Patterns of Hysteresis Between Induction and Emergence of Neuroanesthesia are Present in Spinal and Intracranial Surgeries

Background: Recovery of consciousness is usually seen as a passive process, with emergence from anesthesia depicted as the inverse process of induction resulting from the elimination of anesthetic drugs from their central nervous system sites of action. However, that need not be the case. Recently it has been argued that we might encounter hysteresis to changes in the state of consciousness, known as neural inertia. This phenomenon has been debated in neuroanesthesia, as manipulation of the brain might further influence recovery of consciousness. The present study is aimed at assessing hysteresis between induction and emergence under propofol-opioid neuroanesthesia in humans using estimated propofol concentrations in both spinal and intracranial surgeries. Methods: We identified the moments of loss (LOR) and recovery of responsiveness (ROR) in 21 craniotomies and 25 spinal surgeries. Propofol was given slowly until loss of responsiveness and stopped at the end of surgery. An opioid was present at induction and recovery. Propofol infused was recorded and plasma and effect-site concentrations were estimated using 2 pharmacokinetic models. Dose-response curves were generated. Estimated propofol plasma and effect-site concentrations were compared to assess hysteresis. Results: Estimated propofol concentrations at LOR and ROR showed hysteresis. Whether for spinal or intracranial surgeries, the EC50 of propofol at which half of the patients entered and exited the state of responsiveness was significantly different. Conclusions: Hysteresis was observed between propofol concentrations at LOR and ROR, in both patients presenting for spinal and intracranial surgeries. Manipulation of the brain does not appear to change patterns of hysteresis, suggesting that neural inertia may occur in humans, in a way similar to that found in animal species. These findings justify performing a clinical study in patients using measured propofol concentrations to assess neural inertia. Supported by the Fundação para a Ciência e Tecnologia with the reference projects SFRH/BD/98915/2013 and UID/SEM/50022/2013. The authors have no conflicts of interest to disclose. Address correspondence to: Ana Leitão Ferreira, MSc, MS, Center of Clinical Investigation in Anesthesiology, Service of Anesthesiology, Hospital Center of Porto, Largo Professor Abel Salazar, 4099-001 Porto, Portugal (e-mail: ana.leitao.ferreira@gmail.com). Received April 12, 2018 Accepted September 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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