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

Coppola, Silvia; Froio, Sara; Chiumello, Davide

doi:10.1186/s13054-015-0803-2

Critical Care

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	N°	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
				Preadmission oral use	No β-blockers: 6531		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	Septic, mechanically ventilated patients: 6	↓ 20% HR	Small population
				6–22 mg/min to achieve 20% ↓ HR		↓ Cardiac index
				6–22 mg/min to achieve 20% ↓ HR		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		↓ HR (target 65–95 bpm); ↑ SVI	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
					No β-blockers: 8404		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
						↑ SVI
						↓ NE
				25–2000 mg/h		↓ fluids
				25–2000 mg/h		↓ 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%)			Study design
							Post-hoc analyses
						↑ mortality if discontinuation of β-blockers
					In-hospital survivors: 263	↑ mortality if discontinuation of β-blockers
	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	Other HRLD: 114		No data on spirometry
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			Lack of information on β-blockers
							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
	Riordan, 2007 [48]	Retrospective	446		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
	Inaba, 2008 [42]	Retrospective	1156	In-hospital treatment	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
	Schroeppel, 2010 [49]	Retrospective	2601	Atenolo, carvedilol, esmolol, labetalol, metoprolol, nadolol, propranolol, sotalol	No β-blocker: 2095		Different β-blockers

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.
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.

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