Safety of pain control with morphine: new (and old) aspects of morphine pharmacokinetics and pharmacodynamics

Background: A 26-year-old, 59 kg female was administered morphine 10 mg during tonsillectomy, and 5 mg in the recovery room. She died 5 hours after the operation. Hypoxic cerebral injury, arising from morphine side-effects, was pronounced the cause of death, in spite of morphine being undetectable in blood. Recent pharmacokinetic-pharmacodynamic modelling indicates that, after a single intravenous dose, maximum respiratory depression occurs after 1 hour and 40 minutes and persists for hours. Furthermore, respiratory depression is accompanied by airway obstruction, sleep potentiates respiratory depression and airway obstruction, pain stimulates breathing and antagonises respiratory depression, pain relief unmasks respiratory depression, and a slow breathing rate is uncommon.Methods: Pharmacokinetic-pharmacodynamic simulations were used to estimate the time course of morphine effect-site concentrations in an “average” 59 kg female, and to calculate the degree of resulting respiratory depression.Resu...