MAIN RSI

Sel' CISTI/ICIST MAIN Sel'~

NRC /CNRC

079 v. 39 no . 6 2005 JLtn

106121-028171 Received on: 05-05-08 The Anna l s of pharmacotherapy.

..I.. JUllUU

'fALS OF ~,-,0THERAPY·

VOLUME 39 • NUMBER 6 JUNE 2005

RESEARCH REPORTS

C ARDIOLOGY

997 Diastolic Filling Param e te rs in H ype rte nsive Urge ncy

A NTICOAGU LATIO N

1002 l ow·Dose W arfarin After Orthopedic Surgery 1008 Influe nce of Et hnicity on W arfa rin Dosage

PHARMACOGEN ETICS

1011 PIA Po lym orphism and Aspirin Resistance

C O MPLEMEN TARY AND A LTERNAT IVE M EDIC INE

1019 Herb, Vitam in, and Mineral Use in the Elderly

DIABETES

1024 Point-of-Care HbA lc vs Standard ized Laboratory

NeO NATOLOGY

1029 Efficacy of Sucrose During Eye Examinations for Retinopathy of Prematurity

NePHRO LOGY

10]4 Effect of Indapamide on C alciuria

T OXICOLOGY A ND P OISON C ONTROL

1039 Tramadol Exposures 1045 Atomoxetine Ingest ions in Children

ARTICLES

A M BULATORY C ARE

1049 Anticoagulation Monitoring: Part I

N EW DRUG D EVELOPMENTS

1056 N e larab ine: A Nucleosid e Ana log with Efficacy in T ~ Ce ll and O ther Le ukemias

ARTI C LES (continued)

DRUG INTERACTIONS

1064 P r e dicting In hibitor")' Drug-Drug In t e ract ions and Evaluating Drug Interactio n Reports

CARDIOLO GY

107] NSAIDs' Impact o n the Cardioprotective Effects of Aspir in

COMPLEMENTARY AND A LT ERNATI VE MEDIC IN E

loao Glucosam ine Lo ng-Te rm T reatment a lld Pr0!o:ression of Knee Osteoarthritis

D RUG INFO RMATION R OUN DS

1088 Nebulized Morphine fo r Re lief of Dyspnea

1093 The Effect of Creatine Intake on Rena l Function

RECENT ADVANCES

THERAPEUTIC MONITORINC

1097 Transporters and Their Impact on Drug Disposition

CASE REPORTS

1109 Tacrolimus-Metronidazole Interaction

1114 Hype~ensiti vity Reactions to Oxaliplatin in Two Asian Patients

1119 Extensive Prolongation of aPTT with Argatroban

I 124 MiII'l r F i, h 'lr Variant o f Guilla in-Barr4 Syndrom'l with T acrolimus

1128 Phenazopyridine-Jnduced Sulfhemoglobinemia

1111 Fluphenazine-Induc'ld N e uroleptic Malignant Syndrome

LEITERS AND COMMENTS

I 1)& U~e of Gabapentin for Rest P"'n in C hronic Critical U mb Ischemia

I 116 Levofloxacin-Induced Fatal To)[jc EpidennaJ Necrolysis

I 117 Pure Red C.,U A pl;..,h' A>o .... o; i "'~ ..... wilh O .. p ...... ., T h.,r"f'Y

I 1)8 CelecolCib-lnduced Deep-Vein Thrombosis

I 1)8 Acceleration of Left-Ventriculu D iastolic Dysfunction and Pulmonary Hypertension After TNF-a Blocker

I 1)9 Co .... ection: Imp. d of Stre" Uker Prophyl_i, Alsorithm Study

See Detailed Tobie of Contents Inside

I I <10 New Pubho;at ions II <49 Personnel P".eem"nt I 15 1 N"ws.u.d Comments 11 45 PharmaCE Test Questlon$ 11 49 Educational Ev(>nt5

THE ANNALS OF P COTHERAPY·

VOLUME 39 • NUMBER 6 JUNE 2005

Senior Editor Milap C Nahata MS PharmD

Associate Editor and Director of Operations

Eugene M Sorkin PharmD

A~c:idQnt_ F.ditnr and Director of Professional Services

Stan ley J Lloyd PharmD

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Timothy E Welty PhannD BepS

EJu:~culivt: Dil'\!ctUI" ur Editorial Services

Jerome P Rosenthal PhD

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}'oreignAbstractors ------------ -------------------------- -­fRENCH ; Deny~ Demell DPH, Bruno Edouard PharmD, Chanlll Outvremonl BPharm MSc. SUlaJlJle Laplante BPharm MSc. Marit Larouche OPH, Michel Le Duff PharmD MS, Jean Longtin PharmO. Louise Mallei PharmD. Alain Man:ooe MSc. Plem: Martineau MSt PI1armD BCPS. Nicolas Paquene-Larnonlagne BPharm MSt MBA. MaK Parent OPH MSc BCPS, Marc ~t Pem;auh PhmnO BCfS. Sylvie R~n MSc PharmD BCPS, Marie·Claude Vanier MSc

SPANISH; Alben Figueras MD. Editor. Brenda R Morand PharmD. Editor; Luz M Guti~rrez PharmD. Coordinator: Culos C da Camara PharmD BCPS: Christina Dalmady­I5nJcI PharmD BCPS: Juan del Arco 1'twmD: Juan Fl'IllCisro Feliu PharmD: Maria fQnt PI1armD: Lydia Gom.;!lez f'harmO: Wilma M Gu1.lTWt-Santos PharmD: usbia HenW!dez PharmO: VlOlell Lopez Sanchez BA PhannD: Sonia I Lugo PhD; Wanda T Maldonado PbarmD; Mirza D Martfnez PhannD; Rafael. Mtna BSPharm; Jorst R Miranda-Mamui I'harmD: Hornero A Monsanto PhD; Enrique Mufloz Soler BA; Mitchell Nazario PharmD; Annelle ~rez PharmD; Giselle C Rh<cra-Miranda PharmD; EncarnaciOn C Sulirez PharmD; Corinne lara Yahni PharmO

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Neonatology

Efficacy of Sucrose to Reduce Pain in Premature Infants

During Eye Examinations for Retinopathy of Prematurity

Peter Gal , Grace E Kissling, Will iam 0 Young, Kimberly K Dunaway, Virginia A Marsh, Susan M Jones,

Dawn H Shockley, Nicole L Weaver, Rita Q Car1os, and J Laurence Ransom

BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU). but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns.

OS,Jecnve: To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain oootrol during the ROP eye examination.

METHODS: Neonates born at $;30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine Hel ophthalmic solution 0 ,5% plus 2 mL 01 sucrose 24% or proparacaine Hel ophthalmic solution 0.5'% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures bOth physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and aiter the eye examination and during initial placement 01 the eye speculum. The same ophthalmologist performed all eye examinations. Stwt::n:11 llillerellt lIefiniliorlS 01 iilJ<till re::;por\:xt were iflve::;liyateu.

RESULTS: Twenty-three inlanls were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5

definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After tho ROP examination, pain rc~ponoo~ wore similar with either ~LlCrOGe or placebo.

CONCLUSIONS: Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP.

KEY WORDS: pain, retinopathy of prematurity, sucrose.

Ann Pharmacother 2005;39:1029-33.

Published Online, 26 Apr 2005, www.tfleannals.com. DOll0.134S1aph.l E477

Newborns in intensive care are exposed 10 many painful slimu li. and sucrose has proven to be effective in re­

duci ng procedural pain from a variety of causes_1 The neonalal eye examination required 10 evaluate for the pres­ence of relinopathy of prematuri ty (ROP) is one painfu l procedure for which sucrose has been poorly studied. Painful response oceurs in virtually all neonates during manipulation of the eye.Z•4 In our unit, topical anesthetics reduce, but do not eradicate, pain associated wilh the neonatal eye examination. Consequently, we desig ned a placebo-conttollcd, double-blind, crossover study to deter­mine whether sucrose pretreatment can prevent pai n asso­ciated with neonatal eye examinations.

Author information provided at the end of the text.

Methods

The siudy in the preceding p.llper examined the efficacy of topical anesthetic for eye examlnaIion pain.' This study is a sequel and used an identical ~ign except for mtlline addition of topical anesthetic and oral study drugs. PatienTS \\-ere admineJ \0 lhe siudy if lhey were ;5;]0 weeks' gestation. required at leasl 2 eye examination~ \0 monitor for RQP. were sufficiently clinically stable \0 toterate the eye examin:ltion based on the neonatologist's clinical assessment, and did nOI require an:llgesia (fen­t:lI1yl) or sedation (lora7.eparn) for :ltle.l.~t 12 hoW'S prior to the procedure. The study was approved by the hospital's institutional review board, The n:llUre of the pnx:edure was explained 10 the (XIrtnts. and consent was ob­t.lined. ROP eye e~aminations are mutinely performed in our neon"ta1 in­tensive care unit (NICU) for high-risk patienl~, and:lll &tudy days ooincid­ed with pn:viously scheduled eye examinations. Patients were enrolled by the study nu~. Exammations were pertonncd by a smgle consultant pe­diatric ophth;llmoJogist who has been lhe primary ophthallllology oonsul­tant for our N1CU for >10 years. He was assisted by the NICU nurse re­sponsible for the infant's care on thm day and 2 pain study nurses who

www.fhemmah.com The Anllals of Pharmacotherapy • 2005 June. Volullle 39 • 1029

P (JaJefai.

had gone through sp(X'ial training with the Premature Infant Pain Profile (plPP) scoring system to promote intcrobsaver consislcocy.

Mydriatic eyedrops (phenylephrine HCI 1%, cyclopentolate HCI 0.2%) were administered approximately 60- 90 minutes before tile ex­amination. The inflUlt was swaddled several minutes before the proce­dure and held by a nu~ during the eye examination. The ophthalmolo­gist inserted a spring-loaded wire Sauer premature infant eyelid specu­lum to hold the eyelids open. Tbe retina of each eye was examined with an indirect ophthalmoscope through dilated pupils using a thimble-type Schepens scleral depressor to rotate the eye and indent me sclera to allow thorough C};amination of the retina.

1br.: study observation interval began 5 minutes prior to the procedure and ended 5 minutes after completion of examination of the second eye. For each procedure. 2 pain study nurses performed pain assessments us­ing the PIPP scale' and reached consensus scores that wcre recorded on a study form at 5 different times throughout the observation period. All in­dividuals involved in the direcI care or asse.~sment of the patient were blinded to the sucrose or sterile water administered during the study.

A standard procedure was followed for each eye examination. The ophthalmologist examined patients in the order prescribed by the nurse investigators. allowing the nurses to record baseline PIPP.scores on each infant 5 minutes and I minute prior to the procedure. The patient's nurse admini steted 2 mL of sucrose 24% (Sweet-case, Children's Medical Venture, Murrysville, PAl or 2 mL of sterile water, placing drops on the infant·.~ tongue over 1_2 minutes ~ing aoout 2 minute.~ before the pr0-

cedure. The ophthalmologist administered local anes thetic eye drops (proparacalnc Hel ophthalmiC solution 0.5%, Bausch & Lomb, Tampa, A..), 2 drops in each eye. prior to examination of the first eye, then about 30 ~onrl~ lam· in!:t".I1/"rl an "y.,]ir! ~r1CCulum 10 f3dl it3'" kl'.i'f';ng I~ t .y" open and perfonncd an examination lasting about 5 minutes to complete both eyes. The study nurses recorded PlPP scores during initial insenion of the wire eyelid Sp«:ulum and I and 5 minutcs after complction of the entire ('.)[amination of both eyes.

Treatment allocation wa~ made in groups of 6 based on the results from II dice roll. Thc hospital pharmacist was the only onc familiar with the individual treatmcnt

tion). (3) number of PIPP scores ;::10. (4) number of PIPP score differ­ences ~ points between treatmenl and placebo conditions, and (5) areas under tile PIPP score curves from 5 minuteS before the examination to eyelid speculum inscnion and from lid speculum insertion to 5 minutes after the cxamination. AUCs were calculated using the trapel.oidal rule. Statistica1 analyses compared sucrose 24% and sterile water treauncnts.

For statktical comparisons of the numben; of paticnts with PIPP scores ;::10, increases in PIPP scores 2:4 points from baseline. and differences of ~4 points between m:atment and placebo, the binomial test was used. For comparisons of ac tual PIPP scores and AUCs, paired I-Iests were used. Paired I-tests were also used to compare postnatal age.~ between the su­crose 24% and steri.le water treatments. The innuences of postconccptional age at time of examination and of the order of treatment on PLPP score were examined with a mixed model repeated measures analysis of covari­ance. The nullllxr needed to m:at to expect one patient to benefit from su­crose 24% was estimated as the reciprocal of the absolute risk reduction for patients to experience pain with sucrose than with placebo.

Results

l wenty-three patients were enrolled in the study from January 2003 lhrough June 2004. All patients completed the study without deviation from the protocol. Twelve infanls received su(.:rose fir.st, and II received sterile water first. The length of time between each palienl's 2 eye examinations ranged from 8 to 35 days (median 21). Gestational ages rilllgcd from 24 to 29 weeks, and postnatal ages at time of

treatment ranged from 28 to 93 days. Postnatal ages at time of examination were not significantly differenl between the sucrose and placebo conditions (p = 0.38; Table 1)-

assignments. One inve~[igator who was never pre!>ent during eye examination studies (PC) revicwed interim study results after 12 patients had been treated to ensure that pat ients were not unnecessarily given sterile water if sucrose proved beneficial. 1be study was stopped aftCT 23 inflUlts wcre trcated because a new ophthalmologist was scheduled to rotate onto the service and we did not want to confound the study by altered examination technique.

Table 1. Demographic Information and P IPP Scores for 22 Neonales

Study nurses evaluated pain using the PIPP scale, which measures both physical and physiologic pain indi­cators and has been validated in prior publications ... ·lhc PIPP score is determined by assigning 0-3 points for var­ious factors including gestational age at the time of obser­vation, behavioral state (eg. quiet or active), increase in maximum hean rote, decrease in 0: saluration. and facial features involving brow bulge. eye squeeze, and nasolabi. al furrow. Possible scores can range from I to 21. Four srudy nurses underwent special training to ensure reliable PIPP scores. For each ROP examination, 2 of the study nurses obser .. ed the infant as described above and record· cd their consensus scores 5 minutes and I minute before the examination, at wire eyelid speculum insertion. and I minute and 5 minutes atter the examination.

Each patient received sucrose 24% and the placebo on different days in random order using a double_blind ctm&_

OVe! design. The study was designed assuming that, with­out intervention, 80% of infants would have a pain re­sponse a'iSOCiated with the eye examination. and adminis· !ration of sucrose would reduce this to 40%. We estimated that 24 patients would be needed to detect this effect with a p value <0.05 and a power of 80%.

Statistical analyses ofPlPP scores were perfocmed sev· era! different way' because definitions of pain in prema_ ture infants may vary and arc somewhat arbitrary. Conse­quently. analyses were performed to consider (I) actual PIPP scores, (2) number of PIPP scores increasing by ~ points from baseline (average of I and 5 min prte:o:amina-

o"~ .Ided

p Value.

Treatment Group' from

Paired Patred Pa rameter Sucrose Placebo DIHerence l'-reals

Gestational 26.4 ± 1.5 26.4.t 1.5 NA NA age (wk)

Day 01 tife 47.3.t 15.2 46.82:16.2 - 1.5 :1:21.6 038 PIPP score 5 min pre- 2 .6.t 1.1 2.5: 1.4 -0.1 :1:2.2 0.39 eKamination

1 minpra· 3.1:1: ' _5 3.0: 1.7 -o.2:t 2.6 0_37 examination

eye speculum 8.3:1: 4.5 10.50104.0 -2.2:t 3.9 om insertion

1 min post- 7.7:3.6 8.3:3.5 -0.6:4.1 0.24 examination ~ mtn post- 3.3:1; 1.4 4.1 ± 2.3 -o.9:t 2.7 0.07 eKamination

AUC (cumulative pain) prccxamination 17.3 :t6.2 17.7.t7.1 -o.4 :t 10.5 0.38 postexamiflation 29.8:t 12.5 34.2:t 14.0 -4.4:1: 15.8 0.10

O~ desaturation 2:10% 00 PIPP score

preexllmination 0 0 NA eye speculum 3(17.4%) 7 (30.4%) 0.34 insertionb

postexaminationb , (4.3%) 2 (S.7%) 1.00

NA,: not applicable: PIPP '" Premature Infant Pain Profite_ "Mean :SO. bPercenlages refer 10 the percent of patients who had a ~'O% reduction in Oa sal-ufatiOfl from pre study baseline.

1030 • The Annals of Pharmacotherapy • 2005 June. Volume 39 www.theannals.com

PIPP scores I minute and 5 minutes prior to the cye ex­amination were simi lar in the sucrose and placebo condi­tions. However, PlPP scores during placement of the wire eyelid speculum were significant ly higher wi th placebo compared with sucrose treatment (p = 0.0 I: Table I). At I minute and 5 minutes after completion of the eye examina­lion. PiPP scores, wh ile generally higher with placebo, were not signi ficantly higher compared wi th sucrose.

Table 2 contains a summary of the resu lts for all 5 po­tential definitions of pain response. Defining pain as an in­crease in PIPP score of ~ points from baseline (the aver­age of scores at 5 and I min before examination), 18 (78%) of the 23 infants had a painful reaction with eyelid speculum insertion when placebo was administered, while 13 (57%) had a painful reaction with eyelid speculum in­sertion when sucrose was admini stered. One minute after tile examination. 6 infantS had painful reactions with place­bo but not wi th sucrose and 2 had painfu l reaclions with sucrose but not placebo. Fi ve minutes after the exami na­tion, none of the patients had painfu l reactions with su­crose and 4 had painful reactions with placebo. Using this defi nition of pain ful reaction, there were no stati stically signifi can t differences between Lhe placebo and sucrose pretreatment. Alternatively, defin ing a painfu l reaction as PfPP score 2:10. no patients had a painful reaction 1 or 5 minutes before the examination.

During the examination. painful reacti ons occurred in 14 (61%) placebo- and 9 (39%) sucrose-treated pati ents. Eight infants had painful reactions with the placebo but not sucrose, whi le 3 had painful reactions with sucrose but not pl acebo at eyelid speculum in serti on (binomial test , p = 0.04). One minute after the examination, painful reactions were observed in 4 patients wit/1 placebo but not sucrose

Table 2. Summary of Results Based on Different Definitions for Pain Response

l·sldecl p Values lor OJflerences Between Placebo and Sucrose'

Definition 01 Belore At WIre After Pain Response Examination Insertion Examination

Actual PIPP score 0.39,0.37 0.01 0.24. 0.07 Increase in PIPP 0.06 0.14, 0.06 score by ~ points above basetine

PIPP score <!10 NA.NA 0.04 0.64, 0.50 PtPP scores for 0.69.0.34 0.02 0.66.0 .t3 placebo and sucrose differ by <'4 points

PIPPAUC 0." 0.10

NA = not apptlcable; PIPP = Premature Infant Pain Profile. 'Slgnificant difference identified as p < 0.05. The p values in the Be-fore Examination column apply, respective ly, to Ihe scores for 5 and 1 minute before examination . The p values in the After Examination cot-umn apply, respectively, to the SOOfes lor 1 and 5 minutes after exam' ination, except for the AUC, which was calculated lor all periOds of time before and after examination.

Efficaq o/SlIcrose Dilling /:.)e fualllimlfiolls ill NeO/mJes

and in 4 with sucrose but not placebo (binomial test, p "" 0.64). Five minutes after the ex:unination, painful reactions occurred in one patient with placeoo but not sucrose and in none of the infants with sucrose but not placebo (binomial test. p = 0.50).

Defining a painful reacti on as a di fference of 2:4 points in PIPP scores betwcen the sucrose and pl acebo condi­tions. at placement of the eyelid s(X:Culum. 10 patients had a painful reaction with placebo and 2 had a painful reac­tion with sucrose (binomial test, p = 0,02). One minUie af­ter the procedure. 3 infants had a painful reaction to place­bo, whi le 3 had a painfu l reaction with sucrose (binomial test. p = 0.66). Five minutes after the procedure, 3 patients had painful reactions with placebo and none had painful reactions with sucrose (binomial test. p = 0. 13).

The AUC for PIPP score was used as a global marker of pain for the 5 minutes from beginning the eye exam in a­tion. Before insert ion of the speculum, the AUe for PIPP scores did not differ between the placebo and sucrose con­ditions Cp = 0.38) . After insen ion of the speculum, the AUe for PIPP scores also d id not differ significantly be­twcen the groups (p = 0. 10; Table I).

As a separate issue, tile effect of postcollceptiollal a~e on PIPP scorc was examine d. Postconceptional age. de­fined as gestational age plus day of life allrealment ex­prcs:>ed in weeks, WIlS inversely relatcd to PIP? score as assessed with bi variate correlations. In a mixed-model, re­peated-measures analysis of covariance, a (poslconception­al age x treatment) interaction indicated that the inverse re­lationship was si milar with sucrose and placebo. A similar repeated-measures analysis of covariance showed no order (".iTlXt of the treMments.

Table 3 gives the numbers of patients who experienced less pain with sucrose 24% than with placebo using each of the 5 definitions of pain response. Depend ing on the definition of pain response. Ihc number needed to treat to expect one patient 10 benefit from the sucrose ranges be­tween 1.4 and 23. No adverse events, except pain response due to the eye examination , were associated with either placebo or sucrose.

Table 3. Number Needed to Treallo Expect One Patient to Benefit from Sucrose

Pis. with Less Pain Definition of with Sucrose vs

Pain Flesponse Placebo at Wire, n (%) NNT

Actual PIPP score 16 (70) 1.,

Increase PIPP score by 24 1(4) 23.0 points above baseline

PtPP score 2;10 3 (13) 7.7

PIPP scores for placebo and sucrose differ by 2;4 points 10(39) 2.3

PIPP AUC after lid speculum 13 (57) 1.7 insertion

NNT = number needed to treat; PIPP = Premature Infant Pain Profil e.

www.rheallnals.com The AlUwls of PharmacOlherapy • 2005 Jill/e. Volllme 39 • 1031

P Galtl al.

Discussion

The neonatal eye examination is well documented to cause pain.l.4 The response to pain in neonates is actually ex­aggerated with important physiologic consequences in con­trast to the relative insensitivity to pain previously be­lieved.IO,11 The eye examination in our population caused pain in 78% of the neonates pretreated with topical anesthetic and placebo and, in the previous study without topical anesthetic, occurred in 100% of neonates.! The conrurrent O2 desatura­tion episodes in 30% of placebo-treated patients highlights the importance of these painful evenlS.

As a result of a recent study in our NICU, the use of topical anesthetic prior to the eye examination has become routine in our unit.s The issue was whether oral sucrose would provide additionaJ benefit to patients during eye ex­amination for ROP, since it is well documented to reduce pain in neonates during several other procedures.I,Il-14 Our study used a blinded crossover approach in which p"';ents functioned as their own control, thus increasing the suuisti­cal power to detect differences if they exisl.~ As with prior studies,l,l the reaction to pain in this study was not affected by gestational age. TItis study aJso used the PIPP scale be­cause this test considers both physiologic and physical markers; has good interrater reliability, internal consisten­r..:y, and construct validity; and was dt:vdupt=tl fUf premature infants.6•9 Also, the PIPP scale was used in our previous study examining eye pain prevention in neonates after pre­trcauncnt with a topical ancsthctic/ as wcll as in scvcral other pain studies. 'l,'! The use of sucrose 24% reduced pain during the insertion of the eyelid speculum regardless of the definition for pain that was used. The analgesic ef­fect of sucrose was n~t sustained after lid insertion and does not benefit all patients. but the acute pain prevention benefits are sufficient to justify routine use.

Conclusions

To expect one patient to benefit from sucrose, 2.3 in­fants would need to be treated to prevent one additional patient from elevating PIPP scores by ~ during placement of the eyelid speculum. Since sucrose is inexpensive and relatively nontoxic, it is reasonable to use sucrose to re­duce pain during ROP examination in neonates who are al­ready receiving enteral feedings.

Peter Gal PharmD BCPS FCCP FASHP, Director, Pharmacy Divi­sion. Greensboro Area Health Education Cenler, Greensboro, NC; Clinical Professor. School of Pharmacy, University of North Carolina al Chapel Hill, Chapel Hil l. NC; Pharmacotherapy Specialist. De­partment of Neonatology. Women's Hospital. Greensbolo Grace E Kissling PhD. Staff Scientist. Bioslatistics Branch. Na· tional Institute of Envilonmental Health Sciences. Research Trian­gle Park. NC William 0 Young MD. Consulting Ophthalmologist. Neonatal In­tensive Care Unit. Women's Hospital; Pedlatlic Ophthalmology As­sociates PA, Greensboro KImberly K Dunaway PharmD. Staff Pharmacist. Pharmacy De­partment. Women's Hospital

Virginia A Marsh RN BSN. Staff Nurse. Nursing Department. Neonatal Intensive Cale Unit. Women's Hospital Susan M Jones RNC BSN, Staff Nurse, Nursing Department, Neonatal Intensive Care Unit, Women's Hospital Dawn H Shockley RN BS ADN, St.aff NurS4iJ, Nursing Department, Neonalallnlensive Care Unit, Women's Hospital

NIcole L Weaver RN BSN, Staff NUlse, NUlsing Department , Neonatal Intensive Care Unit. Women's Hospital Rita Q Cartos MD, Neonatologist, Neonatal Intensive Care Unit, Women's Hospital

J Laurence Ransom MD, Medical Director. Neonatallntensrve Gare Un~. Women's Hospital; Clinical Professor, Department of Pediatrics, Schooj of Medicine. Univel'i5ity of North QHoIina at Chapel Hill

ReprInts: Dr. Gal , Greensboro AHEC. Ste. 100.200 E. Northwood 51. , Greensboro, NC 27401 -1020. fax 336/832·7851. peter.gal@ mosescone.com

References

I. Ste"e"~ B. Yamada 1, Oh1!JW1l A. Sucro!>e for allalgo:~;a '" ,ot:wooru ill­fants undergoing painful procedures. Cochrane Database Syst Rev 200U:c0001069.

2. Laws DE. Monon C. WeindJing M. Oar\( D. Systemic effeclS of screen­ing for rmnopnthy ofpremnturity. Br J Ophtholmol 1996;80:425·8.

3. Rush R. Sush S. Nicolau 1. Chapman K. Naqvi M. Systemic manifesta­tions in resplnsc to mydriasis and physical examination during screening for retinopathy of prematurity. Retina 2004:24:242-5.

4. Slevin M. Murphy JFA, Daly L. O'Keefe M. RdillOpllthy of prematurity screening. stress related responses. the role of nesting. Br J Ophthaimol 1997;81:762-4.

5. Marsh VA. Young WOo Dunaway KK. Kissling GE. Carlos RQ. Jones SM. eI at. Efficocy nftopical ane<;thetic<; 10 reil llC,", pain in premMll1'e in_ fants during eye examination for relinopathy of prematurity. Ann Phar­macothcr 2005;39:829-33. DOl 1O.13451aph.E476

6. Stevens B. l ohnston C. PelIyshen P. Taddio A. Premature Infant Pain Profile: development and initial validalion. Clin 1 Pain 1996;12: 13,22.

7. Stevens B. Gibbins S. Clinical utility and clinical significance in the as­sessment and management of pain in vulnerable infants. Clin Perinalol 2002:29:459-68.

8. Anand KJS and the International Evidence-Based Group fOr Neona!al. Pain. Consensus statemenl for the prcvcnlion and management of pain in ihc: newborn. Arch f>rolatr Moiese Mcd 2001 ;155: 173-80.

9. Ballantyne M . Stc\'ens B. McAlIiSl¢r M. Dionne K, Jack A. Validation of the Premature Infant Pain Profile in the clinical setting. Clin J Pain 1':IY'J;15:2'J7-3U3.

10. Anand KJS. Clinical importance of pain and smss in prelerm infanlS. BioI Neonate 1998:73: 1-9.

11 . American Academy of Pediatrics and Canadian Pediatric Society. Pre­vention and management of pain and stress in the neonate. Pediatrics 2000; 105:454-61.

12. Gradin M. Eriksson M. Holmqvist G. Holsl¢in A. $cholin J. Pain reduc­tion at venipuncture in newborns: orat gtueose compared with local iII""~"'t..iC CfC<UII. PWialliu 2002;110;1053-7.

13. Kauffman GE. Cimo S. Miner LW, Blass EM. An evaluation of the ef­fects of sucrose on neonatal pain with 2 commonly used circumcision methods. Am 1 Obstct GynecoI2002:186:564-8.

14. Mastcrs-I larte LO. Abdd-Rahman SM. Sucn»c analgesia for minor pr0-

cedures in newborn infants. Ann PharmllCOlhc:r 2001 ;35:947-52. DOI10.l3451aph.l931l

15. Anand KJS. McintOSh N. Lagcrcrantz H. Young TE. Vasa R. Bartoo BA. Analgesia and sedation in preterm infants who require ventilatory sup­pM. Arch Pediall' Adolese Mal 1999:153:331-8.

INTRQDUCCIOS: Los ellamenes oculares de la retinopatfa del prematuro (ROP) resultnn dolorosos para el neQnlUO. La utitizaci6n de anest~5ieos 16picos en eI namen ocular de ROP es una pcicrica habitual en nuestra NICU (Unidad Neonatal de Cuidados Intensivos). pero ItO elimina par compteto la~ respuestas dolorosas. Se ha demosuruio que la~ soluciones azucamda~ reducen el dotor del procedimiento en el reei.!n nacido.

1032 • The Annals of Pharmacotherapy • 2005 June, Volume 39 www.theanna/s.com

nHJ.:TI\ ·Q: Estc eslUdio cx:unina si la administraciOn de sucrosa aJ 24% junto al anest~ico t6pioo mcjora cI control del dolor del procedimiento durome cl examen oculnrde ROP.

.\ltJ~; En eslC esrudio con asignacioo alealOlia, dOOle ciegQ. coniroilido con plocmo, y cruzado, ge incluycron noonalOS nneidoo ron s30 semanas de gestacioo. Previamenlc al cxamen ocular, se asign6 aIeaIoriameme al paciet11C bien soluci6n oft!lmica de dorhidrmo de proparacaina al 0 .5% m:is 2 mLde sucrosa al 24% 0 bien soluci6n ofMlmica de ck:H'tlKWIQ de proparocnina 111 0.5% nui:l2 mL de agua cst6i1 como placebo. En el examen subsiguicntc. caW pacienle n:cibiO el tratamicnlO ahcmo, La sucrosa oral Y eI agua esltril se prcpararon en la fannada en jeringas similarcs. y 105 m&liC05, enfermerns, y (annacCulK:a5 en 1 .. NIOJ dc~()nodlVl c1 tnltamicnl0 administrudo en cOOa caso. La mcdici6n del dolor se R!a1i7.6 mediante un sistema de pumuaci6n que incluye Ia mcdiciOO fTsica y psiool6gica del dolor, escala PIP!' (Prerrmlure Infant Pain l'rofile), y fue caleulado por 2 cnfenneras, La punluaci6n del dolor (I' IT'I') 3C rcali7,O I y 5 minuI05 anlcs y <k:spues del examen ocular y duranle 1a oolocad6n inicial del cspeculo ocular. Todos los cdmencs oculares fueron realizados porel mismo oftalm6logo. Sc invcstiga1Ol1 diferentes defmieiones de una rcspucsta al dolor.

IU:stJU<Iot)()S.: EI CSludio ineluyO 23 pacicmes, de los cualcs 12 pacientts recibicron in ieialmenle sucrosa como trotamiento y otros II pacientcs recibicfQf1 eI placebo. Para) de las 5 definieiones de R!Spuesta al dolor, el dolor fue signiflCativamcnte inferior durante la colocacioo del espKulO en aqueJlos pacicntcs que recibieron sucrosa en lugar del placeoo. Tras el exarnen de ROP, las rcspucstas al dolor resuharon similarcs t:lnto con sucrosa como con placebo.

COSCLl.. .... Ol'lT.$: La ~ oral puede !\'dueir la respuesta inmediata al dole." en los prematuros que foe someten at examcn ocular de ROP.

Enrique Munoz Soler

R~UME

OBJ[ C1lJ'; L'u!ilisation topiquede solutions anesthesiques est pratique courantt pour eontr61er Ia doulcur associ6e aux examens ocuJaires lOI'S du diagnost ic d'ul1C retinopathie du nouveau-of, Unc ahemmive possible aux anes~iqllCS topiques c:st l' utilisation d'une solution ~ base de sucrose, L'objectif de cenc etude ~tait d'cvaluer si rajout d'une solution de sucrose 24% 0. un anesthtsique topique pouvait riduire la dooleur associc!e a une !elle procedUR!. ~

EjJU:ucy a/SIlCrose Dilring E)'~ &aminlltion.s ill NeollQtes

MtTllOnoU)(:n'~ Les notJ\'eaux-n6s d'un 32C £CSlationnel de, )0 semaines, chez qui un minimum de 2 examens oculaircs c!taicnt antici~, ont ~ inelus dans cetle etude A dooble-insu avec pennulation et contrOlte par placebo, u s patients Ctaient assignes de fa~ aJbtoire 11. une solution ophtalmique d'hydrochlorure de proparocai'ne 0.5% et de sucrose 241}. ainsi qu'i une solution ophtalmique d'hydroc:hlorurc de proparacai'ne 0.5% Cl d'eau stErile. Otaque potient recevait Ie IIaitement a\'antle premier exnmen oculaire puis Ie traitement altematif avant l'examen oculaire .subsequent. Les solutions ocuJ.aires de sucrose 24% et d'eau stal lc Ctaient prepar6::s par Ie dtpanemem de pharmacie dans des seringues a ruberculine d'apparcnce idcntique. Les m6:1ecin~ Its pharm:tciens. et Ies infirm~res de I ' unite nc!onatalc n' cuienl pas inf0rm6: de la nature des so!Ulion. .. adminiSirees.. La douleur etail tne:WJtc: par unc «helle validte (Premature Infant Pain Profile, PIPP) qui utilise des mesures physiologiqucs CI physiques pour ttablir un score \'ariant entre I et 21 , l..e score de la douleurCtait mesure de f3liOO simultan&! par 2 infirmihcs I et 5 minutl:!i a\'ant l'examen oculaire et dumnt Ie placement initial du sp6:ulum, TOllS Ics examcns oculaires Ct.-tient faits]Xll' Ie rot:me oph\.almologiste. Plusieurs interpretations des sccrcs de douleur 0111 etc! invesliguees (~ort: reel PIPp, augmcntation du score PIPP de 4 pnjnl.~, score 1'11'1' surtricllr !t 10 poinr", aire .o;rniS b courbc cVIlluan11e score PIPP en fOlletion du temps, di!f(!rcncc de 4 points Cl plus entre les SCOfCS PIPP du groupe placebo et du groupe sucrose).

lU'..sllL1~l.'S; Vingl,tro;s palients onl th!: ro;:rule.~ pour cene trude; 12 ayan! reoru lots du premier lrai tcmcnt Ia solution Oe sucrose 24% et II 1a solu1ion d'eau st&ile. Pour 3 des 5 mtthodes d'intcrptitation Oe la rc!ponse douloureuse, une dou1eur moins intense a Cle notCe Iotsde l'in,;c,liotl .;Ill ¢ulwil clltt b paliellb aya"1 'COiu la :\OIulioo, ok sucrose par rapport?! la solution d'eau SlOiIe. L'intensile de la douleur c!tait tOUlcfois similaire arm I'exarnen oculaire. OOSCl.Il'iIO)I.."" L'utilisaUon d'une solution de sucrose 24% associ6e ~ une solution ophtalmique anesthesique se.oole n!duirc la ttponse doolourcuse iTJUnl.Xli31e assod~e ~ r e~amen oculaire Iors du diagflOS(ic d'une rtlinopatllie du OOU\'(;3u,nc!.

Sylvie Robcn

www.lheallllais.cum The Afma!s uf Pharmacolltemp), • 2005 June, Voltlme 39 • 1033