Portal de Periódicos da CAPES

Malignant Hyperthermia During Sevoflurane Administration

1995; Lippincott Williams & Wilkins; Volume: 80; Issue: 3 Linguagem: Inglês

10.1097/00000539-199503000-00031

1526-7598

Anne Ducart, P Adnet, Brigitte Renaud, Bruno Riou, R Krivosic-Horber,

S100 Proteins and Annexins

Sevoflurane is a new inhaled anesthetic which has triggered malignant hyperthermia (MH) in three children [1,2] and in swine [3]. We describe a case of MH during sevoflurane administration in which in vitro testing confirmed MH susceptibility. Case Report A 20-yr-old woman had a history of Charcot-Marie-Tooth disease (Type II) and underwent an osteotomy of the right calcaneum. Ten years prior, she had had two surgical procedures (left then right tibial osteotomy) under general anesthesia without problems, although the anesthetics used are unknown. There was no family history of MH or muscle disease. Anesthesia was induced with thiopental (6 mg/kg), fentanyl (2 micro gram/kg), and vecuronium bromide (0.1 mg/kg). ETCO2 and sevoflurane concentrations were monitored continuously, and esophagal temperature was measured using a disposable probe connected to a monitor which also noninvasively measured arterial blood pressure, pulse oximetry, and heart rate. Anesthesia was maintained with sevoflurane Figure 1 and nitrous oxide (65%) in oxygen; ETCO2 concentration was 35 mm Hg and temperature 36.0 degrees C. After 90 min of sevoflurane administration, slight increases in ETCO2 (45 mm Hg) and temperature (36.4 degrees C) were noted. After 110 min of sevoflurane administration, ETCO2 was 60 mm Hg despite an increase in minute ventilation, and temperature was 36.8 degrees C Figure 1. No significant changes in muscle tone and skin appearance were noted. Sevoflurane was discontinued and surgery was stopped. Oxygen 100% was administered through a new anesthetic circuit, and dantrolene (2 mg/kg) was administered intravenously. ETCO2 and temperature returned to baseline values within 20 min after dantrolene administration. In the recovery room, analysis of arterial blood gases showed a pHa of 7.35, PaCO2 39 mm Hg, and plasma creatine phosphokinase level was 1321 IU/L (normal range <or=to 230). The postoperative period was uneventful, and dantrolene administration was continued during 48 h. The creatine phosphokinase level reached a maximum value of 9941 IU/L at the twelfth postoperative hour and was 424 IU/L on the fifteenth postoperative day. General anesthesia was performed again 10 days later with propofol, fentanyl, nitrous oxide, and vecuronium bromide without any signs of MH. Dantrolene was not prophylactically administered.Figure 1: Evolution of heart rate (HR), mean arterial pressure (MAP), ETCO2 and sevoflurane concentrations, and esophageal temperature. Sevoflurane concentration represents the mean of all measures during a 10-min period.Fifteen days after the MH episode, the patient underwent an in vitro contracture test. The biopsy was taken from the lateral vastus muscle under combined block with lidocaine of the femoral and lateral cutaneous nerves of the thigh. The preparation and stimulation of the muscle bundles and experimental apparatus have been described previously [3]. The patient was investigated according to the protocol of the European MH Group [4]. The criteria of MH susceptibility were increases in resting tension of at least 0.2 g, both with a halothane threshold concentration <or=to 2% (in the gas phase) and a caffeine threshold concentration 2% and a caffeine threshold > 2 mmol/L. Other results (i.e., one abnormal response either with halothane or with caffeine) were classified MH-equivocal. A 3% halothane test was performed on one fiber bundle according to the protocol supported by the North American MH Group [5]. The patient was diagnosed as MH susceptibility if the muscle bundle exhibited a contracture >or=to 0.5 g within 10 min of 3% halothane exposure. In addition, sevoflurane was mixed with carbogen by means of a calibrated vaporizer (Sevotec 5 Trademark, Ohmeda, Trappes, France). The anesthetic concentration in the gas phase was monitored with an infrared calibrated analyzer. The anesthetic concentrations used were 1.0, 2.0, and 4.0 vol% sevoflurane equivalent to 0.5, 1, and 2 minimum alveolar anesthetic concentrations (MAC) multiples of halothane in humans at 37 degrees C [6]. The two caffeine in vitro tests developed a contracture of 2.0 g and 1.0 g at 2 mmol/L caffeine, respectively. The two halothane in vitro tests developed a contracture of 3.9 g and 2.0 g at 2 vol% halothane, respectively. The response of the muscle bundle to 3% halothane bolus was also very high, with a 5.0-g contracture. Exposure to increasing concentrations of sevoflurane resulted in a contracture response of 1.6 g at 2 minimum alveolar anesthetic concentrations (4%) sevoflurane Figure 2.Figure 2: Typical in vitro responses of malignant hyperthermia susceptible muscle to increasing concentrations (0.5%-3%) of halothane (upper left panel), bolus dose (3%) of halothane (upper right panel), and increasing concentrations of sevoflurane (lower panel). Muscle bundles from the patient exhibited a contracture of 3.9 g at 2% halothane and a 5.0-g contracture at 3% halothane bolus. Exposure to increasing concentrations of sevoflurane resulted in a contracture response of 1.6 g at 4% sevoflurane.Discussion This is the first case of sevoflurane-induced MH confirmed by a positive in vitro test with caffeine and halothane, and a contracture response of one muscle bundle to increasing concentrations of sevoflurane. Three pediatric cases of MH have been reported with sevoflurane but a definite diagnosis, using in vitro tests, was not obtained [1,2]. Nevertheless, sevoflurane triggers MH in susceptible swine [7] as do all other volatile anesthetics [8]. Moreover, other anesthetics administered to our patient are considered to be safe drugs for MH-susceptible patients. Thus, the present case report demonstrates that sevoflurane, alone, is able to trigger MH in susceptible humans and to induce in vitro muscle contracture. Although all volatile anesthetics are potent MH triggers, several experimental reports suggest a difference in the onset of MH crisis by these anesthetics [9]. Indeed, Wedel et al. [9] have recently shown that halothane exposure results in the fastest (mean 20 min) onset of a MH episode in susceptible swine, as compared to isoflurane (mean 48 min) or desflurane (mean 65 min). Likewise, a previous in vitro study reported that halothane has the greatest ability to potentiate the caffeine-induced contracture in MH-susceptible patients [10]. However, other variables have been proposed because some of the environmental conditions modify volatile anesthetic potency to trigger MH [3]. Hence, further experimental studies either performed in vivo in MH-susceptible swine or in vitro on muscle bundles from MH-susceptible patients are required to confirm this hypothesis. Nevertheless, this clinical report may be important for anesthesiologists because it indicates that MH must be evoked even after an uneventful and long-lasting exposure to sevoflurane. Our patient had a history of Charcot-Marie-Tooth disease and one previous incident has raised the issue of MH in Charcot-Marie-Tooth disease [11]. Nevertheless, the potential link between MH and Charcot-Marie-Tooth disease remains unknown at present and has been considered unlikely [12]. This case report also reemphasized some important issues in MH: 1) the initial symptom was an increase in ETCO2, demonstrating the importance of ETCO (2) monitoring; 2) all signs resolved within 30 min after dantrolene injection, demonstrating the efficacy of its early administration; 3) anesthesia was performed again without any problems with propofol, fentanyl, and vecuronium, which are considered safe in MH-susceptible patients.