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Table 1 Clinical studies investigating the role of β-blocker exposure in critically ill patients

From: β-blockers in critically ill patients: from physiology to clinical evidence

  Author Study design β-blocker Groups Main Outcomes Limitations
ICU Christensen, 2011 [10] Observational 8087 Metoprolol (63.4%), others (36.5%) β-blockers: 1556 β-blocker group: lower 30-day mortality No data on in-hospital β-blocker use
Preadmission oral use No β-blockers: 6531   No data on severity scores
Study design
Septic Shock Gore, 2006 [20] Interventional clinical study 6 Intravenous esmolol Septic, mechanically ventilated patients: 6 ↓ 20% HR No control group
3 hours of infusion Small population
6–22 mg/min to achieve 20% ↓ HR   ↓ Cardiac index  
O2 consumption not altered
Schmittinger, 2008 [22] Retrospective 40 Enteral metoprolol Septic shock and cardiac depression in patients with chronic β-blocker therapy: 40 ↓ HR (target 65–95 bpm); ↑ SVI No control group
Within 48 hours after the onset of shock or ICU admission Study design
↓ NE, AVP and milrinone dosages
↓ lactate, creatinine
Macchia, 2012 [23] Retrospective 9465 Preadmission oral use β-blockers: 1061 β-blocker group: lower 28-day mortality Study design
No β-blockers: 8404 No data on severity scores
Lack of information on β-blockers
Morelli, 2013 [13] RCT 154 Intravenous esmolol β-blocker: 77 β-blocker group: Single center
ICU treated to maintain HR 80–94 bpm Usual care: 77 ↓ HR (80–94 bpm) Arbitrary selection of HR threshold
↓ NE
25–2000 mg/h ↓ fluids
↓ 28-day mortality
Acute Respiratory Failure Noveanu, 2010 [29] Retrospective 314 Preadmission oral use In-hospital non-survivors: 51 More β-blocker use in survivors Study design
Metoprolol (36%), carvedilol (18%), bisoprolol (16%), nebivolo (22%), atenolol (4%), sotalol (3%), celiproplol (2%)
Post-hoc analyses
↑ mortality if discontinuation of β-blockers
In-hospital survivors: 263
Kargin, 2014 [35] Retrospective 188 Intravenous bolus metoprolol + enteral maintenance; enteral bisoprolol or carvedilol β-blockers: 74 Similar mortality Study design
Other HRLD: 114 No data on spirometry
ICU treatment
Trauma Arbabi, 2007 [47] Retrospective 4117 In hospital treatment β-blocker: 303 Similar mortality rate Study design
No β-blocker: 3814 No data on HR
No data on severity scores
Lack of information on β-blockers
Cotton, 2007 [46] Retrospective 420 β-blocker therapy for 2 or more consecutive days in hospital β-blocker: 174 β-blocker: reduction in mortality despite more severe injury, older patients, lower predicted survival Study design
No β-blocker: 246 Lack of information on β-blockers
Metoprolol, propranolol, labetalol, atenolol, esmolol, sotalol
Different β-blockers
No data on neurological outcomes
TBI Riordan, 2007 [48] Retrospective 446 Esmolol (e.v.), propranolol (e.v. or enteral), labetalol (e.v.), metoprolol (e.v. or enteral) β-blocker: 138 Reduced mortality in β-block group despite older and more severely injured patients Study design
No β-blocker: 308 Different β-blockers
Inaba, 2008 [42] Retrospective 1156 In-hospital treatment β-blocker: 203 Reduced mortality in β-block group despite older and more severely injured patients Study design
No β-blocker: 953 Lack of information on β-blockers
Schroeppel, 2010 [49] Retrospective 2601 In-hospital treatment β-blocker: 506 Similar mortality between groups despite older and more severely injured β-blocker patients Study design
Atenolo, carvedilol, esmolol, labetalol, metoprolol, nadolol, propranolol, sotalol No β-blocker: 2095 Different β-blockers
  1. Selection of clinical studies from the last 10 years. Studies are grouped according to specific categories of critical illness: General admission to ICU, septic shock, acute respiratory failure, trauma and traumatic brain injury.
  2. ICU: intensive care unit; HR: heart rate; BP: blood pressure; TBI: traumatic brain injury; HRLD: heart rate-limiting drug; SVI: stroke volume index; NE: norepinephrine; AVP: arginine-vasopressin; RCT: randomized control trial; bpm: beat per minute; e.v.: endovenous.