D-dimer, BNP/NT-pro-BNP, and creatinine are reliable decision-making biomarkers in life-sustaining therapies withholding and withdrawing during COVID-19 outbreak

David M Smadja^{1

2}, Benjamin A Fellous¹, Guillaume Bonnet^{3

4}, Caroline Hauw-Berlemont⁵, Willy Sutter^{3

6}, Agathe Beauvais^{1

7}, Charles Fauvel⁸, Aurélien Philippe^{1

2}, Orianne Weizman⁹, Delphine Mika¹⁰, Philippe Juvin⁷, Victor Waldmann^{3

11}, Jean-Luc Diehl^{1

5}, Ariel Cohen¹², Richard Chocron^{3

7}

Affiliations

¹ Université de Paris-Cité, Innovative Therapies in Haemostasis, INSERM, Paris, France.
² Hematology Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
³ Université de Paris, Paris Cardiovascular Research Centre (PARCC), INSERM, UMR-S970, Paris, France.
⁴ Hôpital Cardiologique Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Unité Médico-Chirurgical de Valvulopathies et Cardiomyopathies, Pessac, France.
⁵ Medical Intensive Care Department AP-HP, Georges Pompidou European Hospital, Paris, France.
⁶ Vascular Surgery Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
⁷ Emergency Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
⁸ Rouen University Hospital, FHU REMOD-VHF, Rouen, France.
⁹ Institut Lorrain du Cœur et des Vaisseaux, CHU de Nancy, Vandoeuvre les Nancy, France.
¹⁰ Université Paris-Saclay, Inserm, UMR-S 1180, Chatenay-Malabry, France.
¹¹ Cardiology Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
¹² Cardiology Department, AP-HP, Saint Antoine Hospital, Paris, France.

PMID: 36148049
PMCID: PMC9485619
DOI: 10.3389/fcvm.2022.935333

D-dimer, BNP/NT-pro-BNP, and creatinine are reliable decision-making biomarkers in life-sustaining therapies withholding and withdrawing during COVID-19 outbreak

David M Smadja et al. Front Cardiovasc Med. 2022.

. 2022 Sep 6:9:935333.

doi: 10.3389/fcvm.2022.935333. eCollection 2022.

Authors

Affiliations

¹ Université de Paris-Cité, Innovative Therapies in Haemostasis, INSERM, Paris, France.
² Hematology Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
³ Université de Paris, Paris Cardiovascular Research Centre (PARCC), INSERM, UMR-S970, Paris, France.
⁴ Hôpital Cardiologique Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Unité Médico-Chirurgical de Valvulopathies et Cardiomyopathies, Pessac, France.
⁵ Medical Intensive Care Department AP-HP, Georges Pompidou European Hospital, Paris, France.
⁶ Vascular Surgery Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
⁷ Emergency Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
⁸ Rouen University Hospital, FHU REMOD-VHF, Rouen, France.
⁹ Institut Lorrain du Cœur et des Vaisseaux, CHU de Nancy, Vandoeuvre les Nancy, France.
¹⁰ Université Paris-Saclay, Inserm, UMR-S 1180, Chatenay-Malabry, France.
¹¹ Cardiology Department, AP-HP, Georges Pompidou European Hospital, Paris, France.
¹² Cardiology Department, AP-HP, Saint Antoine Hospital, Paris, France.

PMID: 36148049
PMCID: PMC9485619
DOI: 10.3389/fcvm.2022.935333

Abstract

Background: The decision for withholding and withdrawing of life-sustaining treatments (LSTs) in COVID-19 patients is currently based on a collegial and mainly clinical assessment. In the context of a global pandemic and overwhelmed health system, the question of LST decision support for COVID-19 patients using prognostic biomarkers arises.

Methods: In a multicenter study in 24 French hospitals, 2878 COVID-19 patients hospitalized in medical departments from 26 February to 20 April 2020 were included. In a propensity-matched population, we compared the clinical, biological, and management characteristics and survival of patients with and without LST decision using Student's t-test, the chi-square test, and the Cox model, respectively.

Results: An LST was decided for 591 COVID-19 patients (20.5%). These 591 patients with LST decision were secondarily matched (1:1) based on age, sex, body mass index, and cancer history with 591 COVID-19 patients with no LST decision. The patients with LST decision had significantly more cardiovascular diseases, such as high blood pressure (72.9 vs. 66.7%, p = 0.02), stroke (19.3 vs. 11.1%, p < 0.001), renal failure (30.4 vs. 17.4%, p < 0.001), and heart disease (22.5 vs. 14.9%, p < 0.001). Upon admission, LST patients were more severely attested by a qSOFA score ≥2 (66.5 vs. 58.8%, p = 0.03). Biologically, LST patients had significantly higher values of D-dimer, markers of heart failure (BNP and NT-pro-BNP), and renal damage (creatinine) (p < 0.001). Their evolutions were more often unfavorable (in-hospital mortality) than patients with no LST decision (41.5 vs. 10.3%, p < 0.001). By combining the three biomarkers (D-dimer, BNP and/or NT-proBNP, and creatinine), the proportion of LST increased significantly with the number of abnormally high biomarkers (24, 41.3, 48.3, and 60%, respectively, for none, one, two, and three high values of biomarkers, trend p < 0.01).

Conclusion: The concomitant increase in D-dimer, BNP/NT-proBNP, and creatinine during the admission of a COVID-19 patient could represent a reliable and helpful tool for LST decision. Circulating biomarker might potentially provide additional information for LST decision in COVID-19.

Keywords: COVID-19; SARS-CoV-2; biomarkers; claeys-léonetti law; ethics; life-sustaining therapies; mortality; withholding or withdrawing.

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Conflict of interest statement

RC, AC, and DS acknowledge the following without any relation with the current manuscript. RC received Consultant fees from Aspen. AC received research grant from RESICARD (research nurses) and consultant and lecture fees from Amgen, AstraZeneca, Bayer Pharma, Alliance BMS-Pfizer, Novartis, and Sanofi-Aventis. DS received consultant, lecture fees or travel awards from Aspen, Bayer, Carmat, Alliance BMSPfizer, Léo Pharma and Boehringer-Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Figure 1**
Evaluation of LST decision on in-hospital mortality in a retrospective study of COVID-19 patients admitted to medical wards during the first wave. **(A)** In-hospital mortality rate of patients with COVID-19 admitted to medical wards treated with or without LST decision. **(B)** LST is a strong predictor of in-hospital mortality in COVID-19 patients admitted to medical wards during the first wave. Forest plot summarizing results of Cox proportional-hazard model for in-hospital mortality adjusted on all covariates.

**Figure 2**
Composite biological criteria (D-dimer, NT-pro-BNP/BNP, and creatinine) help predict LST decision.

See this image and copyright information in PMC

References

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D-dimer, BNP/NT-pro-BNP, and creatinine are reliable decision-making biomarkers in life-sustaining therapies withholding and withdrawing during COVID-19 outbreak

Affiliations

D-dimer, BNP/NT-pro-BNP, and creatinine are reliable decision-making biomarkers in life-sustaining therapies withholding and withdrawing during COVID-19 outbreak

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources