Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

OBJECTIVES: Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. DESIGN: Single-center, retrospective study, 2010-2019. SETTING: Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. PATIENTS: Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. CONCLUSIONS: Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

Continuous renal replacement therapy in neonates and children: what does the pediatrician need to know? An overview from the Critical Care Nephrology Section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion: In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes. • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT. What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality. • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes.

An evaluation of different dilution modes on circuit lifespan during continuous veno-venous hemodiafiltration without anticoagulation.

BACKGROUND: Circuit clotting remains a major problem during continuous kidney replacement therapy (CKRT), particularly in patients with contraindications to anticoagulant use. We hypothesized that the different options of alternative replacement fluid infusion sites might affect circuit lifespan. However, research-based evidence supporting an optimal replacement fluid infusion strategy is limited. Therefore, we aimed to evaluate the effect of three dilution modes (pre-dilution, post-dilution, and pre- to post-dilution) on circuit lifespan during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: This prospective cohort study was conducted between December 2019 and December 2020. Patients requiring CKRT were enrolled to receive pre-dilution, post-dilution, or pre- to post-dilution fluid infusion with CVVHDF. The primary endpoint was circuit lifespan, and the secondary outcomes included the clinical parameters of patients, such as changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, 28-day all-cause mortality, and length of stay. For all patients included in this study, only the first circuit used was recorded. RESULTS: Among the 132 patients enrolled in this study, 40 were in the pre-dilution mode, 42 were in the post-dilution mode, and 50 were in the pre- to post-dilution mode. The mean circuit lifespan was significantly longer in the pre- to post-dilution group (45.72 h, 95% CI, 39.75-51.69 h) than in the pre-dilution group (31.58 h, 95% CI, 26.33-36.82 h) and the post-dilution group (35.20 h, 95% CI, 29.62-40.78 h). There was no significant difference between the pre- and post-dilution group circuit lifespan (p > 0.05). Kaplan-Meier survival analysis revealed a significant difference between the three dilution modes (p = 0.001). No significant differences were observed in terms of changes in the Scr and BUN levels, admission day, and 28-day all-cause mortality among the three dilution groups (p > 0.05). CONCLUSION: The pre- to post-dilution mode significantly prolonged circuit lifespan but did not reduce Scr and BUN levels, compared with the pre-dilution and post-dilution modes during CVVHDF when no anticoagulants were used.

Management and Outcomes of Acute Kidney Injury due to Burns: A Literature Review.

Acute kidney injury (AKI), a common and severe complication following burn injuries, presents a significant challenge due to its broad clinical manifestations and diverse etiologies. AKI, previously known as acute renal failure, can present abruptly following burns or thermal injuries, causing detrimental health outcomes such as progressive kidney dysfunction, increased hospital length of stay, and requirement of renal replacement therapy (RRT). AKI affects the maintenance of homeostasis of fluid and electrolytes, elimination of metabolic wastes and byproducts, and acid-base balance. Aggressive nutritional support is particularly necessitated in burn patients to prevent protein-energy wasting and a negative nitrogen balance. Understanding the pathogenesis of AKI in burns and improving its prevention and early diagnosis are active areas of research in this field. Despite the potential benefits, the optimal timing and threshold for RRT initiation in burn patients with AKI remain unclear, warranting further studies. Ongoing investigations focus on refining RRT techniques, evaluating biomarkers for early detection of AKI, and exploring adjunctive therapies to enhance renal recovery. The aim of this study is to review the etiology, diagnostic tools, and interventions that improve outcomes associated with AKI in burn-related settings.

Acute kidney injury occurs in nearly one-quarter of people with severe burns and leads to increased mortality rates. Burn injuries can be associated with numerous complications, such as hypermetabolic response, hypovolemia, hypotension, and sepsis, and involves early burn- and late burn-related complications. Validated metrics for classifying the extent of burn injuries, such as the Abbreviated Burn Severity Index on admission, Sequential Organ Failure Assessment Score on admission, Modified Marshall Score, baseline blood urea nitrogen, and serum creatinine all serve to discriminate the risk of acute kidney injury. With no current consensus on predictive energy equations or ideal nutritional goals, optimal nutritional support in burn patients with acute kidney injury largely relies on the burn severity, individual presentation of malnourishment, and timely resuscitation. Although novel biomarkers such as plasma and urinary NGAL levels, KIM-1, and IL-18 are still being investigated as diagnostic tools for acute kidney injury in both the early and late burn periods, and artificial intelligence/machine learning may soon be incorporated as an efficacious assessment tool in the future. Renal replacement therapy is often indicated in the setting of acute kidney injury due to severe burns, especially if the metabolic and fluid disturbances due to acute kidney injury are not adequately managed with fluid resuscitation, diuretics, electrolyte repletion, and other supportive measures. However, with over a third of all burn-related acute kidney injury patients requiring some form of renal replacement therapy, elevated mortality rates remain a cause for concern.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Rapid and Effective Elimination of Myoglobin with CytoSorb® Hemoadsorber in Patients with Severe Rhabdomyolysis.

INTRODUCTION: Rhabdomyolysis is characterized by destruction of muscle fibers by various causes and is diagnosed by increased creatine kinase concentrations in the blood. Myoglobin released into the blood may cause acute kidney injury. In this randomized controlled study, we hypothesized that myoglobin elimination would be faster when a hemoadsorber was added to a continuous veno-venous hemodialysis (CVVHD). METHODS: Four patients in the control group received CVVHD with a high cut-off hemofilter using high blood and dialysate flows for 48 h. Four patients in the CytoSorb group received the same treatment, but in addition, the hemoadsorber CytoSorb® was inserted in front of the hemofilter and replaced once after 24 h. Blood samples were drawn simultaneously before (pre) and after (post) the hemofilter or else the hemoadsorber, after 5 and 30 min, as well as after 2, 4, 8, and 24 h. All measurements were repeated the next day after the hemoadsorber had been renewed in the CytoSorb group. Primary outcome was the area under the curve (AUC) of the relative myoglobin concentrations as percent of baseline. To evaluate the efficacy of myoglobin removal, relative reductions in myoglobin concentrations during one passage through each device at each time point were calculated. RESULTS: Patients in the CytoSorb group had a significantly lower AUC during the first 24 h (42 ± 10% vs. 63 ± 6%, p = 0.029) as well as during the observation period of 48 h (26 ± 7% vs. 51 ± 12%, p = 0.029). The relative reductions for myoglobin were considerably higher in the CytoSorb group compared to the control group during the first 8 h. CONCLUSION: Myoglobin concentrations declined considerably faster when CytoSorb was added to a CVVHD. When compared to a high-cut-off hemofilter, efficacy of CytoSorb in myoglobin elimination was much better. Because of saturation after 8-12 h an exchange may be necessary.

Extracorporeal blood purification with Oxiris® filter in critically ill patients with COVID-19 requiring continuous renal replacement therapy.

INTRODUCTION: Severe COVID-19 is associated with a dysregulated immune response that usually leads to cytokine release syndrome. This study aimed to compare the use of extracorporeal blood purification therapy (Oxiris®) versus standard continuous renal replacement therapy (CRRT) in critically-ill patients with severe COVID-19. METHODS: This was a national, multicenter, retrospective study of patients with COVID-19 admitted to the intensive care unit (ICU) between March and October 2020 who required CRRT. Patients were categorized into two groups: Oxiris® CRRT and standard CRRT. The primary outcome was the number of patients alive and ventilator-free at 30-days post-CRRT treatment. Key secondary endpoints included change in inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and PaO2/FiO2 ratio at 24- and 72-h post Oxiris® initiation. RESULTS: Thirty-five patients received Oxiris® CRRT and 23 patients received standard CRRT. The primary outcome was 31.4% in the Oxiris® group versus 4.3% in the standard CRRT group (adjusted odds ratio 5.97, 95% confidence interval [CI], 0.64-55.6; p = 0.117). In the Oxiris® group, interleukin-6 (IL-6) concentrations significantly decreased at 24 and 72-h (p = 0.033) and PaO2/FiO2 ratio significantly increased at 24 and 72 h after Oxiris® initiation (p = 0.001). There was no significant change in SOFA scores at 24- and 72-h after Oxiris® initiation. CONCLUSION: The number of patients alive and ventilator-free at 30-days was higher in the Oxiris® group than that in the standard CRRT group; however, the difference did not reach statistical significance after adjusting for the baseline severity of illness. There was a significant reduction in IL-6 and significant improvement in PaO2/FiO2 ratio after Oxiris® CRRT initiation.

Managing the kidney - The role of continuous renal replacement therapy in neonatal and pediatric ECMO.

Extracorporeal membrane oxygenation (ECMO) represents a lifesaving therapy utilized in in the most critically ill neonates and children with reversible cardiopulmonary failure. As a result of the severity of their critical illness these patients are among the highest risk populations for developing acute kidney injury (AKI) and disorders of fluid balance including the pathologic state of fluid overload (FO). In multiple studies AKI has been shown to occur commonly in 60-80% children treated with ECMO and is associated with adverse outcomes. In early studies evaluating ECMO in neonatal respiratory populations, the importance of fluid balance and the development of FO was recognized as an important contributor to adverse outcomes. Multiple single center studies and multicenter work have confirmed that FO occurs commonly across ECMO populations and is consistently associated with adverse outcomes. As a result of the high rates of AKI and the high rates of FO, continuous renal replacement therapy (CRRT) is increasingly utilized in neonatal and pediatric ECMO. In this state-of-the-art review, we cover the definitions, pathophysiology, incidence, and impact of AKI and FO in neonates and children supported with ECMO and summarize and appraise the evidence regarding the use of CRRT concurrently with ECMO. This review will cover the appropriate timing of this initiation, the options for providing CRRT with ECMO, overview of CRRT prescription, and the long-term implications of kidney support therapy in this population.

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. METHODS: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. RESULTS: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively). CONCLUSIONS: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

Body temperature and infection in critically ill patients on continuous kidney replacement therapy.

PURPOSE: Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection. METHODS: We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection. RESULTS: We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P < .02). CONCLUSION: Body temperature is insufficient to indicate an infection in critically ill patients on CKRT. Clinicians should remain watchful for other signs, symptoms, and indications of infection in patients on CKRT because of expected high infection rates.

Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a widely used standard therapy for critically ill patients with acute kidney injury (AKI). Despite its effectiveness, treatment is often interrupted due to clot formation in the extracorporeal circuits. Anticoagulation is a crucial strategy for preventing extracorporeal circuit clotting during CRRT. While various anticoagulation options are available, there were still no studies synthetically comparing the efficacy and safety of these anticoagulation options. METHODS: Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to October 31, 2022. All randomized controlled trials (RCTs) that examined the following outcomes were included: filter lifespan, all-cause mortality, length of stay, duration of CRRT, recovery of kidney function, adverse events and costs. RESULTS: Thirty-seven RCTs from 38 articles, comprising 2648 participants with 14 comparisons, were included in this network meta-analysis (NMA). Unfractionated heparin (UFH) and regional citrate anticoagulation (RCA) are the most frequently used anticoagulants. Compared to UFH, RCA was found to be more effective in prolonging filter lifespan (MD 12.0, 95% CI 3.8 to 20.2) and reducing the risk of bleeding. Regional-UFH plus Prostaglandin I2 (Regional-UFH + PGI2) appeared to outperform RCA (MD 37.0, 95% CI 12.0 to 62.0), LMWH (MD 41.3, 95% CI 15.6 to 67.0), and other evaluated anticoagulation options in prolonging filter lifespan. However, only a single included RCT with 46 participants had evaluated Regional-UFH + PGI2. No statistically significant difference was observed in terms of length of ICU stay, all-cause mortality, duration of CRRT, recovery of kidney function, and adverse events among most evaluated anticoagulation options. CONCLUSIONS: Compared to UFH, RCA is the preferred anticoagulant for critically ill patients requiring CRRT. The SUCRA analysis and forest plot of Regional-UFH + PGI2 are limited, as only a single study was included. Additional high-quality studies are necessary before any recommendation of Regional-UFH + PGI2. Further larger high-quality RCTs are desirable to strengthen the evidence on the best choice of anticoagulation options to reduce all-cause mortality and adverse events and promote the recovery of kidney function. Trial registration The protocol of this network meta-analysis was registered on PROSPERO ( CRD42022360263 ). Registered 26 September 2022.

Safety and efficacy of continuous renal replacement therapy for children less than 10 kg using standard adult machines.

Continuous Renal Replacement Therapy (CRRT) machines are used off-label in patients less than 20 kg. Infant and neonates-dedicated CRRT machines are making their way into current practice, but these machines are available only in select centres. This study assesses the safety and efficacy of CRRT using adult CRRT machines in children ≤ 10 kg and to determines the factors affecting the circuit life in these children. DESIGN: Retrospective cohort study of children ≤ 10 kg who received CRRT (January 2010-January 2018) at a PICU in a tertiary care centre in London, UK. Primary diagnosis, markers for illness severity, CRRT characteristics, length of PICU admission and survival to PICU discharge were collected. Descriptive analysis compared survivors and non-survivors. A subgroup analysis compared children ≤ 5 kg to children 5-10 kg. Fifty-one patients ≤ 10 kg received 10,328 h of CRRT, with median weight of 5 kg. 52.94% survived to hospital discharge. Median circuit life was 44 h (IQR 24-68). Bleeding episodes occurred with 6.7% of sessions and hypotension for 11.9%. Analysis of efficacy showed a reduction in fluid overload at 48 h (P = 0.0002) and serum creatinine at 24 and 48 h (P = 0.001). Blood priming was deemed to be safe as serum potassium decreased at 4 h (P = 0.005); there was no significant change in serum calcium. Survivors had a lower PIM2 score at PICU admission (P < 0.001) and had longer PICU length of stay (P < 0.001).    Conclusion: Pending neonatal and infant dedicated CRRT machines, CRRT can be safely and effectively applied to children weighing ≤ 10 kg using adult-sized CRRT machines. WHAT IS KNOWN: • Continuous Renal Replacement Therapy can be used for a variety of renal and non-renal indications to improve outcomes for children in the paediatric intensive care unit. These include, persistent oliguria, fluid overload, hyperkalaemia, metabolic acidosis, hyperlactatemia, hyperammonaemia, and hepatic encephalopathy. • Young children ≤ 10 kg are most often treated using standard adult machines, off-label. This potentially places them at risk of side effects due to high extracorporeal circuit volumes, relatively higher blood flows, and difficulty in achieving vascular access. WHAT IS NEW: • This study found that standard adult machines were effective in reducing fluid overload and creatinine in children ≤ 10 kg. This study also assessed safety of blood priming in this group and found no evidence of an acute fall in haemoglobin or calcium, and a fall in serum potassium by a median of 0.3 mmol/L. The frequency of bleeding episodes was 6.7%, and hypotension requiring vasopressors or fluid resuscitation occurred with 11.9% of treatment sessions. • These findings suggest that adult CRRT machines are sufficiently safe and efficacious for routine use in PICU for children ≤ 10 kg and suggest that further research is undertaken, regarding the routine rollout of dedicated machines.

Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

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.

Predicting outcomes of continuous renal replacement therapy using body composition monitoring: a deep-learning approach.

Fluid balance is a critical prognostic factor for patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated whether repeated fluid balance monitoring could improve prognosis in this clinical population. This was a multicenter retrospective study that included 784 patients (mean age, 67.8 years; males, 66.4%) with severe AKI requiring CRRT during 2017-2019 who were treated in eight tertiary hospitals in Korea. Sequential changes in total body water were compared between patients who died (event group) and those who survived (control group) using mixed-effects linear regression analyses. The performance of various machine learning methods, including recurrent neural networks, was compared to that of existing prognostic clinical scores. After adjusting for confounding factors, a marginal benefit of fluid balance was identified for the control group compared to that for the event group (p = 0.074). The deep-learning model using a recurrent neural network with an autoencoder and including fluid balance monitoring provided the best differentiation between the groups (area under the curve, 0.793) compared to 0.604 and 0.606 for SOFA and APACHE II scores, respectively. Our prognostic, deep-learning model underlines the importance of fluid balance monitoring for prognosis assessment among patients receiving CRRT.

Initiating Continuous Renal Replacement Therapy in Patients With Transurethral Resection of Prostate Syndrome: A Case Report.

With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.

Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury.

BACKGROUND: Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. METHODS: A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1-7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models. RESULTS: A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22-2.20) and 4.18 (2.99-5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score). CONCLUSIONS: Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

Impact of connecting methods of continuous renal replacement therapy device on patients underwent extracorporeal membrane oxygenation: A retrospectively observational study.

OBJECTIVE: The objective of this study was to compare the safety and efficiency of different extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) connection methods. BACKGROUND: The number of patients receiving ECMO is increasing, and the fields of application are getting wider. However, patients receiving ECMO are prone to acute kidney injury and fluid overload requiring CRRT. There are few comparative studies of two different systems of connecting CRRT device and ECMO from safety and efficacy perspective. METHODS: This retrospective observational study included patients receiving ECMO in the extracorporeal life support centre of the First Affiliated Hospital of Nanjing Medical University from June, 2015, to December, 2020. Patients were divided into the parallel system group and integrated system group according to the connecting method between ECMO circuit and CRRT line. The outcomes were discharge survival rate, CRRT therapeutic dose completion rate, CRRT catheterisation time, CRRT initiating time, local bleeding at the CRRT catheter site, mean filter life, ECMO circuit thrombosis, ECMO air leakage, or blood leakage due to CRRT. RESULTS: Thirty patients in the parallel system group and 70 patients in the integrated system group were finally included. The discharge survival rate and CRRT therapeutic dose completion rate were not significantly different between the two groups. The parallel system group had significant longer CRRT initiating time (49.0 ± 12.1 min vs. 14.6 ± 2.1 min, P < 0.001) and shorter filter life (11.5 ± 3.2 h vs. 47.3 ± 14.0 h, P < 0.001) than the integrated system group. The occurrence rate of local bleeding was 93.3% in the parallel system group, and there is no bleeding case in the integrated system group. There was no case of ECMO circuit thrombosis from CRRT as well as ECMO air or blood leakage caused by CRRT in either group. ECMO therapy can be adapted by adjusting the position of the CRRT outlet in the integrated system. CONCLUSIONS: Connecting CRRT and ECMO as an integrated system might accelerate CRRT initiation, avoid local bleeding, and prolong filter life compared to the parallel system. The chance of developing CRRT-related ECMO circuit leak and thrombosis is manageable.