Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study

J-L Diehl, N Peron, R Chocron, B Debuc, E Guerot, C Hauw-Berlemont, B Hermann, J L Augy, R Younan, A Novara, J Langlais, L Khider, N Gendron, G Goudot, J-F Fagon, T Mirault, D M Smadja, J-L Diehl, N Peron, R Chocron, B Debuc, E Guerot, C Hauw-Berlemont, B Hermann, J L Augy, R Younan, A Novara, J Langlais, L Khider, N Gendron, G Goudot, J-F Fagon, T Mirault, D M Smadja

Abstract

Rationale: COVID-19 ARDS could differ from typical forms of the syndrome.

Objective: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics.

Methods: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]).

Measurements and main results: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively.

Conclusions: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Keywords: ARDS; COVID-19; Physiological dead-space; Ventilatory ratio.

Conflict of interest statement

All the authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Correlations between different respiratory parameters. a Correlation between physiological dead space and ventilatory ratio in 22 COVID-19 ARDS patients studied early after intubation and initiation of protective ventilation. b Correlation between CO2 total body production and ventilatory ratio

References

    1. Gattinoni L, Coppola S, Cressoni M, Busana M, Chiumello D. Covid-19 does not lead to a « typical » Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202003-0817LE.
    1. Liu X, Liu X, Xu Y, Xu Z, Huang Y, Chen S, et al. Ventilatory Ratio in hypercapnic mechanically ventilated patients with COVID-19 associated ARDS. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202002-0373LE.
    1. Pan C, Chen L, Lu C, Zhang W, Xia J-A, Sklar MC, et al. Lung recruitability in SARS-CoV-2 associated Acute Respiratory Distress Syndrome: a single-center, observational study. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202003-0527LE.
    1. Beloncle FM, Pavlovsky B, Desprez C, Fage N, Olivier P-Y, Asfar P, et al. Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome. Ann Intensive Care. 2020;10(1):55. doi: 10.1186/s13613-020-00675-7.
    1. Mauri T, Spinelli E, Scotti E, Colussi G, Basile MC, Crotti S, et al. Potential for lung recruitment and ventilation-perfusion mismatch in patients with the acute respiratory distress syndrome from coronavirus disease. Crit Care Med. 2020 doi: 10.1097/CCM.0000000000004386.
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
    1. Han H, Yang L, Liu R, Liu F, Wu K-L, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 doi: 10.1515/cclm-2020-0188.
    1. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 doi: 10.1016/j.kint.2020.03.005.
    1. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J Virol. 2020 doi: 10.1128/JVI.00127-20.
    1. Copin M-C, Parmentier E, Duburcq T, Poissy J, Mathieu D, Lille COVID-19 ICU and Anatomopathology Group Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection. Intensive Care Med. 2020 doi: 10.1007/s00134-020-06057-8.
    1. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2015432.
    1. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–1418. doi: 10.1016/S0140-6736(20)30937-5.
    1. Smadja DM, Guerin CL, Chocron R, Yatim N, Boussier J, Gendron N, et al. Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis. 2020 doi: 10.1007/s10456-020-09730-0.
    1. Mercat A, Richard J-CM, Vielle B, Jaber S, Osman D, Diehl J-L, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:646–655. doi: 10.1001/jama.299.6.646.
    1. Lescure F-X, Bouadma L, Nguyen D, Parisey M, Wicky P-H, Behillil S, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30200-0.
    1. Levy M, Bonnet D, Mauge L, Celermajer DS, Gaussem P, Smadja DM. Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. PLoS ONE. 2013;8:e65114. doi: 10.1371/journal.pone.0065114.
    1. Goon PKY, Boos CJ, Lip GYH. Circulating endothelial cells: markers of vascular dysfunction. Clin Lab. 2005;51:531–538.
    1. Smadja DM, Mauge L, Nunes H, d’Audigier C, Juvin K, Borie R, et al. Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis. Angiogenesis. 2013;16:147–157. doi: 10.1007/s10456-012-9306-9.
    1. Woywodt A, Blann AD, Kirsch T, Erdbruegger U, Banzet N, Haubitz M, et al. Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol. J Thromb Haemost. 2006;4:671–677. doi: 10.1111/j.1538-7836.2006.01794.x.
    1. Papazian L, Aubron C, Brochard L, Chiche J-D, Combes A, Dreyfuss D, et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care. 2019;9:69. doi: 10.1186/s13613-019-0540-9.
    1. Marini JJ. Dealing with the CARDS of COVID-19. Crit Care Med. 2020 doi: 10.1097/CCM.0000000000004427.
    1. Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet J-F, Eisner MD, et al. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002;346:1281–1286. doi: 10.1056/NEJMoa012835.
    1. Lucangelo U, Bernabè F, Vatua S, Degrassi G, Villagrà A, Fernandez R, et al. Prognostic value of different dead space indices in mechanically ventilated patients with acute lung injury and ARDS. Chest. 2008;133:62–71. doi: 10.1378/chest.07-0935.
    1. Fengmei G, Jin C, Songqiao L, Congshan Y, Yi Y. Dead space fraction changes during PEEP titration following lung recruitment in patients with ARDS. Respir Care. 2012;57:1578–1585. doi: 10.4187/respcare.01497.
    1. Kallet RH, Zhuo H, Liu KD, Calfee CS, Matthay MA, National Heart Lung and Blood Institute ARDS Network Investigators The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial. Respir Care. 2014;59:1611–1618. doi: 10.4187/respcare.02593.
    1. Beitler JR, Thompson BT, Matthay MA, Talmor D, Liu KD, Zhuo H, et al. Estimating dead-space fraction for secondary analyses of acute respiratory distress syndrome clinical trials. Crit Care Med. 2015;43:1026–1035. doi: 10.1097/CCM.0000000000000921.
    1. Sinha P, Calfee CS, Beitler JR, Soni N, Ho K, Matthay MA, et al. Physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2019;199:333–341. doi: 10.1164/rccm.201804-0692OC.
    1. Gogniat E, Ducrey M, Dianti J, Madorno M, Roux N, Midley A, et al. Dead space analysis at different levels of positive end-expiratory pressure in acute respiratory distress syndrome patients. J Crit Care. 2018;45:231–238. doi: 10.1016/j.jcrc.2018.01.005.
    1. van Meenen DM, Roozeman JP, Serpa Neto A, Pelosi P, de Abreu M, Horn J, et al. Associations between changes in oxygenation, dead space and driving pressure induced by the first prone position session and mortality in patients with acute respiratory distress syndrome. J Thorac Dis. 2019;11:5004–5013. doi: 10.21037/jtd.2019.12.38.
    1. Ospina-Tascón GA, Bautista DF, Madriñán HJ, Valencia JD, Bermúdez WF, Quiñones E, et al. Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study. Ann Intensive Care. 2020;10:35. doi: 10.1186/s13613-020-00651-1.
    1. MARS Consortium. Morales-Quinteros L, Schultz MJ, Bringué J, Calfee CS, Camprubí M, et al. Estimated dead space fraction and the ventilatory ratio are associated with mortality in early ARDS. Ann Intensive Care. 2019;9:128. doi: 10.1186/s13613-019-0601-0.
    1. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 doi: 10.1007/s00134-020-06062-x.
    1. Moussa MD, Santonocito C, Fagnoul D, Donadello K, Pradier O, Gaussem P, et al. Evaluation of endothelial damage in sepsis-related ARDS using circulating endothelial cells. Intensive Care Med. 2015;41:231–238. doi: 10.1007/s00134-014-3589-9.
    1. Greene R, Lind S, Jantsch H, Wilson R, Lynch K, Jones R, et al. Pulmonary vascular obstruction in severe ARDS: angiographic alterations after i.v. fibrinolytic therapy. Am J Roentgenol. 1987;148:501–508. doi: 10.2214/ajr.148.3.501.
    1. Tomashefski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983;112:112–126.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera