Sevoflurane dose and postoperative delirium: a prospective cohort analysis

Jennifer Taylor; Thomas Payne; Cameron Casey; David Kunkel; Maggie Parker; Cameron Rivera; Henrik Zetterberg; Kaj Blennow; Robert A Pearce; Richard C Lennertz; Tim McCulloch; Amy Gaskell; Robert D Sanders

doi:10.1016/j.bja.2022.08.022

Sevoflurane dose and postoperative delirium: a prospective cohort analysis

Br J Anaesth. 2023 Feb;130(2):e289-e297. doi: 10.1016/j.bja.2022.08.022. Epub 2022 Oct 1.

Authors

Affiliations

¹ Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia.
² Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵ Department of Anaesthetics, Waikato Hospital, Hamilton, New Zealand.
⁶ Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia; Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia. Electronic address: robert.sanders@sydney.edu.au.

Abstract

Background: Recent trials are conflicting as to whether titration of anaesthetic dose using electroencephalography monitoring reduces postoperative delirium. Titration to anaesthetic dose itself might yield clearer conclusions. We analysed our observational cohort to clarify both dose ranges for trials of anaesthetic dose and biological plausibility of anaesthetic dose influencing delirium.

Methods: We analysed the use of sevoflurane in an ongoing prospective cohort of non-intracranial surgery. Of 167 participants, 118 received sevoflurane and were aged >65 yr. We tested associations between age-adjusted median sevoflurane (AMS) minimum alveolar concentration fraction or area under the sevoflurane time×dose curve (AUC-S) and delirium severity (Delirium Rating Scale-98). Delirium incidence was measured with 3-minute Diagnostic Confusion Assessment Method (3D-CAM) or CAM-ICU. Associations with previously identified delirium biomarkers (interleukin-8, neurofilament light, total tau, or S100B) were tested.

Results: Delirium severity did not correlate with AMS (Spearman's ρ=-0.014, P=0.89) or AUC-S (ρ=0.093, P=0.35), nor did delirium incidence (AMS Wilcoxon P=0.86, AUC-S P=0.78). Further sensitivity analyses including propofol dose also demonstrated no relationship. Linear regression confirmed no association for AMS in unadjusted (log (IRR)=-0.06 P=0.645) or adjusted models (log (IRR)=-0.0454, P=0.735). No association was observed for AUC-S in unadjusted (log (IRR)=0.00, P=0.054) or adjusted models (log (IRR)=0.00, P=0.832). No association of anaesthetic dose with delirium biomarkers was identified (P>0.05).

Conclusion: Sevoflurane dose was not associated with delirium severity or incidence. Other biological mechanisms of delirium, such as inflammation and neuronal injury, appear more plausible than dose of sevoflurane.

Clinical trial registration: NCT03124303, NCT01980511.

Keywords: anaesthesia; biomarker; cognitive dysfunction; delirium; dose dependency; postoperative; sevoflurane; surgery.

MeSH terms

Anesthetics, Inhalation* / adverse effects
Cohort Studies
Emergence Delirium* / epidemiology
Humans
Prospective Studies
Sevoflurane / adverse effects

Substances

Sevoflurane
Anesthetics, Inhalation

Associated data

ClinicalTrials.gov/NCT01980511
ClinicalTrials.gov/NCT03124303

Grants and funding

R01 AG063849/AG/NIA NIH HHS/United States