British journal of anaesthesia
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Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to halothane but not caffeine (halothane-hypersensitive). Hallmarks of halothane-hypersensitive patients include high incidence of musculoskeletal symptoms at rest and abnormal calcium events in muscle. By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, we reach new insights into the pathological mechanism of malignant hyperthermia susceptibility. ⋯ Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.
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Observational Study
Intraoperative hydromorphone decreases postoperative pain: an instrumental variable analysis.
Intraoperative administration of short-acting opioids might lead to increased postoperative pain and opioid requirements. There are few data describing the effects of intermediate-duration opioids such as hydromorphone on these outcomes. We have previously shown that a switch from a 2 mg to a 1 mg vial of hydromorphone was associated with decreased intraoperative dose administration. As presentation dose affected intraoperative hydromorphone administration and was unrelated to other policy changes, it could serve as an instrumental variable, assuming significant secular trends were not present during the study period. ⋯ This study suggests that intraoperative administration of intermediate-duration opioids does not cause the same effects as short-acting opioids with respect to postoperative pain. Instrumental variables can be used to estimate causal effects using observation data when unmeasured confounding is present.
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The molecular mechanisms of susceptibility to malignant hyperthermia are complex. The malignant hyperthermia susceptibility phenotype should be reserved for patients who have a personal or family history consistent with malignant hyperthermia under anaesthesia and are subsequently demonstrated through diagnostic testing to be at risk.