Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

BACKGROUND: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions. METHODS: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process. RESULTS: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all). CONCLUSIONS: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility. TRIAL REGISTRATION: ChiCTR2100048238 in the Chinese Clinical Trial Registry.

Real-life effects, complications, and outcomes in 39 critically ill neonates receiving continuous kidney replacement therapy.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients' clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates. METHODS: A 7-year single-center retrospective study in a tertiary NICU. RESULTS: Thirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT. CONCLUSIONS: CKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Current practices in pediatric continuous kidney replacement therapy: a systematic review-guided multinational modified Delphi consensus study.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has become an integral part of the care of critically ill children. However, uncertainty exists regarding the current state of how CKRT is prescribed and delivered in children. The main objective of this study was to identify the current practices for pediatric CKRT. METHODS: We conducted a systematic review of the literature from 2012 to 2022 to identify data regarding CKRT timing of initiation, dosing, anticoagulation, fluid removal, and quality monitoring. Using this data, we then performed a two-round modified Delphi process using a multinational internet-assisted survey of prescribers of CKRT. RESULTS: The survey was constructed using 172 articles that met inclusion criteria (12% of studies were pediatric focused). A total of 147 and 126 practitioners completed the survey in rounds 1 and 2, respectively. Participants represented Europe (9.5-11.6%) and North America including pediatric intensivists, nephrologists, and advance practice providers. Consensus (defined as a ≥ 75% participant response of "sometimes" or "always") was achieved for 26 statements. There was consensus in the practices of CKRT initiation, dosing, method of anticoagulation, and fluid removal. In contrast, there appears to be greater variability in the methods used for monitoring anticoagulation and the quality of the delivered treatment. CONCLUSIONS: Our study results suggest that the current state of pediatric CKRT practice is reflective of the literature over the last 10 years, which is largely based on the care of adult patients. This data provides a framework to study best practices to further improve outcomes for children receiving CKRT. A higher resolution version of the Graphical abstract is available as Supplementary information.

A quality initiative to improve recognition of fluid overload among pediatric ICU patients requiring continuous kidney replacement therapy: preliminary results.

BACKGROUND: Initiation of continuous kidney replacement therapy (CKRT) greater than 20% fluid overload is associated with increased morbidity and mortality. We aimed to reduce the number of patients initiated on CKRT greater than 20% fluid overload by 50% in one year by implementation of a quality improvement initiative. METHODS: This is a prospective quality improvement study set in a pediatric ICU of an urban children's hospital of patients initiated on CKRT over 2 years. The intervention included creation of an electronic health record order for daily calculation of net percent fluid overload, incorporation into daily rounds, and education programs tailored to physicians and bedside nursing. We measured adherence with the new order set, percent fluid overload at CKRT initiation, days on CKRT, timing of first nephrology consultation, and death prior to discharge. RESULTS: A total of 32% of patients were initiated on CKRT greater than 20% fluid overload pre-initiative and 9% post-initiative, a 72% reduction over 13 months. Patients initiated on CKRT greater than 20% fluid overload had median CKRT course of 8 (IQR 4-14) vs. 22 days (IQR 13.5-62). CONCLUSION: Creating a system using EHR with education may reduce initiation of CKRT after development of severe fluid overload. A higher resolution version of the Graphical abstract is available as Supplementary information.

Criteria for Continuous Kidney Replacement Therapy Cessation in ICU Patients.

INTRODUCTION: In intensive care unit (ICU) patients with acute kidney injury, specific recommendations to guide the decision to cease continuous kidney replacement therapy (CKRT) are lacking. METHODS: We performed a survey to identify criteria currently used to cease CKRT in real-life clinical practice in the Netherlands. We used an online questionnaire with multiple choice questions designed with web-based software from SurveyMonkey. RESULTS: We received 169 completed questionnaires from intensivists (n = 126) and nephrologists (n = 43). Essential determinants for the cessation of CKRT were a spontaneously increasing diuresis (indicated by 92% of the respondents), absence of fluid overload (indicated by 88% of the respondents), and improvement in creatinine clearance (indicated by 61% of the respondents; intensivists 56%; nephrologists 77%, p = 0.03). Most often mentioned cut-off values used for increase in diuresis were 0.25 and 0.5 mL/kg/h (35% and 33%, respectively). Actual CKRT cessation was often postponed until the filter clots or until circuit disconnection is needed because of patient transport for diagnostic or intervention procedures (indicated by 58% of the respondents). Expected discharge from the ICU was the most frequently reported determinant to switch from CKRT to hemodialysis (indicated by 67% of the respondents). CONCLUSIONS: CKRT cessation in clinical practice is mostly based on spontaneously increasing diuresis, absence of fluid overload, and improvement in creatinine clearance and is often delayed until filter clotting or disconnection of the circuit because of logistic reasons.

[Effects and significance of continuous hemoperfusion on patients with diquat poisoning].

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

Beta-lactam dosing during continuous renal replacement therapy: a survey of practices in french intensive care units.

BACKGROUND: Little information is available on current practice in beta-lactam dosing during continuous renal replacement therapy (CRRT). Optimized dosing is essential for improving outcomes, and there is no consensus on the appropriate dose regimens. The objective of the present study was to describe current practice for beta-lactam dosing during CRRT in intensive care units (ICUs). METHODS: We conducted a nationwide survey by e-mailing an online questionnaire to physicians working in ICUs in France. The questionnaire included three sections: demographic characteristics, CRRT practices, and beta-lactam dosing regimens during CRRT. RESULTS: 157 intensivists completed the questionnaire. Continuous venovenous hemofiltration was the most frequently used CRRT technique, and citrate was the most regularly used anticoagulant. The median prescribed dose at baseline was 30 mL/kg/h. The majority of prescribers (57%) did not reduce beta-lactam dosing during CRRT. The tools were used to adapt dosing regimens during CRRT included guidelines, therapeutic drug monitoring (TDM), and data from the literature. When TDM was used, 100% T > 4 time the MIC was the most common mentioned pharmacokinetic/pharmacodynamic target (53%). Pharmacokinetic software tools were rarely used. Prolonged or continuous infusions were widely used during CRRT (88%). Institutional guidelines on beta-lactam dosing during CRRT were rare. 41% of physicians sometimes consulted another specialist before adapting the dose of antibiotic during CRRT. CONCLUSIONS: Our present results highlight the wide range of beta-lactam dosing practices adopted during CRRT. Personalized TDM and the implementation of Bayesian software appear to be essential for optimizing beta-lactam dosing regimens and improving patient outcomes.

Sustained low efficiency dialysis is non-inferior to continuous renal replacement therapy in critically ill patients with acute kidney injury: A comparative meta-analysis.

BACKGROUND: Critically ill adults with acute kidney injury (AKI) experience considerable morbidity and mortality. This systematic review aimed to compare the effectiveness of continuous renal replacement therapy (CCRT) versus sustained low efficiency dialysis (SLED) for individuals with AKI. METHODS: We carried out a systematic search of existing databases according to standard methods and random effects models were used to generate the overall estimate. Heterogeneity coefficient was also calculated for each outcome measure. RESULTS: Eleven studies having 1160 patients with AKI were included in the analyses. Meta-analysis results indicated that there was no statistically significant difference between SLED versus continuous renal replacement therapy (CRRT) in our primary outcomes, like mortality rate (rate ratio [RR] 0.67, 95% confidence interval [CI] 0.44-1.00; P = .05), renal recovery (RR 1.08, 95% CI 0.83-1.42; P = .56), and dialysis dependence (RR = 1.03, 95% CI 0.69-1.53; P = .89). Also, no statistically significant difference was observed for between SLED versus CRRT in the secondary outcomes: that is, length of intensive care unit stay (mean difference -0.16, 95% CI -0.56-0.22; P = .41) and fluid removal rate (mean difference -0.24, 95% CI -0.72-0.24; P = .32). The summary mean difference indicated that there was a significant difference in the serum phosphate clearance among patients treated with SLED and CRRT (mean difference -1.17, 95% CI -1.90 to -0.44, P = .002). CONCLUSIONS: The analysis indicate that there was no major advantage of using continuous renal replacement compared with sustained low efficiency dialysis in hemodynamically unstable AKI patients. Both modalities are equally safe and effective in treating AKI among critically ill patients.

Comparison of Clinical Outcomes of Different Connection Modes of Extracorporeal Membrane Oxygenation Combine with Continuous Renal Replacement Therapy.

OBJECTIVE: To evaluate the effect of different connection modes of ECMO and CRRT on patients with acute kidney injury (AKI). METHODS: Twenty-one patients received ECMO with AKI. These patients were admitted to our center from December 2018 to February 2021, selected, and treated with both ECMO and CRRT. They were divided into A connection mode (pre-membrane-pre-pump connection) and B connection mode (post-membrane-post-pump connection). We compared clinical indicators and outcomes between two connection modes. RESULTS: There were eight cases (38.91%) in A connection mode and 13 cases (61.09%) in B connection mode, with median durations of ECMO assistance of 5 days and 7 days, respectively. Median flow rates of ECMO of 3.0 L/min and 2.5 L/min, respectively; CRRT flow rates of 200 mL/min and 180 mL/min, respectively. CRRT filter lifetime was over 48h in both connection modes. Except for NT-pro BNP, no significant differences in clinical indicators were observed between the two groups before or after the treatment (P > .05). CONCLUSION: Both connection modes could achieve the therapeutic purpose and need no higher level of anticoagulation for patients simultaneously treated with ECMO and CRRT. Two modes had no impact on treatment effect and clinical indicators in patients. It had no effect on length of ICU stay and prognostic.

Treatment Effect of Regional Sodium Citrate Anticoagulation in Elderly Patients With High-Risk Bleeding Receiving Continuous Renal Replacement Therapy.

OBJECTIVE: To investigate the safety and efficacy of regional citrate anticoagulation (RCA) on elderly patients at high risk of bleeding after continuous renal replacement therapy (CRRT). METHODS: A total of 31 patients at high risk of bleeding who received CRRT in the intensive care unit were collected. The patients were divided into RCA group (n = 17) and no anticoagulation group (NA, n = 14) according to whether RCA was used or not. The levels of creatinine (Cr), blood urea nitrogen (BUN), prothrombin time (PT), activated partial thromboplastin time (APTT), total calcium (tCa), ionized calcium ion (iCa2+), sodium ion (Na+), bicarbonate ion (HCO3-), tCa/iCa2+ ratio, and pH were observed after treatment. The filter use time, number of filters used, filter obstruction events, clinical outcomes, and safety evaluation indexes were compared post-treatment. RESULTS: After treatment, serum Cr and BUN levels, APTT and PT levels in the RCA group were significantly lower than the NA group. The tCa, iCa2+, HCO3-, tCa/iCa2+, and pH were within the normal range after RCA treatment while Na+ levels saw a significant increase. In the RCA group, the filter using time was significantly longer, with significantly reduced numbers of filter use within 72 h and filter disorder events. Additionally, patients in the RCA group showed significant recovery of renal function and a significant reduction in bleeding events and in-hospital mortality. CONCLUSION: RCA treatment significantly improves clinical outcome of patients at high risk of bleeding after CRRT, safely and effectively prolongs the filter life and avoids coagulation incidences.

Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

OBJECTIVES: This study aimed to describe the population pharmacokinetics (PK) of cefepime during extracorporeal membrane oxygenation (ECMO) and through dosing simulations, identify a maximally effective and safe dosing strategy. METHODS: Serial cefepime plasma concentrations were measured in patients on ECMO, and data were analysed using a population PK approach with Pmetrics®. Dosing simulations were used to identify the optimal dosing strategy that achieved target trough concentrations (Cmin) of 8-20 mg/L. Six patients were enrolled, of which one was receiving renal replacement therapy. Cefepime was best described in a two-compartment model, with total body weight and creatinine clearance (CrCL) as significant predictors of PK parameters. The mean clearance and central volume of distribution were 2.42 L/h and 15.09 L, respectively. RESULTS: Based on simulations, patients with CrCL of 120 mL/min receiving 1 g 8-hourly dosing achieved a 40-44% probability of efficacy (Cmin > 8 mg/L) and 1-6% toxicity (Cmin > 20 mg/L). Patients with CrCL 30 mL/min and 65 mL/min receiving 1 g 12-hourly dosing achieved an 84-92% and 46-53% probability of efficacy and 8-44% and 1-8% probability of toxicity, respectively. Simulations demonstrated a lower probability of efficacy and higher probability of toxicity with decreasing patient weight. CONCLUSION: This study reported reduced cefepime clearance in patients receiving ECMO, resulting in an increased risk of cefepime toxicity. To avoid drug accumulation, modified dosing regimens should be used in critically ill patients on ECMO. Clinicians should adopt therapeutic drug monitoring when treating less susceptible organisms and in patients with reduced renal clearance on ECMO.

Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation - An observational case-control study.

BACKGROUND: Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation. METHODS: This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors. RESULTS: Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors. CONCLUSIONS: The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.

Continuous Renal Replacement Therapy Liberation and Outcomes of Critically Ill Patients With Acute Kidney Injury.

OBJECTIVE: To examine the association between continuous renal replacement therapy (CRRT) liberation and clinical outcomes among patients with acute kidney injury (AKI) requiring CRRT. METHODS: This single-center, retrospective cohort study included adult patients admitted to intensive care units with AKI and treated with CRRT from January 1, 2007, to May 4, 2018. Based on the survival and renal replacement therapy (RRT) status at 72 hours after the first CRRT liberation, we classified patients into liberated, reinstituted, and those who died. We observed patients for 90 days after CRRT initiation to compare the major adverse kidney events (MAKE90). RESULTS: Of 1135 patients with AKI, 228 (20%), 437 (39%), and 470 (41%) were assigned to liberated, reinstituted, and nonsurvival groups, respectively. The MAKE90, mortality, and RRT independence rates of the cohort were 62% (707 cases), 59% (674 cases), and 40% (453 cases), respectively. Compared with reinstituted patients, the liberated group had a lower MAKE90 (29% vs 39%; P=.009) and higher RRT independence rate (73% vs 65%; P=.04) on day 90, but without significant difference in 90-day mortality (26% vs 33%; P=.05). After adjustments for confounders, successful CRRT liberation was not associated with lower MAKE90 (odds ratio, 0.71; 95% CI, 0.48 to 1.04; P=.08) but was independently associated with improved kidney recovery at 90-day follow-up (hazard ratio, 1.81; 95% CI, 1.41 to 2.32; P<.001). CONCLUSION: Our study demonstrated a high occurrence of CRRT liberation failure and poor 90-day outcomes in a cohort of AKI patients treated with CRRT.

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.

The efficiency of continuous renal replacement therapy for rewarming of patients in accidental hypothermia--An experimental study.

Severe accidental hypothermia carries high mortality and morbidity and is often treated with invasive extracorporeal methods. Continuous veno-venous hemodiafiltration (CVVHDF) is widely available in intensive care units. We sought to provide theoretical basis for CVVHDF use in rewarming of hypothermic patients. CVVHDF system was used in the laboratory setting. Heat balance and transferred heat units were evaluated for the system without using blood. We used 5L of crystalloid solution at the temperature of approximately 25°C, placed in a thermally insulated tank (representing the "central compartment" of a hypothermic patient). Time of warming the central compartment from 24.9 to 30.0°C was assessed with different flow combinations: "blood" (central compartment fluid) 50 or 100 or 150 mL/min, dialysate solution 100 or 1500 mL/h, and substitution fluid 0 or 500 mL/h. The total circulation time was 1535 minutes. There were no differences between heat gain values on the filter depending on blood flow (P = .53) or dialysate flow (P = .2). The mean heating time for "blood" flow rates 50, 100, and 150 mL/min was 113.7 minutes (95% CI, 104.9-122.6 minutes), 83.3 minutes (95% CI, 76.2-90.3 minutes), and 74.7 minutes (95% CI, 62.6-86.9 minutes), respectively (P < .01). The respective median rewarming rate for different "blood" flows was 3.6°C/h (IQR, 3.0-4.2°C/h), 4.8 (IQR, 4.2-5.4°C/h), and 5.4 (IQR, 4.8-6.0°C/h), respectively (P < .01). The dialysate flow did not affect the warming rate. Based on our experimental model, CVVHDF may be used for extracorporeal rewarming, with the rewarming rates increasing achieved with higher blood flow rates.

Regional citrate anticoagulation "non-shock" protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance.

BACKGROUND: Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of "single starting calcium infusion rate for all patients" puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. METHODS: This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA "Non-shock" protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. RESULTS: Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th-75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91-2.13). CONCLUSIONS: The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of "one starting dose for all" reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.