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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle presenting as a hypermetabolic response to potent volatile anesthetics such as sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced from 80% to less than 10%. For treatment of MH an initial intravenous bolus of 2.5 mg/kg dantrolene based on the actual body weight should be applied. If symptoms are not improving after the initial dose, up to 10 mg/kg dantrolene can be necessary within the first 24 h. In facilities where MH triggering anesthetics and depolarizing muscle relaxants are administered, at least 36 - 48 vials of dantrolene 20 mg should be stocked according to the recent German S1 guideline on MH. If none of these agents are ever used in the facility, the stockage of dantrolene is dispensable. Since dantrolene is not easily dissoluble, preparation requires time and manpower. Due to its pharmacological characteristics, ryanodex, a modern nanocrystalline dantrolene sodium suspension, might be a promising alternative in the treatment of MH.Die maligne Hyperthermie (MH) ist eine subklinische, autosomal-dominant vererbte, pharmakogenetische Erkrankung der Skelettmuskulatur, die durch alle klinisch eingesetzten volatilen Anästhetika (Sevofluran, Desfluran, Isofluran) und das depolarisierende Muskelrelaxans Succinylcholin bei disponierten Patienten ausgelöst werden kann. Durch die Einführung von Dantrolen konnte die Sterblichkeit von vorher über 80% auf deutlich unter 10% reduziert werden. Zur initialen Therapie einer MH wird ein Bolus von 2,5 mg/kg Dantrolen bezogen auf das tatsächliche Patientengewicht verabreicht. Abhängig vom klinischen Verlauf muss dieser gegebenenfalls wiederholt werden. Teilweise sind wiederholte Dantrolen-Gaben bis 10 mg/kg/24 h für eine erfolgreiche Behandlung notwendig. Um im Notfall zeitnah therapeutische Maßnahmen einleiten zu können, wird in der deutschen S1-Leitlinie von 2018 die Bevorratung von 36 – 48 Ampullen Dantrolen 20 mg empfohlen. In Bereichen, in denen konsequent keine MH-Triggersubstanzen eingesetzt werden, kann auf eine Dantrolen-Vorhaltung verzichtet werden. Die Herstellung der injektionsfertigen Lösung ist aufgrund der schlechten Löslichkeit der Dantrolen-Trockensubstanz zeit- und personalintensiv. Ryanodex, eine nanokristalline Suspension von Dantrolen-Natrium, kann deutlich schneller gelöst werden und könnte bei der Therapie der MH eine effizientere Alternative darstellen.

Malignant hyperthermia (MH) is a rare, heterogenic syndrome leading to potentially life-threatening skeletal muscle hypermetabolism following exposure to inhalational anesthetics and succinylcholine. In more than 50% of affected individuals a pathogenic variant in the RYR1 gene coding for the sarcoplasmic reticulum calcium channel is responsible for the underlying pathology of uncontrolled calcium liberation. While the genetic prevalence of MH is as high as 1 : 2750, the incidence of clinical MH reactions is considerably lower, suggesting a dominant pattern of inheritance with incomplete penetrance. During acute MH crisis presenting with characteristic symptoms like hypercarbia, tachycardia, acidosis, hyperthermia, generalized muscular rigidity and rhabdomyolysis, discontinuation of triggering agents and immediate treatment with dantrolene 2.5 mg/kg are vital therapeutic interventions to control the reaction. A predisposition to MH should be investigated in patients following a suspected MH crisis, in relatives from MH-families, after exertional or unexplained perioperative rhabdomyolysis and in patients with idiopathic hyper-CK-aemia. According to recent European guidelines, initial DNA screening is an alternative to muscle biopsy and in-vitro contracture testing, although in cases where no diagnostic variants are found, only contracture testing can safely exclude predisposition to MH.Die maligne Hyperthermie ist ein heterogenes klinisches Syndrom, bei dem es nach Exposition mit volatilen Anästhetika und/oder dem depolarisierenden Muskelrelaxans Succinylcholin zu einer gesteigerten Stoffwechselaktivität der Skelettmuskulatur mit zum Teil lebensbedrohlichen systemischen Auswirkungen auf Herz-Kreislauf-Funktionen, Körpertemperatur und Säure-Basen-Haushalt kommt. Der Beitrag gibt einen aktuellen Überblick über dieses seltene Krankheitsbild.

The prevalence of malignant hyperthermia (MH) in Germany is 1:2000-1:3000 and therefore more common than previously assumed, so that anesthesia personnel will more often be confronted with susceptible patients in the clinical setting. After the initial treatment with 2.5 mg/kg body weight dantrolene, further therapy using up to 10 mg/body weight dantrolene can be indicated for 24 h. Under these circumstances it is important to have a sufficient amount of water available for injection purposes. For outpatient anesthesia a stockage of dantrolene is not necessary as long as the use of MH trigger substances in general is strictly avoided. The introduction of Ryanodex® (Eagle Pharmaceuticals, Woodcliff Lake, NJ, USA), a preparation of dantrolene with clearly improved pharmacological properties, in the clinical practice has not yet been realized in Germany.

In a 59-year-old woman with a perforating eyeball injury to the right eye, the emergency physician induced a preclinical general anesthesia with propofol, fentanyl and the depolarizing muscle relaxant succinylcholine. Anesthesia was maintained using propofol and remifentanil infusion throughout the preoperative period and the subsequent surgical procedure. Postoperatively, isolated rhabdomyolysis with an increase in serum creatine kinase to20,000 U/l was observed. The diagnosis of malignant hyperthermia (MH) susceptibility could be confirmed in the patient 4 months after the acute event by the in vitro contracture test and detection of the MH causative mutation p.Val4849Ile in exon 101 of the ryanodine receptor gene. Due to the variable expression, for a long time MH often remained unrecognized. Warning symptoms, such as unspecific tachycardia or masseter spasm following succinylcholine injection, should alert emergency physicians to include MH susceptibility in the differential diagnostics. With an estimated genetic MH prevalence of 1:2000-3000, individuals with known or so far unrecognized MH disposition are likely to be among patients treated in the preclinical setting. If a person develops MH symptoms after exposure to triggering agents, immediate hospital admission is essential in order to initiate guideline-conform treatment without further delay because preclinically the life-saving causal measures are not possible due to the lack of supply of dantrolene.

According to the 2010 S3 Guidelines, analgosedation is an option for ventilated patients in intensive care units (ICU). Therefore, adverse effects of volatile anesthetics can occur in areas outside of surgical medical fields.The aim is to inform ICU physicians about the clinical and legal challenges of a life-threatening pharmacogenetic reaction to inhalational anesthetics, malignant hyperthermia (MH).Consequences of an MH crisis for doctors, patients, and relatives regarding patient rights legislation, as well as insurance and employment issues with respect to the German Genetic Diagnostics Act are discussed.

A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0-2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness.The goal of this study was an analysis of the stocking situation of dantrolene in Germany. A national survey was conducted amongst members of the German Society of Anaesthesia and Intensive Care (DGAI).A questionnaire consisting of 19 items was posted online to all DGAI members from 2 September to 30 September 2015. The questionnaire dealt with characterization of the participants, the administration of triggering substances in the operating room and in the ICU of the respective hospitals. The main part covered the amount of stocked dantrolene, the place of storage and emergency availability of stocked dantrolene from elsewhere.The questionnaire was posted online to 12,415 DGAI members with a response rate of 13.5% (n = 1673). The highest response rate was from 259 directors and heads of anesthesiology units representing 28.3%. In total 93,7% of participants use volatile anesthetics and 82,3% use succinylcholine. In the event of an MH-crisis 40.4% of participants have 36 or more vials of dantrolene available within 5 min, 27.4% have only 24 vials and 18.7% only have 12 vials. Of the anesthesiologists in outpatient surgery 70.6% have a dantrolene stock of less than 36 vials. In those cases with insufficient dantrolene stock, 35.5% of hospitals have no agreement with neighboring hospitals. In the ICU setting, 51.8% of responding participants indicated the use of volatile anesthetics, but only 25.7% stock dantrolene in the ICU. For succinylcholine, 77.3% stated using the drug in the ICU, and 26.0% have a dantrolene stock in the ICU.Almost all anesthesiologists participating in the online survey use volatile anesthethics and/or succinylcholine. Whereas almost all participants have access to dantrolene, more than half of the units have a stock of dantolene, which is less than that recommended by the DGAI. In the case of low dantrolene stock, only 61% of anesthesia departments have access to additional dantrolene within a time frame of 15min . The results of this online survey demonstrate that the stock of dantrolene may be insufficient in some German hospitals and anesthesiology practices.

Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential. Therapy in NMS includes withdrawal of the causative medication and intensive care treatment possibly with administration of dantrolene.In this case report, we describe the clinical course of a 48 year old man who developed typical clinical symptoms and laboratory parameters of malignant hyperthermia syndrome after injection of haloperidol.

Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.

We report a case of severe neuroleptic malignant syndrome developing in a 28-year-old female patient following deliberate self-poisoning with atypical antipsychotic drugs and serotonin reuptake inhibitors. Because of an increasing loss of consciousness she was rapidly transferred to an Intensive Care Unit. Following this, she became progressively febrile associated with rhabdomyolysis and life-threatening organ dysfunctions. Due to fast diagnosis and immediate therapy the patient was treated successfully. This article describes etiology, pathophysiology and symptoms of neuroleptic malignant syndrome. In addition therapeutic options are discussed.

Malignant hyperthermia is an autosomal dominant disorder of the skeletal muscle that predisposes affected individuals to a life-threatening hypermetabolic reaction in response to volatile anaesthetics and depolarizing muscle relaxants. The underlying heterogeneous genetic defects are mainly point mutations within the ryanodine receptor gene of the sarcoplasmic reticulum. Following the introduction of efficient diagnostic and therapeutic tools--the in vitro contracture test and intravenous treatment with dantrolene--a dramatic decline in mortality rates has been observed. The association of malignant hyperthermia-like reactions with other neuromuscular disorders requires the collaboration of several clinical disciplines to achieve a timely recognition of this still life-threatening disorder.

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.

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.

A 14-month-old boy underwent bilateral antrotomies and adenotomy for bilateral mastoiditis. During the operation, typical symptoms of malignant hyperthermia (MH) became apparent. At the time of operation, pulse oximetry and capnometry were not possible which led to a delay in making the diagnosis. Nevertheless, Dantrolene, which was available in the operating theatre, was immediately administered. The postoperative recovery was complicated by altered cerebral function (inability to concentrate), muscle exhaustion and a coagulopathy which lasted for eleven days. A muscle biopsy of the child's father was positive for MH.

Rigidity, hyperthermia, and elevated levels of creatine phosphokinase are the essential features of "neuroleptic malignant syndrome" (NMS), a clinical condition caused either by pharmacological treatment with dopamine receptor antagonists or by the withdrawal of dopamine receptor agonists. An acute dopaminergic transmission block in the basal ganglia and the hypothalamus is thought to be the pathophysiological mechanism of NMS. NMS, the "malignant dopamine depletion syndrome", and the akinetic Parkinsonian crisis may be considered identical conditions with regard to their presumptive pathogenesis. Centrally acting dopamine receptor agonists and the peripheral calcium antagonist, dantrolene, are the most common adjunctive pharmacological approaches to NMS, although their efficacy has been questioned. The motor symptoms and the autonomic nervous system disturbances of NMS may be related to a relative glutamatergic transmission excess, as a consequence of a dopaminergic block. Therefore, we recommend the application of N-methyl-D-aspartate (NMDA) receptor antagonists such as amantadine or memantine for the management of NMS. These drugs counteract excitatory amino acid neurotransmission and exhibit hypothermic and central muscle relaxant properties. However, identification and reversal of the causative event, such as neuroleptic drug therapy or change of anti-parkinsonian medication, remain the cornerstones for reducing the incidence and mortality of NMS.

Two of the persisting controversies concerning malignant hyperthermia (MH) are discussed: storing and dosage of dantrolene and preoperative tactics to be followed with patients who are MH-susceptible. Reasons are presented for the obligation to store sufficient amounts of dantrolene in every operating suite. The second part discusses the question of pretreatment of MH-susceptible patients with dantrolene.

We report on the fulminant crisis of malignant hyperthermia occurring in a 30-year-old female during kidney transplantation. In the past, she had been anaesthetised repeatedly without complications. Anaesthesia was induced with thiopental and vecuronium and continued with isoflurane/N2O/O2. After an initially normal course of anaesthesia, the patient developed symptoms of a fulminant malignant hyperthermia (MH) including excessive increase in end expiratory CO2, hyperkalaemia, tachycardia and hyperpyrexia. The patient was saved by the timely administration of dantrolene. A surgical revision required the next day because of bleeding was done under dantrolene cover and took an uncomplicated course. The patient was extubated 7.5 hours after the second intervention and transferred to a normal ward after 4 days. A subsequently performed in vitro contracture test clearly revealed susceptibility to malignant hyperthermia.

The neuroleptic malignant syndrome (NMS) is one of the most dramatic psychiatric disorders every doctor in intensive care medicine can be confronted with. Two cases of successful treatment of NMS with intravenous application of dantrolene are presented. Although we used two very different doses, the treatment results were the same. Further studies will therefore be necessary to assess the optimal doses for this therapy.

A 5-year-old boy with acute lymphatic leukemia in remission developed signs of malignant hyperthermia (MH) during general anesthesia for removal of a central venous access port. The anesthetic procedure for implantation of the port 17 months before had been uneventful despite use of the same triggering agents, halothane and succinylcholine. Meanwhile, the patient had received chemotherapy (COALL-03-85). The first sign of MH was masseter spasm following succinylcholine; then tachycardia, acidosis, myoglobinuria, and CPK elevation (8953 IU) appeared. There was only moderate temperature elevation to 37.8 degree C. Rapid improvement and complete recovery occurred after dantrolene i.v. The patient's father was found to have undiagnosed muscle pain and an elevated CPK level. An in vitro contracture test with halothane and caffeine revealed susceptibility to MH and supported the patient's diagnosis and genetic predisposition. Referring to several other cases in the literature concerning MH in patients with lymphomas and leukemias, a possible correlation between the two diseases is discussed. As the MH crisis in our patient was most probably genetic in origin, a common acquired cause such as a viral infection seems less probable. We do not believe the chemotherapy our patient received between the two anesthetics was the cause since about one-half of the patients in the literature had not had chemotherapeutic pretreatment at the time of the MH crisis. We believe that a common genetic predisposition is the most likely link between the two diseases. In any case, patients with leukemias and lymphomas should be monitored very carefully for symptoms of MH.(ABSTRACT TRUNCATED AT 250 WORDS)

Dantrolene is the only known specific treatment of malignant hyperthermia (MH). Following official approval an intravenous formulation of dantrolene became clinically available for emergency treatment of MH. At that time it had been anticipated, that with dantrolene therapy combined with constant vigilance each case of MH could be treated successfully and the mortality rate should be close to zero. Surprisingly enough, reports of death due to MH continue to be published up to the present. Analysis of case reports revealed the following reasons for the discrepancy between the expectations and the clinical reality: 1. Delay in early diagnosis due to preoccupation with the name-giving symptom hyperthermia: lack of MH-sensitive monitoring (i.e. capnometry, pulse oximetry, blood gas analysis). 2. Preoccupation with non specific facets of therapy: measures such as cooling, change of the anaesthesia machine, transfer of the patient to the intensive care unit or the administration of drugs which have been shown to be ineffective in treating MH may not only be a waste of time, but fully disregard the prime factor in therapy--intravenous administration of dantrolene. 3. Administration of an insufficient amount of dantrolene and delayed start of specific therapy due to failure to have immediate access to intravenous dantrolene. 4. Failure to increase minute ventilation immediately after making the diagnosis to meet elevated metabolic demands. A recommendation is presented how to diagnose, to treat and prevent MH, considering present day diagnostic and therapeutic measures in the presence of the presumptive diagnosis of MH.

Activation and inhibition of the calcium release channel of rabbit skeletal muscle heavy sarcoplasmic reticulum (HSR) was investigated by various methods. The calcium release channel is activated by binding of calcium in the micromolar range and by binding of adenine nucleotides in the millimolar range. Ruthenium red and neomycin are potent inhibitors of the channel at nanomolar to micromolar concentrations. Dantrolene inhibits the rate of caffeine-induced calcium release. Several models of the calcium release channel were considered to explain the three-phasic calcium release from HSR vesicles. Simulation of calcium efflux data according to various models suggest that the calcium release channel has at least three states. The experimental results can be explained by assuming one open and two closed states of the calcium release channel, but not by assuming one open and one closed state.

Five subjects, all relatives of two patients who suffered from malignant hyperthermia, were tested for blood CK activity before and after a course of dantrolene sodium. (4 mg/kg/day orally for three days.) In all the cases, the CK levels which were significantly elevated prior to the drug administration, dropped to normal values after three days of treatment returning to the original levels after eight days. The effect of the drug is most likely related to a temporary normalisation of muscle metabolism which may prevent the development of malignant hyperthermia in susceptible patients. The blood CK activity can be a valuable indicator in determining the effective dose of dantrolene. Prophylactic drug therapy should be considered even when special anesthesia techniques are used.

18 members of a MH prone family have been studied to determine the value of various clinical methods which might be helpful in detecting the disposition. Tests included serum levels of CK over a period of 3 years, and of potassium, the influences of muscle provocation and pretreatment with dantrolene, concentration of cholesterol in erythrocytes and cholinesterase (activity and genotype). The results show relative constant measurements of the enzyme; there was, however, no evidence of any other reliable method in assessing the disposition.

The key factor in malignant hyperthermia does not seem to be a defect in the calcium-storing membrane of the skeletal and cardiac muscle cells. The primary cause would appear to be deficiency of adenylate kinase.

In connection with malignant hyperthermia the afflicted girl and her blood relations from 4 generations were investigated. Noteworthy in the case histories were fractures following minor traumas of the brother and epilepsy in 3 cases. The serum CK was increased in 6 individuals. The EMG showed alterations in 3 participants which pointed to discrete myopathy. The muscle biopsies of patient and parents were normal under microscope and electron microscope. The findings are consistent to the accepted theories of hereditary mode. Due to inadequate means of predicting the onset, early recognition and treatment of malignant hyperthermia remain essential. Promising prohibitive and curative results have been brought about with Dantrolene in animal experiments.

The effect of dantrolene (D) on transmembrane potential and contractile force was examined in electrically driven right ventricular papillary muscles of guinea-pigs. Independent of stimulation frequency D (100 mumol/l) caused a significant reduction of contractility by ca. 40% from control levels. Action potential duration measured at the 90% and 50% repolarisation level was significantly increased while plateau phase was slightly depressed by D. Resting membrane potential, action potential amplitude and maximum rate of depolarisation in phase 0 were unaffected. The effect of D on action potential duration was significantly dependent upon the frequency of stimulation. At faster rates action potential duration was increased relatively more than at slower rates. Slow response action potentials were unaffected by D. Unlike Ryanodine D did not flatten the force-frequency-relationship curve and did not influence the force-interval-relationship under extrastimulation. - It is concluded that the direct negative inotropic effect of D is not accompanied by a transsarcolemmal influence such as an inhibition of fast Na+- or slow Ca++-channels. The results are compatible with an intracellular site of action of D as postulated for skeletal muscle. D acts differently from ryanodine, another presumed inhibitor of sarcoplasmic reticulum.

Occasionally a caesarean section we saw a case of malignant hyperthermia with a favourable fate.

Heat stroke is an acute life-threatening disease requiring therapy immediate to cope with the severe pathophysiologic disturbances. Rapid lowering of the high core temperature seems to be the most important therapeutic measure. Besides methods of physical cooling, Dantrolene should also be used in this hyperthermic state. By consequent lowering of the body temperature it will be possible to stabilise circulation and minimise disease-related injuries of different organs.

The effect of dantrolene (2 x 1 mg/kg) on the rise of serum CK activity after combined use of halothane and suxamethonium was the subject of a double-blind-study of 20 children. Dantrolene significantly inhibited the mean enzyme activity both post- and preoperatively. The incidence of suxamethonium-induced fasciculations was significantly reduced by dantrolene. Serum levels of dantrolene and its metabolites showed considerable interindividual variation; a relation between the levels and enzyme activity could not be detected. Comparing the enzyme-inhibiting effects of different methods dantrolene proved to be more effective than alcuronium preceding suxamethonium and "self-taming."

A 5-year-old previously healthy girl, received general anaesthesia for performing an appendectomy. After administration of succinyl choline (20 mg, twice repeated) and halothane (increasing to 2 per cent by volume), the following symptoms of malignant hyperthermia became manifest during anaesthesia: rigor, tachycardia, cardiac dysrhythmia, temperature increase to 42.6 degrees C; anaesthesia was effected with 2 litres O2/min, 4 litres N2O/min, halothane 1.5-2 per cent by volume, using the Kuhn system. Cooling reduced the temperature at first to 40.6 degrees C and subsequently, with additional intravenous administration of dantrolene (initially rapidly 20 mg equal 1 mg/kg body weight, then 10 mg/kg body weight X 24 hrs) within an hour to 37.5 degrees C. The postoperative phase was uncomplicated. The pattern of symptoms and therapy are critically reviewed. Basing on the cases described in literature, as known to the authors, the value of dantrolene in respect of treatment of malignant hypothermia in man is reviewed.

Malignant Hyperthermia is a specific potentially fatal condition which occurs in susceptible individuals in response to various triggering mechanisms, of which anesthetic agents have been found to be the most common offenders. Leading symptoms are generalized muscular rigidity and hyperpyrexia. The etiology seems to be associated with some inherited disturbance in muscle metabolism related to calcium regulation. This syndrome is known for 25 years, the mechanism of triggering, the genetics and the treatment have been able to get examined by animal model as malignant hyperthermia syndrome may occur in swine as well. Pharmacological in-vitro studies on biopsy specimen of muscle fragments are presently one of the most accepted means for pre-anesthetic diagnosis, the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis. Neuroleptic Malignant Syndrome which occurs in patients treated with neuroleptics shows almost identical symptoms. Although the pathogenesis is still unknown, most authors believe a neuroleptic-induced alteration of central neuroregulatory mechanisms is involved. Alternative etiologic mechanisms are suggested by the striking similarities noted between the Neuroleptic Malignant Syndrome and Malignant Hyperthermia. Both disorders might be based on common pathophysiologic mechanisms and might be induced in susceptible patients by a variety of pharmacologic agents. The authors present and compare the actual knowledge concerning symptoms, course and therapy of both syndromes on the basis of 126 case studies of the Neuroleptic Malignant Syndrome from literature.

New publications on malignant hyperthermia (MH), with direct clinical importance, are reported. Since even in the recent past patients have died from MH in spite of therapy with dantrolene, the effectiveness of dantrolene is discussed in particular. Atypical clinical pictures of MH are presented. Special psychiatric syndromes (malignant neuroleptic syndrome and acute febrile catatonia), rhabdomyolysis with myoglobinuria following strenuous exercise or exposure to heat are mentioned, as these disorders appear to be related to MH, in that they are hypermetabolic syndromes implying a muscle membrane dysfunction. The role of slow calcium channel blockers and 5-hydroxytryptamine antagonists as prophylactic or therapeutic agents in MH is discussed. A schedule describing how to diagnose, treat and prevent MH, considering recent advances, is presented.

Malignant hyperthermia (MH) is a rare syndrome seen when susceptible individuals are exposed to one or more of various triggering agents, most commonly a depolarizing muscle relaxant or an inhalational anaesthetic agent. There is a dramatic rise in metabolic rate and oxygen consumption which if not treated promptly and effectively results, in the majority of cases, in the patient's death. Fatal responses to physical stress associated with the familial muscular disease known as MH are being increasingly reported in situations not related to anaesthesia or drugs. Moreover, cases of MH were recognized to be "induced" in the postoperative period when obviously the major effects of anaesthesia were no longer of important consideration. Therefore a more expanded concept of MH seems to develop, including the assumption that one of the other factors in MH is stress. The implication of this extends far beyond the scope of anaesthesiology. The acute hypermetabolic state in MH, resulting in acidosis, heat production and muscular activity is probably due to an inability to control calcium concentration within the skeletal muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. The susceptibility to develop MH is controlled by several genetic factors. Evaluation of affected families is guided by in vitro analysis of drug-induced contractures in muscle biopsy specimens; a practical and reliable non-invasive test to predict the susceptibility is still being sought. At the present time there is incontrovertible evidence that the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis of MH. A concept for the treatment of MH and guidelines for the management of a patient at risk are presented; medico legal aspects of the complication are stressed.

After description of the conditions of innervation and function of the urethra and the urinary bladder, the various possibilities of influencing physiological and pathological functions of these organs by drugs are discussed.