The effects of crystalloid resuscitation on oxygen extration in whole body and gut during endotoxemia

Many investigators advocate aggressive fluid therapy in sepsis, yet changes in the microcirculation may make fluid counterproductive. Sepsis is characterized by a generalized "leak" in capillaries which may promote interstitial edema which in turn, may decrease diffusion of oxygen, incr...

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Bibliographic Details
Main Author: Gow, Kenneth William
Format: Others
Language:English
Published: 2009
Online Access:http://hdl.handle.net/2429/6495
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Summary:Many investigators advocate aggressive fluid therapy in sepsis, yet changes in the microcirculation may make fluid counterproductive. Sepsis is characterized by a generalized "leak" in capillaries which may promote interstitial edema which in turn, may decrease diffusion of oxygen, increase the distance from capillaries to cells, and alter capillary density. Further, fluid administration' may result in capillary hemodilution. Therefore, the author's hypothesis was that crystalloid resuscitation will impair the ability of tissue to extract oxygen. Four groups (n=8) of anesthetized pigs received either normal saline infusion (48 ml-kg-l-hr-1) or no saline, and E coli endotoxin (50 mg/kg i.v.) or no endotoxin. Whole body and gut oxygen delivery and consumption were measured during progressive hemorrhage. Dual line regression analysis was used to determine the onset of ischemia (DO2C) and oxygen extraction ratio (ERc). At onset of ischemia, gut was removed to determine degree of interstitial volume and the capillary hematocrit. With use of radiolabelled microspheres as a marker of blood flow, the gut blood flow transit time was determined. Endotoxin significantly decreased ERc for the whole body (0.82+0.06 to 0.55±0.08, p < 0.05) and gut (0.77 ± 0.07 to 0.52 ± 0.06, p < 0.05). Saline resuscitation also significantly decreased ERc in the control pigs for the whole body (0.82 ± 0.06 to 0.62 ± 0.08, p < 0.05) and gut (0.77 ± 0.07 to 0.67 ± 0.06, p < 0.05) but did not significantly change the already decreased ERc in the endotoxin treated pigs. Morphometric techniques revealed that saline resuscitation increased gut interstitial volume (p < 0.05), and lead to arterial hemodilution (p < 0.05) but not capillary hemodilution (p > 0.05). Using radiolabeled microspheres, saline was shown to increase the relative dispersion of blood flow transit times from 0.33 ± 0.08 to 0.72 ± 0.53 (p < 0.05). Thus, saline resuscitation impairs tissue oxygen extraction possibly due to interstitial edema or increased heterogeneity of microvascular blood flow. After endotoxin infusion, where ERc is already decreased, saline resuscitation has a lesser effect. Therefore, the author questions the use of aggressive crystalloid resuscitation for treatment of sepsis in humans. === Surgery, Department of === Medicine, Faculty of === Graduate