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Several reasons why ketamine as a neuroplastic agent may have failed to prevent postoperative delirium: Implications for future protocols

J. Horacek, R. Janda, N. Görnerova, L. Jajcay, V. Andrashko

. 2023 ; 798 (-) : 137095. [pub] 20230121

Language English Country Ireland

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc23004086

Ketamine exerts anti-inflammatory, neuroprotective and neuroplastic activity, therefore it may counteract the neurotoxic processes underlying postoperative delirium. However, the majority of studies in this field failed. We identified several pharmacological reasons why these studies may have failed, together with suggestions of how to remediate them. Among them, the interaction with intravenous general anesthetics exerting the opposite effect on GABA interneurons than ketamine may be of principal importance. We suggest biomarkers which may elucidate the influence of this interaction on the different steps of neuroplastic pathways. We hypothesize that administering ketamine before or after general anesthesia could both prevent the interactions and strengthen the effect of ketamine by timing surgery within the climax of ketamine-induced neuroplastic changes or by stabilizing AMPA receptors. It is vital to deal with these questions because the protocols of ongoing studies are based again on the administration of ketamine during general anesthesia (the major identified pitfall).

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$a Ketamine exerts anti-inflammatory, neuroprotective and neuroplastic activity, therefore it may counteract the neurotoxic processes underlying postoperative delirium. However, the majority of studies in this field failed. We identified several pharmacological reasons why these studies may have failed, together with suggestions of how to remediate them. Among them, the interaction with intravenous general anesthetics exerting the opposite effect on GABA interneurons than ketamine may be of principal importance. We suggest biomarkers which may elucidate the influence of this interaction on the different steps of neuroplastic pathways. We hypothesize that administering ketamine before or after general anesthesia could both prevent the interactions and strengthen the effect of ketamine by timing surgery within the climax of ketamine-induced neuroplastic changes or by stabilizing AMPA receptors. It is vital to deal with these questions because the protocols of ongoing studies are based again on the administration of ketamine during general anesthesia (the major identified pitfall).
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$a Görnerova, Natalie $u National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Jajcay, Lucia $u National Institute of Mental Health, Klecany, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic
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