| Background and Objective: Sepsis and severe sepsis are major problems in critically ill children.Fluid resuscitation is integral to children with severe sepsis.However,once the infusion fluid exceeds the threshold,it may lead to fluid overload.Although most studies have confirmed that fluid overload will increase the mortality of children,the study of the relationship between fluid overload and prognosis in children is still controversial.The study of the relationship between fluid overload and prognosis in children with severe sepsis is also rarely reported.Currently,the main interventions on fluid overload are diuretics and renal replacement therapy.Despite the common use of Diuretics in clinical practice,its role in the management of pediatric patients remains controversial.The objective of our study were:(1)To analyze the effect of fluid overload on the outcomes in children with severe sepsis comprehensively.First,investigate the relationship between fluid overload(during different periods and different statistical methods)and adverse outcomes such as acute kidney injury(AKI)and mortality in children with severe sepsis.Then compare the predictive value of mortality among fluid overloads during different periods and different statistical methods.(2)To investigate the effects of diuretics on fluid accumulation status,AKI and mortality in children with sepsis.Methods:(1)In the retrospective study,we enrolled children with severe sepsis who were admitted to the pediatric intensive care unit(PICU)between January 2011 and March 2015.(2)In the prospective study,we enrolled children with sepsis who were admitted to PICU between May 2015 and December 2015.Daily fluid accumulation was calculated for each patient during the initial 7 days of a PICU stay according to the following formula: Percentage of fluid accumulation=[fluid intake(L)-fluid output(L)] / PICU admission weight(Kg)×100%.24 h fluid accumulation(fluid accumulation occurring in the first 24 hours of PICU admission),72 h and 7d fluid accumulation(a maximum daily fluid accumulation,an average daily fluid accumulation and a net fluid accumulation occurring in the first 72 hours and 7 days of PICU admission)and the maximum and the minimum daily fluid accumulation obtained during the first 7 days after PICU admission(Max-Min))were calculated.Pediatric Index of Mortality 2 score(PIM2)was calculated during the first 1 hour after PICU admission.Clinical and laboratory data including age,weight and gender were collected on the day of admission.Therapeutic interventions and medication management,including inotropes,diuretics,steroids,antibiotics,mechanical ventilation and renal replacement therapy;and outcomes including AKI?ALI?MODS and death were recorded daily until hospital discharge or death.The length of PICU stay and the length of hospital stay were also recorded.Results:(1)In the retrospective study,of the 202 patients,61(30.2%)died during PICU stay.Multivariate regression analysis showed that fluid overload,PIM2 score,MODS and AKI were independent risk factors for mortality in children with severe sepsis.24 h fluid overload(AOR=1.24;95% CI 1.08-1.41;P<0.001),72 h maximum fluid overload(AOR=1.36;95% CI 1.17-1.62;P<0.001),72 h average fluid overload(AOR=1.49;95% CI 1.23-1.82;P<0.001),72 h net fluid overload(AOR=1.28;95% CI 1.12-1.47;P<0.001),7d maximum fluid overload(AOR=5.47;95% CI 1.15-25.96;P=0.032),7d average fluid overload(AOR=1.48;95% CI 1.21-1.80;P<0.001)and 7d net fluid overload(AOR=1.07;95% CI 1.02-1.13;P=0.011)were significant associated with mortality even after adjustment for age,illness severity assessed by PIM2 scores,etc.There was no significant difference among the performances of 24 h fluid overload and 72 h fluid overload in predicting PICU mortality.72 h average fluid overload achieved the biggest AUC of 0.75 among these.24 h fluid overload,72 h fluid overload,7d fluid overload were significant associated with AKI.(2)A total of 82 children were enrolled during the prospective study period.The research on survivals showed that there was no significant difference in the 24 h fluid accumulation between diuretic and non-diuretic groups(P=0.469).The effects of diuretics on the 7d fluid accumulation were analyzed in all of the children.The results showed that there was significant difference in the maximum fluid accumulation between diuretic and non-diuretic groups.However,there was no significant difference in the average fluid accumulation(P=0.367)and net fluid accumulation(P=0.224)between the two groups.Multivariate regression analysis showed no significant correlation between diuretics and mortality after adjusting for illness severity,etc(P=0.194).Conclusions:(1)24h fluid overload,72 h fluid overload(72h maximum fluid overload,72 h average fluid overload,72 h net fluid overload)and 7d fluid overload(7d maximum fluid overload,7d average fluid overload,7d net fluid overload)were significantly associated with PICU mortality in children with severe sepsis.Fluid overload was an independent risk factor for mortality in children with severe sepsis after adjustment for age,illness severity assessed by PIM2 scores,suggesting that no matter when the fluid overload occurres during the PICU period,it is always closely related to the mortality of children with severe sepsis.(2)Fluid overload is a sensitive indicator of death in children with severe sepsis.And 24 h and 72 h fluid overload have the better predictive value.(3)24h fluid overload,72 h fluid overload,7d fluid overload were significant associated with AKI.Compared with the fluid intake,fluid overload was more significant associated with fluid output.(4)The research on survivals showed that there was no significant difference in the 24 h fluid accumulation between diuretic and non-diuretic groups.The effect of diuretics on the 7d fluid accumulation was analyzed in all of the children.The results showed that there was significant difference in the 7d maximum fluid accumulation between diuretic and non-diuretic groups.However,there was no significant difference in the 7d average fluid accumulation and 7d net fluid accumulation between the two groups.(5)The use of diuretics was more frequent in the non-survivals than the survivals.There was no significant correlation between diuretics and mortality after adjusting for illness severity,etc.In addition,compared with non-diuretics group,diuretics group prone to hypokalemia,hypochloremia and hypercapnia.Due to the small number of samples in this study,further large multi-center prospective studies were needed to assess the relationship among the diuretics,fluid overload and mortality in children with sepsis. |
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