The Gerald W. Ostheimer LectureWhat’s New in Obstetric Anaesthesia - 2012/2013?
Arvind Palanisamy, MD, FRCAAssistant Professor of Anaesthesia
Brigham and Women’s HospitalHarvard Medical School
DisclosureNo relevant financial relationships with commercial interests
Core Syllabus
Anesthesia Obstetrics
Perinatology
To compile the syllabusThree Stage Approach
72 journals, 6387 publications
type of investigation, strength of evidence, clinical relevance, and public health impact
86 syllabus, 20 The Lecture
Syllabus
Grading
Literature Search(Jan - Dec 2012)
Developmental Continuum
Embryo Pregnancy Labor and Delivery Neonatology
Embryo and FetusEmbryonic and fetal neurodevelopment
Maternal DiseasesImpact of maternal diseases, early detection, biomarkers
Neonatal DevelopmentNeonatal analgesia, stress response
Labor and DeliveryLabor, operative delivery, anesthesia, complications
Embryological and Fetal DevelopmentAnesthetic neurotoxicity
Maternal DiseasesPreeclampsia
Neonatal DevelopmentNeonatal outcomes, stress response, neonatal analgesia
Labor and DeliveryLabor, obstetric outcomes, cesarean delivery, complications
1
2
3
From rodents to primatesAnesthetic Neurotoxicity
Association between anesthesia exposure during early childhood and learning disabilities later in life
Dose-dependent neurodegeneration at critical periods of postnatal development
Fetal brain remains vulnerable in a rodent model
What we know so far
Evidence from a primate model
Primate study Pregnant macaques at G120 (2nd trimester)
Neonatal macaques at P6
IV ketamine infusion (dose range)
Primary outcome measureNeuroapoptosis in brain regions
Fetal Anesthetic Neurotoxicity
12 Brambrink AM et. al, Anesthesiology 2012; 116:372-84
Evidence from a primate modelFetal Anesthetic Neurotoxicity
frontal cortex
thalamus
amygdala
cingulate cortex
Evidence from a primate modelFetal Anesthetic Neurotoxicity
2-fold
Neurotoxic effects of propofolFetal Anesthetic Neurotoxicity
Creeley C et. al, Br J Anaesth; 110: i29-i38
2.4-fold 3.8-fold
Neurotoxic effects of isoflurane
Creeley C et. al, Anesthesiology 2013; 116:372-84
4-fold increase
Fetal Anesthetic Neurotoxicity
Non-human primate brain is susceptible to the effects of even a short duration of anesthesia
Effects occur with all classes of anesthetic agents
Fetal brain is differentially susceptible
Both neurons and oligodendrocytes are affected
What These Studies Add
Embryological and Fetal DevelopmentNeurodevelopmental and teratological effects
Maternal DiseasesPreeclampsia
Neonatal DevelopmentNeonatal outcomes, stress response, neonatal analgesia
Labor and DeliveryLabor, obstetric outcomes, cesarean delivery, complications
1
2
3
PreeclampsiaPowe CE et. al, Circulation 2011
What we know so far
Altered circulating angiogenic factorssFlt-1, sEng, PlGF
sFlt-1/PlGF ratioidentifies women with early-onset preeclampsia
sFlt-1/PlGF ratio and the risk of adverse outcomes
Prospective cohort study616 singleton pregnancies evaluated for suspected preeclampsia
Primary outcome measurecorrelation between sFlt-1/PlGF ratio and adverse maternal and fetal outcomes within 2 weeks
18 Rana S et. al, Circulation 2012; 125:911-919
Preeclampsia
sFlt-1/PlGF ratio highly correlated with adverse outcomes
All patients < 34 weeks
Preeclampsia
sFlt-1/PlGF ratio of 85 and specific adverse outcomes
Complications Early delivery
Preeclampsia
Ratio < 85
Ratio > 85
What this study adds
sFlt-1/PlGF ratio > 85
predicts adverse outcomes occurring within 2 weeks
identifies women at risk for imminent delivery
USG determination of optic nerve sheath diameter (ONSD)Preeclampsia
Dubost C et. al, Anesthesiology 2012; 116:1066-107136
Observational study26 preeclamptic women, 25 healthy pregnant women 4-6 weeks before term
ONSD measurement3 mm behind retina, 7.5 Mhz probe, 2-D mode
Eyeball
USG determination of optic nerve sheath diameter (ONSD)Preeclampsia
Preeclampsia Healthy P value
Age (yrs)
Weight (kg)
SBP (mm Hg)
34 (31-36) 31 (28-34) 0.09
80 (70-90) 69 (63-79) 0.04
138-153 102-111 < 0.0001
ONSD (mm) 5.4 (5.2-5.8) 4.5 (4.3-4.8) < 0.0001
USG determination of optic nerve sheath diameter (ONSD)Preeclampsia
Big Question
Does the ONSD really represent raised ICP, or is it just optic nerve sheath edema?
Embryological and Fetal DevelopmentNeurodevelopmental and teratological effects
Maternal DiseasesPreeclampsia, diabetes mellitus, congenital heart disease
Neonatal DevelopmentNeonatal outcomes, stress response, neonatal analgesia
Labor and DeliveryLabor, obstetric outcomes, cesarean delivery, complications
1
2
34
Epidural-associated Fever
Maternal temperature increases during laboretiology is unclear
Recent evidence*suggests that maternal inflammation could be responsible, but role of epidural analgesia still unclear
What we know so far
Maternal fever and adverse neonatal outcomeshigher incidence of neurological depression of neonates
*Segal BS et. al, Anesth Analg 2010; 111 (6): 1467-75
Intrapartum temperature elevation after epidural analgesiaEpidural-associated Fever
Greenwell EA et.al, Pediatrics 2012; 129:e44742
Retrospective cohort study design
Objectivesis epidural analgesia associated with adverse neonatal outcomes in the absence of temperature elevation?
impact of epidural-related temperature elevation on neonatal outcomes?
Outcomes: hypotonia, Apgar scores, assisted ventilation, early-onset seizures
Intrapartum temperature elevation after epidural analgesiaEpidural-associated Fever
Analysis I
absence of temperature elevation (< 99.5 F)
N = 1538 epidural
N = 363 no epidural
Analysis II
neonatal outcomes in epidural group based on
temperature
N = 2784
Outcomes in the ABSENCE of temperature elevationEpidural-associated Fever
No Epidural(n = 363)
Epidural(n = 1538) P
Length of labor (h)Pitocin use (%)Vaginal delivery
HypotoniaAssisted ventilation
5 min Apgar < 7Neonatal seizures
6.4 11 < 0.000128.7% 72.4% < 0.000185.4% 67.2% < 0.000110.7% 10.8% 0.082.5% 4.4% 0.50.6% 0.3% 0.10% 0.1% 0.9
Outcomes in the PRESENCE of temperature elevationEpidural-associated Fever
< 99.5 F(n = 1538)
99.6 - 100.4 F (n = 711)
100.5 - 101 F(n = 297)
> 101 F(n=238)
p orOR
Length of labor (h)
Pitocin use (%)
Vaginal delivery
Hypotonia
Assisted ventilation
5 min Apgar < 7
Neonatal seizures
11 14.2 15.4 16.3 < 0.001
72.4% 82% 86.9% 87% < 0.001
67.2% 57.8% 52.9% 42% < 0.001
10.8% 19% 21.6% 25.2% 1.8-2.2
4.4% 6.8% 8.1% 12.2% 1.3-2.1
0.3% 0.7% 1.4% 2.1% 1.8-4.8
0.1% 0.3% 0.3% 1.3% 1.7-6.5
Caveats to be borne in mindEpidural-associated Fever
Important limitation
Study design
Confounding variables
Repetitive retrospective use of the same database, lack of chronological relationship between epidural placement and fever
Not controlled for usual factors that alter maternal temperature
Lack of a group of febrile women without epidural analgesia for comparison
Factors affecting intrapartum temperatureEpidural-associated Fever
Frolich MA et.al, Anesthesiology 2012; 117 (2); 302-847
Prospective cohort studyParturients admitted for labor induction
Oral temperature hourly after admission
Primary aim: time course of maternal temperature
Secondary aims: duration of labor, epidural analgesia, oxytocin dose, and duration of ROM
Statistical Methods
Epidural-associated FeverFactors affecting intrapartum temperature
Mixed linear model: to track temperature change over time
Regression analysis: to test the effect of covariates
Student t test:
compare those with positive and negative temperature slopes
compare ‘before and after epidural analgesia’ slopes
Factors affecting intrapartum temperatureEpidural-associated Fever
Pre-epidural Post-epidural
Factors affecting intrapartum temperatureEpidural-associated Fever
Postdural Puncture Headache
Variability in management after dural puncturespinal catheter vs. repeat epidural placement?
Emerging evidenceintrathecal catheters do not reduce incidence of PDPH or EBP when used only during labor
What we know so far
Lack of consensus due to lack of prospective studies
Intrathecal catheter vs. repeat epidural after dural puncturePostdural Puncture Headache
Russell IF, Int J Obstet Anesth 2012; 21:7-1662
Prospective controlled studyInstitutional randomization of 19 hospitals
Spinal catheter to remain 24-36 h postpartum
Primary outcome: occurrence of PDPH and need for EBP
Secondary outcomes: complications
Intrathecal catheter vs. repeat epidural after dural puncturePostdural Puncture Headache
Repeat Epidural(n = 47) (%)
Spinal Catheter(n = 50) (%) P
Any HeadachePDPHEBP
Additional attemptsRepeat ADP
31 (66%) 39 (78%) 0.1929 (62%) 36 (72%) 0.226 (55%) 25 (50%) 0.6014 (32%) 4 (8%) < 0.054 (9%) 0 (0%) < 0.05
Quality control
Study design
Confounding variables
Varying practices at different institutions, treatment bias, selective reporting of data
Only 18/55 spinal catheters were left > 24 h, disproportional representation of patients
Cesarean delivery, neuraxial morphine, high BMI
Postdural Puncture HeadacheIntrathecal catheter vs. repeat epidural after dural puncture
Chronic headache after accidental dural puncture (ADP)Postdural Puncture Headache
Webb CA et.al, Anesth Analg 2012; 115:124-3264
Case control study design40 parturients who received ADP
40 age, weight, time of delivery matched controls without ADP
Primary outcome: incidence of chronic headache (12-24 months)
Secondary outcome: incidence of chronic back pain, pain disability
0
13
25
38
5043
15Incid
ence
%
Chronic back pain
0
8
15
23
30 28
5
Incid
ence
%
Chronic headache
ControlDural puncture
ControlDural puncture
P = 0.01 P = 0.01
Postdural Puncture HeadacheChronic headache after accidental dural puncture (ADP)
Big Question
Does an epidural blood patch alter the incidence of chronic headache and back pain?
Chronic headache after accidental dural puncture (ADP)Postdural Puncture Headache
0
15
30
45
6060
32
Incid
ence
%
Chronic back pain
0
10
20
30
4040
20
Incid
ence
%
Chronic headache
Blood patchNo blood patch
Blood patchNo blood patch
P > 0.05 P > 0.05
Postpartum Hemorrhage (PPH)
Trends in peripartum hysterectomy
Study Design: cross-sectional study
Database: NIS, 1994-2007
Objectiveto determine trends in peripartum hysterectomy
contribution of changes in maternal characteristics to these trends
Postpartum Hemorrhage
74 Bateman BT et. al, Am J Obstet Gynecol 2012; 206: 63.e1-8
Trends in peripartum hysterectomyPostpartum Hemorrhage
0
15
30
45
60
75
90
1994-95 1996-97 1998-99 2000-01 2002-03 2004-05 2006-07
Per 1
00,00
0 deli
verie
s
Trends in peripartum hysterectomyPostpartum Hemorrhage
Peripartum hysterectomy
70
75
80
85
90
1994-95 2006-07
82.6
71.6
Abnormal placentation
0
10
21
31
41
1994-95 2006-07
40.5
32.9
Cesarean delivery
0
1
2
3
4
Primary Repeat
4
2.5
11
Fold
incr
ease
Uterine atony
0
8
15
23
30
1994-95 2006-07
25.9
11.2
15% 23%
130% 2.5 X 4 X
Chronic Pain After Childbirth
Incidence of chronic pain 4-10% with vaginal delivery6-18% with cesarean delivery
Lack of high quality studies in this fielddespite scale of public health impact
What we know so far
Not controlled for pre-existing pain
Low incidence of chronic pain at 1-year after delivery
Study MethodologyProspective, multi-center study (US, Europe)
Subjects2518 patients interviewed within 36 h after delivery, followed up at 2, 6, and 12 months
Primary outcomeTo understand the incidence and identify risk factors for chronic pain after delivery up to 12 months
Chronic Pain After Childbirth
78 Eisenach JC et. al, Anesthesiology 2013; 118: 143-51
Low incidence of chronic pain at 1-year after deliveryChronic Pain After Childbirth
1.8%
0.3%
9.8%
Potential mechanismChronic Pain After Childbirth
Gutierrez S et. al, Anesthesiology 2013; 118: 152-9
Study MethodologyMid-trimester spinal nerve ligation
SubjectsPregnant and non-pregnant rats, tested for hypersensitivity to mechanical stimulus during and after pregnancy
Primary outcomeChange in hypersensitivity over time, role of oxytocin
Potential mechanismChronic Pain After Childbirth
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Potential mechanismChronic Pain After Childbirth
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Potential mechanismChronic Pain After Childbirth
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Thanks
BWH
Lawrence TsenBhavani Shankar Kodali
Thomas McElrath
Non-BWH
Alexander ButwickPaloma Toledo
Jill Mhyre
Funding
FAERAll Investigators
Brigham and Women’s
Lawrence TsenBhavani Shankar Kodali
Thomas McElrath
Other Institutions
Alexander ButwickPaloma Toledo
Jill Mhyre
Funding
FAERAll Investigators
