Peer Review Report For: Invasive ventilatory strategies that target ultra-low tidal volumes or minimisation of driving pressure in patients receiving invasive mechanical ventilation on an intensive care unit: a systematic review and meta-analysis [version 1; peer review: 1 not approved]

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Background Our objective was to examine the clinical and cost-effectiveness of ultra-low tidal volume ventilation (ULTV) and limited-driving pressure ventilation in adults and children receiving invasive mechanical ventilation on an intensive care unit. Methods We searched MEDLINE, Embase and other sources from inception to October 2025. We included randomised controlled trials comparing ULTV or driving pressure minimisation strategies to standard care. We included all full economic evaluations. Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias and overall GRADE certainty of evidence. Meta-analyses were conducted with random effects models. Results We included 12 clinical effectiveness trials (13 trial reports) and three health economic evaluations. Seven trials compared ULTV with standard care and five compared driving pressure minimisation strategies with standard care in adult patients receiving mechanical ventilation. We identified no relevant evidence in children. The evidence is very uncertain about the effect of ULTV strategies on duration of invasive ventilation (mean difference [MD] -1.87 days, 95% CI -5.07 to 1.33), 28-day mortality (risk ratio [RR] 1.11, 95% CI 0.97 to 1.28), or any other clinical outcomes. The evidence is also very uncertain about the effect of driving pressure minimisation strategies on duration of invasive ventilation (MD -1.66 days, 95% CI -3.95 to 0.63) or 28-day mortality (RR 1.10, 95% CI 0.80 to 1.50), and other clinical outcomes. The certainty of evidence for all outcomes was assessed as low or very low. Conclusions Current evidence does not support the routine use of ULTV and driving pressure minimisation strategies. Further high-quality randomised trials are needed. Systematic review registration PROSPERO CRD42024554619.

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