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Rescue fibrinolysis in suspected massive pulmonary embolism during SARS-CoV-2 pandemic

  • André Ly
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France

    Univ Paris Est Creteil, Faculté de Santé, F-94010 Créteil, France
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  • Claire Alessandri
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France
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  • Elena Skripkina
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France
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  • Arnaud Meffert
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France
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  • Simon Clariot
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France

    Univ Paris Est Creteil, Faculté de Santé, F-94010 Créteil, France
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  • Quentin de Roux
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France

    U955-IMRB, Equipe 03 “Pharmacologie et Technologies pour les Maladies Cardiovasculaires (PROTECT)”, Inserm, Univ Paris Est Creteil (UPEC), Ecole Nationale Vétérinaire d’Alfort (EnVA), F-94700 Maisons-Alfort, France
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  • Olivier Langeron
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France

    Univ Paris Est Creteil, Faculté de Santé, F-94010 Créteil, France
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  • Nicolas Mongardon
    Correspondence
    Corresponding author at: Service d’Anesthésie-Réanimation Chirurgicale, CHU Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France.
    Affiliations
    Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, F-94010 Créteil, France

    Univ Paris Est Creteil, Faculté de Santé, F-94010 Créteil, France

    U955-IMRB, Equipe 03 “Pharmacologie et Technologies pour les Maladies Cardiovasculaires (PROTECT)”, Inserm, Univ Paris Est Creteil (UPEC), Ecole Nationale Vétérinaire d’Alfort (EnVA), F-94700 Maisons-Alfort, France

    AfterROSC Research Group, F-75014 Paris, France
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      To the Editor:
      We report on 6 systemic fibrinolysis uses for suspected PE among 53 cases with severe coronavirus 2 (SARS-CoV-2) pneumonia managed in our intensive care unit (ICU) since March 23 2020 (Table 1).
      Table 1Characteristics of patients treated with rescue systemic fibrinolysis.
      Patient123–13–245
      Age (years)674163635546
      SexMaleMaleMaleMaleMaleMale
      BMI (kg/m2)26.225.827.227.220.724.3
      SAPS II262247472831
      Invasive MVNoYesYesYesYesYes
      Number of PP sessions011114
      PaO2/FiO2 ratio (mmHg)808580919462
      PaCO2 (mmHg)365676465353
      Respiratory system compliance (ml/cmH2O)NA3330161710
      Driving pressure (cmH2O)NA1215252316
      NE dose (μg/kg/min)2.940.221.062.050.253.46
      VV-ECMONoNoNoNoNoYes
      Antithrombotic regimenCurative LMWHPreventive LMWHCurative LMWHCurative UFHCurative LMWHCurative UFH
      D-Dimer (ng/ml)2281NA4208420877949943
      PR (%)646777717080
      Platelet count (Giga/l)355194391403199176
      Fibrinogen (g/l)7.78.47.06.46.54.8
      Reason for fibrinolysisCACAShockShockShockShock
      ImagingACPACP + CFV thrombosisACPACPACPACP
      ComplicationsFemoral hemorrhage: 8 RBC transfusedJugular + femoral hemorrhage: 3 RBC transfused
      Immediate effectNo ROSCNo ROSC60% NE decrease in 1 hPersistent shockPersistent shock80% NE decrease in 3 h
      Vital statusDeathDeathDeath 3 days laterDeath 2 days laterDeath 3 days laterAlive at 7 days
      All clinical characteristics are reported before initiation of rescue therapy.
      Abbreviations: ACP: acute cor pulmonale, BMI: body mass index, CA: cardiac arrest, CFV: common femoral vein, h: hour, LMWH: low molecular weight heparin, MV: mechanical ventilation, NA: not applied, NE: norepinephrine, PC: platelet concentrate, PE: pulmonary embolism, PP: prone position, PR: prothrombin ratio, RBC: red blood cell, ROSC: return of spontaneous circulation, SAPS II: simplified acute physiology score II, UFH: unfractioned heparin, VV-ECMO: veno-venous extracorporeal membrane oxygenation.
      PE was suspected in 5 patients on combination of obstructive shock or unexpected cardiac arrest (CA) and acute cor pulmonale (ACP) on transthoracic echocardiography. Systemic fibrinolysis consisted of 100 mg Alteplase (Boehringer Ingelheim, France) intravenously. The conditions of 2 patients (#3–1 and #5) with obstructive shock improved, with a decreased norepinephrine dose shortly after fibrinolysis. However, another rescue therapy for the second hit did not succeed (#3–2), leading to multi-organ failure despite veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support. Fibrinolysis in patient #4 did not resolve shock, requiring V-A ECMO. Circumstances of CA were typical: during prone to supine position mobilization (#2) or after tracheal intubation (#1). Chest compressions were performed during 1 h after therapy, without return of spontaneous circulation. Among survivors, thrombolytic therapy was complicated with major hemorrhage requiring transfusion.
      Here, we discuss on the interest of fibrinolysis, because no specific report is available to date in the setting of COVID-19. Since high incidence of thromboembolic events (25–40%) was reported in SARS-CoV-2 patients,
      • Bikdeli B.
      • Madhavan M.V.
      • Jimenez D.
      • et al.
      COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up.
      the majority of our ICU patients was treated with therapeutic doses of anticoagulant agents. Whereas systemic fibrinolysis is the treatment of choice in PE-related shock or CA in the absence of contraindication,
      • Konstantinides S.V.
      • Meyer G.
      • Becattini C.
      • et al.
      2019 ESC Guidelines for the diagnosis and management of management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).
      how could this poor outcome be explained? First, PE may be oversuspected, because ACP does not systematically mean PE diagnosis. Indeed, ACP can be described in as many as 22% cases of acute respiratory distress syndrome (ARDS) due to lung vascular dysfunction driven by inflammation, thrombosis, fluid overload and two hits (pneumonia and mechanical ventilation).
      • Mekontso Dessap A.
      • Boissier F.
      • Charron C.
      • et al.
      Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact.
      Risk factors of ACP are pneumonia as cause of ARDS, severe hypoxemia, hypercapnia, elevated driving pressure, all these elements being encountered in the most severe COVID-19 patients. Second, poor prognosis could be the consequence of deleterious association of 2 severe conditions, namely, ARDS and PE-related shock or CA. At least, COVID-19 pneumonia is to date a dreadful disease, with around 50% mortality in ICU.
      • Bhatraju P.K.
      • Ghassemieh B.J.
      • Nichols M.
      • et al.
      Covid-19 in critically ill patients in the Seattle region – case series.
      In conclusion, despite favorable benefit/risk ratio in medical patients, we highlight that rescue systemic fibrinolysis in suspected PE is associated with poor outcome and that ACP should not always lead to PE diagnosis. To our sense, lower limbs ultrasound should systematically complete echocardiography to search for venous thrombosis, providing further clues for PE diagnosis in case of shock/CA.
      • Sönmez E.
      • Gülen B.
      Ultrasound is useful in cardiac arrest, but we still have concerns.
      Further studies are required to appreciate the place of systemic fibrinolysis during SARS-CoV-2 pandemic.

      Ethics approval and consent to participate

      Approval to analyze these data was granted by the local ethic committee. The need for informed consent was waived in view of the retrospective nature of the report.

      Consent for publication

      Not applicable.

      Availability of data and materials

      All data generated or analyzed during this study are included in this published article.

      Competing interests

      The authors declare that they have no competing interests.

      Funding

      The authors received no funding related to this manuscript.

      Authors’ contribution

      AL and NM wrote the manuscript. CA collected patients’ data. All authors took care of the patients, read and approved the final manuscript. NM conceptualized the main letter and proofread the contents.

      Acknowledgements

      Not applicable.

      References

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