Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl

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.