Anesth Analg 2002;95:251-252
© 2002 International Anesthesia Research Society
LETTERS TO THE EDITOR
Physiological or Functional Fluid Spaces
Robert G. Hahn, MD, PhD
Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
To the Editor: Tollofsrud et al. recently studied the distribution and elimination of two infusion fluids in sheep (1). I would like to question his claim of studying "true physiological spaces" because hemoglobin (Hb) changes probably cannot be used to indicate the distribution of crystalloid fluid between the plasma and extravascular space during intravascular fluid administration. Distribution can only be governed by permeability or perfusion. The Hb changes indicate a distribution process that requires approximately 30 min to be completed (2,3) although the permeability for water is so high that equilibrium across the capillary membrane must be reached much faster (4). Crystalloid fluid has probably equilibrated between the plasma and interstitial fluid spaces in the lung (blood flow 14 L/min per liter tissue water) long before the fluid has even reached the muscles in the legs (0.04 L/min per liter tissue water at rest). My belief is that well-perfused and poorly perfused regions of the body correspond to the reported plasma and extravascular spaces in the Tollofsrud et al. study (1), at least during and for 30 min after infusion. Multiplying the Hb changes with the measured plasma volume at baseline then makes little sense.
As this issue remains unresolved, however, our different interpretations actually prompt an investigation of how crystalloid fluid distributes with respect to physiological spaces.
References
- Tollofsrud S, Elgjo GI, Prough DS, et al. The dynamics of vascular volume and fluid shifts of lactated Ringer’s solution and hypertonic-saline-dextran solutions infused in normovolemic sheep. Anesth Analg 2001; 93: 823–31.[Abstract/Free Full Text]
- Svensén C, Hahn RG. Volume kinetics of Ringer solution, dextran 70, and hypertonic saline in male volunteers. Anesthesiology 1997; 87: 204–12.[Web of Science][Medline]
- Drobin D, Hahn RG. Volume kinetics of Ringer’s solution in hypovolemic volunteers. Anesthesiology 1999; 90: 81–91.[Web of Science][Medline]
- Guyton AC, Hall JE. Textbook of medical physiology, 9th Ed. Philadelphia: WB Saunders, 1996: 185–6.
Response
George C. Kramer, PhD,
Donald S. Prough, MD, and
Stein Tølløfsrud, MD, PhD
In Response: We thank Dr. Hahn for his provocative letter that challenges our use of the term "true physiological spaces" in Tollofsrud et al. (1). Perhaps the adjective "true" is presumptuous, but we stand by our measurements of blood volume, plasma volume, and changes in extravascular volume as correct and representative of traditional physiologic spaces. These spaces and their respective changes with fluid infusion can be analyzed using indicator dilution and mass balance as described (1). Moreover, they provide both the physiologist and the clinician with a useful frame of reference for describing responses to fluid therapy. Dr. Hahn and his colleagues have pioneered the analysis of fluid infusions using a novel volume kinetic approach developed from well-established pharmacokinetic principles (2,3). Volume kinetic analysis describes fluid therapy in terms of model distribution compartments and transfer coefficients. However, the physiology and physical forces governing drug and fluid distribution are quite different. Drugs are distributed between the blood and tissues via diffusion processes and, as Dr. Hahn points out, drug transfer can only be governed by permeability or perfusion. On the other hand, infused fluid is largely water and the transfer of a net fluid volume is determined primarily by forces of convection, mainly filtration or reabsorption in response to hydrostatic and osmotic pressure gradients.
Our analysis begins with measuring plasma volume using the tracer (Evan’s blue dye) dilution technique. We then use the changes in hemoglobin concentration (Hb), as Dr. Hahn uses in the volume kinetic approach, to indicate the dilution of the blood volume and further calculate changes in extravascular volume using cumulative infused volume, urinary output, and mass balance. Dr. Hahn has most often used venous hematocrit and our group used arterial hematocrit, but given the rapid circulation times with normovolemia these should be essentially identical even during the 30-min infusion. Dr. Hahn makes a valid point that one limitation of using Hb as a tracer is that any rapid changes in Hb concentration would be biased to reflect changes in well perfused compartments earlier than those in poorly perfused compartments. If poorly perfused compartments represent a disproportionately large portion of blood volume, then initial Hb dilution would be greater than would occur if infused volume were immediately mixed in the entire blood volume; therefore, our calculated initial volume expansion would overestimate actual expansion. In such a situation, crystalloid solutions would initially be even less efficient than our analysis suggests. Initial expansion during hypertonic saline infusion would be similarly overestimated, unless hypertonic saline were to alter the relative proportion of poorly perfused compartments. As a consequence, our analysis focused on the changes that occurred 30 min after the end of the infusions. An error resulting from a poorly perfused component of the blood volume would be proportional to the size of the poorly perfused component compared to the well-perfused component. However, at some point after infusion (Dr. Hahn suggests 30 min) this error would be negligible. Future studies need to quantify the magnitude and time course of any error resulting from the poorly perfused compartments. Such knowledge should advance modeling based either on indicator dilution-mass balance or volume kinetics. We disagree with Dr. Hahn’s statement that the "poorly perfused regions of the body correspond to the reported extravascular spaces" of our study. Rather, if our initial measurements overestimate vascular expansion, then they underestimate extravascular expansion.
One advantage of our approach to analysis of fluid infusion is that fluid handling is described in terms of traditional physiological spaces that are familiar to both the scientist and the clinician, whereas volume kinetic modeling describes "functional" spaces that are less familiar. Tollofrsrud et al. (1) present the postinfusion time course of the blood volume expansion induced by either 25 mL/kg isotonic lactated Ringer’s solution or 4 mL/kg 7.5% NaCl/6% dextran (HSD). For example, at 30 min after infusion the volume expansion with lactated Ringer’s solution is 1.7 ± 0.6 mL/kg or 0.07 mL per mL infused, whereas with HSD volume expansion is 5.1 ± 0.9 mL/kg or 1.3 mL per mL infused. Such numbers can be used by anesthesiologists to estimate volume expansion after fluid infusion. Many may find it more difficult to interpret volume kinetic analysis (3), which concluded that the primary fluid volume of 25 mL/kg of Ringer’s solution is 71 ± 10 mL/kg for an isotonic crystalloid solution and 15 ± 1 mL/kg for a 3 mL/kg infusion of 7.5% NaCl.
We suggest that a better model, incorporating modifications of the indicator dilution-mass balance technique or volume kinetic analysis or both approaches combined, is needed to provide a clinically useful paradigm of fluid therapy. However, at present these approaches are limited, as suggested by Dr. Hahn, by our incomplete knowledge of the heterogeneity of blood flow and tissue blood volumes.
References
- Tølløfsrud S, Elgo GI, Prough DS, et al. The dynamics of vascular volume and fluid shifts of lactated Ringer’s solution and hypertonic-saline-dextran solutions infused in normovolemic sheep. Anesth Analg 2001; 93: 823–31.
- Ståhle L, Nilsson A, Hahn RG. Modelling the volume of expandable body fluid spaces during IV fluid therapy. Br J Anaesth 1997; 78: 138–43.[Abstract/Free Full Text]
- Svensén C, Hahn RG. Volume kinetics of Ringer solution, dextran 70, and hypertonic saline in male volunteers. Anesthesiology 1997; 87: 204–12.
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