Anesthesiology
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Randomized Controlled Trial
Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers.
The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. ⋯ This first observation that norketamine produces effects in the opposite direction of ketamine requires additional proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions.
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Abnormal cardiac repolarization, indicated by a prolongation of the QT interval, increases the risk for torsades de pointes, a potentially life-threatening arrhythmia. Many perioperatively administered drugs and conditions prolong the QT interval. Despite several reports of perioperative torsades de pointes, systematic evidence regarding perioperative QT interval prolongation is limited. ⋯ Postoperative QT-interval prolongation is common. Several perioperatively administered drugs are associated with a substantial QT-interval prolongation. The exact cause and its clinical relevance are, however, unclear. Nevertheless, an association between postoperative QT prolongation and risk for torsades de pointes is likely.