Letters to the Editor
Acta Anaesthesiol Scand 1990: 34: 605
Neuroleptic malignant syndrome and malignant hyperthermia susceptibilitv J
Sir, The eight patients studied by P. J. Adnet et al. ( l ) , after episodes of Neuroleptic Malignant Syndrome (NMS) were all negative for malignant hyperthermia susceptibility (MHS) by reliable in uitro tests. The authors conclude that precautions against M H are not necessary during anaesthesia in NMS patients, inferring that the risk of M H susceptibility is no greater than in the general population. Is this inference statistically justified? The expected rate of occurrence of a condition in a population, corresponding to a desired P value and a number n of consecutive negative observations, can be calculated; the method was described in Anesthesiology by Joseph Grayzel (2). If R is the rate of occurrence, the probability P of not finding the condition in n consecutive subjects is: P=(l-R)” Therefore the expected rate of occurrence at a given level of confidence is: R = 1-pi/” Thus we can infer with 95% confidence that, after 8 consecutive negative tests, the possible rate of MHS among NMS patients may be as great as 31%. If we include their 6 previous cases for a total of 14 negative tests, the rate may still be 19%. This study alone, therefore, does not justify abandoning precautions against M H in NMS patients. W A Tweed, MD, FRCPC REFERENCES 1. Adnet PJ, Krivosic-Horber RM, Adamantidis MM et al. The association between the neuroleptic malignant syndrome and malignant hyperthermia. Acta Anaesthesiol Scand 1989: 33:
676680. 2. Grayzel J. A statistic for inference based upon negative results (letter). Anesthesiology 1989: 71: 320-321.
Address: Department of Anaesthesia National University of Singapore Singapore 051 1
REPLY Sir, We agree with Dr. Tweed concerning the statistical analysis of the possibility of the occurrence of M H in NMS patients with respect to the small series tested. However, since our first reports (1, 2), we have tested 12 further NMS patients. Eleven of these were classified as M H negative and one as M H “equivocal” to halothane. This latter patient was subsequently found on histochemical examination to have muscle alterations compatible with a myopathy (glycogen storage disease). The increase of our population from 14 to 26 decreases the possible rate of M H among NMS patients from 31% to approximately 10% with 95% confidence. However, we also agree with Dr. Tweed on the necessity of further studies performed using the same methodology in order to determine to what degree there might be cross-reactivity between M H and NMS. Until such results are available, we suggest that all patients with clinical NMS should be tested for M H susceptibility before being considered at risk for M H during anaesthesia. I! 3. Adnet, MD R . M . Kriuosic-Horber, MD REFERENCES 1. Krivosic-Horber R, Adnet P, Guevart E et al. Neuroleptic rnalignant syndrome and malignant hyperthermia: in vitro comparison with halothane and caffeine contracture test. Br 3 Anaesth 1987:
59: 1554-1556. 2. Adnet PJ, Krivosic-Horber RM, Adamantidis MM et al. The association between the neuroleptic malignant syndrome and malignant hyperthermia. Acta Anaesthesiol Scand 1989: 33: 67668 0. Address: DCpartement d’AnesthCsie-RtanirnationChirurgicale I HBpital B Centre Hospitalier Regional Universitaire 59037 Lille Cedex France
Acta Anaesthesiol Scand 1990: 34: 605
Neuroleptic malignant syndrome and malignant hyperthermia susceptibilitv J
Sir, The eight patients studied by P. J. Adnet et al. ( l ) , after episodes of Neuroleptic Malignant Syndrome (NMS) were all negative for malignant hyperthermia susceptibility (MHS) by reliable in uitro tests. The authors conclude that precautions against M H are not necessary during anaesthesia in NMS patients, inferring that the risk of M H susceptibility is no greater than in the general population. Is this inference statistically justified? The expected rate of occurrence of a condition in a population, corresponding to a desired P value and a number n of consecutive negative observations, can be calculated; the method was described in Anesthesiology by Joseph Grayzel (2). If R is the rate of occurrence, the probability P of not finding the condition in n consecutive subjects is: P=(l-R)” Therefore the expected rate of occurrence at a given level of confidence is: R = 1-pi/” Thus we can infer with 95% confidence that, after 8 consecutive negative tests, the possible rate of MHS among NMS patients may be as great as 31%. If we include their 6 previous cases for a total of 14 negative tests, the rate may still be 19%. This study alone, therefore, does not justify abandoning precautions against M H in NMS patients. W A Tweed, MD, FRCPC REFERENCES 1. Adnet PJ, Krivosic-Horber RM, Adamantidis MM et al. The association between the neuroleptic malignant syndrome and malignant hyperthermia. Acta Anaesthesiol Scand 1989: 33:
676680. 2. Grayzel J. A statistic for inference based upon negative results (letter). Anesthesiology 1989: 71: 320-321.
Address: Department of Anaesthesia National University of Singapore Singapore 051 1
REPLY Sir, We agree with Dr. Tweed concerning the statistical analysis of the possibility of the occurrence of M H in NMS patients with respect to the small series tested. However, since our first reports (1, 2), we have tested 12 further NMS patients. Eleven of these were classified as M H negative and one as M H “equivocal” to halothane. This latter patient was subsequently found on histochemical examination to have muscle alterations compatible with a myopathy (glycogen storage disease). The increase of our population from 14 to 26 decreases the possible rate of M H among NMS patients from 31% to approximately 10% with 95% confidence. However, we also agree with Dr. Tweed on the necessity of further studies performed using the same methodology in order to determine to what degree there might be cross-reactivity between M H and NMS. Until such results are available, we suggest that all patients with clinical NMS should be tested for M H susceptibility before being considered at risk for M H during anaesthesia. I! 3. Adnet, MD R . M . Kriuosic-Horber, MD REFERENCES 1. Krivosic-Horber R, Adnet P, Guevart E et al. Neuroleptic rnalignant syndrome and malignant hyperthermia: in vitro comparison with halothane and caffeine contracture test. Br 3 Anaesth 1987:
59: 1554-1556. 2. Adnet PJ, Krivosic-Horber RM, Adamantidis MM et al. The association between the neuroleptic malignant syndrome and malignant hyperthermia. Acta Anaesthesiol Scand 1989: 33: 67668 0. Address: DCpartement d’AnesthCsie-RtanirnationChirurgicale I HBpital B Centre Hospitalier Regional Universitaire 59037 Lille Cedex France
