Net ultrafiltration intensity and mortality in critically ill patients with fluid overload.
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ABSTRACT: Although net ultrafiltration (UFNET) is frequently used for treatment of fluid overload in critically ill patients with acute kidney injury, the optimal intensity of UFNET is unclear. Among critically ill patients with fluid overload receiving renal replacement therapy (RRT), we examined the association between UFNET intensity and risk-adjusted 1-year mortality.We selected patients with fluid overload ? 5% of body weight prior to initiation of RRT from a large academic medical center ICU dataset. UFNET intensity was calculated as the net volume of fluid ultrafiltered per day from initiation of either continuous or intermittent RRT until the end of ICU stay adjusted for patient hospital admission body weight. We stratified UFNET as low (??20 ml/kg/day), moderate (>?20 to???25 ml/kg/day) or high (>?25 ml/kg/day) intensity. We adjusted for age, sex, body mass index, race, surgery, baseline estimated glomerular filtration rate, oliguria, first RRT modality, pre-RRT fluid balance, duration of RRT, time to RRT initiation from ICU admission, APACHE III score, mechanical ventilation use, suspected sepsis, mean arterial pressure on day 1 of RRT, cumulative fluid balance during RRT and cumulative vasopressor dose during RRT. We fitted logistic regression for 1-year mortality, Gray's survival model and propensity matching to account for indication bias.Of 1075 patients, the distribution of high, moderate and low-intensity UFNET groups was 40.4%, 15.2% and 44.2% and 1-year mortality was 59.4% vs 60.2% vs 69.7%, respectively (p?=?0.003). Using logistic regression, high-intensity compared with low-intensity UFNET was associated with lower mortality (adjusted odds ratio 0.61, 95% CI 0.41-0.93, p?=?0.02). Using Gray's model, high UFNET was associated with decreased mortality up to 39 days after ICU admission (adjusted hazard ratio range 0.50-0.73). After combining low and moderate-intensity UFNET groups (n?=?258) and propensity matching with the high-intensity group (n?=?258), UFNET intensity >?25 ml/kg/day compared with ??25 ml/kg/day was associated with lower mortality (57% vs 67.8%, p?=?0.01). Findings were robust to several sensitivity analyses.Among critically ill patients with ??5% fluid overload and receiving RRT, UFNET intensity >?25 ml/kg/day compared with ??20 ml/kg/day was associated with lower 1-year risk-adjusted mortality. Whether tolerating intensive UFNET is just a marker for recovery or a mediator requires further research.
Project description:INTRODUCTION: Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. METHODS: We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. RESULTS: We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. CONCLUSIONS: Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.
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.
Project description:BACKGROUND:Postoperative fluid overload may increase the risk of developing pulmonary complications and other adverse outcomes. We evaluated the impact of excessive fluid administration on postoperative outcomes in critically ill patients. METHODS:We reviewed the medical records of 320 patients admitted to intensive care unit (ICU) after emergency abdominal surgery for complicated intra-abdominal infection (cIAI) between January 2013 and December 2018. The fluid balance data of the patients were reviewed for a maximum of 7 days. The patients were grouped based on average daily fluid balance with a cutoff value of 20 ml/kg/day. Propensity score matching was performed to reduce the underlying differences between the groups. RESULTS:Patients with an average daily fluid balance of ?20 ml/kg/day were associated with higher rates of 30-day mortality (11.8% vs. 2.4%; P=0.036) than those with lower fluid balance (<20 ml/kg/day). Kaplan-Meier survival curves for 30-day mortality in these groups also showed a better survival rate in the lower fluid balance group with a statistical significance (P=0.020). The percentage of patients who developed pulmonary consolidation during ICU stay (47.1% vs. 24.7%; P=0.004) was higher in the fluid-overloaded group. Percentages of newly developed pleural effusion (61.2% vs. 57.7%; P=0.755), reintubation (18.8% vs. 10.6%; P=0.194), and infectious complications (55.3% vs. 49.4%; P=0.539) showed no significant differences between the two groups. CONCLUSIONS:Postoperative fluid overload in patients who underwent emergency surgery for cIAI was associated with higher 30-day mortality and more frequent occurrence of pulmonary consolidation. Postoperative fluid balance should be adjusted carefully to avoid adverse clinical outcomes.
Project description:BACKGROUND AND OBJECTIVES: No data on the development of conventional indications for RRT (refractory acidosis, hyperkalemia, uremia, oliguria/anuria, and volume overload) related to timing of RRT exist. The prevalence of conventional indications among critically ill patients on RRT for AKI was evaluated, and patients manifesting indications versus patients without indications were compared in terms of crude and adjusted 90-day mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this substudy of the Finnish Acute Kidney Injury study conducted in 2011 and 2012 in 17 intensive care units with 2901 patients, patients were classified as pre-emptive (no conventional indications) and classic (one or more indications) RRT recipients. Patients with classic RRT were divided into classic-urgent (RRT initiated ? 12 hours from manifesting indications) and classic-delayed (RRT >12 hours from first indication). Additionally, 2450 patients treated without RRT were matched to patients with pre-emptive RRT. RESULTS: Of 239 patients treated with RRT, 134 (56.1%; 95% confidence interval [95% CI], 49.8% to 62.4%) fulfilled at least one conventional indication before commencing RRT. Crude 90-day mortality of 134 patients with classic RRT was 48.5% (95% CI, 40.0% to 57.0%), and it was 29.5% (95% CI, 20.8% to 38.2%) for the 105 patients with pre-emptive RRT. Classic RRT was associated with a higher risk for mortality (adjusted odds ratio, 2.05; 95% CI, 1.03 to 4.09). Forty-four patients with classic-delayed RRT showed higher crude mortality (68.2%; 95% CI, 54.4% to 82.0%) compared with patients with classic-urgent RRT, and this association persisted after adjustment for known confounders (odds ratio, 3.85; 95% CI, 1.48 to 10.22). Crude 90-day mortality of 67 1:1 matched patients with pre-emptive RRT was 26.9% (95% CI, 6.3% to 37.5%), and it was 49.3% (95% CI, 37.3% to 61.2%; P=0.01) for their non-RRT matches. CONCLUSIONS: Patients on RRT after one or more conventional indications had both higher crude and adjusted 90-day mortality compared with patients without conventional indications. These findings require confirmation in an adequately powered, multicenter, randomized controlled trial.
Project description:INTRODUCTION: In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. METHODS: We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression. RESULTS: Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001). CONCLUSIONS: In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.
Project description:BACKGROUND:The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT. METHODS:FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT. RESULTS:FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P?<? 0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P?=?0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P?=?0.002). CONCLUSION:The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation. TRIAL REGISTRATION:clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.
Project description:INTRODUCTION:Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high mortality. The creatinine-based stage of AKI is considered when deciding to start or delay RRT. However, creatinine is not only determined by renal function (excretion), but also by dilution (fluid balance) and creatinine generation (muscle mass). The aim of this study was to explore whether fluid balance-adjusted creatinine at initiation of RRT is related to 28-day mortality independent of other markers of AKI, surrogates of muscle mass and severity of disease. METHODS:We performed a post-hoc analysis on data from the multicentre CASH trial comparing citrate to heparin anticoagulation during continuous venovenous hemofiltration (CVVH). To determine whether fluid balance-adjusted creatinine was associated with 28-day mortality, we performed a logistic regression analysis adjusting for confounders of creatinine generation (age, gender, body weight), other markers of AKI (creatinine, urine output) and severity of disease. RESULTS:Of the 139 patients, 32 patients were excluded. Of the 107 included patients, 36 died at 28 days (34%). Non-survivors were older, had higher APACHE II and inclusion SOFA scores, lower pH and bicarbonate, lower creatinine and fluid balance-adjusted creatinine at CVVH initiation. In multivariate analysis lower fluid balance-adjusted creatinine (OR 0.996, 95% CI 0.993-0.999, p = 0.019), but not unadjusted creatinine, remained associated with 28-day mortality together with bicarbonate (OR 0.869, 95% CI 0.769-0.982, P = 0.024), while the APACHE II score non-significantly contributed to the model. CONCLUSION:In this post-hoc analysis of a multicentre trial, low fluid balance-adjusted creatinine at CVVH initiation was associated with 28-day mortality, independent of other markers of AKI, organ failure, and surrogates of muscle mass, while unadjusted creatinine was not. More tools are needed for better understanding of the complex determinants of "AKI classification", "CVVH initiation" and their relation with mortality, fluid balance is only one.
Project description:<h4>Introduction</h4>Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.<h4>Methods</h4>We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.<h4>Results</h4>Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P?=?0.04), had more cardiovascular (P <0.001) and renal failures (P?=?0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 ?g/kg/min vs. 0.18 ?g/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P?=?0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.<h4>Conclusions</h4>Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.
Project description:Intensive RRT may have adverse effects that account for the absence of benefit observed in randomized trials of more intensive versus less intensive RRT. We wished to determine the association of more intensive RRT with changes in urine output as a marker of worsening residual renal function in critically ill patients with severe AKI.The Acute Renal Failure Trial Network Study (n=1124) was a multicenter trial that randomized critically ill patients requiring initiation of RRT to more intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 ml/kg per hour) versus less intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 ml/kg per hour) RRT. Mixed linear regression models were fit to estimate the association of RRT intensity with change in daily urine output in survivors through day 7 (n=871); Cox regression models were fit to determine the association of RRT intensity with time to ≥50% decline in urine output in all patients through day 28.Mean age of participants was 60±15 years old, 72% were men, and 30% were diabetic. In unadjusted models, among patients who survived ≥7 days, mean urine output was, on average, 31.7 ml/d higher (95% confidence interval, 8.2 to 55.2 ml/d) for the less intensive group compared with the more intensive group (P=0.01). More intensive RRT was associated with 29% greater unadjusted risk of decline in urine output of ≥50% (hazard ratio, 1.29; 95% confidence interval, 1.10 to 1.51).More intensive versus less intensive RRT is associated with a greater reduction in urine output during the first 7 days of therapy and a greater risk of developing a decline in urine output of ≥50% in critically ill patients with severe AKI.
Project description:BACKGROUND:Extracorporeal carbon-dioxide removal (ECCO2R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) (<?6 ml/kg predicted body weight), plateau pressure (Pplat) (<?30 cmH2O), and driving pressure to limit ventilator-induced lung injury. This study was undertaken to assess the feasibility and safety of ECCO2R managed with a renal replacement therapy (RRT) platform to enable very low tidal volume ventilation of patients with mild-to-moderate acute respiratory distress syndrome (ARDS). METHODS:Twenty patients with mild (n?=?8) or moderate (n?=?12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP adjusted to reach 23???Pplat???25 cmH2O. Standalone ECCO2R (no hemofilter associated with the RRT platform) was initiated when arterial PaCO2 increased by >?20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, Pplat and driving pressure, arterial blood gases, and ECCO2R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO2R and mechanical ventilation were also recorded. RESULTS:While VT was reduced from 6 to 4 ml/kg and Pplat kept <?25 cmH2O, PEEP was significantly increased from 13.4?±?3.6 cmH2O at baseline to 15.0?±?3.4 cmH2O, and the driving pressure was significantly reduced from 13.0?±?4.8 to 7.9?±?3.2 cmH2O (both p?<?0.05). The PaO2/FiO2 ratio and respiratory-system compliance were not modified after VT reduction. Mild respiratory acidosis occurred, with mean PaCO2 increasing from 43?±?8 to 53?±?9 mmHg and mean pH decreasing from 7.39?±?0.1 to 7.32?±?0.10 from baseline to 4 ml/kg VT, while the respiratory rate was not altered. Mean extracorporeal blood flow, sweep-gas flow, and CO2 removal were 421?±?40 ml/min, 10?±?0.3 L/min, and 51?±?26 ml/min, respectively. Mean treatment duration was 31?±?22 h. Day-28 mortality was 15%. CONCLUSIONS:A low-flow ECCO2R device managed with an RRT platform easily and safely enabled very low tidal volume ventilation with moderate increase in PaCO2 in patients with mild-to-moderate ARDS. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02606240. Registered on 17 November 2015.
