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Biomedical subjects

F Wappler

Publications and source records attributed to F Wappler.

At least 73 records · Page 4Linked to original sources
PubMed2000

Respiratory depression under long-term sedation with sufentanil, midazolam and clonidine has no clinical significance.

OBJECTIVE: Assessment of respiratory depression caused by long-term sedation with sufentanil, midazolam and clonidine. DESIGN: Retrospective assessment using data from a patient data management system. SETTING: University hospital anaesthesiological ICU. PATIENTS: Three hundred ninety-five surgical and trauma patients with an ICU stay of more than 48 h. INTERVENTION: None. MEASUREMENTS AND RESULTS: Arterial blood partial pressure of carbon dioxide (PCO2) was evaluated during mechanically assisted spontaneous ventilation (continuous positive airway pressure, synchronised intermittent mandatory ventilation, mandatory minute ventilation, bilevel positive airway pressure). Continuous sedation with sufentanil, midazolam or clonidine or a combination of those drugs was administered to achieve a Ramsay score between 2 and 4. Spontaneously breathing patients without continuous sedation and patients on controlled mechanical ventilation (and sedation) served as control groups. Mean arterial PCO2 from spontaneously breathing patients without continuous sedation was 39.5 +/- 7.3 torr compared with 42.7 +/- 6.8 torr under sufentanil (median 0.44 microg x kg(-1) x h(-1), 98 % of observations between 0.1 and 2.1 microg x kg(-1) x h(-1)), 41.5 +/- 6.1 torr under sufentanil (median 0.90 microg x kg(-1) x h(-1) (0.1-2.8)) plus midazolam (median 45 microg x kg(-1) x h(-1) (7-170)) and 39.8 +/- 5.6 torr under a combination of sufentanil (median 1.15 microg x kg(-1) x h(-1) (0.2-3.6)), midazolam (median 45 microg x kg(-1) x h(-1) (11-216)) and clonidine (median 1.3 microg x kg(-1) x h(-1) (0.2-2.5)). Mean arterial PCO2 from patients on controlled mechanical ventilation was 39.9 +/- 6.1 torr. CONCLUSION: Patients under continuous sedation with sufentanil exhibit a statistically significant rise in arterial PCO2, however this respiratory depression is only slight and has no clinical significance. Mechanically assisted spontaneous ventilation modes can safely be used under continuous sedation with sufentanil, midazolam or clonidine.

Adolescent↗
PubMed2000

Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients.

STUDY OBJECTIVES: To study the in vitro effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible (MHS) and normal (MHN) patients. DESIGN: Prospective study. SETTING: Malignant hyperthermia (MH) laboratory at a university hospital. PATIENTS: 47 patients with clinical suspicion for MH undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. INTERVENTIONS: Biopsies of M. quadriceps femoris were performed in adult patients with a 3-in-1 nerve block and in children with trigger-free general anesthesia. MEASUREMENTS AND MAIN RESULT: Patients were first classified as MHS or MHN by the IVCT according to the protocol of the European MH Group (EMHG). Patients with equivocal results (MHE) or with neuromuscular diseases were excluded from the study. Enoximone was added to the organ bath to surplus vital muscle specimens in single bolus concentrations of 0.4, 0.6, 0. 8, or 1.6 mmol/L. The in vitro effects of enoximone on muscle contractures and twitch were measured. Seventeen patients were classified as MHS and 30 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles in a dose-dependent manner. Contractures of MHS compared to MHN muscle specimens were significantly larger at all concentrations used in this study. No overlap in maximum contractures was seen between MHS and MHN muscles at a bath concentration of 0.6 mmol/L enoximone only. CONCLUSIONS: Diagnosis of MH by an IVCT test with a single bolus administration of enoximone seems to be possible using a concentration of 0.6 mmol/L. The findings of this study may indicate an involvement of the phosphodiesterase-III and cAMP system in pathogenesis of MH. Further in vivo investigation should determine the trigger potency of enoximone in MH susceptible individuals.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Inositol 1,4,5-trisphosphate synthesis in mononuclear white blood cells of malignant hyperthermia-susceptible and normal human beings, following in vitro exposure to halothane, caffeine and ryanodine.

Despite a plethora of findings associated with the pathophysiology of malignant hyperthermia (MH), the in vitro contracture test (IVCT) is the only reliable test for diagnosis of this heterogeneous syndrome in man. An increase of 1,4,5-IP3 (inositol 1,4,5-trisphosphate), a second messenger involved in cellular calcium homeostasis, has been observed in muscle tissue of MH susceptible (MHS) patients. The aim of this study was to evaluate if the known differences of 1,4,5-IP3 content in muscle tissue might be reproduced in mononucleated white blood cells (MWBCs). Subsequently, MWBCs of 23 healthy controls and 12 patients with a clinical suspicion for MH disposition were isolated and screened for 1,4,5-IP3 content. An IVCT according to the protocol of the European Malignant Hyperpyrexia Group (EMHG) was performed on muscle specimens of 12 patients. Eight MHN and four MHS individuals were diagnosed. Additionally, 1,4,5-IP3 synthesis in MWBCs was detected following in vitro exposure to IVCT test substances halothane (2%), caffeine (1-30mM), and ryanodine (1-5 microM). A broad inter-individual variability of 1,4,5-IP3 content was observed in MWBCs of all volunteers, but no differences were detected between MHS and MHN individuals. These findings are in strong contrast to those observed in muscle tissue. In vitro exposure of isolated MWBCs to halothane, caffeine and ryanodine yielded no statistically significant differences between groups. A time- and concentration-dependent increase in cellular 1,4,5-IP3 content could be induced in some but not all individuals of both groups. Since no correlation was obtained between induction of 1,4,5-IP3-synthesis following in vitro exposure of MWBCs to MH test substances and MH disposition, this study was terminated. We conclude from our data that the detection of 1,4,5-IP3 synthesis in MWBCs is not suitable for diagnosis of MH disposition. It remains questionable whether an altered 1,4,5-IP3 metabolism in MWBCs is involved in pathologic cascades of MH. Therefore, other cell tissues should be evaluated in further studies to clarify the role of the 1,4,5-IP3 metabolism in MH.

Anesthetics, Inhalation↗
PubMed2000

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.

Caffeine↗
PubMed1999

5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients.

Administration of 5-HT2 receptor agonists induced malignant hyperthermia (MH) in susceptible pigs. Furthermore, the 5-HT2 receptor antagonist ritanserin prevented 5-HT-induced porcine MH. It has been shown that 5-HT2 receptor agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients. The purpose of this study was to investigate the effects of ritanserin on halothane-induced contractures in muscle specimens from MHS patients. Twenty-five patients aged 8-56 years (29.5+/-13.6) classified as MHS by the in vitro contracture test (IVCT) with halothane and caffeine according to the protocol of the European MH Group participated in this study. Muscle specimens were pretreated with ritanserin 10 micromol/l (n= 14), 20 micromol/l (n=14) and 100 micromol/l (n=12) for 10 min and subsequently halothane was added incrementally (0.11-0.22-0.44 mmol/l) to the tissue bath as described in the European MH protocol. The results of the halothane contracture test were used as control. Following administration of halothane, muscle contractures reached a maximum of 16.9+/-4.2 mN. Ritanserin led to a significant inhibition of halothane-induced contractures in MHS muscles. Following pretreatment with ritanserin, halothane-induced contracture maximum was significantly smaller with 7.5+/-3.1 mN after 10 micromol/l ritanserin, 4.9+/-1.5 mN after 20 micromol/l ritanserin and 0.5+/- 0.2 mN after 100 micromol/l ritanserin than without pretreatment. Administration of ritanserin induced at all concentrations a decrease in muscle twitch height. Increase in muscle twitch following halothane was reduced in a concentration-dependent manner by ritanserin. The presented findings indicate that 5-HT might be involved in the mechanisms of halothane-induced MH in humans. Further studies have to determine the pathophysiological role of the 5-HT system in MH, and whether ritanserin could be an alternative for treatment or prevention of halothane-induced MH.

Adolescent↗
PubMed1999

Anaesthetic management of patients with mucopolysaccharidosis IV presenting for major orthopaedic surgery.

Mucopolysaccharidosis IV, also known as Morquio-Brailsford syndrome, is an inherited autosomal recessive disorder of mucopolysaccharide metabolism leading to accumulation of keratan sulphate in the connective tissue of multiple organ systems. Based on a case report, the anaesthetic implications for the treatment of patients with MPS IV presenting for major orthopaedic surgery are discussed.

Anesthesia↗
PubMed1999

[Interactions of intravenous anesthetics with cerebral alpha-2-adrenoceptors].

OBJECTIVE: Up to date the exact mechanisms of action of anaesthetics on structures of the central nervous system have not been elucidated. Agents acting on central alpha 2-adrenoceptors have been demonstrated to possess potent sedative properties. Beside the classical agonists, general anaesthetics that are currently in clinical use e.g. etomidate have also been shown to act on alpha 2-adrenoceptors. Thus, the aim of this study was to study the effect of the intravenous anaesthetic agents propofol and ketamine on the binding of the specific alpha 2-adrenoceptor agonist paraiodoclonidine at cerebral alpha 2 adrenoceptors. METHODS: After approval of the local animal care committee brain tissue of six Wistar rats was removed and frozen at -80 degrees C. The tissue was sectioned in 15-20 microns thick slices. After washing in TRIS-buffer (pH = 7.5) the slices were incubated with 2.5 nM 125I-paraiodoclonidine (PIC) for determination of specific binding. Unspecific binding was determined in presence of 200 microM unlabeled clonidine. Displacement experiments were performed in presence of propofol (11-530 microM) and ketamine (52-1100 microM) and evaluated autoradiographically. Average exposure time was three days. All films were then analysed by densitometry. Statistical significance calculated by Student's t-test was assumed at a level of p < 0.05. RESULTS: Only at the highest concentration of propofol and ketamine an effect on PIC binding was noticeable. Neither propofol nor ketamine was able to displace PIC completely from cerebral alpha 2-adrenoceptors. CONCLUSION: In contrast to other anaesthetics such as etomidate which was demonstrated to displace PIC completely from alpha 2-adrenoceptors, propofol and ketamine exerted only minor effects on the binding of PIC even at concentrations that exceeded clinical concentrations. These data suggest that an additional site of action of these anaesthetics at cerebral alpha 2-adrenoceptors beside the known actions on GABA receptors or NMDA receptors is unlikely.

Adrenergic alpha-Agonists↗
PubMed1999

Wound infiltration and drain lavage with ropivacaine after major shoulder surgery.

UNLABELLED: Subcutaneous infiltration and wound lavage with ropivacaine is an alternative to opioids after major shoulder surgery. However, the efficacy and potential toxicity of this method remain unclear. We therefore evaluated plasma ropivacaine concentrations after shoulder infiltration and wound lavage. We subsequently quantified the efficacy of two ropivacaine concentrations. Patients undergoing major shoulder surgery were anesthetized with alfentanil and propofol. The initial patients (n = 18) received ropivacaine 7.5 mg/mL and ropivacaine plasma concentrations were measured in 15-min intervals. The subsequent 45 patients were randomly assigned to: 1) isotonic saline, 2) 3.75 mg/mL ropivacaine, or 3) 7.5 mg/mL ropivacaine. Ten milliliters of each solution was administered subcutaneously and 20 mL was injected into the wound drain which was clamped for 10 min. Supplemental postoperative pain relief was provided by patient-controlled anesthesia using the opioid piritramid (3.5-mg boluses, 6-min lock-out). Postoperative pain scores were recorded on a 100-mm visual analog scale for 4 h in the initial patients and for 10 h in the second part of the study. Unbound ropivacaine plasma concentrations peaked after 15 min at 0.08+/-0.09 microg/mL; the maximum was 0.30 microg/mL, compared with a toxic threshold of 0.6 microg/mL. In the second part of the study, pain scores were significantly lower after 3.75 mg/mL (20+/-15 mm) or 7.5 mg/mL (10+/-9 mm) ropivacaine than saline (35+/-10 mm). Piritramid requirements differed significantly in the three groups, being highest with saline and lowest with ropivacaine 7.5 mg/mL. We conclude that wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement. IMPLICATIONS: Wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement.

Amides↗
PubMed1999

4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine.

BACKGROUND: 4-Chloro-m-cresol (4-CmC) induces marked contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MHS). In contrast, 4-CmC induces only small contractures in specimens from normal (MHN) patients. 4-CmC is a preservative within a large number of commercially available drug-preparations (e.g., insulin, heparin, succinylcholine), and it has been suggested that 4-CmC might trigger malignant hyperthermia. This study was designed to investigate the effects of 4-CmC in vivo and in vitro in the same animals. METHODS: After approval of the animal care committee, six Pietrain MHS and six control (MHN) swine were anesthetized with azaperone 4 mg/kg intramuscularly and metomidate 10 mg/kg intraperitoneally. After endotracheal intubation, lungs were mechanically ventilated (inspired oxygen fraction 0.3) and anesthesia was maintained with etomidate 2.5 mg x kg(-1) x h(-1) and fentanyl 50 microg x kg(-1) x h(-1). Animals were surgically prepared with arterial and central venous catheters for measurement of hemodynamic parameters and to obtain blood samples. Before exposure to 4-CmC in vivo, muscle specimens were excised for in vitro contracture tests with 4-CmC in concentrations of 75 and 200 microM. Subsequently, pigs were exposed to cumulative administration of 3, 6, 12, 24, and 48 mg/kg 4-CmC intravenously. If an unequivocal episode of malignant hyperthermia occurred, as indicated by venous carbon dioxide concentration > or = 70 mmHg, pH < or = 7.25, and an increase of temperature > or = 2 degrees C, the animals were treated with dantrolene, 3.5 mg/kg. RESULTS: All MHS swine developed malignant hyperthermia after administration of 4-CmC in doses of 12 or 24 mg/kg. Venous carbon dioxide concentration significantly increased and pH significantly decreased. Temperature increased in all MHS animals more than 2 degrees C. Blood lactate concentrations and creatine kinase levels were significantly elevated. All MHS swine were treated successfully with dantrolene. In contrast, no MHN swine developed signs of malignant hyperthermia. After receiving 4-CmC in a concentration of 48 mg/kg, however, all MHN animals died by ventricular fibrillation. The in vitro experiments showed that both concentrations of 4-CmC produced significantly greater contractures in MHS than in MHN specimens. CONCLUSIONS: 4-CmC is in vivo a trigger of malignant hyperthermia in swine. However, the 4-CmC doses required for induction of malignant hyperthermia were between 12 and 24 mg/kg, which is about 150-fold higher than the 4-CmC concentrations within clinically used preparations.

Animals↗
PubMed1998

[Regional distribution of predisposition to maligant hyperthermia in Germany: tate in 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.

Epidemiologic Studies↗
PubMed1998

[Incidence of disposition for malignant hyperthermia in patients with neuromuscular diseases].

PURPOSE: It has been suggested that malignant hyperthermia (MH) occurs more frequent in patients with neuromuscular diseases (NMD) than in patients without NMD when they are exposed to volatile anaesthetics and/or succinylcholine. However, whereas central core disease (CCD) and MH susceptibility (MHS) are closely associated, the relationship between MH and other NMD is still uncertain. The purpose of this study was to evaluate the MH status of individuals with specific NMD with the in vitro contracture test (IVCT) and to ascertain the risk for MH in individuals with NMD. METHODS: After institutional approval and informed consent, 29 patients of 3-59 years of age (27.2 +/- 17.3) with clinical suspicion for NMD and MH were enrolled in this prospective study. After excision of a skeletal muscle sample from M. vastus lateralis, patients were first classified as MHS, MH-equivocal (MHE) and MH-normal (MHN) by the IVCT according to the European MH protocol. Additionally, small muscle samples were excised from each patient for histological, histochemical and morphometric examination. RESULTS: Fourteen patients were diagnosed by the IVCT as MHS and 9 as MHN. In 6 patients MH status was equivocal. In six patients CCD was diagnosed, in 14 individuals muscular dystrophies and in 5 patients myotonias. Two patients had unspecific myopathies and one patient a carnitine deficiency syndrome. One patient with Friedreich's ataxia was investigated because of a MH crisis and classified as MHE. All CCD patients and two of three individuals with Duchenne's muscular dystrophy were tested as MHS. CONCLUSION: In this study 69% of the NMD patients were diagnosed as susceptible to MH with the IVCT. These results suggest, that NMD patients bear a high risk for MH. On the other hand, it has been discussed that in vitro contracture testing is not specific in NMD patients because skeletal muscle specimens from these patients have an elevated in vitro sensitivity. However, regarding our results and from a clinical point of view, patients with NMD should be treated like MHS individuals, unless they have undergone IVCT and were classified as MH-normal.

Adolescent↗
PubMed1998

[Diagnosis of susceptibility to malignant hyperthermia with an in vitro contracture test with the phosphodiesterase iii inhibitor enoximone].

PURPOSE: Inhibition of phosphodiesterase III (PDE-III) by enoximone elevates cyclic AMP (cAMP) content and intracellular calcium in human cardiac muscle. An involvement of cAMP in the pathogenesis of malignant hyperthermia (MH) has been suggested, because a higher basal content of cAMP was found in skeletal muscles from MH susceptible (MHS) than in normal (MHN) individuals and swine. In this study the in vitro effects of enoximone on skeletal muscles and the possibility to distinguish MHS from MHN patients were investigated. METHODS: Muscle biopsies from 37 patients with clinical suspicion for MH were obtained. The patients were first classified as MHS, MHE (equivocal result) or MHN by the caffeine halothane contracture tests according to the procedure of the European MH Group (EMHG). MHE-patients and patients with neuromuscular diseases were excluded from the study. Enoximone was added cumulatively every five minutes to surplus muscle specimens to obtain organ bath concentrations of 0.2, 0.4, 0.6, 0.8, 1.2 and 1.6 mmol/l. The in vitro effects of enoximone on muscle contractures and twitch were measured. RESULTS: Twelve patients were classified as MHS and 21 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles from all patients. MHS muscles developed contractures at significantly lower bath concentrations of enoximone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 0.4, 0.6, 0.8 and 1.2 mmol/l enoximone. No overlap in maximum contractures was seen between MHS and MHN muscles at bath concentrations of 0.6 and 0.8 mmol/l enoximone. Muscle twitch increased in both groups after administration of enoximone. CONCLUSION: The PDE-III-inhibitor enoximone induces contracture development in skeletal muscles. These contractures were attained at lower concentrations and were larger in MHS compared to MHN muscles. In vitro diagnosis of MH by a contracture test with enoximone appears to be possible. Furthermore, regarding these results a trigger potency for MH by enoximone could not be proved, but the use of enoximone in MHS patients might be dangerous.

Adolescent↗
PubMed1998

Multicentre evaluation of ryanodine contracture testing in malignant hyperthermia. The European Malignant Hyperthermia Group.

A common protocol for in vitro contracture testing using the plant alkaloid ryanodine has been used by the European Malignant Hyperthermia Group since 1993. This protocol describes a test using I mumol/litre of high purity ryanodine (98%) added as a single bolus dose. The main aim of this study was to compare the results obtained with this test between laboratories with a view to assessing the validity of adopting common diagnostic end-points for use in future collaborative studies. In order to do this it was first necessary to determine the optimum cut-off values of the end-points for discriminating between patients diagnosed as susceptible or not to malignant hyperthermia. The end-points under evaluation were expressed in terms of time after application of ryanodine at which a certain degree of contracture develops. In this study, four end-points were investigated: time to initial contracture development (Ot); time to development of a 10-mN contracture (10t); time from addition of ryanodine to when baseline tension exceeds pre-drug tension (0tp); and time for contracture to reach 10 mN above pre-drug baseline tension (10tp). This protocol was developed initially and used by three investigating centres and the initial assessment of the end-points and their discriminatory ability was made using the first 100 patients from each of centres 1 and 2, and the first 90 patients from centre No. 3. Optimal cut-off values for each of the end-points were determined using logistic regression analysis. Discriminatory ability was improved by combining the Ot and 10t end-points (P < 0.05) but not significantly by combining the 0tp and 10tp end-points. Both methods of categorization were highly sensitive and specific compared with the current standard diagnostic tests. Results from eight additional diagnostic centres which have used the ryanodine contracture test more recently, while indicating that susceptible and normal individuals can be distinguished within a single laboratory, produced a level of variability between testing centres for the ryanodine contracture test that is incompatible with the use of common cut-off values. Possible causes for this variability between laboratories are discussed.

Evaluation Studies as Topic↗
PubMed1998

Rhabdomyolysis following severe physical exercise in a patient with predisposition to malignant hyperthermia.

A 21-year-old man suffered from exertional heat stroke with impaired consciousness and rhabdomyolysis after strenuous physical exercise. Within two weeks the patient recovered completely without any specific therapy. Based on the symptoms and laboratory investigations, this episode suggested a moderate form of malignant hyperthermia. An in vitro contracture test was performed and a predisposition to malignant hyperthermia was diagnosed; other muscular diseases were excluded by histological examination. At present, the in vitro contracture test is the only method used to determine susceptibility to malignant hyperthermia and should be performed when the diagnosis is suggested on clinical grounds.

Adult↗
PubMed1998

[Level concept of analgesic dosing in intensive care medicine with sufentanil].

OBJECTIVE: The efficacy of a 3-level regimen of analgesia and sedation was investigated in a clinical setting. Level 1 consisted of continuous administration of sufentanil, in level 2 continuous administration of midazolam and level 3 continuous administration of midazolam and clonidine was added according to patients' needs. METHODS: Sufentanil at 1 microgram/kg/h was given initially. Later it was adjusted to patients' requirements in accordance with the Ramsay score (group 1). Long-term intubated patients received in addition midazolam 0.05 mg/kg/h (group 2). If needed, clonidine 1 microgram/kg/h was added (group 3). Mean drug requirements were investigated during controlled ventilation and during assisted ventilation with spontaneous breathing > 25% of total minute ventilation. In group 1 arterial paCO2 was measured to estimate drug-induced respiratory depression. Values given are median and ranges. RESULTS: With the 3-level-regimen of analgesia and sedation a Ramsay score of 2-3 was achieved in all intensive-care patients. In group 1 (n = 109; 36.7%) paCO2 values were similar at all times. Patients on controlled ventilation needed sufentanil 0.6 (0.075-2.5) microgram/kg/h, on assisted ventilation 0.4 (0.05-2.5) microgram/kg/h. Patients of group 2 (n = 113; 38.1%) had on controlled ventilation a higher requirement of sufentanil 1.2 (0.09-2.7) micrograms/kg/h, in addition Midazolam 0.05 (0.002-0.56) mg/kg/h was given. On assisted ventilation with spontaneous breathing > 25% sufentanil 0.9 (0.05-2.6) microgram/kg/h plus midazolam 0.04 (0.002-0.38) mg/kg/h was sufficient. Group 3 (n = 75; 25.2%) had on controlled ventilation a higher requirement of sufentanil with 1.5 (0.09-4.0) micrograms/kg/h and midazolam 0.05 (0.005-0.52) mg/kg/h, in addition clonidine 1.1 (0.12-2.88) micrograms/kg/h was given. On assisted ventilation with spontaneous breathing > 25% requirement of sufentanil with 1.1 (0.15-2.6) micrograms/kg/h and of midazolam with 0.05 (0.002-0.22) mg/kg/h was slightly lower, whereas more clonidine was needed with 1.3 (0.12-2.88) micrograms/kg/h. CONCLUSION: Continuous infusion of sufentanil only for analgesia and sedation is suitable for intensive-care patients with a short stay in the ICU. Respiratory depression during spontaneous breathing is not significant. The supplementary administration of midazolam and clonidine according to the presented regimen was shown to be of advantage for patients with a longer stay in ICU.

Alfentanil↗