Epidural morphine causes delayed and prolonged ventilatory depression

We measured ventilation, PETCO2 and the Ventilatory response to added carbon dioxide before and at intervals up to six hours after epidural morphine 3.5 mg and 7.0 mg, and before and after subcutaneous injections of the same dose in volunteers. Subcutaneous morphine increased PETCO2 slightly, but did not alter the sensitivity of the response to added carbon dioxide. Epidural morphine reduced ventilation and increased PETCO2 progressively with time and, six hours after injection, reduced the ventilatory response to carbon dioxide considerably. In two subjects tested, these ventilatory effects persisted for twenty-four hours. The added effects of epidural morphine were due primarily to reductions in tidal volume and the tidal volume response to added carbon dioxide. We conclude that epidural morphine causes delayed and very prolonged ventilatory depression, which is of a greater magnitude and a different ventilatory pattern than that which follows the same does of morphine given subcutaneously. Ventilatory depression after lumbar epidural morphine develops slowly, as the lower limb analgesic effect is waning.