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Kidney replacement therapy (KRT) is used to provide supportive therapy for critically ill patients with severe acute kidney injury and various other non-renal indications. Modalities of KRT include continuous KRT (CKRT), intermittent hemodialysis (HD), and sustained low efficiency daily dialysis (SLED). However, circuit clotting is a major complication that has been investigated extensively. Extracorporeal circuit clotting can cause reduction in solute clearances and can cause blood loss, leading to an upsurge in treatment costs and a rise in workload intensity. In this educational review, we discuss the pathophysiology of the clotting cascade within an extracorporeal circuit and the use of various types of anticoagulant methods in various pediatric KRT modalities., Author(s): Rupesh Raina [sup.1] [sup.2] , Ronith Chakraborty [sup.1] [sup.2] , Andrew Davenport [sup.3] , Patrick Brophy [sup.4] , Sidharth Sethi [sup.5] , Mignon McCulloch [sup.6] , Timothy Bunchman [sup.7] [...]

Background: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. Design: Prospective observational quality improvement initiative cohort study. Setting and Participants: A prospective single‐center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. Quality Improvement Plan: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%–30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. Measures: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long‐term outcomes were assessed at the 1‐year follow‐up including adherence to dialysis, renal transplantation, death, and loss to follow‐up. Results: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long‐term outcomes showed 88% adherence to dialysis and 38% renal transplantation. Limitations: This study is characterized by a single‐center design, nonrandomized approach, and limited sample size. Conclusions: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome. [ABSTRACT FROM AUTHOR]

Wide ranges of age and weight in pediatric patients makes renal replacement therapy (RRT) in acute kidney injury (AKI) challenging, particularly in the pediatric intensive care unit (PICU), wherein children are often hemodynamically unstable. Standard hemodialysis (HD) is difficult in this group of children and continuous veno-venous hemofiltration/dialysis (CVVH/D) has been the accepted modality in the developed world. Unfortunately, due to cost constraints, CVVH/D is often not available and peritoneal dialysis (PD) remains the common mode of RRT in resource-poor facilities. Acute PD has its drawbacks, and intermittent HD (IHD) done slowly over a prolonged period has been explored as an alternative. Various modes of slow sustained IHD have been described in the literature with the recently introduced term prolonged intermittent RRT (PIRRT) serving as an umbrella terminology for all of these modes. PIRRT has been widely accepted in adults with studies showing it to be as effective as CVVH/D but with an added advantage of being more cost-effective. Pediatric data, though scanty, has been promising. In this current review, we elaborate on the practical aspects of undertaking PIRRT in children as well as summarize its current status., Author(s): Rajiv Sinha [sup.1] , Sidharth Kumar Sethi [sup.2] , Timothy Bunchman [sup.3] , Valentine Lobo [sup.4] , Rupesh Raina [sup.5] Author Affiliations: (1) 0000 0004 1801 0469, grid.414710.7, Institute [...]

Introduction: Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step‐down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low‐efficiency daily dialysis with pre‐filter replacement (SLED‐f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED‐f as a transition step‐down therapy after CKRT in critically ill pediatric patients with acute kidney injury. Methods: A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi‐organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED‐f. Results: Eleven patients underwent 105 SLED‐f sessions (mean of 9.55 +/− 4.90 sessions per patient), as a part of step‐down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED‐f, urea reduction ratio was 64.1 +/− 5.3%, Kt/V was 1.13 +/− 0.1, and beta‐2 microglobulin reduction was 42.5 +/−4%. Incidence of hypotension and requirement of escalation of inotropes during SLED‐f was 18.18%. Filter clotting occurred twice in one patient. Conclusion: SLED‐f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU. [ABSTRACT FROM AUTHOR]

Author(s): Sidharth Kumar Sethi [sup.1] , Norma Maxvold [sup.2] , Timothy Bunchman [sup.2] , Pranaw Jha [sup.1] , Vijay Kher [sup.1] , Rupesh Raina [sup.3] Author Affiliations: (1) grid.429252.a, 0000000417644857, [...]

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7–19) vs. 7 (5–10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74–14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934–0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates. [ABSTRACT FROM AUTHOR]

COVID‐19 has challenged the global healthcare system through rapid proliferation and lack of existing treatment resulting in over 180 million cases and 3.8 million deaths since December 2019. Although pediatric patients only comprise 1%–2% of diagnosed cases, their incidence of acute kidney injury ranges from 8.2% to 18.2% compared to 49% in adults. Severe infection, initiated by dysregulated host response, can lead to multiorgan failure. In this review, we focus on the use of various blood filters approved for use in pediatric kidney replacement therapy to mitigate adverse effects of severe illness. Therapeutic effects of these blood filters range from cytokine removal (CytoSorb, HA330, HCO/MCO), endotoxin removal (Toraymyxin, CPFA), both cytokine and endotoxin removal (oXiris), and nonspecific removal of proteins (PMMA) that have already been established and can be used to mitigate the various effects of the cytokine storm syndrome in COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a clinical condition characterized by an abrupt increase in serum creatinine levels due to functional changes in the kidneys from a newfound insult or injury. For supportive treatment, continuous renal replacement therapy (CRRT) is one of the most widely used modalities due to its precise control of fluid balance over extended periods of time. However, its complications include circuit clotting, the most frequent cause for CRRT interruption. Vascular access and circuit management were found to be major determinants of performance efficiency. Anticoagulation required to prevent clotting has the downside of increasing the risk of bleeding, especially in the setting of overdosage. Hence, a delicate balance needs to be maintained consistently. Methods: This study explores the adequacy of non‐anticoagulation measures in the prevention of circuit clotting. A comprehensive literature search was conducted using PubMed/Medline and Embase databases to include all relevant studies. Findings The most‐effective CRRT catheter would be made of nonthrombogenic material, noncuffed and nontunneled with separate lumens for arterial and venous blood. Further, studies show that blood flow during the process is optimized at 200 ml/min, which can be lowered in the pediatric population due to more narrow catheters. Platelet count and hematocrit need to be closely monitored as levels above 450,000 × 106/L and 0.40, respectively, increase risk of clotting. Predilution is a non‐anticoagulation technique to reduce the risk of clotting by returning replacement solution to the blood before it reaches the filter. Also, biocompatible membranes such as polyacrylonitrile or polysulfone activate the coagulation cascade significantly less than the conventional cellulose‐based membranes, thereby reducing clotting chances. Discussions: With the advent of such techniques and maneuvers, anticoagulation can be efficiently maintained in patients undergoing CRRT without increasing the risk of bleeding. [ABSTRACT FROM AUTHOR]

The Third International Conference on Pediatric Continuous Renal Replacement Therapy (PCRRT) occurred in Orlando, Florida, USA, 24-26 June 2004. Attendees from 13 countries made up an audience that totaled 230 [...]