ABSTRACT
Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.
ABSTRACT
Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.
ABSTRACT
Objectives: In COVID-19 associated acute respiratory distress syndrome (ARDS) requiring VV-ECMO, ventilator-associated-pneumonia (VAP), pulmonary aspergillosis and viral reactivations are observed frequently, but there is only little knowledge on incidence, onset and causative pathogens. This study analyzes frequency of VAP, pulmonary aspergillus infections, and viral reactivations in a large cohort of patients with ARDS treated with VV-ECMO due to either COVID-19 or Influenza. Method(s): Retrospective analysis of all consecutively patients at the University Hospital Regensburg requiring VVECMO due to COVID-19 (March 2020 and May 2022) or Influenza (May 2012 and December 2022). VAP was diagnosed according to current guidelines. Pulmonary Aspergillosis met criteria of probable COVID-associated Aspergillosis according to current guidelines. Result(s): 147 patients (age (median [IQR]) 55.3 [48.7 - 61.7], SOFA at VV-ECMO initiation 9 [8 - 12], 23 [14 - 38] days on VV-ECMO) suffering from COVID-19 and 72 influenza patients (age 55.3 [46 - 61.3], SOFA at VV-ECMO initiation 13 [10 - 15], 16 [10 - 23] days on VV-ECMO) were included in the analysis. Pulmonary superinfections were more frequent in COVID-19 than in influenza (VAP: 61% vs. 39%, pulmonary Aspergillosis: 33% vs. 22%, CMV reactivation: 19% vs. 4%, HSV reactivation: 49% vs. 26%.) The first episode of VAP in COVID-19 and Influenza was detected 2 days [1 - 15] after and 1 day (-3 - 22) before ECMO initiation, respectively. First VAP-episode in COVID-19 were mainly caused by Klebsiella spp. (29%,), Staphylococcus aureus (27%) and E. coli (11%). Further VAP-episodes (30% in COVID-19) and relapses of VAP were mainly caused by Klebsiella spp. (53%, 64%, respectively). In Influenza, VAP was mainly caused by Staphylococcus aureus (28%) and Streptococcus pneumoniae(28%), further VAP episodes were not observed. Conclusion(s): Superinfections were common in patients treated with VV-ECMO and occur more frequently in COVID-19 ARDS compared to Influenza. VAP occurs early and may significantly contribute to the need of VV-ECMO. Therefore, a meticulous routine microbiologic workup is advisable. The observed differences in the spectrum of secondary infectious agents in COVID19 compared to Influenza are not understood yet.
ABSTRACT
Introduction: The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyper-infammation and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinfammation, particularly in severely ill patients. Method(s): We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defned in a training cohort and subsequently validated in a second cohort (n=45). Morphologic aberrations were further analyzed by electron microscopy (EM) and fow cytometry of lymphocytes was performed. Result(s): We included 45 COVID-19 patients in our study (median age 58 years;82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80% of patients) and monocytes (91%). 84%, 98%, and 98% of patients exhibited aberrations in granulopoiesis, erythropoiesis and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confrmed the multi-lineage aberrations already seen by light microscopy. Conclusion(s): The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defned a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the he-matologic system during the clinical course of COVID-19 patients.
ABSTRACT
Objective: Hemorrhage and thrombotic events are common issues during extracorporeal membrane oxygenation (ECMO). Furthermore, severe COVID-19 infection is frequently associated with coagulopathy, leading to lung embolism and influencing ECMO oxygenator functionality. Therefore, providing ECMO therapy in those patients might be challenging. We aimed to identify differences in coagulation parameters between patients with COVID-19 and non- COVID-19 viral pneumonia on venovenous (VV) ECMO. Methods: A retrospective single-center study on patients supported with VV ECMO for acute respiratory failure associated with COVID-19 or non-COVID-19 viral pneumonia was performed. Coagulation parameters at different time points were analyzed. Results: Between January 2018 and December 2020, 68 patients, including 31 with COVID-19 pneumonia and 37 with non-COVID-19 viral pneumonia, were eligible for the analysis. Activated partial thromboplastin time (aPTT) on day one and international normalized ratio (INR) on day one and five were significantly lower in the COVID-19 group. At all respective time points, COVID-19 patients showed higher levels of platelets and fibrinogen. In contrast, non-COVID-19 patients had greater d-dimer levels on day five. Additionally, significant differences in factor VIII and XIII activity levels were observed (Figure 1). ECMO weaning rate did not differ significantly between the groups. Conclusions: Coagulation parameters before and during the first days of ECMO for acute respiratory failure differed significantly between patients with COVID-19 and non-COVID-19 viral pneumonia. Monitoring coagulation parameters in order to prevent hemostatic complications will play a crucial role in COVID-19 patients and especially anticoagulation management will be of particular importance and should therefore be further investigated in future studies.