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.
| Patient | 1 | 2 | 3–1 | 3–2 | 4 | 5 |
| Age (years) | 67 | 41 | 63 | 63 | 55 | 46 |
| Sex | Male | Male | Male | Male | Male | Male |
| BMI (kg/m2) | 26.2 | 25.8 | 27.2 | 27.2 | 20.7 | 24.3 |
| SAPS II | 26 | 22 | 47 | 47 | 28 | 31 |
| Invasive MV | No | Yes | Yes | Yes | Yes | Yes |
| Number of PP sessions | 0 | 1 | 1 | 1 | 1 | 4 |
| PaO2/FiO2 ratio (mmHg) | 80 | 85 | 80 | 91 | 94 | 62 |
| PaCO2 (mmHg) | 36 | 56 | 76 | 46 | 53 | 53 |
| Respiratory system compliance (ml/cmH2O) | NA | 33 | 30 | 16 | 17 | 10 |
| Driving pressure (cmH2O) | NA | 12 | 15 | 25 | 23 | 16 |
| NE dose (μg/kg/min) | 2.94 | 0.22 | 1.06 | 2.05 | 0.25 | 3.46 |
| VV-ECMO | No | No | No | No | No | Yes |
| Antithrombotic regimen | Curative LMWH | Preventive LMWH | Curative LMWH | Curative UFH | Curative LMWH | Curative UFH |
| D-Dimer (ng/ml) | 2281 | NA | 4208 | 4208 | 7794 | 9943 |
| PR (%) | 64 | 67 | 77 | 71 | 70 | 80 |
| Platelet count (Giga/l) | 355 | 194 | 391 | 403 | 199 | 176 |
| Fibrinogen (g/l) | 7.7 | 8.4 | 7.0 | 6.4 | 6.5 | 4.8 |
| Reason for fibrinolysis | CA | CA | Shock | Shock | Shock | Shock |
| Imaging | ACP | ACP + CFV thrombosis | ACP | ACP | ACP | ACP |
| Complications | – | – | – | – | Femoral hemorrhage: 8 RBC transfused | Jugular + femoral hemorrhage: 3 RBC transfused |
| Immediate effect | No ROSC | No ROSC | 60% NE decrease in 1 h | Persistent shock | Persistent shock | 80% NE decrease in 3 h |
| Vital status | Death | Death | Death 3 days later | Death 2 days later | Death 3 days later | Alive 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,
1
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,- Bikdeli B.
- Madhavan M.V.
- Jimenez D.
- et al.
COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up.
J Am Coll Cardiol. 2020; https://doi.org/10.1016/j.jacc.2020.04.031
2
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).3
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.4
- Bhatraju P.K.
- Ghassemieh B.J.
- Nichols M.
- et al.
Covid-19 in critically ill patients in the Seattle region – case series.
N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2004500
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.
5
Further studies are required to appreciate the place of systemic fibrinolysis during SARS-CoV-2 pandemic.- Sönmez E.
- Gülen B.
Ultrasound is useful in cardiac arrest, but we still have concerns.
Resuscitation. 2019; https://doi.org/10.1016/j.resuscitation.2019.09.039
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
- COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up.J Am Coll Cardiol. 2020; https://doi.org/10.1016/j.jacc.2020.04.031
- 2019 ESC Guidelines for the diagnosis and management of management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2019; : 1-61
- Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact.Intensive Care Med. 2016; 42: 862-870
- Covid-19 in critically ill patients in the Seattle region – case series.N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2004500
- Ultrasound is useful in cardiac arrest, but we still have concerns.Resuscitation. 2019; https://doi.org/10.1016/j.resuscitation.2019.09.039
Article Info
Publication History
Published online: May 20, 2020
Received:
May 9,
2020
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© 2020 Elsevier B.V. All rights reserved.
