[Further education in anesthesiology. Implementation at the University Hospital Hamburg-Eppendorf]. / Weiterbildung in der Anästhesiologie. Umsetzung am Universitätsklinikum Hamburg-Eppendorf.

Due to the lack of physicians and the changing demands of junior staff more attractive curricula are needed in anesthesiology in Germany. In the German Society of Anesthesiology and Intensive Care Medicine as well as the Association of German Anesthesiologists discussions on the optimization of training have a long tradition. The following article gives a description of the concept and the practical approach to the training curricular at the University Hospital Hamburg-Eppendorf and is designed to stimulate discussion on possible concepts for training in anesthesiology.

Influence of resident training on anaesthesia induction times.

BACKGROUND: The effect of resident training in anaesthesiology on operating room (OR) economics is an issue of debate. Comparisons of anaesthesia process times between residents and consultants might be systematically skewed by interactions of anaesthesia technique and patient factors. METHODS: In this prospective, observational study, we analysed anaesthesia process times in 599 cases performed for four different surgical services in a University hospital. The following factors were recorded for each case and used in multivariate analyses of process times: age, American Society of Anesthesiologist (ASA) status, BMI, emergency status, the educational level of the anaesthetist, and the anaesthesia technique. RESULTS: In the non-adjusted comparison, only for two of seven anaesthetic techniques did resident cases have statistically significant longer induction times than consultant cases: general anaesthesia with placement of a central venous catheter [mean (sd) anaesthesia time for resident cases 38.2 (17.0) vs 22.3 (10.0) min for consultant cases, P=0.001] and general anaesthesia with a laryngeal mask airway [resident cases 11.3 (5.5) vs consultant cases 7.3 (5.0) min, P=0.003]. Anaesthetic technique had the greatest effect on anaesthesia induction time. Educational level of the anaesthetist and age of the patients had small, but significant effects. CONCLUSIONS: Anaesthesia cases performed by residents have in some, but not in all, anaesthesia techniques increased process times compared with cases performed by consultants. This limits a possible negative impact on OR economics by resident education. Patient-based factors including ASA status, BMI, and emergency status have minimal or no effect on anaesthesia process times.

[Utilization rates and turnover times as indicators of OR workflow efficiency]. / Auslastung und Wechselzeit als Kennzahlen der OP-Effizienz.

BACKGROUND: In many hospitals operating room (OR) utilization rates and turnover times (the time from the end of the previous surgical procedure to the beginning of the next) are used as indicators of OR workflow inefficiency. However, there have been no detailed studies to determine whether these indicators really provide an adequate picture of avoidable wasting of time in the OR. METHODS: All relevant OR processes in a busy surgical suite with nine ORs were studied in detail over an 8-week period. Productive OR processes, and also reasons for unused times, were recorded by independent observers at 5-minute intervals; they were able to code for 10 different productive activities and 20 different reasons for unused time. Unused time in the OR, the OR utilization rate and the average perioperative turnover times were calculated for each day and a correlation analysis was performed. RESULTS: In all, 3,501 OR hours and 790 surgical cases were studied. Productive processes accounted for 85.7% of the total OR time; the unused times were times with no scheduled cases (7.7%) and waiting times that arose for many different reasons (6.6%). Correlation analysis showed that there was no close correlation between waiting time and OR utilization (Spearman's r(s) 0.104 and r(s) 0.233). The correlations between total unused time (r(s) 0.718 and r(s) 0.745) and time with no scheduled cases (r(s) 0.706 and r(s) 0.620) and utilization were more robust, but for any given OR utilization rate the range of corresponding unused time or time without scheduled cases per day was considerable. The correlation between waiting time and perioperative turnover times was negligible (r(s) 0.185 and r(s) 0.175). When different definitions of utilization rate or perioperative turnover were used the results obtained were virtually identical. CONCLUSIONS: Utilization rate and perioperative turnover time cannot be used as indicators of OR workflow efficiency, since they cannot identify the days during which avoidable waiting times occur. If the aim is to identify underused OR time and factors that hamper workflow efficiency, waiting times and times without scheduled cases need to be recorded directly and separately.

[The new regulations for the licence to practice medicine. Implementation for the faculty of anesthesiology at the University Clinic Hamburg-Eppendorf]. / Die neue Approbationsordnung für Arzte. Umsetzung für das Fach Anästhesiologie am Universitätsklinikum Hamburg-Eppendorf.

After the amendments to the regulations for the licence to practice medicine, the rating of the faculty of anesthesiology has clearly increased. In the following article a concept will be described whereby these standards were implemented at the University of Hamburg. The basic principle, especially the training in the practical proficiencies, is to achieve a continuous learning process from students through to specialists for anesthesiology.

[Key performance indicators of OR efficiency. Myths and evidence of key performance indicators in OR management]. / Kennzahlen der OP-Effizienz. Mythos und Evidenz der Steuerungskennzahlen im OP-Management.

A variety of different key performance indicators, both for process and financial performance, are used to evaluate OR efficiency. Certain indicators like OR utilization and turnover times seem to become common standard in many hospitals to evaluate OR process performance. Despite the general use and availability of these indicators in OR management, the scientific evidence behind these data is relatively low. These process indicators are strongly influenced by artefacts and depend on planning process, resource allocation and documentation. Direct financial indicators become more important with increasing autonomy of OR management. Besides budgetary compliance the focus is set on the net results of internal transfer pricing systems. By taking part in an internal transfer pricing system, OR management develops from a mere passive cost center to an active shaper of perioperative processes. However, detailed knowledge of the origin of costs and pitfalls of internal transfer pricing systems is crucial. The increased transparency due to the free accessibility of diagnosis-related-groups (DRG) cost breakdown data can help to develop tools for economic analysis of OR efficiency.

Phosphodiesterase-III-inhibition with amrinone leads to contracture development in skeletal muscle preparations of malignant hyperthermia susceptible swine.

BACKGROUND AND OBJECTIVE: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated. METHODS: MH-trigger-free general anaesthesia was performed in eight MHS and eight MHN swine. The MH status of the swine was determined by detection of the Arg615-Cys point mutation on chromosome 6 indicating MH susceptibility. Skeletal muscle specimens were excised for the in vitro contracture tests with amrinone. Amrinone was added cumulatively every 5 min to muscle specimens in order to obtain organ bath concentrations between 20 and 400 micromol L(-1). The in vitro effects of amrinone on muscle contractures and twitches were measured. RESULTS: Amrinone-induced contractures in all skeletal muscle preparations. MHS muscles developed contractures at significantly lower bath concentrations of amrinone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 80, 100, 150, 200 and 400 micromol L(-1) amrinone. Muscle twitches remained unchanged up to and including 200 micromol L(-1) amrinone. CONCLUSIONS: Inhibition of PDE-III in general elicited higher contractures in MHS than in MHN muscles. Therefore, a contribution of PDE-III and the cyclic adenosine monophosphate (cAMP) system in the pathophysiology of MH must be suspected.

[Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia]. / Theophyllin induziert Kontrakturen an Skelettmuskelpräparaten des Schweines mit Disposition zu Maligner Hyperthermie.

OBJECTIVE: Theophylline, a methylxanthine, leads to an increase of the cytoplasmic Ca(2+)-concentration in the muscle cell. Since the in-vitro contracture test (IVCT) with halothane and caffeine does not distinguish a 100% between malignant hyperthermia susceptible (MHS) and non-susceptible (MHN), we examined the in-vitro effects of theophylline in porcine skeletal muscle preparations. METHODS: After approval by the local animal care committee ten MHS- and nine MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administrations of theophylline in concentrations of 3.0 respectively 5.0 mmol/l. Muscle contracture development and twitch amplitudes were recorded over a period of 30 minutes. Data are expressed as medians and ranges. RESULTS: After both theophylline bolus administrations MHS-muscles developed significantly higher contractures compared to the MHN-specimens. The MHS-muscles reached a maximum contracture of 17.0 mN (7.2-59.6 mN) after administration of 3.0 mmol/l theophylline. In comparison, two MHN-specimens showed weak contractures with a maximum of 1.4 mN. The 5.0 mmol/l theophylline IVCT resulted in maximum contractures of 19.1 mN (2.1-39.2 mN) for the MHS-preparations. Just in three MHN-muscles weak contractures of 0.0 mN (0.0-0.8 mN) were recorded. Thus, a significant difference without overlap was revealed for the maximum contracture. CONCLUSION: Theophylline in concentrations of 3.0 and 5.0 mmol/l revealed a clear difference between MHS- and MHN-porcine muscle preparations. Further examinations on human skeletal muscles are needed to demonstrate the value of theophylline in the IVCT MH-diagnosis.

Dantrolene--a review of its pharmacology, therapeutic use and new developments.

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.

[Is a presymptomatic malignant hyperthermia in-vitro diagnosis with 4-chloro-3-ethyl phenol possible? A study using porcine skeletal preparations]. / Ist eine präsymptomatische Maligne Hyperthermie in-vitro Diagnostik mit 4-Chlor-3-Ethylphenol möglich? Eine Studie an Skelettmuskelpräparaten des Schweins.

OBJECTIVE: The diagnosis of malignant hyperthermia is currently performed with the in-vitro contracture test (IVCT) with halothane and caffeine. This test has a sensitivity of 99.0 % but only a specificity of 93.6 %. A cumulative IVCT with 4-chloro-3-ethyl-phenole (CEP) has recently been shown to differentiate between MH susceptible (MHS) and MH normal (MHN) swine. The pur-pose of this study was to investigate the ability of bolus CEP-applications to distinguish between porcine MHS- and MHN-muscle specimens using the IVCT. METHODS: After approval by the local animal care committee 8 MHS- and 8 MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administration of CEP in concentrations of 75 resp. 100 micro mol l (-1). Predefined parameters were: (1) onset time of the contracture development, (2) time to the achievement of the 2, 5 and 10 mN contracture level and (3) maximum contracture level. Data are expressed as medians and ranges. RESULTS: After 75 micro mol l (-1) CEP administration all MHS-muscles showed contractures after 0.5 min (0.2 min/0.9 min). The 2 mN contracture level was reached by all MHS-, the 5 mN level by four MHS- and the 10 mN level by one MHS-specimen. The maximum contracture was 5.3 mN (2.4 mN/12.9 mN). The onset time after 100 micro mol l (-1) CEP was registered as 0.3 min (0.1 min/0.7 min) in the MHS-preparations. Again, the 2 mN level was achieved by all MHS-specimens, the 5 mN level by 5 and the 10 mN level by one MHS-bundle. The maximum contracture was measured as 5.9 mN (2.8 mN/13.9 mN). In 7 MHN-specimens no contracture development was measured. After 75 micro mol l (-1) CEP one MHN-muscle showed a maximum contracture of 1.0 mN, after 100 micro mol l (-1) CEP one MHN-bundle demonstrated a maximum contracture of 1.1 mN. Hence, a significant difference between MHS and MHN without overlap was revealed with both CEP-concentrations in the onset time of contracture, in the 2 mN contracture level and the maximum contracture. CONCLUSION: Since a clear differentiation between MHS and MHN porcine specimens was achieved after bolus application of 75 and 100 micro mol l (-1) CEP, MH-diagnosis might be possible with a CEP-IVCT. It seems worthwhile to examine this hypothesis in men.

Dantroleno - Una revisión de su farmacología, uso terapéutico y nuevos desarrollos / Dantronele: a pharmaceutical and therapetical use and new developments

La hipertermia maligna humana es una sensibilidad genética del músculo esquelético a los anestésicos volátiles y las drogas bloqueadoras neuromusculares despolarizantes que ocurre durante la anestesia y que amenaza la vida. El relajante muscular esquelético dantroleno es la única droga actualmente disponible para la terapia específica y efectiva de este síndrome en el hombre. Después de su introducción, la mortalidad de la hipertermia maligna disminuyó del 80/100 en los años sesenta a menos del 10/100 ahora. Rápidamente se descubrió que el dantroleno deprime el mecanismo interno del acoplamiento de la excitación-contracción en el músculo esquelético. Sin embargo su mecanismo de acción preciso y sus objetivos moleculares aún son conocidos incompletamente. Los estudios recientes han identificado los receptores de la ryanodina como los sitios de enlace del dantroleno. Una inhibición directa o indirecta del receptor de la ryanodina, el mayor canal de liberación del calcio del retículo sarcoplásmico del músculo esquelético, se cree que es fundamental en la acción molecular del dantroleno para disminuir la concentración del calcio intracelular. El dantroleno no solamente se use en el tratamiento de la hipertermia maligna, sino también en el manejo del síndrome neuroléptico maligno, la espasticidad y la intoxicación por Extasis. La mayor desventaja del dantroleno es su pobre solubilidad en agua y por esto se experimentan dificultades en la preparación rápida de las soluciones intravenosas en las situaciones de emergencia. Debido a las consideraciones económicas, no se ha introducido ninguna otra droga similar en la rutina de la práctica clínica

Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia.

BACKGROUND: The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated. METHODS: and results. DOI 1 mg kg(-1) was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (Pa(CO(2))), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by Pa(CO(2)) above 70 mm Hg and an increase in body temperature of more than 2 degrees C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann-Whitney U-test (statistical significance P<0.05). MHS and MHN pigs developed muscle fasciculations, significant increases in body temperature and Pa(CO(2)) and a significant decrease in pH after the administration of DOI. These changes were comparable in both groups until the third dose of DOI, when in MHS pigs heart rate and Pa(CO(2)) rose significantly and pH fell significantly compared with MHN pigs. All MHS pigs fulfilled the MH criteria. Body temperature increased by more than 2 degrees C in all MHN pigs and Pa(CO(2)) exceeded 70 mm Hg in two. Thus, two MHN pigs fulfilled the criteria of MH. CONCLUSIONS: The comparability of the clinical presentation following DOI administration in MHS and MHN animals and the order of the development of MH-like symptoms favour the hypothesis of a central serotonergic overstimulation, leading to a serotonin syndrome.

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH. METHODS: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 micromol L(-1) in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min. RESULTS: After bolus administration of 4-chloro-m-cresol, 75 micromol L(-1), 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 micromol L(-1). Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH. CONCLUSIONS: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

[Dantrolene. Pharmacological and therapeutic aspects]. / Dantrolen. Pharmakologische und therapeutische Aspekte.

Malignant hyperthermia (MH) is a genetic, potentially life-threatening disorder of the skeletal muscle presenting during or following general anaesthesia. Trigger agents are volatile anaesthetics and depolarising muscle relaxants. Dantrolene is the only available drug for effective and specific MH therapy, which reduces significantly the mortality rate. Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown. Recent studies identified the ryanodine receptor, the calcium release channel of the sarcoplasmic reticulum, as the direct molecular target of dantrolene. In addition to its use for MH, dantrolene is used in other disorders such as neuroleptic malignant syndrome and spasticity. Since dantrolene is weakly water soluble, the clinical preparation is time and manpower consuming. New agents have been synthesized, but because of economic considerations no registration for clinical usage has been realised.

In vitro effects of 4-chloro-3-ethylphenol in skeletal muscle preparations from malignant hyperthermia susceptible and normal swine.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the current gold standard for diagnosis of malignant hyperthermia. This test has a sensitivity of 99.0% but a specificity of only 93.6%. Therefore, an alternative drug is desirable which distinguishes between malignant hyperthermia-susceptible and malignant hyperthermia-normal subjects with a higher specificity and sensitivity. METHODS: 4-chloro-3-ethylphenol has recently been shown to trigger Ca2+-induced Ca2+-release in skeletal muscle terminal cisternae and to increase the myoplasmic free Ca2+ concentration in skeletal muscle fibres. The purpose of this study was to investigate the ability of 4-chloro-3-ethylphenol to distinguish between malignant hyperthermia-susceptible and malignant hyperthermia-normal porcine muscle specimen in the in vitro contracture test. Ten malignant hyperthermia-susceptible and 14 malignant hyperthermia-normal swine were anaesthetized and muscle biopsies were taken. For the in vitro contracture test muscle specimens were exposed to cumulative concentrations of 4-chloro-3-ethylphenol (12.5 to 200 micromol L(-1)). RESULTS: 4-chloro-3-ethylphenol produced contractures in a concentration-dependent manner in the malignant hyperthermia-susceptible muscle bundles. In contrast, cumulative 4-chloro-3-ethylphenol did not generate contractures in malignant hyperthermia-normal specimens. Contractures were significantly greater (P < 0.05) in the malignant hyperthermia-susceptible compared to the malignant hyperthermia-normal preparations in all 4-chloro-3-ethylphenol concentration steps from 50 micromol L(-1) to 200 micromol L(-1). There was no overlap between the two groups above a concentration of 75 micromol L(-1) in cumulative 4-chloro-3-ethylphenol in vitro contracture tests. CONCLUSIONS: It remains to be verified whether an in vitro contracture test with 4-chloro-3-ethylphenol can also discriminate between malignant hyperthermia-susceptible and malignant hyperthermia-normal humans. Since no prior tested agent revealed a clear differentiation in contracture development without overlap, the 4-chloro-3-ethylphenol test might be a promising new approach to the diagnosis of malignant hyperthermia.

[In-vitro-effects of cocaine in skeletal muscle specimens of patients susceptible to malignant hyperthermia]. / In-vitro-Effekte von Kokain an Skelettmuskelpräparaten von Patienten mit Veranlagung zuMaligner Hyperthermie.

OBJECTIVE: The abuse of cocaine can cause serious medical complications like tachycardia, rhabdomyolysis, and hyperthermia. Because of the clinical similarities, it has been suggested that cocaine might be a trigger of malignant hyperthermia (MH). Therefore, aim of this study was to investigate the in-vitro effects of cocaine in skeletal muscle specimens of MH susceptible (MHS) and normal (MHN) patients. METHODS: 62 patients undergoing the in-vitro contracture test (IVCT) according to the protocol of the European MH Group (EMHG) for diagnosis of MH susceptibility were included in this study. In muscle specimens surplus to diagnostic requirements cocaine was added in order to achieve tissue bath concentrations of 0.01, 0.1 and 1.0 mM. The contracture development and twitch response have been registered. RESULTS: 21 patients were diagnosed as MHS and 36 patients as MHN. 5 patients tested as MH-equivocal (MHE) were excluded from the study. Following bolus administration of cocaine, no contracture development was observed in MHS, as well as MHN specimens. The muscle twitch decreased after cocaine administration significantly in both diagnostic groups. CONCLUSION: In contrast to the established MH trigger substances like volatile anaesthetics, cocaine produced no contracture development in MHS muscle specimens. Furthermore, cocaine produced a negative inotropic effect in all skeletal muscle preparations, which might be explained by local anaesthetic effects. Regarding these results, cocaine seems not to be a MH trigger agent.

[Malignant neuroleptic syndrome after haloperidol administration]. / Malignes neuroleptisches Syndrom nach Haloperidolapplikation.

The neuroleptic malignant syndrome (NMS) is a rare complication of antipsychotic therapy. We report on a 65-year-old patient who was treated with haloperidol, diazepam and mirtazapin because of a severe depressive episode with psychotic symptoms. He exhibited most of the signs and symptoms characteristic of NMS, e.g.: hyperthermia, rigidity, elevated creatine phosphokinase, leukocytosis, elevated liver enzymes, reduced consciousness and autonomic nervous system disturbances. A secondary pneumonia was diagnosed 2 days after the onset of the NMS, which might have been due to chest wall rigidity. Intensive care treatment consisted of immediate discontinuation of the offending agent, supportive therapy with rehydratation and catecholamines as well as application of dantrolen. After 23 days of intensive therapy all pathological parameters were normalised and the patient was transferred to an internal ward. Three main theories on the pathogenesis of NMS exist: 1. blockade of central receptors, 2. a skeletal muscle target model and 3. sympathoadrenal hyperactivity. The differential diagnosis includes among others malignant hyperthermia and serotonin syndrome.

Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.

BACKGROUND: Malignant hyperthermia (MH), heat stroke, and exercise-induced rhabdomyolysis (ER) were suspected to be related syndromes. However, it is not known whether individuals with history of ER have an increased incidence of susceptibility to MH. To establish an association between ER and susceptibility to MH, the authors determined the MH status in patients with a history of MH-like episodes induced by physical stress. METHODS: Twelve unrelated patients with ER, 18 patients with anesthesia-induced MH, and 28 controls were investigated with the in vitro contracture test (IVCT) according to the European MH Group protocol and the ryanodine contracture test. In addition, all patients were screened for genetic mutations, and histology was performed on muscle specimens. RESULTS: Ten ER patients had positive IVCT results, one patient had a negative test result, and one patient showed equivocal responses. Samples from patients with positive IVCT results showed pronounced contractures after exposition to ryanodine, as opposed to specimens from patients with negative IVCT results, which developed contractures slowly. Three ER patients had mutations at the ryanodine receptor gene. All anesthesia-induced MH patients had positive IVCT results, two of them presented the C1840T mutation. The control patients had normal contracture test results and no typical MH mutations. Histologic examination determined no specific myopathies in any patient. CONCLUSIONS: Regarding these results, the authors recommend performing muscle biopsies for histologic examination and IVCT in patients with ER. In addition, the patient should be seen by a neurologist and screened for genetic abnormalities to shed light on the genetics of MH.