A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery.

Guidelines for withholding and withdrawing therapy in the ICU: impact on decision-making process and interdisciplinary collaboration.

INTRODUCTION: Interdisciplinary collaboration in end-of-life decision-making is challenging. Guidelines developed within the interdisciplinary team may help to clarify, describe, and obtain consensus on standards for end-of-life decision-making and care. The aim of the study was to develop, implement, and evaluate guidelines for withholding and withdrawing therapy in the intensive care unit. METHODS: An intervention study in two Danish intensive care units, evaluated in a pre-post design by a retrospective hospital record review and a questionnaire survey. The hospital record review included 1,665 patients at baseline (12-month review) and 897 patients after the intervention (6-month review). The questionnaire survey included 273 nurses, intensivists, and primary physicians at baseline and 229 post-intervention. RESULTS: For patients with therapy withdrawn, the median time from admission to first consideration on level of therapy decreased from 1.1 to 0.4 days (p=0.03), and the median time from admission to a withdrawal decision decreased from 3.1 to 1.1 days (p=0.02). Sixty-five percent of the participants who used the guidelines concerning end-of-life decision-making considered them helpful to high or very high extent. No significant changes were found in satisfaction with interdisciplinary collaboration or in withholding or withdrawing decisions being changed or unnecessarily postponed. The healthcare professionals' perception of the care following withdrawal of therapy increased significantly after implementation of the guidelines. CONCLUSIONS: The study indicates that working with guidelines for withholding and withdrawing therapy in the intensive care unit may facilitate improvements in end-of-life decision-making and patient care, but further studies are needed to provide robust evidence.

Sleep disturbances in critically ill patients in ICU: how much do we know?

Sleep disturbances in the intensive care unit (ICU) seem to lead to development of delirium, prolonged ICU stay, and increased mortality. That is why sufficient sleep is important for good outcome and recovery in critically ill patients. A variety of small studies reveal pathological sleep patterns in critically ill patients including abnormal circadian rhythm, high arousal and awakening index, reduced Slow Wave Sleep, and Rapid Eye Movement sleep. The purpose of this study is to summarise different aspects of sleep-awake disturbances, causes and handling methods in critically ill patients by reviewing the underlying literature. There are no studies of level 1 evidence proving the positive impact of the tested interventions on the critically ill patients' sleep pattern. Thus, disturbed sleep in critically ill patients with all the severe consequences remains an unresolved problem and needs further investigation.

Withholding or withdrawing therapy in Danish regional ICUs: frequency, patient characteristics and decision process.

BACKGROUND: New options for intensive therapy have increased the necessity of considering withholding or withdrawing therapy at intensive care units (ICUs), but the practice varies according to regional and cultural differences. The aim of this study was to investigate the frequency of withholding or withdrawing therapy in two secondary Danish ICUs, to describe the characteristics of patients in whom such decisions were made and to examine the existing documentation of the decision process. METHODS: A retrospective review of hospital records for all patients admitted to two regional Danish ICUs in 2008. The records were searched for all information regarding deliberations or decisions on withholding or withdrawing therapy. RESULTS: Of 1665 patients admitted to the ICUs, 176 patients (10.6%) died; of these, 34 (19.3%) died while still receiving full active therapy, 25 (14.2%) died after therapy was withheld and 117 (66.5%) died after therapy was withdrawn. An additional 88 patients (5.3%) were discharged alive with therapy either withheld or withdrawn. The patients who died had higher severity scores, were older and were more likely to be men than those who were discharged with full therapy. The main reasons for withholding or withdrawing therapy were prognosis for acute illness and the deemed futility of therapy. The median time from admission to a decision on withholding or withdrawing therapy was 1.4 days. CONCLUSION: Withholding or withdrawing therapy is common in Danish ICUs but more research is needed to explore the different aspects of withholding or withdrawing therapy in Danish ICUs.

Efficacy of A-line AEP Monitor as a tool for predicting acceptable tracheal intubation conditions during sevoflurane anaesthesia.

BACKGROUND: It is essential for the clinical anaesthetist to know whether patients are sufficiently anaesthetized to tolerate direct laryngoscopy and endotracheal intubation. Because of the lack of an accurate objective method to determine the level of general anaesthesia, under- or overdosing of anaesthetics may occur. Auditory evoked potential (AEP) is one of several physiological parameters under investigation. We aimed to determine the clinically required depth of anaesthesia, measured by the A-line AEP Monitor and expressed as A-Line ARX Index (AAI) for 90% probability of acceptable conditions for endotracheal intubation. METHODS: We studied 108 patients anaesthetized by mask with increasing concentration of sevoflurane in 30% oxygen and 70% nitrous oxide. Fentanyl 1.5 microg kg(-1) and glycopyrrolate 0.2 mg were administered intravenously immediately before starting induction of anaesthesia. The monitor was programmed to give an alarm at AAI 10, 15, 20, 25 or 30 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was registered and endotracheal intubation was attempted. Intubation conditions were assessed by an observer blinded to the AAI. RESULTS: At AAI 10 we found acceptable conditions in 91% (confidence interval [CI 72-99%]) of patients. The prediction probability value P(K) of AAI was 0.69 (CI 0.59-0.79) and the P(K) of end-expiratory sevoflurane concentration was 0.93 (CI 0.87-0.99). ED(90) (the AAI with a 90% probability of acceptable intubation conditions) was calculated as 8.5 (CI 0-17.5). CONCLUSIONS: AAI indicates the depth of anaesthesia necessary for acceptable endotracheal intubation conditions. Under the conditions of the present study, end-expiratory sevoflurane concentration was a better predictor and may turn out to be more useful in the clinical setting.

Efficacy of the A-line AEP monitor as a tool for predicting successful insertion of a laryngeal mask during sevoflurane anesthesia.

BACKGROUND: The use of clinical signs for assessing depth of anesthesia is unreliable during periods with little noxious stimulation. A patient may appear adequately anesthetized at one moment at a given level of stimulation, but may later, when facing other more intense stimuli, show signs of insufficient anesthesia. In order to prevent under- or overdosing of anesthetics, an anesthesia depth monitor that is able to predict responses to noxious stimulation would therefore be useful. Auditory evoked potentials (AEP) is one of several physiological parameters under investigation. The method has been improved by rapid extraction and conversion of the AEP curve into an index (A-Line ARX Index = AAI). We aimed to determine the clinically required depth of anesthesia, measured by the A-line AEP Monitor, for at least 90% probability of acceptable insertion conditions for a laryngeal mask airway (LMA). METHODS: We studied 112 patients anesthetized by mask with increasing concentration of sevoflurane in oxygen. The monitor was programmed to give an alarm at AAI between 15 and 40 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was recorded and the LMA inserted. Insertion conditions were assessed by an observer blinded to the AAI. RESULTS: The ED(95) and prediction probability (P(K)) for AAI were 14.5 (CI 7.4-21.6) and 0.76 (0.66-0.86), respectively, while the ED(95) and P(K) for expiratory sevoflurane concentration were 4.36% (CI 3.73-4.98) and 0.95 (0.91-0.99). CONCLUSIONS: AAI indicates the level of depth of anesthesia necessary for acceptable laryngeal mask insertion conditions. End-expiratory sevoflurane concentration was the better predictor.

Reproducibility of in vitro contracture test results in patients tested for malignant hyperthermia susceptibility.

BACKGROUND: The in vitro contracture test (IVCT) is the golden standard to diagnose malignant hyperthermia susceptibility (MHS). A high reproducibility is important for a high validity of a test. METHODS: We have therefore analyzed IVCT in 838 patients, investigated in two laboratories. Each halothane and caffeine test was performed in two muscle strips. The test results were analyzed with respect to reproducibility of abnormal outcomes within pairs of tested muscle strips and size of contractures, thresholds and quality criteria. The patients were tested according to the European Malignant Hyperthermia Group protocol (EMHG). To fulfill quality criteria in the EMHG protocol the twitch height should be 10 mN (1 g) or more. For the caffeine test a minimum contracture of 50 mN (5 g) or more at 32 mmol l-1 caffeine could be used as an alternative quality criterion. RESULTS: There was better reproducibility with larger contractures. The correlation between size of contractures and fraction of muscle strips with abnormal contractures was 0.77 or larger. Contractures < 5 mN (0.5 g) were reproducible in less than half of the tests. There was no difference in reproducibility or size of contractures between tests fulfillling all quality criteria and those not fulfillling these criteria. CONCLUSIONS: IVCT responses close to cut off limits, i.e. <5 mN (0.5 g) in the EMHG protocol, are less reproducible and must scientifically be considered as less reliable. The clinical cut off limits must remain unchanged for reasons of clinical safety. The outcome of quality measurements does not influence the test results.

How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator?

BACKGROUND: Clinical malignant hyperthermia (MH) is rare and usually occurs unexpectedly. Prompt diagnosis and correct treatment is crucial for survival of the patient developing fulminant MH. The aims of the present study were to investigate whether anaesthesiologists could make a correct diagnosis of MH and to evaluate their treatment of fulminant MH in a simulator. METHODS: Thirty-two teams (one anaesthesiologist/one nurse anaesthetist) were exposed to an event of clinical MH in a full-scale simulator. Their performance was videotaped for retrospective analysis of the treatment on the basis of the recommendations of the Danish Malignant Hyperthermia Register. RESULTS: All 32 teams asked the surgeon to terminate the surgery as fast as possible, switched off the vaporiser and administered 100% oxygen. Although all intended to hyperventilate the patient, only 14 teams actually managed to perform the hyperventilation. Most problems were found in teams that switched to manual ventilation. All teams treated the patient with dantrolene, and symptomatic treatment was initiated by all even though some elements of the full treatment were lacking, possibly due to the limited time available. CONCLUSION: All teams diagnosed MH in the simulator satisfactorily. The surprising negative finding was that more than half of the participants failed to hyperventilate the "patient" although they intended to do so. This investigation shows that the problem in these teams' treatment of MH was more a question of practical management of the resources than lack of theoretical knowledge.

Between-center variability of results of the in vitro contracture test for malignant hyperthermia susceptibility.

UNLABELLED: The in vitro contracture test (IVCT) remains the standard test for the diagnosis of malignant hyperthermia (MH) susceptibility. The aim of this study was to investigate whether results of the IVCT varied between two diagnostic centers. The study took place at the national MH centers in Denmark and Sweden. Forty-three patients investigated for MH gave informed consent to have four extra muscle specimens excised. These were sent to the other center and immediately used for a parallel IVCT, according to the protocol of the European MH Group. Results of the IVCTs performed in the two centers on muscle samples from the same patients were compared. Each patient was assigned a diagnosis according to the result obtained in the "mother-center." Identical diagnostic results were obtained for 56% of the patients. The differing diagnostic outcomes were almost exclusively seen in cases with contractures of <5 mN (0.5 g) and abnormal results in only one or two muscle strips. We suggest different criteria for the interpretation of results for clinical and scientific purposes. The clinical criteria should remain unchanged. The scientific designation of susceptibility should be used in cases with contractures of > or =5 mN and abnormal results in at least 75% of the tested muscle strips. IMPLICATIONS: The diagnostic outcomes of tests for malignant hyperthermia susceptibility were compared between two laboratories by using muscle tissue from the same patients. Identical outcomes were found for 56% of the patients. Almost all diverging outcomes were seen in cases with a few small contractures near the cutoff limit. Different diagnostic criteria for clinical and scientific purposes are suggested.

Postoperative pain control by epidural analgesia after transabdominal surgery. Efficacy and problems encountered in daily routine.

BACKGROUND: The efficacy of postoperative epidural pain treatment has been well documented in controlled studies. However, the literature concerning results of daily routine use of this method often only emphasises certain aspects of it. METHODS: A prospective study of 168 patients scheduled for major surgery with transabdominal access was performed in order to evaluate efficacy, side effects, complications and rate of acceptance of postoperative epidural pain treatment. The epidural catheter was placed before surgery and the patients received epidural analgesia by a bupivacaine/morphine mixture for 3 days postoperatively, continued by another 3 days with bolus injections of morphine only. RESULTS: Only few complications followed the insertion of the epidural catheter, but in about 16% of the patients the epidural catheter or the drugs administered by it made reinsertion or change in the type of analgesia necessary during the first 3 post-operative days. Despite the possibility for individualising the treatment and p.r.n. analgesics, pain relief when coughing and moving during day 1-3 was insufficient in 30-50% of the patients. Serious side effects were rare, but pruritus was frequent, as were the symptoms of nausea and vomiting. The patients were generally satisfied with the treatment; however, a small group had unacceptable pain when the epidural catheter was inserted. CONCLUSION: Analgesia was insufficient when coughing and moving in an unacceptably large number of the patients. Also the number of epidural catheter related problems was high. In order to make early intervention possible, the patients and epidural catheters should be observed daily and systematically by members of the staff competent to detect possible problems.

Bispectral index monitoring: comparison of two types of electrode.

Bis-monitoring is a new method of monitoring anaesthetic depth. Bis-monitoring is easy to perform, but the Bis-monitor and the original, disposable electrodes are expensive. The aim of this study was to determine whether the original Zipprep electrodes could be replaced by the much cheaper electrocardiogram electrodes. We compared bispectral index measurements, conducted using both types of electrode in the same patients before anaesthesia, and during light and deep anaesthesia, in patients randomly allocated to receive either sevoflurane or propofol anaesthesia. We found very good agreement between the measurements from the two different sets of electrodes. The impedance in the electrocardiogram electrodes was higher than in the Zipprep electrodes, but this did not affect the bispectral index. No other problems with either type of electrode were detected. It is concluded that Zipprep electrodes can be replaced by electrocardiogram electrodes in normal clinical practice.

A multicenter study of 4-chloro-m-cresol for diagnosing malignant hyperthermia susceptibility.

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.

Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that is triggered in genetically predisposed individuals by common anesthetics and muscle relaxants. The ryanodine receptor (RYR1) is mutated in a number of MH pedigrees, some members of which also have central core disease (CCD), an inherited myopathy closely associated with MH. Mutation screening of 6 kb of the RYR1 gene has identified four adjacent novel mutations, C6487T, G6488A, G6502A, and C6617T, which result in the amino acid alterations Arg2163Cys, Arg2163His, Val2168Met, and Thr2206Met, respectively. Collectively, these mutations account for 11% of MH cases and identify the gene segment 6400-6700 as a mutation hot spot. Correlation analysis of the in vitro contracture-test data available for pedigrees bearing these and other RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values. This finding has important ramifications for assignment of the MH-susceptible phenotype, in genotyping studies, and indicates that assessment of recombinant individuals on the basis of caffeine response is justified, whereas assessment on the basis of halothane response may be problematic. Interestingly, the data suggest a link between the caffeine threshold and tension values and the MH/CCD phenotype.

Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia.

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscular blocking agents. To date, eight mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and have identified a G to T transition mutation which results in the replacement of a conserved arginine (Arg) at position 614 with a leucine (Leu). The Arg614Leu mutation was present in three unrelated MHS individuals of 151 investigated. The mutation was not detected in 148 normal chromosomes and segregated precisely with MHS in family members from one of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mutation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cys probands is presented.

In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.

BACKGROUND: Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test. METHODS: Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centres of the EMHG. IVCT was performed according to the EMHG protocol. Patients were included in the study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patients and low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN (1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used. RESULTS: A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for the following reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n = 1), data were lost (n = 3), or none of the muscle bundles fulfilled twitch criteria (n = 7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible (95% confidence interval 94.8-100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2-96.5%). CONCLUSION: The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.

4-Chloro-m-cresol test--a possible supplementary test for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND: In vitro contracture test (IVCT) for diagnosis of MH in our laboratory has a sensitivity of 100% and a specificity of 93%. The results are equivocal in 10-15%, and supplementary tests may thus be required. We have tested the hypothesis that 4-chloro-m-cresol (4-cmc) may be useful for a supplementary test. METHODS: Muscle from 41 consecutive patients from 7 families undergoing diagnostic muscle biopsy with IVCT was exposed in vitro to increasing concentrations of 4-cmc (25, 50, 75, 100, 150, and 200 mumol l-1), and the force development recorded. Diagnosis of MH susceptibility was made with standard halothane and caffeine tests and included as results MHS (MH susceptible), MHN (MH negative), and MHE (equivoval result). RESULTS: At all concentrations of 4-cmc, the increase in baseline force was significantly greater in the MHS group compared to the MHN group (P < 0.05). Muscle from 15 MH-susceptible (MHS) patients responded to 4-cmc with increasing force at a threshold concentration of 75 mumol l-1 or less, whereas muscle from 23 MH-non-susceptible (MHN) patients had thresholds of 100 mumol l-1 or more. The accuracy of the chlorocresol test was thus 100% (95% confidence limits 90.75-100%) at a threshold of 75 mumol l-1. Amplitude of contractures at 2 mmol l-1 caffeine was not different from contractures at 75 mumol l-1 of 4-cmc in either the MHS or the MHN group (P > 0.05). In vivo concentrations of chlorocresol from clinical use of insulin and somatropin are estimated to be 20 times less than the threshold concentration and thus these drugs seem safe in MH patients. CONCLUSION: 4-chloro-m-cresol may be a suitable aid to clarify puzzling results of standard testing of MH susceptibility.

Analysis of anaesthesia in patients suspected to be susceptible to malignant hyperthermia before diagnostic in vitro contracture test.

BACKGROUND: It is well known that patients susceptible to malignant hyperthermia (MH) do not always develop clinical signs of MH at their first anaesthetic. Large material concerning this epidemiological problem do not exist. Therefore, we undertook the present investigation at the Danish Malignant Hyperthermia Register. METHODS: Retrospective analysis of anaesthetics given to 371 patients before in vitro contracture test (IVCT) for susceptibility to MH or before death of MH. Patients (or relatives in the case of a dead patient) gave information about previous anaesthetics and anaesthetic charts were collected and reviewed. RESULTS: Fifteen patients died of clinical MH, 112 patients survived an episode of suspected MH, and 244 patients were relatives of the above. Of the 127 patients with clinical signs of MH, 37% had received anaesthesia before, and trigger agents (potent inhalational agents and/or suxamethonium) were used in 98% of patients with no statistical difference between MH-susceptible (MHS) and non-susceptible (MHN) patients. Emergency anaesthesia was more frequent in patients with fulminant MH compared to those with abortive forms of MH (P < 0.01). Of the 244 relatives, 48% had received anaesthesia before MH was suspected in the family and trigger agents were used in 44% of the anaesthetics without statistical difference between MHS and MHN relatives. In 17 cases, trigger agents were used for anaesthesia after MH was suspected in the family, but before IVCT. CONCLUSION: The clinical expressivity of the MHS phenotype was found to be 34%-54%.

The Sophus anaesthesia simulator v. 2.0. A Windows 95 control-center of a full-scale simulator.

The Sophus group was founded in Denmark in 1992 with the aims of doing research into human error in anaesthesiology. Development of a simulation-environment was seen as one of the tools for research and training. This article describes the PC user interface of the SOPHUS anaesthesia simulator, SOPHUS v. 2.0 for Windows 95, and the script language, SASL v. 1.2. The script language provides possibilities of making scenarios, which develop in different directions according to the treatment of the patient by means of IF/THEN-statements, loops etc.

Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.