BackgroundThis Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research.MethodsThe RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities.ResultsData from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied.ConclusionThe RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.