Anemia of Prematurity - Portal Neonatal

Opioid administration remains the most common means of achieving pain control in surgical patients.
Neonates who are expected to have moderate-to-severe postoperative pain are no exception. Opioids
may be administered safely to neonates when a well-constructed pain management plan is
implemented. While certainly not prohibitive, the risk of apnea cannot be ignored. As during the
intraoperative period, more than one opioid may be considered in managing postoperative pain in the
surgical neonate. Fentanyl and morphine are the most common selections for postoperative opioid
administration.
Fentanyl
This drug is most appropriately administered by IV infusion to neonates who are ventilated
preoperatively and are expected to remain ventilated for a period postoperatively. When administered
by IV bolus (2 mcg/kg/h), fentanyl is associated with more severe episodes of apnea than continuous IV
infusion (1-2 mcg/kg/h). However, respiratory depression may be less problematic when fentanyl is
used in older infants. As with many other medications administered to neonates, fentanyl
pharmacokinetics are highly variable. Of particular interest, neonates who postoperatively have
increased abdominal pressure may have a prolonged fentanyl half-life because of impaired hepatic
blood flow.
Morphine
Morphine remains the opioid analgesic most commonly used for moderate-to-severe pain in neonates
postoperatively. Surgical procedures that may be included in this category include craniotomy,
thoracotomy, sternotomy, and laparotomy. Incremental IV boluses of 20 mcg/kg, not to exceed 100
mcg/kg, are typically administered for acute pain management in the postanesthesia recovery unit.
When a continuous IV infusion is used for postoperative pain management in neonates, the initial rate
varies depending upon the age of the neonate.
Initial IV infusion rates of 10 mcg/kg/h for neonates younger than 1 week are acceptable. Neonates
older than 1 week tolerate 15 mcg/kg/h, while older infants may tolerate 20-40 mcg/kg/h. Supplemental
IV boluses of up to 50 mcg/kg may be administered for breakthrough pain episodes in neonates
receiving morphine by continuous infusion. No difference exists in the respiratory response to morphine
in term neonates compared to older infants and children when identical plasma levels of morphine are
achieved and maintained. Greater caution may be advisable when initiating morphine infusions in
preterm neonates, who may require significantly lower infusion rates to achieve the same plasma levels
of morphine as term neonates. Above a steady-state plasma concentration of 20 ng/mL, respiratory
depression becomes more likely in all neonates.
Practitioners who administer morphine infusions for postoperative pain control should be aware of the
pharmacokinetic disadvantages, which place neonates at risk for respiratory depression (because of
increased plasma concentrations). Neonates have immature hepatic enzyme systems. This may result
in a doubling of the elimination half-life of morphine in neonates (ie, 10-20 h) compared with older
infants (ie, 5-10 h). Lower plasma protein levels in neonates may result in higher levels of free drug and
slower plasma clearance of morphine. Morphine clearance in neonates may be as little 50% of that of
older infants and 25% of adult values. Furthermore, the rate of glucuronidation (the primary metabolic
pathway of morphine) is slower in neonates compared to older infants and adults.
Coexisting surgical and medical conditions may impact the pharmacokinetics of morphine in neonates.
As mentioned before, abdominal surgery that results in increased abdominal pressure postoperatively
may impair drug metabolism or drug elimination, thus increasing the half-life of these medications.
Additionally, the pharmacokinetics of medications may be different in neonates with cardiac comorbidity
compared to those without congenital heart disease. Whether this is secondary to impaired cardiac
performance or the impact of abnormal circulatory dynamics on hepatic or renal function is unclear. Use
of preservative-free morphine should also be considered because neonates are more susceptible to
respiratory depression caused by some preservatives.