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Severe COVID-19 can necessitate multiple organ support including veno-venous extracorporeal membrane oxygenation (vvECMO) and renal replacement therapy. The therapy can be complicated by venous thromboembolism due to COVID-19-related hypercoagulability, thus restricting vascular access beyond the vvECMO cannula. Although continuous renal replacement therapy can be performed via a vvECMO circuit, studies addressing sustained low-efficiency dialysis (SLED) integration into vvECMO circuits are scarce. Here we address the lack of evidence by evaluating feasibility of SLED integration into vvECMO circuits.Retrospective cohort study on nine critically ill COVID-19 patients, treated with integrated ECMO-SLED on a single intensive care unit at a tertiary healthcare facility between December 2020 and November 2021. The SLED circuits were established between the accessory arterial oxygenator outlets of a double-oxygenator vvECMO setup. Data on filter survival, quality of dialysis, and volume management were collected and compared with an internal control group receiving single SLED.This study demonstrates general feasibility of SLED integration into existing vvECMO circuits. Filter lifespans of ECMO-SLED compared with single SLED are significantly prolonged (median 18.3 h vs. 10.3 h, p 0.01). ECMO-SLED treatment is furthermore able to sufficiently normalize creatinine, blood urea nitrogen, and serum sodium, and allows for adequate ultrafiltration rates.We can show that ECMO-SLED is practical, safe, results in adequate dialysis quality and enables sufficient electrolyte and volume management. Our data indicate that SLED devices can serve as potential alternative to continuous-veno-venous-hemodialysis for integration in vvECMO circuits.

Background In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. Methods We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24–72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. Results We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9–40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5–12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P Conclusions Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

Purpose: Acute kidney injury (AKI) is a common occurrence in critically ill patients affecting almost 50% of those admitted to an intensive care unit. (Rachoin JS, et al. CCM. 2019) There remains to be a cure for AKI, but renal replacement therapies (RRT) are being used at an increasing rate to manage these patients during their critical illness. (Rachoin JS, et al. CCM. 2019) Various modalities for RRT exist from intermittent hemodialysis (iHD) to continuous renal replacement therapy (CRRT). Sustained low efficiency dialysis (SLED) is an intermediate or hybrid RRT modality combining aspects of both iHD and CRRT. No RRT modality has been shown to be superior to another, however, each modality has its unique risks and benefits. Furthermore, each RRT modality has a particular impact on drug clearance requiring dose modifications specific to the RRT modality selected. Research and dosing recommendations exist for both iHD and CRRT dosing for many medications, however, less attention has been paid to drug dosing in SLED.

We postulated that renal replacement therapy (RRT) in ICH patients with advanced chronic kidney disease (CKD) is associated with increased frequency and size of perihematomal edema (PHE) expansion and worse patient outcomes. The Get With the Guidelines-Stroke Registry was queried for all patients admitted with ICH (N = 1089). Secondary causes, brainstem ICH, and initial HV

Regional citrate anticoagulation (RCA) is a recommended method for extracorporeal circuit anticoagulation during renal replacement therapy (RRT). Increased risk of citrate accumulation by default of hepatic metabolism limits its use in liver failure patients. A Catot /Caion ratio ≥2.5 is established as an indirect control of plasma citrate poisoning. To investigate the safety of RCA in patients with liver impairment during sustained low-efficiency dialysis (SLED), we conducted a retrospective study of 41 patients with acute or chronic hepatocellular failure requiring RRT between January 2014 and June 2015 in the intensive care unit of the Groupe Hospitalier Sud Ile de France. Sixty-seven SLED sessions were performed. At admission, 32 (78%) patients had acute liver dysfunction and nine (22%) patients had cirrhosis with a median MELD score of 27 (IQR: 18.8, 42.0). Despite a majority of poor prognosis patients (SAPS-II (Simplified Acute Physiology Score II) score 71 [IQR: 58; 87]), with acute liver impairment as a part of multi-organ failure, no dosage of Catot /Caion ratio after SLED sessions exceeded the critical threshold of 2.5. Of the 63 complete sessions, neither dyscalcemia nor major dysnatremia, nor extracorporeal circuit thrombosis were noticed. Observed acid-base disturbances (16.4%) were not significantly correlated with the Catot /Caion ratio (P = .2155). In this retrospective study using RCA during intermittent RRT in ICU patients with severe liver dysfunction, we did not observe any citrate accumulation but monitoring of acid-base status and electrolytes remains necessary to ensure technique safety.

A 31-year-old previously healthy woman was admitted with rapidly progressive respiratory failure from acute respiratory distress syndrome related to infection with SARS-COV-2. Over a 48-hour period, she went from requiring 2-L nasal canula oxygen to maximum ventilator support, and she developed

Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking. The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies. Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses. From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration–time curve from time zero to 24 h [AUC24]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC24 ≥ 700), a loading dose of 2400 mg followed by daily doses of 1600 mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels. In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.

Introduction: Cardiovascular collapse due to large ingestions of isopropanol is rare. We report a case of a pediatric patient who had severe CNS and respiratory depression and cardiovascular collap...

AIMS To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT). METHODS Fifteen patients without RRT, 13 patients receiving sustained low-efficiency dialysis and 12 patients receiving continuous veno-venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration. RESULTS The PK of meropenem was best described by a 1-compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low-efficiency dialysis and continuous veno-venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations. CONCLUSION We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients.

Background Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT. Methods We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets. Results We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75–1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64–1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02–7.81). At one year, there was no difference in mortality or dialysis dependence. Conclusions Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT.

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations., This expert Consensus Statement from the Pediatric Continuous Renal Replacement Therapy (PCRRT) workgroup presents recommendations for the management of hyperammonaemia requiring kidney replacement therapy in paediatric populations. Additional studies are needed to strengthen these recommendations, which will be reviewed every 2 years.

Introduction: Sustained low efficiency dialysis (SLED) is an increasingly common treatment option for acute kidney injury (AKI) patients, but there are few studies examining the survival and predictive outcome of this therapy. The study aims to evaluate survival, pre-SLED predictors and complications associated with SLED. Materials and Methods: This was a retrospective cohort study of 91 patients with AKI treated with SLED in a tertiary hospital from January 2014 to August 2018. The primary outcomes were in-hospital and 30-day mortality. The secondary outcomes were the clinical and laboratory pre-SLED characteristics that were associated with survival and complication of SLED. Results: Median survival of AKI patients treated with SLED was 17 days and the 30-day mortality rate was 58%. Pre-SLED serum levels of creatinine (adjusted HR 0.82, 95% CI 0.71x0.94), albumin (adjusted HR 0.57, 95% CI 0.4–0.81), potassium (adjusted HR 1.38, 95% CI 1.1–1.73) and number of SLED (adjusted HR 0.95, 95% CI 0.91-1) served as predictors of survival. Arrhythmia was found 3.3% and intradialytic hypotension in 13.2% of patients. No patient had bleeding complications. Conclusions: Our study found similar in-hospital and 30-day mortality for AKI patients treated with SLED. High pre-SLED levels of serum albumin, creatinine and number of SLED were significantly associated with reduced risk of death and high pre-SLED serum potassium was associated with increased risk of death. These results indicate that SLED is safe treatment, with few haemorrhage and haemodynamic complications. Key words: Acute kidney injury, Predictors, Sustained low efficiency dialysis, Survival

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Background/purpose The pharmacokinetics of vancomycin in patients who undergo sustained low efficiency daily diafiltration (SLEDD-f) is not clear. This study aimed to determine the appropriate vancomycin dosage regimen for patients receiving SLEDD-f. Methods This prospectively observational study enrolled critically ill patients older than 18 years old that used SLEDD-f as renal replacement therapy and received vancomycin treatment. An 8-h SLEDD-f was performed with FX-60 (high-flux helixone membrane, 1.4 m2). Serial blood samples were collected before, during, and after SLEDD-f to analyse vancomycin serum concentrations. Effluent fluid samples (a mixture of dialysate and ultrafiltrate) were also collected to determine the amount of vancomycin removal. Results Seventeen patients were enrolled, and 10 completed the study. The amount of vancomycin removal was 447.4 ± 88.8 mg (about 78.4 ± 18.4% of the dose administered before SLEDD-f). The vancomycin concentration was reduced by 57.5 ± 14.9% during SLEDD-f, and this reduction was followed by a rebound with duration of one to three hours. The elimination half-life of vancomycin decreased from 64.1 ± 35.7 h before SLEDD-f to 7.0 ± 3.0 h during SLEDD-f. Conclusion Significant amount of vancomycin removed during SLEDD-f. Despite the existence of post-dialysis rebound, a sufficient supplemental dose is necessary to maintain therapeutic range.

We describe a 9-year-old boy with acute liver failure of unknown etiology, unresponsive to standard medical therapy, with increasing hyperammonemia blood level, lactate elevation, a pediatric end liver stage of 20, a hepatic encephalopathy (HE) score of 2, and scheduled for emergent liver transplantation on the waiting list. We admitted him in the pediatric intensive care unit and managed him in the early stages with continuous renal replacement therapy and therapeutic plasma exchange as soon as neurologic impairment started to worsen. He recovered from his HE after 3 days of blood purification and was removed from the transplantation waiting list due to progressive liver function improvement.

To compare hemodynamic instability during continuous, intermittent and hybrid renal replacement therapy (RRT) in critically ill patients, and its association with renal recovery and mortality.The search was conducted in accordance with the PRISMA guidelines which was registered at the PROSPERO Database (CRD42018086504). Randomized clinical trials (RCTs) involving critically ill patients with acute kidney injury (AKI) treated with continuous, intermittent or hybrid RRT were included. The search was performed using PubMed, Embase and Cochrane databases.Out of 3442 citations retrieved, 12 RCTs were included in the systematic analysis, representing 1419 patients. Most studies (n = 8) did not report differences in hemodynamic parameters across different RTT modalities. The incidence of hypotensive episodes varied from 5 to 60% among the studies. Punctual differences on heart rate and blood pressure were observed among studies. However, studies presented high heterogeneity in terms of outcome definitions and measurement, thus making the conduction of meta-analysis impossible.There is very few information available regarding hemodynamic tolerance of renal replacement therapy methods. A better standardization of hemodynamic tolerance and further reports are needed before conclusions can be drawn.

In this study, we developed a subcutaneous insulin-releasing device consisting of a disk-shaped capsule and drug formulation comprised of poly(ethylene glycol) dimethacrylates, then evaluated its efficacy on retinal function in streptozotocin (STZ)-induced diabetic rats. In vitro release studies showed that recombinant human insulin was released with a constant rate for more than 30 days. The device was able to maintain a basal level of blood glucose in diabetic rats for a prolonged period of more than 30 days, simultaneously preventing a decrease in body weight. For assessing the pharmacological effect of the device on retinal function in diabetic rats, electroretinograms were conducted for 12 weeks. The reduction in amplitude and delay in implicit time were attenuated by the device during the initial 4 weeks of application. The increase in gene expression of protein kinase C (PKC)-γ and caspase-3 in the diabetic retina was also attenuated by the device. Immunohistochemistry showed that the increase in glial fibrillary acidic protein expression in the diabetic retina was attenuated by the device. Histological evaluation of subcutaneous tissue around the device showed the biocompatibility of the device. In conclusion, the insulin-releasing device attenuated the reduction of retinal function in STZ-induced diabetic conditions for 4 weeks and the efficacy of the device might be partially related to PKC signaling in the retina. The long-term ability to control the blood glucose level might help to reduce the daily frequency of insulin injections.

Purpose Antibiotic dosing is challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of meropenem and vancomycin in patients undergoing SLED. Methods Consecutive ICU patients undergoing SLED and receiving meropenem and/or vancomycin were prospectively evaluated. Serial blood samples were collected before, during, and at the end of SLED sessions. Antimicrobial concentrations were determined using a validated HPLC method. Noncompartmental PK analysis was performed. AUC was determined for vancomycin. For meropenem, time above MIC was calculated. Findings A total of 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations before SLED were 24.5 and 28.0 μg/mL, respectively; after SLED, 14 and 6 μg/mL. Mean removal was 42% with vancomycin and 78% with meropenem. With vancomycin, 19 (83%), 16 (70%), and 15 (65%) patients would have achieved the target (AUC0–24 >400) considering MICs of 1, 2, and 4 mg/L, respectively. With meropenem, 17 (85%), 14 (70%), and 10 (50%) patients would have achieved the target (100% of time above MIC) if infected with isolates with MICs of 1, 4, and 8 mg/L, respectively. Implications SLED clearances of meropenem and vancomycin were 3-fold higher than the clearance described by continuous methods. Despite this finding, overall high PK/PD target attainments were obtained, except for at higher MICs. We suggest a maintenance dose of 1 g TID or BID of meropenem. With vancomycin, a more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available

The choice of the specific modality and treatment duration of renal replacement therapy (RRT) to adopt in metformin-associated lactic acidosis (MALA) is still debated. We aimed to verify if sustained low-efficiency dialysis (SLED) is a rational choice in patients with MALA and acute kidney injury (AKI). We collected serial serum metformin measurements, clinical parameters, and outcome data in ten consecutive patients (mean age 77 years [range 58–88], 5 males) admitted to our renal intensive care unit for suspected MALA associated with AKI and hemodynamic instability. Patients underwent a 16-h SLED session performed with either conventional dialysis machines or machines for continuous RRT (CRRT). A 2-compartment open-infusion pharmacokinetic model with first-order elimination was fitted to each subject’s serum concentration–time data to model post-SLED rebound and predict the need for further treatments. Two patients died within 24 h after SLED start. Three patients needed one further dialysis session. Surviving patients (n = 8) were dialysis-free at discharge. Metformin levels were in the toxic range at baseline (median [range] 32.5 mg/l [13.6–75.6]) and decreased rapidly by the end of SLED (8.1 mg/l [4.5–15.8], p