scholarly journals Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Uwe Liebchen ◽  
Michael Paal ◽  
Andrea Becker-Pennrich ◽  
Michael Irlbeck ◽  
...  

AbstractThere are different methods of artificial liver support for patients with acute liver dysfunction (ALD). However, CytoSorb (CS) might be a new approved option for those patients. Question of interest is whether the elimination performance of CS was comparable to that of advanced organ support (ADVOS). Patients, treated with CS (integrated into high-flux dialysis) or ADVOS and a total bilirubin > 10 mg/dl were included. Laboratory parameters were evaluated before starting therapy (d0) and 12–24 h thereafter (d1). The Wilcoxon-test with associated samples was used for statistical analysis. Thirty-nine patients (33 CS, 6 ADVOS) were included. The median bilirubin at d0 was 16.9 and 17.7 mg/dl and at d1 was 13.2 and 15.9 mg/dl, in the CS and ADVOS group, respectively. There was a significant bilirubin reduction as well in the CS group (p < 0.001, median relative reduction: 22.5%) as in the ADVOS group (p = 0.028, median relative reduction: 22.8%). There was no significant difference in the relative bilirubin reduction between CS and ADVOS therapies. The use of CytoSorb and ADVOS in patients with ALD led to a significant and comparable decrease in total bilirubin. The easy use of CS might be an advantage compared to other procedures.

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Christina Scharf ◽  
Uwe Liebchen ◽  
Michael Paal ◽  
Michael Irlbeck ◽  
Michael Zoller ◽  
...  

Abstract Background Rhabdomyolysis is frequently occurring in critically ill patients, resulting in a high risk of acute kidney injury (AKI) and potentially permanent kidney damage due to increased myoglobin levels. The extracorporeal elimination of myoglobin might be an approach to prevent AKI, but its molecular weight of 17 kDa complicates an elimination with conventional dialysis membranes. Question of interest is, if myoglobin can be successfully eliminated with the cytokine adsorber Cytosorb® (CS) integrated in a high-flux dialysis system. Methods Patients were included between 10/2014 and 05/2020 in the study population if they had an anuric renal failure with the need of renal replacement therapy, if CS therapy was longer than 90 min and if myoglobin level was > 5.000 ng/ml before treatment. The measurement times of the laboratory values were: d-1 = 24–36 h before CS, d0 = shortly before starting CS and d1 = 12–24 h after starting CS treatment. Statistical analysis were performed with Spearman’s correlation coefficient, Wilcoxon test with associated samples and linear regression analysis. Results Forty-three patients were included in the evaluation (median age: 56 years, 77% male patients, 32.6% ECMO therapy, median SAPS II: 80 points and in-hospital mortality: 67%). There was a significant equilateral correlation between creatine kinase (CK) and myoglobin at all measurement points. Furthermore, there was a significant reduction of myoglobin (p = 0.03, 95% confidence interval (CI): − 9030, − 908 ng/ml) during CS treatment, with a median relative reduction of 29%. A higher median reduction of 38% was seen in patients without ongoing rhabdomyolysis (CK decreased during CS treatment, n = 21). In contrast, myoglobin levels did not relevantly change in patients with increasing CK and therefore ongoing rhabdomyolysis (n = 22, median relative reduction 4%). Moreover, there was no significant difference in myoglobin elimination in patients with and without ECMO therapy. Conclusion Blood purification with Cytosorb® during high-flux dialysis led to a significant reduction of myoglobin in patients with severe rhabdomyolysis. The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment. Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  

Abstract Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.


2013 ◽  
Vol 159 (8) ◽  
pp. 522 ◽  
Author(s):  
Faouzi Saliba ◽  
Christophe Camus ◽  
François Durand ◽  
Philippe Mathurin ◽  
Alexia Letierce ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5585-5585
Author(s):  
Paul J Hampel ◽  
Kari G. Chaffee ◽  
Simonetto A Douglas ◽  
Timothy G. Call ◽  
Wei Ding ◽  
...  

Abstract INTRODUCTION: The prevalence of liver dysfunction in patients with previously untreated chronic lymphocytic leukemia (CLL) is unknown; knowledge of which may provide important context for emerging therapeutic options with possible hepatotoxicity. The impact of liver dysfunction on outcomes of CLL patients is not well described. METHODS: Between 09/1993 and 04/2016, previously untreated CLL patients seen in the Division of Hematology at Mayo Clinic at diagnosis (<12 months) and who had baseline assessment of at least one of the following liver function tests (LFTs): alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin were included in this analysis. Baseline lab values were defined as the closest value to CLL diagnosis for each lab within 12 months prior to diagnosis up through 6 months after CLL diagnosis. Patients with at least one abnormal LFT (defined as greater than 1.5 x the upper limit of normal) were classified as having liver dysfunction at diagnosis. Analysis for factors related to baseline liver function was performed using age- and sex-adjusted logistic regression models. Kaplan-Meier methods and multivariable Cox regression analysis was used to evaluate time to first treatment (TTFT) and overall survival (OS). RESULTS: Of 2336 previously untreated CLL patients who met the inclusion criteria, 123 (5%) patients had at least one abnormal LFT value at time of diagnosis. Thirty five patients had abnormal AST (median value 106 U/L, range 72-745 U/L, reference range 8-48 U/L), 25 patients had abnormal ALT (median 112 U/L, range 82-313 U/L, reference 7-55 U/L), and 54 patients had abnormal total bilirubin (median 2.10 mg/dL, range 1.8-26.5 mg/dL, reference range ≤ 1.2 mg/dL). Forty five patients had abnormal alkaline phosphatase; 35 patients in the year 2003 or later (median 198 U/L, range 172-2269 U/L, reference range 45-115 U/L) and 10 patients in 2002 or earlier (median 471.5 U/L, range 394-706 U/L, reference range 98-260 U/L). Abnormal LFTs were more common among those with advanced Rai stage disease (Rai 0-II=4.7% vs. Rai III-IV=13.4%; p<0.001) and among patients with lower hemoglobin (median 13.1 g/dL vs. 13.9 g/dL; p<0.001) at diagnosis. No difference in the rate of abnormal LFTs was observed based on cytogenetic abnormalities detected by FISH or CD38, CD49d, ZAP-70 or IGHV gene mutation status. There was no significant difference in prior alcohol abuse history between patients with liver dysfunction at diagnosis (6%) and those without (5%) (p=0.63). Similarly, there was no significant difference in body mass index between groups (median 27.8 vs. 27.8; p=0.12). After 12 years of follow-up, an estimated 69% of the cases with abnormal LFTs were treated. The most common type of treatments included anti-CD20 monoclonal antibody therapy only, followed by purine nucleoside based chemoimmunotherapy, and an alkylating agent with a monoclonal antibody. The median time to treatment was 4.3 years for cases with abnormal LFTs compared to 6.3 years for cases without abnormal LFTs (p=0.02). However, after adjusting for age, sex and Rai stage, there was no difference in TTFT among patients with abnormal LFTs at baseline compared to those with normal LFTs (hazard ratio [HR] = 1.2 (95% CI, 0.9-1.6); p=0.23). The median survival of CLL patients with abnormal LFTs at diagnosis was significantly shorter than those with normal LFTs (8.6 vs. 11.6 years, p<0.001, Figure 1). After adjusting for age, sex and Rai stage, multivariable cox regression analysis showed that abnormal LFTs retained independent prognostic significance for OS with a HR of 1.4 (95% CI, 1.1-1.8; p=0.012). CONCLUSION: At the time of CLL diagnosis, ~1 out of every 20 patients with previously untreated CLL has abnormal LFTs. These data provide context to the recent reports of hepatotoxicity with the use of signal inhibitors in untreated CLL. Although the presence of liver dysfunction at diagnosis does not seem to predict a shorter TTFT, the OS of these patients is significantly shorter compared to patients who have normal LFTs. Figure 1 Figure 1. Disclosures Ding: Merck: Research Funding. Kenderian:Novartis: Patents & Royalties, Research Funding. Kay:Pharmacyclics: Research Funding; Tolero Pharmaceuticals: Research Funding; Acerta: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Morpho-Sys: Membership on an entity's Board of Directors or advisory committees; Infinity Pharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Shanafelt:Janssen: Research Funding; Pharmacyclics: Research Funding; GlaxoSmithkKine: Research Funding; Genentech: Research Funding; Cephalon: Research Funding; Celgene: Research Funding; Hospira: Research Funding. Parikh:Pharmacyclics: Honoraria, Research Funding.


2009 ◽  
Vol 150 (51) ◽  
pp. 2299-2307 ◽  
Author(s):  
Csaba Rikker

A májelégtelenség – akár korábbi májbetegség fennállása nélkül alakult ki (akut májelégtelenség), akár krónikus májbetegség akut dekompenzációja („akut a krónikuson” májelégtelenség) következménye – magas halálozással jár. A végállapotú májbetegségek következtében kialakult májelégtelenség egyetlen kuratív megoldása ma a májtranszplantáció. Ennek fő gátját a rendelkezésre álló donorszervek hiánya képezi, emiatt sok, várólistán szereplő beteg exitál. A transzplantáció korlátai tették szükségessé olyan májtámogató rendszerek kifejlesztését, amelyek alkalmasak a beteg életben tartására a szervátültetésig vagy a máj regenerációjáig. A korai próbálkozások (hemodialízis, hemoperfúzió, cseretranszfúzió, kereszthemodialízis, keresztkeringés, plazmaferézis stb.) elégtelennek bizonyultak. Napjainkban a májpótló kezelésnek két fő iránya alakult ki: a sejtalapú, úgynevezett bioarteficiális és a nem sejtalapú, úgynevezett arteficiális rendszerek. A bioarteficiális rendszerek élő állati májsejteket vagy emberi májtumorsejteket tartalmaznak. Jellegzetességük, hogy a beteg vérét vagy szeparált plazmáját a májsejteket tartalmazó bioreaktoron áramoltatják át. Elviekben a májműködést ezek a metodikák modellezik a legtökéletesebben, mert a máj szintetizáló- és detoxikálófunkcióját egyaránt pótolják. Jelenlegi formájukban azonban még távol állnak az ideális megoldástól, alkalmazásuk számos immunológiai, infektológiai, onkológiai és financiális problémát vet fel, ezért egyelőre csak kísérleti célra állnak rendelkezésre. Az arteficiális rendszerek a klinikum számára már elérhetőek, bár széles körben még nem terjedtek el. Csak a máj detoxikálófunkcióját pótolják, a szintetikus funkció részben a hiányzó anyagok (plazmaproteinek, alvadási faktorok) szubsztitúciójával pótolható. Idetartozik a hemodiabszorpció, amely az Amerikai Egyesült Államokban terjedt el (liver dialysis unit), valamint a főleg Európában használatos albumindialízis és a legújabban kifejlesztett frakcionált plazmaszeparáció és -adszorpció (FPSA). Az albumindialízis egyszerű módszere a „single pass albumin dialysis” (SPAD), ennek továbbfejlesztett változata a „molecular adsorbent recirculating system” (MARS). Az FPSA high-flux hemodialízissel kiegészített változata a Prometheus-rendszer. Bár a felsorolt módszerek hatásosságát számos kísérleti és klinikai tanulmány támasztja alá, a konzervatív kezeléssel szemben a túlélésre kifejtett előnyös hatásuk bizonyítására még nagy esetszámot felölelő, randomizált, kontrollált vizsgálatok elvégzésére van szükség.


2014 ◽  
Vol 960-961 ◽  
pp. 47-51
Author(s):  
Ying Ying Pei ◽  
Yi Ze Sun ◽  
Si Jie Sun ◽  
Da Yong Gao ◽  
Wei Ping Ding

The open-loop albumin dialysis mode (OLM) is usually used to remove protein-bound toxins from artificial liver support systems. However, there is still interest in closed-loop albumin dialysis mode (CLM) because this mode could enable the regeneration and reuse of albumin and minimize the physical size of liver support systems. In this paper, the two dialysis modes were theoretically compared under various theoretical conditions. Our results show that at the beginning of the dialysis period, in terms of detoxification efficiency, CLM is better. As the molar ratio of toxin to albumin in the blood (RTA) decreases, the overall performance of CLM approaches that of OLM in 4-hour dialysis. In certain cases, the clearance of albumin-bound toxins by CLM could be as effective as that by OLM; occasionally, CLM is even more effective.


ASAIO Journal ◽  
2000 ◽  
Vol 46 (2) ◽  
pp. 242
Author(s):  
S. Klammt ◽  
S. Mitzner ◽  
J. Stange ◽  
B. Brinkmann ◽  
P. Peszynski ◽  
...  

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