Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress.

Recent interest in the antidepressant and anti-stress effects of subanesthetic doses of ketamine, an NMDA receptor antagonist, has identified mechanisms whereby ketamine reverses the effect of stress, but little is known regarding the prophylactic effect ketamine might have on future stressors. Here we investigate the prophylactic effect of ketamine against neurochemical and behavioral changes that follow inescapable, uncontrollable tail shocks (ISs) in Sprague Dawley rats. IS induces increased anxiety, which is dependent on activation of serotonergic (5-HT) dorsal raphe nucleus (DRN) neurons that project to the basolateral amygdala (BLA). Ketamine (10 mg/kg, i.p.) administered 2 h, 1 week, or 2 weeks before IS prevented the increased extracellular levels of 5-HT in the BLA typically produced by IS. In addition, ketamine administered at these time points blocked the decreased juvenile social investigation produced by IS. Microinjection of ketamine into the prelimbic (PL) region of the medial prefrontal cortex duplicated the effects of systemic ketamine, and, conversely, systemic ketamine effects were prevented by pharmacological inhibition of the PL. Although IS does not activate DRN-projecting neurons from the PL, IS did so after ketamine, suggesting that the prophylactic effect of ketamine is a result of altered functioning of this projection. SIGNIFICANCE STATEMENT: The reported data show that systemic ketamine, given up to 2 weeks before a stressor, blunts behavioral and neurochemical effects of the stressor. The study also advances understanding of the mechanisms involved and suggests that ketamine acts at the prelimbic cortex to sensitize neurons that project to and inhibit the DRN.

Incidence of Postoperative Cognitive Dysfunction Following Inhalational vs Total Intravenous General Anesthesia: A Systematic Review and Meta-Analysis.

Postoperative cognitive dysfunction (POCD) has been increasingly recognized as a contributor to postoperative complications. A consensus-working group recommended that POCD should be distinguished between delayed cognitive recovery, ie, evaluations up to 30 days postoperative, and neurocognitive disorder, ie, assessments performed between 30 days and 12 months after surgery. Additionally, the choice of the anesthetic, either inhalational or total intravenous anesthesia (TIVA) and its effect on the incidence of POCD, has become a focus of research. Our primary objective was to search the literature and conduct a meta-analysis to verify whether the choice of general anesthesia may impact the incidence of POCD in the first 30 days postoperatively. As a secondary objective, a systematic review of the literature was conducted to estimate the effects of the anesthetic on POCD between 30 days and 12 months postoperative. For the primary objective, an initial review of 1913 articles yielded ten studies with a total of 3390 individuals. For the secondary objective, four studies with a total of 480 patients were selected. In the first 30 days postoperative, the odds-ratio for POCD in TIVA group was 0.46 (95% CI = 0.26-0.81; p = 0.01), compared to the inhalational group. TIVA was associated with a lower incidence of POCD in the first 30 days postoperatively. Regarding the secondary objective, due to the small number of selected articles and its high heterogeneity, a metanalysis was not conducted. Given the heterogeneity of criteria for POCD, future prospective studies with more robust designs should be performed to fully address this question.