Precision‐based approaches to delirium in critical illness: a narrative review
Precision‐based approaches to delirium in critical illness: a narrative review
Delirium occurs in critical illness and is associated with poor clinical outcomes, having a longstanding impact on survivors. Understanding the complexity of delirium in critical illness and its deleterious outcome has expanded since early reports. Delirium is a culmination of predisposing and precipitating risk factors that result in a transition to delirium. Known risks range from advanced age, frailty, medication exposure or withdrawal, sedation depth, and sepsis. Because of its multifactorial nature, different clinical phenotypes, and potential neurobiological causes, a precise approach to reducing delirium in critical illness requires a broad understanding of its complexity. Refinement in the categorization of delirium subtypes or phenotypes (i.e., psychomotor classifications) requires attention. Recent advances in the association of clinical phenotypes with clinical outcomes expand our understanding and highlight potentially modifiable targets. Several delirium biomarkers in critical care have been examined, with disrupted functional connectivity being precise in detecting delirium. Recent advances reinforce delirium as an acute, and partially modifiable, brain dysfunction, and place emphasis on the importance of mechanistic pathways including cholinergic activity and glucose metabolism. Pharmacologic agents have been assessed in randomized controlled prevention and treatment trials, with a disappointing lack of efficacy. Antipsychotics remain widely used after “negative” trials, yet may have a role in specific subtypes. However, antipsychotics do not appear to improve clinical outcomes. Alpha-2 agonists perhaps hold greater potential for current use and future investigation. The role of thiamine appears promising, yet requires evidence. Looking forward, clinical pharmacists should prioritize the mitigation of predisposing and precipitating risk factors as able. Future research is needed within individual delirium psychomotor subtypes and clinical phenotypes to identify modifiable targets that hold the potential to improve not only delirium duration and severity, but long-term outcomes including cognitive impairment.
biomarkers, critical care, critical illness, delirium, intensive care units, phenotypes, precision medicine
1139-1153
Ankravs, Melissa J.
e0af994c-661a-47ef-98b0-8adc0a61306d
McKenzie, Cathrine A.
ec344dee-5777-49c5-970e-6326e82c9f8c
Kenes, Michael T.
486e82f8-4e53-4236-b9cd-c8d4b0677955
November 2023
Ankravs, Melissa J.
e0af994c-661a-47ef-98b0-8adc0a61306d
McKenzie, Cathrine A.
ec344dee-5777-49c5-970e-6326e82c9f8c
Kenes, Michael T.
486e82f8-4e53-4236-b9cd-c8d4b0677955
Ankravs, Melissa J., McKenzie, Cathrine A. and Kenes, Michael T.
(2023)
Precision‐based approaches to delirium in critical illness: a narrative review.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 43 (11), .
(doi:10.1002/phar.2807).
Abstract
Delirium occurs in critical illness and is associated with poor clinical outcomes, having a longstanding impact on survivors. Understanding the complexity of delirium in critical illness and its deleterious outcome has expanded since early reports. Delirium is a culmination of predisposing and precipitating risk factors that result in a transition to delirium. Known risks range from advanced age, frailty, medication exposure or withdrawal, sedation depth, and sepsis. Because of its multifactorial nature, different clinical phenotypes, and potential neurobiological causes, a precise approach to reducing delirium in critical illness requires a broad understanding of its complexity. Refinement in the categorization of delirium subtypes or phenotypes (i.e., psychomotor classifications) requires attention. Recent advances in the association of clinical phenotypes with clinical outcomes expand our understanding and highlight potentially modifiable targets. Several delirium biomarkers in critical care have been examined, with disrupted functional connectivity being precise in detecting delirium. Recent advances reinforce delirium as an acute, and partially modifiable, brain dysfunction, and place emphasis on the importance of mechanistic pathways including cholinergic activity and glucose metabolism. Pharmacologic agents have been assessed in randomized controlled prevention and treatment trials, with a disappointing lack of efficacy. Antipsychotics remain widely used after “negative” trials, yet may have a role in specific subtypes. However, antipsychotics do not appear to improve clinical outcomes. Alpha-2 agonists perhaps hold greater potential for current use and future investigation. The role of thiamine appears promising, yet requires evidence. Looking forward, clinical pharmacists should prioritize the mitigation of predisposing and precipitating risk factors as able. Future research is needed within individual delirium psychomotor subtypes and clinical phenotypes to identify modifiable targets that hold the potential to improve not only delirium duration and severity, but long-term outcomes including cognitive impairment.
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Accepted/In Press date: 21 March 2023
e-pub ahead of print date: 3 May 2023
Published date: November 2023
Additional Information:
Funding Information:
M.J.A. and M.T.K report no conflicts of interest. C.A.M. reports receiving an honorarium for her work as editor‐in‐chief for Critical Illness ( www.medicinescomplete.com ) published by the Pharmaceutical Press (London). C.A.M also receives funding from the National Institute for Health and Care Research Applied Research Collaborative, Wessex. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care.
Publisher Copyright:
© 2023 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.
Keywords:
biomarkers, critical care, critical illness, delirium, intensive care units, phenotypes, precision medicine
Identifiers
Local EPrints ID: 477160
URI: http://eprints.soton.ac.uk/id/eprint/477160
PURE UUID: b6ce38a9-c247-4d8c-87d9-8553cc3bb1f9
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Date deposited: 30 May 2023 16:48
Last modified: 17 Mar 2024 04:23
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Contributors
Author:
Melissa J. Ankravs
Author:
Cathrine A. McKenzie
Author:
Michael T. Kenes
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