Prehabilitation for Prevention of Postoperative Cognitive Dysfunction?

Anesthesiology, V 123 • No 1 7 July 2015 S URGERY sets the old brain on fire and prehabilitation is a fire retardant. That is conclusion of an interesting study by Kawano et al.1 in this issue of AnEsthEsioloGY. specifically, they hypothesized that the old brain is more vulnerable than a young one to surgery-induced neuroinflammation because its innate immune cells, principally microglia, develop an exaggerated inflammatory response to a peripheral surgical procedure. Furthermore, in a novel twist, Kawano et al.1 theorized that preoperative environmental enrichment (PEE) consisting of both physical and cognitive activity would attenuate the neuroinflammation and prevent postoperative cognitive impairment. They tested these hypotheses by exposing young adult and old rats to brief abdominal surgery under isoflurane anesthesia with or without a 2-week period of PEE, while age-matched controls were housed under standard laboratory conditions. They discovered that reference memory was impaired, and hippocampal concentrations of the cytokines tumor necrosis factor-α and interleukin-1β were increased 7 days after surgery in old sedentary but not young adult rats and that PEE negated both the neuroinflammation and memory impairment in the old animals. Moreover, they found that microglia from the hippocampus of PEE-exposed rats had markedly lower lipopolysaccharidestimulated cytokine release in vitro compared with those from sedentary cage controls. hence, Kawano et al.1 provide evidence that prehabilitation might prevent surgery-induced cognitive impairment in old subjects and identify a cellular mechanism by which it could occur. neuroinflammation is a credible candidate mechanism for postoperative cognitive dysfunction (PoCD). surgery causes tissue injury, release into the circulation of damage-associated and proinflammatory molecules which, by stimulating vagal cholinergic afferents or directly entering the central nervous system (Cns), activate astrocytes and microglia to release a host of proinflammatory mediators.2–6 Many of these mediators disturb neuronal function and, if concentrations become high enough and last long enough, can kill neurons. it is no surprise then that an inflamed, smoldering brain does not work well. in fact, neuroinflammation is implicated in the pathogenesis of a wide array of acute (e.g., delirium) and chronic cognitive impairments (e.g., dementia).7,8 Thus, it is an attractive theory for PoCD—the brain fog of which patients complain after surgery. This cascade of surgery, neuroinflammation, and cognitive impairment has been studied previously but often using young animals and short-term outcomes.3,4 What makes the study by Kawano et al.1 relevant is that they used an aged animal model, looked at cognitive and biochemical outcomes a week postoperatively, and investigated a natural nonpharmacologic potential remedy. These are not trivial considerations because longlasting postoperative cognitive debility is mainly an affliction of the old. Furthermore, the immune system becomes dysregulated with age; Cns responses are either hypoactive or hyperactive (i.e., primed) and resolution of inflammation is impaired.9,10 inasmuch as a coordinated neuroimmune, response is thought to be beneficial and promote recovery, whereas an exaggerated, uncoordinated response is deleterious, and it is easy to see how older age might predispose to greater vulnerability to and slower recovery from surgeryinduced cognitive impairment. like others,5,6 Kawano et al.1 found this to be the case. in fact, they identified no change in hippocampal cytokines or behavioral performance in the Prehabilitation for Prevention of Postoperative Cognitive Dysfunction?