To the Editor:—

We read with much interest the study of Aida et al.  1regarding the “preemptive” analgesic effects of intravenous ketamine and epidural morphine in gastrectomy patients. The improved postoperative analgesia, particularly in the group to which both medications were administered, is certainly a useful clinical effect. However, we disagree with the authors’ use of the term preemptive analgesia to describe their results.

As noted by McQuay, 2attributing improved pain control to a “preemptive analgesic” effect requires a comparison of the prestimulus (“preemptive”) therapy with an identical therapy administered after the stimulus. Comparing groups to which a prestimulus analgesic was administered with a placebo group to which no poststimulus dose was administered merely examines the effects of increasing the total dose of analgesic. The study of Aida et al.  1is an example of this phenomenon. There were no groups to which equivalent poststimulus doses of either ketamine or morphine were administered.

In addition, the prolonged duration of epidural morphine (6–24 h) may have contributed to the postoperative analgesia in the epidural morphine groups. Although the authors attempted to compensate for this by administering a single dose of intravenous naloxone “after skin closure to block the continued effect of the preemptive morphine,”1the validity of this is based on a series of assumptions: first, that the naloxone entered the spinal cord in sufficient quantities to release all the morphine from its receptors; then, that all the morphine diffused into the systemic circulation; and finally, that the morphine was completely eliminated from the body so that it could not reenter the spinal cord and bind to its receptors when the naloxone effects dissipated. Without evidence supporting these assumptions, the possibility remains that the “preemptive” epidural morphine was still present in sufficient quantities to produce postoperative analgesia.

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
McQuay HJ: Pre-emptive analgesia. Br J Anaesth 1992; 69: 1–3