key: cord-0947281-ugucj7xt
authors: Baert, Valentine; Beuscart, Jean-Baptiste; Recher, Morgan; Javaudin, François; Hugenschmitt, Delphine; Bony, Thomas; Revaux, François; Mansouri, Nadia; Larcher, Fanny; Chazard, Emmanuel; Hubert, Hervé
title: Coronavirus Disease 2019 and Out-of-Hospital Cardiac Arrest: No Survivors*
date: 2021-10-04
journal: Crit Care Med
DOI: 10.1097/ccm.0000000000005374
sha: 8129e4432e2dfea40d851925d1eb24086055d347
doc_id: 947281
cord_uid: ugucj7xt

To describe and compare survival among patients with out-of-hospital cardiac arrest as a function of their status for coronavirus disease 2019. DESIGN: We performed an observational study of out-of-hospital cardiac arrest patients between March 2020 and December 2020. Coronavirus disease 2019 status (confirmed, suspected, or negative) was defined according to the World Health Organization’s criteria. SETTING: Information on the patients and their care was extracted from the French national out-of-hospital cardiac arrest registry. The French prehospital emergency medical system has two tiers: the fire department intervenes rapidly to provide basic life support, and mobile ICUs provide advanced life support. The study data (including each patient’s coronavirus disease 2019 status) were collected by 95 mobile ICUs throughout France. PATIENTS: We included 6,624 out-of-hospital cardiac arrest patients: 127 cases with confirmed coronavirus disease 2019, 473 with suspected coronavirus disease 2019, and 6,024 negative for coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The “confirmed” and “suspected” groups of coronavirus disease 2019 patients had similar characteristics and were more likely to have suffered an out-of-hospital cardiac arrest with a respiratory cause (confirmed: 53.7%, suspected coronavirus disease 2019: 56.5%; p = 0.472) than noncoronavirus disease 2019 patients (14.0%; p < 0.001 vs confirmed coronavirus disease 2019 patients). Advanced life support was initiated for 57.5% of the confirmed coronavirus disease 2019 patients, compared with 64.5% of the suspected coronavirus disease 2019 patients (p = 0.149) and 70.6% of the noncoronavirus disease 2019 ones (p = 0.002). The survival rate at 30-day postout-of-hospital cardiac arrest was 0% in the confirmed coronavirus disease 2019 group, 0.9% in the suspected coronavirus disease 2019 group (p = 0.583 vs confirmed), and 3.5% (p = 0.023) in the noncoronavirus disease 2019 group. CONCLUSIONS: Our results highlighted a zero survival rate in out-of-hospital cardiac arrest patients with confirmed coronavirus disease 2019. This finding raises important questions with regard to the futility of resuscitation for coronavirus disease 2019 patients and the management of the associated risks.

rate in France fell during the COVID-19 pandemic (from 5.3% to 3.1%) (5) . To date, published studies of COVID-19 and OHCA pooled confirmed and suspected cases of COVID-19 or compared prepandemic and per-pandemic cohorts (5, 8) . Furthermore, none of the studies described the survival rate and other characteristics in a specific cohort of OHCA patients with confirmed COVID-19.

In this context, our primary objective of the present study was to describe the survival rate 30 days after OHCA among confirmed COVID-19 patients. Our secondary objective was to compare the confirmed COVID-19 patients with suspected COVID-19 patients and non-COVID-19 patients having experienced OHCA during the same period.

Data were extracted from the French National OHCA Registry (RéAC). The RéAC records OHCAs managed by mobile ICUs (MICUs) in France and has been described elsewhere (9) . The French prehospital emergency medical system has two tiers: the fire department acts as the first professional responder and intervenes rapidly to provide basic life support (BLS), whereas MICUs provide advanced life support (ALS). An MICU comprises at minimum an ambulance driver, a nurse, and a senior emergency medicine physician. The RéAC data entry form meets the requirements of the French emergency medical services and complies with the Utstein Resuscitation Registry's template (10) .

We analyzed cases of OHCA recorded in the RéAC between March 1, 2020, and December 31, 2020. Data were gathered by 95 centers in France. The investigating physicians filled out the patients' COVID-19 status in the RéAC database. We excluded patients with prolonged downtime and unwitnessed arrest with signs of rigor mortis and those whose COVID-19 status was not known. We separated the OHCA study population into three groups (confirmed COVID-19, suspected COVID-19, and non-COVID-19), according to the World Health Organization (WHO)'s definition. Hence, confirmed cases were defined as patients with laboratory-confirmed COVID-19 (after inhospital or outpatient screening) and who were allowed to return home or remain at home (because of nonseverity). Suspected cases in our study were defined as patients who: 1) had consulted a family physician before the OHCA, 2) were suspect cases according to the WHO definitions A, B, or C, and 3) did not have a laboratory confirmation of COVID-19 (11) .

The normality of the data distribution for categorical variables was assessed using the Kolmogorov-Smirnov test. Quantitative variables were described as the median and first and third quartiles (Q1-Q3). Qualitative variables were described as the frequency (percentage), and 95% CIs were computed. Bivariate analyses were assessed using Pearson chi-square test or Fisher exact test for categorical variables and the nonparametric Mann-Whitney test for continuous variables. All tests were two-sided, and the threshold for statistical significance was set to p < 0.05.

The study was approved by the French Advisory Committee on Information Processing in Material Research in the Field of Health ("Comité Consultatif sur le Traitement de l'Information en Matière de Recherche dans le Domaine de la Santé") and registered with the French National Data Protection Commission ("Commission Nationale de l'Informatique et des Libertés": reference number: 910946).

Between March 1, 2020, and December 31, 2020, the participating MICUs registered 9,255 patients in the RéAC registry. A total of 6,624 of these patients were included in our study (Fig. 1 ). There were 127 (1.9%) confirmed cases of COVID-19, 473 (7.1%) suspected cases, and 6,024 (90.9%) non-COVID-19 patients.

Council ALS algorithm was implemented), the time between the call to emergency services and the arrival of the first professional responder, "no-flow" status, and "low-flow" status ( Table 1 ). In the confirmed COVID-19 group, as soon as an ALS was implemented, intubation was performed. No difference was observed between the confirmed and suspected COVID-19 patients regarding intubation (p = 0.085). The median (Q1-Q3) time between the emergency call and the MICU's arrival was shorter in the confirmed COVID-19 group (19 min [12-25 min] ) than that in the suspected COVID-19 group (20 min [14-30 min]; p = 0.026).

The confirmed COVID-19 patients and the non-COVID-19 patients did not differ significantly with regard to sex, diabetes, a history of cardiovascular disease, a history of another disease, and the provision of BLS (except for defibrillator use, which was less frequent in the confirmed COVID-19 group: 7.9%, versus 17.1% in the non-COVID-19 group; p = 0.009). No differences were observed with regard to the first cardiac rhythm recorded by the MICU or other timings. The confirmed COVID-19 patients were more likely to have a history of respiratory disease (20.5% versus 12.3% in the non-COVID-19 group; p = 0.009), and the OHCA was more likely to have a medical cause (cardiac, neurologic, respiratory, or other medical cause) (95.3% vs 81.6%; p < 0.001). More than half the OHCA with a medical cause in the confirmed COVID-19 group were due to respiratory disease (53.7%, vs 14.0% in the non-COVID-19 group; p < 0.001). ALS provision by the MICU was less frequent (57.5%, vs 70.6% in the non-COVID-19 group; p = 0.002). The intubation was also less frequent in the confirmed COVID-19 group compared with the non-COVID-19 one (57.5% vs 64.7%; p = 0.002).

The D30 survival rate (95% CI) in the confirmed COVID-19 group was 0.00% (0.00-2.93), which was significantly lower than that in the non-COVID-19 group (3.5%; 95% CI [3.10-4.06]; p = 0.023) and lower (albeit not significantly) than in the suspected COVID-19 group (0.9%; 95% CI [0.34-2.20]; p = 0.583).

There were no significant differences between the confirmed and suspected COVID-19 patients in terms of return of spontaneous circulation (ROSC: 17.3% vs 16.1%, respectively; p = 0.787) and survival at hospital admission (D0 survival: 11.8% vs 11.0%; p = 0.753) (Fig. 2) . Likewise, there were no significant differences between the confirmed COVID-19 patients and non-COVID-19 patients with regard to ROSC (17.3% vs 19.8%, respectively; p = 0.573) and D0 survival (11.8% vs 16.6, respectively; p = 0.183) (Fig. 2) .

To the best of our knowledge, the present study is the first to have specifically described patients with confirmed COVID-19 (according to the WHO definition [11] ) having experienced OHCA. The study's main finding was that none of the OHCA patients with confirmed COVID-19 were alive 30 days after the event.

In our study, we observed a difference in survival rates between the confirmed COVID-19 patients and non-COVID ones. Even though the post-OHCA survival rate has fallen markedly during the COVID-19 pandemic, survivors were always observed. It is extremely rare to observe a survival rate of zero (95% CI, 0.00-2.93) in a specific cohort of OHCA patients. However, researchers working in the state of Georgia (United States) did not observe any survivors among a cohort of 63 patients affected by the coronavirus who experienced inhospital cardiac arrest (survival rate [95% CI], 0.00% [0.00-5.69]) (12) . This finding raises questions about the futility of resuscitation for confirmed COVID-19 patients.

In our study, we noticed that a low proportion (57.5%) of the patients known to have COVID-19 received ALS. This proportion is much lower than that for the non-COVID-19 patients in our study. This could partially explain the difference in survival. Overall, patients with suspected COVID-19 were treated in the same way as those with confirmed COVID-19. This lower level of ALS initiation during the COVID-19 era has been observed previously (5, 13) . It has been suggested that resuscitation procedures can generate aerosols and, thus, risks for healthcare professionals, although the evidence has a very low degree of certainty (14) . The WHO listed cardiopulmonary resuscitation (CPR) as an aerosol-generating procedure, and the international liaison committee on resuscitation confirmed this hypothesis (10). Initially, the scientific literature advised rescuers to consider their own safety before resuscitation or to change the ALS algorithm (15) (16) (17) .

International guidelines on resuscitation of COVID-19 patients came very late. The European Resuscitation Council COVID-19 guidelines suggested considering defibrillation before chest compression and ventilation while wearing personal protective equipment (PPE) (14) . Professionals who provide ALS must take account of the patient's context and medical history when assessing personal risks associated with treatment (14) . Furthermore, the ethic in resuscitation suggests to take into account the prognostication of patient when to start ALS. Hence, regarding ethic, the futility of the resuscitation based on a zero survival rate is questioned. In this context, the high ALS initiation rate (57.5%) observed here with systematic intubation for each of the resuscitated patients testifies to MICU team members' level of commitment.

We observed that medical OHCAs in confirmed COVID-19 patients were mainly due to respiratory distress (53.7%). Furthermore, confirmed COVID-19 patients were significantly more likely to have a history of respiratory disease than the other OHCA patients studied here. Hence, it is important to follow up COVID-19 patients carefully, especially when a history of respiratory disease is known or if the patients have few or only mild symptoms and have not been hospitalized. Indeed, acute respiratory distress syndrome (ARDS) can even occur in patients without comorbidities and who do not receive expert, individual medical follow-up. ARDS can rapidly lead to multiple organ failure and cardiac arrest (18) .

The present study had a number of strengths. It was based on a large, national registry fed by MICUs throughout France (including both rural and urban areas). However, participation by the MICUs was voluntary, and some French MICUs did not participate in the study. The study also had some limitations. First, this study might be not generalizable to some other countries. The present study population was predominantly Caucasian and had some specific characteristics that prevented us from generalizing our results further. In addition, this study was carried out on a "stay and play" emergency system model and then may be not fully generalizable to countries applying a "scoop and run" model. Second, some OHCAs may have been misclassified with regard to their COVID-19 status.

Indeed, some of the "non-COVID-19" cases might have been false-negatives, and we did not have access to postmortem information. Furthermore, suspected cases of COVID-19 could have been misclassified. However, we did not observe significant differences in the characteristics of suspected COVID-19 patients and confirmed COVID-19 patients, and so the error level was probably low. Third, our knowledge of inhospital data was limited. Hence, some of these cares, as a withdrawal of care in the confirmed COVID-19 group, might explain the absence of difference in ROSC and D0 survival and the presence of difference at D30. Finally, we performed a cohort study and excluded 1,245 patients because their COVID-19 status was unknown. Thus, their COVID group and vital status were not observed, and this could have changed some results. However, we worked on a large sample of 6,624 patients, which allows us to observe some effects.

Our results highlighted a zero survival rate in OHCA patients with confirmed COVID-19. The current resuscitation guidelines suggest that professional emergency responders use PPE and assess the risk before to starting CPR in suspected or confirmed cases of COVID-19. The risk-benefit balance for resuscitating confirmed COVID-19 patients should be investigated. The survival of OHCA patients with confirmed COVID-19 should be analyzed in other countries.

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The French National Cardiac Arrest Registry is supported by the French Society of Emergency Medicine; a patient foundation, the Fédération Française de Cardiologie; the Mutuelle Générale de l'Education Nationale, and Lille University. The registry is funded by the Hauts-de-France Regional Council and the European Union via the European Regional Development Fund.The authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: valentine.baert@ univ-lille.fr