Morphine pharmacokinetics and pain assessment in premature newborns,☆☆,

Presented in part at the 1994 Annual American Pediatric Society and the Society for Pediatric Research Meeting, May 4, 1994, Seattle, Washington; and the 3rd International Symposium on Pediatric Pain, June 8, 1994, Philadelphia, Pennsylvania.
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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. (J Pediatr 1999;135:423-9)

Section snippets

METHODS

Ethical approval was obtained from The University of British Columbia and The British Columbia’s Children’s Hospital. Informed consent was obtained from parents or guardians before study entry.

RESULTS

A total of 496 neonates received morphine infusions during the study period, October 9, 1991, through December 4, 1993; 48 individual newborns (33 boys) completed the protocol (Table I).

. Clinical profile of infants completing protocol

PCA groupPCA at entry (wk)GA at entry (wk)PNA at entry (d)Birth weight (g)Sex (M:F)Sedation (n)Clinical indicationsMechanical ventilation during morphine (n)
Analgesia for surgery (n)Analgesia (other) (n)
1 (n = 10)26.8 ± 0.726.6 ± 0.71.1 ± 0.31083 ± 1748:29019
2 (n =

DISCUSSION

The study findings provide evidence that morphine provides analgesia in premature neonates and that morphine clearance increases with PCA. Neonates aged 24 to 27 weeks had the lowest clearance, as expected. Authors have suggested that gestational age weakly correlates with morphine clearance.16, 18 Our data suggest that PCA more accurately reflects morphine clearance.

In the absence of urinary excretion data for morphine and its metabolites, we can only speculate that the lower Cl values, and

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    Supported by the B.C. Health Research Foundation (grant No. 5-53006).

    ☆☆

    Reprint requests: Christy Silvius Scott, PharmD, BCPS, Assistant Professor, School of Pharmacy, Division of Pharmacotherapy, The University of North Carolina, CB No. 7360, Beard Hall, Chapel Hill, NC 27599-7360.

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