PurposeAs the middle-ear cavity is one of the noncompliant gas-filled cavities, an increase in middle-ear pressure (MEP) instead of volume expansion is observed with inhalation of nitrous oxide (N2O). Changes in MEP cause many complications, such as ear pain, temporary hearing impairment, and postoperative emesis. Therefore, we investigated changes in MEP during total intravenous anesthesia (TIVA) with propofol, fentanyl, and ketamine (PFK) and inhalation of N2O.MethodsTwelve patients were anesthetized with PFK until 60 min after the induction of anesthesia, and then N2O (60%) inhalation was started. MEP was measured by impedance audiometry (ranging from −300 daPa to +200 daPa) at 10-min intervals during PFK, and at 2-min intervals after the inhalation of N2O.ResultsMEP gradually but significantly increased from the preanesthetic value of 16±8 to 34±12 (SEM) daPa 50 min after the induction of PFK. However, MEP did not exceed the normal limit. The values of MEP in all patients were more than 200 daPa within 36 min after the start of inhalation of N2O in oxygen.ConclusionPFK had a minimal effect on MEP, whereas addition of N2O to PFK increased MEP dramatically. Therefore, TIVA, or at least PFK, would be a better choice for patients with middle-ear or upper-airway diseases.