March 2000

Morphine Pharmacokinetics and Pain Assessment in Premature Newborns

Scott CS; Riggs KW; Ling EW; Fitzgerald CE; Hill ML; Grunau RV; Solimano A; Craig KD
J Pediat 1999 Oct;135(4):423-9.

Commentary by Charles Coté, M.D.

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[ see abstract below ]

Scott et al examined the pharmacokinetics versus postconceptual age of morphine in preterm infants. The plasma half-life of fentanyl was inversely related to postconceptual age with regards to developmental changes in cardiac output, hepatic function and renal function, as would be expected. The half-life was also longer than that previously reported. The authors attempted to correlate pain scores with blood levels of morphine. They were unable to demonstrate a relationship. This certainly is not an unexpected finding given the wide variation in levels associated with analgesia for either morphine or fentanyl in both adults and older children. We do not know how many of these infants had increased intraabdominal pressure, which could have greatly influence individual patients� pharmacokinetic parameters. In addition, the pain score was dependent upon facial expressions/grimace, which is difficult to assess in most intubated babies. Nevertheless, these authors are to be congratulated for helping to better define the pharmacokinetics of morphine in this population. Perhaps the most important observation is that the long half-life and great patient-to-patient variability suggest that intermittent dosing rather than an infusion may prevent drug accumulation. The authors correctly point out the difficulty of assessing pain in infants who are premature, intubated and paralyzed! We have much work to do in the treatment of pain and stress in the NICU but these three studies suggest that a lot of good people are actively pursuing this research.

ABSTRACT Morphine pharmacokinetics and pain assessment in premature newborns Scott CS; Riggs KW; Ling EW; Fitzgerald CE; Hill ML; Grunau RV; Solimano A; Craig KD SOURCE: J Pediatr 1999 Oct;135(4):423-9 COMMENT: Comment in: J Pediatr 1999 Oct;135(4):403-5 ABSTRACT: OBJECTIVES: To determine morphine pharmacokinetics in premature neonates varying in postconceptional age (PCA) and evaluate behavioral pain response in relationship to serum morphine concentrations. METHODS: Premature neonates (n = 48), stratified by weeks of PCA (group 1 = 24-27 weeks, group 2 = 28-31 weeks, group 3 = 32-35 weeks, and group 4 = 36-39 weeks) received morphine infusions. Blood samples were drawn at 48, 60, and 72 hours and at discontinuation of morphine, followed by 3 samples obtained during the next 24 hours. Newborns were videotaped during heel lances and restful states, with morphine at steady-state concentrations and without morphine. Pain was assessed by using the Neonatal Facial Coding System (NFCS). Statistical analysis included regression between NFCS score changes from baseline to painful procedure with and without morphine. RESULTS: Morphine clearance for groups 1, 2, 3, and 4 was calculated as 2.27 +/- 1.07, 3.21 +/- 1.57, 4.51 +/- 1.97, and 7.80 +/- 2.67 mL/kg/min, respectively, and correlated with PCA (r = 0.63, P <.001). Pain measured by facial expression was diminished; however, it did not correlate with morphine concentrations. CONCLUSION: Morphine clearance in premature neonates is less than reported, increasing with PCA. Facial activity discloses morphine analgesia; however, it is unrelated to morphine concentrations.