ANESTHESIA AND ANALGESIA . . . Current Researches VOL.56, NO.3, MAY-SUNE,1977
466
MALIGNANT HYPERTHERMIA SYNDROME To the Editor:
I believe the article by Fraser and coworkersl summarizes many of the important steps in the treatment of the malignant hyperthermia (MH) syndrome. However, I take issue with their recommendation for the use of chlorpromazine as part of the treatment of MH. Chlorpromazine and caffeine have been shown to have similar effects on skeletal muscle in vitro.2 Both drugs cause muscle contracture by themselves and both enhance the contractile response of human muscle to halothane. The augmentation caused by chlorpromazine is greater than that with caffeine.3 Finally, chlorpromazine, in high enough concentrations, may uncouple mitochondria1 respiration, possibly leading to inefficiencies of ATP production.4 Although clinically, chlorpromazine has been used as an adjunct in the treatment of MH, its role in reducing temperature is hard to evaluate because of all the other therapeutic maneuvers taking place simultaneously. Also, its effects may be related to dose administered. The butyrophenone compounds (haloperido1 and droperidol) may be helpful in the treatment of MH, since they have been shown to reverse or inhibit the characteristic contracture response of malignant hyperthermic muscle during exposure to halothane.3 Although dantrolene sodium is not yet available for IV use, the oral preparation of this drug has been recommended as a pre-
treatment for patients with known susceptibility to MH, prior to undergoing surgery. Henry Rosenberg, MD Department of Anesthesia University of Pennsylvania Philadelphia, Pennsylvania
REFERENCES 1. Fraser JG, Crumrine Rs, Izant RJ Jr: A preplanned treatment for malignant hyperpyrexia. Anesth Analg 55:713-716, 1976 2. Bianchi CP: Contraction of skeletal muscle, Cellular Pharmacology of Excitable Tissues. Edited by T Narahashi. Springfield, Illinois, Charles C Thomas, Publisher, 1975, p 499
3. Gratz I, Reed S, Strobel GE: Chlorpromazine potentiation of halothane contractures in skeletal muscle of frog, normal and malignant hyperthermic man; comparison with droperidol. Abstracts of Scientific Papers, American Society of Anesthesiologists Annual Meeting, 1975, p 317 4. Bank W: Partial uncoupling of muscle mitochondria] oxidation by chlorpromazine. American Academy of Neurology Meeting. April 1, 1976 K
Q
h
To the Editor: We thank Dr. Henry Rosenberg for properly pointing out that chlorpromazine may well be contraindicated in the treatment of MH. We have deleted from our protocol any reference to chlorpromazine to obtain a degree of vasodilatation, based on the animal and human in-vitro muscle studies cited by Dr. Rosenberg. John G. Fraser, MD Department of Anesthesiology Case Western Reserve University School of Medicine Cleveland, Ohio
466
MALIGNANT HYPERTHERMIA SYNDROME To the Editor:
I believe the article by Fraser and coworkersl summarizes many of the important steps in the treatment of the malignant hyperthermia (MH) syndrome. However, I take issue with their recommendation for the use of chlorpromazine as part of the treatment of MH. Chlorpromazine and caffeine have been shown to have similar effects on skeletal muscle in vitro.2 Both drugs cause muscle contracture by themselves and both enhance the contractile response of human muscle to halothane. The augmentation caused by chlorpromazine is greater than that with caffeine.3 Finally, chlorpromazine, in high enough concentrations, may uncouple mitochondria1 respiration, possibly leading to inefficiencies of ATP production.4 Although clinically, chlorpromazine has been used as an adjunct in the treatment of MH, its role in reducing temperature is hard to evaluate because of all the other therapeutic maneuvers taking place simultaneously. Also, its effects may be related to dose administered. The butyrophenone compounds (haloperido1 and droperidol) may be helpful in the treatment of MH, since they have been shown to reverse or inhibit the characteristic contracture response of malignant hyperthermic muscle during exposure to halothane.3 Although dantrolene sodium is not yet available for IV use, the oral preparation of this drug has been recommended as a pre-
treatment for patients with known susceptibility to MH, prior to undergoing surgery. Henry Rosenberg, MD Department of Anesthesia University of Pennsylvania Philadelphia, Pennsylvania
REFERENCES 1. Fraser JG, Crumrine Rs, Izant RJ Jr: A preplanned treatment for malignant hyperpyrexia. Anesth Analg 55:713-716, 1976 2. Bianchi CP: Contraction of skeletal muscle, Cellular Pharmacology of Excitable Tissues. Edited by T Narahashi. Springfield, Illinois, Charles C Thomas, Publisher, 1975, p 499
3. Gratz I, Reed S, Strobel GE: Chlorpromazine potentiation of halothane contractures in skeletal muscle of frog, normal and malignant hyperthermic man; comparison with droperidol. Abstracts of Scientific Papers, American Society of Anesthesiologists Annual Meeting, 1975, p 317 4. Bank W: Partial uncoupling of muscle mitochondria] oxidation by chlorpromazine. American Academy of Neurology Meeting. April 1, 1976 K
Q
h
To the Editor: We thank Dr. Henry Rosenberg for properly pointing out that chlorpromazine may well be contraindicated in the treatment of MH. We have deleted from our protocol any reference to chlorpromazine to obtain a degree of vasodilatation, based on the animal and human in-vitro muscle studies cited by Dr. Rosenberg. John G. Fraser, MD Department of Anesthesiology Case Western Reserve University School of Medicine Cleveland, Ohio
