Adverse Effects of Fluid Overload

The accumulation of interstitial and alveolar fluid in the lungs plays a central role in the pathogenesis of ARDS. The detrimental impact of pulmonary edema may not be immediately apparent clinically because the quantity of pulmonary edema fluid, which is reflected by extravascular lung water, can increase two- to threefold prior to a significant decrease in arterial oxygenation [14]. However, clinical data suggest that the quantity of edema fluid in patients appears to be an important determinant of hospital morbidity and mortality in patients with ARDS. Almost 30 years ago, Simmons et al. observed that an increase in body weight and fluid balance in ARDS patients was correlated with survival [15]. Humphrey et al. subsequently demonstrated that patients with ARDS who achieved goal-directed fluid removal had a statistically greater hospital survival compared to those not attaining this therapeutic end point [16]. In a later study, Sakr et al. showed that even after controlling for degree of organ dysfunction and size of tidal volumes, patients with ARDS who survived their ICU stay had a net negative fluid balance compared to nonsurvivors [17]. The association between positive fluid balance and adverse outcome has also been reported in the pediatric population [18]. Other studies have focused on quantification of the amount of pulmonary edema using measures of extravascular lung water (EVLW) obtained by thermodilution techniques and evaluated the influence on outcome in patients at risk for ARDS. Sakka et al. retrospectively analyzed 373 intensive care unit (ICU) patients and found that the maximum quantity of EVLW was significantly higher in nonsurvivors than in survivors [19]. However, the prognostic effect of the quantity of edema fluid, measured by thermodilution, was not found in patients presenting with ARDS in this study. However, studies where EVLW was indexed to ideal body weight (extravascular lung water index, EVLWI) have found EVLW to be a significant predictor of mortality. Phillips et al. found that the EVLWI measured on day 1 of ARDS was found to be predictive of mortality [20]. In another study, Cordemans et al. reported that the maximum difference between EVLWI measurements during the patient’s stay in the ICU was related to poor prognosis [21]. More recently, Jozwiak et al. reported that in patients with ARDS, both the EVLWI and pulmonary vascular permeability index, a measure of the integrity of the alveolar-capillary barrier obtained by thermodilution, were independent risk factors for mortality [22].