Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.
Journal
Circulation
Journal Volume
150
Journal Issue
7
Start Page
e158
End Page
e180
ISSN
1524-4539
Date Issued
2024-06-27
Author(s)
Perkins, Gavin D
Neumar, Robert
Hsu, Cindy H
Hirsch, Karen G
Aneman, Anders
Becker, Lance B
Couper, Keith
Callaway, Clifton W
Hoedemaekers, Cornelia W E
Lim, Shir Lynn
Meurer, William
Olasveengen, Theresa
Sekhon, Mypinder S
Skrifvars, Markus
Soar, Jasmeet
Vengamma, Bhuma
Nolan, Jerry P
DOI
10.1161/CIR.0000000000001219
Abstract
This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.
Subjects
AHA Scientific Statements
acute brain injuries
cardiopulmonary resuscitation
post-cardiac arrest syndrome
rehabilitation
resuscitation
SDGs
Publisher
Lippincott Williams and Wilkins
Type
review