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Does Modafinil Improve Recovery?

Larijani, Ghassem E. PharmD; Goldberg, Michael E. MD

doi: 10.1213/01.ANE.0000137452.25564.0A
Letters to the Editor: Letters & Announcements
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Department of Anesthesiology; University of Medicine and Dentistry of New Jersey; Cooper University Hospital; Camden, NJ; larijani-ghassem@cooperhealth.edu

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In Response:

Few data are available regarding postdischarge symptoms in patients recovering from general anesthesia. Recovery from general anesthesia can resemble narcolepsy with respect to tiredness, sleepiness, and the general feeling of “being down.” As stated in the article, this was a proof of a concept study with its own limitations. Furthermore, we believe in the face validity of subjective symptoms reported by the patients. Prior to performing our study, we evaluated the face validity of the items in the questionnaire by asking a group of five patients to read each question and judge whether they had any problem understanding the meaning of the questions. While fatigue, worn-out, and exhaustion are similar, they are qualitatively different. A patient may feel fatigue and worn-out without being exhausted.

Frazer et al. question the validity of the last two sentences of our study. They question why we stated in our article “patients recovering from general anesthesia can significantly benefit from modafinil.” This sentence was supported by the previous sentences stating, “Modafinil significantly reduces the degree of fatigue, incidence of moderate to severe fatigue, and postoperative distress.” We believe that a significant reduction in the degree of fatigue, exhaustion, or feeling worn out signifies significant improvement and benefit. In addition, as has been stated in the article, content analysis of the patient’s description of recovery from general anesthesia demonstrates improved feelings of alertness and energy in those receiving modafinil. We do understand that there is much to learn about recovery from general anesthesia. We also believe that the effect of modafinil on recovery from anesthesia is measurable and that its effect on drug-induced central nervous system (CNS) depression warrants further evaluation.

The Methods section of the study states that both parametric and nonparametric statistics were used to analyze data. In addition, our recalculation shows that 11.3 (9.1) is significantly different than 21.0 (13.8) (The difference between sample means = 9.7, standard error of the difference = 4.01, df = 32, t = 2.04, 95% confidence interval for the difference between means is 1.53 to 17.9.)

We have seen many patients with a history of exaggerated postoperative CNS depression; many of them require a few days to recover to their preoperative cognitive states. These patients may be the group that would benefit the most from modafinil. We understand that much more work needs to be done if modafinil is to be recommended for this new indication. We also understand that thorough dose-response evaluation, including different doses or multiple dosing, will be needed before such recommendations are made. We stand behind our findings, statements, and interpretations of our results.

Ghassem E. Larijani, PharmD

Michael E. Goldberg, MD

Department of Anesthesiology

University of Medicine and Dentistry of New Jersey

Cooper University Hospital

Camden, NJ

larijani-ghassem@cooperhealth.edu

© 2004 International Anesthesia Research Society