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PurposeTo describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design.MethodsUsing data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland–Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population.ResultsChanges in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9 cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate.ConclusionsThe lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R.

PurposeAcute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure.MethodsWe searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.ResultsWe identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain.ConclusionsECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Extracorporeal life support (ECLS) has become increasingly popular as a salvage strategy for critically ill adults. Major advances in technology and the severe acute respiratory distress syndrome that characterized the 2009 influenza A(H1N1) pandemic have stimulated renewed interest in the use of venovenous extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal to support the respiratory system. Theoretical advantages of ECLS for respiratory failure include the ability to rest the lungs by avoiding injurious mechanical ventilator settings and the potential to facilitate early mobilization, which may be advantageous for bridging to recovery or to lung transplantation. The use of venoarterial ECMO has been expanded and applied to critically ill adults with hemodynamic compromise from a variety of etiologies, beyond postcardiotomy failure. Although technology and general care of the ECLS patient have evolved, ECLS is not without potentially serious complications and remains unproven as a treatment modality. The therapy is now being tested in clinical trials, although numerous questions remain about the application of ECLS and its impact on outcomes in critically ill adults.

Background Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). Methods Patients undergoing coronary artery bypass grafting were randomized to MiECC ( n  = 30) and CECC ( n  = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1β, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. Results Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2–4.5 vs. CECC 4.6 pg/mL; CI 3.4–5.6; p  = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. Conclusions Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. Clinical registration number NCT03216720.

Background The aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure. Methods Patients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4 % albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model. Results Sixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median −68 μmol/L, interquartile range [IQR] −107.5 to −33.5, p  = 0.001; SPAD: −59 μmol/L, −84.5 to +36.5, p  = 0.001). However, bile acids (MARS: −39 μmol/L, −105.6 to −8.3, p  < 0.001; SPAD: −9 μmol/L, −36.9 to +11.4, p  = 0.131), creatinine (MARS: −24 μmol/L, −46.5 to −8.0, p  < 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L, p  = 0.314) and urea (MARS: −0.9 mmol/L, −1.93 to −0.10, p  = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68, p  = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10 %, −0.8 to +20.9 %, p  < 0.001; SPAD: +7 %, −7.5 to +15.5 %, p  = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD. Conclusions Both procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation. Trial registration German Clinical Trials Register ( www.drks.de ) DRKS00000371 . Registered 8 April 2010.

Introduction The aim of the study was to evaluate the feasibility and safety of avoiding invasive mechanical ventilation (IMV) by using extracorporeal CO 2 removal (ECCO 2 R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure refractory to noninvasive ventilation (NIV). Methods Case–control study. Patients with acute hypercapnic respiratory failure refractory to NIV being treated with a pump-driven veno-venous ECCO 2 R system (iLA-Activve ® ; Novalung, Heilbronn, Germany) were prospectively observed in five European intensive care units (ICU). Inclusion criteria were respiratory acidosis (pH ≤ 7.35, PaCO 2  > 45 mmHg) with predefined criteria for endotracheal intubation (ClinicalTrials.gov NCT01784367). The historical controls were patients with acute hypercapnic respiratory failure refractory to NIV who were treated with IMV. The matching criteria were main diagnosis, age, SAPS-II score and pH. Results Twenty-five cases (48.0 % male, mean age 67.3 years) were matched with 25 controls. Intubation was avoided in 14 patients (56.0 %) in the ECCO 2 R group with a mean extracorporeal blood flow of 1.3 L/min. Seven patients were intubated because of progressive hypoxaemia and four owing to ventilatory failure despite ECCO 2 R and NIV. Relevant ECCO 2 R-associated adverse events were observed in 11 patients (44.0 %), of whom 9 (36.0 %) suffered major bleeding complications. The mean time on IMV, ICU stay and hospital stay in the case and control groups were 8.3 vs. 13.7, 28.9 vs. 24.0 and 36.9 vs. 37.0 days, respectively, and the 90-day mortality rates were 28.0 vs. 28.0 %. Conclusions The use of veno-venous ECCO 2 R to avoid invasive mechanical ventilation was successful in just over half of the cases. However, relevant ECCO 2 R-associated complications occurred in over one-third of cases. Despite the shorter period of IMV in the ECCO 2 R group there were no significant differences in length of stay or in 28- and 90-day mortality rates between the two groups. Larger, randomised studies are warranted for further assessment of the effectiveness of ECCO 2 R.

Hyperlactatemia occurs during or after extracorporeal circulation in the form of lactic acidosis, increasing the risk of postoperative complications and the mortality rate. The aim of this study was to evaluate whether continuous high-volume hemofiltration with volume replacement through a polyethersulfone filter during the extracorporeal circulation procedure decreases postoperative lactatemia and its consequences. This was a randomized controlled trial. Patients were randomly divided into two groups of 32: with or without continuous high-volume hemofiltration through a polyethersulfone membrane. Five patients were excluded from each group during the study period. The sociodemographic characteristics, filter effects, and blood lactate levels at different times during the procedure were evaluated. Secondary endpoints were studied, such as the reduction in the intubation time and time spent in ICU. Lactatemia measurements performed during the preoperative and intraoperative phases were not significantly different between the two groups. However, the blood lactate levels in the postoperative period and at 24 hours in the intensive care unit showed a significant reduction and a possible clinical benefit in the hemofiltered group. Following extracorporeal circulation, the mean lactate level was higher (difference: 0.77 mmol/L; CI 0.95: 0.01-1.53) in the nonhemofiltered group than in the hemofiltered group (p<0.05). This effect was greater at 24 hours (p = 0.019) in the nonhemofiltered group (difference: 1.06 mmol/L; CI 0.95: 0.18-1.93) than in the hemofiltered group. The reduction of lactatemia is associated with a reduction of inflammatory mediators and intubation time, with an improvement in liver function. The use and control of continuous high-volume hemofiltration through a polyethersulfone membrane during heart-lung surgery could potencially prevent postoperative complications. The reduction of lactatemia implied a reduction in intubation time, a decrease in morbidity and mortality in the intensive care unit and a shorter hospital stay.

To evaluate a novel anticoagulation strategy in an extracorporeal circuit, we introduce a device that induces local hypothermia as blood flows through the circuit. Using a pig model, we assessed its technical feasibility, biocompatibility, and safety. Sixteen pigs were randomly assigned to either the cooled group or the control group and underwent midline laparotomy to establish extracorporeal circulation (blood flow 500 ml/min) via the caudal vena cava for up to four hours. Blood samples were collected at baseline and at 15, 60, and 240 min during the experiment. In the cooled group, blood was cooled to 20 °C and then rewarmed to 37 °C, while in the control group, blood was maintained at 37 °C. A total of 6 cooled and 4 control pigs completed 4 h of the experiment. Our findings confirm the technical feasibility of the proposed device, which effectively maintained the required temperature differentials while keeping the pressure differentials in the circuit within 150 mmHg. No issues with circuit patency were observed. Additionally, no adverse effects were detected on erythrocyte stability. Within the limitation of the short observation period, no adverse effects were observed on renal, liver, or cardiac function. Our data suggest that local hypothermia in the extracorporeal circuit may mitigate surgery-induced inflammation.

Background With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO 2 removal (ECCO 2 R). However, current evidence in these indications is limited. A European ECCO 2 R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. Methods A modified Delphi-based method was used to collate European experts’ views to better understand how ECCO 2 R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. Results Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO 2 R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO 2 R therapy ( n  = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO 2 R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO 2 levels. Driving pressure (≥ 14 cmH 2 O) followed by plateau pressure ( P plat ; ≥ 25 cmH 2 O) was considered the most important criteria for ECCO 2 R initiation. Key treatment targets for patients with ARDS undergoing ECCO 2 R included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmH 2 O) and P plat (< 25 cmH 2 O). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO 2 and no decrease in respiratory rate were key criteria for initiating ECCO 2 R therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30–7.35), respiratory rate (< 20–25 breaths/min), decrease of PaCO 2 (by 10–20%), weaning from NIV, decrease in HCO 3 − and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group. Conclusions Insights from this group of experienced physicians suggest that ECCO 2 R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.

Background Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines. Methods This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH). Results Five men and five women with a mean age of 57.30 ± 18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60% ± 3.94% and increased to 92.13% ± 3.28% after them ( p  < 0.001). Serum IL-6 showed a reduction from 139.70 ± 105.62 to 72.06 ± 65.87 pg/mL ( p  = 0.073); and c-reactive protein decreased from 136.25 ± 84.39 to 78.25 ± 38.67 mg/L ( P  = 0.016). Conclusions Extracorporeal hemoadsorption could improve the general condition in most of recruited patients with severe coronavirus disease; however, large prospective multicenter trials in carefully selected patients are needed to definitely evaluate the efficacy of hemoperfusion in COVID-19 patients. Trial registration The research protocol has been registered in the website of Iranian Registry of Clinical Trials with the reference number IRCT20150704023055N2 .