Opioid-induced analgesia in neonatal dogs: pharmacodynamic differences between morphine and fentanyl

Whether the analgesic effects of opioids change as a neonate matures is not well understood. To address this issue, we determined the pharmacokinetics and pharmacodynamics of analgesic effects of morphine and fentanyl in 35 dogs aged 1 to 34 days. Opioids were infused to produce analgesia, response times to a noxious thermal stimulus were measured and plasma opioid concentrations were determined. An effect compartment pharmacodynamic model was fit to the values for time to response to determine the rate constant for equilibration (Keo) between plasma and effect-site (Ce) concentrations and analgesic effect (increase in time to response to a noxious stimulus) above baseline per microgram/ml of Ce (delta). A time-to-event data analysis (modeled with a Weibull function) was used to account for censored time to response values. For both opioids, values for Keo did not vary with age. Values for delta decreased with age (i.e., decreasing sensitivity with increasing age), and the magnitude of the change during the first month of life was similar for the two opioids. In the context of our previous study concerning ventilatory depressant effects of these opioids (that sensitivity to morphine, but not to fentanyl, decreased markedly during the first month of life), these results in dogs suggest that fentanyl has greater utility than morphine in neonates during spontaneous ventilation.