Same but Different-ECMO in COVID-19 and ARDS of Other Etiologies. Comparison of Survival Outcomes and Management in Different ARDS Groups.

Background: COVID-19 has led to increased numbers of patients in need of venovenous extracorporeal membrane oxygenation (ECMO) support, but knowledge on management in comparison to acute respiratory distress syndrome (ARDS) of other etiologies is still lacking. We analyzed venovenous ECMO management and survival outcomes in patients with COVID-19 in comparison to influenza ARDS and pulmonary ARDS of other origin. Results: Retrospective analysis of prospective venovenous ECMO registry-based data collection was performed. One hundred consecutive venovenous ECMO patients with severe ARDS were included (41 COVID-19, 24 influenza A, 35 ARDS of other etiologies). Patients with COVID-19 had higher BMI (body mass index), lower SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, lower C-reactive protein and procalcitonin levels and less vasoactive support at ECMO initiation. Significantly more patients were mechanically ventilated for more than 7 days prior to ECMO initiation in the COVID-19 group, however they were ventilated with lower tidal volumes and more often received additional rescue therapies prior to and on ECMO. COVID-19 patients had significantly more barotrauma and thrombotic events on ECMO. There were no differences in weaning of ECMO, however duration of ECMO runs and ICU length of stay was significantly longer in the COVID-19 group. The leading cause of death in the COVID-19 group was irreversible respiratory failure, while uncontrolled sepsis and multiorgan failure were leading causes in the other 2 groups. All patients who survived ICU treatment were discharged out of hospital, and there were no differences in survival among groups at 180 days. Conclusions: Survival outcomes of venovenous ECMO patients do not differ between COVID-19 and ARDS of other pulmonary etiologies. ARDS guidelines were in greater proportion adhered to in COVID-19 patients, with, however, longer time to ECMO initiation. COVID-19 ARDS seems specific as a more single-organ disease with longer ECMO duration and irreversible respiratory failure as a main cause of ICU mortality.

High fidelity ECMO simulation: a reality check with reality-use of simulation in ECMO teaching program.

Simulation based learning is becoming a crucial part in ECMO education. Simulation can provide a safe but also very realistic learning experience depending on simulation fidelity. In our institution we developed a simulation based ECMO training program that incorporates low- and high-fidelity simulation. Aim of this study was to evaluate effectiveness of low- and high-fidelity simulation teaching strategies in ECMO novices. We conducted four consecutive ECMO training courses that included fifty-one ECMO novices. We describe ECMO training execution and evaluate training effectiveness and perception by structured pre- and post-training questionnaires analysis. Results of our study show extremely high satisfaction rate with simulation training (4.9 ± 0.3, Lickert 5 point scale). High-fidelity simulation was perceived as very realistic and as such represents an important tool in learning immersion and experience. However, participants reported significant decline from their expectations with regard to structured approach to troubleshooting (4.7 ± 0.5 vs 4.3 ± 0.7, p = 0.02) and efficiency improvement (4.7 ± 0.5 vs 4.3 ± 0.6, p = 0.002) after high-fidelity simulation. There was also a significant decline from their expectation on self-confidence improvement (4.7 ± 0.5 vs 4.2 ± 0.7, p = 0.001). Our results therefore show, that complex high-fidelity simulation should probably be used with caution in novice participants, not to discourage them from further learning.

Immediate Platelet Inhibition Strategy for Comatose Out-of-Hospital Cardiac Arrest Survivors Undergoing Percutaneous Coronary Intervention and Mild Therapeutic Hypothermia.

Background: Comatose survivors of out-of-hospital cardiac arrest (OHCA) undergoing percutaneous coronary intervention (PCI) and target temperature management (TTM) are at increased risk of stent thrombosis (ST), partly due to delayed platelet inhibition even with more potent P2Y12 agents. We hypothesized that periprocedural cangrelor would induce immediate platelet inhibition, bridging the "P2Y12 inhibition gap". Methods: In our pilot study, we randomized 30 comatose OHCA patients undergoing PCI and TTM (32-34 °C) into cangrelor and control groups. Both groups received unfractioned heparin, acetylsalicylic acid, and ticagrelor via enteral tube. The cangrelor group also received an intravenous bolus of cangrelor followed by a 4 h infusion. Platelet inhibition was measured using VerifyNow® and Multiplate® ADP at baseline and 1, 3, 5, and 8 h post PCI. Results: Patient characteristics did not differ between groups. VerifyNow® showed significantly decreased platelet reactivity with cangrelor at 1 h (30 vs. 221 PRU; p < 0.001) and 3 h (24 vs. 180 PRU; p < 0.001), with differences at 5 and 8 h. Similarly, the proportion of patients with high on-treatment platelet reactivity (HPR) in the cangrelor group was significantly lower at 1 h (0% vs. 67%; p < 0.001) and 3 h (0% vs. 47%; p = 0.007). Multiplate® ADP was also decreased at 1 h (14 vs. 48 U; p < 0.001) and 3 h (11 vs. 42 U; p = 0.001), with no difference at 5 and 8 h. The occurrence of bleeding events was similar in both groups. Conclusions: Cangrelor safely induced immediate and profound platelet inhibition. We observed no significant drug-drug interaction with ticagrelor.

A matched case-control study on the effectiveness of extracorporeal cytokine adsorption in critically ill patients.

Extracorporeal cytokine adsorption aims to reduce cytokine levels in critically ill patients. However, little convincing data exist to support its widespread use. This retrospective study compared interleukin-6 (IL-6) levels in patients treated with or without cytokine adsorber (CytoSorb®). Intensive care patients between Jan 2017 and Dec 2021 who had at least two IL-6 measurements were included. They were divided into an adsorber group and a standard of care group. We screened 3865 patients and included 52 patients in the adsorber group and 94 patients in the standard of care group. Matching was performed and the groups were compared regarding IL-6, lactate, CRP, procalcitonin, vasopressor requirement, and mortality rate. After matching, there were 21 patients in each group. Patients had similar age, ECMO and renal replacement therapy use, baseline noradrenaline requirement, serum lactate, pH, CRP, and IL-6 levels. There were no significant differences in the time course of IL-6, lactate, CRP, procalcitonin and noradrenaline requirement between groups. Two-day and ICU mortality and Kaplan-Meier estimated survival were also comparable. In this matched case-control study no difference in IL-6, inflammatory parameters, noradrenaline requirement or mortality was observed between patients treated with adsorber or standard of care.

Effect of CytoSorb Coupled with Hemodialysis on Interleukin-6 and Hemodynamic Parameters in Patients with Systemic Inflammatory Response Syndrome: A Retrospective Cohort Study.

Excessive release of cytokines during systemic inflammatory response syndrome (SIRS) often leads to refractory hypotension and multiple organ failure with high mortality. Cytokine removal with hemoadsorption has emerged as a possible adjuvant therapy, but data on interleukin-6 (IL-6) reduction and outcomes in clinical practice are scarce. We aimed to evaluate the effect of CytoSorb hemoadsorption on laboratory and clinical outcomes in shocked patients with SIRS. We designed a retrospective analysis of all patients with SIRS treated with CytoSorb in intensive care units (ICU). IL-6, laboratory and hemodynamic parameters were analyzed at approximate time intervals during CytoSorb treatment in the whole cohort and in a subgroup with septic shock. Observed and predicted mortality rates were compared. We included 118 patients with various etiologies of SIRS (septic shock 69%, post-resuscitation shock 16%, SIRS with acute pancreatitis 6%, other 9%); in all but one patient, CytoSorb was coupled with renal replacement therapy. A statistically significant decrease in IL-6 and vasopressor index with an increase in pH and mean arterial pressure was observed from 6 h onward. The reduction of lactate became significant at 48 h. Results were similar in a subgroup of patients with septic shock. Observed ICU and in-hospital mortalities were lower than predicted by Sequential Organ Failure Assessment (SOFA) (61% vs. 79%, p = 0.005) and Acute Physiology and Chronic Health Evaluation (APACHE) II (64% vs. 78%, p = 0.031) scores. To conclude, hemoadsorption in shocked patients with SIRS was associated with a rapid decrease in IL-6 and hemodynamic improvement, with improved observed vs. predicted survival. These results need to be confirmed in a randomized study.

Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Mechanism and extent of myocardial injury associated with out-of-hospital cardiac arrest.

AIM: We investigated the mechanism and extent of myocardial injury associated with out-of-hospital cardiac arrest (OHCA). METHODS: 159 consecutive patients undergoing immediate coronary angiography after OHCA were included and divided into groups with acute culprit lesion (A), stable obstructive coronary disease (B) and non-obstructive or absent coronary disease (C). Post-resuscitation electrocardiogram (ECG) and serial measurements of high sensitivity cardiac troponin I (cTnI) were compared. RESULTS: ST-elevation myocardial infarction (STEMI) was documented in 65% in group A, 26% in group B, and 11% in group C (p < 0.001). cTnI, which was 0.88 ng/mL, 0.44 ng/mL and 0.19 ng/mL in groups A, B and C on admission (p < 0.001), increased to a maximum of 63.96 ng/mL, 10.00 ng/mL and 2.35 ng/mL, respectively (p < 0.001). Within the group A, cTnI was significantly larger in patients with acute occlusion than in patients with spontaneous reperfusion at initial angiography. Within groups B and C, peak cTnI correlated with duration of resuscitation, number of defibrillations and cumulative adrenaline (epinephrine) dose. If admission cTnI exceeded 0.46 ng/mL and STEMI was present in ECG, sensitivity for detection of acute culprit lesion was 88% and specificity 54%. CONCLUSIONS: Significant myocardial injury associated with OHCA occurs in the presence of acute culprit lesion while extent of myocardial injury in stable or absent coronary disease is significantly smaller and correlates with the duration and intensity of cardiac resuscitation. Admission cTnI, although combined with post-resuscitation ECG, have insufficient accuracy to securely predict presence of acute culprit lesion.