The ARDSnet predicted body weight equation overestimates lung sizes of female critically ill patients and mediates higher mortality at guideline-adherent tidal volumes.

Background To prevent ventilator-induced lung injury (VILI), global guidelines recommend low tidal volumes (Vt) in mechanically ventilated critically ill patients. In this, Vt is scaled to the predicted body weight (PBW) as a proxy for functional lung size. However, concerns exist regarding algorithmic bias of the PBW equation, which may lead to increased VILI risk in specific subgroups, even at guideline-adherent Vts. We assessed whether the ARDSnet PBW equation overestimates female lung volumes and whether this translates into increased mortality risk. Methods From ten randomized trials and two retrospective datasets, we included 30,516 mechanically ventilated critically ill patients ([ Fig. 1 ]). Additionally, spirometry data of 12,078 healthy individuals collected by the Centers for Disease Control and Prevention (CDC) were analyzed. The risk of high driving pressure (≥15 cmH₂O) at the same Vt scaled to ARDSnet PBW, as well as lung volume measurements at the same ARDSnet PBW, were compared between sexes. Logistic and linear regression were used and adjusted for baseline factors to isolate sex-specific differences, including age, PF-ratio, paCO 2 , arterial pH, and the non-pulmonary SOFA score. Results Ventilation at the same Vt scaled to PBW resulted in an absolute 4.2% (95%CI 3.2 to 5.3, p