Impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation.
ABSTRACT: PURPOSE:To assess the relationship between early daily fluid balance (FB) and 90-day outcome in adult patients treated with extracorporeal membrane oxygenation (ECMO). DESIGN:Retrospective observational study. SETTING:Tertiary referral centre for ECMO. PATIENTS:115 patients treated with ECMO for refractory heart failure and 57 patients treated with ECMO for refractory respiratory failure. METHODS:We analysed the association between early daily FB versus hospital and 90-day mortality using multivariable logistic regression model, Cox proportional-hazards model and propensity score. RESULTS:We obtained detailed demographic, clinical, and biochemical data, daily FB, and continuous renal replacement days. Fifty-seven per cent of patients had acute kidney injury (AKI) at ECMO initiation, and 60 % (n = 103) of patients received continuous renal replacement therapy (CRRT) during ECMO course, beginning at a median of 1 (0-3.5) days after ECMO initiation. Overall 90-day mortality was 24 %. Survivors exhibited lower daily FB from day 3 to day 5. After adjustments, Acute Physiology and Chronic Health Evaluation (APACHE) III, CRRT during the first 3 days, major bleeding event at day 1 and positive FB on day 3 were independent predictors of 90-day mortality. Positive FB at ECMO day 3 remained an independent predictor of hospital and 90-day mortality, regardless of the statistical model used or the inclusion of a propensity score to have positive FB. CONCLUSIONS:Positive FB at ECMO day 3 is an independent predictor of 90-day mortality. Further interventional studies aimed at testing the value of strategy of tight control of FB during the early ECMO period are now warranted.
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:INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model. METHODS: Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models. RESULTS: In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and hemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P?=?0.03) and predictive ability (likelihood ratio test, P?<?0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively. CONCLUSIONS: While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
Project description:Intravascular hemolysis with elevated plasma-free hemoglobin (PFH) complicates extracorporeal membrane oxygenation (ECMO). In 50 consecutive pediatric cardiac patients requiring ECMO, we sought to describe the relationship between PFH and clinical outcomes; primary outcomes were acute kidney injury (AKI) and prolonged (>14 days) renal replacement therapy (RRT). Median age was 35 days, median weight 3.9 kg, and median ECMO duration 4.2 days. Seventy-eight percent (39/50) weaned off ECMO; survival to discharge was 50% (25/50). Seventy percent (35/50) had AKI on ECMO. Seventy-seven percent (30/39) required RRT post-ECMO; median duration was 5.2 days (0, 14.2). Prolonged RRT was associated with higher daily PFH (67.5 mg/dL [54.1, 102.5] vs. 46.7 mg/dL [40, 72.6], p = .025) and higher peak PFH (120 mg/dL [90, 200] vs. 60 mg/dL [40, 135], p = .016). After adjusting for ECMO duration and oliguria/elevated creatinine on ECMO day 0, peak PFH >90 mg/dL was associated with prolonged RRT (operating room [OR] = 18, confidence interval [CI] 1.9-167.8). Patients who died had higher daily PFH (65 mg/dL [51.6, 111.7] vs. 42.5 mg/dL [37.5, 60], p = .0040). Adjusting for ECMO duration and blood product administration, daily PFH >53 mg/dL was associated with mortality (OR 4.8, CI 1.01-23.3). Elevated PFH during pediatric cardiac ECMO is associated with prolonged RRT and non-survival to discharge. Initiatives to decrease PFH burden may improve clinical outcomes.
Project description:BACKGROUND:Patients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO. METHODS:This retrospective cohort study was done in the Paris-Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1-4): on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-state Cox model stratified for each possible transition. Follow-up was right-censored on July 10, 2020. FINDINGS:From March 8 to May 2, 2020, 492 patients with COVID-19 were treated in our ICUs. Complete day-60 follow-up was available for 83 patients (median age 49 [IQR 41-56] years and 61 [73%] men) who received ECMO. Pre-ECMO, 78 (94%) patients had been prone-positioned; their median driving pressure was 18 (IQR 16-21) cm H2O and PaO2/FiO2 was 60 (54-68) mm Hg. At 60 days post-ECMO initiation, the estimated probabilities of occupation in each state were 6% (95% CI 3-14) for state 1, 18% (11-28) for state 2, 45% (35-56) for state 3, and 31% (22-42) for state 4. 35 (42%) patients had major bleeding and four (5%) had a haemorrhagic stroke. 30 patients died. INTERPRETATION:The estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care. FUNDING:None.
Project description:PURPOSE:Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients. METHODS:In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality. RESULTS:Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure - PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO2/FiO2, higher arterial pH and lower PaCO2 levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03-1.10)]. CONCLUSION:In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.
Project description:BACKGROUND:No study has specifically investigated the duration of continuous renal replacement therapy (CRRT) in patients who experienced acute kidney injury during extracorporeal membrane oxygenation (ECMO) support. However, there are concerns that prolonged CRRT may be futile. METHODS:We conducted a retrospective population-based cohort study using Taiwan National Health Insurance Research Database data collected between January 1, 2007 and December 31, 2013. Patients who received ECMO and CRRT during the study period were included. We divided patients into three groups based on the duration of CRRT received: ≤ 3 days, 4-6 days, and ≥ 7 days. The outcomes were all-cause mortality, end-stage renal disease, ventilator dependency, and readmission rate. RESULTS:There were 247, 134 and 187 patients who survived the hospitalization in the CRRT for ≤3 days, 4-6 days and > 7 days respectively. Survival after discharge did not differ significantly between CRRT for 4-6 days vs. ≤ 3 days (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 0.85-1.57), between CRRT for > 7 days vs. ≤ 3 days (aHR 1.001, 95% CI 0.73-1.38) and between CRRT for > 7 days vs. 4-6 days (aHR 0.87, 95% CI 0.62-1.22). The patients who received CRRT for ≥7 days had a higher risk of ESRD than did those who received CRRT for ≤3 days (adjusted hazard ratio [aHR] 3.46, 95% confidence interval [CI] 1.47-8.14) and for 4-6 days (aHR 3.10, 95% CI 1.03-9.29). The incidence of ventilator dependence was higher in the patients with CRRT ≥7 days than in those with ≤3 days (aHR 2.45, 95% CI 1.32-4.54). The CRRT ≥7 days group also exhibited a higher readmission rate than did the 4-6 days and ≤ 3 days groups (aHR 1.43, 95% CI 1.04-1.96 and aHR 1.67, 95% CI 1.13-2.47, respectively). CONCLUSIONS:Our study found similar long-term survival but increased ESRD and ventilator dependency among ECMO patients who underwent CRRT for ≥7 days. These results offer reason to be concerned that this aggressive life support may maintain patient survival but do so at the cost of long-term disabilities and a lower quality of life.
Project description:BACKGROUND:The survival predictors and optimal mechanical ventilator settings in patients with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) are uncertain. This study was designed to investigate the influences of clinical variables and mechanical ventilation settings on the outcomes for severe ARDS patients receiving ECMO. METHODS:We reviewed severe ARDS patients who received ECMO due to refractory hypoxemia from May 2006 to October 2015. Serial mechanical ventilator settings before and after ECMO and factors associated with survival were analyzed. RESULTS:A total of 158 severe ARDS patients received ECMO were finally analyzed. Overall intensive care unit (ICU) mortality was 55.1%. After ECMO initiation, tidal volume, peak inspiratory pressure and dynamic driving pressure were decreased, while positive end-expiratory pressure levels were relative maintained. After ECMO initiation, nonsurvivors had significantly higher dynamic driving pressure until day 7 than survivors. Cox proportional hazards regression model revealed that immunocompromised [hazard ratio 1.957; 95% confidence interval (CI) 1.216-3.147; p = 0.006], Acute Physiology and Chronic Health Evaluation (APACHE) II score (hazard ratio 1.039; 95% CI 1.005-1.073; p = 0.023), ARDS duration before ECMO (hazard ratio 1.002; 95% CI 1.000-1.003; p = 0.029) and mean dynamic driving pressure from day 1 to 3 on ECMO (hazard ratio 1.070; 95% CI 1.026-1.116; p = 0.002) were independently associated with ICU mortality. CONCLUSIONS:For severe ARDS patients receiving ECMO, immunocompromised status, APACHE II score and the duration of ARDS before ECMO initiation were significantly associated with ICU survival. Higher dynamic driving pressure during first 3 days of ECMO support was also independently associated with increased ICU mortality.
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:Purpose To assess the effect of venovenous extracorporeal membrane oxygenation (ECMO) compared to conventional management in patients with severe acute respiratory distress syndrome (ARDS). Methods We conducted a systematic review and individual patient data meta-analysis of randomised controlled trials (RCTs) performed after Jan 1, 2000 comparing ECMO to conventional management in patients with severe ARDS. The primary outcome was 90-day mortality. Primary analysis was by intent-to-treat. Results We identified two RCTs (CESAR and EOLIA) and combined data from 429 patients. On day 90, 77 of the 214 (36%) ECMO-group and 103 of the 215 (48%) control group patients had died (relative risk (RR), 0.75, 95% confidence interval (CI) 0.6–0.94; P?=?0.013; I2?=?0%). In the per-protocol and as-treated analyses the RRs were 0.75 (95% CI 0.6–0.94) and 0.86 (95% CI 0.68–1.09), respectively. Rescue ECMO was used for 36 (17%) of the 215 control patients (35 in EOLIA and 1 in CESAR). The RR of 90-day treatment failure, defined as death for the ECMO-group and death or crossover to ECMO for the control group was 0.65 (95% CI 0.52–0.8; I2?=?0%). Patients randomised to ECMO had more days alive out of the ICU and without respiratory, cardiovascular, renal and neurological failure. The only significant treatment-covariate interaction in subgroups was lower mortality with ECMO in patients with two or less organs failing at randomization. Conclusions In this meta-analysis of individual patient data in severe ARDS, 90-day mortality was significantly lowered by ECMO compared with conventional management. Electronic supplementary material The online version of this article (10.1007/s00134-020-06248-3) contains supplementary material, which is available to authorized users.
Project description:Electrolyte and mineral disturbances remain a major concern in patients undergoing continuous renal replacement therapy (CRRT); however, it is not clear whether those imbalances are associated with adverse outcomes in patients with septic acute kidney injury (AKI) undergoing CRRT. We conducted a post-hoc analysis of data from a prospective randomized controlled trial. A total of 210 patients with a mean age of 62.2 years (136 [64.8%] males) in 2 hospitals were enrolled. Levels of sodium, potassium, calcium, and phosphate measured before (0?hour) and 24 hours after CRRT initiation. Before starting CRRT, at least 1 deficiency and excess in electrolytes or minerals were observed in 126 (60.0%) and 188 (67.6%) patients, respectively. The excess in these parameters was greatly improved, whereas hypokalemia and hypophosphatemia became more prevalent at 24 hours after CRRT. However, 1 and 2 or more deficiencies in those parameters at the 2 time points were not associated with mortality. However, during 28 days, 89 (71.2%) deaths occurred in patients with phosphate levels at 0?hour of ?4.5?mg/dL as compared with 49 (57.6%) in patients with phosphate levels <4.5?mg/dL. The 90-day mortality was also significantly higher in patients with hyperphosphatemia. Similarly, in 184 patients who survived at 24 hours after CRRT, hyperphosphatemia conferred a 2.2-fold and 2.6-fold increased risk of 28- and 90-day mortality, respectively. The results remained unaltered when the serum phosphate level was analyzed as a continuous variable. Electrolyte and mineral disturbances are common, and hyperphosphatemia may predict poor prognosis in septic AKI patients undergoing CRRT.