Twenty-three studies with 3,395 patients were included in the review.

Fifteen studies assessed clonidine, six assessed dexmedetomidine and two assessed mivazerol. Twenty-two studies compared alpha-2-agonists with placebo, and one compared dexmedetomidine with propofol.

Fifteen studies (n=3,128) reported 78 deaths (2.5%). Patients given alpha-2-agonists had lower mortality (relative risk, RR=0.64, 95% confidence interval, CI: 0.42, 0.99, P=0.05). Tests for heterogeneity did not detect significant differences among the trials (P=0.92).

The individual alpha-2-agonists each showed similar but non significant effects on mortality. The RR was 0.48 (95% CI: 0.15, 1.6, P=0.20) for clonidine, 0.57 (95% CI: 0.17, 1.88, P=0.40) for dexmedetomidine and 0.69 (95% CI: 0.42, 1.15, P=0.15) for mivazerol.

Thirteen studies (n=3,090) reported myocardial infarctions with 188 (6%) occurrences. Patients given alpha-2-agonists showed a lower rate of events, but this difference was not significant (RR 0.85, 95% CI: 0.65, 1.11, P=0.20). Tests for heterogeneity did not detect significant differences between the trials (P=0.55). The RR was 0.61 (95% CI: 0.25, 1.48, P=0.30) for clonidine, 0.47 (95% CI: 0.11, 2.03, P=0.30) for dexmedetomidine and 0.91 (95% CI: 0.68, 1.21, P=0.50) for mivazerol.

Sixteen studies (n=1,320) reported ischaemia with 336 (25.5%) occurrences. Patients given alpha-2-agonists had a reduced rate of ischaemia (RR 0.76, 95% CI: 0.63, 0.91, P=0.003). Tests for heterogeneity did not detect significant differences between the trials (P=0.59). However, the subgroup analyses showed a greater reduction in RR for patients given clonidine (RR 0.67, 95% CI: 0.54, 0.84, P=0.0005) than for those given dexmedetomidine (RR 0.85, 95% CI: 0.57, 1.27, P=0.40) or mivazerol (RR 1.14, 95% CI: 0.67, 1.97, P=0.60).

Four studies (n=243) reported supraventricular tachyarrhythmias with 33 (12%) occurrences. There was no difference in the rate of occurrence between groups given alpha-2-agonists and others (RR 1.04, 95% CI: 0.56, 1.93, P=0.90). Tests for heterogeneity did not detect significant differences between the trials (P=0.87).

Ten studies assessed cardiac surgery. In these studies alpha-2-agonists significantly reduced myocardial ischaemia (RR 0.71, 95% CI: 0.54, 0.92, P=0.01). There were also non significant reductions in mortality (RR 0.49, 95% CI: 0.12, 1.98, P=0.30) and myocardial infarction (RR 0.83, 95% CI: 0.35, 1.96, P=0.70). Tests for heterogeneity did not detect significant differences between the trials on any outcome.

Eight studies assessed vascular surgery. In these studies alpha-2-agonists significantly reduced mortality (RR 0.47, 95% CI: 0.25, 0.90, P=0.02) and myocardial infarction (RR 0.66, 95% CI: 0.46, 0.94, P=0.02). There was also a non significant reduction in ischaemia (RR 0.83, 95% CI: 0.64, 1.07, P=0.15). Tests for heterogeneity did not detect significant differences between the trials on any outcome.

Three studies assessed nonvascular surgery and found no significant effect of alpha-2-agonists on mortality (RR 1.05, 95% CI: 0.52, 2.09, P=0.90), infarction (RR 1.35, 95% CI: 0.83, 2.21, P=0.2) or ischaemia (RR 0.20, 95% CI: 0.02, 1.62, P=0.13).

Further analyses explored the effect of prior medication with calcium antagonists or beta-blockers, and the occurrence of adverse events during different categories of surgery.