Anesthesiology
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Succinylcholine-induced masseter muscle rigidity (MMR) is a potentially life-threatening complication of anesthesia and is closely correlated with the heterogeneous disorder malignant hyperthermia (MH) susceptibility. MMR also is identified with a variety of neuromuscular disorders, including the myotonias, that are associated with abnormal in vitro contracture test (IVCT) results. Recently, mutations in the adult skeletal muscle sodium channel alpha-subunit gene (SCN4A) have been shown to cause generalized nondystrophic myotonias, some of which are associated with mild nonspecific symptoms. The purpose of the current investigation was to begin to evaluate the molecular genetic relationship between known mutations in the SCN4A gene, MMR, and the results of the IVCT used to diagnose MH-susceptibility. ⋯ The current report provides direct evidence that succinylcholine-induced MMR, whole-body rigidity, and an abnormal IVCT result are associated with a mutation in the SCN4A gene.
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Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. ⋯ 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.
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Rocuronium is a new nondepolarizing muscle relaxant with a rapid onset and intermediate duration of action. Although the pharmacokinetics of rocuronium have been determined in adults and the elderly, similar data are lacking in children. Accordingly, rocuronium's pharmacokinetics were determined in children aged 4-11 yr. ⋯ Maturational changes were observed in rocuronium's weight-normalized clearance but not in its weight-normalized distributional clearance or volume of distribution. Assuming that the duration of rocuronium's neuromuscular effects is influenced by its pharmacokinetics, repeated administration or continuous infusion of rocuronium should result in larger dose requirements and more rapid recovery in younger, compared to older, children.
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Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (O2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO. ⋯ [NO2] increased with increased FIO2 and [NO], decreased VE, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan-Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems.
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Comparative Study
A comparison of the effects of hypothermia, pentobarbital, and isoflurane on cerebral energy stores at the time of ischemic depolarization.
In an accompanying article, we report that hypothermia (27-28 degrees C) delayed postischemic cortical depolarization longer than did large-dose pentobarbital or isoflurane anesthesia, even though preischemic cerebral metabolic rates for glucose were similar in the three groups. To examine the mechanism that may underlie these differences, we measured the cerebral concentrations of high-energy phosphates (including adenosine triphosphate [ATP] and adenosine diphosphate) in normal conditions and at the moment of depolarization. ⋯ The ATP/energy charge threshold for cortical depolarization was similar in all groups despite differing temperature or anesthetic conditions. Because hypothermia increased the time until depolarization, the rate of decrease in ATP concentration must have been slower in these animals than in the two groups receiving large-dose anesthetics, despite similar preischemic cerebral metabolic rates for glucose. This finding is similar to that of earlier studies and indicates that factors other than preischemic metabolic rate are responsible for controlling energy utilization after ischemia.