Epidural Morphine in Children: Pharmacokinetics and CO2 Sensitivity

The effects of epidural morphine (50 micrograms X kg-1) after abdominal and urologic surgery were studied in 20 children ranging in age from 2 to 15 yr and weighing between 9 and 54 kg. The onset and the duration of analgesia were 30 +/- 12 min and 19.5 +/- 8 h, respectively (mean +/- SD). Side effects were pruritus (4/20), nausea and vomiting (8/20), and urinary retention (4/14). No apnea was observed. Ventilation control was studied in seven children. No significant change in resting respiratory variables occurred after both surgery and epidural morphine injection. However, the slope of the ventilatory response to CO2 was significantly (P less than 0.05) decreased after surgery but before morphine, as compared with its preoperative control value (0.84 +/- 0.44 versus 1.51 +/- 0.72 l X min-1 X mmHg-1), and remained low for 22 h after epidural morphine (0.90 +/- 0.57 l X min-1 X mmHg-1). Sixty minutes after morphine injection, the plasma morphine concentration was always less than 12 ng X ml-1 in the seven children studied. Pharmacokinetic parameters were similar to those observed after epidural injection of morphine in adults, except for a shorter terminal half-life (73.8 +/- 41.6 min) attributed to a greater total body clearance of morphine in the children (28.3 +/- 3.4 ml X min-1 X kg-1). It is concluded that epidural morphine provides effective and prolonged analgesia in children after abdominal and urologic surgery and that it is associated with prolonged respiratory depression that requires close monitoring for at least 24 h.