Insulin signaling in the central nervous system, a possible pathophysiological mechanism of anesthesia-induced delayed neurocognitive recovery/postoperative neurocognitive disorder: a narrative review

Introduction: Impairment in neurocognitive functions ranges between delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorders (pNCD). Incidence varies from 11% after noncardiac surgery to 60% after cardiac surgery. Areas covered: Insulin receptors (IRs) signaling pathway in the central nervous system (CNS) could be a possible pathophysiological mechanism of anesthesia-induced DNR/pNCD and perioperative intranasal insulin administration could be a preventive approach. This hypothesis is supported by the following evidence: effects of IRs-CNS signaling pathway on neuromodulation; higher incidence of DNR/pNCD in patients with insulin resistance; neurotoxicity of IRs signaling pathways after anesthetic exposure; improvement of neurocognitive impairment after insulin exposure. This narrative review was conducted after a literature search of PubMed, EMBASE and SCOPUS online medical data performed in May 2022. Expert opinion: Perioperative intranasal insulin is shown to be protective and future studies should address: the role of insulin as a neuromodulator; its integration into neuroprotection approaches; patient populations that might benefit from this approach; a well-defined protocol of intranasal insulin administration in a perioperative background and other disciplines; and possible collateral effects.