Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

BACKGROUND: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. METHODS: In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS: A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS: In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).

Routine Extracorporeal Life Support in Infarct-Related Cardiogenic Shock: 1-Year Results of the ECLS-SHOCK Trial.

Extracorporeal life support (ECLS) has been increasingly used in the treatment of severe infarct-related cardiogenic shock in the last decade. The randomised ECLS-SHOCK trial demonstrated no benefit of early routine use on 30-day all-cause death. We herein present mid-term results. At 1-year follow-up, there were no significant differences in all-cause or cardiovascular mortality, neurologic outcome, recurrent myocardial infarction, repeat revascularisation and rehospitalisations for heart failure between ECLS and usual medical care.

Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting.

BACKGROUND: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. RESULTS: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. CONCLUSIONS: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion.

Association between adverse effects under azathioprine therapy and inosine triphosphate pyrophosphatase activity in patients with chronic inflammatory bowel disease.

BACKGROUND: Inosine triphosphate pyrophosphatase (ITPA) catalyzes the pyrophosphohydrolysis of inosine triphosphate to inosine monophosphate. Recently, single-nucleotide polymorphisms in the ITPA gene, associated with decreased enzyme activity, have been reported. Some clinical studies have demonstrated that the 94C>A mutation is linked to flu-like symptoms, rash, and pancreatitis during azathioprine (AZA) therapy and to early AZA discontinuation. In this study, we investigated whether the enzyme phenotype is also related to adverse effects (AEs). METHODS: Patients suffering from inflammatory bowel disease who were treated with AZA (N=160; age 43±12 years) were included. Data were categorized into quartiles according to the ITPA activity. Information about the therapeutic regimen, AEs [leucopenia, increased hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), flu-like symptoms, and pancreatitis], cotherapy, and comorbidity was obtained from the responsible clinicians and patients by using a standardized questionnaire. ITPA activity was measured by a validated high-performance liquid chromatography procedure. In patients with decreased ITPA activity, the 94C>A and IVS2+21A>C genotypes were determined. RESULTS: AEs were reported significantly more often for patients with low ITPA activity than for patients with high ITPA activity; the highest odds ratio for occurrence of AEs was found to be below a threshold of 59.9 µmol/(gHb·h) [hemoglobin (Hb)]. Decreased ITPA activities [particularly <89.2 µmol/(gHb·h)] were frequently accompanied by leucopenias, whereas very low enzyme activities [<37.3 µmol/(gHb·h)] were associated with a higher incidence of increased liver enzymes. CONCLUSIONS: The results demonstrate a relationship between low ITPA activity and AEs and support the idea that the determination of ITPA phenotype might be an appropriate alternative to genotyping.