Incidence of Heparin Resistance and Heparin Failure in Patients Receiving Extracorporeal Membrane Oxygenation - an Exploratory Retrospective Analysis.

BACKGROUND: Unfractionated heparin (UFH) is used in most centres for extracorporeal membrane oxygenation (ECMO) anticoagulation. When standard doses do not achieve desired target values, heparin resistance is reported, most commonly defined as doses of UFH >35,000 IU/day. OBJECTIVES: To study the incidence of heparin resistance and its association with thromboembolic complications in patients requiring ECMO support. METHODS: In this observational cohort study, we included adults who received venovenous (VV), venoarterial (VA) ECMO, and extracorporeal CO2-removal (ECCO2R) between January 2010 and May 2022. Main risk factor was heparin resistance (UFH >35,000 IU/day or >20 IU/kg/h), the outcome was thromboembolism. Multivariable Poisson regression was used to estimate the effects of heparin resistance, adjusted for several clinical variables on the thromboembolism rate per 100 ECMO patient-days. RESULTS: Of the 197 patients included, 33 (16.8%) required UFH >35,000 IU/day, and 14 (7.1%) required >20 IU/kg/h. Thromboembolic complications occurred at a rate of 5.89/100 ECMO days. Heparin resistance was not associated with thromboembolic events (incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.14 to 5.82), whereas COVID-19 (IRR 2.33, CI 1.4 to 3.96, p<0.001) and ECMO type (VA ECMO: IRR 2.29, CI 1.34 to 3.92, p=0.002; ECCO2R: IRR 2.89, CI 1.46 to 5.59, p=0.002; reference VV ECMO) were significantly associated with the risk of thromboembolic events. CONCLUSIONS: A significant proportion of patients fulfilled the common definition of heparin resistance. However, this did not influence the occurrence of thromboembolic events.

The Impact of Chronic Oral Beta-Blocker Intake on Intravenous Bolus Landiolol Response in Hospitalized Intensive Care Patients with Sudden-Onset Supraventricular Tachycardia-A Post Hoc Analysis of a Cross-Sectional Trial.

Background: Landiolol, a highly cardioselective agent with a short half-life (2.4-4 min), is commonly used as a perfusor or bolus application to treat tachycardic arrhythmia. Some small studies suggest that prior oral ß-blocker use results in a less effective response to intravenous ß-blockers. Methods: This study investigated whether prior chronic oral ß-blocker (Lß) or no prior chronic oral ß-blocker (L-) intake influences the response to intravenous push-dose Landiolol in intensive care patients with acute tachycardic arrhythmia. Results: The effects in 30 patients (67 [55-72] years) were analyzed, 10 (33.3%) with and 20 (66.7%) without prior oral ß-blocker therapy. Arrhythmias were diagnosed as tachycardic atrial fibrillation in 14 patients and regular, non-fluid-dependent, supraventricular tachycardia in 16 cases. Successful heart rate control (Lß 4 vs. L- 7, p = 1.00) and rhythm control (Lß 3 vs. L- 6, p = 1.00) did not significantly differ between the two groups. Both groups showed a significant decrease in heart rate when comparing before and after the bolus administration, without significant differences between the two groups (Lß -26/min vs. L- -33/min, p = 0.528). Oral ß-blocker therapy also did not influence the change in mean arterial blood pressure after Landiolol bolus administration (Lß -5 mmHg vs. L- -4 mmHg, p = 0.761). Conclusions: A prior chronic intake of ß-blockers neither affected the effectiveness of push-dose Landiolol in heart rate or rhythm control nor impacted the difference in heart rate or mean arterial blood pressure before and after the Landiolol boli.

Anticoagulation with argatroban using hemoclot™ targets is safe and effective in CARDS patients receiving venovenous extracorporeal membrane oxygenation: An exploratory bi-centric cohort study.

Direct thrombin inhibitors, including argatroban, are increasingly used for anticoagulation during venovenous extracorporeal membrane oxygenation (VV ECMO). In many centers activated partial thromboplastin time (aPTT) is used for monitoring, but it can be affected by several confounders. The aim of this study was to evaluate the safety and efficacy of anticoagulation with argatroban titrated according to diluted thrombin time targets (hemoclot™ assay) compared to anti-Xa guided anticoagulation with unfractionated heparin (UFH). METHODS: This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4-0.6 µg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2-0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range). RESULTS: From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44-2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26-0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23-54 %) vs. 46 % (37 %-57 %), p = 0.45). CONCLUSION: Anticoagulation with argatroban according to hemoclot™ targets (0.4-0.6 µg/ml) compared to antiXa guided UFH (0.2-0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO.

Prevalence of FXII-Deficiency and Its Relevance to Monitoring Anticoagulation in Adults Receiving Extracorporeal Membrane Oxygenation.

During extracorporeal membrane oxygenation (ECMO) blood is exposed to artificial surfaces, resulting in contact activation of the intrinsic coagulation pathway initiated by coagulation factor XII (FXII). Little is known about the prevalence of acquired FXII-deficiency, especially during ECMO. The primary outcome was the prevalence of acquired FXII-deficiency (FXII activity <60%) during ECMO. Secondary outcomes included differences in hemorrhagic/thromboembolic complications, doses of unfractionated heparin administered, and time points of anticoagulation within target ranges between patients with and without FXII-deficiency. Of 193 adults receiving ECMO therapy between 2013 and 2021, FXII testing was performed in 64 (33%) patients. Of these, 89% ( n = 57) had an acquired FXII-deficiency. Median complication-free intervals were not different between patients with and without acquired FXII-deficiency (bleeding: 28 days [6-145] vs. 12 days [11-not available], p = 0.85; thromboembolism: 16 days [8-54] vs. 13 days [3-15], p = 0.053). Patients with acquired FXII-deficiency received less heparin (16,554 IU/day vs. 25,839 IU/day; p = 0.009) and were less likely to be within aPTT-target ranges (23.1% [14.3%-36.4%] vs. 37.8% [33.7%-58.3%], p = 0.005). Acquired FXII-deficiency is common during ECMO and may affect monitoring of anticoagulation. The impact of FXII-activity on complications needs to be determined in future studies.

Prevalence and Impact of Lupus Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation.

BACKGROUND: Monitoring of blood coagulation is essential in ECMO patients. We investigated the prevalence of lupus anticoagulant (LA) and its association with coagulation testing and hemostaseologic complications in patients treated with ECMO. METHODS: This is a retrospective analysis including adult patients who received ECMO at a medical intensive care unit at the Medical University of Vienna. The primary outcome was the prevalence of LA. Secondary outcomes included conditions associated with LA positivity, rates of bleeding and thromboembolic events, as well as the proportions of aPTT and antiXa measurements within the target range. RESULTS: Between 2013 and 2021 193 patients received ECMO, in 62 (32%) of whom LA diagnostics were performed. Twenty-two (35%) patients tested positive. LA positive patients had more frequently received VV ECMO (77.3% vs 34.3%; p = 0.002), were more frequently diagnosed with viral respiratory infections (SARS-CoV2: 45.5% vs 20%; p = 0.041, influenza virus: 22.7% vs 0%; p = 0.003), had a longer ECMO treatment duration (25 vs 10 days; p = 0.011) and a longer ICU stay (48 vs 25 days; p = 0.022), but similar rates of bleeding and thromboembolic events.

Hemodynamic and Rhythmologic Effects of Push-Dose Landiolol in Critical Care-A Retrospective Cross-Sectional Study.

BACKGROUND: The highly ß1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. METHODS: We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring. RESULTS: Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130-150) vs. 105 (100-125) bpm, p < 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO2 after the bolus application did not differ significantly. No serious adverse events were seen. CONCLUSIONS: Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted.

The Feasibility of Ultra-Sensitive Phonocardiography in Acute Chest Pain Patients of a Tertiary Care Emergency Department (ScorED Feasibility Study).

BACKGROUND: Thoracic pain is one of the most frequent chief complaints at emergency departments (EDs). However, a respective workup in cases without clear electrocardiographic signs is complex. In addition, after having ruled out acute coronary syndrome (ACS), patients are often left with an unclear etiology of their symptoms. Ultra-sensitive phonocardiography is already used to rule out stable coronary artery disease (CAD); however, its feasibility in an ED-setting remains unknown. METHODS: We prospectively used ultra-sensitive phonocardiography via the CADScor®System to measure hemodynamically stable patients with the chief complaint of chest pain during routine waiting times at a high-volume tertiary ED. RESULTS: A total of 101 patients (49% male; 94% Caucasian; 61 (51-71) years; BMI 28.3 (24.2-31.6)) were enrolled. Patient workflow was not hindered, and no adverse events were recorded. In 80% of cases, a score was successfully calculated, with 74% at the first, 5% at the second, and 1% at the third attempt. Feasibility was judged as 9.0 (±1.8) by the patients, and 8.9 (±2.6) by the investigators on a 10-point Likert scale. CONCLUSIONS: Ultra-sensitive phonocardiography was found to be feasible in acute chest pain patients presenting to a tertiary ED. Thus, the CAD score measured during routine waiting times could potentially serve as an additional tool in a diagnostic pathway for thoracic pain.