Positive Cumulative Fluid Balance Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome in the Setting of Acute Kidney Injury.
ABSTRACT: OBJECTIVES:As acute kidney injury and elevated cumulative fluid balance commonly co-occur in pediatric acute respiratory distress syndrome, we aimed to identify risk factors for their development and evaluate their independent relationships with mortality. We hypothesized that acute kidney injury and elevated cumulative fluid balance would be associated with markers of inflammation and that children with elevated cumulative fluid balance and concomitant acute kidney injury would have worse outcomes than other children. DESIGN:Prospective observational study using the pediatric Risk, Injury, Failure, Loss, End-Stage acute kidney injury classification. SETTING:Five academic PICUs. PATIENTS:Two-hundred sixty patients 1 month to 18 years old meeting the Berlin definition of acute respiratory distress syndrome between 2008 and 2014. INTERVENTIONS:None. MEASUREMENTS AND RESULTS:PICU mortality was 13% (34/260). Relative to survivors, nonsurvivors had greater cumulative fluid balance on day 3 of acute respiratory distress syndrome (+90.1?mL/kg; interquartile range 26.6-161.7 vs +44.9?mL/kg; interquartile range 10.0-111.3; p = 0.008) and also had higher prevalence of acute kidney injury on day 3 of acute respiratory distress syndrome (50% vs 23%; p = 0.001). On stratified analysis, greater cumulative fluid balance on day 3 of acute respiratory distress syndrome was associated with mortality among patients with concomitant acute kidney injury (+111.5?mL/kg for nonsurvivors; interquartile range 82.6-236.8 vs +58.5?mL/kg for survivors; interquartile range 0.9-176.2; p = 0.041) but not among patients without acute kidney injury (p = 0.308). The presence of acute kidney injury on acute respiratory distress syndrome day 3 was associated with mortality among patients with positive cumulative fluid balance (29.1% vs 10.4% mortality; p = 0.001) but not among patients with even or negative cumulative fluid balance (p = 0.430). Day 1 plasma interleukin-6 levels were associated with the development of day 3 positive cumulative fluid balance, day 3 acute kidney injury, and PICU mortality and the association between elevated day 1 interleukin-6 and PICU mortality was partially mediated by the interval development of day 3 positive cumulative fluid balance and day 3 acute kidney injury (p < 0.001). CONCLUSIONS:In pediatric acute respiratory distress syndrome, elevated cumulative fluid balance on day 3 of acute respiratory distress syndrome is associated with mortality specifically in patients with concomitant acute kidney injury. Plasma interleukin-6 levels are associated with the development of positive cumulative fluid balance and acute kidney injury, suggesting a potential mechanism by which inflammation might predispose to mortality.
Project description:In the Fluid and Catheter Treatment Trial (FACTT) of the National Institutes of Health Acute Respiratory Distress Syndrome Network, a conservative fluid protocol (FACTT Conservative) resulted in a lower cumulative fluid balance and better outcomes than a liberal fluid protocol (FACTT Liberal). Subsequent Acute Respiratory Distress Syndrome Network studies used a simplified conservative fluid protocol (FACTT Lite). The objective of this study was to compare the performance of FACTT Lite, FACTT Conservative, and FACTT Liberal protocols.Retrospective comparison of FACTT Lite, FACTT Conservative, and FACTT Liberal. Primary outcome was cumulative fluid balance over 7 days. Secondary outcomes were 60-day adjusted mortality and ventilator-free days through day 28. Safety outcomes were prevalence of acute kidney injury and new shock.ICUs of Acute Respiratory Distress Syndrome Network participating hospitals.Five hundred three subjects managed with FACTT Conservative, 497 subjects managed with FACTT Liberal, and 1,124 subjects managed with FACTT Lite.Fluid management by protocol.Cumulative fluid balance was 1,918 ± 323 mL in FACTT Lite, -136 ± 491 mL in FACTT Conservative, and 6,992 ± 502 mL in FACTT Liberal (p < 0.001). Mortality was not different between groups (24% in FACTT Lite, 25% in FACTT Conservative and Liberal, p = 0.84). Ventilator-free days in FACTT Lite (14.9 ± 0.3) were equivalent to FACTT Conservative (14.6 ± 0.5) (p = 0.61) and greater than in FACTT Liberal (12.1 ± 0.5, p < 0.001 vs Lite). Acute kidney injury prevalence was 58% in FACTT Lite and 57% in FACTT Conservative (p = 0.72). Prevalence of new shock in FACTT Lite (9%) was lower than in FACTT Conservative (13%) (p = 0.007 vs Lite) and similar to FACTT Liberal (11%) (p = 0.18 vs Lite).FACTT Lite had a greater cumulative fluid balance than FACTT Conservative but had equivalent clinical and safety outcomes. FACTT Lite is an alternative to FACTT Conservative for fluid management in Acute Respiratory Distress Syndrome.
Project description:Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients.Retrospective cohort study.Urban academic medical center ICU.ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15?mL/min/1.73 m or receiving chronic dialysis were excluded.None.A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9?L for acute kidney injury+/chronic kidney disease+; 3.8?L for acute kidney injury-/chronic kidney disease+; 4.3?L for acute kidney injury+/chronic kidney disease-; and 1.5?L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury.Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.
Project description:It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality.Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter.Acute Respiratory Distress Syndrome Network hospitals.One thousand patients.None.The incidence of acute kidney injury, defined as an absolute rise in creatinine of ?0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18).Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.
Project description:INTRODUCTION:Acute respiratory distress syndrome (ARDS) is characterized by acute, diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability, pulmonary oedema and loss of aerated tissue. Previous literature showed that restrictive fluid therapy in ARDS shortens time on mechanical ventilation and length of ICU-stay. However, the effect of intravenous fluid use on mortality remains uncertain. We investigated the relationship between cumulative fluid balance (FB), time on mechanical ventilation and mortality in ARDS patients. MATERIALS AND METHODS:Retrospective observational study. Patients were divided in four cohorts based on cumulative FB on day 7 of ICU-admission: ?0 L (Group I); 0-3.5 L (Group II); 3.5-8 L (Group III) and ?8 L (Group IV). In addition, we used cumulative FB on day 7 as continuum as a predictor of mortality. Primary outcomes were 28-day mortality and ventilator-free days. Secondary outcomes were 90-day mortality and ICU length of stay. RESULTS:Six hundred ARDS patients were included, of whom 156 (26%) died within 28 days. Patients with a higher cumulative FB on day 7 had a longer length of ICU-stay and fewer ventilator-free days on day 28. Furthermore, after adjusting for severity of illness, a higher cumulative FB was associated with 28-day mortality (Group II, adjusted OR (aOR) 2.1 [1.0-4.6], p = 0.045; Group III, aOR 3.3 [1.7-7.2], p = 0.001; Group IV, aOR 7.9 [4.0-16.8], p<0.001). Using restricted cubic splines, a non-linear dose-response relationship between cumulative FB and probability of death at day 28 was found; where a more positive FB predicted mortality and a negative FB showed a trend towards survival. CONCLUSIONS:A higher cumulative fluid balance is independently associated with increased risk of death, longer time on mechanical ventilation and longer length of ICU-stay in patients with ARDS. This underlines the importance of implementing restrictive fluid therapy in ARDS patients.
Project description:Despite declining mortality, acute respiratory distress syndrome is still involved in up to one third of pediatric intensive care deaths. The recently convened Pediatric Acute Lung Injury Consensus Conference has outlined research priorities for the field, which include the need for accurate bedside risk stratification of patients. We aimed to develop a simple yet robust model of mortality risk among pediatric patients with acute respiratory distress syndrome to facilitate the targeted application of high-risk investigational therapies and stratification for enrollment in clinical trials.Prospective, multicenter cohort.Five academic PICUs.Three hundred eight children greater than 1 month and less than or equal to 18 years old, admitted to the ICU, with bilateral infiltrates on chest radiograph and PaO2/FIO2 ratio less than 300 in the clinical absence of left atrial hypertension.None.Twenty clinical variables were recorded in the following six categories: demographics, medical history, oxygenation, ventilation, radiographic imaging, and multiple organ dysfunction. Data were measured 0-24 and 48-72 hours after acute respiratory distress syndrome onset (day 1 and 3) and examined for associations with hospital mortality. Among 308 enrolled patients, mortality was 17%. Children with a history of cancer and/or hematopoietic stem cell transplant had higher mortality (47% vs 11%; p < 0.001). Oxygenation index, the PaO2/FIO2 ratio, extrapulmonary organ dysfunction, Pediatric Risk of Mortality-3, and positive cumulative fluid balance were each associated with mortality. Using two statistical approaches, we found that a parsimonious model of mortality risk using only oxygenation index and cancer/hematopoietic stem cell transplant history performed as well as other more complex models that required additional variables.In the PICU, oxygenation index and cancer/hematopoietic stem cell transplant history can be used on acute respiratory distress syndrome day 1 or day 3 to predict hospital mortality without the need for more complex models. These findings may simplify risk assessment for clinical trials, counseling families, and high-risk interventions such as extracorporeal life support.
Project description:Soluble suppression of tumorigenicity-2 is a biomarker of myocardial strain and inflammation. The characteristics of acute respiratory distress syndrome include inflammation and cardiovascular dysfunction. We sought to determine whether plasma soluble suppression of tumorigenicity-2 concentration is associated with outcome and response to conservative fluid management and whether soluble suppression of tumorigenicity-2 concentration discriminates acute respiratory distress syndrome from decompensated heart failure.A retrospective analysis of the Fluid and Catheter Treatment Trial, a multi-center randomized controlled trial of conservative fluid management in the acute respiratory distress syndrome, as well as of a cohort of patients with decompensated heart failure.Twenty acute care hospitals.Eight hundred twenty-six patients with acute respiratory distress syndrome and 209 patients with acutely decompensated heart failure.Nonsurvivors had higher day 0 (p < 0.0001) and day 3 (p < 0.0001) soluble suppression of tumorigenicity-2 concentrations. After adjustment for severity of illness, higher soluble suppression of tumorigenicity-2 concentration was associated with mortality, with odds ratioadj 1.47 (95% CI, 0.99-2.20; p = 0.06) at day 0, 2.94 (95% CI, 2.00-4.33; p < 0.0001) at day 3, and 3.63 (95% CI, 2.38-5.53; p < 0.0001) if soluble suppression of tumorigenicity-2 increased between days. Cumulative fluid balance was more positive among patients with higher day 0 (median, 5,212 mL [interquartile range, 200-12,284 mL] vs median, 2,020 mL [interquartile range, -2,034 to 7,091 mL]; p < 0.0001) and day 3 soluble suppression of tumorigenicity-2 (median, 7,678 mL [interquartile range, 2,217-14,278 mL] vs median, 1,492 mL [interquartile range, -2,384 to 6,239 mL]; p < 0.0001). Soluble suppression of tumorigenicity-2 showed excellent discriminative ability between the Fluid and Catheter Treatment Trial and heart failure populations (area under receiver-operating characteristic curve = 0.98; p < 0.0001).Higher soluble suppression of tumorigenicity-2 concentrations are associated with worse outcome in acute respiratory distress syndrome and may have value for discriminating acute respiratory distress syndrome from heart failure.
Project description:BACKGROUND:The interactive effect of cumulative input and output on achieving optimal fluid balance has not been well elucidated in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated the interrelation of fluid components with mortality in patients with AKI requiring CRRT. METHODS:This is a retrospective observational study conducted with a total of 258 patients who were treated with CRRT due to AKI between 2016 and 2018 in the intensive care unit of Ewha Womans University Mokdong Hospital. The amounts of fluid input and output were assessed at 24-h and 72-h from the initiation of CRRT. The study endpoints were 7- and 28-day all-cause mortality. RESULTS:The mean patient age was 64.7 ± 15.8 years, and 165 (64.0%) patients were male. During the follow-up, 7- and 28-day mortalities were observed in 120 (46.5%) and 157 (60.9%) cases. The patients were stratified into two groups (28-day survivors vs. non-survivors), and the cumulative fluid balances (CFBs) at 24 h and 72 h were significantly higher in the 28-day non-survivors compared with the survivors. The increase in 24-h and 72-h CFB was significantly associated with an increase in 7- and 28-day mortality risks. To examine the interactive effect of cumulative input or output on the impact of CFB on mortality, we also stratified patients into three groups based on the tertile of 24-h and 72-h cumulative input or output. The increases in 24-h and 72-h CFBs were still significantly related to the increases in 7-day and 28-day mortality, irrespective of the cumulative input. However, we did not find significant associations between increase in 24-h and 72-h CFB and increase in mortality risk in the groups according to cumulative output tertile. CONCLUSIONS:The impact of cumulative fluid balance on mortality might be more dependent on cumulative output. The physicians need to decrease the cumulative fluid balance of CRRT patients as much as possible and consider increasing patient removal.
Project description:In acute respiratory distress syndrome, conservative fluid management increases ventilator-free days without affecting mortality. Response to fluid management may differ based on patients' initial central venous pressure. We hypothesized that initial central venous pressure would modify the effect of fluid management on outcomes.Retrospective analysis of the Fluid and Catheter Treatment Trial, a multicenter randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. We examined the relationship between initial central venous pressure, fluid strategy, and 60-day mortality in univariate and multivariable analysis.Twenty acute care hospitals.Nine hundred thirty-four ventilated acute respiratory distress syndrome patients with a central venous pressure available at enrollment, 609 without baseline shock (for whom fluid balance was managed by the study protocol).None.Among patients without baseline shock, those with initial central venous pressure greater than 8 mm Hg experienced similar mortality with conservative and liberal fluid management (18% vs 18%; p = 0.928), whereas those with central venous pressure of 8 mm Hg or less experienced lower mortality with a conservative strategy (17% vs 36%; p = 0.005). Multivariable analysis demonstrated an interaction between initial central venous pressure and the effect of fluid strategy on mortality (p = 0.031). At higher initial central venous pressures, the difference in treatment between arms was predominantly furosemide administration, which was not associated with mortality (p = 0.122). At lower initial central venous pressures, the difference between arms was predominantly fluid administration, with additional fluid associated with increased mortality (p = 0.013).Conservative fluid management decreases mortality for acute respiratory distress syndrome patients with a low initial central venous pressure. In this population, the administration of IV fluids seems to increase mortality.
Project description:<h4>Objectives</h4>Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients.<h4>Design</h4>Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study.<h4>Setting</h4>Single-center quaternary level PICU.<h4>Patients</h4>One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (? 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality.<h4>Conclusions</h4>The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.
Project description:BACKGROUND:Fluid overload is associated with morbidity and mortality in patients receiving renal replacement therapy (RRT). We aimed to explore whether fluid overload at initiation of RRT was independently associated with mortality and whether changes in cumulative fluid balance during RRT were associated with outcome. METHODS:We retrospectively analysed the data of patients who were admitted to the multidisciplinary adult intensive care unit (ICU) in a tertiary care centre in the UK between 2012 and 2015 and received continuous RRT (CRRT) for acute kidney injury for at least 24?h. We collected baseline demographics, body mass index (BMI), comorbidities, severity of illness, laboratory parameters at CRRT initiation, daily cumulative fluid balance (FB), daily prescribed FB target, fluid bolus and diuretic administration and outcomes. The day of the lowest cumulative FB during CRRT was identified as nadir FB. RESULTS:Eight hundred twenty patients were analysed (median age 65?years; 49% female). At CRRT initiation, the median cumulative FB was +?1772?ml; 89 patients (10.9%) had a cumulative FB?>?10% body weight (BW). Hospital survivors had a significantly lower cumulative FB at CRRT initiation compared to patients who died (1495 versus 2184?ml; p <?0.001). In the 7?days after CRRT initiation, hospital survivors had a significant decline in cumulative FB (mean decrease 473?ml per day, p <?0.001) whilst there was no significant change in cumulative FB in non-survivors (mean decrease 112?ml per day, p =?0.188). Higher severity of illness at CRRT initiation, shorter duration of CRRT, the number of days without a prescribed FB target and need for higher doses of noradrenaline were independent risk factors for not reaching a FB nadir during CRRT. Multivariable analysis showed that older age, lower BMI, higher severity of illness, need for higher doses of noradrenaline and smaller reductions in cumulative FB during CRRT were independent risk factors for ICU and hospital mortality. Cumulative FB at CRRT initiation was not independently associated with mortality. CONCLUSION:In adult patients receiving CRRT, a decrease in cumulative FB was independently associated with lower mortality. Fluid overload and need for vasopressor support at CRRT initiation were not independently associated with mortality after correction for severity of illness.