Positive Cumulative Fluid Balance Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome in the Setting of Acute Kidney Injury

Zinter, Matt S; Spicer, Aaron C.; Liu, Kathleen D.; Orwoll, Benjamin; Alkhouli, Mustafa F.; Brakeman, Paul; Calfee, Carolyn S.; Matthay, Michael A.; Sapru, Anil

doi:10.1097/pcc.0000000000001845

Cited by 34 publications

(36 citation statements)

References 56 publications

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“…Regarding the outcome of AKI, the addition of IL-6 as a covariate to the subgroup adjusted model decreased the Day 1 total FGF23 OR from 1.42 (95% CI 0.95, 2.14; p = 0.09) to 1.26 (95% CI 0.81, 1.96; p = 0.31) ( Table 4 ). In this adjusted model, plasma IL-6 concentrations were independently associated with Day 3 AKI (OR 1.59 [95% CI 1.13, 2.22], p = 0.007), similar to what has been observed in other analyses of this cohort [35]. Given the association between IL-6 and AKI, we performed mediation analysis to quantify the degree to which variation in IL-6 concentrations mediated the FGF23-AKI association.…”

Section: Resultssupporting

confidence: 86%

“…Given the presence of partial mediation, these data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and AKI. Regarding possible inflammation-dependent effects, previous studies have demonstrated that higher circulating IL-6 levels are independently associated with AKI [35, 53–55], and that IL-6 may play a role in AKI pathophysiology [56]. Regarding possible inflammation-independent effects, the pathophysiologic mechanisms related to high concentrations of FGF23 fragments remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with the pediatric Risk, Injury, Failure, Loss, End-Stage (pRIFLE) criteria [34], AKI was defined as a decrease in estimated GFR (eGFR) of ≥50%. As baseline (prior to Day 1) serum creatinine measurements were not available, a baseline eGFR of 120 mL/min/1.73 m 2 was assumed, as has been done in previous analyses of AKI in this cohort [35]. As a measurement of disease severity, Pediatric Risk of Mortality (PRISM) 3 scores were calculated [36].…”

Section: Methodsmentioning

confidence: 99%

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Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome

et al. 2019

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Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p<0.001), but Day 1 intact FGF23 was not. In a model adjusted for demographics and disease severity, total FGF23 remained associated with AKI (OR 1.52 [95% CI 1.02, 2.26], p = 0.039). In unadjusted models, both higher Day 1 total and intact FGF23 were associated with 60-day mortality (OR 1.43 [95% CI 1.07, 1.91], p = 0.014; and OR 1.44 [95% CI 1.02, 2.05], p = 0.039, respectively). In the adjusted model, only total FGF23 remained associated with 60-day mortality (OR 1.62 [95% CI 1.07, 2.45], p = 0.023). In a subgroup analysis of patients with Day 1 plasma IL-6 concentrations available, inflammation partially mediated the association between total FGF23 and AKI. Our data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and clinical outcomes in pediatric ARDS patients.

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Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome

et al. 2019

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“…Several clinical studies have reported that FO increases mortality in patients with sepsis [13,23], acute respiratory distress syndrome [9] and AKI [10,11,22]. The Beijing Acute Kidney Injury Trial (BAKIT) group [11] and other researchers [12,24] have considered FO as an accumulation of a fluid balance greater than 10% of the body weight in kilograms and showed that FO was a risk factor for the incidence of AKI.…”

Section: Fluid Administration Is An Integral Component Of the Managemmentioning

confidence: 99%

“…Optimal fluid resuscitation can ensure hemodynamic stability and improve tissue and organ perfusion [1], but ordinary fluid administration may frequently lead to fluid overload (FO) [2,3]. FO is associated with a poor prognosis, including a prolonged length of hospital stay and duration of MV [4], and FO is also related to a higher mortality rate in critically ill patients [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The dose - response association between fluid overload and hospital mortality in critically ill patients: a multicenter, prospective, observational cohort study

Wang

Zhu²,

et al. 2020

Preprint

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Background Fluid management is important for ensuring hemodynamic stability in critically ill patients but easily leads to fluid overload. However, the optimal fluid balance plot or range for critically ill patients is unknown. This study aimed to explore the dose-response relationship between fluid overload (FO) and hospital mortality in critically ill patients.Methods Data were derived from the China Critical Care Sepsis Trial (CCCST). Patients with sequential fluid data for the first 3 days of admission to the ICU were included. FO was expressed as the ratio of the cumulative fluid balance (L) and initial body weight (kg) at ICU admission as a percentage. Maximum fluid overload (MFO) was defined as the peak FO value during the first 3 days of ICU admission. We used logistic regression models with restricted cubic splines to assess the relationship between MFO and the risk of hospital mortality.ResultsIn total, 3850 patients were included, 929 (24.1%) of whom died in hospital. For each 1% L/kg increase in the FO, the risk of hospital mortality increased by 4% (HR 1.04, 95% CI 1.03 - 1.05, P < 0.001). FO greater than 10% was associated with a 44% increased HR of hospital mortality compared with FO less than 5% (HR 1.44, 95% CI 1.27 - 1.67). Notably, we also found a non-linear dose-response association between MFO and hospital mortality.Conclusions Both higher and lower fluid balance were associated with an increased risk of hospital mortality. Further studies should explore this relationship and seek for the optimal fluid management strategies for critically ill patients.

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Fluid overload in children with pediatric acute respiratory distress syndrome: A retrospective cohort study

Leow

Wong

Mok

et al. 2021

Pediatric Pulmonology

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Objectives: To assess the association of cumulative fluid overload (FO) up to 14 days from the diagnosis of pediatric acute respiratory syndrome (PARDS) with pediatric intensive care unit (PICU) mortality, 28-day mechanical ventilation free days (VFD), and 28-day intensive care unit free days (IFD). We hypothesized that fluid overload, even beyond the acute period, would be associated with increased morbidity and mortality.Methods: We conducted a retrospective cohort study of PARDS patients admitted to PICU from 2009 to 2015. For repeated admissions, we considered the admission with the highest oxygenation index (OI). Daily FO (%) was calculated as (intake − output)/weight at PICU admission × 100. Peak cumulative FO (CFO) was the highest CFO from the diagnosis of PARDS to Day 14 or to PICU discharge or mortality, whichever was earliest. Rate to peak CFO was the peak CFO divided by the number of days to reach that highest CFO. The association of FO with mortality, VFD and IFD were analyzed with logistic and linear regression models, with the following covariates: Pediatric Index of Mortality 2 score, PARDS severity, and the presence of acute kidney injury (AKI).Results: There were 165 patients included in this study, with a mortality rate of 45.5% (75/165), median age 3.2 years (interquartile range [IQR] 0.7-9.9) and OI 15.8 (IQR 9.5-27.9). Seventy-three (44.2%) patients had severe PARDS and 64 (38.8%) had AKI. AKI (aOR [adjusted odds ratio] 3.19, 95% CI [confidence interval] 1.43-7.09, p = 0.004) and rate to peak cumulative FO (aOR 1.23, 95% CI 1.07-1.42, p = 0.004) were associated with mortality. AKI and peak cumulative FO were associated with decreased VFD and IFD. Conclusion:The rate to peak CFO over the first 14 days of PARDS was associated with mortality and peak CFO was associated with decreased VFD and IFD.

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Positive Cumulative Fluid Balance Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome in the Setting of Acute Kidney Injury

Abstract: Objective: As acute kidney injury (AKI) and elevated cumulative fluid balance (CFB) commonly co-occur in pediatric ARDS, we aimed to identify risk-factors for their development and evaluate their independent relationships with mortality. We hypothesized that AKI and elevated CFB would

Cited by 34 publications

References 56 publications

Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome

Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome

The dose - response association between fluid overload and hospital mortality in critically ill patients: a multicenter, prospective, observational cohort study

Fluid overload in children with pediatric acute respiratory distress syndrome: A retrospective cohort study

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