Anesthesiology:
doi: 10.1097/ALN.0b013e31825580de
Correspondence

In Reply

Sharma, Anshuman M.D.; Kharasch, Evan D. M.D., Ph.D.*

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We are glad to learn of the interest of Drs. Gurnaney, Kraemer, and Ganesh in the pediatric use of methadone,1 a clinically effective and utilitarian perioperative opioid.2 Gurnaney et al. write that they “had a few questions and comments.” We find no questions in their letter, but can explicate their comments.
Gurnaney et al. comment that the study was “primarily designed to evaluate the pharmacokinetics of methadone and not its opioid sparing effects.” They are correct. As was indeed stated in the manuscript, “The primary purpose was to determine the pharmacokinetics of intravenous methadone in children. A secondary purpose was to assess postoperative opioid consumption in pediatric surgical patients who receive methadone.”1 Gurnaney et al. also comment that “the study may not have the power and design to look at the clinical effects of methadone in the postoperative period.” As Gurnaney et al. surely know, studies are not powered for secondary outcomes. Indeed, the manuscript explicitly stated “The investigation was not powered specifically to evaluate opioid consumption, which was a secondary outcome” and it was reiterated in the Discussion that the study was not designed primarily to assess opioid-sparing effects of methadone.1
Gurnaney et al. suggest that “lack of standardization of the intraoperative and postoperative pain management may lead to multiple recognized and unrecognized confounding factors being unadjusted between the treatment groups, (which) may be responsible for a lack of difference in the amount of postoperative opioid consumption between the controls and the three-methadone groups.” Unfortunately, they did not identify these multiple recognized and unrecognized confounding factors. Certainly it was not the amount of opioid (either nonmethadone or total) administered intraoperatively, which was not statistically different between the methadone treatment groups.1
Gurnaney et al. comment that other studies have shown a postoperative opioid-sparing effect of methadone. Others have. We reviewed this previously,2 and also discussed it quite extensively in the article.1 Potential reasons for a difference between our and previous investigations were also well articulated in the article, including differences in surgical procedures, associated severity of pain, use of additional intraoperative opioids, the deliberately low methadone dose, and the dose of methadone relative to the total intraoperative opioid dose.1 Gurnaney et al. suggest that the reason was “confounding factors” or sample sizes. Perhaps.
Gurnaney et al. state that one potential approach to achieving statistically significant differences in opioid consumption by scoliosis patients treated with 0.1–0.3 mg/kg methadone would be to increase sample sizes. Their sample size arithmetic is correct. However, as clearly stated in the manuscript, higher methadone doses are likely needed for scoliosis surgery, and other much more painful procedures. That seems a better approach to achieving statistical significance while delivering better care to our patients.
Anshuman Sharma, M.D., Evan D. Kharasch, M.D., Ph.D.* *Washington University in St. Louis, St. Louis, Missouri. kharasch@wustl.edu
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References

1. Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED: Perioperative pharmacokinetics of methadone in adolescents. ANESTHESIOLOGY 2011; 115:1153–61

2. Kharasch ED: Intraoperative methadone: Rediscovery, reappraisal, and reinvigoration? Anesth Analg 2011; 112:13–6

© 2012 American Society of Anesthesiologists, Inc.

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