Evidence-based morphine dosing for postoperative neonates and infants.

Clinical pharmacokinetics (2014-02-06)
Elke H J Krekels, Dick Tibboel, Saskia N de Wildt, Ilse Ceelie, Albert Dahan, Monique van Dijk, Meindert Danhof, Catherijne A J Knibbe
ABSTRACT

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. 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. 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). 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Sigma-Aldrich
Acetonitrile, for HPLC, for UV, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Acetonitrile, analytical standard
Sigma-Aldrich
Acetonitrile, ReagentPlus®, 99%
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Acetonitrile, ≥99.5% (GC)
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
Supelco
Residual Solvent - Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Sigma-Aldrich
Acetonitrile, for preparative HPLC, ≥99.8% (GC)
Sigma-Aldrich
Acetonitrile
Sigma-Aldrich
Acetonitrile solution, NMR reference standard, 0.23 wt. % in D2O (99.9 atom % D), water 0.05 wt. %, NMR tube size 6.5 mm × 8 in.
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Millipore
Acetonitrile solution, suitable for HPLC, acetonitrile:water 5:95% (v/v), 10 mM Ammoniumbicarbonate, pH 10,0
Sigma-Aldrich
Acetonitrile, configured for PerkinElmer 8900, configured for Polygen, for DNA synthesis
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Ultrapure Acetonitrile

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

Merck

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.