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June 1997
Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision.
Taddio A, Stevens B, Craig K, Rastogi P, Ben-David S, Shennan A, Mulligan P, Koren G; NEJM 1997; 336:1197-1201.
[ see abstract below ]
Any study of medication use must address the issues of the safety and efficacy of the drug. In the past, discussions of appropriate analgesia for infants sometimes were simply terminated by assertions that infants do not feel pain. This argument is clearly inappropriate and now rarely used.
However, selection of outcome measures to evaluate efficacy and the elucidation of the physiologic differences which impact on drug safety in infants (see reviews of two articles on the pharmacology of drugs commonly used in neonates in the April AnesthesiaWeb site) still challenge investigators.
A recent lead article in the New England Journal of Medicine on the efficacy and safety of EMLA cream during circumcision summarizes many of these issues clearly. This multidisciplinary (pediatrics, pharmacy, nursing, medicine and psychology) and multi-institutional (University of Toronto and University of British Columbia) study by Taddio et al. reports the results of a double-blind, randomized controlled trial of 68 term infants who underwent circumcision during the first few days of life.
Efficacy measures included behavioral (facial action, crying) and physiologic (heart rate and blood pressure) variables, and safety was assessed with measurements of blood methemoglobin and plasma lidocaine, prilocaine and o-toluldine.
Behavior is always a difficult thing to use as an indicator of a subjective experience such as pain or anxiety; this is particularly true in infants, since their repertoire of behaviors is relatively limited. The authors of this study have done an excellent job at this task: the Neonatal Facial Coding System has been well validated, and the research assistant who did the assessments was trained and the results of that raining documented with an excellent kappa of 0.93.
Nonetheless, the facial activity scores more than doubled (worsened) from baseline, just with restraint of the infant, and only increased slightly more during the procedure itself in the placebo group. The lidocaine-prilocaine infants recovered from their distress at being restrained and showed facial activity close to baseline during dorsal incision and foreskin cutting. Clearly, EMLA cream does help to prevent pain during circumcision, but even the best behavior measurements have limitations in identifying pain as the specific source of an infant s distress.
The discussion section of this paper also contains useful reminders of the long-term effects of untreated pain in infants, and of the importance of using the full range of measures available (in this situation, acetaminophen, the use of a pacifier, and administration of sucrose) to address the multidimensional nature of pain in patients of all ages.
To be involved in ongoing case-based discussions of pain in infants and children, you can subscribe to the PEDIATRIC-PAIN electronic mail list by sending an e-mail message to: MAILSERV@ac.dal.ca. The first line of the body of the message should read: "subscribe PEDIATRIC-PAIN."
A quarterly review of data-based research papers and book reviews on this subject is available by subscription to The Pediatric Pain Letter. Contact Managing Editor Julie Goodman, Psychology Department, Dalhousie University, Halifax, Nova Scotia, B3H 4J1, Canada. Email: jgoodman@is2.dal.ca
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Background: Neonatal circumcision is a painful surgical procedure often performed without analgesia. We assessed the efficacy and safety of 5 percent lidocaine-prilocaine cream (Emla) in neonates undergoing circumcision.
Methods: We carried out a double-blind, randomized, controlled trial in 68 full-term male neonates: 38 were assigned to receive lidocaine-prilocaine cream, and 30 to receive placebo. One gram of lidocaine-prilocaine or placebo cream was applied to the penis under an occlusive dressing for 60-80 minutes before circumcision.
Behavioral (facial activity and time spent crying) and physiologic (heart rate and blood pressure) responses were recorded during the procedure. Blood samples were obtained at various times after drug application for measurements of methemoglobin and plasma lidocaine, prilocaine, and o-toluldine (a metabolite of prilocaine).
Results: A total of 68 and 59 neonates were included in the safety and efficacy analyses, respectively. Demographic characteristics such as gestational age and birth weight did not differ between the lidocaine-prilocaine and placebo groups. During circumcision, the neonates in the lidocaine-prilocaine group had less facial activity (P = 0.01), spent less time crying (P < 0.001), and had smaller increases in heart rate (P = 0.007) than the neonates in the placebo group.
Facial-activity scores were 12 to 49 percent lower during various steps of the procedure in the lidocaine-prilocaine group. As compared with neonates in the placebo group, infants in the lidocaine-prilocaine group cried less than half as much and had heart rate increases of 10 beats per minute less.
Blood methemoglobin concentrations (expressed as a percentage of the hemoglobin concentration) were similar (1.3 percent) in both groups. Lidocaine and prilocaine were detected in plasma in 23 (61percent) and 21 (55 percent) of the infants treated with lidocaine-prilocaine cream, respectively.
Conclusions: Lidocaine-prilocaine cream is efficacious and safe for the prevention of pain from circumcision in neonates.
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