Morphine pharmacokinetics and pain assessment in premature newborns

Objectives: To determine morphine pharmacokinetics in premature neonates va rying in postconceptional age (PCA) and evaluate behavioral pain response i n 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 = 3 6-39 weeks) received morphine infusions. Blood samples were drawn at 48, 60 , and 72 hours and at discontinuation of morphine, followed by 3 samples ob tained during the next 24 hours. Newborns were videotaped during heel lance s and restful states, with morphine at steady-state concentrations and with out 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 2.2 7 +/- 1.07, 3.21 +/- 1.57, 4.51 +/- 1.97 and 7.80 +/- 2.67 mL/kg/min, respe ctively, and correlated with PCA (r = 0.63, P < .001). Pain measured by fac ial 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.