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Objective: To evaluate a least squares fitting technique for the purpose of measuring total respiratory compliance (Crs) and resistance (Rrs) in patients submitted to partial ventilatory support, without the need for esophageal pressure measurement., Design: Prospective, randomized study., Setting: A general ICU of a University Hospital., Patients: 11 patients in acute respiratory failure, intubated and assisted by pressure support ventilation (PSV)., Interventions: Patients were ventilated at 4 different levels of pressure support. At the end of the study, they were paralyzed for diagnostic reasons and submitted to volume controlled ventilation (CMV)., Measurements and Results: A least squares fitting (LSF) method was applied to measure Crs and Rrs at different levels of pressure support as well as in CMV. Crs and Rrs calculated by the LSF method were compared to reference values which were obtained in PSV by measurement of esophageal pressure, and in CMV by the application of the constant flow, end-inspiratory occlusion method. Inspiratory activity was measured by P0.1. In CMV, Crs and Rrs measured by the LSF method are close to quasistatic compliance (-1.5 +/- 1.5 ml/cmH2O) and to the mean value of minimum and maximum end-inspiratory resistance (+0.9 +/- 2.5 cmH2O/(l/s)). Applied during PSV, the LSF method leads to gross underestimation of Rrs (-10.4 +/- 2.3 cmH2O/(l/s)) and overestimation of Crs (+35.2 +/- 33 ml/cmH2O) whenever the set pressure support level is low and the activity of the respiratory muscles is high (P0.1 was 4.6 +/- 3.1 cmH2O). However, satisfactory estimations of Crs and Rrs by the LSF method were obtained at increased pressure support levels, resulting in a mean error of -0.4 +/- 6 ml/cmH2O and -2.8 +/- 1.5 cmH2O/(l/s), respectively. This condition was coincident with a P0.1 of 1.6 +/- 0.7 cmH2O., Conclusion: The LSF method allows non-invasive evaluation of respiratory mechanics during PSV, provided that a near-relaxation condition is obtained by means of an adequately increased pressure support level. The measurement of P0.1 may be helpful for titrating the pressure support in order to obtain the condition of near-relaxation.