Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury
Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. β-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI.
Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI.
A retrospective cohort study of patients age ≥ 40 years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome.
Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05).
Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.
KeywordsAngiotensin-converting enzyme inhibitor β-Blockers Isolated Mortality Traumatic brain injury
Angiotensin-converting enzyme inhibitor
Abbreviated Injury Scale
Glasgow Coma Scale
Injury Severity Score
Systolic blood pressure
Traumatic brain injury
The authors thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation.
JSC performed data collection or management, data analysis, protocol/project development, and manuscript writing/editing. AJC contributed to protocol/project development and manuscript writing/editing. MD, JMA, JG, SB, CDM, and ACW performed manuscript writing/editing. LPH was involved in data collection or management. ML was involved in data analysis. JMZ performed manuscript writing/editing/approval. DRF performed protocol/project development and manuscript writing/editing. The authors confirm that authorship requirements have been met and the final manuscript was approved by all authors.
Source of Support
There was no support for this work.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was waived on IRB approval and was not obtained because of the retrospective nature of the study with minimal risk to patients.
- 1.Ma VY, Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil. 2014;95(5):986–95.CrossRefGoogle Scholar
- 2.Coronado VG, Xu L, Basavaraju SV, McGuire LC, Wald MM, Faul MD, et al. Surveillance for traumatic brain injury-related deaths–United States, 1997–2007. MMWR Surveill Summ. 2011;60(5):1–32.Google Scholar
- 6.Coronado VG, Xu L, Basavaraju SV, et al. Surveillance for traumatic brain injury-related deaths—United States, 1997–2007. MMWR Surveill Summ. 2011;60(5):1–32.Google Scholar
- 9.McIntosh TK, Smith DH, Meaney DF, et al. Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Investig. 1996;74(2):315–42.Google Scholar
- 10.Albert-Weissenberger C, Mencl S, Hopp S, Kleinschnitz C, Sirén AL. Role of the kallikrein–kinin system in traumatic brain injury. Front Cell Neurosci. 2014;8:345.Google Scholar
- 18.Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery: an analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort. Anesthesiology. 2017;126(1):16–27.CrossRefGoogle Scholar
- 32.Mosenthal AC, Lavery RF, Addis M, et al. Isolated traumatic brain injury: age is an independent predictor of mortality and early outcome. J Trauma. 2002;52(5):907–11.Google Scholar
- 37.Palmer C. Major trauma and the injury severity score—where should we set the bar? Annu Proc Assoc Adv Automot Med. 2007;51:13–29.Google Scholar