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Clin Pharmacokinet. 2014 Jun;53(6):553-63. doi: 10.1007/s40262-014-0135-4.

Evidence-based morphine dosing for postoperative neonates and infants.

Author information

1
Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.

Abstract

BACKGROUND AND OBJECTIVES:

From a previously validated paediatric population pharmacokinetic model, it was derived that non-linear morphine maintenance doses of 5 μg/kg(1.5)/h, with a 50 % dose reduction in neonates with a postnatal age (PNA) <10 days, yield similar morphine and metabolite concentrations across patients younger than 3 years. Compared with traditional dosing, this model-derived dosing regimen yields significantly reduced doses in neonates aged <10 days.

METHODS:

Concentration predictions of the population model were prospectively evaluated in postoperative term neonates and infants up to the age of 1 year who received morphine doses according to the model-derived algorithm. The efficacy of this dosing algorithm was evaluated using morphine rescue medication and actual average infusion rates.

RESULTS:

Morphine and metabolite concentrations were accurately predicted by the paediatric pharmacokinetic morphine model. With regard to efficacy, 5 out of 18 neonates (27.8 %) with a PNA of <10 days needed rescue medication versus 18 of the 20 older patients (90 %) (p = 0.06). The median (interquartile range [IQR]) total morphine rescue dose was 0 (0-20) μg/kg in younger patients versus 193 (19-362) μg/kg in older patients (p = 0.003). The median (IQR) actual average morphine infusion rate was 4.4 (4.0-4.8) μg/kg/h in younger patients versus 14.4 (11.3-23.4) μg/kg/h in older patients (p < 0.001).

CONCLUSION:

Morphine paediatric dosing algorithms corrected for pharmacokinetic differences alone yield effective doses that prevent over-dosing for neonates with a PNA <10 days. The fact that many neonates and infants with a PNA ≥10 days still required rescue medication warrants pharmacodynamic studies to further optimize the dosing algorithm for these patients.

PMID:
24496960
DOI:
10.1007/s40262-014-0135-4
[Indexed for MEDLINE]

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