To the Editor:—

Aida et al.  1present intriguing results regarding the intraoperative administration of epidural morphine combined with intravenous ketamine. However, I question their conclusion that these results provide definitive evidence for a preemptive analgesic effect. Because there was no control group to which similar doses of analgesics were administered nonpreemptively, the possibility must be considered that the results of this study were due to persistent effects of the analgesic regimen rather than a true preemptive effect.

The experimental design of this study included postoperative administration of a single intravenous dose of naloxone to the patients to whom preemptive epidural morphine had been administered. The authors postulate that this single dose of naloxone displaces the epidurally administered morphine from the spinal receptors and that the morphine present in the neuraxis is then distributed around the body. They further postulate that morphine will no longer be present in adequate concentrations to exert an analgesic effect once the naloxone has been eliminated. No evidence was provided to support this assertion.

The patients in this study to whom preemptive epidural morphine was administered without intravenous ketamine had significantly less postoperative pain than the patients to whom only postoperative epidural morphine was administered. This result is consistent with a prolonged effect of the preemptively administered morphine. (The average dose of intraoperative epidural morphine in the preemptive group was approximately 7.7 mg.) Because of its hydrophilic nature, clearance of morphine from the cerebrospinal fluid is slow. 2It seems likely that epidurally administered morphine is not rapidly redistributed after a dose of naloxone. Rather, a significant reservoir of neuraxial morphine may be expected to persist well beyond the duration of effect of the naloxone.

Aida S, Yamakura T, Baba H, Taga K, Fukuda S, Shimoji K: Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: A randomized double-blind study. A nesthesiology 2000; 92: 1624–30
Ummenhofer WC, Arends RH, Shen DD, Bernards CM: Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. A nesthesiology 2000; 92: 739–53