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A noninvasive algorithm for estimating cardiac output is discussed. The technique is based on a differential form of the CO 2 Fick equation applied during normal ventilation and a 30-s period of partial rebreathing using additional deadspace. Using the Fick equation in a differential form eliminates the need to estimate mixed venous pCO 2, also the sensitivity of the cardiac output estimate to changes in the alveolar deadspace fraction is greatly reduced. The procedure is fully automated, requires minimal staff supervision, and provides cardiac output estimates every 3 1/2-min. Estimates of cardiac output when compared to thermodilution yielded a correlation coefficient of 0.92 with a linear regression slope of 0.92 (n=451). Temporary increases in alveolar deadspace did not significantly alter this relationship. Cardiac output estimates obtained during period of increased pulmonary shunt due to oleic acid infusion yielded a correlation coefficient of 0.90 with a linear regression slope of 0.92 when compared to direct thermodilution measurements.