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BACKGROUND: Since the spread of Severe Acute Respiratory Syndrom Corona Virus 2 (SARS-CoV­2) in Germany, intensive care beds have been kept free for patients suffering from Corona Virus Disease (COVID-19). Also, after the number of infections had declined, intensive care beds were kept free prophylactically; however, the percentage of beds reserved for COVID-19 differ in the individual federal states in Germany. The aim of this article is to define a necessary clearance quota of intensive beds for COVID-19 patients in Germany. An escalation and de-escalation scheme was created for rising and falling numbers of infected patients. METHODS: Data from the COVID-19 resource board of the state of Baden-Württemberg, the daily situation report of the Robert Koch Institute (RKI), the register of COVID-19 intensive care beds of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) as well as the daily report of COVID-19 Baden-Württemberg from April to November 2020 were used for the calculation. RESULTS: At the end of November 2020 approximately 13.5% of intensive care beds in Germany were used by COVID-19 patients. Of all persons tested positive for SARS-CoV­2, 1.5% were admitted to an intensive care unit. The hospitalization rate was 6% and the mean age of infected persons was 43 years. Based on these numbers hospitals are recommended to keep 10% of intensive care beds available for COVID-19 patients in the case of less than 35 new infections/100,000 in the catchment area, 20% should be kept free in case of an advanced warning level of 35 new infections/100,000 inhabitants and 30% for a critical limit of 50 new infections/100,000 inhabitants. Further internal hospital triggers, such as the occupancy of the intensive care beds with COVID-19 patients, should be considered. CONCLUSION: If the number of infections is low a general nationwide retention rate of more than 10% of intensive care beds for COVID-19 patients is not justified. Locally increasing numbers of infections require a local dynamic approach. If the number of infections increases, the free holding capacity should be increased according to a step by step concept in close coordination with the local health authorities and other internal hospital triggers. In order not to overwhelm hospital capacities in the event of local outbreaks, a corresponding relocation concept should be considered at an early stage.

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BACKGROUND: There is a risk of terror attacks in the Federal Republic of Germany, which might increase in the future. A timely comprehensive strategy for treatment and care of a large number of casualties helps minimize chaos and improve the outcome of patients. Adequate training is vital for successful implementation of an emergency plan. Therefore, the effectiveness of training should be assessed and evaluated; however, data collection capabilities for training events are extremely limited, so that publications on the topic are almost impossible to find. OBJECTIVE: This study aimed to collect data from a simulated terrorist attack in order to draw conclusions from a clinical point of view concerning the improvement of preclinical and clinical management, taking interface problems into consideration. MATERIAL AND METHODS: On 19 October 2019 the Ministry of the Interior, Digitalization and Migration of Baden-Württemberg conducted a large-scale simulation of a terrorist attack in the city center of Constance, called the Baden-Württemberg counterterrorism exercise (BWTEX). The simulation included an explosion of a car bomb as well as the use of firearms by terrorists. The large scale of the simulation with the high number of participants in combination with close cooperation between military and civil forces was unprecedented. The police force, the armed forces, civil protection forces, air rescue teams and staff from Constance, Friedrichshafen and Sigmaringen regional hospitals in southwest Germany worked together to treat simulated injuries to victims of the attack. The following parameters were recorded when the injured patients arrived at the hospital: prehospital triage time, prehospital triage score, initial treatment and quality of documentation on site as well as triage time, triage score, injury severity scale (ISS) score based on the specified injury pattern, treatment, and quality of documentation on hospital arrival. RESULTS: Out of a total of 84 "injured patients" 55 were admitted to hospital and 80% were triaged at the scene. Injured patients of triage category 1 (TK1 red: life-threatening injury, immediate treatment) arrived at the hospital 198 ± 50 min after the attack, injured patients of triage category 2 (TK2 yellow: severely injured, urgent treatment) after 131 ± 44 min and injured patients of triage category 3 (TK3 green: slightly injured, non-urgent treatment) arrived after 157 ± 46 min. There was no significant difference in terms of arrival time at the hospital between the triage scores (r = 0.2) or between the ISS scores (r = 0.43). The authors assume that approximately 44% of TK1 patients would have died due to avoidable time delays. Prehospital medical documentation was insufficient in 78% and insufficient in 65% in the hospitals. CONCLUSION: A mass casualty incident resulting from a terrorist attack differs greatly from a conventional mass casualty incident. The scene of the attack has to be evacuated as quickly as possible, which means that a large number of patients arrive untreated at the nearest hospitals. The setting up of treatment facilities in city centers and areas close to the city seems to be counterproductive because the time delay may result in higher mortality rates of victims. The particularities of mass casualties caused by a terrorist attack have to be incorporated into terrorist attack training.

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BACKGROUND: 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. OBJECTIVE: 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). DISCUSSION: 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.

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Quantification of myofibroblasts is a promising method for assessing tissue properties in the field of fascia research. This is commonly performed by immunohistochemistry for α-smooth muscle actin. However, usually larger tissue samples sizes are required for quantification. The aim of this investigation was to explore whether a microscopic quantification of myofibroblasts can be conducted with fascial tissue samples derived via percutaneous needle biopsy. Fascial tissues were derived via percutaneous needle biopsy from the fascia lata of 11 persons (aged 19-40 years). Following immunohistochemistry, selected fields for photomicroscopic analysis were chosen by a Monte Carlo method based randomization procedure. On these fields, a digital quantification for the relative density of α-smooth muscle actin was attempted. The newly developed quantification method could successfully be applied in all tissue samples. The median α-smooth muscle actin density in the selected tissue samples ranged between 0% and 1.7% (median 0%, IQR 0%-0.001%). The applied protocol proved to be workable for the purpose of an estimation of the α-smooth muscle actin density in fascial tissue samples derived via percutaneous needle biopsy. Since this type of biopsy is less invasive than the commonly performed open muscle biopsy, this offers a new and useful perspective for future histological investigations of fascial tissue properties in living patients. Clin. Anat. 31:368-372, 2018. © 2018 Wiley Periodicals, Inc.

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BACKGROUND: 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. OBJECTIVE: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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INTRODUCTION: While two laboratory techniques are commonly used to assess the tensile properties of muscle tissue, emerging evidence suggests that the fascial components of these tissues also serve an active role in force generation. Hence, we investigated whether these techniques are sensitive for assessment of fascial micromechanics. METHODS: Force measurements on dissected fascial tissue were performed either using the classical immersion organ bath or using an improved superfusion approach simulating pulsed pharmacological triggers. Rat deep dorsal fascial strips as well as rat testicular capsule were pharmacologically challenged either with mepyramine or oxytocin. RESULTS: The classical immersion technique yielded a lower force response to mepyramine than the superfusion method (median: 367.4 vs. 555.4µN/mm(2)). Pause in irrigation before application reduced irregularities during bolus application. The superfusion approach was improved further by the following points: The high sensitivity of the superfusion method to bolus addition was voided by deviation of fluid supply during bolus addition. CONCLUSION: Although both methods demonstrated pharmacologically induced contractile responses in lumbar fascia samples, the modified superfusion method may improve force registrations of slow contracting fascial tissue and minimize artefacts of fluid application.

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Pharmacotherapy is a key component of anesthesiology and intensive care medicine. The individual genetic profile influences not only the effect of pharmaceuticals but can also completely alter the mode of action. New technologies for genetic screening (e.g. next generation sequencing) and increasing knowledge of molecular pathways foster the disclosure of pharmacogenetic syndromes, which are classified as rare diseases. Taking into account the high genetic variability in humans and over 8000 known rare diseases, up to 20 % of the population may be affected. In summary, rare diseases are not rare. Most pharmacogenetic syndromes lead to a weakening or loss of pharmacological action. In contrast, malignant hyperthermia (MH), which is the most relevant pharmacogenetic syndrome for anesthesia, is characterized by a pharmacologically induced overactivation of calcium metabolism in skeletal muscle. Volatile anesthetic agents and succinylcholine trigger life-threatening hypermetabolic crises. Emergency treatment is based on inhibition of the calcium release channel of the sarcoplasmic reticulum by dantrolene. After an adverse pharmacological event patients must be informed and a clarification consultation must be carried out during which the hereditory character of MH is explained. The patient should be referred to a specialist MH center where a predisposition can be diagnosed by the functional in vitro contracture test from a muscle biopsy. Additional molecular genetic investigations can yield mutations in the genes for calcium-regulating proteins in skeletal muscle, e.g. ryanodine receptor 1 (RyR1) and calcium voltage-gated channel subunit alpha 1S (CACNA1S). Currently, an association to MH has only been shown for 35 mutations out of more than 400 known and probably hundreds of unknown genetic variations. Furthermore, MH predisposition is not excluded by negative mutation screening. For anesthesiological patient safety it is crucial to identify individuals at risk and warn genetic relatives; however, the legal requirements of the Patients Rights Act and the Human Genetic Examination Act must be strictly adhered to. Specific features of insurance and employment law must be respected under consideration of the Human Genetic Examination Act.

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Malignant hyperthermia is a dreaded complication of general anaesthesia. Predisposed individuals can be identified using the standardised caffeine/halothane in-vitro contracture test on a surgically dissected skeletal muscle specimen. Skeletal muscle is composed of muscle fibres and interwoven fascial components. Several malignant hyperthermia-associated neuromuscular diseases are associated with an altered connective tissue composition. We analysed adjacent fascial components of skeletal muscle histologically and physiologically. We investigated whether the fascial tissue is sensitive to electrical or pharmacological stimulation in a way similar to the in-vitro contracture test for diagnosing malignant hyperthermia. Using immunohistochemical staining, α-smooth muscle actin-positive cells (myofibroblasts) were detected in the epi-, endo- and perimysium of human fascial tissue. Force measurements on isolated fascial strips after pharmacological challenge with mepyramin revealed that myofascial tissue is actively regulated by myofibroblasts, thereby influencing the biomechanical properties of skeletal muscle. Absence of electrical reactivity and insensitivity to caffeine and halothane suggests that, reassuringly, the malignant hyperthermia diagnostic in-vitro contracture test is not influenced by the muscular fascial tissue.

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Fascia is composed of collagenous connective tissue surrounding and interpenetrating skeletal muscle, joints, organs, nerves, and vascular beds. Fascial tissue forms a whole-body, continuous three-dimensional viscoelastic matrix of structural support. The classical concept of its mere passive role in force transmission has recently been disproven. Fascial tissue contains contractile elements enabling a modulating role in force generation and also mechanosensory fine-tuning. This hypothesis is supported by in vitro studies demonstrating an autonomous contraction of human lumbar fascia and a pharmacological induction of temporary contraction in rat fascial tissue. The ability of spontaneous regulation of fascial stiffness over a time period ranging from minutes to hours contributes more actively to musculoskeletal dynamics. Imbalance of this regulatory mechanism results in increased or decreased myofascial tonus, or diminished neuromuscular coordination, which are key contributors to the pathomechanisms of several musculoskeletal pathologies and pain syndromes. Here, we summarize anatomical and biomechanical properties of fascial tissue with a special focus on fascial dysfunctions and resulting clinical manifestations. Finally, we discuss current and future potential treatment options that can influence clinical manifestations of pain syndromes associated with fascial tissues.

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Convulsive status epilepticus is defined as a general or focal epileptic seizure lasting longer than 5 min or recurrent seizures without regaining consciousness between seizures. Status epilepticus is a life-threatening condition caused by underlying pathologies (e.g., stroke, meningitis, cerebral hypoxia, cerebral edema). In addition, patients are in danger of physical injury and impaired brain stem reflexes. This also applies to nonconvulsive status epilepticus, which is often characterized by an "unclear loss of consciousness". Although it can only be diagnosed by electroencephalography, it is an important differential diagnosis in the prehospital or emergency room situation, which may be decisive for the therapeutic strategy. Benzodiazepines are the first choice treatment for status epilepticus. This article summarizes a guideline-directed therapy with different pharmaceutical substances and ways of application. A pragmatic approach for limited diagnostic and therapeutic possibilities in the emergency situation is presented.

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BACKGROUND: Sevoflurane is a known triggering agent of malignant hyperthermia (MH). The present study analyzed different effects of sevoflurane on skeletal muscle of MH susceptible and nonsusceptible individuals in vitro and compared the results to the standardized test protocol with halothane and caffeine. A potential influence of a present ryanodine receptor type 1 (RyR1) mutation was investigated. METHODS: Muscle bundles of 24 MH-susceptible patients with or without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8 vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was performed. RESULTS: The in vitro parameters initial length, weight, predrug resting tension, and predrug twitch height did not differ between the groups. Sevoflurane caused significant contractures in MH-susceptible but not in MH-nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the susceptible patients developed contractures ≥ 2 mN after increasing concentrations while 83% did so after rapid bolus administration. Presence of an RyR1 mutation was detected in 36% of the examined MH-positive patients but had no influence on developing contractures. CONCLUSION: Sevoflurane-induced contractures do not reliably detect MH susceptibility on an individual level. Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation-specific effects regarding contracture sizes after incubation with sevoflurane, halothane, or caffeine were not found.

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BACKGROUND: A common form of congenital myotonia, myotonia congenita (MC), is caused by mutations in the skeletal muscle Cl(-) channel gene type 1 (CLCN1). Due to the reduced Cl(-) conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during general anaesthesia. The clinical symptoms resemble malignant hyperthermia (MH), which may lead to mistreatment of the patient. METHODS: Muscle specimens of ADR mice (an animal model of MC) as well as of human individuals were used and exposed to potent ryanodine receptor type 1 (RyR1) activators and increasing K(+) concentration. Muscle force was monitored by a standardized diagnostic method for MH, the so-called in vitro contracture test. RESULTS: Neither muscle of ADR mice nor MC muscle (murine and human myotonic muscle) showed pathological contractures after exposure to the potent RyR1 agonists caffeine and halothane. Increasing concentrations of K(+) had a dose-dependent preventive effect on myotonic stiffness. CONCLUSION: We conclude that the adverse anaesthetic MH-like episodes observed in MC patients do not primarily originate from an altered Ca(2+) release in skeletal muscle. In MC muscle, this hypermetabolism is facilitated by a (pharmacologically induced) sustained depolarization due to an instable membrane potential. The in vitro results suggest that these patients benefit from tight K(+) monitoring because of the membrane potential stabilizing effect of K(+) .

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Dense connective tissue sheets, commonly known as fascia, play an important role as force transmitters in human posture and movement regulation. Fascia is usually seen as having a passive role, transmitting mechanical tension which is generated by muscle activity or external forces. However, there is some evidence to suggest that fascia may be able to actively contract in a smooth muscle-like manner and consequently influence musculoskeletal dynamics. General support for this hypothesis came with the discovery of contractile cells in fascia, from theoretical reflections on the biological advantages of such a capacity, and from the existence of pathological fascial contractures. Further evidence to support this hypothesis is offered by in vitro studies with fascia which have been reported in the literature: the biomechanical demonstration of an autonomous contraction of the human lumbar fascia, and the pharmacological induction of temporary contractions in normal fascia from rats. If verified by future research, the existence of an active fascial contractility could have interesting implications for the understanding of musculoskeletal pathologies with an increased or decreased myofascial tonus. It may also offer new insights and a deeper understanding of treatments directed at fascia, such as manual myofascial release therapies or acupuncture. Further research to test this hypothesis is suggested.

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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.

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Xenon has many characteristics of an ideal anaesthetic agent. It is not known whether xenon is a safe alternative to the potent inhalational anaesthetics in patients susceptible to malignant hyperthermia (MH). We investigated the effect of xenon, halothane and caffeine on muscle specimens of 31 individuals, referred to the MH Unit of the University of Ulm, and performed genetic epidemiology. Thirteen individuals were classified as MH susceptible and 18 as MH negative. Xenon 70% did not cause an increase in baseline tension of any MH-susceptible muscle specimen in contrast to halothane and caffeine. The evoked twitch response increased transiently in MH-susceptible and normal specimens indicating a mechanism independent of MH susceptibility. These results suggest that xenon, in concentrations up to 70% may be a safe anaesthetic for MH-susceptible patients.

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UNLABELLED: Standardization of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility has resulted in very rare false negative tests. However, false positive results stigmatizing the patient seem to be more frequent than false negative results and make supplementary tests desirable. This multicenter approach studied the usefulness of an IVCT with 4-chloro-m-cresol (4-CmC), a ryanodine receptor-specific agonist for a better definition of MH susceptibility. Diagnosis made by the standard IVCT was compared with the results of this 4-CmC test on muscle specimens of 202 individuals from 6 European MH centers. In the 4-CmC test, the results of the MH susceptible group differed significantly from both the MH normal and the MH equivocal group. 4-CmC revealed a qualitatively dose response-curve similar to caffeine. A correlation index of r = 0.79 for the concentration thresholds underlined the strong concordance of the caffeine and the 4-CmC effects. The optimal threshold concentration was determined to be 75 microM in the pooled data of all centers and is much lower than that of caffeine (2 mM), suggesting a more than 25-fold higher affinity of 4-CmC. The predictive value of 4-CmC is as high as that of caffeine and consequently higher than that of halothane. 4-CmC seems to be a suitable drug to refine diagnosis of MH susceptibility and could be used as an additional test substance. IMPLICATIONS: Although in vitro contracture testing for malignant hyperthermia diagnosis is well standardized, with a relatively high sensitivity and specificity, false test results cannot be excluded and may be associated with serious disabilities for the concerned individuals. In this multicenter study, 4-chloro-m-cresol was evaluated as a new test substance for the in vitro contracture testing. Its use improves the accuracy of in vitro diagnosis of malignant hyperthermia susceptibility.

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Malignant hyperthermia (MH) in man is an autosomal dominant disorder of skeletal muscle Ca(2+)-regulation. During anesthesia in predisposed individuals, it is triggered by volatile anesthetics and depolarizing muscle relaxants. In >50% of the families, MH susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum, on chromosome 19q12-13.2. To date, 21 RYR1 mutations have been identified in a number of pedigrees. Four of them are also associated with central core disease (CCD), a congenital myopathy. Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg. In one CCD family, the disease was caused by a recently reported MH mutation, Arg-2454-His. Two novel mutations, Thr-2206-Arg and Arg-2454-Cys were detected, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations cosegregation between genetic result and IVCT was almost perfect, only three genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembraneous region of RYR1 did not yield a new mutation confirming the cytosolic portion of the protein to be of main functional importance for disease pathogenesis.

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