Clinical science
Beta-blocker exposure in the absence of significant head injuries is associated with reduced mortality in critically ill patients

https://doi.org/10.1016/j.amjsurg.2012.02.007Get rights and content

Abstract

Background

The effect of β-blockade in trauma patients without significant head injuries is unknown. The purpose of this investigation was to determine the impact of β-blocker exposure on mortality in critically injured trauma patients who did not sustain significant head injuries.

Methods

Critically ill trauma patients (Injury Severity Score ≥ 25) admitted to the surgical intensive care unit from January 2000 to December 2008 without severe traumatic brain injuries (head Abbreviated Injury Score ≥ 3) were included in this retrospective review. Patients who received β-blockers within 30 days of intensive care unit admission were compared with those who did not. The primary outcome measure evaluated was in-hospital mortality.

Results

During the 9-year study period, 663 critically injured patients (Injury Severity Score ≥ 25) were admitted to the intensive care unit. Of these, 98 patients (14.8%) received β-blockers. Patients exposed to β-blockers had significantly lower in-hospital mortality (11.2% vs 19.3%, P = .006). Stepwise logistic regression identified β-blocker use as an independent protective factor for mortality (adjusted odds ratio, .37; P = .007) in critically injured patients.

Conclusions

Beta-blocker exposure was associated with reduced mortality in critically injured patients without head injuries. Prospective validation of this finding is warranted.

Section snippets

Methods

After approval by the institutional review board, we retrospectively reviewed all trauma patients admitted to the Los Angeles County + University of Southern California Medical Center surgical intensive care unit (SICU) from January 2000 to December 2008. Patients sustaining moderate to severe head injuries, defined as a head Abbreviated Injury Score (AIS) ≥ 3, were excluded.

Demographic and clinical information collected included age, gender, mechanism of injury (blunt vs penetrating), blood

Results

During the 9-year study period, 5,180 patients were admitted to the SICU. After the exclusion of 2,231 patients with moderate to severe head injuries (head AIS ≥ 3), 663 patients with ISS ≥ 25 and 2,286 patients with ISS < 25 were available for analysis (Fig. 1). Beta-blocker exposure was consistent across both populations, with 14.8% of patients with ISS ≥ 25 and 15.1% of those with ISS < 25 exposed during the first 30 days of SICU admission.

Table 1 compares the demographic and clinical injury

Comments

The role of catecholamines in critical illness was established in the early 1900s,27 and modulation of this response has been an area of intense research investigation in the past decade. Severe injury is associated with sympathetic hyperactivity due to an exaggerated catecholamine response that has been shown to have a positive relationship to ISS.6 Many deleterious effects of the catecholamine surge are mediated through the β-adrenergic receptor, regardless of the source of insult.27

Conclusions

Our study suggests that there is another trauma population that may benefit from β-adrenergic blockade. In patients sustaining severe injuries, as defined by ISS ≥ 25, in the absence of significant head injuries, β-blocker exposure appears to be associated with a mortality benefit and may offer a simple therapeutic intervention. The protective mechanism of β-blocker administration remains to be elucidated given the multiple systemic effects of catecholamines and their respective β-receptors.

References (38)

  • R.G. Douglas et al.

    Metabolic response to sepsis and trauma

    Br J Surg

    (1989)
  • D.N. Herndon et al.

    Reversal of catabolism by beta-blockade after severe burns

    N Engl J Med

    (2001)
  • P.J. Devereaux et al.

    Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk

    CMAJ

    (2005)
  • R.E. Barrow et al.

    The use of beta-adrenergic blockade in preventing trauma-induced hepatomegaly

    Ann Surg

    (2006)
  • D.P. Cioca et al.

    Apoptosis of peripheral blood lymphocytes is induced by catecholamines

    Jpn Heart J

    (2000)
  • D.T. Mangano et al.

    Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery

    N Engl J Med

    (1996)
  • A. Wallace et al.

    Prophylactic atenolol reduces postoperative myocardial ischemia

    Anesthesiology

    (1998)
  • D. Poldermans et al.

    The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery

    N Engl J Med

    (1999)
  • D.N. Herndon et al.

    Effect of propranolol administration on hemodynamic and metabolic responses of burned pediatric patients

    Ann Surg

    (1988)
  • Cited by (25)

    • The effects of beta blockade and clonidine on persistent injury-associated anemia

      2018, Journal of Surgical Research
      Citation Excerpt :

      Future research should seek to build on the trial performed by Bible et al.9 by enrolling more patients, quantifying operative and phlebotomy blood losses, and assessing the effects of clonidine as well as BB on anemia. Future studies should also investigate other mechanisms by which BB may improve outcomes among critically ill patients, a phenomenon which has been observed in the presence and absence of traumatic brain injury.25,26 Critically ill trauma patients who received BB or clonidine for ≥25% of their hospital stay had favorable Hb trends when accounting for OBL, PBL, and RBC transfusion.

    • Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma

      2017, Journal of the American College of Surgeons
      Citation Excerpt :

      Endothelial glycocalyx breakdown and syndecan-1 shedding triggers neurohormonal overactivation, coagulopathy, endothelial dysfunction, and increased permeability.2,11,19,24,29 These systemic effects are potential therapeutic targets, which has prompted the study of interventions ranging from β-blockers to modulate the catecholamine surge to plasma to repair the endothelium.29-34 Therapies such as plasma-based resuscitation seem to re-establish syndecan-1 on the cell surface and reduce shedding, while also decreasing endothelial hyperpermeability and modulating inflammation.5,13,29,32,35,36

    • Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: A prospective study

      2013, Journal of Critical Care
      Citation Excerpt :

      We infer that endogenous heparinization through shedding of the glycocalyx, represents one of several mechanisms influenced by catecholamines that contributes to hypocoagulability in critical illness [8]. Given the widespread use of vasopressor/inotropic therapy in critically ill patients, including septic patients, and the ongoing debate on the balance between its associations with beneficial vs adverse events [4,61], including evidence for the potential beneficial effects of modulating the sympathoadrenal response in critical illness [62-69], there is a need for improved understanding of the effects of catecholamines, whether endogenous and exogenous, on the vascular system, the endothelium and whole blood hemostasis in particular. The present study has several limitations.

    • Advances in the Management of the Critically Injured Patient in the Operating Room

      2013, Anesthesiology Clinics
      Citation Excerpt :

      Beta blockade has been suggested to be protective in human studies in subjects with brain injuries. Retrospective database reviews indicated improved neurologic outcome and reduced morbidity and mortality in patients receiving peri-insult beta blockade.12–14 Beta blockade in head injuries was initially thought to be deleterious insofar as it may decrease mean arterial pressure (MAP).

    View all citing articles on Scopus
    View full text