The present study found that the ECW/TBW was significantly higher in 30-day non-survivors than in 30-day survivors of septic shock (0.412 vs. 0.400, p = 0.001) and that the optimal cutoff value for predicting 30-day mortality was 0.40. ECW/TBW > 0.40 was the only parameter of body composition analysis associated with 30-day mortality in patients with septic shock. Septic shock patients with higher ECW/TBW were more likely to have active cancer, lower Hb concentrations, and higher PT than patients with lower ECW/TBW. To our knowledge, this is the first study to investigate the association between ECW/TBW and mortality of patients with septic shock.
BIA is an objective method that measures and analyzes body composition by sending a weak electrical current through the body. It is also a reproducible method that can be performed at the bedside. Its efficacy and accuracy in predicting body water composition are comparable to those of more classic methods.[19, 20] Thus, multi-frequency BIA can be used to assess the volume and nutritional status of patients with various diseases.[21–23] Furthermore, several studies have reported significant relationships between BIA-determined imbalances in body fluid and clinical outcomes in patients with, for example, chronic renal failure, chronic liver disease, and chronic obstructive pulmonary disease.[23–25] Extracellular fluid retention may play an important role in the progression and deterioration of diseases, indicating that pathophysiologic alterations in body fluid composition are associated with poor clinical outcomes.[26–28]
ECW/TBW as determined by BIA is frequently used to assess abnormal fluid status,[22, 29] and is a sensitive indicator of hydration changes.[30] Higher ECW/TBW ratios have been reported to predict clinical outcomes in patients with heart failure, liver diseases, renal disorders, and malignancies.[21–23, 31] Alterations in body fluid distribution without effective volume expansion result in excess fluid retention in the extracellular space, which can cause poor outcomes in critically ill patients.[32, 33] The present study found that ECW/TBW was the only statistically significant body composition variable associated with mortality in patients with septic shock.
Inflammatory processes during septic shock induce endothelial damage, increasing vascular permeability and shifting fluid from the intracellular to the extracellular space.[34–36] These alterations in body water distribution, such as ECW expansion, exacerbate the deterioration of cell membrane function.[37] In responding to cardiac dysfunction during septic shock, fluid retention volume may be increased by fluid resuscitation.[38] This accumulation of fluid in a third space leads to a vicious cycle, in which the patient’s condition deteriorates, further contributing to fluid retention during septic shock.
The normal range of ECW/TBW is between 0.360–0.390, with ratios ≥ 0.400 indicating an overhydrated state.[39, 40] The present study found that the optimal ECW/TBW cutoff value was 0.4, with ratios > 0.400 significantly associated with mortality in septic shock patients. The optimal cutoff was determined by calculating the area under the ROC curve, which showed that ECW/TBW > 0.4 was 1.67 times more frequent in 30-day non-survivors than in 30-day survivors. A previous study reported the average of ECW/TBW in patients with bacteremia was 0.510, suggesting that ECW/TBW can be higher in various conditions associated with reduced lean muscle mass, not only in septic shock.[41–44] The average ECW/TBW was found to be 0.42 in non-survivors admitted to the ICU, patients who tended to be malnourished.[32] Average ECW/TBW ratios were found to be 0.412 in patients with acute heart failure [23] and 0.40 in chronic dialysis patients.[45] Although these averages were higher than the normal reference value, they were lower in patients with chronic diseases than in those who were critically ill.
Fluid resuscitation and administration of multiple drugs to septic shock patients can result in faster and more dynamic hemodynamic changes. BIA is not only a prognostic tool but may be an effective and objective method of assessing real-time hemodynamic parameters at the bedside. Most importantly, BIA can repeatedly provide useful information about body fluid distribution or hydration status. Further studies are required to evaluate co-morbidities that can affect body fluid composition, enabling more accurate prediction of patient prognosis and determining whether fluid resuscitation is warranted in patients with septic shock.
The major limitation of this study was that it involved patients at a single-center. Local patterns of illness and racial characteristics may differ at other centers. In addition, it is unclear whether factors other than those considered can affect the results of BIA. The timing of fluid loading or BIA measurement, the presence of other electrical devices, and skin temperature or sweating could be sources of data disruption. Furthermore, the results of BIA may have been confounded by co-morbidities, such as chronic liver disease, chronic renal disease, and malignancies.