The Effect Of Furosemide On Acute Kidney Injury And Mortality In Critically Ill Children With Fluid Overload

Background and Objective:Acute kidney injury(AKI)is a common clinical syndrome.Early fluid resuscitation is one of the important measures of rescue therapy in the pediatric intensive care unit(PICU).Given the complexity of the disease in pathogenesis and the individual difference of the children with PICU,excessive resuscitation may lead to fluid overload(FO)in critically ill children.In recent years,FO has been proved to be associated with AKI and predictive of the hospital mortality in critically ill children.Furosemide os the most commonly used loop diuretic in clinic.Studies have found that furosemide may improve the survival of AKI patients by increasing urine output,but cannot reverse the deterioration of renal fimction.However,the data on whether furosemide can effectively reduce FO,and therefore reducing the occurrence of AKI and improving outcomes in critically ill children are scarce.The purpose of this study was:(1)to investigate the effects of furosemide on FO,AKI and mortality in critically ill children within 7 days after PICU admission;(2)to investigate the effect of furosemide on AKI and mortality in critically ill children with FO.Methods:(1)In the retrospective study,we enrolled the critically ill children who were admitted to the PICU between January and December 2016.(2)Among all critically ill children,those with FO≥5%during the first 24 hours after PICU admission were included for further study.Clinical and laboratory data including age,weight,gender,admission diagnosis and various signs were collected on the day of admission;blood test results,including the blood gas analysis,electrolytes,blood biochemical within the first 24 hours in PICU;clinical manifestation and diagnosis,including oliguria,sepsis,shock,disseminated intravascular coagulation(DIC),acute lung injury(ALI),multiple organ dysfunction syndrome(MODS);and AKI within 7 days of the PICU;medication management and therapeutic interventions,including mechanical ventilation(MV)and renal replacement therapy(RRT),furosemide,inotropes,steroids,antibiotics,et al;and the length of PICU stay and the length of hospital stay were also recorded.AKI is defined as any of the following:1)increase in serum creatinine(SCr)by≥0.3 mg/dl(≥26.5 μmol/l)within 48 hours;or 2)increase in SCr toΘ1.5 times baseline,which is known or presumed to have occurred within the prior 7 days;or 3)urine volume<0.5 ml/kg/hour for 6 hours.Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)was calculated during the first 24 hours after PICU admission.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=(daily fluid intake-total output)(L)/PICU weight at admission(kg)x 100%.The daily dose of furosemide(total dose,frequency of administration)was counted in the PICU for 7 days.The average single furosemide dose was calculated for each patient according to the following formula:The average single dose=total furosemide dose/(PICU admit weight × frequency of administration).Mortality was the primary outcome.Secondary outcomes included length of PICU stay and the length of hospital stay.According to the use of furosemide in critically ill children within 7 days of PICU,they were divided into treatment group and control group;according to the use of furosemide in critically ill children with FO≥5%during the first 24h after admission on 2nd-7th day of PICU,they were divided into treatment group and control group.Multiple linear regression analysis was used to evaluate the effect of furosemide on maximum FO and mean FO.Multivariate logistic regression analysis was used to evaluate the relationship between firosemide and AKI and mortality after adjusting for confounding factors.Result:(1)This study enrolled 518 critically ill children.The use rate of furosemide was 50.6%,the AKI incidence rate was 23.4%,and the mortality rate was 18.5%.Compared with the control group,the maximum FO level(4.23%vs.3.77%,P=0.012)was higher,and the mean FO level(1.24%vs.2.04%,P<0.001)was lower in the treatment group.Stepwise multiple linear regression analysis showed that furosemide is one of the factors affecting the maximum FO(B=0.020,P=0.003),but not the mean FO(P>0.05).Compared with the control group,the incidence of AKI(33.5%vs.12.9%,P<0.001)and mortality(26.6%vs.10.2%,P<0.001)were significantly higher,and the length of PICU and hospital stay was longer(P<0.001)in the treatment group.Multivariate logistic regression analysis showed that fiurosemide was an independent risk factor for AKI(AORFI3.181,95%Cl:1.944-5.206,P<0.001),but not for mortality(P=0.266)in critically ill children after adjusting for confounding factors.(2)The second part of the study included 129 critically ill children with FO≥5%during the first 24h after admission.The use rate of furosemide on the 2nd-7th day of the PICU was 32.6%,the AKI incidence rate in the PICU 7 days was 29.5%,and the mortality rate was 28.7%.Compared with the control group,the mean FO level(0.93%vs.3.67%,P=0.007)was significantly lower in the treatment group.There was no significant difference in maxin.tm FO between the two groups(P=0.984).Mxultivariate logistic regression analysis firther confirmed that furosenide was an independent risk factor for AKI(AOR=2.668,95%Cl:1.420-12.460,P=0.042),but not for mortality(P>0.05)in critically ill children with FO≥5%during the first 24h after admission.Conclusion:1.The maximum FO level in the furosemide treatment group was higher than that in the control group,but the mean FO was lower in the furosemide treatment than in the control group.After adjusting for the relevant confounders,furosemide is only associated with the maximum FO and is one of the factors affecting the maximum FO level in critically ill children.2.The use rate of furosemide in the AKI or non-survival group was higher than that in the non-AKI or the survival group.Furosemide was an independent risk factor for AKI in critically ill children after adjusting for confounding factors.However,it was not associated with mortality after adjustment.3.In critically ill children with FO≥5%during the first 24 hours after adnission,the use of furosemide within the 2-7 days of the PICU may reduce the mean FO level.However,furosemide remained as an independent risk factor for AKI in critically ill children with FO≥5%.