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Background Postoperative cognitive decline (PCD) requires microglial activation. Voltage-gated Kv1.3 potassium channels are involved in microglial activation. We determined the role of Kv1.3 in PCD and the efficacy and safety of inhibiting Kv1.3 with phenoxyalkoxypsoralen-1 (PAP-1) in preventing PCD in a mouse model. Methods After institutional approval, we assessed whether Kv1.3-deficient mice (Kv1.3–/–) exhibited PCD, evidenced by tibial-fracture surgery-induced decline in aversive freezing behaviour, and whether PAP-1 could prevent PCD and postoperative neuroinflammation in PCD-vulnerable diet-induced obese (DIO) mice. We also evaluated whether PAP-1 altered either postoperative peripheral inflammation or tibial-fracture healing. Results Freezing behaviour was unaltered in postoperative Kv1.3–/– mice. In DIO mice, PAP-1 prevented postoperative (i) attenuation of freezing behaviour (54 [17.3]% vs 33.4 [12.7]%; P=0.03), (ii) hippocampal microglial activation by size (130 [31] pixels vs 249 [49]; P Conclusions Microglial-mediated PCD requires Kv1.3 activity, determined by genetic and pharmacological targeting approaches. Phenoxyalkoxypsoralen-1 blockade of Kv1.3 prevented surgery-induced hippocampal microglial activation and neuroinflammation in mice known to be vulnerable to PCD. Regarding perioperative safety, these beneficial effects of PAP-1 treatment occurred without impacting fracture healing. Kv1.3 blockers, currently undergoing clinical trials for other conditions, may represent an effective and safe intervention to prevent PCD.

Checklists are recognised as powerful tools to prevent avoidable errors in high-reliability organisations. In healthcare, the perioperative area has been a leading field in the development of a wide range of checklists. However, clinical literature on this subject is still sparse and heterogeneous, producing results that are sometimes conflicting. This systematic review assesses the current literature on perioperative routine and crisis checklists. Literature searches did not use a date limit and included articles up to March 2019. The methodological heterogeneity precluded combining data from the individual studies into a quantitative meta-analysis. Data are presented by means of a qualitative comparison with the reference groups based on a content analysis approach. Of the 874 identified articles, 25 were included in this review. Most identified studies (23, 92%) have shown that the use of checklists in anaesthesia can decrease human error, improve patient safety and teamwork, and increase quality of care. Beyond the WHO surgical time-out, anaesthesia-specific checklists have been shown to be useful for provider handoffs, emergencies, and routine anaesthesia procedures. However, literature on anaesthesia-specific checklists is still limited and very heterogeneous. More large-scale studies are necessary to identify an ideal anaesthesia checklist and its most appropriate implementation method.

The brain is both the orchestrator as well as the target of the innate immune system’s response to the aseptic trauma of surgery. When trauma-induced inflammation is not appropriately regulated persistent neuro-inflammation interferes with the synaptic plasticity that underlies the learning and memory aspects of cognition. The complications that ensue, include Postoperative Delirium (POD) and Postoperative Cognitive Dysfunction (POCD) at two poles of a constellation that is now termed Perioperative Neurocognitive Disorders. While the relationship of acute POD to the more indolent POCD is not completely understood both can be further complicated by earlier-onset of dementia and higher mortality. How and why these disorders occur is the focus of this report. The innate immune system response to peripheral trauma signals to the brain through a regulated cascade of cellular and molecular actors producing a teleological defense mechanism, “sickness behavior,” to curtail further injury and initiate repair. Sickness behavior, including disordered cognition, is terminated by neural and humoral pathways that restore homeostasis and launch the organism on a path to good health. With so many “moving parts” the innate immune system is vulnerable in clinical settings that include advanced age and lifestyle-induced diseases such as “unhealthy” obesity and the inevitable insulin resistance. Under these conditions inflammation may become exaggerated and long-lived. Consideration is provided how to identify the high-risk surgical patient and both pharmacological (including biological compounds) and non- pharmacological strategies to customize care.