The Rate-Volume Trade-off in Mechanically Ventilated Patients: Respiratory Rate and 28-Day Mortality Across Two Independent Cohorts.

BACKGROUND: In mechanically ventilated patients, similar minute ventilation can be achieved through different combinations of respiratory rate (RR) and tidal volume (VT). Whether this rate-volume trade-off is associated with 28-day mortality, and whether this association is altered by mechanical power stratification, remains unclear. METHODS: We performed a retrospective analysis of two independent intensive care unit (ICU) cohorts, MIMIC-IV (n=10,337; primary) and eICU-CRD (n=9,540; replication), including 19,877 adults receiving invasive mechanical ventilation for at least 24 hours. Time-weighted 24-hour averages of respiratory rate, tidal volume, minute ventilation and mechanical power were calculated. Multivariable logistic regression estimated odds ratios (OR) for 28-day mortality across respiratory-rate and tidal-volume quintiles within strata of predicted body weight (PBW) normalized minute ventilation and, secondarily, mechanical power, adjusting for pre-specified confounders including driving pressure. RESULTS: Higher respiratory rate was consistently associated with higher 28-day mortality in both cohorts (MIMIC-IV Q5 vs Q1: OR 1.93, 95% CI 1.48-2.51; eICU: OR 1.79, 1.23-2.61; p-trend <0.001). Within the lung-protective tidal volume range (median 7.1 ml/kg PBW), higher tidal volume was associated with lower mortality, a weaker association in the opposite direction, reflecting the rate-volume trade-off rather than a benefit of higher tidal volume. The association persisted after mechanical power stratification and across sensitivity analyses. CONCLUSIONS: Within comparable minute ventilation, the rate-volume trade-off was asymmetric. Respiratory rate carried a stronger adverse association with mortality than tidal volume within the lung-protective range. Respiratory rate is a clinically relevant and currently under-specified component of lung-protective ventilation, warranting prospective evaluation.