Management of Acute Pain in Children: Pharmacologic

Opioid Analgesics

For the vast majority of children, opioids provide excellent analgesia with a wide margin of safety. Developmental differences, however, can make dosing difficult, especially in the first several months of life. In the first week of a newborn's life, the elimination half-life of morphine is more than twice as long as that in older children and adults. This appears to be due to several factors, most important of which is the immaturity of the newborn infant's hepatic enzyme systems. Clearance of morphine is dependent on conjugation of the drug to the metabolites' morphine-3-glucuronide and the morphine-6-glucuronide; the latter contributes a substantial fraction of morphine's analgesic effects. This reaction is catalyzed by mixed function oxidases and the cytochrome P450 system, which, though present, have attained only a portion of their full function. Fentanyl and sufentanil also have diminished hepatic metabolism in premature and term neonates. Glomerular filtration is reduced in the first week of life, leading to slower elimination of morphine's active metabolites.

Equally important in determining safe opioid dosing in infants is an understanding of the immaturity of central respiratory control mechanisms. Infants in the first 3 to 6 months of life have inadequate and sometime paradoxical ventilatory responses to both hypoxia and hypercapnia.^21,37 As a result, they may develop apnea or periodic breathing after receiving even small doses of opioids. Cardiorespiratory monitoring and careful observation is recommended whenever opioids are administered to infants less than 2 to 3 months of age. Premature infants and former premature infants with chronic lung disease continue to show depressed hypoxic drive for several months, and often require careful monitoring after opioid administration up to 5 to 6 months of age.