Biomedical subjects
M G Larach
Publications and source records attributed to M G Larach.
Prediction of malignant hyperthermia susceptibility in low-risk subjects. An epidemiologic investigation of caffeine halothane contracture responses. The North American Malignant Hyperthermia Registry.
The most commonly used laboratory test for predicting malignant hyperthermia susceptibility is the caffeine halothane contracture test. However, the specificity and sensitivity of proposed North American diagnostic guidelines for this test have never been evaluated in a large, human study population. Therefore, the authors conducted a multiinstitutional, prospective study of skeletal muscle contracture responses in a subject population at low risk for malignant hyperthermia susceptibility to help determine the specificity of the proposed guidelines. Subjects were selected arbitrarily from a population of patients undergoing surgery unrelated to performance of a diagnostic muscle biopsy. Subjects were admitted to this study and were presumed nonsusceptible if there was no evidence of any of the following malignant hyperthermia risk factors: prior abnormal response to triggering anesthetic agents, myopathy, or family history of malignant hyperthermia susceptibility. The authors suggested rejection of the proposed diagnostic guidelines if an 85% specificity estimate among subjects could not be obtained. The authors analyzed the responses of 1,022 muscle fascicles, derived from 176 subjects, to the following: 1) separate administration of 3% halothane or incremental caffeine concentrations, or 2) the joint administration of 1% halothane and incremental caffeine concentrations. The following contracture results were obtained. First, for individual fascicles, 9.2% exceeded a greater than 0.7 g threshold for 3% halothane, 15.2% exceeded a greater than or equal to 0.2 g threshold for 2 mM caffeine, 32.4% exceeded a 1-g increase for less than 4 mM caffeine, 2.6% had a greater than 7% maximal increase in tension at 2 mM caffeine, and 63.5% had a "halothane caffeine-specific concentration" at less than or equal to 1 mM caffeine. Second, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold were as follows: 45.8% for the four-component, 28.8% for the three-component, and 32.7% for the two-component contracture test. Third, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold for both halothane and caffeine were as follows: 9.5% for 3% halothane and 2 mM caffeine, 2.0% for 3% halothane and 7% maximal increase in tension at 2 mM caffeine, and 11.0% for 1% halothane and 2 mM caffeine. Fourth, center-to-center differences were the major source of variation in the rate that subjects exceeded proposed thresholds. These data demonstrate that proposed diagnostic guidelines must be modified to improve specificity estimates before adoption by diagnostic centers.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparison of the safety and efficacy of intranasal midazolam or sufentanil for preinduction of anesthesia in pediatric patients.
Nasal administration of sufentanil or midazolam is effective for preinduction of pediatric patients, but there are no data on which to base a choice between them. This blinded randomized study compares behavioral and physiologic responses to sedation with one of these medications followed by inhalation or intravenous induction. Ninety-five patients aged 0.5-10 yr scheduled for elective surgery were stratified by age: 30 infants 0.5-2 yr, 38 preschoolers 2.1-5 yr, and 27 school-age children 5.1-10 yr. They were randomized to receive 0.04 ml/kg of midazolam (0.2 mg/kg) or sufentanil (2 micrograms/kg). Hemoglobin oxygen saturation by pulse oximetry (SpO2) and sedation score were recorded prior to drug administration, at 2.5-min intervals for 10 min, at separation, and during induction with graded halothane in oxygen. Intubation was performed under deep halothane or 3 mg/kg of thiopental and 0.1 mg/kg of pancuronium. Chest wall compliance was assessed qualitatively in all patients prior to intubation. To assess the effects of a mild standardized stress on unpremedicated patients, 75 of the children with parents present were scored before and after oximeter probe placement: of these, in 63% the sedation score did not change; 33% appeared more anxious; and only 4% seemed reassured. Children of all ages reacted negatively to physicians, and 23% were crying prior to administration of drugs. Sufentanil appeared less unpleasant to receive than midazolam: children cried 46 +/- 100 versus 76 +/- 73 s (P less than 0.05), respectively, but by 7.5 min, no child was crying. Median behavior scores at maximum anxiolysis were not different, but response to sufentanil was more variable.(ABSTRACT TRUNCATED AT 250 WORDS)
Standardization of the caffeine halothane muscle contracture test. North American Malignant Hyperthermia Group.
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Cardiopulmonary bypass interference with dantrolene prophylaxis of malignant hyperthermia.
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Prediction of malignant hyperthermia susceptibility by clinical signs.
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Halothane selectively attenuates alpha 2-adrenoceptor mediated vasoconstriction, in vivo and in vitro.
The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional alpha 1- and alpha 2-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: in vivo blood pressure response in pithed rats, and in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti-vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an alpha 2-adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an alpha 1-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P less than 0.0001) to azepexole in pithed rats, and a 3.2-fold rightward shift of the log dose-response curve (P less than 0.0001). Similarly, in vitro, halothane significantly attenuated alpha 2- but not alpha 1-adrenoceptor responsiveness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P less than 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P less than 0.0001). The observed selective interference with alpha 2-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca+2 entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at alpha 2-adrenoceptors by halothane may explain why alpha 1-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenuation of alpha 2- but not alpha 1-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation.