Tehran University of Medical Sciences Archives of Anesthesiology and Critical Care 2423-5849 0 0 2025 11 18 1358 1358 Mohammad Reza Habibzadeh Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. & Department of Anesthesia and Critical Care, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Mahmoud Saghaei Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. & Department of Anesthesia and Critical Care, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Mohammad Shojaei Department of Anesthesia and Critical Care, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 2025 07 27 2025 08 11 Background: Pulmonary compliance measurement is a critical component of monitoring mechanically ventilated patients with respiratory failure. The traditional method calculates compliance by dividing delivered tidal volume by the resultant airway pressure (plateau pressure minus positive end-expiratory pressure [PEEP]). However, this approach requires intermittent ventilator disconnection, limiting its frequency. A novel method using multiple linear regression (MLR) analysis of continuous pressure and flow waveforms enables breath-to-breath compliance measurement without disrupting ventilation. This study compares pulmonary compliance values obtained by MLR and traditional methods. Methods: In this clinical study, pulmonary compliance was measured and compared in consecutive mechanically ventilated patients using both traditional and MLR methods. MLR-derived compliance was obtained using the ventilator’s integrated monitoring function, while traditional compliance was calculated as tidal volume divided by (plateau pressure – PEEP). Results: Among 200 enrolled patients, the two methods showed strong correlation (*r* = 0.9, *p* < 0.01). However, MLR-derived compliance values were consistently lower than those from the traditional method (44.74 ± 21.78 mL/cmH₂O vs. 57.95 ± 26.64 mL/cmH₂O, *p* < 0.01). Conclusion: MLR is a reliable alternative for continuous pulmonary compliance monitoring, though its systematically lower values—likely reflecting dynamic rather than static compliance—may necessitate a correction factor. The method’s ability to provide breath-to-breath measurements offers significant clinical advantages over traditional intermittent assessments. https://aacc.tums.ac.ir/index.php/aacc/article/view/1358