Sustained Low-efficiency Dialysis Session Research Articles

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.

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.

#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.

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

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. 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. 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±2.1mg/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<.05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P=.012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P=0.033)]. 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.

Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study)

BackgroundHemodynamic instability is a frequent complication of sustained low-efficiency dialysis (SLED) treatments in the ICU. Intravenous hyperoncotic albumin may prevent hypotension and facilitate ultrafiltration. In this feasibility trial, we sought to determine if a future trial, powered to evaluate clinically relevant outcomes, is feasible.MethodsThis single-center, blinded, placebo-controlled, randomized feasibility trial included patients with acute kidney injury who started SLED in the ICU. Patients were randomized to receive 25% albumin versus 0.9% saline (control) as 100 mL boluses at the start and midway through SLED, for up to 10 sessions. The recruitment rate and other feasibility outcomes were determined. Secondary exploratory outcomes included ultrafiltration volumes and metrics of hemodynamic instability.ResultsSixty patients (271 SLED sessions) were recruited over 10 months. Age and severity of illness were similar between study groups. Most had septic shock and required vasopressor support at baseline. Protocol adherence occurred for 244 sessions (90%); no patients were lost to follow-up; no study-related adverse events were observed; open label albumin use was 9% and 15% in the albumin and saline arms, respectively. Ultrafiltration volumes were not significantly different. Compared to the saline group, the albumin group experienced less hemodynamic instability across all definitions assessed including a smaller absolute decrease in systolic blood pressure (mean difference 10.0 mmHg, 95% confidence interval 5.2–14.8); however, there were significant baseline differences in the groups with respect to vasopressor use prior to SLED sessions (80% vs 61% for albumin and saline groups, respectively).ConclusionsThe efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible.Trial registration ClinicalTrials.gov (NCT03665311); First Posted: Sept 11th, 2018. https://clinicaltrials.gov/ct2/show/NCT03665311?term=NCT03665311&draw=2&rank=1

16 Sustained Low Efficiency Dialysis (SLED) in Burn Patients with Acute Kidney Injury

Abstract Introduction Acute Kidney Injury (AKI) is common among patients with major burns and may require treatment with renal replacement therapy (RRT). Although continuous renal replacement therapy (CRRT) modalities are widely used and offer many advantages over traditional intermittent hemodialysis (IHD), CRRT is expensive, labour-intensive, and may not be available in some burn centers. Sustained Low Efficiency Dialysis (SLED) is a moderately efficient alternative to IHD, but its use in burn patients with AKI has not been described. The purpose of this study was to review our experience with SLED. Methods Retrospective review of adult burn patients with AKI treated by SLED between 07/2013 and 03/2020 at an adult regional ABA-verified burn center. Data was obtained from the electronic medical record including daily dialysis forms completed by the nephrology service. Values are shown as mean +/- SD or median (IQR) as appropriate. Results We evaluated 367 distinct SLED sessions provided to 33 patients [age 55.8 +/- 14 yrs., %TBSA burn 33 +/-19, % TBSA full thickness burn 10.5 (0, 35.8), and 54.5% with inhalation injury]. The serum creatinine (sCr) prior to the start of SLED was 2.96 (2.3, 4.17) mg/dL. SLED was initiated 5 (3, 10.8) days (range 0–24 d) post burn, and 7 (3.3, 12.8) sessions (range 1–44) with a duration of 4 (4,6) hours each were given per patient. Heparinization was required in 22 sessions (6%), and 46 sessions (12.5%) were aborted, most commonly due to clotting of the lines or circuit, and rarely (4%) due to hypotension. The net ultrafiltrate removal was 1.2 (0.7–2) L, with a dialysate flow rate of 350 (350, 500) mL/min. Among 208 sessions where patients were not on vasopressors (VPs) Pre-SLED, one or more VPs were required in 19 sessions (9%) during or at the termination of SLED. Among 116 sessions where patients were receiving norepinephrine (NEpi) infusions pre-SLED, the NEpi dose dropped from 7.3 +/- 4.2 µgm/min to 6 +/- 4.5 µgm/min (p=0.03). Pre and Post SLED values for blood pressure, creatinine, and potassium are shown in the table. The mortality rate was 36.4%, hospital length of stay was 42 (20.5, 61.5) days, and among surviving patients, 2 (9.5%) required dialysis post discharge. Conclusions SLED was effective and well tolerated. Hemodynamic instability was infrequently encountered.

Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury.

In recent studies, 5%–20% of hospitalized patients with coronavirus disease 2019 (COVID-19) developed AKI requiring RRT (CoV-AKI-RRT) (1,2) (L. Chan et al., unpublished observations). Hypercoagulability has been recognized as a salient feature of COVID-19 in the critically ill (3,4) and there have been anecdotal accounts of unexpectedly frequent dialysis filter clotting. However, there are limited data describing the magnitude of the problem. A recent report described clotting events in 28 of 29 patients with CoV-AKI-RRT and shorter filter lifespan compared with a historical control, but no details were provided regarding anticoagulation (4). Our objective was to examine the delivery of RRT and circuit interruptions in patients with CoV-AKI-RRT in comparison with those in the pre-COVID-19 era. With approval of the Institutional Review Board, waiver of informed consent, and in accordance with the Declaration of Helsinki, we conducted a retrospective single-center study, ancillary from our previously reported cohort (2). We identified hospitalized patients with COVID-19 (positive severe acute respiratory syndrome coronavirus 2 RNA PCR by nasopharyngeal swab) and AKI, who underwent RRT by sustained low-efficiency dialysis (SLED) for ≥8 hours in an intensive care unit between March and April of 2020 (study period: 4 weeks) by either prolonged intermittent or continuous RRT modality (5,6) using Fresenius 2008K/K2 (Bad Homburg, Germany) machines. At our hospital, continuous venovenous hemodiafiltration (CVVHDF) with PrismaFlex (Deerfield, IL) machines was restricted to the neurointensive care unit and was not expanded during the pandemic due to logistics. As pre-COVID-19 control, we included consecutive patients (reverse chronological order) with AKI without COVID-19 who underwent SLED in December of 2019. Electronic medical records were accessed and RRT flowsheets were manually reviewed to extract timing of initiation and interruption, blood flow rate (BFR), dialysate flow rate, and filter transmembrane pressure (TMP). Standard BFR was 200 …

Pharmacokinetics of Vancomycin in Critically Ill Patients Undergoing Sustained Low-Efficiency Dialysis.

Vancomycin pharmacokinetic data in critically ill patients receiving sustained low-efficiency dialysis (SLED) is limited. Published data using vancomycin with intermittent hemodialysis and continuous renal replacement therapy may not be applicable to hybrid dialysis modalities such as SLED. Current drug references lack recommendations for vancomycin dosing in patients receiving SLED. The objective of this study was to determine vancomycin pharmacokinetics during SLED. A total of 20 patients who were critically ill with oliguric or anuric renal failure who received vancomycin and SLED were included in the study. Surrounding one SLED session, serum vancomycin blood samples were drawn before the initiation of SLED, at the termination of SLED, and 4hours after completion of SLED treatment. Following this, patients received vancomycin, dosed to target a goal peak of 20-30mcg/ml. A vancomycin peak level was drawn 1hour after the end of the infusion. SLED treatment duration was at least 7hours. Continuous data are reported as median (interquartile range) and categorical data as percentage. The vancomycin elimination rate and half-life were 0.051hours (0.042-0.074 hours) and 13.6hours (9.4-16.6 hours), respectively. SLED reduced vancomycin serum concentrations by 35.4% (31.5-43.8%), and vancomycin rebound was 9.8% (2.5-13.7%). The vancomycin dose administered post-SLED was 1000mg (875-1125 mg). For 18 patients, the patient-specific volume of distribution was 0.88L/kg (0.67-1.1 L/kg), vancomycin clearance was 3.5L/hr (2.2-5.2 L/hr), and the area under the concentration-time curve during the study time period was 280.8mg·hr/L (254.7-297.3 mg·hr/L). Vancomycin is significantly removed during SLED with little rebound in serum concentrations 4hours after completion of SLED. Based on study findings, patients who are critically ill require additional vancomycin dosing after each SLED session to maintain therapeutic post-SLED vancomycin concentrations. Therapeutic drug monitoring of vancomycin is recommended during SLED.

Sustained low-efficiency dialysis with regional citrate anticoagulation for patients with liver impairment in intensive care unit: A single-center experience.

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.

P1113TREATMENT OF ACUTE LITHIUM INTOXICATION WITH SUSTAINED LOW-EFFICIENCY DIALYSIS (SLED)

Abstract Background and Aims Lithium salts are widely used in psychiatry for prophylaxis and treatment of bipolar affective disorders. Given its narrow therapeutic range, drug overdosage is not infrequent, and lithium intoxication has potentially fatal neurologic and cardiac side effects. Owing to its low molecular weight (7 Da), relatively small volume of distribution, and its negligible protein binding, lithium can be efficiently removed by any extracorporeal modality of renal replacement therapy (RRT). Although conventional intermittent haemodialysis (IHD) is effective in promptly cleating lithium, postdialysis rebound is common. The use of sustained low-efficiency dialysis (SLED) in lithium intoxication seems to be a valid therapeutic strategy, but strong evidence is still lacking in the literature. We present here two cases of lithium intoxication, in one case acute (naïve patient) and in the other case acute-on-chronic (a deliberate overdose in a patient previously on lithium therapy), successfully treated with SLED. Method: Patient A - A 47 years-old woman without history of lithium consumption was admitted to the ER. after a voluntary acute lithium ingestion of 40 tablets of lithium carbonate (8.12 mEq lithium each). Notwithstanding treatment with intravenous crystalloids and gastric lavage, lithium concentration increased up to 4.18 mEq/l at about 24 h after admission. She developed mental status changes, oliguria, hypotension and bradycardia. Patient B – A 58 years-old man on lithium therapy for bipolar syndrome was admitted to ER after a voluntary acute lithium ingestion of an unknown quantity of lithium carbonate tablets. Lithium concentration, after an initial level of 0.4 mEq/L, increased up to 4.35 mEq/l about 15 h from admission, despite irst-line therapies with intravenous crystalloids and gastric lavage were promptly started. His mental status worsened, together with oliguria, bradycardia and hypotension. Results: Patient A - A 8-hour SLED session with regional citrate anticoagulation (RCA) was planned [blood flow rate (Qb) 200 mL/min; dialysis fluid rate (Qd) 300 mL/min; countercurrent flow direction]. Lithium serum levels decreased by 87% during treatment (0.55 mEq/L), and the patient fully awoke recovering a normal mental status within the first 4 h of treatment. SLED was completed safely within the prescribed time. After the end of treatment, lithium rebound was unremarkable and renal function completely recovered and the patients was discharged after 3 days. Patient B - A 12-hour SLED session with RCA was planned (Qb 200 mL/min; Qd 500 mL/min; countercurrent flow direction). Serum lithium levels decreased by 55% (2.10 mEq/L) during treatment, and the patient awoke, recovering a normal mental status. At the end of treatment, rebound of lithium concentration was observed at 4 hours from SLED end detected (from 2.1 to 2.5 mEq/L), with initial signs of mental deterioration. A second SLED (12 h) was performed, with the same operative parameters and, by the end of the second treatment, lithium concentration was 0.49 mEq/L. Afterward, mental status and renal function fully recovered and no rebound rebound was observed. The patient was discharged after 6 days. Conclusion SLED could represent a good therapeutic strategy to treat acute lithium intoxication, providing an initial rapid clearance with resolution of symptoms, and limiting major rebound.

Efficacy and Safety of Regional Anticoagulation with 4% Trisodium Citrate Versus Heparin in Extended Hemodialysis among Critical Patients with Cancer and Acute Kidney Injury

Introduction: Patients with cancer admitted to critical care units are at increased risk of being affected with acute kidney injury (AKI) and mortality. Sustained low-efficiency dialysis (SLED) combines the cardiovascular stability of continuous therapy with the operational facility of conventional hemodialysis (HD). Citrate has become an alternative to heparin in anticoagulation because it favors the maintenance of filter patency and reduces bleeding. We analyzed the efficacy and safety of citrate versus heparin use in extended HD for patients with cancer and AKI. Methods: This retrospective cohort study evaluated patients with cancer and dialytic AKI who received SLED with anticoagulation using citrate versus heparin from January 2014 to June 2017. After stratifying patients by the type of anticoagulation received, we evaluated demographic and clinical data, plus SLED session characteristics. We also analyzed dialysis outcomes, including insufficient session time, hypotension, poor catheter flow, line inversion, and dialysis system coagulation. Results: We identified 423 SLED sessions among 124 patients (41 patients in the heparin group and 83 patients in the citrate group). More sessions with citrate (26.6 vs. 40.9%, p < 0.001) had serum platelet concentrations <50,000/mm³ or <100,000/m³ and ionic calcium (Ca⁺⁺) values <1.16 mmol/L (33.2 vs. 18.5%, p < 0.001). Dialysis intercurrence occurred in 27% of sessions. The highest odds were associated with heparin sessions (OR 2.88). Compared with the citrate group, the heparin group was subject to more dialysis system coagulation (12.3%), the need for line reversal (9.8%), and insufficient session time (23.9%). Conclusion: Citrate represents a safe and effective anticoagulant for SLED for cancer patients with AKI undergoing treatment in the intensive care unit.

“Removal of nitrate and nitrite by hemodialysis in end-stage renal disease and by sustained low-efficiency dialysis in acute kidney injury”

Background & purposeIt is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. Methods & resultsPlasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. ConclusionsOur results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.

Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury.

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 77years [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 24h 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] 32.5mg/l [13.6-75.6]) and decreased rapidly by the end of SLED (8.1mg/l [4.5-15.8], p < 0.001 vs. baseline), without differences according to the dialysis machine used (p = 0.84). We observed a slight 4-h post-SLED rebound (9.7mg/l [3.5-22.0]), which could be predicted by our pharmacokinetic model. Accordingly, we predicted that the majority of patients would need one additional dialysis session performed the following day to restore safe metformin levels. A 16-h SLED session, performed with either conventional dialysis machines or CRRT machines, allows effective metformin removal in patients with MALA and AKI. However, due to possible post-SLED rebound in serum metformin levels, one additional dialysis treatment is required the following day in the majority of patients.

A novel citrate-based protocol versus heparin anticoagulation for sustained low-efficiency dialysis in the ICU: safety, efficacy, and cost

BackgroundThe high cost, complexity of the available protocols, and metabolic complications are the major barriers that impede the clinical utilization of regional citrate anticoagulation (RCA) for sustained low efficiency dialysis (SLED) in critically ill patients. By comparing a novel protocol for SLED using 30% citrate solution with common protocol using unfractionated heparin, this study aimed to provide new insights for clinical applications of RCA.MethodsIn this retrospective study, a total of 282 critically ill patients who underwent SLED with citrate and/or heparin anticoagulation in six adult ICUs were enrolled. These patients were divided into three groups based on the anticoagulation regimens they had received during the treatment in ICU: Group 1 (Citrate) had only received treatment with citrate anticoagulation (n=75); Group 2 (Heparin) only with heparin anticoagulation (n=79); and Group 3 (Both) with both citrate and heparin anticoagulation (n=128). We compared the mortality, metabolic complications as well as cost among these groups using different anticoagulation regimens.ResultsThe in-hospital mortality did not significantly differ among groups (p> 0.1). However, three patients in heparin group suffered from severe bleeding which led to death, while none in citrate group.Overall, 976 SLED sessions with heparin anticoagulation and 808 with citrate were analyzed. The incidence of extracorporeal circuit clotting was significantly less in citrate (5%), as compared to that in heparin (10%) (p< 0.001). Metabolic complications and hypotension which led to interruption of SLED occurred more frequently, though not significantly, in citrate (p= 0.06, p= 0.23).Furthermore, with 30% citrate solution, the cost of anticoagulant was reduced by 70% in comparison to previously reported protocol using Acid Citrate Dextrose solution A (ACD-A).ConclusionsOur results indicated that anticoagulation regimens for SLED did not significantly affect the mortality of patients. Citrate anticoagulation was superior to heparin in preventing severe bleeding and circuit clotting. The protocol adopted in this study using 30% citrate solution was safe as well as efficacious. In the meantime, it was much more cost-efficient than other citrate-based protocol.

Hemodynamic Tolerability of Sustained Low Efficiency Dialysis in Critically Ill Patients with Acute Kidney Injury

Background: Sustained low efficiency dialysis (SLED) has been evolved in recent years as technical hybrid of continuous renal replacement therapy and intermittent hemodialysis. It offers optimized hemodynamic stability of the critically ill patients with acute kidney injury (AKI). Our aim was to evaluate the hemodynamic tolerability of SLED in hemodynamically unstable patients with AKI.Methods: This prospective experimental study was conducted in Intensive Care Unit of BIRDEM General Hospital, Dhaka over a period of one year.Results: Forty three hemodynamically unstable patients with AKI were treated with one fifty three sessions of SLED. Mean arterial pressure of the patients before starting dialysis were 80.58±10.92 mmHg and 69.8% patients were on inotrope support. There were no significant differences (p&gt;0.05) in mean arterial pressure during the procedure. No significant changes (p&gt;0.05) occurred in pulse, respiratory rate and temperature during the sessions. Only thirty six out of 153 SLED sessions were associated with complications and hypotension was the commonest one (20.26%). Hypotensive episodes were effectively managed with addition or dose escalation of inotropes. No dialysis had to be discontinued because of hypotension/arrhythmia.Conclusion: SLED is an effective renal replacement therapy for the critically ill patients with AKI which maintains their hemodynamic stability.Birdem Med J 2016; 6(2): 84-90

Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis.

To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED). This study was performed in ICUs of a university hospital. We collected blood samples during three consecutive days of SLED sessions in patients receiving ceftazidime. Concentration versus time curves were analysed using a population PKs approach with Pmetrics ® . Monte Carlo simulation for the first 24 h including a 6 h SLED session was performed with the final model. The fractional target attainment against the MIC of Pseudomonas aeruginosa was executed using targets of 50 and 100% fT > MIC . In total, 211 blood samples of 16 critically ill patients under SLED were collected. SLED treatments were 299.3 (68.4) min in duration. A two-compartment linear population PK model was most appropriate. The mean (SD) CL of ceftazidime on SLED, and off SLED were 5.32 (3.2), 1.06 (1.0) L/h respectively. The PTA for 50% fT > MIC for a dose of 1 g intravenously every 8 h was 98%. Assuming a target of 100% fT > MIC a dose of 2 g every 12 h covers isolates with MIC ≤8 mg/L with a PTA of 96%. In critically ill patients receiving SLED, ceftazidime 1 g every 8 h and ceftazidime 2 g every 12 h appear to be sufficient for achieving traditional (50% fT > MIC ) and aggressive PD targets (100% fT > MIC ) for susceptible isolates (MIC ≤8 mg/L), respectively.

The Report of Sustained Low-Efficiency Dialysis (SLED) Treatment in Fifteen Patients of Severe Snakebite

To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog(+) dialyzer (B. Braun, Germany). SLED sessions were 6-12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 ± 3.8, but decreased significantly to 7.9 ± 1.4, 6.2 ± 1.1, and 4.2 ± 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates.

Efficacy and Safety of a Citrate-Based Protocol for Sustained Low-Efficiency Dialysis in AKI Using Standard Dialysis Equipment

A simple anticoagulation protocol was developed for sustained low-efficiency dialysis (SLED) in patients with AKI, based on the use of anticoagulant citrate dextrose solution formulation A (ACD-A) and standard dialysis equipment. Patients' blood recalcification was obtained from calcium backtransport from dialysis fluid. All patients treated with SLED (8- to 12-hour sessions) for AKI in four intensive care units of a university hospital were studied over a 30-month period, from May 1, 2008 to September 30, 2010. SLED interruptions and their causes, hemorrhagic complications, as well as coagulation parameters, ionized calcium, and blood citrate levels were recorded. This study examined 807 SLED sessions in 116 patients (mean age of 69.7 years [SD 12.1]; mean Acute Physiology and Chronic Health Evaluation II score of 23.8 [4.6]). Major bleeding was observed in six patients (5.2% or 0.4 episodes/100 person-days follow-up while patients were on SLED treatment). Citrate accumulation never occurred, even in patients with liver dysfunction. Intravenous calcium for ionized hypocalcemia (< 3.6 mg/dl or < 0.9 mmol/L) was needed in 28 sessions (3.4%); in 8 of these 28 sessions (28.6%), low ionized calcium was already present before SLED start. In 92.6% of treatments, SLED was completed within the scheduled time (median 8 hours). Interruptions of SLED by impending/irreversible clotting were recorded in 19 sessions (2.4%). Blood return was complete in 98% of the cases. In-hospital mortality was 45 of 116 patients (38.8%). This study protocol affords efficacious and safe anticoagulation of the SLED circuit, avoiding citrate accumulation and, in most patients, systematic calcium supplementation; it can be implemented with commercial citrate solutions, standard dialysis equipment, on-line produced dialysis fluid, and minimal laboratory monitoring.

Prevention of Intradialytic Hypotension in Patients with Acute Kidney Injury Submitted to Sustained Low-Efficiency Dialysis

Objectives: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). Methods: Patients were randomly assigned to two SLED prescriptions—control group, dialysate temperature was 37.0°C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5°C with a variable sodium concentration [150–138 mEq/L] and UF rate. Results: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 ± 1.25 L vs. 1.59 ± 1.03 L in control, p = 0.04) when compared with control group. Conclusions: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

Antibiotic dosing during sustained low-efficiency dialysis: Special considerations in adult critically ill patients*

To address issues of antibiotic dosing during sustained low-efficiency dialysis by using available pharmacokinetic data, intermittent and continuous renal replacement therapy dialysis guidelines, and our experience with sustained low-efficiency dialysis. Published clinical trials, case reports, and reviews of antibiotic dosing in humans during sustained low-efficiency dialysis. A search of electronic databases (MEDLINE, PubMed, and Ovid) was conducted by using key words of extended daily dialysis, sustained low-efficiency dialysis, antibiotics, antimicrobial agents, and pharmacokinetics. MEDLINE identified 32 sustained low-efficiency dialysis articles, and PubMed identified 33 articles. All papers describing antibiotic clearance prospectively in patients were considered for this article. We identified nine original research articles and case reports that determined the impact of sustained low-efficiency dialysis on antibiotic clearance in patients. The blood and dialysate flow rates, duration of dialysis, type of filter, and the pharmacokinetic parameters were extracted from each article. If multiple articles on the same drug were published, they were compared for consistency with the aforementioned dialysis parameters and then compared with forms of continuous renal replacement therapy. Antibiotic clearance by sustained low-efficiency dialysis was determined to be similar or higher than continuous renal replacement therapy therapies. The estimated creatinine clearance during sustained low-efficiency dialysis was approximately 60 mL/min to 100 mL/min depending on the blood and dialysate flow rates and the type of filter used. The potential for significant drug removal during an 8-hr-or-longer sustained low-efficiency dialysis session is evident by the limited number of studies available. Because significant amounts of drug may be removed by sustained low-efficiency dialysis combined with altered pharmacokinetic variables in critically ill patients, the risk for suboptimal drug concentrations and pharmacodynamics must be considered. Appropriate dose and calculation of dosing intervals is essential to provide adequate antibiotic therapy in these patients. It is recommended that institutions who utilize sustained low-efficiency dialysis establish dosing guidelines for all pharmacists and physicians to follow to provide consistent delivery of antibiotics at adequate concentrations.