Comparative risks and clinical outcomes of midazolam versus other intravenous sedatives in critically ill mechanically ventilated patients: A systematic review and meta-analysis of randomized trials

• Published in: Intensive & critical care nursing Vol. 89; p. 103945
• Main Authors: Chen, Yu-Xin, Ho, Mu-Hsing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2025; Elsevier Limited
• Subjects: Age; Anesthesia; Benzodiazepines; Bias; Bradycardia; Cardiac arrhythmia; Clinical medicine; Clinical outcomes; Clinical trials; Critical care; Critical Illness - therapy; Delirium; Extubation; Health risks; Humans; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - pharmacology; Hypnotics and Sedatives - therapeutic use; Hypotension; Intensive care; Intensive Care Units - organization & administration; Length of stay; Length of Stay - statistics & numerical data; Literature reviews; Mechanical ventilation; Medical Subject Headings-MeSH; Meta-analysis; Meta-analysis as topic; Midazolam; Midazolam - adverse effects; Midazolam - pharmacology; Midazolam - standards; Midazolam - therapeutic use; Mortality; Patients; Pediatrics; Randomized Controlled Trials as Topic - statistics & numerical data; Respiration, Artificial - adverse effects; Respiration, Artificial - methods; Risk factors; Sedation; Sedative drugs; Systematic review; Ventilation; Ventilators; Delirium; Intensive care; Meta-analysis as topic; Midazolam; Sedation; Mechanical ventilation
• ISSN: 0964-3397; 1532-4036; 1532-4036
• DOI: 10.1016/j.iccn.2025.103945

This systematic review synthesized literature evidence and compared midazolam’s risks and clinical outcomes with other sedatives in critically ill mechanically ventilated patients. We included randomized controlled trials (RCTs) from databases of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL without language restrictions. We used relative risk (RR) for binary outcomes and standardized mean difference (SMD) for continuous outcomes, with corresponding 95% confidence interval (CI). 17 RCTs involving 1509 patients were included. Compared to other sedatives, midazolam significantly increased the incidence of delirium (RR 2.39, 95 % CI, 1.75 to 3.26), the time up to extubation (SMD 1.99, 95 % CI, 0.81 to 3.16) and ICU length of stay (SMD 0.63, 95 % CI, 0.20 to 1.08), but significantly reduced the incidence of bradycardia (RR 0.52, 95 % CI, 0.36 to 0.76). No differences were identified in hypotension incidence (RR 0.69, 95 % CI, 0.37 to 1.31) or duration of mechanical ventilation (SMD 0.28, 95 % CI, −0.22 to 0.78). Midazolam caused a higher risk of delirium, a longer time up to extubation, and ICU length of stay, but a lower incidence of bradycardia. No significant evidence indicated midazolam was associated with a higher risk of hypotension or increased duration of mechanical ventilation. Clinicians should balance midazolam’s potential risks with its benefits. While other sedatives may be catering to patients at a higher delirium risk, midazolam remains indispensable for hemodynamically compromised patients, such as those with bradycardia. Precise sedation management is crucial for patient safety and outcomes.