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1.
Crim Law Forum ; : 1-34, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36811023

RESUMEN

Dilemma scenarios have always been among the most common problems of moral philosophy and criminal law theory. One only has to contemplate the Plank of Carneades, the classic thought experiment whereby two shipwrecked people's only hope of rescue is a floating board that can only be occupied by one person. Other scenarios are Welzel's switchman case and the well-known Trolley Problem. In most of the debated cases the death of one or more people is absolutely unavoidable. The protagonists do not cause the situation but are fated to come into conflict. The focus of this article is on one recent and one future variant. First, the prioritization of medical aid (also known as "triage") is the subject of intense debate, because the COVID-19 pandemic posed a permanent risk of a temporary collapse in the health system in several countries. Situations had arisen whereby some patients can no longer be treated owing to lack of capacity. It can be asked whether a decision to treat may be based on which patients have a better chance of survival, whether reckless previous behaviour may play a role, and whether a treatment, once started, may be discontinued in favour of another. Second, dilemma scenarios are also one of the last remaining (largely unresolved) legal difficulties of autonomous vehicles. Never before has a machine been given the power to determine the life or death of human beings. Even though the automotive industry promises that such situations will hardly ever occur, the problem could prove to be a tangible obstacle to acceptance and innovation. The article offers solutions for those distinct scenarios, but it is also intended to demonstrate the underlying legal concepts of German law: namely, the tripartite analysis of criminal law and the idea of human dignity as a fundamental principle of the German constitution.

2.
Artículo en Alemán | MEDLINE | ID: mdl-34038975

RESUMEN

Malignant hyperthermia is a rare, subclinical pharmacogenetic syndrome leading to potentially life-threatening skeletal muscle hypermetabolism. Providing a safe and trigger-free anesthesia in predisposed individuals is essential to avoid serious harm to the patient. Especially the management of malignant hyperthermia predisposition in the context of pregnancy poses a huge challenge to the attending anesthesiologist. In May 2019 the European Malignant Hyperthermia Group published a guideline on malignant hyperthermia during pregnancy. The article summarizes and discusses the recommendations and provides practical advice for treatment of pregnant women or their fetus with known or suspected susceptibility to malignant hyperthermia.


Asunto(s)
Anestesia , Anestesiología , Hipertermia Maligna , Femenino , Humanos , Hipertermia , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/terapia , Embarazo , Síndrome
3.
Anesthesiology ; 131(5): 983-991, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31206373

RESUMEN

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal disorder triggered by certain anesthetics. Mutations in the ryanodine receptor 1 (RYR1) gene account for about half of MH cases. Discordance between the low incidence of MH and a high prevalence of mutations has been attributed to incomplete penetrance, which has not been quantified yet. The authors aimed to examine penetrance of MH-diagnostic RYR1 mutations and the likelihood of mutation carriers to develop MH, and to identify factors affecting severity of MH clinical expression. METHODS: In this multicenter case-control study, data from 125 MH pedigrees between 1994 and 2017 were collected from four European registries and one Canadian registry. Probands (survivors of MH reaction) and their relatives with at least one exposure to anesthetic triggers, carrying one diagnostic RYR1 mutation, were included. Penetrance (percentage of probands among all genotype-positive) and the probability of a mutation carrier to develop MH were obtained. MH onset time and Clinical Grading Scale score were used to assess MH reaction severity. RESULTS: The overall penetrance of nine RYR1 diagnostic mutations was 40.6% (93 of 229), without statistical differences among mutations. Likelihood to develop MH on exposure to triggers was 0.25 among all RYR1 mutation carriers, and 0.76 in probands (95% CI of the difference 0.41 to 0.59). Penetrance in males was significantly higher than in females (50% [62 of 124] vs. 29.7% [30 of 101]; P = 0.002). Males had increased odds of developing MH (odds ratio, 2.37; 95% CI, 1.36 to 4.12) despite similar levels of exposure to trigger anesthetics. Proband's median age was 12 yr (interquartile range 6 to 32.5). CONCLUSIONS: Nine MH-diagnostic RYR1 mutations have sex-dependent incomplete penetrance, whereas MH clinical expression is influenced by patient's age and the type of anesthetic. Our quantitative evaluation of MH penetrance reinforces the notion that a previous uneventful anesthetic does not preclude the possibility of developing MH.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/genética , Mutación/genética , Penetrancia , Canal Liberador de Calcio Receptor de Rianodina/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Adulto Joven
4.
Artículo en Alemán | MEDLINE | ID: mdl-31525786

RESUMEN

Malignant hyperthermia (MH) is a rare, heterogenic syndrome leading to potentially life-threatening skeletal muscle hypermetabolism following exposure to inhalational anesthetics and succinylcholine. In more than 50% of affected individuals a pathogenic variant in the RYR1 gene coding for the sarcoplasmic reticulum calcium channel is responsible for the underlying pathology of uncontrolled calcium liberation. While the genetic prevalence of MH is as high as 1 : 2750, the incidence of clinical MH reactions is considerably lower, suggesting a dominant pattern of inheritance with incomplete penetrance. During acute MH crisis presenting with characteristic symptoms like hypercarbia, tachycardia, acidosis, hyperthermia, generalized muscular rigidity and rhabdomyolysis, discontinuation of triggering agents and immediate treatment with dantrolene 2.5 mg/kg are vital therapeutic interventions to control the reaction. A predisposition to MH should be investigated in patients following a suspected MH crisis, in relatives from MH-families, after exertional or unexplained perioperative rhabdomyolysis and in patients with idiopathic hyper-CK-aemia. According to recent European guidelines, initial DNA screening is an alternative to muscle biopsy and in-vitro contracture testing, although in cases where no diagnostic variants are found, only contracture testing can safely exclude predisposition to MH.


Asunto(s)
Anestésicos por Inhalación , Hipertermia Maligna , Dantroleno , Humanos , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/terapia , Succinilcolina
5.
Artículo en Alemán | MEDLINE | ID: mdl-31525788

RESUMEN

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle presenting as a hypermetabolic response to potent volatile anesthetics such as sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced from > 80% to less than 10%. For treatment of MH an initial intravenous bolus of 2.5 mg/kg dantrolene based on the actual body weight should be applied. If symptoms are not improving after the initial dose, up to 10 mg/kg dantrolene can be necessary within the first 24 h. In facilities where MH triggering anesthetics and depolarizing muscle relaxants are administered, at least 36 - 48 vials of dantrolene 20 mg should be stocked according to the recent German S1 guideline on MH. If none of these agents are ever used in the facility, the stockage of dantrolene is dispensable. Since dantrolene is not easily dissoluble, preparation requires time and manpower. Due to its pharmacological characteristics, ryanodex, a modern nanocrystalline dantrolene sodium suspension, might be a promising alternative in the treatment of MH.


Asunto(s)
Anestésicos , Dantroleno , Hipertermia Maligna , Fármacos Neuromusculares Despolarizantes , Anestésicos/efectos adversos , Dantroleno/uso terapéutico , Humanos , Hipertermia Maligna/tratamiento farmacológico , Fármacos Neuromusculares Despolarizantes/uso terapéutico , Succinilcolina
6.
Anesthesiology ; 129(5): 989-999, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30204593

RESUMEN

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Halothane and caffeine induce excessive sarcoplasmic calcium liberation and skeletal muscle contracture in patients susceptible to malignant hyperthermia (MH) and are utilized for diagnosis in the in vitro contracture test. Intramuscular injection previously caused a marked local lactate increase in MH-susceptible but not in MH-nonsusceptible individuals in vivo. Using shear-wave elastography, this study evaluated localized changes in muscle stiffness after intramuscular injection of halothane and caffeine. METHODS: Microdialysis probes were placed into the gracilis muscle of 16 pigs (9 MH-susceptible and 7 MH-nonsusceptible). After local injection of either halothane or caffeine in different concentrations, changes of tissue elasticity surrounding the probe were examined by quantitative shear-wave elastography. Local lactate concentrations were analyzed spectrophotometrically. RESULTS: Ultrasound elastography detected a temporary increase in local muscle rigidity in MH-susceptible but not in MH-nonsusceptible pigs after 2.5 and 5 vol% halothane and after 10, 40, and 80 mM caffeine, whereas there were no differences in the control groups (median [interquartile range] for maximum effect after 5 vol% halothane: MH-susceptible: 97 [31 to 148] vs. MH-nonsusceptible: 5 [-6 to 18] kPa; P = 0.0006; maximum effect after 80 mM caffeine: 112 [64 to 174] vs. -3 [-6 to 35] kPa; P = 0.0002). These effects were seen rapidly within 5 min. Local lactate concentrations were higher in MH-susceptible versus nonsusceptible pigs after 1 and 2.5 vol% halothane and 10, 40, and 80 mM caffeine (2.5 vol% halothane: MH-susceptible: 2.8 [1.9 to 4.4] vs. MH-nonsusceptible: 0.6 [0.6 to 0.7] mmol/l; P < 0.0001; 80 mM caffeine: 5.2 [4.1 to 6.3] vs. 1.6 [1.2 to 2.4] mmol/l; P < 0.0001). After 10 vol% halothane, rigidity and lactate levels were increased in both MH-susceptible and MH-nonsusceptible animals. CONCLUSIONS: This pilot study revealed shear-wave elastography as a suitable technique for real-time detection of altered tissue elasticity in response to pharmacologic stimulation. By considering the variability of these results, further test protocol optimization is required before elastography could serve as a minimally invasive MH diagnostic test.


Asunto(s)
Cafeína/farmacología , Diagnóstico por Imagen de Elasticidad/métodos , Halotano/farmacología , Hipertermia Maligna/fisiopatología , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Anestésicos por Inhalación/farmacología , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Modelos Animales de Enfermedad , Músculo Esquelético/diagnóstico por imagen , Proyectos Piloto , Porcinos
7.
BMC Anesthesiol ; 18(1): 182, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30509180

RESUMEN

BACKGROUND: The calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH. METHODS: Muscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 µg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D'Agostino & Pearson test for normal distribution and student's t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant. RESULTS: There were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (- 3.0 [- 5.2-0.2] mN) compared to MHS (- 7.5 [- 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 µg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 µg/ml in MHS muscle bundles (3.3 [0.9-6.1] mN) compared to MHN (- 0.7 [- 1.3-0.0] mN) (p < 0.0001). CONCLUSIONS: This in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo.


Asunto(s)
Hipertermia Maligna/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacos , Inhibidores de Fosfodiesterasa 3/farmacología , Simendán/farmacología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Hipertermia Maligna/fisiopatología , Contracción Muscular/efectos de los fármacos , Inhibidores de Fosfodiesterasa 3/administración & dosificación , Simendán/administración & dosificación , Porcinos
9.
BMC Anesthesiol ; 14: 14, 2014 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-24606822

RESUMEN

BACKGROUND: While the impact of volatile anaesthetics to induce malignant hyperthermia (MH) is abundantly clear, the role of succinylcholine still remains controversial. To evaluate the influence of succinylcholine on porcine MH events, the authors investigated the hemodynamic and metabolic responses in MH susceptible (MHS) and non-susceptible (MHN) swine following either succinylcholine or halothane application alone or a combination of both substances. METHODS: With approval of the local animal care committee 27 MHS and 30 MHN pigs were anaesthetized and mechanically ventilated. Fiberoptic probes for continuous PCO2 measurement were inserted into the femoral vein and the triceps muscle. Group A received succinylcholine 4 mg/kg, group B incremental doses of halothane (0.5, 1.0 vol%) and group C succinylcholine and halothane simultaneously. Vital signs were recorded continuously. RESULTS: Prior to drug application measured values did not differ between MHS and MHN. While MHN pigs did not show relevant alterations, succinylcholine, halothane and the combination of both lead to significant hemodynamic and metabolic changes in MHS swine. CONCLUSIONS: Hemodynamic and metabolic alterations following succinylcholine were similar to halothane in MHS pigs. The combination of both pharmacological agents potentiated the observed effects. According to these results succinylcholine acted as an independent and supportive factor during onset of an MH episode.


Asunto(s)
Hipertermia Maligna/sangre , Hipertermia Maligna/patología , Succinilcolina/toxicidad , Animales , Análisis de los Gases de la Sangre/métodos , Monitoreo de Gas Sanguíneo Transcutáneo/métodos , Halotano/administración & dosificación , Halotano/toxicidad , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Succinilcolina/administración & dosificación , Porcinos
10.
J Med Case Rep ; 18(1): 119, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38414080

RESUMEN

BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.


Asunto(s)
Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Trombofilia , Trombosis , Humanos , Masculino , Anticoagulantes/uso terapéutico , Colgajos Tisulares Libres/irrigación sanguínea , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/cirugía , Complicaciones Posoperatorias , Estudios Retrospectivos , Trombofilia/complicaciones , Trombofilia/tratamiento farmacológico , Trombosis/etiología , Persona de Mediana Edad
11.
Muscle Nerve ; 47(5): 677-81, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23400941

RESUMEN

INTRODUCTION: Persistently elevated serum creatine kinase (CK) is frequently associated with predisposition to malignant hyperthermia (MH). We investigated whether a minimally invasive metabolic test is suitable to diagnose MH susceptibility among patients with hyperCKemia. METHODS: Thirty-nine participants were included: 10 were MH susceptible (MHS); 21 MH were non-susceptible (MHN); and 8 had MHN with persistent hyperCKemia >500 U/L. Microdialysis probes were inserted into the vastus lateralis muscle, and halothane or caffeine was injected via an attached microtubing catheter. Lactate concentrations in dialysis samples were measured spectrophotometrically. RESULTS: Baseline lactate did not differ between the groups. After local application of halothane or caffeine, a significant lactate increase was detected only in the MHS group. CONCLUSIONS: Test results were not influenced by hyperCKemia. To avoid risks and complications of a surgical muscle biopsy this microdialysis test might be a useful screening tool for MH susceptibility among patients with persistent CK elevation.


Asunto(s)
Creatina Quinasa/sangre , Ácido Láctico/metabolismo , Hipertermia Maligna/diagnóstico , Músculo Esquelético/metabolismo , Adulto , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Hipertermia Maligna/complicaciones , Hipertermia Maligna/metabolismo , Microdiálisis , Persona de Mediana Edad
12.
BMC Anesthesiol ; 13(1): 24, 2013 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-24053352

RESUMEN

BACKGROUND: Malignant hyperthermia (MH), a metabolic myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, is a potentially lethal complication of general anesthesia in susceptible patients. The implementation of modern inhalation anesthetics that research indicates as less potent trigger substances and the recommended limitations of succinylcholine use, suggests there may be considerable decline of fulminant MH cases. In the presented study, the authors analyzed suspected MH episodes during general anesthesia of patients that were referred to the Wuerzburg MH unit between 2007 and 2011, assuming that MH is still a relevant anesthetic problem in our days. METHODS: With approval of the local ethics committee data of patients that underwent muscle biopsy and in vitro contracture test (IVCT) between 2007 and 2011 were analyzed. Only patients with a history of suspected MH crisis were included in the study. The incidents were evaluated retrospectively using anesthetic documentation and medical records. RESULTS: Between 2007 and 2011 a total of 124 patients were tested. 19 of them were referred because of suspected MH events; 7 patients were diagnosed MH-susceptible, 4 MH-equivocal and 8 MH-non-susceptible by IVCT. In a majority of cases masseter spasm after succinylcholine had been the primary symptom. Cardiac arrhythmias and hypercapnia frequently occurred early in the course of events. Interestingly, dantrolene treatment was initiated in a few cases only. CONCLUSIONS: MH is still an important anesthetic complication. Every anesthetist must be aware of this life-threatening syndrome at any time. The rapid onset of adequate therapy is crucial to avoid major harm and possibly lethal outcome. Dantrolene must be readily available wherever MH triggering agents are used for anesthesia.

13.
Anesth Analg ; 115(4): 925-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22696611

RESUMEN

BACKGROUND: The 5-HT(3)-receptor antagonist ondansetron, commonly used to treat nausea and vomiting, was suspected of triggering malignant hyperthermia (MH) when a 5-year-old boy died after receiving a therapeutic dose of ondansetron. To evaluate a possible influence of ondansetron on the onset of MH, we investigated its effect on muscle specimens of MH-susceptible (MHS) and MH-nonsusceptible (MHN) individuals in vitro. METHODS: Muscle bundles of 6 MHS and 10 MHN patients were incubated in a tissue bath with ondansetron at increasing concentrations (0.1 to 300 µg/mL). Changes in resting tension and twitch height were monitored continuously. Data are reported as median and interquartile range; Mann-Whitney U test for differences between the groups (P < 0.05). RESULTS: Weight, length, initial resting tension, and twitch height of the muscle bundles did not significantly differ between the investigated groups. An increasing twitch amplitude after ondansetron application was observed in both groups. However, contractures developed only in MHS but not in MHN muscle at ondansetron concentrations of 50 µg/mL (MHS 2.5 [2.1 to 4.0] vs. MHN 0 [0 to 0] mN) and 100 µg/mL (18.0 [11.8 to 22.8] vs 0 [0 to 0] mN). At 300 µg/mL ondansetron, a muscular response was also observed in MHN (23.3 [20.1 to 40.1] vs 1.8 [0.3 to 4.9] mN). CONCLUSIONS: Ondansetron induced contractures in skeletal muscle bundles in vitro. The effect was significantly higher in MHS than in MHN muscle. Because the necessary concentration of ondansetron exceeded the therapeutic plasma levels by a minimum of 500 times, a trigger potency in vivo seems unlikely.


Asunto(s)
Hipertermia Maligna , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Ondansetrón/farmacología , Antagonistas del Receptor de Serotonina 5-HT3/farmacología , Adulto , Susceptibilidad a Enfermedades/inducido químicamente , Susceptibilidad a Enfermedades/fisiopatología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Hipertermia Maligna/genética , Hipertermia Maligna/fisiopatología , Persona de Mediana Edad , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Ondansetrón/efectos adversos , Técnicas de Cultivo de Órganos , Antagonistas del Receptor de Serotonina 5-HT3/efectos adversos
14.
Muscle Nerve ; 44(2): 213-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21607984

RESUMEN

INTRODUCTION: Malignant hyperthermia (MH) is a potentially lethal anesthetic complication characterized by muscle hypermetabolism and generalized rigor. The exact mechanism of succinylcholine as an MH trigger cannot be examined in existing in vitro models. Therefore, a novel in vivo model was used to examine the metabolic response to succinylcholine. METHODS: With institutional review board approval, 6 MH susceptible (MHS) and 6 MH non-susceptible (MHN) pigs were anesthetized with hemodynamic and systemic metabolic monitoring. Microdialysis catheters were placed intramuscularly. After equilibration, succinylcholine, halothane, and Ringer solution were injected. Lactate was measured in the dialysate and statistically analyzed by Mann-Whitney U-test (significance level P < 0.05). RESULTS: Hemodynamic and systemic metabolic parameters were not different between the groups throughout the experiment. In the MHS pigs, halothane induced a significant increase of lactate. In MHN pigs, no substance induced a reaction. CONCLUSIONS: Halothane, but not succinylcholine, induced a hypermetabolic reaction in this model. Therefore, the role of succinylcholine as an MH trigger remains questionable.


Asunto(s)
Hipertermia Maligna/etiología , Músculo Esquelético/efectos de los fármacos , Fármacos Neuromusculares Despolarizantes/farmacología , Unión Neuromuscular/efectos de los fármacos , Succinilcolina/farmacología , Animales , Susceptibilidad a Enfermedades , Femenino , Hemodinámica/efectos de los fármacos , Masculino , Hipertermia Maligna/genética , Hipertermia Maligna/metabolismo , Músculo Esquelético/metabolismo , Unión Neuromuscular/metabolismo , Porcinos
15.
Muscle Nerve ; 44(2): 208-12, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21607983

RESUMEN

INTRODUCTION: The mechanisms of fluoroquinolone-induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. An in vitro contracture test used to investigate cellular processes in malignant hyperthermia (MH) can be applied to study the effects of fluoroquinolones. METHODS: With approval of the local ethics committee, muscle biopsies of 18 MH susceptible (MHS) and 12 MHS non-susceptible (MHN) pigs were performed. Individual bundles were mounted on an isometric force transducer, preloaded, and electrically stimulated. After equilibration they were exposed to ciprofloxacin or levofloxacin. The measured baseline tension was analyzed (Wilcoxon test: P < 0.05). RESULTS: There were no differences in weight, length, or predrug tension between the groups. Both levofloxacin an ciprofloxacin induced significant contractures in MHS muscle bundles but not in MHN. CONCLUSIONS: Fluoroquinolones appear to have a pathological influence on intracellular calcium handling. A pre-existing impairment of the calcium homeostasis, however, seems to be necessary for this behavior.


Asunto(s)
Calcio/metabolismo , Fluoroquinolonas/farmacología , Hipertermia Maligna/metabolismo , Músculo Esquelético/efectos de los fármacos , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Animales , Ciprofloxacina/farmacología , Susceptibilidad a Enfermedades , Levofloxacino , Hipertermia Maligna/genética , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/metabolismo , Ofloxacino/farmacología , Porcinos
16.
Anesth Analg ; 112(5): 1174-8, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21474662

RESUMEN

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal hypermetabolic syndrome. Volatile anesthetics and/or succinylcholine lead to an increase of the intracellular calcium concentration resulting in activation of various intracellular processes. A production of carbon dioxide, and later lactate, are early signs of increased cellular energy consumption. On a cellular level, magnesium acts as a physiological calcium inhibitor resulting in less-intense calcium liberation from the sarcoplasmic reticulum. In this study, we examined the effects of IV magnesium administration on the clinical course of an MH crisis. METHODS: Sixteen Pietrain pigs (10 MH-susceptible [MHS] and 6 MH-nonsusceptible [MHN]) were anesthetized without an MH trigger substance. Invasive hemodynamic monitoring was established before 4 mg/kg succinylcholine was administered. Four of the MHS pigs received 10 mg/kg magnesium sulfate 10 minutes later. Hemodynamic changes (heart rate, mean arterial blood pressure, and oxygen saturation as measured by pulse oximetry) were continuously monitored. Venous and arterial blood gases (pH, Pco(2), Po(2), base excess, and lactate) were taken at 15-minute intervals. The H test and U test were used with P < 0.05 for significant differences among the groups. RESULTS: No differences among the groups were seen for weight, hemodynamic, and metabolic variables before administration of succinylcholine. In all MHS animals, succinylcholine led to a marked decrease of mean arterial blood pressure and increase of heart rate. Animals in both MHS groups developed combined metabolic and respiratory acidosis. Succinylcholine had no effect on animals in the MHN group. Hemodynamic and metabolic values were not different between the 2 MHS groups but were between groups MHS and MHN. CONCLUSION: Succinylcholine led to a hemodynamic and metabolic reaction in only MHS pigs. Treatment with magnesium did not influence the clinical course. The intervention had no beneficial effect in the acute phase of an MH crisis.


Asunto(s)
Sulfato de Magnesio/administración & dosificación , Hipertermia Maligna/prevención & control , Succinilcolina , Animales , Biomarcadores/sangre , Dióxido de Carbono/sangre , Modelos Animales de Enfermedad , Metabolismo Energético , Hemodinámica , Concentración de Iones de Hidrógeno , Infusiones Intravenosas , Ácido Láctico/sangre , Hipertermia Maligna/sangre , Hipertermia Maligna/etiología , Hipertermia Maligna/fisiopatología , Oximetría , Oxígeno/sangre , Porcinos , Factores de Tiempo , Insuficiencia del Tratamiento
17.
Anesth Analg ; 113(5): 1120-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21965348

RESUMEN

BACKGROUND: A diagnosis of malignant hyperthermia (MH) can be determined by performing an in vitro (muscle) contracture test (IVCT) or by identifying a known MH causative mutation in the ryanodine receptor 1 gene (RYR1). Genetic diagnosis has an advantage over IVCT because it is less invasive. Direct sequencing of the very large RYR1 coding region (15.117 bases) is a laborious and expensive task. In this study, we applied the High Resolution Melting (HRM) curve analysis as a tool to screen the entire coding region of the gene. METHODS: Genomic DNA was extracted from peripheral blood samples in a cohort of 16 MH-susceptible patients diagnosed by the IVCT. The total coding region of RYR1 was divided and amplified by polymerase chain reaction in 131 DNA fragments and the melting profiles were compared with those of control samples. HRM curves were evaluated by Rotor-Gene Q software and visual inspection. Fragments showing aberrant melting profiles were sequenced to identify the underlying sequence variation. RESULTS: A subset of 520 of 2520 DNA fragments (21%) showed significantly aberrant melting profiles. Upon sequencing, 131 known polymorphisms and 17 known or suspected mutations were found in 13 of 16 MH-susceptible patients (81%). Thus, the workload of sequencing was reduced by 79%. CONCLUSION: HRM curve analysis is a sensitive and cost-effective tool for the identification of nucleotide sequence variants in complex genes such as the RYR1 gene.


Asunto(s)
Pruebas Genéticas , Hipertermia Maligna/genética , Mutación/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , ADN/sangre , ADN/genética , Cartilla de ADN , Exones/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
18.
Eur J Anaesthesiol ; 28(4): 251-5, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20827211

RESUMEN

BACKGROUND: Malignant hyperthermia is a potentially lethal inherited hypermetabolic syndrome that develops in susceptible individuals following administration of depolarising neuromuscular relaxants or volatile anaesthetics. Genetic analysis can only confirm a diagnosis of malignant hyperthermia in about 70%, and in the remainder an in-vitro contracture test, with halothane and caffeine, on muscle obtained from open muscle biopsy is required to establish the diagnosis. As the licence for clinical use of halothane expired in 2005, its continuing availability is in doubt. More modern volatile anaesthetics such as enflurane, isoflurane, desflurane and sevoflurane are less potent triggers of malignant hyperthermia in humans and pigs. The aim of this study was to investigate whether these agents can be considered possible substitutes for halothane in a modified in-vitro contracture test. METHOD: With institutional review board approval and prior written consent, muscle bundles of 30 patients with a personal or family history of malignant hyperthermia were investigated. Of these, 13 were diagnosed malignant hyperthermia susceptible and 17 nonsusceptible. Surplus muscle was tested with increasing concentrations of enflurane, isoflurane, desflurane and sevoflurane. RESULTS: There were no differences in weight, length or predrug tension of the muscle bundles. At increasing concentration, all volatile anaesthetics except sevoflurane induced significantly greater contractures in malignant hyperthermia susceptible compared to malignant hyperthermia nonsusceptible muscle. In malignant hyperthermia susceptible muscle bundles, halothane led to significantly higher contractures compared to the other investigated substances. CONCLUSION: Halothane was the strongest discriminator for malignant hyperthermia in the in-vitro contracture tests. It remains the ideal substance for diagnostic testing and cannot simply be replaced by other agents in this test.


Asunto(s)
Anestésicos por Inhalación , Halotano , Hipertermia Maligna/diagnóstico , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Biopsia , Estudios de Casos y Controles , Desflurano , Relación Dosis-Respuesta a Droga , Enflurano , Humanos , Isoflurano/análogos & derivados , Hipertermia Maligna/etiología , Hipertermia Maligna/fisiopatología , Éteres Metílicos , Músculo Esquelético/fisiopatología , Valor Predictivo de las Pruebas , Sevoflurano
19.
J Emerg Med ; 41(3): 326-32, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20605389

RESUMEN

BACKGROUND: According to different algorithms of airway management, emergency cricothyrotomy is the final step in managing the otherwise inaccessible airway. As an alternative to an open surgical procedure, minimally invasive approaches exist. Various sets for different methods are commercially available. QuickTrach™ (VBM Medizintechnik GmbH, Sulz am Neckar, Germany) contains a plastic cannula over a metal needle for direct placement in the trachea, whereas a guide-wire is used for the actual placement of the cannula in the Melker Set™ (Cook Group Incorporated, Bloomington, IN). OBJECTIVE: We hypothesize that the direct puncture involving less discrete steps is faster to perform. However, it will lead to more complications due to the higher force needed to place the relatively thick needle. METHOD: After approval of the local ethics committee, the study was performed on cadavers of 16 adult sheep. A wire-guided cricothyrotomy was compared with a catheter-over-needle technique. Successful placement and performance time were compared. Complication rate and maximal achieved airway pressure were evaluated. Data is given as mean and interquartile range, and Mann-Whitney U-test (p < 0.05) for significant differences. RESULTS: With the wire-guided technique, successful placement was possible in all attempts. The catheter-over-needle method was successful in 63% and had a higher complication rate (75% vs. 13%). The cannula-over-needle method allowed a faster cricothyrotomy (32 [2-34] vs. 53 [52-56] s). Both methods allowed the delivery of similar maximal airway pressures (50 [44-51] vs. 48 [43-53] mbar). CONCLUSION: The wire-guided method proved to be the more reliable technique, leading to fewer complications. However, the direct puncture was faster to perform. Placed accurately, both devices allowed sufficient ventilation.


Asunto(s)
Cartílago Cricoides/cirugía , Medicina de Emergencia/métodos , Cartílago Tiroides/cirugía , Traqueotomía/instrumentación , Animales , Cadáver , Distribución Aleatoria , Ovinos , Traqueotomía/métodos
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