BackgroundThis systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical ventilation.MethodsWe performed a comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane trial registry. We identified RCTs that compared clonidine to any non-clonidine regimen in critically ill patients, excluding neonates, requiring mechanical ventilation. The GRADE method was used to assess certainty of evidence.ResultsWe included eight RCTs (n = 642 patients). In seven of the trials clonidine was used for adjunctive rather than stand-alone sedation. There was no difference in the duration of mechanical ventilation (mean difference (MD) 0.05 days, 95% confidence interval (CI) = -0.65 to 0.75, I2 = 86%, moderate certainty), ICU mortality (relative risk (RR) 0.98, 95% CI = 0.51 to 1.90, I2 = 0%, low certainty), or ICU length of stay (MD 0.04 days, 95% CI = -0.46 to 0.53, I2 = 16%, moderate certainty), with clonidine. There was a significant reduction in the total dose of narcotics (standard mean difference (SMD) -0.26, 95% CI = -0.50 to -0.02, I2 = 0%, moderate certainty) with clonidine use. Clonidine was associated with increased incidence of clinically significant hypotension (RR 3.11, 95% CI = 1.64 to 5.87, I2 = 0%, moderate certainty).ConclusionsUntil further RCTs are performed, data remains insufficient to support the routine use of clonidine as a sedative in the mechanically ventilated population. Clonidine may act as a narcotic-sparing agent, albeit with an increased risk of clinically significant hypotension.