Meta-Analysis

. 2017 Dec;266(6):952-961.

doi: 10.1097/SLA.0000000000002286.

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline

Aziz S Alali¹, Kaushik Mukherjee, Victoria A McCredie, Eyal Golan, Prakesh S Shah, James M Bardes, Susan E Hamblin, Elliott R Haut, James C Jackson, Kosar Khwaja, Nimitt J Patel, Satish R Raj, Laura D Wilson, Avery B Nathens, Mayur B Patel

Affiliations

Affiliation

¹ *Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada †Division of Acute Care Surgery, Department of Surgery, Loma Linda University Medical Center, Loma Linda, CA ‡Eastern Association for the Surgery of Trauma, Chicago, IL §Department of Critical Care, University Health Network, Toronto, ON, Canada ¶Division of Critical Care and Department of Medicine, Mackenzie Health, Toronto, ON, Canada ||Department of Pediatrics, University of Toronto, Toronto, ON, Canada **Department of Surgery, West Virginia University, Morgantown, WV ††Department of Surgery, USC+LAC, Los Angeles, CA ‡‡Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN §§Departments of Surgery, Anesthesiology/Critical Care Medicine, and Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD ¶¶Division of Pulmonary and Critical Care Medicine and Center for Health Services Research, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN ||||Research Service, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN ***Departments of Surgery and Critical Care Medicine, McGill University Health Centre, Montreal, QC, Canada †††Division of Trauma, Critical Care, and Burns, Department of Surgery, MetroHealth Medical Center, Cleveland, OH ‡‡‡Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, AL, Canada §§§Department of Communication Sciences and Disorders, Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK ¶¶¶Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, Nashville, TN ||||||Department of Surgery, University of Toronto, Toronto, ON, Canada ****Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada ††††Division of Trauma, Emergency General Surgery, and Surgical Critical Care, Departments of Surgery, Neurosurgery, and Hearing and Speech Sciences, Section of Surgical Sciences, Vanderbilt Brain Institute, Vanderbilt Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN ‡‡‡‡Surgical Service, General Surgery Section, Nashville VA Medical Center, Tennessee Valley Healthcare System, US Department of Veterans Affairs, Nashville, TN.

PMID: 28525411
PMCID: PMC5997270
DOI: 10.1097/SLA.0000000000002286

Meta-Analysis

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline

Aziz S Alali et al. Ann Surg. 2017 Dec.

. 2017 Dec;266(6):952-961.

doi: 10.1097/SLA.0000000000002286.

Authors

Affiliation

¹ *Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada †Division of Acute Care Surgery, Department of Surgery, Loma Linda University Medical Center, Loma Linda, CA ‡Eastern Association for the Surgery of Trauma, Chicago, IL §Department of Critical Care, University Health Network, Toronto, ON, Canada ¶Division of Critical Care and Department of Medicine, Mackenzie Health, Toronto, ON, Canada ||Department of Pediatrics, University of Toronto, Toronto, ON, Canada **Department of Surgery, West Virginia University, Morgantown, WV ††Department of Surgery, USC+LAC, Los Angeles, CA ‡‡Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN §§Departments of Surgery, Anesthesiology/Critical Care Medicine, and Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD ¶¶Division of Pulmonary and Critical Care Medicine and Center for Health Services Research, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN ||||Research Service, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN ***Departments of Surgery and Critical Care Medicine, McGill University Health Centre, Montreal, QC, Canada †††Division of Trauma, Critical Care, and Burns, Department of Surgery, MetroHealth Medical Center, Cleveland, OH ‡‡‡Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, AL, Canada §§§Department of Communication Sciences and Disorders, Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK ¶¶¶Department of Hearing and Speech Sciences, Vanderbilt University School of Medicine, Nashville, TN ||||||Department of Surgery, University of Toronto, Toronto, ON, Canada ****Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada ††††Division of Trauma, Emergency General Surgery, and Surgical Critical Care, Departments of Surgery, Neurosurgery, and Hearing and Speech Sciences, Section of Surgical Sciences, Vanderbilt Brain Institute, Vanderbilt Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN ‡‡‡‡Surgical Service, General Surgery Section, Nashville VA Medical Center, Tennessee Valley Healthcare System, US Department of Veterans Affairs, Nashville, TN.

PMID: 28525411
PMCID: PMC5997270
DOI: 10.1097/SLA.0000000000002286

Abstract

Objective: To determine if beta-(β)-blockers improve outcomes after acute traumatic brain injury (TBI).

Background: There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with β-blockers offers a potentially beneficial approach.

Methods: Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was β-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I).

Results: Data were extracted from 9 included studies encompassing 2005 unique TBI patients with β-blocker treatment and 6240 unique controls. Exposure to β-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified.

Conclusions: In adults with acute TBI, observational studies reveal a significant mortality advantage with β-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital β-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after β-blocker use for TBI.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST WITH OTHER SOURCES OF SUPPORT:

Dr. Patel has been or is supported by the Vanderbilt Institute for Clinical and Translational Research awards (VR1584, VR5351, VR9276, VR12073) via CTSA grant UL1TR000011 (NCRR/NCATS/NIH), a 2013 EAST Trauma Foundation Research Scholarship, and speaker fees from Pfizer. Drs. Haut and Patel have served on the EAST Guidelines Section and Board of Directors. Dr. Haut is the primary investigator of a AHRQ grant (R01HS024547) of a PCORI contract (CE-12–11–4489). Dr. Haut receives book royalties from Lippincott, Williams, Wilkins (“Avoiding Common ICU Errors”), consultant and speaker fees from VHA/Vizient IMPERATIV® Advantage Performance Improvement Collaborative, and consultant and speaker fees for the Illinois Surgical Quality Improvement Collaborative. Dr. Haut was the paid author of a paper commissioned by the National Academies of Medicine.

Figures

**Figure 1**
PRISMA flow diagram for systematic review phases of Beta-Blockers after traumatic brain injury

**Figure 2**
Forest plot of Beta-blocker exposure after acute traumatic brain injury versus no exposure with in-hospital mortality outcome

**Figure 3**
Practice management guideline for Beta-Blockers after traumatic brain injury *Provided that common ICU complications of hypotension (i.e., usually defined as systolic blood pressure<90mmHg) and symptomatic bradycardia (is, usually defined as heart rate<50 with symptoms) are avoided

See this image and copyright information in PMC

References

1. Menon DK, Zahed C. Prediction of outcome in severe traumatic brain injury. Current Opinion in Critical Care. 2009 Oct;15(5):437–41. - PubMed
1. Heffernan DS, Inaba K, Arbabi S, Cotton BA. Sympathetic Hyperactivity After Traumatic Brain Injury and the Role of Beta-Blocker Therapy. The Journal of Trauma: Injury, Infection, and Critical Care. 2010 Dec;69(6):1602–9. - PubMed
1. Tran TY, Dunne IE, German JW. Beta blockers exposure and traumatic brain injury: a literature review. Neurosurgical Focus. 2008 Oct;25(4):E8. - PubMed
1. Ley EJ, Berry C, Mirocha J, Salim A. Mortality is Reduced for Heart Rate 80 to 89 After Traumatic Brain Injury. Journal of Surgical Research. 2010 Sep;163(1):142–5. - PubMed
1. Radosevich JJ, Patanwala AE, Erstad BL. Emerging pharmacological agents to improve survival from traumatic brain injury. Brain Inj. 2013 Nov 11;27(13–14):1492–9. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline

Affiliation

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline

Authors

Affiliation

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources