The role of the ADVanced Organ Support (ADVOS) system in critically ill patients with multiple organ failure.
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ABSTRACT: Background
Multi-organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification.Methods
We performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system.Results
In porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water-soluble and protein-bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2 ) effectively with rapid correction of pH abnormalities, achieving normalization of CO2 , and bicarbonate levels. In patients with COVID-19 infection, ADVOS enables rapid correction of acid-base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi-organ failure and has been shown to be safe with minimal adverse events.Conclusions
From the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water-soluble and protein-bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid-based direct removal of acid and CO2 . ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi-organ failure, and is well-tolerated. Larger randomized trials are now necessary to further validate these encouraging results.
SUBMITTER: Acharya M
PROVIDER: S-EPMC9306712 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevalence of multiple organ failure (MOF) in critically ill patients is increasing and associated mortality remains high. Extracorporeal organ support is a cornerstone in the management of MOF. We report data of an advanced hemodialysis system based on albumin dialysis (ADVOS multi device) that can regulate acid-base balance in addition to the established properties of renal replacement therapy and albumin dialysis systems in critically ill patients with MOF.Methods34 critically ill patients with MOF received 102 ADVOS treatment sessions in the Department of Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf. Markers of metabolic detoxification and acid-base regulation were collected and blood gas analyses were performed. A subgroup analyses were performed in patients with severe acidemia (pH < 7.2).ResultsMedian number of treatment sessions was 2 (range 1-9) per patient. Median duration of treatment was 17.5 (IQR 11-23) hours per session. Treatment with the ADVOS multi-albumin dialysis device caused a significant decrease in bilirubin levels, serum creatinine, BUN and ammonia levels. The relative elimination rate of bilirubin was concentration dependent. Furthermore, a significant improvement in blood pH, HCO3- and PaCO2, was achieved during ADVOS treatment including six patients that suffered from severe metabolic acidosis refractory to continuous renal replacement therapy. Delta pH, HCO3- and PaCO2 were significantly affected by the ADVOS blood flow rate and pH settings. This improvement in the clinical course during ADVOS treatments allowed a reduction in norepinephrine during ADVOS therapy. Treatments were well tolerated. Mortality rates were 50% and 62% for 28 and 90 days, respectively.ConclusionsIn this case series in patients with MOF, ADVOS was able to eliminate water-soluble and albumin-bound substances. Furthermore, the device corrected severe metabolic and respiratory acid-base disequilibrium. No major adverse events associated with the ADVOS treatments were observed.
| S-EPMC7364697 | biostudies-literature
Project description:AbstractThe objective of this registry is to collect data on real-life treatment conditions for patients for whom multiple organ dialysis with Advanced Organ Support (ADVOS) albumin hemodialysis is indicated.This registry was performed under routine conditions and without any study-specific intervention, diagnostic procedures, or assessments. Data on clinical laboratory tests, health status, liver function, vital signs, and examinations were collected (DRKS-ID: DRKS00017068). Mortality rates 28 and 90 days after the first ADVOS treatment, adverse events and ADVOS treatment parameters, including treatment abortions, were documented.This analysis was performed 2 years after the first patient was included on January 18, 2017. As of February 20, 2019, 4 clinical sites in Germany participated and enrolled 118 patients with a median age of 60 (IQR: 45, 69) of whom 70 were male (59.3%). Patients had a median SOFA Score of 14 (IQR: 11, 16) and a predicted mortality of 80%. The median number of failing organs was 3 (IQR: 2, 4).Four hundred twenty nine ADVOS treatments sessions were performed with a median duration of 17 hours (IQR: 6, 23). A 5.8% of the ADVOS sessions (25 of 429) were aborted due to device related errors, while 14.5% (62 of 429) were stopped for other reasons. Seventy nine adverse events were documented, 13 of them device related (all clotting, and all recovered without sequels).A significant reduction in serum creatinine (1.5 vs 1.2 mg/dl), blood urea nitrogen (24 vs 17 mg/dl) and bilirubin (6.9 vs 6.5 mg/dl) was observed following the first ADVOS treatment session. Blood pH, bicarbonate (HCO3-) and base excess returned to the physiological range, while partial pressure of carbon dioxide (pCO2) remained unchanged. At the time of the analysis, 28- and 90-day mortality were 60% and 65%, respectively, compared to an expected ICU-mortality rate of 80%. SOFA score was an independent predictor for outcome in a multivariable logistic regression analysis.The reported data show a high quality and completion of all participating centers. Data interpretation must be cautious due to the small number of patients, and the nature of the registry, without a control group. However, the data presented here show an improvement of expected mortality rates. Minor clotting events similar to other dialysis therapies occurred during the treatments.
| S-EPMC7899840 | biostudies-literature
Project description:Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO3- levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.
| S-EPMC8444686 | biostudies-literature
Project description:BackgroundADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF.AimOur aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward.Methods and resultsIn this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®.ConclusionConcentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.
| S-EPMC9144177 | biostudies-literature
Project description:A substantial part of COVID-19-patients suffers from multi-organ failure (MOF). We report on an 80-year old patient with pulmonary, renal, circulatory, and hepatic failure. We decided against the use of extracorporeal membrane oxygenation (ECMO) due to old age and a SOFA-score of 13. However, the patient was continuously treated with the extracorporeal multi-organ- "ADVanced Organ Support" (ADVOS) device (ADVITOS GmbH, Munich, Germany). During eight 24h-treatment-sessions blood flow (100-300 mL/min), dialysate flow (160-320 mL/min) and dialysate pH (7.6-9.0) were adapted to optimize arterial PaCO2 and pH. Effective CO2 removal and correction of acidosis could be demonstrated by mean arterial- versus post-dialyzer values of pCO2 (68.7 ± 13.8 vs. 26.9 ± 11.6 mmHg; p < 0.001). The CO2-elimination rate was 48 ± 23mL/min. The initial vasopressor requirement could be reduced in parallel to pH-normalization. Interruptions of ADVOS-treatment repeatedly resulted in reversible deteriorations of paCO2 and pH. After 95 h of continuous extracorporeal decarboxylating therapy the patient had markedly improved circulatory parameters compared to baseline. In the context of secondary pulmonary infection and progressive liver failure, the patient had a sudden cardiac arrest. In accordance with the presumed patient will, we decided against mechanical resuscitation. Irrespective of the outcome we conclude that extracorporeal CO2 removal and multiorgan-support were feasible in this COVID-19-patient. Combined and less invasive approaches such as ADVOS might be considered in old-age-COVID-19 patients with MOF.
| S-EPMC8041450 | biostudies-literature
Project description:IntroductionMultiple organ dysfunction (MOD) is a common pathway to morbidity and death in critically ill children. Defining organ dysfunction is challenging, as we lack a complete understanding of the complex pathobiology. Current pediatric organ dysfunction criteria assign the same diagnostic value-the same "weight"- to each organ system. While each organ dysfunction in isolation contributes to the outcome, there are likely complex interactions between multiple failing organs that are not simply additive.ObjectiveDetermine whether certain combinations of organ system dysfunctions have a significant interaction associated with higher risk of morbidity or mortality in critically ill children.MethodsWe conducted a retrospective observational cohort study of critically ill children at two large academic medical centers from 2010 and 2018. Patients were included in the study if they had at least two organ dysfunctions by day 3 of PICU admission based on the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) criteria. Mortality was described as absolute number of deaths and mortality rate. Combinations of two pediatric organ dysfunctions were analyzed with interaction terms as independent variables and mortality or persistent MOD as the dependent variable in logistic regression models.ResultsOverall, 7,897 patients met inclusion criteria and 446 patients (5.6%) died. The organ dysfunction interactions that were significantly associated with the highest absolute number of deaths were cardiovascular + endocrinologic, cardiovascular + neurologic, and cardiovascular + respiratory. Additionally, the interactions associated with the highest mortality rates were liver + cardiovascular, respiratory + hematologic, and respiratory + renal. Among patients with persistent MOD, the most common organ dysfunctions with significant interaction terms were neurologic + respiratory, hematologic + immunologic, and endocrinologic + respiratory. Further analysis using classification and regression trees (CART) demonstrated that the absence of respiratory and liver dysfunction was associated with the lowest likelihood of mortality.Implications and future directionsCertain combinations of organ dysfunctions are associated with a higher risk of persistent MOD or death. Notably, the three most common organ dysfunction interactions were associated with 75% of the mortality in our cohort. Critically ill children with MOD presenting with these combinations of organ dysfunctions warrant further study.
| S-EPMC9081807 | biostudies-literature
Project description:BackgroundADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available.AimEvaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort.Methods and resultsIn this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites' including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59).ConclusionDiscontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.
| S-EPMC8016329 | biostudies-literature
Project description:BackgroundContinuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients.MethodsPatients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman's rank test.ResultsAmong a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors (P = 0.002) and the matched survivors (P = 0.004).ConclusionsThis study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.
| S-EPMC6417231 | biostudies-literature
Project description:Perilipin 2 (PLIN2) is a lipid droplet protein with various metabolic functions. However, studies investigating PLIN2 in the context of inflammation, especially in systemic and acute inflammation, are lacking. Hence, we assessed the relevance of serum PLIN2 in critically ill patients. We measured serum PLIN2 serum in 259 critically ill patients (166 with sepsis) upon admission to a medical intensive care unit (ICU) compared to 12 healthy controls. A subset of 36 patients underwent computed tomography to quantify body composition. Compared to controls, serum PLIN2 concentrations were elevated in critically ill patients at ICU admission. Interestingly, PLIN2 independently indicated multiple organ dysfunction (MOD), defined as a SOFA score > 9 points, at ICU admission, and was also able to independently predict MOD after 48 h. Moreover, serum PLIN2 levels were associated with severe respiratory failure potentially reflecting a moribund state. However, PLIN2 was neither a predictor of ICU mortality nor did it reflect metabolic dysregulation. Conclusively, the first study assessing serum PLIN2 in critical illness proved that it may assist in risk stratification because it is capable of independently indicating MOD at admission and predicting MOD 48 h after PLIN2 measurement. Further evaluation regarding the underlying mechanisms is warranted.
| S-EPMC8468514 | biostudies-literature
Project description:BackgroundShock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA).MethodsThis was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels.ResultsOf 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC.ConclusionsThe addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction.
| S-EPMC8573766 | biostudies-literature