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Before obtaining results of arterial blood gas analysis in mechanically ventilated patients undergoing neurosurgery, the volume of ventilation is primarily adjusted according to endtidal CO2 (EtCO2). We characterized the impact of various arterial blood pressure changes on arterial PCO2 (PaCO2) to EtCO2 differences (PaCO2-EtCO2) in patients anesthetized for craniotomy.Seventy-two elective craniotomy patients were enrolled in this prospective study. Noninvasive blood pressure was measured before anesthesia induction. Anesthesia was induced with thiopental, rocuronium or suxamethonium, and fentanyl and was maintained with inhaled anesthetics or propofol and remifentanil. Volume-controlled ventilation was adjusted after intubation according to the clinical judgment. The first arterial blood gas analysis was taken just before the head pinning. Systolic, diastolic, and mean arterial blood pressures (MAP) and heart rate were registered after intubation every 5 minutes until the head pinning.PaCO2-EtCO2 correlated positively with percentage difference between MAP awake at arrival in operating room and during arterial CO2 determination (P=0.0008, r=0.388). In analysis according to a MAP decrease of less than 20% (n=17), 20% to 29% (n=24), 30% to 35% (n=16), and more than 35% (n=15), the mean (SD) PaCO2-EtCO2 was greater in patients with MAP decrease of over 35% or 30% to 35% than in patients with MAP decrease of less than 20%. The mean (SD) absolute values of the PaCO2-EtCO2 were 0.96 (0.43) kPa or 0.85 (0.31) kPa versus 0.55 (0.24) kPa, respectively (P<0.05 between categories). Mean EtCO2 was not different in the various MAP difference categories, but PaCO2 was greatest when MAP decreased more than 35% (P<0.05).There was a positive correlation between PaCO2-EtCO2 and MAP decrease shortly after induction of anesthesia. PaCO2-EtCO2 is recommended to be interpreted together with change in MAP during early phase of neuroanesthesia to guarantee optimal mechanical ventilation.