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Objective To compare the development of postoperative cognitive dysfunction ( POCD) under total inhalation anesthesia with sevoflurane versus total intravenous anesthesia with propofol in elderly patients. Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-77 yr, weighing 43-78 kg, with preoperative Mini?Mental State Examination ( MMSE) score≥25, scheduled for elective surgery for oral and maxillofacial carcinoma, were divided into 2 groups ( n=30 each) using a random number table: total inhalation anesthesia with sevoflurane group ( group S) and total intravenous anesthesia with propofol?based anesthesia group ( group P ) . The patients were tracheally intuba?ted under local infiltration anesthesia. In group S, anesthesia was induced with inhalation of 8% sevoflurane (oxygen flow rate 8 L∕min), rocuronium 0?9 mg∕kg was injected intravenously when the bispectral index ( BIS) value reached 45, and the patients were mechanically ventilated; anesthesia was maintained with inhalation of sevoflurane with the end?tidal concentration of 2%-3%. In group P , anesthesia was induced with iv propofol 2 mg∕kg and sufentanil 0?3μg∕kg, rocuronium 0?9 mg∕kg was injected intravenously when the BIS value reached 45, and the patients were mechanically ventilated; anesthesia was maintained with target?controlled infusion of propofol ( target plasma concentration 3-5μg∕ml) and remifentanil ( target plas?ma concentration 3-5 ng∕ml). In both groups, intermittent iv boluses of cisatracurium 0?04 mg∕kg were given to maintain muscle relaxation during operation, and BIS value was maintained at 40-60 during opera?tion. Before intubation ( T1 ) , immediately after onset of intubation ( T2 ) , at 10 min of intubation ( T3 ) , immediately after begninning of skin incision ( T4 ) , while operating on the base of tongue or sawing the low?er jaw ( T5 ) , at the end of operation ( T6 ) and on the morning of the postoperative day 1 ( T7 ) , blood sam?ples from the elbow vein were collected for determination of plasma norepinephrine and epinephrine concen?trations by high?performance liquid chromatography and electrochemistry. At T1?7 and on the morning of the postoperative day 3 ( T8 ) , blood samples from the elbow vein were collected for measurement of plasma cor?tisol concentrations by radioimmunoassay. MMSE was used to assess the cognitive function on the postopera?tive day 7. MMSE score< 24 was defined as POCD, and the occurrence of POCD was recorded. Results Compared with group S, the plasma concentrations of norepinephrine and epinephrine were significantly de?creased at T4 and T5 , the plasma cortisol concentration was significantly decreased at T4?7 ( P<0?05) , and no significant change was found in the incidence of POCD on the postoperative day 7 in group P ( P>0?05) . Conclusion Although the probability of the development of POCD is low when the two anesthetic methods are used, total intravenous anesthesia with propofol?based anesthesia induces a marked decrease in periop?erative stress responses when compared with total inhalation anesthesia with sevoflurane.