Fluid resuscitation is the basis for maintaining hemodynamic stability and organ and tissue perfusion and for increasing oxygen delivery during the rescue phase of septic shock . Studies have shown that early resuscitation can reduce the mortality of patients with sepsis and septic shock [8–10]. However, excessive fluid resuscitation may be harmful to patients. Many studies have shown that a positive fluid balance or FO is closely associated with the occurrence of acute kidney injury (AKI) and poor patient prognosis [11–16]. Chao et al.  found that a negative cumulative body fluid balance from days 1 to 4 reduced the mortality of patients with severe influenza. Judith et al.  found that cumulative FO during the first 5 days of pediatric ICU (PICU) admission was an independent risk factor for poor prognosis in children with septic shock. A recent prospective study also showed that in patients who underwent cardiac or aortic surgery, continuous positive fluid balance was associated with AKI and hemodialysis and that the risk of AKI in patients with a continuous positive fluid balance increased by 7.1 times . Our study found that the total fluid balance from days 1 to 5 for patients in the deceased group was significantly higher than that for patients in the survival group, suggesting that total fluid balance from days 1 to 5 may be associated with poor patient prognosis. Furthermore, Cox regression analysis indicated that the total fluid balance from days 1 to 5 was an independent risk factor for poor patient prognosis; the risk of death increased by 0.1% for every 1 ml increase. However, a previous study  has shown that after adjusting for disease severity and the lactate clearance rate, cumulative fluid balance was not associated with increased mortality. The reason for this result may be related to the retrospective nature of the analysis. The results of our study showed that there was no significant difference in the mortality rate between sexes, among different nationality groups, and among different ages (P>0.05); however, the mortality rate was significantly different among different sources (P<0.05), with the mortality rate for sepsis patients from wards being the highest. One explanation for this result may be that ICU physicians paid more attention to sepsis than general ward physicians or that patients in wards received more fluid therapy. This is just speculation, as relevant data were not collected to address that issue. The comparison of clinical factors showed that there was no difference in fluid balance between sexes, among different nationality groups, and among different sources (P >0.05), indicating that these clinical factors had no effect on fluid balance. However, the fluid balance for patients with shock was significantly higher than that for patients with stable hemodynamics at the time of ICU admission, and the mortality rate for patients with septic shock was significantly higher (49.85% vs. 27.7%), a finding that is consistent with the clinical situation. However, it is not clear whether the poor prognosis of patients is due to septic shock or due to a positive fluid balance. More fluid therapy or a more positive fluid balance may be related to severe vascular leakage and third space leakage, but whether it is a direct cause of increased mortality remains unclear. Because this was a retrospective study, it can only be concluded that a more positive fluid balance may be associated with poor patient prognosis. Cox regression analysis showed that APACHE II score, SOFA score, PLT, and Lac were associated with poor patient prognosis. Studies have confirmed that APACHE II and SOFA scores are associated with poor patient prognosis . Regarding the prediction of poor patient prognosis, the ROC curve results indicated a sensitivity of 55.6% and specificity of 76.6% for APACHE II > 20 points and a sensitivity of 51.6% and specificity of 80.0% for SOFA > 8 points. The decrease in PLT may be related to the progression of sepsis and dilution caused by the increased body volume resulting from a positive fluid balance. Regression analysis indicated that for every unit increase in PLT, the risk of death decreased by 0.2%. Elevated Lac represents oxygen utilization disorder in the body, which may be caused by oxygen uptake, and oxygen utilization disorder in the tissues, which may be due to the widening of the capillary space after fluid treatment. Among the clinical factors, fluid balance was significantly increased when Lac>2.0 mmol/L. Lac and fluid balance may have a causal relationship. Unfortunately, this study could not determine cause and effect as it was a retrospective analysis. BUN and CREA in the deceased group were significantly increased at the time of ICU admission; these findings may explain the excessive total fluid load from days 1 to 5 in the deceased group.
Based on the above research results, we need more rigorous studies to re-examine fluid resuscitation therapy for sepsis . Degradation or damage to the glycocalyx layer of the vascular endothelial cell membrane can occur in the early stage of sepsis, and fluid resuscitation therapy may further damage the glycocalyx layer, especially during rapid infusions and transfusions that result in hypervolemia [23, 24]. The destruction of the glycocalyx layer of vascular endothelial cells may cause capillary leakage, local tissue edema, and oxygen utilization disorder, which may be side effects of fluid resuscitation treatment, thereby affecting the prognosis of patients. The use of hypertonic fluid for small volume resuscitation in patients with sepsis also requires further study.