Abnormally increased physiologic deadspace volume (Vd(phys)), consisting of alveolar deadspace volume and airway deadspace volume, is one of several causative factors predisposing to compromised arterial blood gas exchange. We compared the effects of two methods of general anesthesia on Vd(phys) when combined with positive pressure ventilation (PPV): total IV anesthesia (TIVA) and inhaled anesthesia with isoflurane. Forty patients with no history of pulmonary pathology undergoing elective surgery in the supine position were studied. A crossover design was used, and all patients received both anesthetic methods sequentially in randomized order. PPV and TIVA significantly increased Vd(phys) compared with baseline (preoperative and breathing spontaneously) from 164 +/- 60 mL to 264 +/- 79 mL (P < 0.05). Isoflurane inhalation combined with PPV significantly enhanced this increase, resulting in a twofold increase in Vd(phys) to 315 +/- 80 mL (P < 0.05). Also, alveolar deadspace volume increased by more than 200% with isoflurane. Furthermore, isoflurane inhalation (1.15% end-tidal concentration) resulted in impaired arterial oxygenation, as evidenced by a significant decrease in the Pao(2)/fractional inspired oxygen concentration ratio compared with baseline values from 387 +/- 35 to 310 +/- 70 (P < 0.05). Although significant increases in Vd(phys) resulted with PPV combined with TIVA, these adverse changes were much less compared with isoflurane inhalation and PPV. These findings may apply to subjects with compromised pulmonary function (i.e., acute respiratory distress syndrome or severe inhalational burn injury).