Is Oral Sucrose an Effective Analgesic in Neonates?

JASMINE CHEN GATTI, M.D., Johns Hopkins Community Physicians Montgomery Grove Health Center, Rockville, Maryland

The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Jasmine Chen Gatti, M.D., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.

Clinical Scenario

A new mother is concerned about the pain her child may feel during a routine heel stick and venipuncture. She asks if there is any nonpharmacologic way to alleviate the pain.

Clinical Question

Is oral sucrose effective in providing analgesia during painful procedures in neonates?

Cochrane Abstract Background. Management of pain for neonates is less than optimal. The administration of sucrose with and without non-nutritive sucking (e.g., pacifiers) has been the most frequently studied nonpharmacologic intervention for relief of procedural pain in neonates. Objectives. To determine the efficacy, effect of dose, and safety of sucrose for relieving procedural pain as assessed by validated individual pain indicators and composite pain scores. Search Strategy. The authors1 used standard methods as per the Neonatal Collaborative Review Group. Relevant randomized controlled trials (RCTs) were identified through a MEDLINE search from January 1966 to April 2001, an EMBASE search from 1993 to 2001, and a search of the Cochrane Library, Issue 2, April 2001. Key words and terms included infant/newborn, pain, analgesia, and sucrose. Language restrictions were not imposed. Bibliographies, personal files, the most recent relevant neonatal and pain journals, and recent major pediatric pain conference proceedings were searched manually. Unpublished studies or studies reported only as abstracts were not included. Additional information from published studies was obtained. Selection Criteria. RCTs in which term and/or preterm neonates (postnatal age, maximum of 28 days after reaching 40 weeks' corrected gestational age) received sucrose via oral syringe, nasogastric tube, dropper, or pacifier for procedural pain from heel lance or venipuncture. In the control group, water, pacifier, or positioning/containing was used. Studies in which the painful stimulus was circumcision were excluded. Data Collection and Analysis. Trial quality was assessed according to the methods of the Neonatal Collaborative Review Group. Quality measures included blinding of randomization, blinding of intervention, completeness of follow-up, and blinding of outcome measurement. Data were abstracted and independently checked for accuracy by three investigators. Statistical Analysis. The statistical package (RevMan 4.1) of the Cochrane Collaboration was used. For meta-analysis, a weighted mean difference (WMD) with 95 percent confidence intervals (CIs) using the fixed-effects model was reported for continuous outcome measures. Primary Results. Thirty-eight studies were identified for possible inclusion in the review. Seven studies reported only as abstracts, and 14 additional studies were excluded, leaving 17 studies included in this review. Sucrose in a wide variety of doses generally was found to decrease physiologic (heart rate) and behavioral (mean percent time crying, total cry duration, duration of first cry, and facial action) pain indicators and composite pain scores in neonates undergoing heel stick or venipuncture. When pain scores from the Premature Infant Pain Profile were pooled for three studies (Gibbins 2001, Johnston 1999, Stevens 1999), scores were significantly reduced in infants who were given sucrose (dose range, 0.012 g to 0.12 g) compared with the control group at 30 seconds (WMD, -1.64 [95 percent CI, -2.47, -0.81]; P = 0.0001) and at 60 seconds (WMD, -2.05 [95 percent CI, -3.08, -1.02]; P = 0.00010) after heel lance. When results for change in heart rate were pooled for two studies (Haouari 1995, Isik 2000), there were no significant differences in infants given sucrose (dose range, 0.5 g to 0.6 g) compared with the control group at one minute (WMD, 0.90 [95 percent CI, -5.81, 7.61]; P = 0.8) and at three minutes (WMD, -6.20 [95 percent CI, -15.27, 2.88]; P = 0.18) after heel lance. Reviewers' Conclusions. Sucrose is safe and effective in reducing procedural pain from single events (e.g., heel lance, venipuncture). There was inconsistency in the dose of sucrose that was effective (dose range, 0.012 g to 0.12 g). Therefore, an optimal dose to be used in preterm and/or term infants could not be identified. The use of repeated administrations of sucrose in neonates needs to be investigated, as does the use of sucrose in combination with other behavioral interventions (e.g., facilitated tucking, kangaroo care) and pharmacologic interventions (e.g., morphine, fentanyl). The use of sucrose in neonates who are unstable, ventilated, and/or of very low birth weight also needs to be addressed. These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in The Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (www.cochrane.org).

Evidence-Based Answer

The use of oral sucrose, with or without pacifiers, has been shown to relieve pain in neonates, as assessed by physiologic and behavioral pain indicators and pain scores.

Cochrane Critique

Did the authors address a focused clinical question? Yes.

Were the criteria used to select articles for inclusion appropriate? Yes.

Is it likely that important relevant articles were missed? No.

Was the validity of the individual articles appraised? Yes. Ten of the 17 RCTs did not have assured blind randomization and were not double blinded. Certain studies had small sample sizes. Eleven studies did not specifically report allocation concealment. Definitions of pain varied, as did methods. For instance, whether painful stimuli were equally intense, lasted as long, or were as frequent was not measurable. It is also not known whether researchers failed to report adverse effects because of insufficient observation time after heel lance.

Were the assessments of studies reproducible? Yes.

Were the results similar from study to study? Despite inconsistent outcome measures, overall outcomes showed similar results.

How precise were the results? With the exception of the 1993 trial by Rushforth, all 12 trials assessing behavior outcomes had confidence intervals with acceptable precision.

Can the results be applied to patient care? Yes.

Do the conclusions make biologic and clinical sense? Yes.

Are the benefits worth the harms and the costs? If parents perceive pain as a barrier to immunization, venipuncture, or heel lance, analgesia would improve compliance and further the public health mandate that all infants be immunized. The original review included intramuscular injections or immunizations as painful procedures. The recent update did not include immunizations, primarily because the inclusion age of 28 days would not encompass many infants who receive immunizations.

Practice Pointers

Giving sucrose for analgesia seems to be such a simple act to implement. Why have few practitioners used it? Perhaps the myth that neonates do not feel pain persists. Although this Cochrane review focused on neonates, there is evidence that sucrose also reduces pain in infants receiving immunizations.^2,3 Perhaps we can try sucrose in our own practices by giving neonates and infants oral sucrose solution two minutes before painful minor procedures, followed by a pacifier. The articles reviewed used small doses of sucrose. Doses of 0.01 to 0.02 g were beneficial in pain reduction in premature infants. Larger doses of 0.24 to 0.50 g helped reduce pain in term infants, as assessed by crying times. The effective dose range was 0.012 to 0.12 g (0.05 to 0.5 mL of 24 percent solution), given two minutes before the procedure. After nurses and parents chart a pain scale, the parents can choose whether they would like to use this intervention before the next immunization. The infant, parent, and doctor might feel better. At the same time that we are helping to comfort our patients, we are facilitating preventive medicine and putting the evidence into practice.

REFERE NCES

1. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2003;1:CD001069.
2. Ramenghi LA, Webb AV, Shevlin PM, Green M, Evans DJ, Levene MI. Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: a randomized, placebo-controlled trial. Biol Neonate 2002;81:163-9.
3. Abu-Arafeh I, Callaghan M, Hill A, Hislop S. Randomised controlled trial of sucrose by mouth for the relief of infant crying after immunisation. Arch Dis Child 1998;79:465-6.

Jasmine Chen Gatti, M.D., is a medical writer and family physician at Johns Hopkins Community Physicians Montgomery Grove Health Center, Rockville, Md. She received her medical degree from Georgetown University School of Medicine, Washington, D.C., and completed a family practice residency at the University of Maryland Medical Center, Baltimore. Dr. Gatti was a fellow at the Cochrane Collaboration.

Address correspondence to Jasmine Chen Gatti, M.D., JHCP Montgomery Grove Health Center, 15201 Shady Grove Rd., Suite 202, Rockville, MD 20850. (e-mail: jgatti@jhmi.edu). Reprints are not available from the author.