Isoflurane but not mechanical ventilation promotes extravascular fluid accumulation during crystalloid volume loading

Background: The combination of isoflurane anesthesia and mechanical ventilation reduces urinary output and promotes redistribution of a crystalloid bolus into the extravascular space. The authors hypothesized that mechanical ventilation rather than isoflurane causes this alteration. Methods: The fate of a 25-ml/kg, 20-min, 0.9% saline fluid bolus was studied in four different experiments per sheep: while conscious and spontaneously ventilating (CSV), while conscious and mechanically ventilated (CMV), while anesthetized with isoflurane and mechanical ventilated (ISOMV), and while anesthetized with isoflurane and spontaneously ventilating (ISOSV). Results: By calculations based on the indicator dilution and mass balance principles, plasma expansion was similar between protocols. Isoflurane but not mechanical ventilation reduced urinary output and increased interstitial fluid volume (P < 0.001): At 180 min, mean total urinary outputs were 15.6 ± 2.1 and 15.9 ± 2.9 ml/kg in the CSV and CMV protocols and 2.7 ± 0.6 and 3.1 ± 1.1 ml/kg in the ISOSV and ISOMV protocols, respectively. The net changes in extravascular volume, assumed to be interstitial fluid volume, were 8.6 ± 3.3 and 8.1 ± 3.1 ml/kg, and 22.5 ± 1.5 and 22.1 ± 1.6 ml/kg in the corresponding protocols. Volume kinetic analysis demonstrated extravascular fluid accumulation associated with isoflurane anesthesia similar to the calculated interstitial accumulation of 20.2 ± 0.5 and 26.5 ± 0.3 ml/kg in the ISOSV and ISOMV protocols, respectively. Conclusion: Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.