[Malignant hyperthermia]. / Maligne Hyperthermie.

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.

[Guidance of axillary multiple injection technique for plexus anesthesia. Ultrasound versus nerve stimulation]. / Steuerung der axillären Multiinjektionstechnik zur Plexusanästhesie. Ultraschall vs. Nervenstimulation.

BACKGROUND: Ultrasound guidance is still a young method in regional anesthesia when compared to nerve stimulation and only a few studies exist comparing these two techniques in an axillary multiple injection approach. AIM: This prospective, randomized, observer-blinded study compared an ultrasound-guided (SONO) quadruple injection axillary block (out of plane, perineural) with a nerve stimulation-guided (STIM) triple injection axillary block for upper limb surgery. MATERIAL AND METHODS: A total of 60 patients were randomized to either the SONO (n = 30) or STIM (n = 30) group. For the block 40-50 ml mepivacaine 1.5 % (plexus) and 5-10 ml mepivacaine 0.5 % (subcutaneous in the medial skin of the arm) was used. Anesthesia time was recorded as the primary end point. After evaluation of block-related pain using a visual analog scale (VAS) a blinded observer tested sensory and motor function of the median nerve (MED), ulnar nerve (ULN), radial nerve (RAD), musculocutaneous nerve of the upper limb (MUC) and medial cutaneous nerve of the forearm (CAM) at defined times. The main outcome variable was onset time (defined loss of sensory/motor function). RESULTS: No differences were observed between the groups in terms of onset time (single nerves 10-20 min, plexus 20-25 min) and success rate (SONO 90 %, STIM 89 %). Patient satisfaction as measured by block-related pain score (VAS 2 cm), complications (vascular puncture SONO 7 %, STIM 11 %; paresthesia SONO 21 %, STIM 22 %) and patient acceptance (SONO 92 %, STIM 91 %) showed no differences. Performance time was shorter in the SONO group (6.68 ± 1.72 min vs. 8.05 ± 2.58, p = 0.02). CONCLUSION: Nerve stimulation-guided axillary plexus blocks performed by trained anesthesiologists may result in similar onset times and success rates compared to ultrasound-guided blocks.

Sevoflurane as a potential replacement for halothane in diagnostic testing for malignant hyperthermia susceptibility: results of a preliminary study.

BACKGROUND: To diagnose malignant hyperthermia (MH) susceptibility, muscle bundles are exposed to halothane and caffeine. We investigated whether sevoflurane, which is more clinically relevant but less potent of an anesthetic, could replace halothane in diagnostic MH testing. METHODS: With prior written consent, muscle bundles from 6 malignant hyperthermia susceptible (MHS) and 5 non-susceptible (MHN) individuals were exposed to increasing concentrations of sevoflurane (1.3; 2.6; 5.2 vol%). In addition, muscles from 9 MHS and 8 MHN were tested with a rapid exposure to 8 vol% of sevoflurane. Maximal contractures were measured and statistically analyzed (Mann-Whitney-U-test; P<0.05). RESULTS: There were no differences in weight, length or pre-drug tension of the muscle bundles. Incremental sevoflurane concentrations induced no differences in contracture between susceptible and non-susceptible muscles. The rapid application of sevoflurane induced significant contractures in all malignant hyperthermia susceptible compared with non-susceptible individuals. CONCLUSION: The rapid application of a high sevoflurane concentration but not an increasing stepwise application allowed for the diagnostic discrimination of susceptible individuals.

Statins alter intracellular calcium homeostasis in malignant hyperthermia susceptible individuals.

AIMS: Statines, HMG-CoA reductase inhibitors, are widely used to treat hypercholesterinemia. These substances are well tolerated, but myotoxic effects have been reported. The exact mechanisms of the induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. Individuals susceptible to malignant hyperthermia (MH) have an impaired calcium homeostasis. An in vitro test measuring contracture responses of isolated muscle bundles is used to investigate cellular processes of MH. Aim of this study was to investigate if statins modify the contracture response of isolated muscle bundles from MH susceptible (MHS) and nonsusceptible (MHN) pigs. METHODOLOGY: With approval of the local ethics committee muscle biopsies of 18 MH susceptible and 12 nonsusceptible pigs were performed. Muscle bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After establishment of a stable baseline, muscle bundles were exposed to simvastatin, atorvastatin, gemfibrocil, and the pure solvent. Baseline tension was measured and analyzed for changes with P < 0.05 considered to be significant. RESULTS: There were no differences in weight, length, and predrug baseline tension between the groups. Both simvastatin and atorvastatin induced significant contractures in muscle bundles from MHS pigs. Gemfibrocil and the solvent methanol showed no effect. In MHN muscle bundles, none of the tested substances induced a contracture. Statines induce contractures only in MHS muscle bundles. CONCLUSION: We therefore conclude that the underlying mechanism may be a pathologic influence on intracellular calcium handling that is absent in MHN. A preexisting impairment of the calcium homeostasis seems to be necessary for this behavior because muscle bundles of MHN pigs showed no pathologic reaction. A higher muscle cell vulnerability toward statins is assumed in MHS patients. Statins ought to be used with caution in these individuals. Analogous a diagnostic workup for MH should be considered for patients with statin-induced rhabdomyolyis.

[Malignant hyperthermia and its differential diagnosis]. / Maligne Hyperthermie und deren Differenzialdiagnosen.

Hyperthermia affects almost all endogenous regulatory systems, where especially cardiovascular and central nervous system interactions can result in life threatening complications. This review illustrates signs and symptoms, pathophysiology and therapeutic options of the three most common hyperthermic syndromes in neurology: malignant hyperthermia, serotonine-syndrom and malignant neuroleptic syndrome. The aim of this contribution is to enable the reader to make the differential diagnosis of these three disease entities. Furthermore the association of other specific myopathies and hyperthermia syndromes is discussed.

Arteriovenous extracorporeal lung assist as integral part of a multimodal treatment concept: a retrospective analysis of 22 patients with ARDS refractory to standard care.

BACKGROUND AND OBJECTIVES: Pumpless arteriovenous extracorporeal lung assist is increasingly used as a rescue therapy in acute respiratory distress syndrome. Arteriovenous extracorporeal lung assist is highly efficient in eliminating carbon dioxide and allows the application of ventilator techniques that prioritize lung protection and aim to reduce ventilator-induced lung injury and remote organ dysfunction. METHODS: Retrospective data analysis performed in a 12-bed university hospital ICU. In all, 22 patients with acute respiratory distress syndrome refractory to standard care were included. Arteriovenous extracorporeal lung assist as central part of a multimodal treatment concept was combined with tidal volume (VT) reduction below 4 mL kg-1 predicted body weight, a positive end-expiratory pressure titrated to optimize oxygenation and continuous axial rotation. RESULTS: Hypercapnia was reversed within 24 h in survivors (39 mmHg (35-42) (median and interquartile range) vs. 65 mmHg (54-72), P < 0.05) and non-survivors (5.2 kPa (5.5-6.0) vs. 10 kPa (6.9-13.9), P < 0.05). Oxygenation was significantly improved in survivors after 24 h (PaO2/FiO2 ratio 20.7 kPa (17.4-22.7) vs. 11.7 kPa (7.3-20.8), P < 0.05). All patients required norepinephrine infusion and volume resuscitation. The overall complication rate was 23%, predominantly due to reversible lower limb ischaemia. One patient (5%) was permanently disabled due to amputation of a seriously injured lower leg 9 days after initiation of arteriovenous extracorporeal lung assist therapy; however, the patient survived without neurological deficits despite an initial oxygenation index of 4.4 kPa. The overall mortality rate was 27%. CONCLUSIONS: A multimodal treatment concept with arteriovenous extracorporeal lung assist as its central part provides reversal of hypercapnia and stabilization of oxygenation. In an attempt to maximize lung protection and potentially reduce ventilator-induced lung injury, a further VT reduction below 4 mL kg(-1) predicted body weight combined with a high mean airway pressure and continuous axial rotation is safely possible.

[In-vivo diagnosis of malignant hyperthermia susceptibility: a microdialysis study]. / In-vivo-Diagnostik einer malignen-Hyperthermie-Disposition: Eine Mikrodialysestudie.

BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.

A minimally invasive metabolic test with intramuscular injection of halothane 5 and 6 vol% to detect probands at risk for malignant hyperthermia.

We hypothesised that intramuscular halothane injection increases local Pco(2) concentrations in malignant hyperthermia susceptible (MHS) but not in non-susceptible (MHN) individuals. Pco(2) probes with attached microtubing catheters for halothane injection were placed into the lateral vastus muscle of eight MHS and eight MHN probands. Following equilibration, a single bolus of 200 microl halothane 5 and 6 vol% was injected. Pco(2) was measured spectrophotometrically. Baseline Pco(2) concentrations were similar between groups. Maximum Pco(2) and maximum rate of Pco(2) increase was significantly enhanced by halothane 5 and 6 vol% in MHS compared to MHN probands. Systemic haemodynamic and metabolic parameters did not differ between both groups. Local halothane application induces a hypermetabolic reaction with a significant Pco(2) increase in MHS compared to MHN probands, indicating a susceptibility to malignant hyperthermia. Intramuscular halothane injection with Pco(2) measurement seems to be a suitable method for the development of a minimally invasive metabolic test to diagnose malignant hyperthermia susceptibility.

Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1.

Volatile anesthetics have been shown to activate various two-pore (2P) domain K(+) (K(2P)) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive K(+) channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether K(2P) channels were also potentially important targets of intravenous anesthetics. Whole cell patch-clamp techniques were used to determine the effects of the commonly used intravenous anesthetics etomidate and propofol on the acid-sensitive K(+) current in rat ventricular myocytes (which strongly express TASK-1) and selected human K(2P) channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier K(+) (K(ir)) current (I(K1)) and acid-sensitive outward K(+) current at positive potentials, suggesting that this drug may inhibit TASK channels. Indeed, in addition to inhibiting guinea pig Kir2.1 expressed in oocytes, etomidate inhibited human TASK-1 (and TASK-3) in a concentration-dependent fashion. Propofol had no effect on human TASK-1 (or TASK-3) expressed in oocytes. Moreover, we showed that, similar to the known effect of halothane, sevoflurane and the purified R-(-)- and S-(+)-enantiomers of isoflurane, without stereoselectivity, activated human TASK-1. We conclude that intravenous and volatile anesthetics have dissimilar effects on K(2P) channels. Human TASK-1 (and TASK-3) are insensitive to propofol but are inhibited by supraclinical concentrations of etomidate. In contrast, stimulatory effects of sevoflurane and enantiomeric isoflurane on human TASK-1 can be observed at clinically relevant concentrations.

[The present role of interventional lung assist (ILA) in critical care medicine]. / Welchen Stellenwert hat die pumpenlose interventionelle Lungenassistenz (ILA) in der Intensivmedizin?

The development of low resistance oxygenators widens the therapeutic options for patients with acute respiratory failure (ARDS). Pumpless arteriovenous interventional lung assist systems (ILA) can be used in a subgroup of patients with ARDS. ILA might be indicated in earlier stages of ARDS following a multimodal treatment approach.

[Knotted intravascular catheters--what should be done?]. / Der verknotete intravasale Katheter--was tun?

INTRODUCTION: Fixed intravasal catheters are mainly caused by knots. Removal can be achieved by intervention or surgical exploration, but this is associated with additional morbidity and mortality. METHODS: 2 patients were operated for knotted catheters in our institution during the last 2 years, and their records are demonstrated. Treatment options, possible complications, catheter types and locations of knotting are analyzed by a medline search. RESULTS: the search revealed the data from 115 patients. 53 (46.1%) of all "lost" catheters were Swan-Ganz catheters. In 60.9% the catheters could be removed by radiological interventions. Open revision was necessary in 33% of all cases. The catheters were left in place when the clinical condition of the patient did not allow removal (n = 7). However, these patients suffered from a high mortality (5 of 7 patients). Over all mortality reached 8.7%. In the own two cases one removal by sternotomy and one by exploration of the right internal jugular vein were necessary, both operations succeeded without complications. CONCLUSION: Most of all "lost" intravasal catheters are removed by radiological intervention; only one third needs open surgical therapy. These procedures are harmful for the patient and bear considerable risks for complications.

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.

Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

Intolerance to neuroleptics and susceptibility for malignant hyperthermia in a patient with proximal myotonic myopathy (PROMM) and schizophrenia.

We report a patient with proximal myotonic myopathy who was treated with neuroleptics because of exacerbating schizophrenia. Under therapy with fluanxol, the patient developed muscle stiffness and oculogyric cramps. Treatment with both amisulpride and olanzapine lead to markedly elevated serum creatine kinase levels. An in-vitro contracture test was positive for halothane. Thus, in patients with all kinds of multisystemic myotonic myopathies, a susceptibility for malignant hyperthermia and intolerance towards neuroleptics should be taken into account.

The impact of 4-chloro-m-cresol in heparin formulas on malignant hyperthermia: in vitro and in vivo.

BACKGROUND: The preservative 4-chloro-m-cresol (4CmC) is a specific activator of sarcoplasmic Ca2- release and induces contractures in skeletal muscles of malignant hyperthermia susceptible (MHS) patients in vitro. Clinical formulas of heparin contain 4CmC. We studied whether (a) these heparin formulas induce contractures in isolated MHS and normal (MHN) human skeletal muscles and whether (b) significant serum levels of 4CmC are reached after heparinization in cardiopulmonary bypass patients. METHODS: (a) In vitro, muscle bundles of 16 MHS and 22 MHN patients were exposed to the heparin formula Liquemin (containing 4CmC 0.08 mg/500 IU), to chlorocresol and to preservative-free heparin in the in vitro contracture test. (b) In vivo, serum 4CmC levels of 12 patients receiving Liquemin 500 IU/ kg before cardiopulmonary bypass were determined at 1, 5 and 60 min by high-pressure liquid chromatography. RESULTS: (a) For Liquemin and 4CmC, significant contractures were measured with MHS muscles compared to MHN muscles at 61.4 microM 4CmC. (b) In control sera, the detection threshold for 4CmC was 4 microM. Concentrations of 4CmC in all patients' serum samples were below this threshold. CONCLUSION: Heparin formulas, containing 4CmC, induce dose-dependent contractures in vitro in MHS human skeletal muscle at about 60 microM 4CmC. However, in vivo, 4CmC serum concentrations with therapeutic heparinization are less than 1/15 of the in vitro concentration. The lipophilicity of 4CmC with a high volume of distribution may account for these findings. MHS patients seem not to be at risk from clinical heparin formulas containing chlorocresol.

[Are morphologic changes in skeletal muscles of patients with malignant hyperthermia diagnostically useful?]. / Sind morphologische Veränderungen im Skelettmuskel von Patienten mit Maligner Hyperthermie diagnostisch verwertbar?

Malignant Hyperthermia (MH) represents a functional myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, and leading to metabolic disturbances of intracellular Calcium homeostasis. Central-Core-like-structures (CCLS) were recently described as central defects in enzyme-histochemical stains and well correlated to the autosomal-dominant MH-predisposition. We studied the correlation of a MH-predisposition with specific myopathological signs. Skeletal muscles of suspected MH-individuals were histochemically stained by SDH-, NADH-, COX-, Gomori-Trichrome-, ATPase-, Acid Phosphatase-, Oil-red O- und PAS-stain und evaluated without knowing MH-diagnosis by the in-vitro-contracture test. Out of 118 patients (30% MHS ["susceptible"], 63% MHN [normal], 7% MHE ["equivocal"]) 19% revealed pathological findings corresponding to CCLS. 45% of these findings were associated with MHS/MHE. With HE-staining internal nuclei were not specific, but increased with the probability of MHS/MHE from 24% to 80%. Central Cores were correlated in 100% with MHS/MHE (4 out of 118 patients). CCLS were found with about similar frequency in skeletal muscle of MHS/MHE and MHN individuals. Internal nuclei were, however, not specifically, associated with MHS. In contrast, Central Cores correlated significantly with MHS/MHE diagnosis. In conclusion, histopathological findings in skeletal muscle seem to be a reliable marker for MH-predisposition only with Central Cores.

[Regional distribution of predisposition to maligant hyperthermia in Germany: tate in 1997]. / Die regionale Verbreitung der Veranlagung zur Malignen Hyperthermie in Deutschland: Stand 1997.

Malignant hyperthermia (MH) is a rare autosomally dominantly hereditary and potentially life-threatening disease. The prevalence of the genetic MH predisposition is estimated as 1:10,000 to 1:20,000. In Germany no data on the regional distribution are available. Therefore, the purpose of this investigation is to summarise and present the epidemiological data of all German MH laboratories. Nine German hospitals offer the specific in vitro contracture test to diagnose the MH predisposition. All German MH laboratories carry out the examination in accordance with the standardised protocol of the European Malignant Hyperthermia Group. The laboratories were asked to provide the number of all patients investigated, excluding those suffering from other neuromuscular diseases, separated according to diagnostic groups and their places of residence, the number of the identified MH-families as well as the number of the clinically suspected and investigated MH cases with their places of residence. Eight MH laboratories provided the requested data. Until September 1997 a total of 2620 patients were investigated. In 865 patients (34%) MH suspicion was confirmed (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH-suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients 757 were clinically suspected MH cases. 35% of these suspected MH cases were classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients places of residence classified as MHS and MHE into a map of Germany demonstrates an exhaustive distribution with an increased regional prevalence in the areas of the MH laboratories. This concentration in the area of the MH laboratories becomes even more evident, when the places of residence of the MH suspected cases are demonstrated. In conclusion, the distribution of the MH predisposition is uniform and exhaustive in Germany. The presented regional concentration of clinically suspected MH cases among the MH laboratories is mainly interpreted as an expression of effective regional education and information. Considering the overall incidence of the MH predisposition as described above only 15-20% of the MH patients have so far been identified. The MH laboratories have already released about 10,000 patients from the suspicion of MH predisposition. A preliminary prevalence of at least 1:60,000 to 1:80,000 in Germany can be estimated according to the presented data.

[Problems with infusion of vasoactive drugs]. / Probleme bei der Infusion vasoaktiver Pharmaka.

An infusion system that is insufficiently equipped with an alarm device in case the syringe pumps are obstructed, may gravely endanger patient safety. In a patient with septic shock, an obstruction of the infusion system led to periodic application of norepinephrine boli. Sudden haemodynamic disturbances in critically ill patients should be evaluated for pathological causes as well as for technical failure in the infusion system. A sensitive alarming system of syringe pumps may help to eliminate inappropriate drug delivery. For safe infusion of vasoactive drugs the following conditions are highly recommended: a singular syringe pump, a high volume delivery at a low drug concentration, a pressure-controlled infusion device and a short and pressure-resistant infusion system.

Malignant hyperthermia (MH) diagnostics: a comparison between the halothane-caffeine- and the ryanodine-contracture-test results in MH susceptible, normal and control muscle.

Recent studies demonstrated different contracture responses in muscle from malignant hyperthermia susceptible (MHS) compared to normal (MHN) individuals following exposure to the plant alkaloid ryanodine in-vitro. To confirm if ryanodine has a specific action in MHS muscle, the effect of a single concentration was investigated in skeletal muscle from MHS, MHN and control subjects using a new evaluation technique. In-vitro contracture test (IVCT) and MH diagnosis were performed according to the European Protocol in 86 patients sent to us for MH diagnostic testing and in 24 controls. Viable fresh muscle bundles were exposed to a single bolus of ryanodine 1.0 microM. Contracture onset time (OTp: defined as the time (min) from administration of ryanodine to the start of a contracture as measured by a contracture exceeding predrug baseline height), and the time to an increase of the baseline height to 10 mN above the predrug level (10Tp) were recorded. 29 patients were identified by IVCT to be MHS, 50 MHN, 7 MHE (equivocal) and 24 controls MHN. The indices from the ryanodine test separated all MHS (OTp: < 16 min; 10Tp < 27.4 min) from MHN (> 18 and > 27.7 min) and control subjects (> 17.4 and > 29 min). Values for MHE (equivocal) individuals ranged from 17.1 to 27.8 min for the OTp and from 32 to 49.2 min for the 10Tp. 5 patients with fulminant MH crises were included in the MHS group and showed the 95% confidence intervals (CI) of the median value < or = 8.05 min (OTp) and < or = 13.35 min (10TP) for MHS. In contrast, CI of the median value for the control group were found to be > or = 25.2 min (OTp) and 43.15 min (10Tp) for normal muscle. Thus the ryanodine test protocol showed markedly different contractures in MHS and MHN or control muscle. These results suggest that MHS muscle has a higher sensitivity to ryanodine. However, the protocol should be investigated for reproducibility and validation of thresholds by other laboratories. Ryanodine can help to improve MH diagnostic tests.

Gasoline vapors induce severe rhabdomyolysis.

A young patient developed rhabdomyolysis after accidentally inhaling gasoline vapors. Although there had been no preexistent myopathy, the caffeine and halothane contracture test classified the patient as being malignant hyperthermia-susceptible (MHS). Abnormal contractures also occurred after exposure of muscle bundles to benzine (at 0.01%); in four control tests, benzine-induced contractures (at 0.1%) could be elicited in MHS, but not in normal, muscles. The complex composition of benzine seems to contain potentially hazardous agents that trigger MH.