PMID: 8594008Nov 1, 1995Paper

Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl

Journal of Applied Physiology
P BraggD M Fisher

Abstract

Clinical experience and laboratory studies suggest that neonates are more sensitive than adults to the ventilatory depressant effects of morphine. Similar sensitivity has been cited, but not demonstrated, for fentanyl. To examine this issue, we determined ventilatory pharmacodynamics of morphine and fentanyl in 28 dogs aged 2-35 days. During isohypercapnia, morphine or fentanyl was infused to depress minute ventilation by > 50% and arterial plasma opioid concentrations were measured. For each drug, an effect compartment pharmacodynamic model was fit to the values for minute ventilation to determine the steady-state opioid plasma concentration depressing ventilation by 50% (C50) and the rate constant for equilibration between plasma concentration and effect (keo). For morphine, there was a marked age-related increase in C50 but no change in keo. For fentanyl, there was a small maturational increase in C50 and no change in keo. We conclude that there are marked maturational changes in the ventilatory depressant effects of morphine resulting from maturational changes in sensitivity rather than in equilibration. Maturational changes in the ventilatory effects of fentanyl are much smaller in magnitude than those for morphine.

Citations

Mar 8, 2003·European Journal of Anaesthesiology·M WestphalG Brodner
Mar 8, 2003·European Journal of Anaesthesiology·D HarmonD Lowe
Mar 8, 2003·European Journal of Anaesthesiology·B HeindlB F Becker
Mar 8, 2003·European Journal of Anaesthesiology·N AnzawaA Matsuki
Mar 8, 2003·European Journal of Anaesthesiology·C D HanningE K Perry
Mar 8, 2003·European Journal of Anaesthesiology·O A P SantanenM P J Paloheimo
Mar 8, 2003·European Journal of Anaesthesiology·R TytherG Shorten
Sep 26, 2003·Anesthesiology·Thomas BouillonSteven L Shafer
Mar 8, 2003·European Journal of Anaesthesiology·R BogdanskiE Kochs
Mar 8, 2003·European Journal of Anaesthesiology·H Erolçay, L Yüceyar
Mar 8, 2003·European Journal of Anaesthesiology·J J LehotO Bastien
Mar 8, 2003·European Journal of Anaesthesiology·K MikawaY Niwa
Sep 11, 2008·Pharmacogenomics·Parvaz Madadi, Gideon Koren
Mar 8, 2003·European Journal of Anaesthesiology·G KierzekJ L Pourriat
Mar 8, 2003·European Journal of Anaesthesiology·T BouillonA Hoeft
Jul 13, 2005·Pediatric Clinics of North America·Christine Greco, Charles Berde
Oct 29, 2008·The Veterinary Clinics of North America. Small Animal Practice·Karol A Mathews

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