A Systematic Review and Meta-Analysis of Hypothermia in Experimental Traumatic Brain Injury: Why Have Promising Animal Studies Not Been Replicated in Pragmatic Clinical Trials?
J Neurotrauma
; 37(19): 2057-2068, 2020 10 01.
Article
in English
| MEDLINE | ID: covidwho-245006
ABSTRACT
Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long-term functional outcome is neutral or negative, despite apparently promising pre-clinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects, and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multi-variate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity, and blinded outcome assessment appeared to predict neurobehavioral outcome on multi-variate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The pre-clinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting pre-clinical TBI studies in the future.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Brain Injuries, Traumatic
/
Hypothermia, Induced
Type of study:
Diagnostic study
/
Prognostic study
/
Randomized controlled trials
/
Reviews
/
Systematic review/Meta Analysis
Topics:
Long Covid
Limits:
Animals
/
Humans
Language:
English
Journal:
J Neurotrauma
Journal subject:
Neurology
/
Traumatology
Year:
2020
Document Type:
Article
Affiliation country:
Neu.2019.6923
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