Anti-Xa activity and hemorrhagic events under extracorporeal membrane oxygenation (ECMO): a multicenter cohort study.

BACKGROUND: Hemorrhagic events remain a major concern in patients under extracorporeal membrane oxygenation (ECMO) support. We tested the association between anticoagulation levels and hemorrhagic events under ECMO using anti-Xa activity monitoring. METHODS: We performed a retrospective multicenter cohort study in three ECMO centers. All adult patients treated with veno-venous (VV)- or veno-arterial (VA)-ECMO in 6 intensive care units between September 2017 and August 2019 were included. Anti-Xa activities were collected until a hemorrhagic event in the bleeding group and for the duration of ECMO in the non-bleeding group. All dosages were averaged to obtain means of anti-Xa activity for each patient, and patients were compared according to the occurrence or not of bleeding. RESULTS: Among 367 patients assessed for eligibility, 121 were included. Thirty-five (29%) presented a hemorrhagic complication. In univariate analysis, anti-Xa activities were significantly higher in the bleeding group than in the non-bleeding group, both for the mean anti-Xa activity (0.38 [0.29-0.67] vs 0.33 [0.22-0.42] IU/mL; p = 0.01) and the maximal anti-Xa activity (0.83 [0.47-1.46] vs 0.66 [0.36-0.91] IU/mL; p = 0.05). In the Cox proportional hazard model, mean anti-Xa activity was associated with bleeding (p = 0.0001). By Kaplan-Meier analysis with the cutoff value at 0.46 IU/mL obtained by ROC curve analysis, the probability of survival under ECMO without bleeding was significantly lower when mean anti-Xa was > 0.46 IU/mL (p = 0.0006). CONCLUSION: In critically ill patients under ECMO, mean anti-Xa activity was an independent risk factor for hemorrhagic complications. Anticoagulation targets could be revised downward in both VV- and VA-ECMO.

Effects of high oxygen tension on healthy volunteer microcirculation.

INTRODUCTION: Previous studies have highlighted hyperoxia-induced microcirculation modifications, but few have focused on hyperbaric oxygen (HBO) effects. Our primary objective was to explore hyperbaric hyperoxia effects on the microcirculation of healthy volunteers and investigate whether these modifications are adaptative or not. METHODS: This single centre, open-label study included 15 healthy volunteers. Measurements were performed under five conditions: T0) baseline value (normobaric normoxia); T1) hyperbaric normoxia; T2) hyperbaric hyperoxia; T3) normobaric hyperoxia; T4) return to normobaric normoxia. Microcirculatory data were gathered via laser Doppler, near-infrared spectroscopy and transcutaneous oximetry (PtcO2). Vascular-occlusion tests were performed at each step. We used transthoracic echocardiography and standard monitoring for haemodynamic investigation. RESULTS: Maximal alterations were observed under hyperbaric hyperoxia which led, in comparison with baseline, to arterial hypertension (mean arterial pressure 105 (SD 12) mmHg vs 95 (11), P < 0.001) and bradycardia (55 (7) beats·min⁻¹ vs 66 (8), P < 0.001) while cardiac output remained unchanged. Hyperbaric hyperoxia also led to microcirculatory vasoconstriction (rest flow 63 (74) vs 143 (73) perfusion units, P < 0.05) in response to increased PtcO2 (104.0 (45.9) kPa vs 6.3 (2.4), P < 0.0001); and a decrease in laser Doppler parameters indicating vascular reserve (peak flow 125 (89) vs 233 (79) perfusion units, P < 0.05). Microvascular reactivity was preserved in every condition. CONCLUSIONS: Hyperoxia significantly modifies healthy volunteer microcirculation especially during HBO exposure. The rise in PtcO2 promotes an adaptative vasoconstrictive response to protect cellular integrity. Microvascular reactivity remains unaltered and vascular reserve is mobilised in proportion to the extent of the ischaemic stimulus.

SARS-CoV-2 Versus Influenza-associated Acute Respiratory Distress Syndrome Requiring Veno-venous Extracorporeal Membrane Oxygenation Support.

No study has compared patients with COVID-19-related refractory ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO) to a relevant and homogenous control population. We aimed to compare the outcomes, the clinical characteristics, and the adverse effects of COVID-19 patients to a retrospective cohort of influenza patients. This retrospective case-control study was conducted in the ICUs of Lille and Rouen University Hospitals between January 2014 and May 2020. Two independent cohorts of patients with ARDS requiring V-V ECMO infected with either COVID-19 (n = 30) or influenza (n = 22) were compared. A 3-month follow-up was completed for all patients. Median age of COVID-19 and influenza patients was similar (57 vs. 55 years; p = 0.62). The 28-day mortality rate did not significantly differ between COVID-19 (43.3%) and influenza patients (50%, p = 0.63). There was no significant difference considering the cumulative incidence of ECMO weaning, hospital discharge, and 3-month survival. COVID-19 patients had a lower SAPS II score (58 [37-64] vs. 68 [52-83]; p = 0.039), a higher body mass index (33 [29-38] vs. 30 [26-34] kg/m2; p = 0.05), and were cannulated later (median delay between mechanical support and V-V ECMO 6 vs. 3 days, p = 0.004) compared with influenza patients. No difference in overall adverse events was observed between COVID-19 and influenza patients (70% vs. 95.5% respectively; p = 0.23). Despite differences in clinical presentation before V-V ECMO implantation, 28-day and 3-month mortality rate did not differ between COVID-19 and influenza patients. Considering the lack of specific treatment for COVID-19, V-V ECMO should be considered as a relevant rescue organ support.