BACKGROUND: A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. High PaCO2 can be permitted to lower airway pressures as in permissive hypercapnia (PH). Intratracheal pulmonary ventilation (ITPV) was developed to allow a decrease in physiological dead space during mechanical ventilation. We compared the effect of hybrid ventilation (HV) as a modification of ITPV with PH on the decrease of tidal volume and airway pressures in rabbits with acute respiratory failure. METHODS: Tracheostomy was performed in 7 rabbits ventilated under volume-controlled mode in the supine position. Arterial blood gas analysis, airway pressures, and dead space ventilation were measured at respiratory rate of 20/min as control values. Oleic acid (OA) of 0.06 ml/kg was injected to induce acute respiratory failure. Tidal volume (VT) was elevated to maintain PaCO2 in the normal range. The same parameters were measured as OA values. Then VT was reduced to the control level to allow PH. HV was initiated by inserting a reverse thrust catheter (RTC) into the endotracheal tube. HV consists of a pressure-controlled mode of mechanical ventilation and ITPV while flushing fresh gas continuously via the RTC. Respiratory parameters were compared under control, OA, PH and HV conditions. RESULTS: Oleic acid injection decreased PaO2 from 401+/-35 mmHg to 129+/-39 mmHg, increased VT from 42+/-5 ml to 52+/-10 ml, and increased VD/VT ratio from 0.65+/-0.07 to 0.71+/-0.07. During PH, the increase in PaCO2 was accompanied by the increase in VD/VT ratio from 0.71+/-0.07 to 0.79+/-0.03 and by the decrease of peak inspiratory pressure (PIP) from 19.4+/-4.0 cmH2O to 16.8+/-3.1 cmH2O. PaCO2 was lowered from 50+/-5 mmHg in PH to 39+/-5 mmHg in HV with a lower VT. VD/VT ratio in HV was as low as that in control. CONCLUSION: HV is an effective and easy-to-use ventilatory modality to reduce PaCO2 and airway pressures by the reduction in VD/VT ratio in acute respiratory failure model.