Opioid pharmacodynamics in neonatal dogs: differences between
morphine and fentanyl.
Bragg, Paul, Maurice S. Zwass, Marie Lau, Dennis M. Fisher.
Department of Anesthesia, University of California, San Francisco,
CA 94143-0648
APStracts 2:0303A, 1995.
Clinical experience and laboratory studies suggest that neonates are
more sensitive than adults to morphine's ventilatory depressant
effects. 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 isohypercapnea, morphine or fentanyl were infused to depress
minute ventilation > 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 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 morphine's ventilatory depressant effects resulting from
maturational changes in sensitivity rather than in equilibration.
Maturational changes in fentanyl's ventilatory effects are much
smaller in magnitude than those for morphine.
Received 28 November 1994; accepted in final form 27 June 1995.
APS Manuscript Number A1202-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.