obstetrics, Complications

INTRoDucTIoN: Although strong opinions arc often expressed (Collier)’ concerning the details of cpidural catheterization in obstetrics, such as type of cpiduml catheter, distance inserted into the cpidural space, and utility of manipulating poorly functional catheters; there is little systematic, controlled experience upon which to base these options. As part of a series of systematic studies of such details,* we compared uniport (single distal port) and multiport (closed end, three lateral ports) catheters for epidural labor analgesia

METHODS: After IRB approval and informed consent, 487 parhuients requesting epidural analgesia were randomized to have either a uniport or multiport epidural catheter (B Braun Medical) inserted 6cm into the epidural space. The incidence of intravenous cannulation, unilateral sensory analgesia, and catheter manipulation, failure, or replacement was recorded. Statistical analyses included Wilcoxon Rank Sum Test, Chi Square, and Fisher’s Exact with Holms sequentially rejective Bonferroni correction as appropriate (PcO.05 significant).

w: Demographic variables were similar between groups. Multiport epidural catheters were less likely to result in unilateral sensory analgesia or require manipulation; however, the incidence of intravenous cannulation and catheter failure or replacement was similar between groups (Table). No catheter was associated with multi compartment (epidural, intrathecal, intravenous) placement.

COMPLICATIONS (“/9 Complication Multiport uniport

n=245 n=242 Intravenous Cannulation 6.5 7 Unilateral Analgesia 21* 32 Catheter Manipulation 31* 44 Catheter Failure 3 3 Catheter Replacement 10 10

* PcO.05 compared to uniport catheters

CONCLUSIONS: We find that while similar in many respects, multiport epidural catheters reduce the incidence of two common complications: unilateral sensory analgesia and epidural catheter manipulation. Therefore, we conclude that although uniport epidural catheters are not unacceptable, multiport epidural catheters potentially reduce manpower demands.

Referencess: ‘Collier CB et al. Regional Anesth 19:378, 1994; ?D’Angelo R, et al. Anesthesiology 84:88, 1996

175

AN IA’ V/V0 EVALUATION OF FOUR SPINAL NEEDLES USED IN THE COMBINED SPINAL-EPIDURAL TECHNIQUE

L M. Newman, PhD, MD, J. B. Jaffee MD, E. C. Perez, MD, A. D. Ivankovich, MD

Department of Anesthesiology, Rush Medical College at Rush-Presbyterian St. Lukes Medical Center, Chicago Illinois

Combined spinal-epidural analgesia, labor analgesia, Spinal needles; pencil point, paresthesias

INTRODUCTION: The use of the combined spinal epidural(CSE) technique accounts for over 90% of the anesthetic techniques done for obstetrical anesthesia/analgesia at our institution, There are little data on the efficacy or complications of the different spinal needles used for CSE. The study evaluated four different spinal needles used for CSE employing the needle through the needle method. METHODS: After IRB approval we randomly assigned patients to one of four groups corresponding to the four long spinal needles used for the CSE technique. We evaluated the 27 gauge 4 11 II 6 Whitacre needle, the 27 and 25 gauge DurasafeTM needles, as well as the Gertie MarxTM 26 gauge needle. The needles were evaluated for success rate in obtaining CSF as well as the incidence of paresthesias from the subarachnoid puncture and post dural puncture headaches (PDPH). Data were analyzed with x2 and p c .05 was considered statistically significant. RESULTS: 407 patients were studied and the results are presented in the table. In all patients the epidural portion of the CSE was effective.

1 Whitacre 27g 1 Durasafe 27a 1 Durasafe 25o 1 G. Marx 26a 1 Total I

*p c.05 when compared to G. Marx 269 ‘p ~05 279 Whitacre + Durasafe vs 25 + 269

The larger needles (25 & 26 gauge) produced significantly more paresthesias than did the 27 gauge needles. There was no signficant difference in the failure rate for the spinal portion of the CSE technique between different needles (3 to 4.9%). Only two patients reported post dural puncture headaches. DISCUSSION; This study confirms the needle through the needle method of the CSE technique leads to a high degree of success for the spinal (95.1 to 97%) and epidural (100%) segments. The zero incidence of failure for the epidural portion of the CSE is less that the 1.5 to 5% reported for continuous lumbar epidural analgesia alone. ‘.* It is felt the greater success is a function of the use of the CSE method. The data also corroborate the known low rate of PDPH using pencil point spinal needles. The unexpected high rate of paresthesias from the needles is felt due to the long tip of the needle. The occurrence of paresthesias were not associated with any residua. The data suggest the use of a smaller gauge spinal needle will decrease the incidence of paresthesias associated with subarachnoid puncture. REFERENCE& 1 .Glosten, B: Local Anesthetic Techniques, Obstetric Anesthesia: Principles and Practice. Edited by Chestnut DH. St. Louis, Mosby, 1994, pp 368. 2. Norris et al. Anesth Analg, 1994:79;529

176

Anaesthesia Related Maternal Mortality in Calabar. (A Six Year Retrospective Study)

Dr. Ekaete Udo-Affah, Dr. Sylvia Akpan, Dr. E. E. J. Asuquo.

Key words: Anaesthesia, Maternal Mortality

INTRODUCTION: Calabar is an old coastal city in the South Eastern part of Nigeria. This

study was carried ou; at the University of Calabar Teaching Hospital which is a 352 bedded

referral centre. The maternity unit has 100 of these beds.

Since the St. Margaret Hospital which commenced in 1895, became the teaching hospital in 1982

no study on anaesthesia related maternal deaths has .been done. The aim of this retrospective

study was to evaluate the incidence of anaesthesia related maternal mortality (Non obstetric cases

such as ectopic pregnancies, abortions, molar pregnancies were excluded).

METHOD: Maternal mortality records over a six year period (January 1989 to December

1994) were reviewed.

RESULTS: 9,45 1 women, (> 28/52 gestation) were admitted and treated over the period. 95

maternal deaths were recorded. Of these 95 deaths 51 of them had anaesthesia during the course

of their treatment. Amongst those anaesthesized 5 (9.8%) died from causes directly attributed

to anaesthesia (1, a sickler with difficult airway, 2 difficult airway and aspiration, 2 silent

regurgitation and aspiration).

Many pregnant women presented late and in very poor physical status, therefore constituting

severe anaesthetic risks. Some had already spent days with the traditional birth attendants and

in prayer houses before reporting in the hospital.

CONCLUSION: Maternal deaths as a whole could be reduced if adequately trained manpower

and facilities are readily available in government owned hospitals. Likewise, women of child

bearing age should be encouraged to attend antenatal clinics and report to hospital early rather

than waste precious time at prayer homes.

177

AEsIRAcl-FoRh4

TITLE: Consumer Education and Patient Attitude Towards Labor Analgesia

WIHORS M. Cascio MD, J. Rabazie MD, S. Ramanathan MD

GFKmT1ON: Department of Anesthesiology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket St., Pittsburgh, PA 15213

mcuLB Consumer Education, Obstetric Analgesia

Introduction: Regional analgesia (RA) for labor is very popular in many centers. A variety of information sources (IS) is available to the consumer and only rarely an anesthesiologist may be the direct IS for the consumer. We did a survey of our consumers to see the impact of consumer education (CE) on the patient’s attitude towards RA for labor. Methods: A preanesthesia interview to explain risk/benefit was done by the anesthesiologist prior to the procedure. Patients were asked to fill out a questionnaire after pain relief The important questions were: 1) what was their IS?, 2) who influenced them the most in choosing RA?, 3) what was their worst fear about RA?, 4) did they continue to have the same fear after the procedure?, 5) did the IS discuss problems associated with RA’?, 6) was the S accurate?, 7) were they satisfied with RA?, 8) did they feel guilty?, 9) would they have liked to talk to the anesthesiologist prior to hospitalization ? Results: Approximately 80% of patients receive RA for labor in our institution. A total of 300 forms were Shed out. Important IS were childbirth CE classes and obstetricians (Table). Friends and family members were most influential in the patient’s choice to have RA. Fear of needles, paralysis and possible adverse baby outcome were most frequent fears (Table) and 82% of patients lost that fear after the procedure. Sixty- one percent of patients said that risks of IL4 were not mentioned by the IS. Yet, only 27% preferred to have had a discussion with the anesthesiologist prior to hospitalization. Ninety-nine percent of patients were satisfied with the

Headache 6

Conclusion: Our data show that CE classes and obstetricians are major information sources and therefore anesthesiologists must focus on educating these two sources adequately so that accurate information may be disseminated to the consumer. The satisfaction rate was high and only a small percentage of patients had a guilty feeling.

178

Practice Patterns of Anesthesiologists Regarding Situations in Obstetric Anesthesia where Clinical Management is Controversial

Y. Beilin MD, E.M. Haddad BS, C.A. Bodian, Dr.PH, A.B. Leibowitz MD

Departments of Anesthesiology and Biomathematical Sciences, Mount Sinai School of Medicine, New York, NY 100296574

Academic practice, complications, controversy, private practice, survey

INTRODUCTION: The goal of this study was to assess the practice patterns of anesthesiologists in both academic (acad) and private (pvt) practice when confronted with situations in obstetric anesthesia for which management is controversial, and to determine if there is a difference in practice between the two groups. METHODS: A survey containing 47 questions, 40 regarding clinical practice and 7 regarding demographics, was mailed to 153 directors of obstetric anesthesia in acad practice and to 153 anesthesiologists in pvt practice. Questions relating to the following areas of practice were asked: 1) preoperative laboratory testing; 2) preeclampsia and possible coagulopathies; 3) epidural placement in women with “spinal problems”; and 4) use of epidural opioids and intravenous supplementation. Results were analyzed with the chi square, ManteCHaenszel and Student t-tests where appropriate. P < 0.05 was considered significant. RESULTS: Surveys were returned by 113 (74%) acad anesthesiologists and 94 (61%) pvt practice anesthesiologists. By univariate analysis, 14 questions showed a significant difference in response between those in acad and pvt practice, but only 8 remained significant after accounting for the amount of time currently devoted to obstetric anesthesia (greater than or less than 50%). Below are some of the results, the remainder will be presented at the meeting. The most frequently ordered laboratory tests prior to epidural placement in the otherwise healthy parturient is a complete blood count (acad=45%, pvt=68%, ~~0.05) and a platelet count (acad=17%, pvt=31%, pcO.05). The majority of responding anesthesiologists would place an epidural anesthetic when the platelet count is between 80,000 and 100,000~mm” (acad=66%, pvt=55%). Most requested a platelet count in mild preeclampsia (acad=93%, pvt=93%) and severe preeclampsia (acad=98%, pvt=lOO%). Fewer anesthesiologists requested a prothrombin time (acad=23%, pvt=39%), partial thromboplastin time (acad=21%, pvt=39%) or fibrinogen (acad=5%, pvt=l8%, ~~0.05) in mild preeclampsia than in severe preeclampsia (prothrombin time: acad=73%, pvt=90%, ~~0.05; partial thromboplastin time: acad=73%, pvt =89%; or fibrinogen: acad=42%, pvt=68%, ~~0.05). The bleeding time test is frequently used to aid in the decision about placing an epidural anesthetic in a preeclamptic patient or one with a low platelet count (acad=48%, pvt=76%, pcO.05). Most would place an epidural anesthetic if a woman has amnionitis after antibiotics are administered and her temperature decreases below IOl’F (acad=89%, pvt=74%, p<O.O5). Most would place an epidural anesthetic in a woman with a Harrington rod (acad=86%, pvt=81%), scoliosis (acad=96%, pvt=93%), symptomatic herniated disc (acad= %, pvt=93%), and asymptomatic herniated disc (acad= %, pvt=71%). Ketamine is the most commonly used drug (acad=76%, pvt=64%) to supplement a regional anesthetic during cesarean section, followed by fentanyl (acad = 65%, pvt = 44%, p c 0.05) and midazolam (acad = 31%, pvt = 16%, p c 0.05) CONCLUSIONS: Although there were some differences in the responses between those in acad and pvt practice, overall they were similar. The amount of time currently devoted to obstetric anesthesia was also a determinant of some practice patterns.

179

TITLE: Obstetric Anesthesia Safety Improvement Study (OASIS): Results of a survey of 320 hospitals

AUTHOR: Barbara Zucker-Pinchoff, MD

AFFILIATION:Department of Anesthesiology, The Mount Sinai Medical Center, New York, NY

KEYWORDS: complications, obstetric anesthesia, outcomes, risks

INTRODUCTION: Serious complications of obstetric anesthesia are rare, but their consequences can be devastating. There are about 4 million births per year in the United States, so it can be conservatively estimated that at least 1.5 million obstetric anesthetics are administered annually to parturients. Few data have been collected on the incidence of serious complications occurring in this population. Closed claims analysis ‘!* has yielded some information, but is necessarily limited to those cases that come to litigation. These data also yield no denominator data, such as the total number of deliveries, which makes estimates of the overall incidence of adverse events impossible. The obstetric anesthesia work force survey” provided information about the current practice of obstetric anesthesia in the United States, but was not designed to look at outcomes. METHODS: Questionnaires were sent to one SOAP member at each of 320 institutions throughout the United States. The survey included data elements to provide denominator data, as well as questions regarding complications for calendar year 1995. The returned questionnaires are completely anonymous since anonymity is an important issue when studying events which may lead to litigation. RESULTS: Thus far, completed questionnaires have been received from 126 hospitals, representing 368,124 deliveries (updated data will be presented). The number of deliveries per institution varied from 250 to 11,000. The percent of parturients receiving epidural or spinal analgesia for labor was between 5% and 95%, the percent of cesarean deliveries varied from 2.5% to 39%. Linear regression showed no relationship between the number of deliveries per year, and the percent cesarean deliveries (p=O.91). Neither was there any relationship between the percent of parturients receiving spinal or epidural analgesia for labor and the percent of cesarean deliveries (p=O.81). The most frequently reported complication was unanticipated high block. 119 high blocks were reported, of which 68 required intubation; no sequelae were associated with these events. Pulmonary edema was reported 44 times, mostly in association with preterm labor and its treatment, all without sequelae. Difficult intubations were reported 27 times, with 2 cases of aspiration. Eleven deaths were reported, for a rate of approximately 4.6 per 100,000 anesthetics. All of the reported deaths involved major pathologic processes, such as amniotic fluid embolus, uncontrollable hemorrhage, or severe pre-eclampsia. Seven cases of permanent disability were reported; 2 neurologic (a peroneal nerve palsy and an obturator palsy), 2 difficult intubations complicated by aspiration1 ARDS complicating pre-eclampsia, 1 epidural hematoma in a patient with multiple back surgeries, and 1 broken spinal needle. CONCLUSIONS: Among the responding institutions, the use of neuraxial analgesia is not related to the cesarean delivery rate. Complications resulting in permanent disability or death are rare, and the majority are related to underlying pathologic processes, REFERENCES: 1. Chadwick HS, Gunn HC, Ross BK, Glosten B, Posner K. Anesthesiology 1995;83:A951 2. Chadwick HS, Posner K, Caplan RA, Ward RJ, Cheney FW. Anesthesiology 1991;74:242-9 3. Hawkins JL, Gibbs CP, Orleans M, Schmid K. Anesthesiology 1994;81 :A1 128

180

a2-ADRENERGIC RECEPTOR NUMBER AND FUNCTION DURING PREGNANCY

Caroi B. Pantuck, BA, Richard M. Smiley, MD, PhD

Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY 10032

Alpha-adrenergic receptor, pregnancy, sympathetic nervous system

INTRODUCTION: Alpha-2 adrenergic receptors (a2ARs) exist in presynaptic and post-synaptic locattons throughout the nervous system and peripheral organs. Effects of cr2AR stimulation include uterine contraction, vasoconstriction, and

modulation of neural pathways of analgesia and neurotransmitter release. Little is known about possible a2AR regulation in

pregnancy.l These receptors are increased in some tissues in hypertensive states, and there has been at least one report of increased ct2ARs in women with pregnancy-induced hypertension. 2 The ol2ARs of human platelets have been used as a

model for similar receptors on vascular, uterine and other tissue. 3,4 We have assessed the number and function of CQARS on

platelets obtained from pregnant women to determine if there are predictable alterations in this receptor system during pregnancy. METHODS: With IRB approval and after written informed consent, blood samples (35 ml) were obtained at 10 weeks, 20 weeks, 30 weeks, 37 weeks gestation, and lo-14 weeks postpartum. No patient was receiving any medication other than prenatal vitamins, and all were free of significant medical conditions. Platelets were isolated from platelet-rich plasma by centrifugation. Cyclic AMP (CAMP) production, in the presence of propranolol to eliminate B-receptor activity, was determined in platelets exposed to 10 pM prostaglandin El (PGEl) alone or in the presence of 10 pM epinephrine (EPI). The ability of a2AR stimulation by EPI to inhibit CAMP production was used as a measure of receptor function. aAR number

and binding affinity were determined using 3H-yohimbine (l-20 nM), with 10 pM phentolamine to assess non-specific binding. Binding data were evaluated by Scatchard analysis. Data were analyzed using repeated measures ANOVA, with p < 0.05 considered statistically significant. RESULTS: Twenty one women were entered into the study, 16 of them by 10 weeks gestation. No significant changes in receptor number, binding affinity, or CAMP production were detected over the course of pregnancy.

DISCUSSION: The establishment of a normal baseline for o2AR number and function during human pregnancy is a prerequisite to understanding possible alterations in adrenergic receptor signal transduction in women with complications of pregnancy, particularly gestational hypertension and preeclampsia. Understanding AR function during pregnancy may contribute to increased understanding of the mechanisms of labor and can help to rationalize the use of qagonists for labor, operative, or postoperative analgesia. REFERENCES:

1. Dahle LO, Anderson RGG, Berg G, et al. Gynecol Obstet Invest 1993; 36:75-80 2. Sanchez A, SBz J, Sbz B, et al. J Hypertension 1992; 10:831-7. 3. Brodde O-E, Seher U, Nohlen M, et al. Eur J Pharmacol 1988; 150: 403-4. 4. Motomura S, Schnepel B, Seher U, et al. J Hypertension 1989; 7 (Suppl 6): S50-1. This work was supported in part by a Clinical Scholar Award from the International Anesthesia Research Society.

181

S-ADRENERGIC RECEPTOR NUMBER AND FUNCTION DURING HUMAN PREGNANCY

Carol B. Pantuck, BA, Richard M. Smiley, MD, PhD

Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY 10032

Beta-adrenergic receptor, pregnancy, sympathetic nervous system

INTRODUCTION: Stimulation of the B-adrenergic receptor (OAR) mediates relaxation of uterine muscle, vasodilatation, positive chronotropic and inotropic cardiac effects, and is involved in a variety of metabolic regulatory processes. Drugs which stimulate the l3AR remain a mainstay of the treatment of preterm labor. Pregnancy alters the physiologic response to multiple drugs, hormones and neurotransmitters. Down-regulation (decreased number) and desensitization (decreased function) of BARS may occur during normal or complicated pregnancy or following treatment of preterm labor with O-agonists and may be involved in the onset of normal labor. ’ 3 Human lymphocytes possess l32ARs which appear to reflect the status of

receptors on less-accessible organs, such as the heart, lung, and uterus.2,4 Previous studies disagree on whether lymphocyte BARS are altered during pregnancy.5-7 We have investigated number and function of B2ARs on lymphocytes obtained from women throughout pregnancy to determine if there are predictable alterations in this receptor system during human pregnancy. METHODS: With IRB approval and after written informed consent, blood samples (35 ml) were obtained from pregnant women at 10 weeks, 20 weeks, 30 weeks, 37 weeks gestation, and lo-14 weeks postpartum. No patient was receiving any medication other than prenatal vitamins, and all were free of significant medical conditions. After removal of platelet-rich plasma, lymphocytes were isolated by density gradient centrifugation through Ficoll. Cyclic AMP (CAMP) production was determined in unstimulated lymphocytes (Basal) and in response to stimulation by 10 PM isoproterenol (ISO), 1 pM forskolin (FSK), and 10 uM prostaglandin El (PGEl). BAR number (B ,,,ax) and binding affinity (KB) were determined using

1251-iodopindolol (2.5-240 PM), with 10 uM propranolol to assess non-specific binding. Binding data were evaluated by Scatchard analysis. Data were analyzed using repeated measures ANOVA, with p < 0.05 considered statistically significant. RESULTS: Twenty-one women were entered into the study, 16 of them by 10 weeks gestation. No significant changes in receptor number, binding affinity, or CAMP production were detected over the course of pregnancy. One subject who received 5 weeks of terbutaline treatment for preterm labor starting at 31 weeks bad a 60% decrease in B,,, at 36 weeks compared to

her value at 30 weeks. A similar reduction was seen postpartum in a woman using an albuterol inhaler for a few days. LYMPHOCYTE BARS DURING PREGNANCY

10 weeks 20 weeks 30 weeks ~737 weeks Postpartum n (subjects) 16 21 21 20 19 Basal CAMP (pmo1/1Oecells/1O min) 6.4 f 1.2 4.7 f 0.7 5.0 * 0.9 4.9 * 0.9 5.7 f 0.7 IS0 CAMP (pmo1/106cells/10 min) 17.6 f 3.2 11.5 + 1.4 13.9 f 2.7 11.4 f 1.7 14.1 + 1.6 FSK CAMP (pmo1/1Oecehs/10 min) 9.8 f 1.3 10.3 * 3.0 9.0 * 1.9 7.6 + 1.0 10.1 f 1.2 PGEl CAMP (pmoI/1Oecehs/10 min) 86.9 f 17.9 70.2 f. 9.4 87.9 + 21.9 78.4 f 9.9 99.9 * 11.0 B,,, (receptors/cell) 1541 + loo 1244 + 89 1407 f 224 1091 f. 78 1342 * 132 Kn (PM) 40.6 f 10.5 39.6 f 8.2 22.3 + 3.6 17.2 + 2.2 25.0 f 5.1

Data are mean * SEM. DISCUSSION: Like Santala et al.,5 but unlike von Mandach et al.‘&nd Nwosu et al.,7we found no significant alteration in BAR number or function during pregnancy. The establishment of a normal baseline for BAR number and function in pregnant women is a prerequisite for the study of receptor properties in women with gestational hypertension, or diabetes, preterm labor, or other complications of pregnancy. It can also serve as a starting point for investigations into the possible role of signal transduction systems in the onset and maintenance of normal labor. Understanding AR function during pregnancy may improve management of hemodynamically compromised pregnant women such as those with preeclampsia or pre-existing cardiac valvular disease and rationalize the use of 8-2 agonists for the treatment of preterm labor, REFERENCES: 1. DeSimone CA, Leighton BL, Norris MC, et al. Anesthesiology 1988; 69: 626-628. 2. Michel MC, Pingsmann A, Nohlen M, et al. Clin Pharmacol Ther 1989; 45: l-8. 3. Breuiller M, Doualla-Bell F, Litime MH, et al. Adv Prostagiand Thromb Leukot Res 1990; 21:811-814. 4. Brodde O-E, Kretsch R, Ikezono K, et al. Science 1986; 231: 1584-5. 5. Santala M, Vilska S, Saarikoski S, Cast& 0. Eur J Obstet Gynecol Reprod Biol 1990; 34: 79-87. 6. von Mandach U, Gubler HP, Engel G, et al. Br J Pharmacol 1993; 108: 356-62. 7. Nwosu UC, Rice PJ. Proc Sot Exp Biol Med 1995; 209:157-62.

This work was supported in part by a Clinical Scholar Award from the International Anesthesia Research Society.

182

. . Thrombopolet.tn in Pregnancv

S.B. Corn, M.D., M.A. Frolich, M.D., S. Datta, M.D. FFARCS (Eng)

Department of Anesthesia, Brigham and Women’ s Hospital Harvard Medical School, Boston, MA 02115

Thrombopoietin, Pregnancy, Platelets, Coagulation

Introduction: In late pregnancy, there is increased activation of the platelet, clotting, and fibrinolytic systems in vivo (I). Increased platelet activation leads to platelet aggregation in vivo and a reduction in platelet counts. The hypothesis of platelet hyperdestruction is supported by the considerable variation in platelet counts and the increased platelet distribution widths found in late pregnancy (2). In 1994 de Sauvage et. al. (3) purified the human genomic ligand of a viral gene (c-Mpl) known to induce a myeloproliferative leukemic state in mice. Later the c- Mpl ligand was shown to be thrombopoietin (TP0)(4), for which an assay became available in spring of 1995. Presently it is not known if there are qualitative changes of TPO in pregnancy. We undertook this study to test the null hypothesis that there are no significant differences in TPO levels in term parturients compared to the non-parturient control group. The TPO ELISA assays were conducted by courtesy by the research laboratories of Amgen, Inc., Thousand Oaks. CA. Methods: We compared the TPO plasma levels of healthy term pregnant patients (#17) with TPO plasma levels of healthy non-pregnant controls (#15). The patient groups were demographically similar. Patients with any significant medical problems and/or tobacco, alcohol or drug use were excluded. Samples in pregnant patients were obtained before the onset of labor (scheduled labor inductions or scheduled Cesarean sections). Non-pregnant controls were identified in our day-surgery unit. Results: 300

224 x 109/L f I9 for pregnant 250

Platelet counts were 200 patients and 756 x 109/L f 21 (mean + SE) for 150 non-pregnant controls (non-significant at p = 0.05). 100 --.._

TPO ;~ssavs were 272 pg/ml k I9 for pregnant 50 ( n Thrombopolebn

patients &d 165 pg/ml + 21 for non-pregnant 0 .) ) OPIatelets

controls (statistically highly significant, p = 0.0007, Non-Pregnant One-way Anova).

Pregnant

Conclusion: This study is the first to report thrombopoietin (TPO) levels in pregnancy. We observed that TPO levels are significantly higher in pregnant patients compared to non-pregnant controls. This finding is consistent with previous reports which demonstrate increased platelet turnover in pregnancy (2). Our ongoing study includes patients with disease states associated with thrombocytopenia, i.e., pre-eclampsia and HELLP. Results of this study may lead to a role for recombinant TPO in the peripartum management of parturients affected by thrombocytopenia and in the treatment of these disorders. References: I. Increased intravascular coagulation associated with pregnancy, Gerbasi, F.R.,

Obstet Gynecol 75: 385-389(1990). 2. Platelets in pregnancy: hyperdestruction in pregnancy, Fay, R.A., et al.,

Obster Gynecol 61: 238-240(1983). 3. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand, de

Sauvage F.G. et al., Nature 369: 533-538(1994).

4. Thrombopoietin - at last, Metcalf, D., Nature 369: 519-520(1994).

183

Anti-Opioid Peptide Levels in the Cerebrospinal Fluid of Pregnant versus Non-Pregnant Women

SJ Larson, GL Roark, SN Baja, JS Portilla, RI3 Rothman and AP Harris

The Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, and the National Institute of Drug Abuse (NIH) Baltimore, Maryland

Anti-Opioid Peptides, Cholecystokinin

INTRODUCTION: Anti-opioid peptides (AOPs) are endogenous neuropeptides which attenuate opioid effects at the spinal cord level. Production of these AOPs may play an important role in individual variation in pain thresholds, analgesic requirements and narcotic dependence and withdrawal. Although an increased pain threshold has been described to exist during pregnancy, its etiology has not been proven. We hypothesized that an increase in endogenous neuraxial AOPs may play a role in this change in pain threshold during pregnancy. In this study, we quantitated and compared cerebrospinal fluid (CSF) levels of cholecystokinin (CCK, one of the AOPs) in pregnant and non- pregnant females.

METHODS: The protocol was approved by our institutional review board for human investigation. Thirty-two females of childbearing age were studied, including 18 parturients and 14 non-pregnant age-matched controls. The 18 parturients included 10 patients undergoing cervical suture placement under spinal anesthesia and 8 patients undergoing elective cesarean section at term under spinal anesthesia. The 14 control patients were undergoing gynecologic or lower extremity elective surgery under spinal anesthesia. No patients in either group had chronic pain syndromes or were taking any pain medications. After placement of the spinal needle, ICC of CSF was removed for quantitative analysis of CCK levels. The difference in CCK levels between pregnant and non-pregnant females, and between early and term pregnancy were analyzed using non-parametric methods. Data are expressed as mean f SEM, or median with range.

RESULTS: The gestational age was 13kl wks in the early pregnancy (cervical suture) group, and 39f 1 wks in the term pregnancy (c-section group). There were no differences in CCK levels between pregnant ( < 5, < 5-350) and non-pregnant (< 5, < 5-184) patients, as well as between early pregnant (< 5, < 5-12) and term pregnant (< 5, < 5-350) patients. Only 2 of the 32 patients had markedly elevated CCK levels: 1 patient in the control group and 1 patient in the term pregnant group.

CONCLUSIONS: We conclude that CCK levels are not elevated in the CSF during early or late pregnancy relative to the non-pregnant state. Whether another AOP may play a role in the increased pain threshold associated with pregnancy remains to be determined.

184

.MSlRAmORIVL I 1

TITLE: Maternal Stress Response During Labor Under Regional Analgesia with Epidural Lidocaine or Intrathecal Fentanyl

I AUIHORS: M. Cascio MD, C. Bemett BS, S. Ramanathan MD

~F~~TIo$)epartment of Anesthesiology, Magee-Womens Hospital, University of Pittsburgh Medical Center, 300 Halket St., Pittsburgh, PA 152 13

mm Labor Analgesia, Epidural Analgesia, Intrathecal Fentanyl, Maternal Stress, Cortisol

Introduction: Plasma cortisol levels have been shown to increase during labor in response to maternal stress(l). Labor epidural analgesia(LEA) with local anesthetics may not only prevent this increase but may decrease plasma cortisol level(2). Intrathecal fentanyl(ITF) analgesia has been shown to decrease maternal epinephrine levels during labor(3). In this study we report the effect of ITF or LEA on maternal cortisol levels. Methods: After IRB approval, and informed consent, 24 women at term in labor received ITF (n=12) or epidural Lidocaine (LEA) for analgesia. All patients received 500 ml of lactated ringers i.v. Venous blood samples were drawn at baseline and once every 5 min for 30 min from an indwelling venous cannula. Maternal BP and pain visual analog scores (VAS) were recorded. Cortisol levels were measured using radioimmunoassay. A combined spinal-epidural technique was used to inject 25 pg fentanyl intrathecally. Lido 1.5% 10 ml was injected via an epidural needle. Results were expressed as mean + 1 SE and compared using parametric or nonparametric ANOVA for repeated measures at p < 0.05. Results: There was a small but significant decrease in cortisol levels after LEA(Fig. 1). ITF had an inconsistent effect on maternal cortisol levels (Fig. 1). VAS pain scores were significantly decreased in both groups (Fig. 2). Conclusions: The results show that LEA affects maternal cortisol levels more than ITF does. This is probably due to a lack of neural blockade and hypothalamic deafferentation with the ITF. However, the effects of these two techniques on maternal cortisol levels are small compared to their effects on maternal epinephrine (Fig 2, previous study (3)).

Fig. 1 RasrraGsrtid Lc3ds

*=pc.o5

References: 1. Maltau J et. al., Am J. Obstet Gynecol 1979: 134:681-4. 2. Neumark et. al., Acta Anaesthesiol Stand 1985:29:555-9. 3. Cascio et. al. Anesthesiology suppl 83:3A pg. A943.

TITLE: Sub&me P and Met-Eakephalin Levelr in Cerebroapinal Fluid in Preg~~pncy

AL’THORS: P. Dalby MD, S. Ramanathan MD, C. Bernett. BS

AFFILIATION: Department of Anesthesiology and CCM, Magee-Womens Hospital; University of Pittsburgh; Pgh, PA

m= No&&m, Cerebrospinal fluid, Substance P, Met-enkephalin, Pregnancy

x ntroduction: Prcgnency is known to reduce local anesthetic requirement which is attributed to increased progesterone levels ‘. L mal anesthetics are believed to inhibit substance P (SP) binding with NKl receptor ‘. Previous research has shown decreased

P slasma SP in late pregnancy ‘. It is not known whether pregnancy alters CNS SP levels. Therefore we studied CSF SP levels in n elation to progesterone and other neurotransmitters: @ndotphin and met-enkephalin (Met-enk) in pregnant and nonpregnant v {omen.

n rlethods: IRE approval was obtained and the women gave written tiormed consent. Venous blood and CSF were obtained fl rom two groups of healthy women for the purpose of measuring SP, progesterone, g-endorphin , and met-enkephalin (Met-enk) 1 ‘erm pregnant women (n=lO) awaiting eleotive C-sections and nonpregnant women (n=l 1) awaiting gynecologic procedures \I mre studied. CSF was obtained before spinal anesthetic drug administration. Commercial radioimmunoassay kits were used for n measurements. Results were expressed as mean i 1 SD and analyzed utilizing t-test and regression analysis at p < 0.05.

tesults: Progesterone and Met-enk level in the CSF of pregnant women were signiflcautly higher than that in nonpreguant women. The level of progesterone in the CSF did not correlate signitIcantly with Met-E&, SP, or 8 -endorphin levels in pregnant lr nonpregnant women. However, CSF Met-et& level correlated inversely with CSF SP level (Fig 1; Met-enk CSF = 50.7 - 0.26xSP-CSF); I= - 0.61; p = 0.04) in nonpreguant women. In preguant women a direct correlation between Met-et& CSF and ;P-CSF was noted (Fig 2; Met-enk CSF = 25.5 + (0.26xSP-CSF): r = 0.75; p = 0.01).

hxussion: The scmce of CSF SP is thought to be primarily central terminal of the peripheral afferent ncciceptors. Previous tudies indicate that Met-Enk regulates the release of SP from these central terminals ’ .Our data show that the relationship etween SP and one of the endonenous ouiates is altered in pregnancy. Further work is needed to detetmine if this might result in

AlFslR4cTFoRh4

eduocd local anesthetic require&tit in pregnancy.

16 . .

. , NONPREGNANT

-‘---~.. . . . . . . . . . . ..__....._..~~.

PIG1 Referencea: 1. Butterworth JF, et al: Anesthesiology 72: %2-965,1987 2. Yue-Ming Li, PhD et al: Anesthesiology 82: 166-173,199s 3. Dalby PL, et al: Anesthesiology 79: A978, 1992 4. Levine JD, et al J Neuros&nce 13 : 2273-2286,1993

186

Peripartum Cerebrospinal Fluid Concentrations of Substance P and Neuropeptide Y

Christopher F. Ciliberto, M.D.*, Richard M. Smiley, M.D., PhD.*,

Jeffrey D. Friedlander, M.D.*, Erlinda Samaniego, B.S.*, Lena S. Sun, M.D.*?

Departments of Anesthesiology* and Pediatrics?, Columbia University College of Physicians and Surgeons, New York, NY 10032

substance P, neuropeptide Y, cerebrospinal fluid, pregnancy, analgesia, pain

Introduction: Substance P (SP) is a neuropeptide that has been identified in the spinal cord and cerebrospinal fluid (CSF) during episodes of stimulated pain. Recent studies that have investigated the role of neuropeptides in the responses to nociception have implicated neuropeptide Y (NPY) as a possible anal esic in pain states. Both SP and NPY have been shown to be elevated in rat spinal cord after noxious stimuli. 72 Therefore, it has H

been suggested that SP and NPY have a role in the pathophysiology of and response to pain. Xu showed that supraphysiologic doses of NPY possess antinociceptive properties. 3 The antinociceptive properties of NPY appear to be distinct from the opioid and alpha-2 adrenergic receptors, since these NPY effects were not reversed by opioid or alpha-2 antagonists. We measured NPY and SP concentrations in CSF during the peripartum period to demonstrate any possible role for these substances in the regulation of the acute pain of labor. Methods: After IRB approval, informed consent was obtained from 64 patients in the peripartum period. CSF (1.5 - 2.0 ml) was obtained from each participant by gentle aspiration through a 25G Whitacre spinal needle used during the institution of anesthesia or analgesia. Four groups of subjects were studied; all participants were ASA 1 and 2 with gestational ages ranging from 36 - 41 weeks. Group 1 (n = 20) consisted of parturients receiving intrathecal opioid at the time of epidural placement for labor analgesia (LA); Group 2 (n = 20) were patients undergoing elective cesarean under spinal anesthesia (EC); Group 3 (n = 11) consisted of patients undergoing cesarean section under spinal anesthesia after a trial of labor (LC); Group 4 (n = 13) were patients receiving spinal anesthesia for tubal ligations 8 - 24 hours post partum (BTL). NPY and SP concentrations were measured by radioimmunoassay, and data were analyzed by factorial ANOVA. Data are presented as means _+ SEM. Results: There were no significant differences between groups for either neuropeptide.

iA E-C LC BTL LA EC LC BTL

Discussion: Previous studies have demonstrated elevated levels of neuropeptides during episodes of acute pain.4 These have led to the speculation that NPY may have some usefulness for its analgesic potential. CSF concentration of NPY and norepinephrine (NE) vary in parallel. CSF concentrations of NPY were found to be increased only when norepinephrine concentrations could be maintained. 5 Tinkanen et al. demonstrated that NE concentrations in CSF were not affected by pregnancy or labor pain. 6 In our study we were unable to show a change in the CSF concentrations of NPY or SP during labor, while both have been shown to be elevated in post-operative pain states.7 Our negative results would suggest that these neuropeptides are not involved in the modulation of the labor pain. References: 1) Zhang R-X, Mi Z-P, Qiao J-T. Reg Peptides 1994; 51:25-32 2) Zhang X, Ji R-R, Nilsson S, et al. Eur J Neurosci_1995; 7:367-80 3) Xu X-J, Hao J-X, Hijkfelt T, Wiesenfeld-Hallin Z. Neurosci 1994; 63:817-26 4) Hua X-Y, Boublik J H, Spicer M A, et al. J Pharmacol Exp Ther 1991; 258:243-S 5) Modin A, Pemow J, Lundberg J M. J Auton Nerv Syst 1994; 49:123-34 6) Tinkanen H, Rorarius M, Mets&Ketell T. Gynecol Obstet Invest 1993; 35:7-11 7) Sjijstrijm S. Tamsen A, Hartvig P, et al. Anesth Analg 1988; 67:976-81

187

ACCIDENTAL DURAL PUNCTURE IN OBSTETRICAL PATIENTS: THE FAILURE RATE OF SINGLE EPIDURAL BLOOD PATCH

Gary J. Hunter, D.O., Steven T. Fogel, M.D., Barbel Hohmann, M.D.

Washington University Medical Center, Washington University School of Medicine, St. Louis, MO.

Obstetrical Anesthesia, Epidural, Post Dural Puncture Headache, Blood Patch

Introduction: Accidental dural puncture(ADP) and post dural puncture headache (PDPH) are recognized complications of cpidural anesthesia in obstetric patients. Reports have varied with respect to incidence of ADP and efficacy of therapeutic measures.’ A retrospective study was done to determine the incidence of ADP, PDPH, and efficacy of epidural blood patch (EBP) at the Washington University Medical Center. Methods: Data regarding ADP and PDPH following epidural catheter placement in an obstetric population was gathered and analyzed to determine the incidence of ADP, both recognized and unrecognized, and to evaluate the efficacy of conservative therapy and epidural blood patch (EBP). Data Ram all patients with documented ADP and clinical signs and symptoms of PDPH from the period July 1993 through June 1995 was gathered and reviewed in a retrospective manner. Patients with spinal or combined spinal-epidural procedures were excluded. The incidence of ADP and/or PDPH was determined. The efficacy of conservative and EBP therapy was evaluated. Results: The incidence of ADP in 3428 epidural catheter placements was 2.1%. ADP was recognized in 67% and unrecognized in 33%. Conservative therapy was efficacious in 32% of ADPs while EBP was required in 68% of the patients with ADP. A second EBP was required in 44% of patients receiving EBP (tables 1 & 2)

Table 1

Discussion: The incidence of ADP is similar to previously reported surveys. The success rate of fust EBPs however is tower than what has been reported by other authors.2~3 The reason for this is unclear, but a possibility is the method of follow-up. It is our practice to maintain contact with our patients for at least 48hrs until the headache is resolved without recurrence. If continuous follow-up was not practiced by previous authors, it may be that some failures of first EBPs were missed. Conftrmation of this point is suggested by Taivainen et aL4, who sent a questionnaire to patients for long-term follow-up. While an initial success rate of 91% was reported, long-term success rate was reported to bc onlyGl%. References: 1. Weeks. SK. Postpartum Headache, in Chestnut, DH, Ed. Obstetric Anesthesia 1994. Mosby Year Book Inc. 2. Brownridge P. The management of headache following accidental dural puncture in obstetric patients. Anesthesia and Intensive Care. 1 l( 1):4- 15, 1983 Feb. 3. Wu YW, Hui YJ, Tan PP. Experience of epidural blood patch for post-dural puncture headache. Acta Anaesthesiologica Sinica. 32(2): 137-40, 1994 Jun. 4. Taivainen T, Pitkanen M, Tuomincn M, Rosenberg PH. Eficacy of cpidural blood patch for post dural puncture headache. Acta Anaesthesiologica Scandinavica. 37(7):702-5, 1993 Oct.

188

EFFICACY OF GREATER THAN 20 CC VOLUME FOR EPIDURAL BLOOD PATCH.

S. D. Pratt MD, M. C. Sarna MD, A. K. Soni MD and N. E. Oriol MD.

Dept. of Anesthesia and Critical Care, Beth Israel Hospital, Harvard Medical School, Boston MA.

Epidural, Blood patch, Headache, Volume, Outcome.

moduction: Epidural blood patch (EBP) has become the gold standard treatment of post-dural puncture headaches

(PDPH). While reported initial success rates are highlX4, data on long term su::ess are less available. Two recent

reports suggest that EBP results in only a 50-60% p;rmanent cure of PDPH ’ . Further, the impact of injectate

volume on ;,yccess of EBP has not been well studied , and the practice of injecting up to 20 cc has come from “experience , and anecdotal reports. It has been the practice of our department to inject blood until the subject reports mild back pressure, and not to stop at a prescribed volume. This practice has lead to EBP injections of greater than 20 cc. We report our experience with this technique.

Methods: A computerized database of obstetric anesthetics was used to identify women who had received an EBP over a 20 month period. After chart review, women were contacted by telephone by a single investigator (SDP).

Data on the procedure itself, and initial results were obtained from the chart. Data on long term results and complications were from the follow-up phone interview. Verbal consent was obtained from each woman contacted.

Statistical analysis was done using the student-t test for parametric data, Kruskal-Wallis for nonparametric data, and chi square for frequencies. A p value of less that 0.05 was considered significant.

&&&: The search revealed 57 women who received a total of 68 EBP. The initial EBP was done on average 2

days after the dural puncture (range O-S), and the average volume injected was 23 cc (range 10-40). Of the 57 women, 4 had prophylactic EBP, and two had incomplete charts. Analysis of the remaining 51 revealed that 40 (78.3%) obtained complete relief at the time of the EBP, while 6 (11.7%) described improvement of symptoms without complete relief. Thus, only 5 of 51 (9.8%) were considered initial failures. 41 of the 51 (80.4%) were reached for follow-up. 24 of 41 (58.5%) said they had complete and permanent relief, while 9 (21.9%) said the headache returned after initial complete relief. 5 of 41 (12.2%) women had partial relief of symptom, and 3 (7.3%)

felt they got little or no benefit from the EBP.

We then analyzed the data by injectate volume: Group I had received 120 cc and group II >20 cc. There were no differences between the groups regarding demographics and timing of the first EBP. Twenty of 23 (87.0%) in the group II reported complete initial relief, and 15/23 (65.2%) had permanent relief. In group I 12/18 (66.7%) had initial and 9/l 8 (50%) had permanent relief. While the differences did not reach statistical significance (P=O. 15 for

initial results), there was a trend toward better efficacy with larger injectate volumes. Complications rates were low, consisting primarily of backache, and were similar in both groups.

Conclusions: Our data concur with recent reports which demonstrate that the permanent relief of PDPH with an EBP may not be as high as earlier data suggested. Furthermore, larger injectate volumes appear safe and may be associated with improved long term success. Additional prospective research is warranted to demonstrate the effect of injectate volume on success rate.

References: 1. DiGiovanni AJ, Anesth Analg 1972; 5 1:226-232 2. Stride PC, Cooper GM, Anaesthesia 1993; 48:247-255 3. Taivainen T, Acta Anaesth Stand 1993; 37:702-705 4. Crawford JS, Anaesthesia 1985; 40:381

189

Title: Metoclopramide Does Not Shorten the Duration of Labor or Decrease the Cesarean Delivery Rate in Term Parturients

Authors: C. Danae Steele, M.D., Louis M. Boxer, M.D., Barbara L. Leighton, M.D., Fazeela Ferouz, M.D., Ronald Wapner, M.D., Mark C. Norris, M.D.

Affiliation: Departments of Anesthesiology and Obstetrics and Gynecology (Division of Maternal-Fetal Medicine), Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Keywords: Metoclopramide; Labor, duration; Cesarean delivery

Introduction: Metoclopramide, a central dopamine antagonist and peripheral cholinergic agonist, induces strong peristalsis in uterine, ureteral and gastro-intestional smooth muscle. It hastens delivery in second trimester prostaglandin-induced abortions (1,2). A small study found a nonsignificant trend toward shorter labor in patients receiving one dose of metoclopramide 10 mg IV. We designed this randomized, double-blind study to determine if metoclopramide 10 mg IV every 6 hours affects the duration of term labor or the mode of delivery.

Methods: Sixty-eight healthy term parturients presenting in spontaneous or induced labor with cervical dilation c 5 cm and single vertex fetuses consented to participate in this IRB-approved study. Patients randomly received intravenous metoclopramide IO mg or saline 2 mL every 6 hrs until delivery. The patients and their obstetricians were unaware of the group assignment. Upon request for analgesia, patients received intrathecal sufentanil 10 pg followed by a continuous epidural infusion of bupivacaine, fentanyl and epinephrine. Oxytocin was used for labor induction or augmentation at the discretion of the attending obstetrician, Cesarean sections were performed for the usual indications. We recorded demographic data, modified Bishop scores on study admission, length of the first (4 to 10 cm cervical dilation), second (10 cm to delivery of head), and third (delivery of head to placental delivery) stages of labor, type of delivery (spontaneous vaginal, assisted vaginal, cesarean), neonatal sex, weight, Apgar scores, and umbilical venous and arterial blood gas values. Results were analyzed using the unpaired t-test, ANOVA and multivariate analysis, as appropriate.

Results: There were no statistically significant differences between the metoclopramide and placebo group in age, race, parity, cervical dilation, height, weight, or incidence of oxytocin use. There were no differences in the length of first or second stages of labor or in the incidence of maternal emesis between the two groups. The intergroup difference in the duration of the third stage of labor approached significance (p-z 0.096). The rates of cesarean and operative vaginal delivery did not differ between the groups. Neonatal outcome, including Apgar scores and cord blood gases, did not differ.

Dlscussion: Metoclopramide decreases the time to fetal expulsion by 50% in prostaglandin- induced abortions (1,2), yet it does not affect the length of the first or second stage of spontaneous or oxytocin-induced labor (3). Metoclopramide may augment prostaglandin more than oxytocin induced contractions. Alternatively, factors such as cervical collagen content (4) and maternal anatomy may affect labor duration more than the peristaltic quality of the uterine contractions. The trend we saw toward a shorter third stage (a stage hampered by neither cervical nor bony impedances) supports this latter hypothesis. In conclusion, metoclopramide does not affect the duration of term labor. the rate of cesarean section or the incidence of maternal vomiting in labor.

References: 1. Anesth Analg 1991;73:553-5. 2. Anesth Analg 1992;75:760-3. 3. Anesthesiology 1995;83:A996. 4. Am J Obstet Gynecol 1983; 147:662-6

190

Fetal Heart Rate Changes in the Lateral Versus the Sitting Position During Regional Anesthesia in the Parturient

T.K. Abboud, M.D., J. Dimowo, M.D., J. Zhu, M.D., G. Gill, M.D., D. Miller, M.D.

Departments of Anesthesiology and Obstetrics and Gynecology, Los Angeles County+University of Southern California Medical Center, Los Angeles, CA 90033

Fetal Heart Rate, Aortocaval Compression

INTRODUCTION: Hypotension due to Aortocaval compression in the parturient has been reported and demonstrated in the supine recumbent and lateral decubitus position. Concealed aortocaval compression may result in decreased maternal mean arterial pressure and decreased uterine blood flow which might adversely affect fetal well being, Previous studies have demonstrated that identification of the epidural space in the sitting position is associated with less aortocaval compression compared to the lateral position as ascertained by less changes in maternal hemodynamic parameters (1). However, no evaluation of fetal heart rate parameters was performed. The purpose of the present study is to assess the fetal and maternal effects of concealed aortocaval compression in the lateral and sitting position in parturients at term during epidural catheter placements.

METHODS: After approval of the Institutional Review Board and Informed Consents, one hundred healthy parturients at term with no evidence of fetal distress requiring epidural analgesia or anesthesia for vaginal delivery or cesarean section were studied. Patients were randomized into two groups using a computer generated randomization table, the lateral decubitus position group (n = 50) and the sitting position group (n = 50). Patients were prehydrated using lactated Ringers solution and epidural catheters were placed in the routine manner. None of the patients were on Pitocin during epidural placement. Parameters recorded during the study included fetal heart rate (FI-IR), uterine activity (UA), maternal blood pressures and heart rates and oxygen saturation. Data were analyzed for statistical significance using student’s t-test or chi-square when appropriate. A P value of CO.05 was considered statistically significant.

RESULTS: There were no significant differences between groups for maternal blood pressures, heart rates, UA, or oxygen saturation. FHR abnormalities (variable, late or prolonged decelerations, non- reactive FHR and decreased variability) were not significantly different between the two groups.

CONCLUSIONS: Results from our study indicate that maternal position during placement of epidural catheters has no significant effect on the maternal hemodynamic or the fetal heart rate parameters. Maternal positioning during epidural catheter placement should be determined according to the patient’s comfort and the anesthesiologist’s preference.

REFERENCE: (1) Andrews, PJD, Ackerman III, WE, Juneja, MM. Aortocaval Compression in the Sitting and Lateral Decubitus Positions During Extradural Catheter Placement in the Parturient. Canadian Journal of Anaesthesia 1993,40:320-324.

191

EPIDURAL ALFENTANIL (A) CAN ABOLISH SHIVERING IN THE PARTURIENT PATIENTS DURING LABOR ANALGESIA.

B. GORUKANT1,M.D.; S. VADIVELU,M.D.; S. M. TRIVED1,M.D.; K. SHEVDE,M.D.

DEPARTMENT OF ANESTHESIOLOGY, MAIMONIDES MEDICAL CENTER, BROOKLYN, NY 11219

EPIDURAL, ALFENTANIL, PARTURIENT, SHIVERING

INTRODUCTION: Shivering is a minor but annoying symptom seen in 10% of patients in labor without and 20-75% of patients with epidural analgesia. Shivering utilizes unnecessary energy contributing to unwanted increase in oxygen consumption and cardiac output. We evaluated the effect of epidural A in abolishing shivering during labor analgesia in a randomized double blinded study.

METHODS: Following approval by IRB and individual wrriten informed consents, 55 pregnant patients scheduled for labor analgesia were studied. Patients with ruptured membrane and on

antibiotics were excluded. Patients were randomized into groups A and B. Group A received 15 mcglKg of epidural A prior to the administeration of Bupivacaine. Group B received Bupivacaine only.Maternal parameters such as temperature (tympanic),heart rate, blood pressure,respiratory rate,shivering grade ( O=none and 3 =severe ) at 1, 5, 10, 15 and 30 minutes following the epidural were noted by an observer blinded to the procedure. All patients received IV fluids at room temperature.

Fetal heart rate was monitored and Apgar scores recorded at 1, 5 and 10 minutes after birth.

RESULTS: Table 1. Incidence of shivering.

Fig. 1. Incidence of shivering.

NO shivering

Shivering

Croup A (N -27) (Alfentanil)

Group El (N -28) (No alfentanil)

2s

14

02

14 Group

A

Group

p - 0.0005 ( Chi-squared test ) Study groups

CONCLUSION; Shivering in pregnant women can increase the metabolic rate by 200% and is associated with increase in plasma catecholamines that may constrict the uterine arteries. Pregnancy increases the thermoregulatory setpoint. The incidence of shivering is increased by epidural anesthesia due to thermoregulatory responce triggered by hypothermia which results from sympathectomy- induced heat loss. Our study shows that epidural A given before the local anesthetic drug improves pregnant patients’ comfort by decreasing the incidence of shivering associated with epidural analgesia.

REFERANCES: 1. P. J. Webb,M.D.et al ; Anesthesiology 55: 706-707, 1981 2. M. D. Johnson,M.D.et al ; Anesth Analg, 68: 70-71, 1989 3. D. I. Sessler, M.D.et al ; Anesthesiology, 72:816-821,199O 4. D. I. Sessler, M.D., Anesthesia by Miller, 3rd Edi., 1237-39 This project was not funded.

192

TITLE: Intravenous Fluid Bolus Modifies the Effects of Intrathecal Fentanyl on Uterine Activity

ALTHOR% J. Thimons MD, S. Laifer MD, S. Ramanathan MD

Al_FILIATION: The Departments of Anesthesiology and Obstetrics and Gynecology, Magec-Womens Hospital, Umversity of Pittsburgh School of Medicine, Pittsburgh, PA, 152 13

ECJ?%CXuX Uterine activity, intrathecal fentanyl, intravenous fluids

ltmduetion: We previously reported that intrathecal fentanyl (ITF) administered for labor analgesia reduced the uterine ;tiv&y transiently (1). However, these patients were given a 500 ml i.v. fluid bolus prior to block. This study assesses whether ‘F will produce the same effect in the absence of a fluid bolus. lethods: After IRB approval and informed consent, 10 patients requiring intrauterine pressure (IUP) monitoring for their jstetrical management were included. Seven of ten patients were receiving oxytocin augmentation. Uterine activity: (maximum nplitude, frequency of contractions and Montevideo units) were obtained for three lo-minute epochs prior to the institution of e block. A combined spinal-epidural technique was then performed and 2.5pg fentanyl injected into the subarachnoid space. 11 pressure recordings were made with 15 O lefi uterine displacement for the next six IO-minute epochs. Pain relief was assessed ith visual analogue scores (VAS). The preblock uterine activity was compared to postblock activity using repeated measures lalysis of variance. Visual analogue scores were compared using non-parametric methods. esults: Following ITF , VAS scores decreased significantly. No significant decrease occurred in amplitude (Fig 1, No fluids) Montevideo units (Fig 2, No fluids) after ITF administration. Frequency did not change significantly. The amplitude

creased reaching statistical significance at epoch 6 (Fig 1). However, no hypcrtonus or fetal heart abnormality was noted. onclusion: Data show that when fluid bolus is omitted, ITF does not cause the transient decrease and in fact is associated with 1 increase in amplitude. When preceded by a fluid bolus, ITF administration causes a transient decrease in both amplitude and [ontevideo units (Fig I and 2, Fluids, previous study).

30 0 W tAmevideo U”b

Amplitude Na ““ids

5 5 P Fii 1

f

0 0

ii a 5 5

I 1

B 0 !J -w -W

6 6 s P -5 -B

-W -20 -20

*

-al Q 25 Pmkk El E2 E3 E4 ES W

-2s P&c& El El E3 E4 ES E6

emends for the B@IIW: Figs 1 and 2: Data are mean Error bars are not shown to improve clarity, :parate epochs) ; El-E6 - post block epochs. MU - Montevideo units;

Pre- preblock (average of 3

ffcrent from all other values. * - significantly different from preblock values. @ -

eferences: Thimons J et al: SOAP 95. Abstract book, p 39,199s.

193

Anesthesia for Post Pat-turn Tubal Ligation: Comparison of Lidocaine, Bupivacaine and Meperidine

T.K. Abboud, J. Zhu, M.D., J. Lee, M.D., G. Gill, M.D., P. Singh, M.D.

Department of Anesthesia, Los Angeles County+University of Southern California Medical Center, Los Angeles, CA.

Tubal Ligation, Meperidine, Lidocaine, Bupivacaine, Spinal

INTRODUCTION: Spinal anesthesia using hyperbaric 5% lidocaine is frequently used for post partum tubal ligation, however radicular irritation in some patients has been reported. The purpose of the present study is to evaluate and compare different agents for spinal anesthesia in patients undergoing post partum tubal ligation. METHODS: Following approval by the Institutional Review Board and informed consents, thirty-six patients undergoing post pat-turn tubal ligation were studied. Patients were randomly assigned to receive 5% hyperbaric (60-90mg) lidocaine, L group n = 14, 0.75% hyperbaric bupivacine (9-12mg), B group n = 1 lor hyperbaric Meperidine (50-SOmg), M Group n = 11. All patients were prehydrated and spinal anesthesia was performed in the sitting position. Patients were assessed for segmental level of analgesia by pin prick method and motor block (Bromage Score 0 -3). Side effects and first request for pain medication were also noted. RESULTS: Results are presented in the table and they indicate that meperidine was associated with less motor block and longer duration of analgesia without significant side effects. Bupivacaine was similar to lidocaine as far as the duration of analgesia with longer motor block. CONCLUSIONS: Results from our study indicate that meperidine or bupivacaine are good alternatives to 5% lidocaine for spinal anesthesia in postpartum tubal ligation.

- TABLE -

Duration of Motor Block ( Min.) Bromage (0)

Injection to first pain medication

Analgesics required: None NSAID Narcotics

Side effects: Hypotension Nausea, vomiting Pruritus

Values are Mean 2 SD

156.7 2 20.2 143.0+ 22.9 201.2 + 52.7 B vs L, M PcO.05

734.62392.7 156.45 96.9 3 14.4 + 395.5 M vs L, B PcO.05

1 0 -I- 10 2 0 12

4 1 2 0 1 0

Bupivacaine n=ll

1 3 I

5 L vs M, B PcO.05 1 NS 0 NS

P Value

M vs L, B PcO.05

194

Postpartum tubal ligation after pregnancies complicated by pregnancy-induced hypertension

R.D. Vincent, M.D., R.W. Martin, M.D.

Departments of Anesthesiology and Obstetrics and Gynecology University of Mississippi Medical Center, Jackson, MS.

Postpartum tubal ligation, pregnancy-induced hypertension

INTRODUCTION: It is unclear whether postpartum tubal sterilization can be considered after vaginal delivery in women with pregnancy-induced hypertension (PIH) (i.e., gestational hypertension or preeclampsia). The American College of Obstetricians and Gynecologists has opined that “in patients who have had medical or obstetric complications during their pregnancy the procedure should be deferred unless their are overriding medical indications for proceeding.” On the other hand, there are no data to confirm whether PIH increases the anesthetic or surgical morbidity associated with postpartum tubal ligation surgery. The purpose of the present study was to review the preoperative maternal state, intraoperative hemodynamic changes, and postoperative morbidity among women who underwent postpartum tubal sterilization after pregnancies complicated by PIH. METHODS: Medical records were reviewed for 53 women who underwent postpartum tubal ligation after a pregnancy complicated by PIH. Only women given intravenous seizure prophylaxis with either magnesium sulfate or phenytoin were included in this group. For each PIH patient, a matched control patient was designated by selecting the next chronologically listed patient in our database who also underwent postpartum tubal ligation surgery but who did not have PIH. Women with chronic hypertension were not excluded from the control group unless they also developed superimposed preeclampsia. Women who had an epidural catheter reinjected immediately after delivery (i.e., before regression of the original segmental block established during labor) were excluded from both groups since immediate postpartum tubal ligation was rarely performed in PIH women. RESULTS: Women in the PIH group had a higher incidence of chronic hypertension and greater mean body weight than their counterparts in the control group. Preoperative blood pressure measurements (mmHg f SD.) were greater in the PIH group than in the control group (158 + 22 I 91 f 12 versus 126 + 13 / 71 + 10, P<O.OOOl). The incidence of failed spinal anesthetics was greater in the PIH group than in the control group (21% versus 5%, [P<O.OS]). Among women successfully anesthetized with subarachnoid block, minimum intraoperative systolic blood pressure was lower (PcO.05) in the control group than in the PIH group (fig.). But, the maximum percentage decrease in systolic blood pressure was greater in the PIH group than in the control group (33 + 14% versus 22 * IO%, PcO.05). Finally, the percentage of patients discharged after the first postoperative day was greater in the PIH group than in the control group (23% versus 8%, P<O.OS).

Svstolic BP 180 1

CONCLUSIONS: Greater patient weight may have contributed to the high incidence of unsuccessful spinal anesthetics in the PIH group. Nevertheless, postpartum tubal ligation may be considered after vaginal delivery in women with PIH who have received adequate seizure prophylaxis and do not have any evidence of pulmonary edema, thrombocytopenia, or persistent oliguria.

195

Efficacy of Spinal Anesthesia fo r Delayed Postpartum BTL after Epidural Analgesia for Labor

BY. Fragneto, M.D., C.H. Moore, Ph.D., Ft. Andrade, M.S., D. Wade, B.S.

Dept. of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA

bilateral tubal ligation, postpartum; anesthesia, spinal; analgesia, labor epidural

Introduction: Delayed postpartum bilateral tubal ligations (PPBTL) are frequently performed several hours after delivery. Previous investigators have found that epidural anesthesia using an in situ catheter from labor and delivery is less likely to be successful if the BTL is delayed 5 4 hr. Viscomi found at his institution that spinal anesthesia for delayed PPBTL is more cost effective than reactivating an existing epidural catheter. For these reasons, we routinely use spinal anesthesia for delayed PPBTL. However, it appeared empirically that spinal anesthesia was more frequently inadequate for surgery in patients who had received epidural analgesia for labor.

Methods: A retrospective chart review of all delayed PPBTLs performed under spinal anesthesia between Sept. 1993 and Feb. 1995 was undertaken. The following data was collected from each chart: demographic data; presence or absence of a labor epidural; duration of epidural analgesia; and local anesthetic agents and doses used for labor analgesia. Data collected concerning anesthesia for BTL included: local anesthetic agent and dose used for spinal; final sensory level; and whether spinal anesthesia was inadequate for surgery. Spinal anesthesia was considered inadequate if any of the following criteria were met: alternative anesthesia technique required (i.e. GA, epidural anesthesia or repeat spinal); supplementation with 50% N2C by mask; excessive I.V. sedation (defined as requiring a combination of drugs >2 mg midazolam + 100 mcg fentanyl + 30 mg ketamine), or infiltration of the surgical field with local anesthesia. Data was analyzed using Chi square, logistic regression, and independent samples t-test as appropriate. Statistical significance was considered p < 0.05.

Results: 2 13 delayed PPBTLs were performed under spinal anesthesia during the 1 8 month period reviewed. Epidural labor analgesia had been provided to 105 of these patients while 108 patients had not received epidural analgesia during labor. Demographic variables were similar between the groups. Amcfg the patients who did receive epidural analgesia, 17.0% had inadequate spinal anesthesia (1 8/l 05) while only 7.4% (8/l 08) of those who did not receive an epidural had inadequate anesthesia. This difference was significant (p=O.O3) Among the patients who did receive epidural analgesia, there was no association found between inadequate spinal anesthesia and any of the following factors: duration of epidural analgesia, local anesthetic agents used for labor analgesia; or doses of local anesthetic agents used.

Conclusions: A retrospective chart review confirmed our clinical impression that patients who have received epidural analgesia for labor are less likely to receive adequate spinal anesthesia for delayed PPBTL than patients who have not received epidural analgesia. The etiology remains unclear. In the current health care environment, immediate PPBTLs are more cost effective than delaying the procedure until the morning following delivery. In patients with functioning epidurals, our observation provides further impetus to proceed with PPBTL in the immediate postpartum period.

196

NORCOCAINE IS MORE TOXIC THAN COCAINE IN PREGNANT RATS

R.A. WHIl-TINGTON, MD, A. ISO, MD, S. NOMURA, MD, K. KHAN, BS, T.B. COOPER, MA, H.O. MORISHIMA, MD, PhD

Departments of Anesthesiology and Psychiatry, College of Physicians & Surgeons, Columbia University, NY, NY, 10032

Norcocaine, Cocaine, Toxicity, Rat

INTRODUCTION: The metabolism of cocaine in humans is partly dependent on N-demethylation which results, in the formation of norcocaine, a pharmacologically active metabolite.‘. Despite the fact that cocame abuse du,r!ng pregnancy continues to be a major health problem, no information is currently available regarding the disposttion and toxicity of this metabolite in the pregnant state. Furthermore, little is known in regard to how the toxicity of norcocaine compares to cocaine. Consequently, the purpose of this study was to compare the toxicity of norcocaine to cocaine in pregnant rats.

METHODS: The protocol was approved by the Columbia University Animal Care and Use Committee. One day prior to the study, near-term (gestational day 19-21), pregnant Sprague-Dawley rats had catheters placed in the carotid artery and jugular vein under ketamine and xylazine anesthesia. After a 24 hour recovery period, an intravenous infusion of either cocaine (N=8) or norcocaine (N=5) was administered at a rate of 2 mglkglmin until the development of circulatory collapse. Blood pressure as well as heart rate were monitored continuously, and the animals were observed for the onset of convulsions, hypotension, and circulatory collapse. Data are expressed as mean + SE. Statistical analysis was performed using ANOVA and p < 0.05 was considered statistically significant.

RESULTS: Norcocaine (NC) produced advanced CNS and cardiovascular manifestations at significantly smaller doses than cocaine (COC) (Figure). Similarly, the onset of toxic manifestations occurred earlier in NC. Convulsions occurred at 5.9 + 1.0 and 17.6 + 1.5 min in NC and COC, respectively. This was followed by hypotension at 7.3 + 1.2 min in NC and 22.3 f 1.8 min in COC and, lastly, circulatory collapse at 8.6 + 1.2 and 24.1 + 1.9 min in NC and COC, respectively.

0 CorAlsion Hypotension Circ. Collapse

CONCLUSION: In the pregnant rat, norcocaine produces advanced CNS and cardiovascular toxic manifestations more quickly and at lower doses than cocaine. is enhanced during pregnancy’.

We have previously reported in the rat that the toxicity of cocaine Since norcocaine is more lethal than its parent compound, special consideration

should be given to its toxicity during pregnancy, particularly in the setting of cocaine and alcohol co-ingestion, a situation previously demonstrated to increase norcocaine formation4.

REFERENCES: 1. Hawks RL, Life Sci 1975;15:2189-2195 2. Stewart DJ, Clin Pharm Ther 1979;25:464-468 3. Morishima HO, Anesthesiology 1989;71:A1188 4. Farre M, J Pharm Exp Ther 1992;266:1364-1373

Supported in part by NIDA Grant ROI DA 06648 and NIMH Grant MHCRC 30906.

197

An In Vitro Evaluation of Fentanyl and P-Chloroprocaine Interactions at Mu and Kappa Opioid Receptors

B.A. Coda, M.D., S. Bausch, B.S., R.T. (R), C. Chavkin, Ph.D

Departments of Anesthesiology and Pharmacology, University of Washington, Seattle, WA

P-Chloroprocaine, Opioid Receptors, Hippocampal Slice Preparation

INTRODUCTION: Epidural 2-chloroprocaine (PCP) can decrease the analgesic effectiveness of subsequently administered fentanyl. In addition, 2CP has binding affinity for both p- and K-opioid receptors in vitro.’ However, the presence of binding affinity does not address the question of mether 2CP is likely to act as an agonist, antagonist, or partial agonist at these receptors. We examined the effect of 2CP on p- and K-mediated actions using an electrophysiologic model, the hippocampal slice preparation.

METHODS: This study model employs extracellular recording of the stimulation-evoked population responses in the CA1 and dentate gyrus of hippocampal slices for measurement of p and K actions, respectively.’ Hippocampal slices were prepared from freshly dissected rat or guinea pig brain slices, submerged in a temperature-controlled chamber, and continuously superfused with oxygenated Krebs-bicarbonate buffer. CA1 pyramidal cell responses were evoked by stimulation in the stratum radiatum and recorded extracellularly in the stratum pyramidale. Dentate granule responses were stimulated by activation of the perforant path in the outer molecular layer of the dentate avrus and recorded in the stratum aranulosum. Concentric bipolar electrodes were used for stimulation, and glass micropipettes filled tith 3 M NaCl Are used for recording extracellular changes in potential.

RESULTS: In the rat CA1 region, application of 2CP decreased the population spike amplitude evoked by a maximal stimulus in a dose-dependent manner. Fentanyl had an excititory effect on the stumulus response curve in the CA1 region, which is typical of p agonists. Fentanyl increased the amplitude of the evoked response across a range of stimulus intensities, as well as inducing an afterdepolarization (secondary spike). 2CP reversed the increase in excitability caused by fentanyl and brought the stimulus-evoked response back to control amplitudes. However, the addition of naloxone reduced the response still further, suggesting that the fentanyl-2CP interaction was the result of a nonspecific depression of CA1 excitability, or that any specific antagonist activity wds very weak (Figure 1). In addition, 2CP did not reverse the afterdepolarization caused by fentanyl, whereas naloxone did.

In the guinea pig dentate gyrus, the K agonist U69, 593 caused a 40% reduction in the amplitude of the stimulus-evoked response, tiich was reversed by naloxone. Similar to U69,593,2CP caused a 25% reduction in the stimulus-evoked response, but this effect was not reversed by naloxone (Figure 2). The lack of naloxone sensitivity suggests that this effect of 2CP was a result of neuronal depression rather than activation of receptors.

CONCLUSIONS: Although 2-CP has binding affinity at p-and K- opioid receptors, it does not appear to be acting through an opioid receptor to antagonize physiological effects of fentanyl.

1. Coda (Abs) Neuroscience 17:813, 1991 2. Neumaier. J Pharmacol Exp Ther 244:564, 1988. Supported by NIDA grants DA04123 and DA05513

Fig. 1 CA1 Region lnteradions 30

1

ig. 2 Deft& R@n lrterac+ions

198

TITLE: A Dose-Response Study of Intrathecal Morphine for Post Cesarean Section Analgesia

AUTHORS: HJ Huffnagle, DO, MC Norris, MD, BL Leighton, MD, VA Arkoosh, MD, SL Huffnagle,DO

AFFILIATION: Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson Univer- sity, Phildelphia, Pa.

KEYWORDS: Intrathecal Morphine, Post Operative Analgesia, Cesarean Section

INTRODUCTION: Intrathecal morphine can provide analgesia after cesarean section. Adequate pain relief has been obtained with doses as low as 0.1 mg, 132 but doses up to 0.6mg have been described.3 This study was

designed to define the optimal dose of intrathecal morphine in patients having either primary or repeat cesarean delivery. METHODS: After IRB approval, eighty ASA I and II term parturients undergoing elective cesarean delivery (40 primary, 40 repeat) gave written informed consent to participate in this randomized, prospective double-blinded study. All patients received 15 mg hyperbaric bupivacaine for their spinal anesthetic. In addi- tion, patients were randomly allocated to receive intrathecal preservative-free morphine: 0, 0.1, 0.125 or 0.2 mg. Additional postoperative analgesia was provided with morphine via IV PCA. At 24 hours after induction, patients rated their overall pain, itching, and nausea on a 10 cm VAS. Total 24 hour IV morphine consumption

also was recorded. Itching was treated with diphenhydramine, 25 mg IV and nausea/vomiting with metoclopramide, 10 mg IV, as needed. RESULTS: Groups were similar in age, height, weight, gravidity and parity (Kruskal-Wallis). Women having primary and repeat cesarean sections had similar 24 hour morphine consumption and VAS scores for pain, itching and nausea/vomiting (ANOVA). Therefore we combined these patients for data analysis. Patients in the control group (0 mg IT morphine) used significantly more IV PCA morphine than patients who received intrathecal morphine. Although not statistically significant, there was a trend toward decreasing IV PCA mor- phine use with increasing doses of intrathecal morphine (mean 66.1 > 28.1 > 17.7 > 16.0 mg). There were no differences between the groups in incidence or severity of side effects. CONCLUSIONS: Patients undergoing primary or repeat cesarean delivery consumed the same amount of IV PCA mor- phine and had similar VAS pain scores. This result suggests that women experience similar pain after either procedure.

Although intrathecal morphine decreases systemic mor- phine consumption, it did not completely or reliably eliminate the need for supplemental IV PCA morphine in the doses stud- ied. Our data suggest that the analgesic effect of intrathecal morphine plateaus between 0.125 and 0.2 mg. Failure of in- trathecal morphine to activate supra-spinal opioid receptors4 may explain this phenomenon. Perhaps the best method of post- cesarean-section analgesia is a combination of intrathecal mor- phine plus IV PCA morphine. REFERENCES: I. Abboud TK, et al. Anesth Analg 1988;67: 137.2. Palmer CM, et al. SOAP Abstracts 1994;48. 3. Zakowski M, et al.Anesthesiology 1989;71 :A870. 4. Yeung JC, Rudy TA. J Pharmacol ExpTher 1980;215:633.

199

*pc O.OSvsOmg

Omg 0.1 mg 0.125 mg 0.2 mg Dose Intrathecal Morphine

Figure: IV PCA morphine use vs. intrathecal morphine dose. Circles represent individual patients. Boxes represent mean 2 SD for each dose of intrathecal morphine.

WHAT IS THE OPTIMAL DOSE OF EPIDURAL MORPHINE FOR POST-CESAREAN ANALGESIA? A DOSE-RESPONSE STUDY.

JV Pettv. MD. CM Palmer. MD, WM Nogami, MD, RC Marquez, MD, G Van Maren, MD, DM Al&, RN

Department of Anesthesiology, AZ, a5724

University of Arizona Health Sciences Center, Tucson,

Analgesia, epidural: morphine. Morphine, epidural: side effects. Cesaraan delivery.

LNTRODUCTION: Epidural morphine is commonly used for postoperative analgesia following epidural anesthesia for cesarean delivery. Doses described in the obstetric anesthesia literature range from 2-7.5 mg. (1,2) This study attempts to define the ‘optimal” dose forthii purpose in terms of analgesia and side effects in the first twenty-four postoperative hours. MFTHODS: Forty-eight ASA I and II term padurients undergoing non-urgent cesarean delivery gave written, Informed consent and enrolled in thii ongoing IRB-approved study. All patients received epidural anesthesia with 2% lllocaine with 1:200,000 epinephrine In volumes of 20-30~~; patients were randomized In double-blind fashion to one of five groups, receiving 0.0 (Controi-Group I; n = lo), 1.25 (Group II; n = 9), 2.5 (Group Ill; n = lo), 3.75 (Group N; n = 11). or 5.0 (Group V; n = 8) mg epktural morphine. Postoperatively, all patients received PCA (1.5 mg MS04 q 8 min on demand only). Cccurrence of slde effeds (nausea, vomiting, pruritus) and their severity (scale, O-2) were recorded in each 4 hr Interval for 24 hrs postoperatively. At patient request nausea and vomiting (N/V) were treated with droperktolO.625 mg N and pruritus wtth nalbuphiie 10 mg RI. Post-operative morphine use via PCA was recorded. Data was analyzed using ANOVA, student’s t-test, and Mann-Whitney U test as appropriate. RFSULTS: Groups were demographically similar. ANOVA PCA Use vs Tlme, All Groups revealed a significant difference between groups in (Mean. +/- SEW

postoperative PCA morphine use (p < 0.001) (Fig. 1). A posteriotitests revealed groups Ill, IV, and V used significantly

ao- _,: o,omg

less PCA morphine than control, and groups IV and V also used -T- III: 2.5 nlg signkicantiy lessthan group II; groups Ill, IV, and V did not differ - -o- lw 3.75 mg significantly from each other. Pruritus scores were significantly higher in all treatment groups than control (p<O.O5, Mann- Whitney); there was no difference between treatment groups .9 40- (Fii. 2). There was no difference between any groups with 8 regard to nausea or vomiting. DISCUSSION: Recent investigation has indicated that the dose- g M- response curve for intrathecal morphine analgesia is very steep, and that the minimal effective dose is much lower than previously thought (3). This series indicated that the analgesic dose-response curve of epidural morphine, over the clinically- utilized dose range, is considerably flatter, and the analgesic potency ratio of intrathecal to epidural morphine is approximately 4O:l. This ratio is likely due to the pharmaco- kinetic difference between these routes of administration. Further investigation will better define the analgesic response in the 2.5 to 3.75 mg range.

The lack of difference between groups in nausetiomiting scores indicates that epklural morphine, in this dose range, is an unlikely cause of these side effects, and treatment of NN with opioid antagonists in the post-operative period would not be efficacious.

REFERENCES: 1. Arresltresia, Miller RD, Ed. (4” ed). 1994, pp. 2031-2076. 2. Obstetric Anesthesia, Chestnut DH, Ed. 1994, pp. 458-

486. 3. Anesthesiology 81,3: Al 151,1994.

24 hr Prurltus Score All GIVUPS

(Mean +/- SEM)

0 0.00 1.25 2.50 3.75 5.00

Ejaldurei Mwphine Dose (‘p405, contmt”S. baatmant goups,

Mann-Whitney u-test)

200

Does Epidural Chloroprocaine Antagonize the Side Effects of Intrathecal Morphine?

S Loeb, MD, HS Chadwick, MD, B Coda, MD, B Glosten, MD, H Gunn, MD, B Ross PhD, MD

Department of Anesthesiology, University of Washington, Seattle, WA

Chloroprocaine, Morphine, Labor analgesia, Opioid side effects

INTRODUCTION: Neuraxial opioids are effective analgesics in early labor. Morphine (MS), with its long duration of action, is well suited for the nulliparous patient in early labor. However, the frequency and duration of associated side effects (pruritus, nausea and urinary retention) can be problematic( 1). Epidural2- chloroprocaine (2-CP) can antagonize analgesia resulting from neuraxial MS(2), although its effects on opioid-induced side effects has not been studied. We tested the hypothesis that epidural Z-CP administered at the time of delivery antagonizes the side effects of intrathecal MS previously administered for labor analgesia. METHODS: This study was approved by the IRB and written consent was obtained from the study patients. Women, in early labor (cervical dilation of 14 cm.), who requested analgesia were given intrathecal MS 250 pg. and fentanyl 12.5 pg, at the time of epidural catheter placement. Catheters were tested with 3 ml. of 0.25% bupivacaine with epinephrine 1:200K. When additional analgesia was requested a second test dose was given followed by 5-10 ml. of 0.25% bupivacaine and an infusion of 0.0625% bupivacaine at 8-12 ml./hr. Patients were randomized to receive 5-15 ml. of either 2-CP (2%-3%) or lidocaine (l%-2%) for perineal analgesia at the time of delivery. The delivery dose was administered by a blinded member of the anesthesia team. On the first postpartum day a blinded interviewer questioned the patients regarding the frequency and severity of postpartum side effects, and quality of analgesia during labor and during delivery. Postpartum satisfaction scores’were also obtained. Other data collected included demographic information, cervical exam at the time of intrathecal opioid administration, and time elapsed until delivery. Statistical analyses of data included unpaired Student’s t-test, chi square analysis and Fisher’s Exact test as appropriate. PcO.05 was considered significant. RESULTS: Thirty six patientssf a planned 60 patients have been enrolled to date. Eighteen completed the protocol and are included in the analyses. Of these, 11 received 2-CP and 7 received lidocaine. Of those not completing the study, eleven women were delivered by cesarean section, 4 did not receive a delivery dose, and 3 did not complete the postpartum survey. The groups are similar in maternal age, height and weight, infant weight and Apgar scores. There is no statistically significant difference in the frequency or severity of pruritus, nausea or urinary retention between the 2-CP and the lidocaine groups. (see table) DISCUSSION: From this work in progress we have insufficient statistical power to draw valid conclusions. The data thus far have shown no diminution in incidence or severity of side effects when 2-CP is used for delivery. If this remains true when the study is complete, a number of mechanisms might explain the finding. First, epidural2-CP does not reach supraspinal mu opioid receptors(3). Alternatively, antagonism of spinally mediated side effects does occur, but the duration was too brief to be measured by this study. Finally, 2-CP antagonism of intrathecal MS analgesia may be mediated by different receptors or receptor subtypes than those that mediate side effects.

Maternal Cervical dilation Time elapsed # Patients with # Patients with Age (yrs.) (time of SAB opioids) SAB until delivery nausea/vomiting pruritus

2-CP 24.2f5.7 2.6kl.l cm. 585+388 min. 4 (36%) 2 (18%) n=ll

Lidocaine 23.7k4.1 3.3f0.7 cm. 464*170 min. 3 (43%) 2 (28%) n=7

MeatiStd. There are no significant differences between the groups.

1. HS Chadwick, et al, Anesthesiology 1988; 68:925-929. 2. J Eisenach, et al, Anesthesia and Analgesia 1991; 73: 119-123. 3. D Thomas et al, Anesthesiology 1993;79:548-54.

201

ANALGESlA AND SIDE EFFECTS OF EPIDURAL OPIATES USED FOR POSTOPERATIVE PAIN CONTROL IN CESAREAN DELNERY PATIENTS

EC Perez, MD, LM Newman, PhD MD, JB Jaffee, MD, EM Hopkins, RN, and AD Ivankovich, MD

Department of Anesthesiology, Rush Medical College at Rush-Presbyterian St. Lukes Medical Center, Chicago Illinois

Postoperative pain, epidural analgesia, morphine, nalbuphine, hydromorphone, meperidine

INTRODUCTION: Patient-assisted epldural analgesia has been shown to reduce opioid requirements, and improve patient satisfaction, but not affect the incidence of side effects’. Nalbuphine has been shown to decrease the incidence of pruritus with intrathecal sufentanil’, and epidural fentanyf , but not intrathecal morphine . The aim of this study is to evaluate the efficacy of four patient-assisted epidural infusions and compare the incidence of side effects. METHODS: After IRB approval, 124 women were randomly assigned to receive one of the following epidural infusions after cesarean delivery: morphine (MS), morphine-nalbuphine (MN), meperidine (MEP), and hydromorphone (HM). The parameters of the infusions are presented in table 1. VAS pain scores (O-10) patient satisfaction (l-4) and incidence of pruritus, nausea and voming, and parenteral analgesic supplementation (either 2 mg morphine or ketorolac 30 mg im) were evaluated. The data were analyzed using Chi-square analysis and ANOVA with p<.O5 considered statistically significant.

MS

Infusion Concentration Basal Bolus Lockout Four Hour

Infusion Size Interval Limit

I 2mg I MS 50 mcg/ml 4 ml/hr 1 ml 10 min 40 ml

HM 0.4 mg Hydromorphone 10 mcglml 4 ml/hr 1 ml 10 min 40 ml

RESULTS: The results are seen in the following table. There was no statistical significance in VAS pain scores, incidence of nausea and vomiting, need for parenteral supplementation, or satisfaction scores between the four groups. There was a significant difference between the four groups for incidence of pruritus. Individual comparison of the MS vs MN groups for pruritus had a p value of 0.10, while the incidence of pruritus for MEP was significantly different from the other groups.

N VAS Score SatisfactionScores

Mean f SEM % itch % N&V % NUMB %Supp

Mean f SEM

MS 36 2.93 * 0.3 47.2 2.8 0 16.7 3.7 f 0.08

MN 32 2.55 f 0.4 28.1 12.5 0 18.8 3.7 f 0.12

MEP 28 4.18 f 0.41 7.1’ 0 17.9’ 25.0 3.6 f 0.14

HM 28 3.77 f 0.39 39.3 7.1 0 32.1 3.4 f 0.18 l p < .05 when compated to MS, MN or HM *p<.OOO5 when compared to MS, MN, or HM

CONCLUSION: Patient-assisted epktural analgesia with either MS, MN, MEP, or HM provides excellent analgesia with pruritus being a significant side effect for MS, MN, and HM. While the pruritus is significantly reduced in the MEP group, the high incidence of numbness may limit its usefulness since numbness may interfere with postoperative ambulation. The low inddence of nausea and vomiting seen with MS compared to previous studies may be attributable to the low initial bolus and patient titration allowed by this technique. 5 The addition of nalbuphine to morphine for epidural infusion has no statistically significant effect on pain scores, pruritus, or nausea and vomiting. Further study is required to determine whether the potentially clinically relevant effects of adding nalbuphine to morphine on nausea and vomiting as well as pruritus can be validated in a larger sample. Based upon a power analysis with 01= .05 and a power of 80%, this will require approximately 100 patients per group. REFERENCES: 1. Lubenow, TR et al. Reg Anesth 1994;19:212-215. 2. Wlodarski, JC et al. Anesth Analg 1994;78:S483. 3. Newman, LM et al. Anesth Analg lQQ2;74:S219. 4. Hays, RL et al. Anesthesiology 1995;83:A982. 5. Fuller, JG et al. Can J Anaesth 1990,37;6:636-40

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ADDING LOW DOSES OF EPIDURAL NALBUPHINE TO MORPHINE FOR POSTCESAREAN ANALGESIA

C.F. James, M.D., E.O. Nelson, M.D., P.B. Langevin, M.D., R.K. Hawkins, M.D., E.A. Radson, B.S.

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida

Analgesia, cesarean, nalbuphine

INTRODUCTION: With the high incidence of pruritus and nausea with epidural morphine, the addition of epidural nalbuphine, 10 mg, or more has been used to alleviate these side effects with conflicting results (1, 2). Thus, we studied the addition of lower doses of epidural nalbuphine (5 and 7.5 mg) to morphine to attempt to alleviate the side effects without affecting postcesarean analgesia.

METHODS: After institutional aooroval and informed consent of this double-blind study, 53 term patients undergoing elective cesarean reckived epidural anesthesia with lidocaine 2% with epinephrine (1:200,000) and fentanyl, 100 pg, and, after delivery, were randomly assigned to receive epidural morphine, 4 mg, with preservative-free normal saline (n = 15) or nalbuphine, either 5 mg (n = 18) or 7.5 mg (n = 20). For 24 hr, pain was assessed by visual analog scale (0 [no pain]-lo), and pruritus and nausea by a rank order scale (0 [none]-3). Severe pruritus or nausea was treated with nalbuphine, 5 mg iv. Data were analyzed by chi-square and Kruskal- Wallis test, P < 0.05 being significant.

Table. Effect of Adding Epiduml Nalbuphine to MO+ vhine for Postcesarean Section Analgesia

Pain score* 2 hr 4 hr 8 hr 12 hr 18 hr 24 hr

Nausea Pruritus Severe Pruritus

ti -I(

Mor- phine

0 (7) 1.0 (6) 2.0 (6) 1.0 (8) 2.0 (8) 3.0 (7) 33.3% 93.3% 73.3%

- Nalbur

5 mg 7.5 mg

0 (8) 1.5 (9) 3.0 (6)t 3.0 (1o)t 2.0 (7) 2.5 (9) 2.0 (7) 1.0 (8)

0.5 (8)t 1 .O (8)t 1.5 (5)-t 1.5 (6)t

50% 45% 83.3% 80%

33.3%$ 35%$

lian and range (highest

RESULTS: Pain scores were higher with nalbuphine than without it at 4 hr but lower with nalbuphine than without at 18 hr and later (ta- ble). The incidence of pruritus, 85% overall, did not differ among groups; but severe pruritus oc- curred less often with nalbuphine at either dose

*Scale: 0 [none] 1; data are n - lowest value). p < 0.05 compared with morphine by tKruskal Wallis and by $chi square.

(table). The incidence of nausea, 43% overall, did not differ among groups.

DISCUSSION: Although the addition of a relatively small dose of epidural nalbuphine (5 or 7.5 mg) to morphine did not decrease the overall incidence of pruritus, it did decrease the incidence of severe pruritus (pruritus requiring treatment). The incidence of nausea was not statistically different among the groups. Analgesia was not appreciably affected by the addition of nalbuphine, however, the pain scores were higher earlier in the postpartum period (4 hr), but lower later compared with morphine alone.

REFERENCES 1. Anesth Analg 1993; 925-933. 2. Anesth Analg 1992; 74:S219.

203

TITLE: Comparison of Post-Cesarean Section Pain Relief and Side Effects with Two Doses of lntrathecal Morphine

AUTHORS: P.F. Norman, M.D., C.F. Werhan, M.D., T.R. Ray, M.D., and B.K. Tsang, M.D.

AFFILIATION: Department of Anesthesiology University of Mississippi Medical Center, Jackson, MS

KEYWORDS: Analgesics, opioid: morphine. Anesthetic technique spinal: Anesthesia obstetric cesarean section.

INTRODUCTION: Several studies have suggested that subarachnoid morphine 0.1 to 0.15 mg may be equally effective to larger doses (e.g. 0.25 mg) and that these lower doses result in less pruritus and nausea. ’ We compared a lower dose of 0.1 mg morphine to a higher 0.25 mg dose. METHODS: Patients who had selected spinal anesthesia for their non-emergent cesarean section were enrolled in this IRB approved study and randomized in a double blind fashion to either a 0.1 mg (N = 50) or a 0.25 mg (N = 50) subarachnoid morphine group. All patients received spinal anesthesia with 10.5 mg of hyperbaric bupivacaine plus fentanyl 15 pg. They were evaluated at 12 and 24 hours for supplemental pain medications and at 24 hours for pruritis, nausea and satisfaction prior to and after ambulation. Therapeutic interventions for pruritis and nausea/vomiting were recorded through 24 hours. RESULTS: In the 0.1 mg group, 32% of patients requested supplementary pain medication within 12 hours post cesarean section, whereas only 16% of the patients in the 0.25 mg group requested additional pain medication (P<O.l, Chi Square test).

Additional Pain Medication

Satisfaction prior to amb Satisfaction after amb

MS 0.25 mg MS 0.1 mg

16% (12 hrs) 32% (12 hrs) 66% (24 hrs) 62% (24 hrs)

92% 92% 78% 80%

P value

0.1 NS

NS NS

Pruritis 72% 60% NS Pruritis requiring meds 44% 30% NS

Nausea 30% 18% NS Nausea requiring meds 4% 10% NS

CONCLUSION: Reducing the dose of intrathecal morphine to 0.1 mg resulted in an unacceptably high percentage (32%) of women requiring interventions for inadequate analgesia. Although the frequency of patients requiring treatment of pruritus was marginally higher in the 0.25 mg group, these data do not appear to support the use of very small doses of intrathecal morphine. REFERENCE: 1. Palmer CM: Abstract SOAP 1994, 48

DOES HIGHER DILUENT VOLUME IMPROVE QUALITY OF EPIDURAL-PCA INFUSION POST CESAREAN SECTION?

Shaul Cohen MD, D Amar MD, CB Pantuck BA, EJ Pantuck MD, A Yama MD

Departments Anesthesia, Robert Wood Johnson Medical School, New Brunswick, NJ; Albert Einstein College of Medicine, Bronx, NY; Memorial Sloan-Kettering Cancer Center, NY, NY; Columbia U Coil of Phys & Surg, NY, NY

Fentanyl, Bupivacaine, Epinephrine, Analgesia, Epidural

INTRODUCTION: Higher diluent volume of epidural fentanyl bolus injection shortened onset & prolonged the duration of post C/S analgesia [l]. The combination of bupivacaine with epidural fentanyl provides high quality analgesia along with sensory & motor blockade post C/S which may interfere with ambulation [2]. We compared the effects on quality of analgesia, dosage & side effects of varying diluent volumes of fentanyl-bupivacaine-epinephrine given by epidural-PCA infusion.

METHODS: Following IRB approval, we studied 80 consenting pat-turients scheduled for elective C/S. Upon arrival in the PACU, patients were randomized to 4 epidural-PCA Groups as shown in Table I. Pain & overall satisfaction were assessed with a 1 O-point scale.

RESULTS: There were no demographic differences among the groups. Infusion durations(hrs) were: 44.1k3.9, 54.0+3.8, 5O.Ok3.3, 48.4k3.8 for group I-IV respectively & did not differ among the groups. Groups l&It had higher infusion rates for 48hr than either Group Ill or IV. The average infusion rate was lower for group Ill than for group I (p c.05). Overall satisfaction was high and similar among the groups. Pain relief was satisfactory for all groups but was better for groups II &Ill than for I & IV (p<.OOl). No patient was markedly sedated or had a respiratory rate < 12 br/min). The incidence of pruritus requiring treatment and nausea did not differ among the groups. Transient lower extremity sensory loss which interfered with ambulation and urinary retention were seen only in group I. Catheter leak & dislodge was seen only in group IV.

CONCLUSION: Epidural-PCA in all 4 groups was safe 8. provided high quality analgesia with minimal side effects. The diluent volumes of 10 & 15 ml/hr used for groups II & Ill were optimal, providing better analgesia without sensory loss, urinary retention, catheter leak or dislodge.

TABLE I: EPIDURAL INFUSION CHARACTERISTICS

GROUP FENTANYL BUPIVACAINE EPINEPHRINE CONTINUOUS BOLUS LOCKOUT

(&ml) (“4 (&ml) INFUSION (ml/h) DOSE (ml) TIME (min)

I (N=20) 6 0.03 2 5 1 15

II (N=20) 3 0.015 1 10 2 15

11 Ill (N=20) 1 2 1 0.01 1 0.67 1 15 1 3 1 15

IV (N-20) 1.5 0.0075 0.5 20 4 15

References: 1. Anesth Analg 68:808-810; 1989 2. Anesth Analg 67:559-563; 1988

205

DOES THE ADDITION OF BUPIVACAINE (0.01%) OR EPINEPHRINE IMPROVE THE QUALITY OF POST C/S EPIDURAL FENTANYL ANALGESIA?

Shaul Cohen, MD, I Lowenwirth, M.D., CB Pantuck, BA, EJ Pantuck, MD, D Amar, MD, T Davidov, BS

Dept Anesthesia, Robt Wood Johnson Med School, New Brunswick, NJ; New York Hospital Center of Queens, Queens, NY; Columbia U Coll of Phys & Surg, NY, NY; Mem Sloan-Kettering Cancer Ctr, NY, NY

Fentanyl, Bupivacaine, Epinephrine, Analgesia, Epidural

INTRODUCTION: Whether bupivacaine 0.01% and/or epinephrine added to epidural fentanyl improve quality of analgesia is not well established.

METHODS: We conducted a double blind study (IRB approved) of 81 consenting patients undergoing elective C/S with epidural lidocaine 2% and epinephrine 5 ug/ml. Following delivery patients were randomized to one of 4 treatment regimens (Table 1). The initial infusion rate was 16 ml/h. PCA boluses were 3 ml with 10 min lockout. Pain and overall satisfaction were assessed with a IO-point scale (O-worst, lo-best). The infusion was continued for 48h with adjustments of the rate by 2 ml/h to achieve a pain score < 3. Newborns were breast fed and assessed with the Neurobehavioral Adaptive Capacity Score (scale O-40) at 2 and 48h of life. Results were analyzed by parametric or nonparametric ANOVA or Chi square, as appropriate.

RESULTS: There were no significant differences among the groups in age, weight, height or parity. Data from several patients were not included in the analysis. Catheters became dislodged from three patients, one each from groups 1, 3, 8 4. Four patients from Gr. 1 (pc.001) and 1 patient from Gr. 3 requested termination of the infusion because of inadequate pain relief. Data (mean + SE) for infusion rates, total dose of fentanyl and overall satisfaction and neurobehavioral scores are shown in Table II. Gr. 1 patients had greater fentanyl requirements and lower satisfaction scores when compared to the other groups and Gr. 3 patients had lower satisfaction scores than Gr. 2 or 4 patients. Incidence of mild pruritus, (75%-94%) sedation (73%-81%) nausea (O%-17%) and vomiting (O%-8%) was similar among the groups.

TABLE I: FENTANYL BUPIVACAINE EPINEPHRINE

(w/ml) % Gr. 1 (n=17) 3 0 Gr. 2 (n=23) 3 0.01 Gr. 3 (n=18) 3 0 Gr. 4 (n=23) 3 0.01

TABLE II: Group 1 Group 2 (n=12) (n=23)

Infusion Rate 19.3+0.6* 15.7kO.4 (ml/h) Total Dose of 2792.7+90.4* 2262.2k60.4 Fentanyl (pg) Overall Satisfaction 5.5kO.2’ 8.620.1 Neurobehavioral Scores at 2 h 35.420.5 34.0+0.6

48h 38.8kO.2 38.620.2

‘p<.OO5 Gr. 1 vs. Gr. 2-4, l *P<.O5 Gr. 3 vs. Gr. 2 or 4

MW) 0 0 0.5 0.5

Group 3 Group 4 (n=16) (n=22) 15.4kO.6 14.3kO.4

2223293.7 2058.3k56.7

6.6kO.2” 8.8kO.l

34.7kO.5 35.2kO.5 39.1kO.2 38.620.2

CONCLUSION: Gr. 1 patients, who received the highest dose of fentanyl, were least satisfied with their pain relief and 24% requested discontinuation of treatment. Addition of epinephrine to fentanyl improved satisfaction but not as much as low dose bupivacaine. Addition of epinephrine to fentanyl plus bupivacaine (Gr. 4) did not further increase satisfaction. No neonatal effects due to fentanyl in breast milk were seen.

206