Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC).

BACKGROUND: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. METHODS: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. RESULTS: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26). CONCLUSION: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. TRIAL REGISTRATION: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

Early restrictive fluid balance is associated with lower hospital mortality independent of acute disease severity in critically ill patients on CRRT.

Fluid overload (FO) with coincident acute kidney injury has been associated with increased mortality. However, it is unclear whether FO is an independent determinant of mortality for disease severity. We aimed to explore whether the development of fluid balance (FB) during the first 72 h of continuous renal replacement therapy (CRRT) is independently associated with hospital mortality. All patients admitted to a single centre ICU requiring CRRT for at least 24 h between years 2010-2019 were included. Extracted data included patient demographics and clinical parameters including daily cumulative fluid balance (FBcum), lactate, SOFA score and vasoactive requirement at the initiation and during the first 72 h of CRRT. 399 patients were included in the analysis. Hospital survivors had a significantly lower FBcum at CRRT initiation compared to non-survivors (median 1382 versus 3265 ml; p = 0.003). Hourly fluid balance per bodyweight (FBnet) was lower in survivors at 0-24, 24-48 and 48-72 h after initiation of CRRT (p < 0.008 for all comparisons). In the survival analysis (analyzed with counting process model) significant time-dependent explanatory variables for hospital mortality were FBnet (per ml/kg/h: HR: 1.319, 95% CI 1.038-1.677, p = 0.02), lactate (HR: 1.086, 95% CI 1.030-1.145, p = 0.002) and SOFA score (per ml/kg/h: HR: 1.084, 95% CI 1.025-1.146, p = 0.005) during the first 72 h of CRRT. Even after careful adjustment for repeated measures of disease severity, FBnet during the first 72 h of CRRT remains independently associated with hospital mortality, in critically ill patients with AKI.

Continuous renal replacement therapy in COVID-19-associated AKI: adding heparin to citrate to extend filter life-a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

Machine learning model to predict hypotension after starting continuous renal replacement therapy.

Hypotension after starting continuous renal replacement therapy (CRRT) is associated with worse outcomes compared with normotension, but it is difficult to predict because several factors have interactive and complex effects on the risk. The present study applied machine learning algorithms to develop models to predict hypotension after initiating CRRT. Among 2349 adult patients who started CRRT due to acute kidney injury, 70% and 30% were randomly assigned into the training and testing sets, respectively. Hypotension was defined as a reduction in mean arterial pressure (MAP) ≥ 20 mmHg from the initial value within 6 h. The area under the receiver operating characteristic curves (AUROCs) in machine learning models, such as support vector machine (SVM), deep neural network (DNN), light gradient boosting machine (LGBM), and extreme gradient boosting machine (XGB) were compared with those in disease-severity scores such as the Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II. The XGB model showed the highest AUROC (0.828 [0.796-0.861]), and the DNN and LGBM models followed with AUROCs of 0.822 (0.789-0.856) and 0.813 (0.780-0.847), respectively; all machine learning AUROC values were higher than those obtained from disease-severity scores (AUROCs < 0.6). Although other definitions of hypotension were used such as a reduction of MAP ≥ 30 mmHg or a reduction occurring within 1 h, the AUROCs of machine learning models were higher than those of disease-severity scores. Machine learning models successfully predict hypotension after starting CRRT and can serve as the basis of systems to predict hypotension before starting CRRT.

The effectiveness of a specialized team intervention on prognosis in patients undergoing continuous renal replacement therapy: A retrospective cohort study.

AIMS: Limited evidence is available regarding the effectiveness of a specialized continuous renal replacement therapy (CRRT) team approach. Hence, we aimed to evaluate the effectiveness of a specialized CRRT team intervention in a Japanese hospital. MATERIALS AND METHODS: We retrospectively identified adult patients who underwent CRRT in the intensive care unit (ICU) from July 2015 to June 2019 and divided them into two groups based on whether or not they received CRRT team intervention. We extracted data from the electronic medical record database. The concurrent effects of various factors on study outcomes were analyzed by multivariate analysis using a generalized linear model. RESULTS: A total of 540 patients were included. Baseline characteristics were similar in the two groups. In univariate analysis, no significant differences were found in in-hospital mortality (34.0 vs. 30.8%; risk difference, -3.2%; 95% confidence interval, -12.6 to 6.1), total duration of ICU stay, total CRRT time, and the proportion of patients starting maintenance hemodialysis during hospitalization between both groups. Multivariate analysis also indicated no significant differences. CONCLUSION: In this study, no significant difference was found in patient outcomes between both groups. The results suggest that the CRRT team should have integrated protocols and play a core role in CRRT management.

Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation.

To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Accelerated Venovenous Hemofiltration as a Transitional Renal Replacement Therapy in the Intensive Care Unit.

BACKGROUND: Continuous renal replacement therapy (CRRT) is commonly employed in the intensive care unit (ICU), though there are no guidelines around the transition between CRRT and intermittent hemodialysis (iHD). Accelerated venovenous hemofiltration (AVVH) is a modality utilizing higher hemofiltration rates (4-5 L/h) with shorter session durations (8-10 h) to "accelerate" the clearance and volume removal that normally is spread out over a 24-h period in CRRT. We examined AVVH as a transition therapy between CRRT and iHD, with the aim of decreasing time on CRRT and providing a more graduated transition for hemodynamically unstable patients requiring RRT. METHODS: Retrospective cohort study describing the clinical outcomes and quality initiative experience of the integration of AVVH into the CRRT program at an academic tertiary care center. Outcomes of interest included mortality, ICU length of stay and readmission rates, and technical characteristics of treatments. RESULTS: In total, 97 patients received a total of 298 AVVH treatments (3.1 ± 3.3 treatments per patient). Totally, 271/298 (91%) treatments were completed successfully. During an average treatment time of 9.5 ± 1.6 h with 4.2 ± 0.5 L/h -replacement fluid rate, urea reduction ratio was 23 ± 26% per 10-h treatment, and net ultrafiltration volume was 2.4 ± 1.3 L/treatment. Inpatient mortality was 32%, mean total hospital length of stay was 54 ± 47 days. Sixty-four out of 97 (66%) patients recovered renal function by discharge. Among those who transferred out of the ICU, 7/62 (11%) patients required readmission to the ICU after developing hypotension on iHD. CONCLUSION: AVVH can serve as a transition therapy between CRRT and iHD in the ICU and has the potential to decrease total time on CRRT, improve patient mobility, and sustain low ICU readmission rates. Future study is needed to analyze the implications on resource use and cost of this modality.

Machine learning algorithm to predict mortality in patients undergoing continuous renal replacement therapy.

BACKGROUND: Previous scoring models such as the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scoring systems do not adequately predict mortality of patients undergoing continuous renal replacement therapy (CRRT) for severe acute kidney injury. Accordingly, the present study applies machine learning algorithms to improve prediction accuracy for this patient subset. METHODS: We randomly divided a total of 1571 adult patients who started CRRT for acute kidney injury into training (70%, n = 1094) and test (30%, n = 477) sets. The primary output consisted of the probability of mortality during admission to the intensive care unit (ICU) or hospital. We compared the area under the receiver operating characteristic curves (AUCs) of several machine learning algorithms with that of the APACHE II, SOFA, and the new abbreviated mortality scoring system for acute kidney injury with CRRT (MOSAIC model) results. RESULTS: For the ICU mortality, the random forest model showed the highest AUC (0.784 [0.744-0.825]), and the artificial neural network and extreme gradient boost models demonstrated the next best results (0.776 [0.735-0.818]). The AUC of the random forest model was higher than 0.611 (0.583-0.640), 0.677 (0.651-0.703), and 0.722 (0.677-0.767), as achieved by APACHE II, SOFA, and MOSAIC, respectively. The machine learning models also predicted in-hospital mortality better than APACHE II, SOFA, and MOSAIC. CONCLUSION: Machine learning algorithms increase the accuracy of mortality prediction for patients undergoing CRRT for acute kidney injury compared with previous scoring models.

Therapeutic plasma exchange in pediatric intensive care: Indications, results and complications.

Therapeutic plasma exchange (TPE) is an effective treatment method in selective indications. Secondary to access and technical features, it is more difficult to apply in pediatric population than adults. The aim of this study is investigate safety, clinical indications, and results of this method in critically ill pediatric patients who need TPE treatment. All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 4 years (2015-2019) were evaluated retrospectively. TPE procedures (635) were performed for 135 patients. Median age was 34 months (10-108). Ninety-seven patients had mechanical ventilation support. Sepsis with multiple organ failure was the most frequent indication and accounted for 44.4% (n = 60) of the indications followed by hematological and neurological diseases (19.2% and 9.6% respectively). TPE was performed alone in 469 cases (73.9%), in combination with continuous renal replacement therapy in 154 cases (24.2%), and additional to extracorporeal membrane oxygenation in 12 cases (1.9%). Hematological disease and sepsis subgroups had the highest intubation rate, mechanical ventilation period, PRISM score, organ failure count, and mortality. Fresh frozen plasma (FFP) was the most frequently used replacement fluid in 90.4% of the procedures. The most frequent anticoagulant used in TPE was acid citrate dextrose solution (79.3%). Procedural complications were detected in 104 cases (16.3%) and occurred during TPE sessions. Overall survival rate was 78.5%. We found that the non-survivor group had significantly higher rates of organ failures (P = 0.0001), higher PRISM scores on admission (P = 0.0001), and higher rates of invasive ventilation support needed (P = 0.012). TPE is a treatment method which can be safely provided in healthcare facilities with necessary medical and technical requirements. Although it is riskier to provide such treatment to critically ill children, complications can be minimized in experienced healthcare facilities. Overall results are good and can vary depending on indication.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort. METHODS: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007, to December 31, 2011, at six tertiary care children's hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis. MEASUREMENTS AND MAIN RESULTS: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p = 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p = 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p = 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p = 0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00-1.18, p = 0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03-1.19, p = 0.01) were independently associated with hospital mortality. CONCLUSIONS: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Survey on available treatment for acute kidney injury in the Southern African Development Community and Nigeria: are we ready for zero deaths by 2025 in sub-Saharan Africa?

OBJECTIVES: The International Society of Nephrology (ISN) has called for zero deaths by 2025. This survey aimed to determine the preparedness of Southern African Development Community (SADC) countries and Nigeria to heed this call. SETTING: A questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved. PARTICIPANTS: Clinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire. RESULTS: Completed questionnaires were received from 12 of the 15 SADC countries and Nigeria, covering 48 service providers. The government provided partial funding for dialysis in 41.7% of services. There was no funding for acute dialysis in two countries. Interdisciplinary teams in 72.9% of hospitals covered the intensive care units (ICUs), which included at least one nephrologist in 75%. Only 77% were able to provide dialysis in ICU. Intermittent haemodialysis was the most common modality available (91.7% of facilities), sustained low-efficiency dialysis in 50%, continuous therapies in 35% and peritoneal dialysis in 33.3%. Almost half (47.9%) of the sites were limited to one mode of dialysis and unable to care for severely ill patients. The clinical status was used to initiate and monitor dialysis, with very few sites having clear written standard operating procedures. CONCLUSION: In the 16 countries surveyed, the majority had limited ability to provide comprehensive dialysis programmes for patients with AKI due to lack of facilities and government funding. Additionally, nephrologists are scarce; modes of dialysis are limited; as is the care for severely ill patients and lack of standard operating procedures. Resources, training and funding need to be made available to create universal coverage of dialysis for AKI. The ISN goal of providing renal replacement therapy to all by 2025 is unlikely to be achieved in SADC and Nigeria.

Analysis of survival after initiation of continuous renal replacement therapy in patients with extracorporeal membrane oxygenation.

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.

Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration: A Secondary Analysis of the Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy Trial.

Importance: Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear. Objective: To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration. Design, Setting, and Participants: The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019. Exposures: Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight. Main Outcomes and Measures: Risk-adjusted 90-day survival. Results: Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (ß = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08). Conclusions and Relevance: Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings. Trial Registration: ClinicalTrials.gov identifier: NCT00221013.

Predictors of short-term successful discontinuation of continuous renal replacement therapy: results from a prospective multicentre study.

BACKGROUND: Prediction of successful discontinuation of continuous renal replacement therapy (CRRT) might reduce complications of over- and under-treatment. The aim of this study was to identify renal and non-renal predictors of short-term successful discontinuation of CRRT in patients in whom CRRT was stopped because renal recovery was expected and who were still in the Intensive Care Unit (ICU) at day 2 after stop CRRT. METHODS: Prospective multicentre observational study in 92 patients alive after discontinuation of CRRT for acute kidney injury (AKI), still in the ICU and free from renal replacement therapy (RRT) at day 2 after discontinuation. Successful discontinuation was defined as alive and free from RRT at day 7 after stop CRRT. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and clinical variables were collected. Logistic regression and Receiver Operator Characteristic (ROC) curve analysis were performed to determine the best predictive and discriminative variables. RESULTS: Discontinuation of CRRT was successful in 61/92 patients (66%). Patients with successful discontinuation of CRRT had higher day 2 urine output, better renal function indicated by higher creatinine clearance (6-h) or lower creatinine ratio (day 2/day 0), less often vasopressors, lower urinary NGAL, shorter duration of CRRT and lower cumulative fluid balance (day 0-2). In multivariate analysis renal function determined by creatinine clearance (Odds Ratio (OR) 1.066, 95% confidence interval (CI) 1.022-1.111, p = 0.003) or by creatinine ratio (day 2/day 0) (OR 0.149, 95% CI 0.037-0.583, p = 0.006) and non-renal sequential organ failure assessment (SOFA) score (OR 0.822, 95% CI 0.678-0.996, p = 0.045) were independently associated with successful discontinuation of CRRT. The area under the curve of creatinine clearance to predict successful discontinuation was 0.791, optimal cut-off of 11 ml/min (95% CI 6-16 ml/min) and of creatinine ratio 0.819 (95% CI 0.732-0.907) optimal cut-off of 1.41 (95% CI 1.27-1.59). CONCLUSION: In this prospective multicentre study we found higher creatinine clearance or lower creatinine ratio as best predictors of short-term successful discontinuation of CRRT, with a creatinine ratio of 1.41 (95% CI 1.27-1.59) as optimal cut-off. This study provides a practical bedside tool for clinical decision making.

High Hemoglobin Is an Independent Risk Factor for the Development of Hemolysis During Pediatric Extracorporeal Life Support.

OBJECTIVE: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. DESIGN: Retrospective, single-center study. SETTING: Pediatric intensive care unit. PATIENTS: Two hundred thirty-six children who received extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. CONCLUSIONS: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.

Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation.

OBJECTIVE: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy. DESIGN: Retrospective observational study based on a prospective registry. SETTING: Tertiary and quaternary referral 30-bed PICU. PATIENTS: Critically ill children undergoing continuous renal replacement therapy were included in the study. INTERVENTIONS: Continuous renal replacement therapy. MEASUREMENTS AND MAIN RESULTS: Overall mortality was 36% (n = 58) among the 161 patients treated with continuous renal replacement therapy during the study period and was significantly higher in patients on extracorporeal membrane oxygenation (47.5%, 28 of 59) than in patients not requiring extracorporeal membrane oxygenation (28.4%, 29 of 102; p = 0.022). According to the admission diagnosis, we found the highest mortality in patients with onco-hematologic disease (77.8%) and the lowest in patients with renal disease (5.6%). Based on multivariate logistic regression analysis, the presence of higher severity of illness score at admission (adjusted odds ratio, 1.49; 95% CI, 1.18-1.89; p < 0.001), onco-hematologic disease (odds ratio, 17.10; 95% CI, 4.10-72.17; p < 0.001), fluid overload 10%-20% (odds ratio, 3.83; 95% CI, 1.33-11.07; p = 0.013), greater than 20% (odds ratio, 15.03; 95% CI, 4.03-56.05; p < 0.001), and timing of initiation of continuous renal replacement therapy (odds ratio, 1.01; 95% CI, 1.00-1.01; p = 0.040) were independently associated with mortality. In our population, the odds of dying increases by 1% for every hour of delay in continuous renal replacement therapy initiation from ICU admission. CONCLUSIONS: Mortality in children requiring continuous renal replacement therapy remains high and seems to be related to the underlying disease, the severity of illness, and the degree of fluid overload. In critically ill children at high risk for developing acute kidney injury and fluid overload, earlier initiation of continuous renal replacement therapy might result in decreased mortality.

Outcomes Analysis of Children Diagnosed With Hemophagocytic Lymphohistiocytosis in the PICU.

OBJECTIVES: Describe a single center experience of hemophagocytic lymphohistiocytosis in a PICU over a 10-year period, to identify clinical features that may be associated with worse outcomes, including mortality, hospital and ICU length of stay, and functional and cognitive impairments on discharge. DESIGN: Retrospective electronic medical record review, 2007-2017. SETTING: PICU located in a large urban academic quaternary care children's hospital. PATIENTS: All children admitted with hemophagocytic lymphohistiocytosis to our PICU from 2007 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were identified utilizing International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes. Each chart was reviewed for demographic information, hemophagocytic lymphohistiocytosis diagnostic criteria, laboratory data, Pediatric Risk of Mortality Score III, clinical features and events of ICU stay, and PICU and hospital (length of stay). Mortality at 1 year and change in Functional Status Scale from admission to discharge were recorded. There were 42 admissions with 33 unique patients. Median Pediatric Risk of Mortality score at admission was 9 (interquartile range, 7-16). Median PICU length of stay was 7 days (interquartile range, 2-21 d) and hospital length of stay was 24 days (interquartile range, 14-37 d). During their ICU stay, 56% of patients received mechanical ventilation, 43% required vasoactives, 18% required continuous renal replacement therapy, and 5% received extracorporeal life support. Clinical factors related to increased PICU length of stay included Pediatric Risk of Mortality III score (p = 0.019), maximum lactate dehydrogenase (p = 0.017), maximum total bilirubin (p = 0.042), need for mechanical ventilation (p = 0.002), vasoactive use (p = 0.02), and secondary infection (p = 0.007). The most common therapies for hemophagocytic lymphohistiocytosis included steroids (93%), etoposide (55%), and anakinra (48%). Of the 26 patients who survived to hospital discharge, 19% had newly acquired morbidities. Overall 1-year mortality was 42%. CONCLUSIONS: Hemophagocytic lymphohistiocytosis diagnosed in the PICU is a disease with high mortality. Patients who survive to discharge had relatively little morbidity, however, the mortality risk in the year following discharge continued to remain high.