PURPOSE: To evaluate the effects of acute hypercapnia induced by positive end-expiratory pressure (PEEP) variations at constant plateau pressure (P (plat)) in patients with severe acute respiratory distress syndrome (ARDS) on right ventricular (RV) function. METHODS: Prospective observational study in two academic intensive care units enrolling 11 adults with severe ARDS (PaO(2)/FiO(2) <150 mmHg at PEEP >5 cmH(2)O). We compared three ventilatory strategies, each used for 1 h, with P (plat) at 22 (20-25) cmH(2)O: low PEEP (5.4 cmH(2)O) or high PEEP (11.0 cmH(2)O) with compensation of the tidal volume reduction by either a high respiratory rate (high PEEP/high rate) or instrumental dead space decrease (high PEEP/low rate). We assessed RV function (transesophageal echocardiography), alveolar dead space (expired CO(2)), and alveolar recruitment (pressure-volume curves). RESULTS: Compared to low PEEP, PaO(2)/FiO(2) ratio and alveolar recruitment were increased with high PEEP. Alveolar dead space remained unchanged. Both high-PEEP strategies induced higher PaCO(2) levels [71 (60-94) and 75 (53-84), vs. 52 (43-68) mmHg] and lower pH values [7.17 (7.12-7.23) and 7.20 (7.16-7.25) vs. 7.30 (7.24-7.35)], as well as RV dilatation, LV deformation and a significant decrease in cardiac index. The decrease in stroke index tended to be negatively correlated to the increase in alveolar recruitment with high PEEP. CONCLUSIONS: Acidosis and hypercapnia induced by tidal volume reduction and increase in PEEP at constant P (plat) were associated with impaired RV function and hemodynamics despite positive effects on oxygenation and alveolar recruitment ( ClinicalTrials.gov #NCT00236262).