Anesthesiology
-
Subanesthetic doses of (R,S)-ketamine are used in the treatment of neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)-ketamine are associated with increased activity and function of mammalian target of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the contribution of its metabolites to increased mTOR signaling is unknown. ⋯ The data demonstrate that (R,S)-norketamine and (2S,6S)-hydroxynorketamine have potent pharmacological activity both in vitro and in vivo and contribute to the molecular effects produced by subanesthetic doses of (R,S)-ketamine. The results suggest that the determination of the mechanisms underlying the antidepressant and analgesic effects of (R,S)-ketamine requires a full study of the parent compound and its metabolites.
-
Editorial Comment
Untangling the triple low: causal inference in anesthesia research.
-
Observational Study
Lysis Onset Time as Diagnostic Rotational Thromboelastometry Parameter for Fast Detection of Hyperfibrinolysis.
Rotational thromboelastometry is increasingly used to detect hyperfibrinolysis, which is a predictor of unfavorable outcome in patients with coagulation disturbances. In an in vitro study, the authors investigated which thromboelastometric hemostatic parameters could be valuable for fast diagnosis of the severity of hyperfibrinolysis and confirmed their findings in a patient population with hyperfibrinolysis. ⋯ This study shows that the LOT may be used for fast detection of severe hyperfibrinolysis, with a better resolution than the maximum lysis, and should be further evaluated for optimization of therapeutic strategies in patients with severe clot breakdown.