Anesthesiology
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The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In vitro expression studies suggest that there is subunit specificity to anesthetic responses at the GABA(A) receptor. The authors tested whether genetically engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in their sensitivities to several general anesthetic agents. ⋯ The beta3 subunit of the GABA(A) receptor appears to be important in the mediation of the immobilizing (tail clamp) but not obtunding (loss-of-righting reflex) effects of the volatile anesthetic agents enflurane and halothane. These data support the hypotheses that separate components of the anesthetic state are mediated via different central nervous system loci; that the GABA(A) receptor is a likely target for the immobilizing response to volatile anesthetic agents; and that the beta3 subunit plays a direct or indirect role in the mediation of this response. Absence of the beta3 subunit appears to attenuate the obtunding effect of midazolam and etomidate but appears not to alter the obtunding effect of pentobarbital, enflurane, and halothane, suggesting that these anesthetic agents produce hypnosis by different specific molecular mechanisms.
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Phenotyping malignant hyperthermia (MH) by contracture testing has a low but quantifiable degree of inaccuracy, measured by its sensitivity and specificity. Quantifying the limitations inherent in diagnostic testing for MH can help resolve issues in clinical practice, such as the interpretation of a negative test and the apparent lack of complete genetic linkage to RYR1. ⋯ Diagnostic contracture testing for MH is clinically useful because of high NPV and can exclude MH with near certainty. For MH probands, the clinical grading scale for MH may guide PTP estimation, whereas for relatives of probands, PTP is a function of kinship to a known MH-susceptible relative. A sequential testing strategy optimizes diagnostic information by maximizing PTP within a pedigree. Incomplete testing of parents of an MH susceptible child can pose a significant risk of false-negative results for the untested parent. Even with optimal pedigree testing strategies, the PPV drift effect results in a considerable source of phenotypic uncertainty for genetic linkage studies.
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Although pulmonary function is minimally changed by neuraxial blockade in most cases, ventilatory arrest may ensue in rare cases. The authors examined the mechanism of apnea in a rabbit model of sudden ventilatory arrest during the combination of epidural anesthesia and hypoxia. ⋯ Epidural anesthesia results in a narrowed margin of safety for oxygen delivery to the brain and predisposes subjects to ventilatory arrest during hypoxia. This results from the combined effects of decreased blood oxygen content, which is due to decreased inspired oxygen concentration superimposed on circulatory depression due to neural blockade.