In Reply:
The management of acute postsurgical pain in opiate-dependent patients is one of the most difficult clinical challenges in perioperative medicine. Although ketamine has been shown to be of value in some surgical settings for opiate-naïve patients, there is little information available pertaining to its use in opiate-dependent patients who need to undergo major and painful surgery.
Therefore, we designed our recent study1to determine the role, if any, of an easily implemented intraoperative ketamine protocol on postoperative recovery parameters. The study, if positive, was designed to be the beginning of an ongoing effort to define optimal treatment for surgical patients who suffer from chronic preoperative pain. As such, we appreciate the opportunity to clarify the issues raised by Dr. Seigne.
Dr. Seigne expressed concern and asked for clarification regarding the fact that the amount of opiate used in the 48-h postoperative period differed between the population reviewed in order to power the study and the actual study control group. The standard deviations for both groups are quite large. Thus, there was no statistically significant difference. Further, one would expect the groups to be different, given the intrinsic variability in the surgical population of interest.
Dr. Seigne was also concerned by the fact that the study patients, in both the treatment and placebo groups, appear to be using more pain medications at 6 weeks as compared to baseline, and that preoperative morphine use is presented as median (interquartile range) whereas postoperative use is reported as mean (SD). Preoperative morphine use is reported as median (interquartile range) because of the skewed nature of the data; this measure is a better reflection of the population. This was not the case for postoperative morphine use, however, making mean (SD) the more appropriate presentation. Results are reported in intravenous morphine equivalents, as stated in the manuscript. As expected, after major and painful surgery, patients in both study groups are using more pain medicine at 6 weeks as compared with baseline. We would consider a steady decrement in opiate consumption per hour to represent an expected recovery process. Note again the 3- or 4-fold difference in opiate consumption between control and treatment groups at 6 weeks.
Dr. Seigne also wondered whether the statistical significance reached between the treatment and control groups in terms of the number of levels of surgery might have clinical relevance. We do not consider this factor to be clinically significant. We direct readers' attention to equal surgical times and blood loss.
In terms of Dr. Seigne's questions regarding longer term follow-up, this study was planned as the beginning to further studies. If we did further follow-up, we would either get the same results (better recovery in the treatment group) or there would be no difference at, say, 1 yr. At some point, we expect the latter to appear, which identifies the key question for any follow-up study, namely: What is the most relevant outcome parameter to measure in this type of study? Patient satisfaction? Functional activity level?
*Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. randy.loftus@hitchcock.org
