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Prevention and treatment of traumatic brain injury-related delirium: a systematic review

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Abstract

Background

Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care.

Methods

We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies—of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting.

Results

We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome.

Conclusions

We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.

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Abbreviations

AE:

Adverse event

CAM:

Confusion assessment method

CAM-ICU:

Confusion Assessment Method for the Intensive Care Unit

CAM-ED:

Confusion Assessment Method for the Emergency Department

CENTRAL:

Cochrane Central Register of Controlled Trials

CFS:

Clinical Frailty Score

CT:

Computed tomography

DSM–5:

Diagnostic and statistical manual of mental disorders

ED:

Emergency Department

GCS:

Glasgow Coma Scale

ICP:

Increase intracranial pressure

ICU:

Intensive Care Unit

INCOG:

International team of researchers and clinicians

MVA:

Motor vehicle accident

NR:

Not reported

OT:

Occupational therapist

PTCS:

Posttraumatic confusional state

PTA:

Posttraumatic amnesia

PROSPERO:

International Prospective Register of Systematic Reviews

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

RCT:

Randomized controlled trial

RASS:

Richmond Area Sedation Scale

RoB2:

Version 2 of the Cochrane risk-of-bias tool for randomized trials tool for RCTs

ROBINS-I:

Risk Of Bias In Non-Randomized Studies-of Interventions

SWiM:

Synthesis without meta-analysis

TBI:

Traumatic brain injury

TICU:

Trauma intensive care unit

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Acknowledgements

We thank Ms. Elizabeth Uleryk, medical librarian, for reviewing our literature search strategy.

Author information

Authors and Affiliations

  1. Division of Geriatric Medicine, Department of Medicine, University of Toronto, 190 Elizabeth Street, R. Fraser Elliott Building, 3-805, Toronto, ON, M5G 2C4, Canada

    Yu Qing Huang & Jennifer Ann Watt

  2. Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 209 Victoria Street, East Building, Toronto, ON, M5B 1W8, Canada

    Yu Qing Huang & Jennifer Ann Watt

  3. Temerty Faculty of Medicine, University of Toronto, 6 Queen’s Park Crescent West, Third Floor, Toronto, ON, M5S 3H2, Canada

    Sophie Weiss & Edwin Wong

  4. Division of Neurology, Department of Medicine, University of Toronto, 6th Floor, Stroke and Neurology Clinic, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    Priti Gros & Manav V. Vyas

  5. Division of Infectious Diseases, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada

    Pierre-Philippe Piché

  6. Division of Physical Medicine and Rehabilitation, Department of Medicine, University of Toronto, Toronto, ON, M5G 2C4, Canada

    Alan Ka Ho Tam

  7. St. Michael’s Hospital, 36 Queen St East, Toronto, ON, M5B 1W8, Canada

    Jennifer Ann Watt

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Contributions

YQH: conceptualization, methodology, validation, formal analysis, writing—original draft preparation. SW: validation, formal analysis, writing—review and editing. PG: validation, formal analysis. EW: validation. P-PP: methodology, writing—review and editing. MVV: methodology, supervision, writing—review and editing, AKHT: writing—review and editing. JAW: methodology, supervision, writing—review and editing.

Corresponding author

Correspondence to Jennifer Ann Watt.

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Conflicts of interest

All authors have no conflict of interest to declare. This paper was presented at the Canadian Geriatrics Society 41st Annual Scientific Meeting on April 16, 2023.

Financial disclosure statement

This study did not receive any funding. YQH is supported by funding from the Ministry of Health—Clinician Investigator Program at University of Toronto and the Margaret Watson Award from Department of Geriatric Medicine, University of Toronto.

Ethical standard statement

Ethical approval was not required because this study retrieved and synthesized data from published studies.

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Huang, Y.Q., Weiss, S., Gros, P. et al. Prevention and treatment of traumatic brain injury-related delirium: a systematic review. J Neurol 270, 5966–5987 (2023). https://doi.org/10.1007/s00415-023-11889-7

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