Sustained Low-efficiency Dialysis Research Articles

#2232 Personalized kidney replacement therapy in critically ill patients: unity makes strength!

Abstract Background and Aims The complexity of the critically ill patient with kidney disease has increased in recent years. A holistic and multidisciplinary approach is, therefore, necessary in order to provide the best therapeutic guidance. Multiple modalities of kidney replacement therapies (KRT) are available in this setting, namely continuous kidney replacement therapies (CKRTs) and hybrid therapies, also such as sustained low-efficiency dialysis (SLED) and slow continuous ultrafiltration (SCUF). These techniques can be used in conjunction with other extracorporeal clearance therapies such as plasmapheresis (PF), and immunoadsorption (IA). Their prescription must be individualized according to the characteristics of each patient. In our hospital all KRT and extracorporeal techniques used are reviewed daily by a nephrologist. This study aims to describe the 20-year experience of our centre in individualized KRT prescription in intensive care. Methods A retrospective cohort, single centre study was conducted. We reviewed adult patients (age ≥18 years) admitted in all the ICUs of our hospital centre between January 2002 and December 2022, who required a KRT. We aimed to describe demographic data, different stages of kidney disease [AKI, AKI in CKD, chronic hemodialysis (HD), peritoneal dialysis (PD), kidney transplant (KT), rapidly progressive kidney failure (RPKF), other causes], the KRT used and the main outcomes. Results During the study period, 1578 patients who required a KRT were admitted to the ICU. Median age was 65 (IQR: 45-81) years old and 59.9% were male. Among these patients 715 (45.3%) had AKI, 380 (24.1%) were in HD, 315 (20%) had AKI in CKD, 130 (8.2%) had a KT and 31 (2%) were in PD. Four patients had RPKF and 3 patients had other causes for KRT, such as hyperammonemia and sodium valproate poisoning. The main KRT performed were: SLED—1365 (86.5%) patients; continuous venovenous hemodiafiltration (cvvHDF)—120 (7.6%) patients; SLED + cvvHDF—66 (4.2%). Other KRT executed were SLED + PF (11 patients), continuous venovenous hemofiltration (cvvHF) (8 patients) and SCUF (2 patients). Among all patients mortality rate was 42.3%, 33% had renal recovery and 7.4% started chronic HD. In AKI group the median age was 64 (IQR: 48-80) years and 56.3% were male. 576 (80.7%) performed SLED, 91 (12.7%) did cvvHDF and 36 (5.0%). Mortality rate was of 52.1%, renal recovery 45% and 2.9% started chronic HD. Conclusion Our ICU multidisciplinary approach model with a critical care nephrology specialists team translates into a large amount of accumulated experience with SLED. Our results are comparable to centres that predominantly use CKRTs. The range of different techniques used reflects the fact that KRT has become a complex treatment for critically ill patients, which allows for the prescription to be precisely tailored to the different daily clinical needs.

Experience of Sustained Low-Efficiency Dialysis (SLED) in an Intensive Care Unit of a Quaternary Care Hospital.

In critically ill patients, sustained low-efficiency dialysis (SLED) has become a viable option for treating acute kidney injury (AKI) instead of continuous renal replacement therapy (CRRT). This study aimed to evaluate clinical outcomes in critically ill patients receiving SLED. In our ICU, we performed a retrospective cohort study on hemodynamically unstable patients requiring dialysis in the form of SLED. Demographics, clinical, and biochemical variables were analyzed. A total of 58 patients were enrolled in the study. The mean age was 48.58 ± 15 with a male-to-female ratio of 3:1. Higher APACHE II score, high international normalized ratio, thrombocytopenia, and septic shock were found to be poor prognostic markers, with an overall observed mortality of 56.9%. SLED can be considered as an alternative to CCRT for selected hemodynamically unstable patients requiring renal replacement therapy.

Removal of common antimicrobial agents by sustained low-efficiency dialysis.

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.

Sustained low-efficiency dialysis with regional citrate anticoagulation is a suitable therapeutic option for refractory hypermagnesemia in critically ill patients with AKI.

Sustained low-efficiency dialysis with regional citrate anticoagulation is a suitable therapeutic option for refractory hypermagnesemia in critically ill patients with AKI.

The Use of Sustained Low-efficiency Dialysis in the Treatment of Sepsis-associated Acute Kidney Injury in a Low-income Country: A Prospective Cohort Study.

Limited data are available regarding the management and outcomes of patients with sepsis-associated acute kidney injury (SA-AKI) requiring dialysis in Sudan. Continuous renal replacement therapy (CRRT) is a highly favored treatment modality in such patients. However, it stays unavailable and expensive treatment in most low-income countries. We aimed to evaluate the use of sustained low-efficiency dialysis (SLED) in the treatment of hemodynamically unstable patients with SA-AKI admitted to the intensive care unit (ICU). A prospective cohort was conducted in Baraha Medical City, Khartoum, Sudan. Patients above 18 years of age, who were admitted to the ICU between January and September 2020 with SA-AKI, and required SLED or CRRT were enrolled. These were followed up till death or discharge from the ICU. They were observed regarding their dialysis tolerance, rate of renal recovery, ICU mortality, and cost of therapy. Data analysis was done using SPSS. Fifty-three adults were enrolled. Their mean age was 62 ± 11 years, and 56.6% were males. Thirty-one patients (58.5%) received SLED and 22 (41.5%) underwent CRRT. Patients in the two groups were age and sex matched and showed no significant differences in their comorbid conditions, source of sepsis, sequential organ failure assessment (SOFA) score, and their indications for dialysis (p > 0.05). Patients treated with SLED showed similar dialysis tolerance, rate of renal recovery, length of ICU admission, and risk of death compared to those treated with CRRT (p > 0.05). Moreover, SLED treatments were less expensive than CRRT, and the costs of ICU admission among the SLED group were significantly less (p < 0.001). Our study shows that SLED is safe and effective. It is readily available and can be routinely performed in the treatment of hemodynamically unstable patients with SA-AKI at a significantly lower cost. Taha AKA, Shigidi MMT, Abdulfatah NM, Alsayed RK. The Use of Sustained Low-efficiency Dialysis in the Treatment of Sepsis-associated Acute Kidney Injury in a Low-income Country: A Prospective Cohort Study. Indian J Crit Care Med 2024;28(1):30-35.

Comparison of outcomes of different modalities of renal replacement therapy in patients of acute kidney injury: a single centre prospective observational study.

Acute Kidney Injury (AKI) is one of the most important causes of in-hospital mortality. The global burden of AKI continues to rise without a marked reduction in mortality. As such, the use of renal replacement therapy (RRT) forms an integral part of AKI management, especially in critically ill patients. There has been much debate over the preferred modality of RRT between continuous, intermittent and intermediate modes. While there is abundant data from Europe and North America, data from tropical countries especially the Indian subcontinent is sparse. Our study aims to provide an Indian perspective on the dialytic management of tropical AKI in a tertiary care hospital setup. 90 patients of AKI, 30 each undergoing Continuous Renal Replacement Therapy (CRRT), Intermittent Hemodialysis (IHD) and SLED (Sustained Low-Efficiency Dialysis) were included in this prospective cohort study. At the end of 28 days of hospital stay, discharge or death, outcome measures were ascertained which included mortality, duration of hospital stay, recovery of renal function and requirement of RRT after discharge. In addition median of the net change of renal parameters was also computed across the three groups. Lastly, Kaplan Meier analysis was performed to assess the probability of survival with the use of each modality of RRT. There was no significant difference in the primary outcome of mortality between the three cohorts (p=0.27). However, CRRT was associated with greater renal recovery (p= 0.015) than IHD or SLED. On the other hand, SLED and IHD were associated with a greater net reduction in blood urea (p=0.004) and serum creatinine (p=0.053). CRRT, IHD and SLED are all complementary to each other and are viable options in the treatment of AKI patients.

Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience

Abstract Sustained low-efficiency dialysis (SLED) is usually performed over 6–12 h among hemodynamically unstable patients. Conduction of 4-h SLED may spare time and manpower during hospitalization. Therefore, we conducted a retrospective observational study to explore the appropriateness and clinical outcomes of 4-h SLED among critically ill patients admitted to our center from 1/06/2016 to 1/06/2020. Renal parameters including blood urea nitrogen, serum creatinine, sodium, phosphorus, potassium, and bicarbonate were determined on the day of dialysis before SLED and within 24 h after SLED, and clinical outcomes including, acute kidney injury (AKI) recovery, in-hospital mortality, 30-day mortality, 180-day mortality, and re-admission with AKI, were evaluated. Of the 304 patients included, 69.4% were male. The majority of patients were from the Middle East (65.8%), followed by 28.6% from Asia. Four-hour SLED resulted in a significant improvement in the renal parameters. Recovery from AKI was observed in 25.4%, in-hospital mortality rate was 48.7%, while the 30- and 180-day mortality outcomes were 3.2 and 9.6%, respectively, and re-admission with AKI was observed in 16.9%. Our findings suggest that 4-h SLED significantly improved renal parameters and was associated with favorable clinical outcomes in terms of survival and AKI recovery, suggesting possible utilization of SLED shorter than 6 h in the acute settings to preserve time and manpower for procedures.

Treatment of dabigatran intoxication in critically ill patients with Acute Kidney Injury: The role of Sustained Low-Efficiency Dialysis.

The use of dabigatran in patients with non-valvular atrial fibrillation (AF) has widely increased in the last decades, due to its positive effects in terms of safety/efficacy. However, because of the risk of major bleeding, a great degree of attention has been suggested in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Thus, the early start of Extracorporeal Kidney Replacement Therapy (EKRT) could be indicated to remove the drug and to reverse the associated excess anticoagulation. Sustained Low-Efficiency Dialysis (SLED) could represent an effective therapeutic option to reduce the dabigatran plasma levels rapidly while avoiding post-treatment rebound. We present here a case series of three AKI patients with acute dabigatran intoxication, effectively and safely resolved with a single SLED session.

Linezolid dosing in critically ill patients undergoing various modalities of renal replacement therapy: a pooled population pharmacokinetic analysis

Altered pharmacokinetics (PK) of linezolid is pronounced in critically ill patients undergoing different modalities of renal replacement therapy (RRT). This study aimed to provide a pooled population PK analysis of linezolid in RRT patients and to evaluate the pharmacodynamic (PD) target attainment of linezolid standard dosing (600 mg q12h). A total of 414 pooled linezolid concentration observations from 69 patients undergoing intermittent hemodialysis (IHD), sustained low-efficiency dialysis (SLED), or continuous renal replacement therapy were used to develop the population PK model. Probability of target attainment (PTA) for the efficacy markers of 85% T>MIC and AUC/MIC>100 was evaluated, and the risk of toxicity was estimated based on the trough concentration threshold of 10 mg/L. Linezolid concentration data were adequately described by a two compartmental model. Renal function and body weight were identified as significant modifiers for endogenous clearance of linezolid. Simulations demonstrated that the PTA of 85% T>MIC and AUC/MIC>100 targets was all unacceptably low (0-58.6%, MIC ≥ 1 mg/L) in RRT patients with preserved renal function, while desirable 85% T>MIC attainment (≥ 90%, MIC ≤ 2 mg/L) was achieved in anuric RRT patients. The predicted risk of toxicity is negligible (<1.0%) in the patients with preserved renal function (regardless of the RRT modalities), while the probability of reaching the trough level of 10 mg/L was high (17.9-20.9%) for anuric patient population undergoing IHD or SLED. In conclusion, standard linezolid dosing is adequate for anuric RRT patients with an MIC ≤ 2 mg/L.

Archetypal sustained low-efficiency daily diafiltration (SLEDD-f) for critically ill patients requiring kidney replacement therapy: towards an adequate therapy.

Sustained low-efficiency dialysis is a hybrid form of kidney replacement therapy that has gained increasing popularity as an alternative to continuous forms of kidney replacement therapy in intensive care unit settings. During the COVID-19 pandemic, the shortage of continuous kidney replacement therapy equipment led to increasing usage of sustained low-efficiency dialysis as an alternative treatment for acute kidney injury. Sustained low-efficiency dialysis is an efficient method for treating hemodynamically unstable patients and is quite widely available, making it especially useful in resource-limited settings. In this review, we aim to discuss the various attributes of sustained low-efficiency dialysis and how it is comparable to continuous kidney replacement therapy in efficacy, in terms of solute kinetics and urea clearance, and the various formulae used to compare intermittent and continuous forms of kidney replacement therapy, along with hemodynamic stability. During the COVID-19 pandemic, there was increased clotting of continuous kidney replacement therapy circuits, which led to increased use of sustained low-efficiency dialysisalone or together with extra corporeal membrane oxygenation circuits. Although sustained low-efficiency dialysis can be delivered with continuous kidney replacement therapy machines, most centers use standard hemodialysis machines or batch dialysis systems. Eventhough antibiotic dosing differs between continuous kidney replacement therapy and sustained low-efficiency dialysis, reports of patient survival and renal recovery are similar for continuous kidney replacement therapy and sustained low-efficiency dialysis. Health care studies indicate that sustained low-efficiency dialysis has emerged as acost-effectivealternative to continuous kidney replacement therapy. Although there is considerable data to support sustained low-efficiency dialysis treatments for critically ill adult patients with acute kidney injury, there are fewer pediatric data, even so, currently available studies support the use of sustained low-efficiency dialysis for pediatric patients, particularly in resource-limited settings.

#6306 SUSTAINED LOW-EFFICIENCY DIALYSIS VERSUS CONTINUOUS VENO-VENOUS HEMODIAFILTRATION OUTCOME IN CRITICALLY ILL PATIENTS

Abstract Background and Aims Acute kidney injury due to sepsis is the most common cause of AKI in critical care settings. Different modalities of renal replacement therapies (RRT) have been used to manage this condition including Continuous Renal Replacement Therapy (CRRT) and sustained low efficiency dialysis (SLED). The aim of this work was to compare the outcome of SLED and CRRT in the form of continuous veno-venous hemodiafiltration (CVVDHF) as methods of dialysis in sepsis induced AKI. Method We retrospectively analysed data from 120 patients; 20 patients received CVVHDF to manage AKI in the context of sepsis, 47 patients received SLED to manage AKI in the context of sepsis and the third group included 53 patients who have been treated with SLED to manage AKI not due to sepsis. Age was found to be significantly higher in sepsis induced AKI patients treated with SLED than patients treated with CVVHDF (65±10.1# 59.5±9.3 y, p = 0.03). Sex distribution or incidences of hypertension, diabetes mellitus, malignancy or liver disease were not statistically different between groups. Results Unadjusted 30 day mortality was 44.7% (21pt) in the SLED group Vs 50% (10pt) in the CVVHDF group, p = 0.07. Adjusted mortality was not statically significant between SLED and CVVHDF (OR 0.97, CI = 0.95-1.06). Hypotension occurred more frequently in patients treated with SLED (24 pt = 51.1% #5 pt = 25%, p &amp;lt; 0.001).Clotting occurred more frequently in the CVVHDF group as compared to SLED group (7 pt = 35% Vs 4pt = 8.5% p &amp;lt; 0.001). Conclusion Sustained low efficiency dialysis (SLED) and CVVHDF had comparable 30 day mortality as modalities of RRT in critically ill Patients with sepsis induced AKI. SLED still an attractive alternative to CRRT modalities due to lower cost and lower incidence of complications. Further larger studies are recommended.

#6376 TREATMENT OF DABIGATRAN INTOXICATION IN CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY: THE ROLE OF SUSTAINED LOW-EFFICIENCY DIALYSIS

Abstract Background and Aims Dabigatran, a direct thrombin inhibitor, is a commonly used direct oral anticoagulant (DOAC) prescribed for non-valvular atrial fibrillation. Despite its benefits in term of safety/effectiveness along with the possibility to treat patients who were ineligible for vitamin K inhibitors (VKAs), a great degree of attention is required in elderly patients with multiple comorbidities. Notably, dabigatran mainly undergoes renal elimination, and dose adjustment is recommended in patients with Chronic Kidney Disease (CKD). In this regard, the onset of an abrupt decrease of kidney function may further affect dabigatran pharmacokinetic profile, increasing the risk of acute intoxication. Idarucizumab is the approved antagonist in the case of dabigatran-associated major bleeding or concomitant need of urgent surgery, but its clinical use is limited by the lack of data in patients with Acute Kidney Injury (AKI). Given the dabigatran PK parameters (low MW, low Vd, negligible protein binding), the early start of Extracorporeal Kidney Replacement Therapy (EKRT) may represent the optimal reversal strategy. We present a case series of three critically ill patients with AKI and dabigatran overdose treated with Sustained Low-Efficiency Dialysis (SLED). Methods Three critically ill patients (Table 1) were admitted to the Renal Intensive Care Unit (ICU) for stage 3 AKI and intercurrent dabigatran intoxication. SLED sessions with Regional Citrate Anticoagulation (RCA) were prescribed with SURDIAL X machine, ELISIO-21M filter (Nipro Co., Osaka, Japan) [blood flow rate 200 mL/min, dialysis fluid rate 300 mL/min; citrate flow rate 350 mL/h (ACD Fresenius Kabi, Italia)]. Dabigatran plasma levels (dilute thrombin time, dTT) along with coagulation parameters were monitored before, during and after SLED session. Results A rapid and sustained decreased of plasma dabigatran level was observed in each patient in course of SLED sessions. No clinically relevant post-treatment rebound was reported (Figure 1). Conclusions SLED meets the requirements to be a viable reversal anticoagulation option in the context of dabigatran overdose. Indeed, it efficiently provides dabigatran removal, by reaching a safe plasma concentration within the first hours and avoiding significant rebound effect.

#6578 ACUTE KIDNEY INJURY IN PATIENTS WITH VENTRICULAR SEPTAL RUPTURE: A SINGLE CENTER STUDY

Abstract Background and Aims Ventricular septal rupture (VSR) is an infrequent but dreaded complication of acute myocardial infarction(AMI). Acute kidney injury(AKI) is one of the major determinants of morbidity and mortality in these patients. Renal replacement therapy (RRT) is, in this set of patients of high-risk nature and can be prolonged. Focused data on the management of AKI in patients with VSR from developing countries is scarce. We present a large cohort of patients presenting with VSR from a tertiary care Centre in South India, evaluating the incidence of AKI, RRT, and short-term outcomes in this cohort. Method Observational study of all adult patients diagnosed with VSR following AMI over 5 years in a single centre in Chennai, India. Demographic characteristics, co-morbidities,clinical and laboratory,Serial renal function tests and urine output was noted. eGFR was calculated using the CKD-EPI formula.AKI definition and staging -KDIGO clinical Practice Guidelines. Data analysis was done using the IBM SPSS version 24. P-value less than 0.05 is used to indicate statistical significance. Results During the study period, 3024 patients presented to our hospital with acute coronary syndrome (ACS) and seventy patients presented with VSR (2.3%). Of these, forty-seven (67.1%) developed AKI. A nephrology consult was obtained for thirty-three (70%) patients. Older age, higher total count and lower systolic blood pressure were significantly associated with the occurrence of AKI. The mortality in the AKI group was significantly higher (63.8%). VSR closure was done in 12.7% and 21.7% of the AKI and non-AKI groups respectively. Surgical VSR repair was done in 61.7% and 60.8% of the patients with and without AKI respectively. Most of the patients (26, 55.3%) presented with KDIGO stage 3 AKI and all were oliguric. 10 and 11 patients were staged into KDIGO stages 1 and 2 respectively. 26 patients with Stage 3 AKI, only 14 (29.7%%) of them received nephrology consult.. RRT was initiated in fifteen patients (31.9%). The indications for RRT were oliguria, pulmonary oedema, metabolic acidosis, and worsening electrolyte disturbance.Acute peritoneal dialysis was initiated in 11 patients (73.3%) using a 43cm swan neck double cuffed tunnelled Tenckhoff peritoneal dialysis catheter placed at the bedside. Percutaneous peritoneal dialysis catheter insertion by a nephrologist was done in and the rest was inserted by open laparotomy technique by a trained general surgeon. All 11 were initiated on urgent low volume supine exchanges. Of these ten patients had manual exchanges done by a trained peritoneal dialysis nurse and one patient was put on automated peritoneal dialysis. The average volume per dwell was 500 ml±250 ml which was gradually increased if there was no leak. The total average peritoneal dialysis volume per day was 10L±2 L. The strength of bags (1.36%, 2.25%, 3.86%) dextrose was determined based on volume status and patients’ hemodynamics. No patient had a leak or peritoneal dialysis-related peritonitis. All patients’ peritoneal dialysis catheter was immobilized with a tight abdominal dressing. One patient continued continuous ambulatory peritoneal dialysis at home as there was no recovery of renal function and was lost to follow up. Sustained low-efficiency dialysis was performed on four patients. Duration of Sustained low-efficiency dialysis ranged from 6-8 hours with average blood flows of 150 ml/min and average fluid removal between 1.5-3L. Unfractionated heparin was used in three patients, and one was heparin free saline dialysis. Discharge eGFR in the AKI group was significantly lower as compared to the non-AKI group. (38 vs 104ml/min/1.73m2, p&amp;lt;0.001). Follow up was done on 14 at 3 months, The mean eGFR was 57.8ml/min/1.73 m2 when compared to 81.8 ml/min/1.73 m2. Conclusion The incidence of AKI is high and is associated with a high rate of mortality in patients with VSR. Peritoneal dialysis is a safe and effective option for those patients requiring RRT. Follow up of AKI patients at three months did not show a significant decline in renal function

Switching from continuous veno-venous hemodiafiltration to intermittent sustained low-efficiency daily hemodiafiltration (SLED-f) in pediatric acute kidney injury: A prospective cohort study.

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. 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. 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. SLED-f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU.

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

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. KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0mmol/L, HCO3- 22.0mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20mmol/20mL, 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. 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 <2.5mg/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. 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. NCT03976440 (registered 6 June 2019).

SLED1 Promoting Cell Proliferation and Inhibiting Apoptosis in Acute Myeloid Leukemia: a Study.

In this study, we aimed to explore long non-coding RNA (lncRNA) sustained low-efficiency dialysis (SLED1) correlated with Bcl-2 apoptosis pathway in acute myeloid leukemia (AML). This study further aimed to determine its role in the regulation of AML progression and its action as a potential biomarker for better prognosis. AML microarray profiles GSE97485 and probe annotation from the Gene Expression Omnibus (GEO) database from the National Center for Biotechnology Information (NCBI) were detected using the GEO2R tool ( http://www.ncbi.nlm.nih.gov/geo/geo2r/ ). The expression of AML was downloaded from the TCGA database ( http://cancergenome.nih.gov/ ). The statistical analysis of the database was processed with R software. Bioinformatic analysis found that lncRNA SLED1 is highly expressed in AML patients and is associated with poor prognosis. We found that the increased SLED1 expression levels in AML were significantly correlated with FAB classification, human race, and age. Our study has shown that upregulation of SLED1 promoted AML cell proliferation and inhibited cell apoptosis in vitro; RNA sequencing showed increased expression of BCL-2 and indicated that SLED1 might promote the development of AML by regulating BCL-2. Our results showed that SLED1 could promote the proliferation and inhibit the apoptosis of AML cells. SLED1 might promote the development of AML by regulating BCL-2, but the mechanism involved in the progression of AML is unclear. SLED1 plays an important role in AML progression, may be applied as a rapid and economical AML prognostic indicator to predict the survival of AML patients, and help guide experiments for potential clinical drag targets.

607. Establishing Pharmacokinetic Profile of β -lactams in Critically Ill Patients on Continuous Sustained Low-efficiency Dialysis (C-SLED)

Abstract Background Critically ill patients have altered pharmacokinetic (PK) due to severity of illness and multi-organ failure. The lack of pharmacokinetic and pharmacodynamic data in Continuous Sustained Low-efficiency Dialysis (C-SLED) further perpetuates the uncertainty of efficacy with current antimicrobial dosing strategies. The objective of this study is to evaluate patient-specific PK of various β-lactams antibiotics in critically ill patients on C-SLED to assess if the current dosing strategy leads to therapeutic drug levels. Methods This prospective observational cohort study was performed at an academic medical center from November 2021 to June 2022. It included patients age &amp;gt; 18 years and on β-lactam antibiotics while on C-SLED. Therapeutic drug monitoring (TDM) was performed by checking two levels (peak and trough). These levels were used to calculate patient-specific elimination rate constant (k), half-life, and the fraction of time above MIC (fT&amp;gt;MIC). Other data collected included demographics, β-lactam regimens, source of infection, microbiology data, mortality on days 7 and 30, and length of stay. Descriptive statistics were used for data analysis. Results There were 11 patients included in the study with a median age of 55 and 82% (n = 9) of patients were male. β-lactam daily regimen was dosed as creatinine clearance (CrCl) &amp;gt; 50mL/min in 71.4% of patients (n = 10), CrCl 30-50 mL/min in 28.5% (n = 4), and &amp;lt; 30mL/min in 0% of patients. An extended infusion dosing strategy was used in 35.6% of patients (n = 5). The therapeutic drug target (50%fT &amp;gt; MIC for penicillins, 60%fT &amp;gt; MIC for cephalosporins, 40%fT &amp;gt; MIC for carbapenems) was achieved in 100% (n=14) of patients. Dose adjustment was not needed in all 14 cases. However, 100%fT &amp;gt; MIC was only achieved in 64% (n=9) patients. The median hospital length of stay was 60 days. Mortality on days 7 and 30 was 9% (n=1) and 27% (n=3), respectively. Conclusion Preliminary analysis shows that β-lactam daily dose based on CrCl of &amp;gt;30mL/min leads to therapeutic drug levels in patients on C-SLED. Disclosures All Authors: No reported disclosures.

ODP224 Metformin Associated Lactic Acidosis in a Nondiabetic Young Female

Abstract Background Metformin is the first line of treatment for patients with Diabetes Mellitus type 2. Despite multiple benefits, metformin is contraindicated in stage 4 renal disease due to an increased risk of metformin associated lactic acidosis (MALA). MALA is estimated to have a high mortality rate of 30-50%. The presentation of MALA can mimic sepsis and organ failure. Clinical Case We report a case of a 32 year old female who presented with generalized weakness and shortness of breath. She was found to have severe metabolic acidosis (PH 7. 04, PCO2 40 mmHg, Bicarb 15 mmol/L, anion gap 14 mmol/L, lactic acid 8.7 mmol/L), hypotension (82/46 mmHg), pancytopenia, moderate transaminitis, severe acute kidney injury (creatinine 3.2 mg/dL, GFR 17 mL/min/1.73 m2), and profound hypoglycemia (serum glucose 42 mg/dL). Endocrinology was consulted due to hypoglycemia and suspected adrenal insufficiency. During the encounter the patient was alert and oriented, but reported severe nausea and appeared in significant distress. On review of medications, she reported taking phentermine and metformin for weight loss, hydrochlorothiazide for hypertension, and fluoxetine for depression. She denied taking other supplements. She denied any history of diabetes mellitus or prediabetes. Computed tomography (CT) of the chest and abdomen were unremarkable. The patient's potassium was normal. Lactic acidosis continued to increase (16.1 mmol/L) despite intravenous fluids, empiric broad spectrum antibiotics, and stress dose steroids. Approximately 19 hours after the arrival, she underwent dialysis due to suspected MALA. Her lactic acid improved after dialysis transiently (6.1 mmol/L), but later worsened again (11.3 mmol/L). Urine and blood cultures returned positive for Klebsiella Pneumoniae (pan-sensitive). She was treated appropriately for sepsis since presentation to the emergency room, but her clinical condition (and lactic acid) continued to deteriorate. On the second day of admission, the patient developed respiratory failure requiring intubation and mechanical ventilation. Her hypotension persisted and she required multiple pressors. Sustained low-efficiency dialysis was restarted due to worsening of metabolic acidosis. Patient then became unresponsive on hospital day 4. Sedation was stopped and CT of the brain revealed significant edema and mild bilateral subarachnoid hemorrhage. Patient was confirmed brain dead by perfusion study. Conclusion This case illustrated a constellation of factors that led to a poor outcome. Off label use of metformin for weight loss, late diagnosis of acute severe renal failure, and delayed diagnosis of MALA all contributed to the poor outcome in this patient. Even though MALA has a relatively low estimated incidence rate, this case emphasizes the importance of medication reconciliation and the need for recognition that MALA can present as sepsis. Presentation: No date and time listed

The Role of Sustained Low-Efficiency Dialysis (SLED) in the Intensive Care Unit

Renal replacement therapies are frequently used in the intensive care unit, most often in patients with severe acute kidney injury, a common complication in this setting. The choice of a prolonged intermittent renal replacement therapy (PIRRT) has grown in its popularity. Nevertheless, not all clinicians are familiar with it. The most frequently performed PIRRT is sustained low-efficiency dialysis. The aim of this article is to review the sustained low-efficiency dialysis technique, namely the necessary machinery, the prescription specificities, its complications and the particularities related to intoxications and drug dosing. Lastly, when to start sustained low-efficiency dialysis and its advantages and disadvantages over intermittent hemodialysis and continuous renal replacement therapies is discussed.

Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution (Vd). Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups (P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups (P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.