Efficacy and safety of intravenous esmolol for cardiac protection in non-cardiac surgery. A systematic review and meta-analysis

Figures & data

Figure 1. Flowchart of study selection. RCT: randomized controlled trial; ESM: electronic supplementary material.

Table 1. Characteristics of the studies included in the Meta-analysis.

	Raby		Urban		Balser
Journal	Anesth Analg		Anesth Analg		Anesthesiology
Year of publication	1999		2000		1998
Study design	Double-blind		Open		Open
No. of patients (esmolol)	15		52		34
No. of patients (control)	11		55		30^b
No. of groups	2		2		2
Preoperative beta-blocker administration,% of randomised patients (esmolol/control)	33/36		27/29		39/30
Intervention	Esmolol 100–300 µg/kg/min		Esmolol 250 mg/h		Esmolol with a bolus of 12.5–250 mg followed by an infusion of 50–150 µg/kg/min
Length of administration	48 hours		18–24 hours^a		12 hours
Starting time of intervention	After surgery		After surgery		After surgery
Control	Placebo		Placebo		Diltiazem with a bolus of 20–45 mg followed by an infusion of 10–15 mg/h
Haemodynamic target	Postoperative HR 20% below the ischaemic threshold (minimum of 60 bpm)		Postoperative HR below 80 bpm		Postoperative HR between 80–100 bpm
No. of patients treated with any beta-blockers in the control group	9 (81.8)		18 (32.7)		0
Type of surgery	Peripheral vascular		Orthopaedic		Non-cardiac^c
Urgency	NR		Elective		NR
Outcomes n (%)	Esmolol	Control	Esmolol	Control	Esmolol	Control
MI	0	1 (9.1)	1 (1.9)	3 (5.5)	NR	NR
Myocardial ischaemia	5 (33.3)	8 (72.7)	3 (5.8)	8 (14.5)	NR	NR
Cardiac arrest	NR	NR	NR	NR	NR	NR
Cardiac death	0	0	NR	NR	NR	NR
Heart failure	0	0	NR	NR	NR	NR
UAP	1 (6.6)	0	NR	NR	NR	NR
New-onset arrhythmias	NR	NR	NR	NR	NR	NR
Composite of cardiac events (1)	1 (6.7)	1	7 (13.5)	12 (21.8)	NR	NR
AKI	NR	NR	NR	NR	NR	NR
Composite of renal events (2)	NR	NR	NR	NR	NR	NR
Bradycardia	NR	NR	3 (5.8)	0	0	0
Hypotension	NR	NR	1 (1.9)	0	2 (5.9)	1 (3.3)
Stroke	NR	NR	NR	NR	NR	NR
Bronchospasm	NR	NR	NR	NR	NR	NR
Comatose symptoms	NR	NR	NR	NR	NR	NR
Serious infection/sepsis	NR	NR	NR	NR	NR	NR
All-cause mortality	NR	NR	NR	NR	10.5 (30.8)	11 (37.9)

(1) MI, unstable angina, heart failure, new-onset arrhythmias, cardiac death; (2) AKI, need for RRT, worsening development of chronic kidney failure.

HR: heart rate; bpm: beats per minute; NR: not reported; MI: myocardial infarction; UAP: unstable angina pectoris; AKI: acute kidney injury.

^a On the first postoperative morning esmolol was switched to oral metoprolol (starting dose 25 mg twice a day) that was titrated to keep HR below 80 bpm and continued for the next 48 hours.

^bOne patient included at two separate times.

^cSurgeries including major abdominal, urologic, thoracic, vascular, neurosurgery, and general surgery operations.

Figure 2. (A) Forest plots of the comparisons (panel A) myocardial ischaemia, (panel B) myocardial infarction, (panel C) unstable angina pectoris, and (panel D) a composite of cardiac events. (B) Forest plots of the comparisons (panel A) bradycardia, (panel B) hypotension, and (panel C) all-cause mortality.

Table 2. Summary of the main results.

	Number of trials	Esmolol n/N (%)	Control n/N (%)	NNT/NNH [95% CI]	RR [95% CI]	p – effect	p – heterogeneity	I2 (%)	Quality of the evidence (GRADE)
Myocardial ischaemia	2	8/67 (11.9)	16/66 (24.2)	9 [4–159]^b	0.43 [0.21–0.88]	.02	.84	0	Moderate +++-
PMI	2	1/67 (1.5)	4/66 (6.1)	22 [9–53]^b	0.31 [0.05–1.92]	.21	.86	0	Low ++--
UAP	1	1/15 (6.7)	0/11	15 [5–17]^a,b	2.25 [0.10–50.5]	.61	NA	NA	Low ++--
Composite of cardiac events	2	8/67 (11.9)	13/66 (19.7)	13 [5–22]^b	0.63 [0.28–1.41]	.26	.90	0	Low ++--
Bradycardia	2	3/86 (3.5)	0/85	29 [14–257]^a,b	7.4 [0.29–139.8]	.18	NA	NA	Low ++--
Hypotension	2	3/86 (3.5)	1/85 (1.2)	44 [15–46]^a,b	2.21 [0.34–14.4]	.41	.77	NA	Low ++--
All-cause mortality	1	11/34 (32.4)	11/29 (37.9)	18 [3–6]^b	0.85 [0.44–1.67]	.64	NA	NA	Low ++--

n/N: events/ randomized patients; NNT: number needed to treat; RR: risk ratio; CI: confidence interval; PMI: perioperative myocardial infarction; UAP: unstable angina pectoris; NA: not applicable; GRADE: GRADE Working Group grades of evidence [33].

^a NNH: number needed to harm.

^bCI for absolute risk reduction extends from a negative to a positive number.

Figure 3. Summary of the risk of bias of the selected studies.

Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–926.

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