589 Role of Liver Support Systems in The Management of Post Hepatectomy Liver Failure: A Meta-Analysis and Systematic Review of Literature

Aim Post hepatectomy liver failure (PHLF) is a rare but serious complication following liver resection. PHLF is associated with high mortality of up to 50% in severe cases. With limited treatment options available, there is a need to evaluate the role of systems that support the function of the liver as treatment modalities following PHLF development. Method The aim of this study was to review the literature and summarise the role of liver support systems (LSS) in the management of PHLF. Publications of interest were identified using systematically designed searches. Following screening, data from the relevant publications were extracted, pooled where possible, and analysed. Results Systematic review identified ten studies, which used either Plasma Exchange (PE) or Molecular Adsorbent Recirculating System (MARS) as LSS after PHLF development. The sample sizes of included studies were small, ranging from N = 2 to N = 13. Across all studies, the pooled 90-day mortality rate was 40% (95% CI: 15% - 68%). However, there was substantial heterogeneity (I2=64%), likely since the studies used a variety of definitions for PHLF and had different selection criteria for patient eligibility for LSS treatment. Conclusions Despite potential benefits, the current evidence is insufficient to recommend LSS for the routine management of severe PHLF, with the current literature consisting of only a limited number of studies. There is a definite need for larger, multicentre, prospective studies evaluating the conventional and newer modalities of support systems with a view to improve the outcomes in this group of patients.

Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial

<b><i>Introduction:</i></b> Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). <b><i>Methods:</i></b> We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity &#x3c;50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. <b><i>Results:</i></b> Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (−83 ± 67 μmol/L after MARS; −122 ± 118 μmol/L after SPAD session), conjugated bilirubin (−82 ± 61 μmol/L after MARS; −105 ± 96 μmol/L after SPAD session), and bile acid levels (−64 ± 75 μmol/L after MARS; −56 ± 56 μmol/L after SPAD session), all nondifferent comparing MARS to SPAD. <b><i>Conclusion:</i></b> A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Hemodynamic impact of molecular adsorbent recirculating system in refractory vasoplegic shock due to calcium channel blocker poisoning

Objective: To report the hemodynamic effect of to the molecular adsorbent recirculating system (MARS™) therapy for patients in refractory vasoplegic shock due to calcium channel blocker (CCB) poisoning Methods: We report a retrospective cohort of patients who were hospitalized for CCB poisoning with refractory vasoplegic shock and treated by MARS therapy, at Amiens Hospital University, from January 2010 to December 2019. Improvement in hemodynamic was assessed by dynamic changes in mean arterial pressure (MAP) and norepinephrine levels over a 24-h period after MARS therapy. Cardiac function was assessed by transthoracic echocardiography. Results: MARS therapy was performed on seven patients for CCB poisoning. CCB poisoning included nicardipine ( n = 3, 43%) amlodipine ( n = 3, 43%), and verapamil ( n = 1, 14%). The median time to start MARS therapy was 24 [14–27] h after drug ingestion and 6 [2–9] h after ICU admission. Cardiac output was preserved for all patients. MAP values improved from 56 [43–58] to 65 [61–78] 16 mmHg ( p = 0.005). Norepinephrine dose significantly decreased from 3.2 [0.8–10] µg/kg/min to 1.2 [0.1–1.9] µg/kg/min ( p = 0.008) and lactate level decreased from 3.2 [2.4–3.4] mmol/l−1 to 1.6 [0.9–2.2] mmol/l−1 ( p = 0.008). The median length of ICU stay was 4 (2–7) days and hospital stay was 4 (4–16) days. No complication related to the MARS therapy were reported. No patient died and all were discharged from the hospital. Conclusion: We reported the largest case-series of MARS therapy for refractory vasoplegic shock due to CCB poisoning. We observed that MARS therapy was associated with an improvement of hemodynamic parameters.

Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).

Molecular adsorbent recirculating system (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) for diltiazem removal: An in vitro study

The objective of the present study was to evaluate the efficacy of the molecular adsorbent recirculating system (MARS) vs continuous veno-venous hemodiafiltration (CVVHDF). Diltiazem poisoning was simulated in a central compartment consisting in a 5L dialysis solute spiked with diltiazem at two different toxic concentrations: 750 and 5000 µg/L. For CVVHDF, mean extraction coefficients (EC = (in concentration − out concentration)/in concentration) were concentration-dependent with a decrease all along the dialysis. At the end of the sessions the mean amounts remaining in the central compartment were 8% and 7% of the initial dose at 750 and 5000 µg/L, respectively. The mean cumulative amounts found in the effluent were 60% and 75% of the initial dose, respectively. The missing amounts accounted for 32% and 18% of the initial dose, respectively, corresponding to an adsorption to the dialysis membrane. In contrast, the different compartments of the MARS resulted in undetectable output concentration earlier that the end of the session. The mean concentrations of diltiazem remaining in the central compartment were <1 µg/L at the end of the sessions. Global ECs were around 50% all along the experiment at both concentrations, and the average charcoal cartridge ECs was 80% throughout the experiments. CVVHDF system in the developed model was efficient for diltiazem removal, mainly by diffusion, convection and to a lesser extent by adsorption to the dialysis membrane. In MARS system, resin cartridge and hemodialysis components are ineffective, charcoal cartridge is responsible for almost all drug removal.

Bleeding Complications Associated With the Molecular Adsorbent Recirculating System: A Retrospective Observational Study

Background: The molecular adsorbent recirculating system (MARS) is an artificial liver support system that supports excretory liver function in patients with liver failure and is used as bridge therapy for patients waiting for liver transplantation. However, MARS may increase the tendency for bleeding. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications. Methods: We retrospectively analyzed data from 15 patients undergoing a total of 36 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values. Results: MARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and activated partial thromboplastin time and reduced fibrinogen, thus negatively impacting coagulation. Seven patients had bleeding complications and were classified into the bleeder group. Pre MARS hemoglobin was significantly lower in the bleeder group (8.3 mg/dl) than in the non bleeder group (10.0 mg/dl, P=0.014). When comparing the upper and lower 25 % of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre MARS hemoglobin and factor V (P=0.008 and P=0.032, respectively). Conclusions: MARS appears to alter coagulation related factors and increase the risk of bleeding complications. However, individual differences among patients were large, and various factors, such as low hemoglobin and factor V levels, appear to be involved.