Correspondence  |   November 2003
Isoflurane Promotes Extravascular Fluid Accumulation in Humans: In Reply:—
Author Affiliations & Notes
  • George C. Kramer, Ph.D.
  • *Resuscitation Research Laboratory, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas.
Article Information
Correspondence   |   November 2003
Isoflurane Promotes Extravascular Fluid Accumulation in Humans: In Reply:—
Anesthesiology 11 2003, Vol.99, 1243. doi:
Anesthesiology 11 2003, Vol.99, 1243. doi:
In Reply:—
We would like to thank Drs. Weiss and Pizov for their comments regarding our recent publication. 1 The main finding of our study was that isoflurane anesthesia increases extravascular accumulation after a bolus infusion of 0.9% NaCl in normovolemic sheep, and the response was associated with an antidiuresis. In our anesthetized and ventilated experiments, a fractional inspired oxygen tension of 50% was administered with a tidal volume of 10–15 ml/kg and respiratory rates between 10 and 15 per min. In the ventilated protocols, a mean end-tidal carbon dioxide of 36 mmHg was achieved. Arterial blood gases were not routinely measured in these experiments, but mixed venous oxygen saturation measured with a fiberoptic pulmonary artery catheter was not lower than that in the conscious groups. We believe that there was no hypoxemia, but we cannot provide direct evidence for or against pulmonary edema.
Although it was determined in our study that isoflurane alone causes a significant extravascular accumulation of a crystalloid bolus, the specific organ distribution of the fluid was not determined. We were surprised when we first found that isoflurane anesthesia alone could have such a profound effect on acute fluid accumulation; we would again be surprised if this increased fluid accumulation caused significant pulmonary dysfunction. If the extravascular accumulation of 22.5 ml/kg at 3 h after bolus was evenly distributed by organ weight (assuming lung weight is 420 g, body weight is 70 kg, and normal extravascular lung water is 4.3 ml/kg body weight) the extravascular lung water would have increased to only 4.4 ml/kg, or by 3.1%. Most experimental studies have shown the lungs to be remarkably refractory to dysfunctional pulmonary edema in the absence of an inflammatory increase in capillary permeability. 2 
We certainly agree with Drs. Weiss and Pizov that studies measuring the effects of different anesthetics on extravascular lung water and pulmonary function are needed in humans and animals subjected to fluid therapy in a variety of clinical scenarios. The use of thermal dye dilution monitoring of extravascular lung water and blood gas analysis, along with calculations of changes in plasma volume and total extravascular volume, would be useful in this regard. 3 
Connolly CM, Kramer GC, Hahn RG, Chaisson NF, Svensén C, Kirschner RA, Hastings DA, Chinkes D, Prough DS: Isoflurane but not mechanical ventilation promotes third-space fluid losses during crystalloid volume loading. A nesthesiology 2003; 98: 670–81Connolly, CM Kramer, GC Hahn, RG Chaisson, NF Svensén, C Kirschner, RA Hastings, DA Chinkes, D Prough, DS
Tranbaugh RF, Lewis FR, Christensen IM, Elings VB: Lung water changes after thermal injury: The effects of crystalloid resuscitation and sepsis. Ann Surg 1980; 192: 47–9Tranbaugh, RF Lewis, FR Christensen, IM Elings, VB
Bellomo R, Uchino S: Cardiovascular monitoring tools: Use and misuse. Curr Opin Crit Care 2003; 9: 225–9Bellomo, R Uchino, S