title: Metoprolol improves survival in severe traumatic brain injury independent of heart rate control.
abstract: BACKGROUND
  Multiple prior studies have suggested an association between survival and beta-blocker administration in patients with severe traumatic brain injury (TBI). However, it is unknown whether this benefit of beta-blockers is dependent on heart rate control. The aim of this study was to assess whether rate control affects survival in patients receiving metoprolol with severe TBI. Our hypothesis was that improved survival from beta-blockade would be associated with a reduction in heart rate.
  
  
  METHODS
  We performed a 7-y retrospective analysis of all blunt TBI patients at a level-1 trauma center. Patients aged >16 y with head abbreviated injury scale 4 or 5, admitted to the intensive care unit (ICU) from the operating room or emergency room (ER), were included. Patients were stratified into two groups: metoprolol and no beta-blockers. Using propensity score matching, we matched the patients in two groups in a 1:1 ratio controlling for age, gender, race, admission vital signs, Glasgow coma scale, injury severity score, mean heart rate monitored during ICU admission, and standard deviation of heart rate during the ICU admission. Our primary outcome measure was mortality.
  
  
  RESULTS
  A total of 914 patients met our inclusion criteria, of whom 189 received beta-blockers. A propensity-matched cohort of 356 patients (178: metoprolol and 178: no beta-blockers) was created. Patients receiving metoprolol had higher survival than those patients who did not receive beta-blockers (78% versus 68%; P = 0.04); however, there was no difference in the mean heart rate (89.9 ± 13.9 versus 89.9 ± 15; P = 0.99). Nor was there a difference in the mean of standard deviation of the heart rates (14.7 ± 6.3 versus 14.4 ± 6.5; P = 0.65) between the two groups. In Kaplan-Meier survival analysis, patients who received metoprolol had a survival advantage (P = 0.011) compared with patients who did not receive any beta-blockers.
  
  
  CONCLUSIONS
  Our study shows an association with improved survival in patients with severe TBI receiving metoprolol, and this effect appears to be independent of any reduction in heart rate. We suggest that beta-blockers should be administered to all severe TBI patients irregardless of any perceived beta-blockade effect on heart rate.
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Bardiya
authors.initials: B
authors.lastname: Zangbar
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Khalil
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Peter
authors.initials: P
authors.lastname: Rhee
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Bellal
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Narong
authors.initials: N
authors.lastname: Kulvatunyou
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tang
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Friese
authors.affiliation: Division of Trauma, Critical Care, Burn and Emergency Surgery, Department of Surgery, University of Arizona, Tucson, Arizona. Electronic address: tokeeffe@surgery.arizona.edu.
authors.forename: Terence
authors.initials: T
authors.lastname: O'Keeffe
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D015600:Glasgow Coma Scale; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D057216:Propensity Score; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol
keywords: Beta-blockers; Heart rate control; Metoprolol; Propensity score matching; Traumatic brain injury