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Department of Anesthesiology, Centre Mèdico-Chirurgical Saint Paul, Clairiëre, Fort de France, Martinique, alainvanel@hotmail.com
To the Editor:
We read with interest the article by Kwok et al. (1). The authors demonstrated that small dose of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine provides preemptive analgesia in patients undergoing gynecologic laparoscopic surgery.
There are conflicting results in the literature concerning preemptive effect of ketamine. Studies have documented a preemptive effect (2–5) and others have not (6–10). The efficacy of ketamine is linked to activation of NMDA receptors of the dorsal horn of the spinal cord. In case of adequate perioperative analgesia, NMDA receptors activation is likely to be suppressed and ketamine administration useless. In the studies that have documented a preemptive effect of ketamine (2–5), the perioperative opioid analgesia is questionable and likely to have induced intraoperative activation of NMDA receptors. In the study of Kwok et al. (1) patients were administered an average total dose of 2 µg/kg of fentanyl. Surgery lasted more than 60 min. Given the pharmacokinetics of fentanyl, we can wonder whether intraoperative analgesia was adequate, even in these minimally invasive surgery procedures. Inadequate analgesia might have, therefore, led to NMDA receptor activation and subsequent positive action of ketamine.
The real challenge, however, in the clinical setting might not be to use the least amount of analgesic drug but to minimize long-term complications and occurrence of chronic pain syndromes. The study of Kwok et al. would have gained in interest if they had more focused on the long-term follow-up of the patients, using clinical assessment of allodynia and hyperalgesia.
References
Department of Anaesthesia and Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Department of Anesthesia and Intensive Care,, Chinese University of Hong Kong,, Prince of Wales Hospital,, Shatin, Hong Kong, mtvchan@cuhk.edu.hk
In Response:
We thank Van Elstraete et al. for their interest in our paper (1). They reported an interesting observation that "adequate" intraoperative analgesic obscures the preemptive effects of ketamine analgesia. This is not surprising, because opioid produces preemptive analgesia on its own (2). However, large doses of opioids induce hypotension, nausea, and vomiting and may delay recovery times. These side effects limit the role of intraoperative opioid for preemptive analgesia. In our study, we chose to administer fentanyl 2 µg/mL during induction of anesthesia because this is a common dosage for the prescribed surgery. Although the mean (± SD) pain scores in the postanesthesia care unit for the placebo group (37 ± 25) were higher than the treatment groups (31 ± 18, P < 0.001), they were acceptable to many patients. We believe intraoperative analgesia in our study is not grossly inadequate.
We totally agree with Van Elstraete et al. that we should avoid surrogate measures and focus on long-term outcomes. We have already detected a trend towards better quality of recovery in the preincision ketamine group compared with control over the first month after surgery. In addition, we wish to report that none of our patients developed chronic pain syndrome 1 to 2 years after surgery.
References
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