key: cord-0891615-by28excm
authors: Soumagne, Thibaud; Winiszewski, Hadrien; Besch, Guillaume; Mahr, Nicolas; Senot, Thomas; Costa, Patricia; Grillet, Franck; Behr, Julien; Mouhat, Basile; Mourey, Guillaume; Fournel, Alexandra; Meneveau, Nicolas; Samain, Emmanuel; Capellier, Gilles; Piton, Gaël; Pili-Floury, Sébastien
title: Pulmonary embolism among critically ill patients with ARDS due to COVID-19
date: 2020-09-17
journal: Respir Med Res
DOI: 10.1016/j.resmer.2020.100789
sha: 46cc467f3f33211823565f58fab9a6d08ddd4d39
doc_id: 891615
cord_uid: by28excm

nan

Recent reports have suggested that patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) have high incidence of acute pulmonary embolism (APE) [1, 2] . However, specific information characterizing these patients are scarce. We therefore aimed to investigate clinical, radiological and ventilation characteristics associated with APE among critically ill patients with COVID-19 ARDS.

All consecutive patients admitted between March 17 and April 5, 2020 in the ICUs at the Besançon University Hospital meeting the criteria of ARDS (Berlin definition) [3] , with laboratory-confirmed SARS-CoV-2 infection and available computed tomography pulmonary angiography (CTPA) (performed during ICU stay according to the course of the clinical respiratory status) were enrolled. Relevant clinical, laboratory data, ventilator settings and respiratory-system mechanics were obtained from medical records. In the context of the Forty-four patients with COVID-19 ARDS were included. The mean age was 63.8 ± 12.0 years, 82% were male and only one patient was current smoker. Hypertension (50%), diabetes (27%), obesity (49%) and cardiovascular disease (20%) were the most frequent comorbidities.

Mean sequential organ failure assessment (SOFA) was 4.4 ± 1.7 and all patients had moderate to severe ARDS.

Seventeen patients (39%) had confirmed APE. Demographic characteristics, comorbidities and SOFA were similar between patients with and without APE (table 1A) . Regarding COVID-19 CT pattern, all patients had bilateral lesions and more than half had more than 50% of affected lung parenchyma. There was no relationship between CT pattern or disease severity and the presence of APE (table 1A) . Most patients with APE had only segmental emboli (59%) and none had proximal emboli. In addition, none of the patients exhibited acute right heart failure.

At the time of APE diagnosis, no differences were found between both groups for the use of anticoagulant therapy, invasive mechanical ventilation, neuromuscular blockers, inhaled pulmonary vasodilators, renal replacement and vasopressor (table 1B). In addition, ventilator settings, respiratory-system mechanics including lung compliance and PaO2/FiO2 ratio did not differ in patients with and without APE. However, patients with APE had significantly more prone positioning sessions (table 1B) . Furthermore, APE was associated with higher levels of D-dimer but not with higher levels of troponin and BNP. Finally, mortality and outcome at 28 days did not differ between patients with and without APE (table 1A) .

Recent studies have reported that COVID-19 in critically ill patients was associated with a high incidence of APE [1, 2, 4] . This suggest that CTPA should probably be performed systematically in patients with COVID-19 ARDS at ICU admission and in case of respiratory worsening during ICU stay. Several mechanisms might explain this high frequency. Prone positioning increases intra-abdominal pressure and therefore can lead to inferior vena cava compression and lower limb venous congestion [5] . It may therefore be possible that the higher rate of prone positioning sessions in ARDS due to COVID-19 could be associated with the occurrence of APE consecutive to inferior vena cava compression. Another possible mechanism is that the alternance of supine and prone position at regular intervals, could Page 4 of 8 J o u r n a l P r e -p r o o f 4 promote multiple successive embolization from peripheral clots. Moreover, the average number of sessions in our study was higher than in non-COVID-19 ARDS [6] . In addition, mechanical ventilation with high PEEP level increases pulmonary vascular resistance and contributes to right ventricular dysfunction and venous return impairment [7, 8] . Another important feature of our study is that patients with and without APE had similar PaO2/FiO2 ratio concurrently with similar lung static compliance. This might indicate that APE seems not to account significantly for additional gas exchange impairment among patients with COVID-19 ARDS.

Finally, the fact that all patients with APE had segmental emboli and that none had proximal embolism could suggest localized thrombus formation in the pulmonary arteries (i.e. in situ thrombosis). This reinforces the hypothesis that COVID-19 is associated with micro-vascular rather than macro vascular impairment [11] .

5 Limitations of the current study include the relatively small number of patients, the singlecenter setting and its observational nature and the absence of multivariate analysis regarding risk factors for APE.

To conclude, we found that higher rate of prone positioning sessions could be associated with pulmonary embolism among patients with COVID-19 ARDS. Further studies are needed to confirm these results.

Values are mean ± standard deviation or number of patients (percentage of total). Abbreviations used: APE: acute pulmonary embolism, ARDS: acute respiratory distress syndrome, CVD: cardiovascular disease, DVT: deep venous thrombosis, SOFA: sequential organ failure assessment *Legend of CT pattern [12] : stage 1 (early): mainly ground glass opacities (GGO) with partial crazy-paving pattern; stage 2 (progressive): GGO extended to more pulmonary lobes with more crazy-paving pattern and consolidation; stage 3 (peak): mainly consolidation with decreased ratio of GGO and crazy-paving pattern; stage 4 (absorption) : consolidation is partially absorbed without any crazy-paving pattern. 

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Acute respiratory distress syndrome: the Berlin Definition

Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients

Beneficial hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome

Prone positioning in severe acute respiratory distress syndrome

Effects of high PEEP and fluid administration on systemic circulation, pulmonary microcirculation, and alveoli in a canine model

Cyclic changes in right ventricular output impedance during mechanical ventilation

The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease

Traitement anticoagulant pour la prévention du risque thrombotique chez un patient hospitalisé avec COVID-19 et surveillance de l'hémostase

The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications

Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia