British Journal of Anaesthesia 1991; 66: 138-140
MUSCLE BIOPSY FOR DIAGNOSIS OF MALIGNANT HYPERTHERMIA SUSCEPTIBILITY IN TWO PATIENTS WITH SEVERE EXERCISE-INDUCED MYOLYSIS W. HACKL, M. WINKLER, W. MAURITZ, P. SPORN AND K. STEINBEREITHNER
Patient A A 28-yr-old, well trained male took a physical test to qualify for a military unit. After 2 h of extensive exercising in an environmental temperature of approximately 21 °C, painful swelling of thigh muscles occurred. The patient felt extremely hot and "short of breath." Twentyfour hours later, generalized muscle pain was still present and his urine turned dark. The patient was admitted to the military medical department. He had fever (37.8 °C), a CK serum concentration of 64800 u litre"1 and serum concentration of LDH was 5880 u litre"1. Other liver enzymes and KEY WORDS coagulation screen remained within the normal Hyperthermia: malignant range; blood count was not unusual apart from slight leucocytosis (15000 nl"1). The diagnosis Malignant hyperthermia (MH) is a rare metabolic was heat stroke. No specific therapy was disorder presenting almost exclusively during administered and the patient received i.v. anaesthesia. Apart from this classical appearance, infusions for 3 days. He recovered fully and was a considerable number of MH episodes induced discharged 5 days after the event. An anaesthetist by either emotional or physical stress have been among the patient's circle of friends suspected a reported. Some of these case reports remain link between the above mentioned symptoms and unproven, as MH was assumed or diagnosed by MH trait and sent the patient to us. An in vitro methods not generally accepted [1,2]. In others, contracture test confirmed MH susceptibility however, MH susceptibility was confirmed by in (MHS according to the European MH Group •vitro muscle testing [3] in either the proband [4—6] Protocol). The patient had had one uneventful or close relatives [5, 7]. Of 85 MH-like reactions reported to our unit between 1983 and 1989, 82 (96.5%) occurred during anaesthesia and only three (3.5%) during W. HACKL*, M.D. ; M. WINKLER, M.D. ; W. MAURITZ, M.D. ; K. MH-Investigation Unit of the Ludwig exercise. However, two of the latter patients were STEINBEREITHNER; Boltzmann Institute of Experimental Anaesthesiology and identified as carriers of the MH trait by in vitro Research in Intensive Care Medicine, Spitalgasse 23, A-1090 muscle testing. Vienna, Austria. P. SPORN, M.D., Department of We present the case history of one of these Anaesthesiology, Krankenanstalt Rudolfstiftung, Juchgasse A-1030 Vienna, Austria. Accepted for Publication: July 2, MH-patients and compare it with that of another 25, 1990. patient who had similar symptoms but was * Address for correspondence: University Department of diagnosed as MH-negative (MHN) by in vitro Anaesthesiology and Intensive Care Medicine, Vienna muscle testing. Medical School, Spitalgasse 23, A-1090 Vienna, Austria. Muscle biopsy and in vitro contracture tests for diagnosis of susceptibility to malignant hyperthermia (MH) were performed in two patients who had developed fever and severe myolysis during exercise. MH susceptibility was confirmed in one patient, but in the other, exercise-induced heat stroke proved to be the correct diagnosis. Clinical presentation and epidemiology of exercise-induced MH and its relation to the heat stroke syndrome are discussed.
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
CASE REPORTS
SUMMARY
EXERCISE-INDUCED MYOLYSIS AND MH anaesthetic for an appendicectomy at 12 years of age.
In vitro testing was suggested by an anaesthetist; the test result was MHN, and thus
confirmed the clinical diagnosis of exerciseinduced heat stroke. DISCUSSION
The case history of patient A clearly indicates the existence of the "human stress syndrome", confirming other authors' reports [4—7]. There is no doubt that exercise-induced symptoms as a primary manifestation of MH are much rarer than MH reactions triggered by anaesthesia. However, patients referred for muscle biopsy and in vitro testing are preselected by referring physicians. As anaesthetists have grown familiar with the symptoms of MH, adverse reactions during anaesthesia are reported immediately to specialized departments. In contrast, patients with exercise-induced signs are referred usually to other specialists unfamiliar with MH. Interestingly, probands A and B were referred to us by anaesthetists. Epidemiological data from a group of patients in whom we performed muscle biopsies (table I) revealed that the frequency of exercise-induced symptoms (muscular cramps, pain and stiffness, and pyrexia) was greatest in MHS patients (nine of 86 = 10.4%). It was similar in MHE patients (8.5 %), but was considerably smaller in the MHN group (1.8%). Although the difference was not statistically significant (MHS + MHE vs MHN: 0.05 < P < 0.1), these findings support the results of Smith [8], who studied the personal histories of MHS, MHN and control patients and found that the presence of muscle cramps or weakness and intermittent fever were discriminating factors between the diagnostic groups. The similarity between the case histories of
TABLE I. Frequency and severity (number (%)) of exercise-induced symptoms in MHS, MHE and MHN patients. Data obtained from questionnaires completed by 311 patients before biopsy. ^Patient A, present study; % patient B, present study
Test results MHS MHE MHN
Total
86(100) (28) 59(100) (19) 166 (100) (53) 311(100) (100)
Total frequency 9(10.4) (53) 5 (8.5) (29) 3(1.8) (18) 17(5.5) (100)
Muscle pain
Muscle pain Muscle pain + myolysis + pyrexia (myoglobinuria)
5 (5.8)
3(3.5
2 (3.4)
3(5.1)
2(1.2)
0
1 (0.6)*
9 (2.9)
6(1.9)
2 (0.6)
1 (1.2)t
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
Patient B A normally trained man, aged 26 yr, had the following symptoms during a mountain tour (military training in an environmental temperature of approximately 26 °C): after several hours on foot he felt dizzy and extremely hot. Several minutes later he lost consciousness and generalized muscle rigidity occurred. The helicopter rescue service was summoned and the patient was given diazepam, the trachea was intubated and controlled ventilation initiated. On arrival at the hospital he was still comatose, arterial pressure was not detectable and the heart rate was 210 beat min"1. Metabolic addosis was present (base excess —7.7, HCO 3 14 mmol litre"1, PacO] 2.8 kPA, pH 7.40) and hypoxaemia was evident from a Pa,^ of 5.8 kPa. Body temperature was 41.7 °C. Serum concentration of CK was 3358 u litre"1 and this increased to 45320 u litre"1 within a few hours. The patient received cooled infusions and after 3 h his temperature had decreased to 38.2 °C; arterial pressure was stable (110/70 mm Hg) and heart rate decreased to 120 beat min"1. Myoglobinuria developed the next day. Renal function was preserved by infusion therapy. Severe coagulation defects and thrombocytopenia required administration of fresh frozen plasma and platelet concentrates. Gas exchange was now adequate with spontaneous ventilation. Subsequently, the patient recovered fully without any specific treatment and was discharged 6 days later.
139
140
BRITISH JOURNAL OF ANAESTHESIA
Livingstone, 1985; 186-187. 11. Whitworth JAG, Wolfman MJ. Fatal heat stroke in a long distance runner. British Medical Journal 1983; 287: 948. REFERENCES 12. Danzl DF. Hyperthermic syndromes. American Family Physician 1988; 37: 157-162. 1. Dickinson JG. Heat-exercise hyperpyrcxia. Journal of the Royal Army Medical Corps 1989; 135: 27-29. 13. Hart GR, Anderson RJ, Crumpler CP, Shulkin A, Reed G, Knochel JP. Epidemic classical heat stroke: clinical 2. Pamukcoglu T. Sudden death due to malignant characteristics and course of 28 patients. Medicine 1982; hypcrthermia. American Journal of Forensic Medicine and 61: 189-197. Pathology 1988; 9: 161-162.
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
probands A and B suggest a possible link between 3. The European Malignant Hyperpyrexia Group. A protocol for the investigation of malignant hyperpyrexia MH and heat stroke [1, 4,9-12]. In the so-called (MH) susceptibility. British Journal of Anaesthesia 1984; exercise form of heat stroke, muscles generate 56: 1267-1270. more heat than the body can dissipate, resulting in 4. Denborough MA. Heat stroke and malignant the symptoms reported in case report B. Heat hyperpyrexia. Medical Journal of Australia 1982; 6: 204-205. production in MH is generated pathologically, but the outcome is the same in both cases. 5. Britt BA. Combined anesthetic- and stress-induced malignant hyperthermia in two offspring of malignant However, there is no clear evidence that MH hyperthermic-susceptible parents. Anesthesia and Anpatients are more liable to heat stroke than are algesia 1988; 67: 393-399. normal individuals, nor is there clear evidence 6. Gronert GA, Thompson RL, Onofrio BM. Human malignant hyperthermia: awake episodes and correction that heat stroke victims are liable to be MHS. by dantrolene. Anesthesia and Analgesia 1980; 59: This was established only in one case history [4]; the muscle biopsy required for the in vitro 7. 377-378. Ranklev E, Fletcher R, Krantz P. Malignant hyperpyrexia contracture test is obviously so invasive that and sudden death. American Journal of Forensic Medicine large-scale clinical studies of heat stroke victims and Pathology 1985; 6: 149-150. 8. Smith RJ. Preoperative assessment of risk factors. British did not include tests for MH diagnosis [13]. Journal of Anaesthesia 1988; 60: 317-319. In conclusion, MH susceptibility should be 9. Ellis FR. Fatal heat stroke in a long distance runner. considered in patients reporting muscular pain, British Medical Journal 1983; 287: 1548-1549. cramps or swelling, fever, or both, during or 10. Ellis FR, Heffron JJA. Clinical and biochemical aspects of malignant hyperpyrexia. In: Atkinson RS, Adams AP, immediately after physical exercise. The same eds. Recent Advances in Anaesthesia and Analgesia. applies also to heat stroke victims. Edinburgh, London, Melbourne, New York: Churchill
MUSCLE BIOPSY FOR DIAGNOSIS OF MALIGNANT HYPERTHERMIA SUSCEPTIBILITY IN TWO PATIENTS WITH SEVERE EXERCISE-INDUCED MYOLYSIS W. HACKL, M. WINKLER, W. MAURITZ, P. SPORN AND K. STEINBEREITHNER
Patient A A 28-yr-old, well trained male took a physical test to qualify for a military unit. After 2 h of extensive exercising in an environmental temperature of approximately 21 °C, painful swelling of thigh muscles occurred. The patient felt extremely hot and "short of breath." Twentyfour hours later, generalized muscle pain was still present and his urine turned dark. The patient was admitted to the military medical department. He had fever (37.8 °C), a CK serum concentration of 64800 u litre"1 and serum concentration of LDH was 5880 u litre"1. Other liver enzymes and KEY WORDS coagulation screen remained within the normal Hyperthermia: malignant range; blood count was not unusual apart from slight leucocytosis (15000 nl"1). The diagnosis Malignant hyperthermia (MH) is a rare metabolic was heat stroke. No specific therapy was disorder presenting almost exclusively during administered and the patient received i.v. anaesthesia. Apart from this classical appearance, infusions for 3 days. He recovered fully and was a considerable number of MH episodes induced discharged 5 days after the event. An anaesthetist by either emotional or physical stress have been among the patient's circle of friends suspected a reported. Some of these case reports remain link between the above mentioned symptoms and unproven, as MH was assumed or diagnosed by MH trait and sent the patient to us. An in vitro methods not generally accepted [1,2]. In others, contracture test confirmed MH susceptibility however, MH susceptibility was confirmed by in (MHS according to the European MH Group •vitro muscle testing [3] in either the proband [4—6] Protocol). The patient had had one uneventful or close relatives [5, 7]. Of 85 MH-like reactions reported to our unit between 1983 and 1989, 82 (96.5%) occurred during anaesthesia and only three (3.5%) during W. HACKL*, M.D. ; M. WINKLER, M.D. ; W. MAURITZ, M.D. ; K. MH-Investigation Unit of the Ludwig exercise. However, two of the latter patients were STEINBEREITHNER; Boltzmann Institute of Experimental Anaesthesiology and identified as carriers of the MH trait by in vitro Research in Intensive Care Medicine, Spitalgasse 23, A-1090 muscle testing. Vienna, Austria. P. SPORN, M.D., Department of We present the case history of one of these Anaesthesiology, Krankenanstalt Rudolfstiftung, Juchgasse A-1030 Vienna, Austria. Accepted for Publication: July 2, MH-patients and compare it with that of another 25, 1990. patient who had similar symptoms but was * Address for correspondence: University Department of diagnosed as MH-negative (MHN) by in vitro Anaesthesiology and Intensive Care Medicine, Vienna muscle testing. Medical School, Spitalgasse 23, A-1090 Vienna, Austria. Muscle biopsy and in vitro contracture tests for diagnosis of susceptibility to malignant hyperthermia (MH) were performed in two patients who had developed fever and severe myolysis during exercise. MH susceptibility was confirmed in one patient, but in the other, exercise-induced heat stroke proved to be the correct diagnosis. Clinical presentation and epidemiology of exercise-induced MH and its relation to the heat stroke syndrome are discussed.
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
CASE REPORTS
SUMMARY
EXERCISE-INDUCED MYOLYSIS AND MH anaesthetic for an appendicectomy at 12 years of age.
In vitro testing was suggested by an anaesthetist; the test result was MHN, and thus
confirmed the clinical diagnosis of exerciseinduced heat stroke. DISCUSSION
The case history of patient A clearly indicates the existence of the "human stress syndrome", confirming other authors' reports [4—7]. There is no doubt that exercise-induced symptoms as a primary manifestation of MH are much rarer than MH reactions triggered by anaesthesia. However, patients referred for muscle biopsy and in vitro testing are preselected by referring physicians. As anaesthetists have grown familiar with the symptoms of MH, adverse reactions during anaesthesia are reported immediately to specialized departments. In contrast, patients with exercise-induced signs are referred usually to other specialists unfamiliar with MH. Interestingly, probands A and B were referred to us by anaesthetists. Epidemiological data from a group of patients in whom we performed muscle biopsies (table I) revealed that the frequency of exercise-induced symptoms (muscular cramps, pain and stiffness, and pyrexia) was greatest in MHS patients (nine of 86 = 10.4%). It was similar in MHE patients (8.5 %), but was considerably smaller in the MHN group (1.8%). Although the difference was not statistically significant (MHS + MHE vs MHN: 0.05 < P < 0.1), these findings support the results of Smith [8], who studied the personal histories of MHS, MHN and control patients and found that the presence of muscle cramps or weakness and intermittent fever were discriminating factors between the diagnostic groups. The similarity between the case histories of
TABLE I. Frequency and severity (number (%)) of exercise-induced symptoms in MHS, MHE and MHN patients. Data obtained from questionnaires completed by 311 patients before biopsy. ^Patient A, present study; % patient B, present study
Test results MHS MHE MHN
Total
86(100) (28) 59(100) (19) 166 (100) (53) 311(100) (100)
Total frequency 9(10.4) (53) 5 (8.5) (29) 3(1.8) (18) 17(5.5) (100)
Muscle pain
Muscle pain Muscle pain + myolysis + pyrexia (myoglobinuria)
5 (5.8)
3(3.5
2 (3.4)
3(5.1)
2(1.2)
0
1 (0.6)*
9 (2.9)
6(1.9)
2 (0.6)
1 (1.2)t
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
Patient B A normally trained man, aged 26 yr, had the following symptoms during a mountain tour (military training in an environmental temperature of approximately 26 °C): after several hours on foot he felt dizzy and extremely hot. Several minutes later he lost consciousness and generalized muscle rigidity occurred. The helicopter rescue service was summoned and the patient was given diazepam, the trachea was intubated and controlled ventilation initiated. On arrival at the hospital he was still comatose, arterial pressure was not detectable and the heart rate was 210 beat min"1. Metabolic addosis was present (base excess —7.7, HCO 3 14 mmol litre"1, PacO] 2.8 kPA, pH 7.40) and hypoxaemia was evident from a Pa,^ of 5.8 kPa. Body temperature was 41.7 °C. Serum concentration of CK was 3358 u litre"1 and this increased to 45320 u litre"1 within a few hours. The patient received cooled infusions and after 3 h his temperature had decreased to 38.2 °C; arterial pressure was stable (110/70 mm Hg) and heart rate decreased to 120 beat min"1. Myoglobinuria developed the next day. Renal function was preserved by infusion therapy. Severe coagulation defects and thrombocytopenia required administration of fresh frozen plasma and platelet concentrates. Gas exchange was now adequate with spontaneous ventilation. Subsequently, the patient recovered fully without any specific treatment and was discharged 6 days later.
139
140
BRITISH JOURNAL OF ANAESTHESIA
Livingstone, 1985; 186-187. 11. Whitworth JAG, Wolfman MJ. Fatal heat stroke in a long distance runner. British Medical Journal 1983; 287: 948. REFERENCES 12. Danzl DF. Hyperthermic syndromes. American Family Physician 1988; 37: 157-162. 1. Dickinson JG. Heat-exercise hyperpyrcxia. Journal of the Royal Army Medical Corps 1989; 135: 27-29. 13. Hart GR, Anderson RJ, Crumpler CP, Shulkin A, Reed G, Knochel JP. Epidemic classical heat stroke: clinical 2. Pamukcoglu T. Sudden death due to malignant characteristics and course of 28 patients. Medicine 1982; hypcrthermia. American Journal of Forensic Medicine and 61: 189-197. Pathology 1988; 9: 161-162.
Downloaded from http://bja.oxfordjournals.org/ at UB der TU Muenchen on November 11, 2014
probands A and B suggest a possible link between 3. The European Malignant Hyperpyrexia Group. A protocol for the investigation of malignant hyperpyrexia MH and heat stroke [1, 4,9-12]. In the so-called (MH) susceptibility. British Journal of Anaesthesia 1984; exercise form of heat stroke, muscles generate 56: 1267-1270. more heat than the body can dissipate, resulting in 4. Denborough MA. Heat stroke and malignant the symptoms reported in case report B. Heat hyperpyrexia. Medical Journal of Australia 1982; 6: 204-205. production in MH is generated pathologically, but the outcome is the same in both cases. 5. Britt BA. Combined anesthetic- and stress-induced malignant hyperthermia in two offspring of malignant However, there is no clear evidence that MH hyperthermic-susceptible parents. Anesthesia and Anpatients are more liable to heat stroke than are algesia 1988; 67: 393-399. normal individuals, nor is there clear evidence 6. Gronert GA, Thompson RL, Onofrio BM. Human malignant hyperthermia: awake episodes and correction that heat stroke victims are liable to be MHS. by dantrolene. Anesthesia and Analgesia 1980; 59: This was established only in one case history [4]; the muscle biopsy required for the in vitro 7. 377-378. Ranklev E, Fletcher R, Krantz P. Malignant hyperpyrexia contracture test is obviously so invasive that and sudden death. American Journal of Forensic Medicine large-scale clinical studies of heat stroke victims and Pathology 1985; 6: 149-150. 8. Smith RJ. Preoperative assessment of risk factors. British did not include tests for MH diagnosis [13]. Journal of Anaesthesia 1988; 60: 317-319. In conclusion, MH susceptibility should be 9. Ellis FR. Fatal heat stroke in a long distance runner. considered in patients reporting muscular pain, British Medical Journal 1983; 287: 1548-1549. cramps or swelling, fever, or both, during or 10. Ellis FR, Heffron JJA. Clinical and biochemical aspects of malignant hyperpyrexia. In: Atkinson RS, Adams AP, immediately after physical exercise. The same eds. Recent Advances in Anaesthesia and Analgesia. applies also to heat stroke victims. Edinburgh, London, Melbourne, New York: Churchill
