# Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study

Mikhael Giabicani, Christophe Le Terrier, Antoine Poncet, Bertrand Guidet, Jean-Philippe Rigaud, Jean-Pierre Quenot, Marie-France Mamzer, Jérôme Pugin, Emmanuel Weiss, Simon Bourcier, et al.

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## ► To cite this version:

Mikhael Giabicani, Christophe Le Terrier, Antoine Poncet, Bertrand Guidet, Jean-Philippe Rigaud, et al.. Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study. Critical Care, 2023, 27 (1), pp.103. 10.1186/s13054-023-04349-1 . hal-04399172

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# Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study

Mikhael Giabicani¹,²†, Christophe Le Terrier³†, Antoine Poncet⁴,⁵, Bertrand Guidet⁶, Jean-Philippe Rigaud⁷, Jean-Pierre Quenot⁸, Marie-France Mamzer²,⁹, Jérôme Pugin³, Emmanuel Weiss¹ and Simon Bourcier³* ID on behalf of COVID-ICU study investigators

**Abstract**

**Background** Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients.

**Methods** We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions.

**Results** Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3–21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1–11) after LST limitations.

**Conclusions** In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

**Keywords** COVID-19, Outcome, Life-sustaining therapy, Ethical, Acute respiratory distress syndrome, Critical care

<footnote>†Mikhael Giabicani and Christophe Le Terrier have contributed equally.</footnote>

<footnote>This article has online supplement, which is accessible from this issue's table of content online at https://www.ccforum.biocentral.com/</footnote>

<footnote>*Correspondence:</footnote>

<footnote>Simon Bourcier
simonlouisbourcier@gmail.com</footnote>

<footnote>Full list of author information is available at the end of the article</footnote>
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# Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study

Mikhael Giabicani¹,²†, Christophe Le Terrier³†, Antoine Poncet⁴,⁵, Bertrand Guidet⁶, Jean-Philippe Rigaud⁷, Jean-Pierre Quenot⁸, Marie-France Mamzer²,⁹, Jérôme Pugin³, Emmanuel Weiss¹ and Simon Bourcier³* ID on behalf of COVID-ICU study investigators

**Abstract**

**Background** Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients.

**Methods** We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions.

**Results** Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3–21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1–11) after LST limitations.

**Conclusions** In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

**Keywords** COVID-19, Outcome, Life-sustaining therapy, Ethical, Acute respiratory distress syndrome, Critical care

<footnote>†Mikhael Giabicani and Christophe Le Terrier have contributed equally.</footnote>

<footnote>This article has online supplement, which is accessible from this issue's table of content online at https://www.ccforum.biocentral.com/</footnote>

<footnote>*Correspondence:</footnote>

<footnote>Simon Bourcier
simonlouisbourcier@gmail.com</footnote>

<footnote>Full list of author information is available at the end of the article</footnote>
## Background

In spring 2020, Europe experienced the first surge of the SARS-CoV-2 pandemic, leading to a large number of intensive care unit (ICU) admissions of severe COVID-19 patients requiring both prolonged mechanical ventilation and ICU stay, and placing an unprecedented strain on ICUs and healthcare systems. High mortality related to the most severe forms, including acute respiratory distress syndrome (ARDS), was initially reported as reaching 40% [1]. However, mortality rates decreased over time, with a regional variability observed between centres [2, 3]. Nationwide studies in the USA, the United Kingdom, France and Belgium investigated the reasons of the variability in mortality rates, with an emphasis on organizational aspects [2–7]. Importantly, findings suggested an increased COVID-19-related mortality when ICUs were overwhelmed. Facing an important surge of COVID-19 patients, facilities expanded their ICU capacities and, in some instances, scarcity of ventilators, ICU beds, staff resources, or drug use raised ethical dilemmas related to critical care resource allocation and triage [8, 9]. Ethical discussions are part of the daily process of care in the ICU where decisions to withdraw or withhold life-sustaining treatments (LST) are common. The recent Ethicus-2 study including 199 ICUs across four countries and 36 countries found an LST limitation cumulative incidence rate of 11.8% and an associated mortality of 71.9% and 88.5%, respectively, after withholding and withdrawing LST [10]. In addition, one half of deaths are preceded by LST decisions in the ICU [11, 12]. Age, comorbidities, and illness severity are considered important features when discussing LST limitations [13], but a substantial variability has been reported worldwide regarding the frequencies, modalities and timing of LST decisions, as well as between ICUs within countries [10, 14–16].

Before the COVID-19 pandemic, pressure on ICU capacity was suggested to influence both mortality [17, 18] and LST decisions [19]. However, few data have been reported to date on LST decisions in critically ill COVID-19 patients during the pandemic or when ICU capacities are facing an exceptional challenge. We sought to investigate the prevalence, cumulative incidence, timing and modalities of LST decisions in critically ill COVID-19 patients, as well as the individual and organizational factors associated with these decisions.

## Methods

### Study design and patients

We did an ancillary analysis of the COVID-ICU study, a multicentre, prospective, cohort study conducted in 164 ICUs across three European countries (France, Belgium, and Switzerland), which described outcomes and

risk factors of 90-day mortality of critically ill COVID-19 patients [1]. The study was launched by the Réseau Européen de recherche en Ventilation Artificielle (REVA) and included all consecutive patients aged > 16 years admitted to participating ICUs with laboratory-confirmed SARS-CoV-2 infection between February 25 and May 4, 2020. The ethics committees of the French Intensive Care Society (CE-SRLF 20-23), Belgium (2020-294), and Switzerland (BASEC #2020-00704) approved the study according to regulations for each participating country. All patients or next of kin were informed that patient data would be anonymously included in the COVID-ICU database. Patients and relatives had the possibility to decline participation in the study. In that case, data were not collected. The study followed the STROBE statement for the reporting of observational studies [20].

All patients with laboratory-confirmed SARS-CoV-2 infection and available data regarding LST decisions and day-90 vital status were included in the study. Laboratory confirmation for SARS-CoV-2 was defined as a positive result of a real-time reverse transcriptase-polymerase chain reaction assay from either nasal or pharyngeal swabs, or lower respiratory tract samples.

### Data collection

Day 1 was defined as the first day when the patient was present in the ICU at 10 am. Each day, study investigators completed a standardized electronic case report form. Data collected included baseline demographic characteristics within the first 24 h after ICU admission (day 1), comorbidities, simplified acute physiology score (SAPS-II) [21], sequential organ failure assessment (SOFA) score [22], the clinical frailty scale score [23], date of first symptom/s, and ICU admission date. Local investigators documented the following information in a daily expanded dataset: presence of a respiratory support device (oxygen mask, high-flow nasal cannula, noninvasive or invasive mechanical ventilation); arterial blood gases; $FiO_2$; $PaO_2/FiO_2$ ratio; use of neuromuscular blockers or corticosteroids (regardless of the indication and the dose); and standard laboratory parameters. Data were also collected on complications and organ dysfunction during the ICU stay, including acute kidney injury treated with renal replacement therapy, thromboembolic complications, ventilator-associated pneumonia and cardiac arrest, as well as detailed treatment limitation decisions.

If an LST limitation was decided upon during ICU stay, investigators were asked to record in detail the following items: cardiovascular support (vasopressors, do-not-resuscitate order); ventilatory support (invasive or non-invasive, intubation, tracheotomy, respiratory device settings, $FiO_2$); renal replacement therapy; blood
## Background

In spring 2020, Europe experienced the first surge of the SARS-CoV-2 pandemic, leading to a large number of intensive care unit (ICU) admissions of severe COVID-19 patients requiring both prolonged mechanical ventilation and ICU stay, and placing an unprecedented strain on ICUs and healthcare systems. High mortality related to the most severe forms, including acute respiratory distress syndrome (ARDS), was initially reported as reaching 40% [1]. However, mortality rates decreased over time, with a regional variability observed between centres [2, 3]. Nationwide studies in the USA, the United Kingdom, France and Belgium investigated the reasons of the variability in mortality rates, with an emphasis on organizational aspects [2–7]. Importantly, findings suggested an increased COVID-19-related mortality when ICUs were overwhelmed. Facing an important surge of COVID-19 patients, facilities expanded their ICU capacities and, in some instances, scarcity of ventilators, ICU beds, staff resources, or drug use raised ethical dilemmas related to critical care resource allocation and triage [8, 9]. Ethical discussions are part of the daily process of care in the ICU where decisions to withdraw or withhold life-sustaining treatments (LST) are common. The recent Ethicus-2 study including 199 ICUs across four countries and 36 countries found an LST limitation cumulative incidence rate of 11.8% and an associated mortality of 71.9% and 88.5%, respectively, after withholding and withdrawing LST [10]. In addition, one half of deaths are preceded by LST decisions in the ICU [11, 12]. Age, comorbidities, and illness severity are considered important features when discussing LST limitations [13], but a substantial variability has been reported worldwide regarding the frequencies, modalities and timing of LST decisions, as well as between ICUs within countries [10, 14–16].

Before the COVID-19 pandemic, pressure on ICU capacity was suggested to influence both mortality [17, 18] and LST decisions [19]. However, few data have been reported to date on LST decisions in critically ill COVID-19 patients during the pandemic or when ICU capacities are facing an exceptional challenge. We sought to investigate the prevalence, cumulative incidence, timing and modalities of LST decisions in critically ill COVID-19 patients, as well as the individual and organizational factors associated with these decisions.

## Methods

### Study design and patients

We did an ancillary analysis of the COVID-ICU study, a multicentre, prospective, cohort study conducted in 164 ICUs across three European countries (France, Belgium, and Switzerland), which described outcomes and

risk factors of 90-day mortality of critically ill COVID-19 patients [1]. The study was launched by the Réseau Européen de recherche en Ventilation Artificielle (REVA) and included all consecutive patients aged > 16 years admitted to participating ICUs with laboratory-confirmed SARS-CoV-2 infection between February 25 and May 4, 2020. The ethics committees of the French Intensive Care Society (CE-SRLF 20-23), Belgium (2020-294), and Switzerland (BASEC #2020-00704) approved the study according to regulations for each participating country. All patients or next of kin were informed that patient data would be anonymously included in the COVID-ICU database. Patients and relatives had the possibility to decline participation in the study. In that case, data were not collected. The study followed the STROBE statement for the reporting of observational studies [20].

All patients with laboratory-confirmed SARS-CoV-2 infection and available data regarding LST decisions and day-90 vital status were included in the study. Laboratory confirmation for SARS-CoV-2 was defined as a positive result of a real-time reverse transcriptase-polymerase chain reaction assay from either nasal or pharyngeal swabs, or lower respiratory tract samples.

### Data collection

Day 1 was defined as the first day when the patient was present in the ICU at 10 am. Each day, study investigators completed a standardized electronic case report form. Data collected included baseline demographic characteristics within the first 24 h after ICU admission (day 1), comorbidities, simplified acute physiology score (SAPS-II) [21], sequential organ failure assessment (SOFA) score [22], the clinical frailty scale score [23], date of first symptom/s, and ICU admission date. Local investigators documented the following information in a daily expanded dataset: presence of a respiratory support device (oxygen mask, high-flow nasal cannula, noninvasive or invasive mechanical ventilation); arterial blood gases; $FiO_2$; $PaO_2/FiO_2$ ratio; use of neuromuscular blockers or corticosteroids (regardless of the indication and the dose); and standard laboratory parameters. Data were also collected on complications and organ dysfunction during the ICU stay, including acute kidney injury treated with renal replacement therapy, thromboembolic complications, ventilator-associated pneumonia and cardiac arrest, as well as detailed treatment limitation decisions.

If an LST limitation was decided upon during ICU stay, investigators were asked to record in detail the following items: cardiovascular support (vasopressors, do-not-resuscitate order); ventilatory support (invasive or non-invasive, intubation, tracheotomy, respiratory device settings, $FiO_2$); renal replacement therapy; blood
transfusion; enteral or parenteral nutrition; surgical
emergency treatment; antibiotics; and intracranial pres-
sure monitoring.

Definitions

Geographical areas (hereafter referred to as “regions”)
were set as the national administrative divisions, i.e.,
provinces for Belgium, departments for France, and can-
tons for Switzerland. To assess the strain on ICU capaci-
ties caused by the surge of COVID-19 patients, the ICU
load was first computed at the regional level on a daily
basis as:

death during ICU stay as competing risks. Kaplan–Meier survival curves were plotted for the estimation of time to death from the first treatment limitation decision. In further analyses, the treatment limitation decision was dichotomized as LST withholding or withdrawal versus no limitation. Associations between variables and treatment limitation were estimated in a complete case analysis using a random intercept logistic regression model to account for the clustering of patients within centres. The following baseline variables obtained during the first 24 h in the ICU were included in the multivariable model and defined a priori (no

Number of ICU beds occupied by COVID-19 patients on a given day
Total number of baseline ICU beds before the pandemic

This dynamic parameter was defined according to Bra-
vata et al. [4] The ICU load at the patient level was finally
defined as the mean ICU load in the region during the
patient's ICU stay. An ICU load of 100% reflected that all
baseline ICU beds were occupied by COVID-19 patients,
while an ICU load over 100% meant that the number of
COVID-19 patients exceeded the baseline ICU hospi-
talization capacity. The number of baseline regional ICU
beds before the pandemic and daily regional ICU bed
occupancy during the first surge of the pandemic were
based on data publicly available from official epidemio-
logical reports on governmental websites including Pub-
lic Health France and the French Ministry of Health,
the Belgium Health Public Institute “Sciensano”, and the
Swiss Federal Office of Public Health (see Additional
file 1: Data Supplement, p 4). Treatment limitations were
categorized as LST withholding or withdrawal, accord-
ing to the decision recorded in the daily expanded dataset
by local investigators (see Additional file 1: Data Supple-
ment, p 5). A patient with a decision of LST withdrawal
after an LST withholding decision was classified in the
“LST withdrawal” group.

Statistical analysis

Patients' baseline characteristics, first 24-h in-ICU var-
iables, treatments, organizational parameters, and ICU
load at the patient level were described overall accord-
ing to the following LST groups: (1) no LST; (2) LST
withholding; and (3) LST withdrawal, whether or not
preceded by an LST withholding decision. Continu-
ous variables were described as medians (interquartile
range [IQR]) and categorical variables as counts and
percentages. Time to LST withholding and withdrawal
decisions from ICU admission was estimated using a
cumulative incidence function with ICU discharge and

statistical variable selection method was planned): age;
gender; nursing home resident; clinical frailty scale
score (non-frail [1–3], pre-frail [4], frail [≥ 5]); body
mass index ≥ 30 kg/m²; diabetes; hypertension; chronic
heart failure; ischemic cardiomyopathy; chronic respir-
atory disease; chronic kidney disease; immunodepres-
sion; past hematologic disease; time between first signs
and ICU admission; ICU admission period; ICU load;
SOFA cardiovascular component ≥ 3; SOFA renal com-
ponent ≥ 3; and ARDS severity during the first 24 h in
the ICU. A sensitivity analysis was performed in centres
including ≥ 10 patients.

Heterogeneity in withholding/withdrawal decisions between centres was investigated using meta-analytical methods to combine proportions on a logit scale and evaluated using a likelihood ratio test. Variability between centres was assessed with the tau statistic (standard deviation of the random effect) [24]. This analysis was restricted to centres including 10 patients or more. Subgroup analyses were performed according to the number of patients included by centre (i.e., 10–29 patients, 30–49 patients, ≥ 50 patients) and in centres including at least 10 patients aged 75 years or over.

Analyses were performed on a complete case analy-
sis with no missing data imputation. Statistical sig-
nificance was set at the two-sided 0.05 value for all
analyses. Analyses were computed with R software, ver-
sion R-4.0.2 (R Foundation for Statistical Computing,
Vienna, Austria, https://www.r-project.org).

Role of the funding source

The funders of the study had no role in study design,
data collection, data analysis, data interpretation,
transfusion; enteral or parenteral nutrition; surgical
emergency treatment; antibiotics; and intracranial pres-
sure monitoring.

Definitions

Geographical areas (hereafter referred to as “regions”)
were set as the national administrative divisions, i.e.,
provinces for Belgium, departments for France, and can-
tons for Switzerland. To assess the strain on ICU capaci-
ties caused by the surge of COVID-19 patients, the ICU
load was first computed at the regional level on a daily
basis as:

death during ICU stay as competing risks. Kaplan–Meier survival curves were plotted for the estimation of time to death from the first treatment limitation decision. In further analyses, the treatment limitation decision was dichotomized as LST withholding or withdrawal versus no limitation. Associations between variables and treatment limitation were estimated in a complete case analysis using a random intercept logistic regression model to account for the clustering of patients within centres. The following baseline variables obtained during the first 24 h in the ICU were included in the multivariable model and defined a priori (no

Number of ICU beds occupied by COVID-19 patients on a given day
Total number of baseline ICU beds before the pandemic

This dynamic parameter was defined according to Bra-
vata et al. [4] The ICU load at the patient level was finally
defined as the mean ICU load in the region during the
patient's ICU stay. An ICU load of 100% reflected that all
baseline ICU beds were occupied by COVID-19 patients,
while an ICU load over 100% meant that the number of
COVID-19 patients exceeded the baseline ICU hospi-
talization capacity. The number of baseline regional ICU
beds before the pandemic and daily regional ICU bed
occupancy during the first surge of the pandemic were
based on data publicly available from official epidemio-
logical reports on governmental websites including Pub-
lic Health France and the French Ministry of Health,
the Belgium Health Public Institute “Sciensano”, and the
Swiss Federal Office of Public Health (see Additional
file 1: Data Supplement, p 4). Treatment limitations were
categorized as LST withholding or withdrawal, accord-
ing to the decision recorded in the daily expanded dataset
by local investigators (see Additional file 1: Data Supple-
ment, p 5). A patient with a decision of LST withdrawal
after an LST withholding decision was classified in the
“LST withdrawal” group.

Statistical analysis

Patients' baseline characteristics, first 24-h in-ICU var-
iables, treatments, organizational parameters, and ICU
load at the patient level were described overall accord-
ing to the following LST groups: (1) no LST; (2) LST
withholding; and (3) LST withdrawal, whether or not
preceded by an LST withholding decision. Continu-
ous variables were described as medians (interquartile
range [IQR]) and categorical variables as counts and
percentages. Time to LST withholding and withdrawal
decisions from ICU admission was estimated using a
cumulative incidence function with ICU discharge and

statistical variable selection method was planned): age;
gender; nursing home resident; clinical frailty scale
score (non-frail [1–3], pre-frail [4], frail [≥ 5]); body
mass index ≥ 30 kg/m²; diabetes; hypertension; chronic
heart failure; ischemic cardiomyopathy; chronic respir-
atory disease; chronic kidney disease; immunodepres-
sion; past hematologic disease; time between first signs
and ICU admission; ICU admission period; ICU load;
SOFA cardiovascular component ≥ 3; SOFA renal com-
ponent ≥ 3; and ARDS severity during the first 24 h in
the ICU. A sensitivity analysis was performed in centres
including ≥ 10 patients.

Heterogeneity in withholding/withdrawal decisions between centres was investigated using meta-analytical methods to combine proportions on a logit scale and evaluated using a likelihood ratio test. Variability between centres was assessed with the tau statistic (standard deviation of the random effect) [24]. This analysis was restricted to centres including 10 patients or more. Subgroup analyses were performed according to the number of patients included by centre (i.e., 10–29 patients, 30–49 patients, ≥ 50 patients) and in centres including at least 10 patients aged 75 years or over.

Analyses were performed on a complete case analy-
sis with no missing data imputation. Statistical sig-
nificance was set at the two-sided 0.05 value for all
analyses. Analyses were computed with R software, ver-
sion R-4.0.2 (R Foundation for Statistical Computing,
Vienna, Austria, https://www.r-project.org).

Role of the funding source

The funders of the study had no role in study design,
data collection, data analysis, data interpretation,
writing of the report, or the decision to submit for publication.

## Results

### Study population

Among the 4746 patients included in the study from February 25 to May 4, 2020, LST status recorded in the daily dataset report form was missing for 75 patients (Fig. 1). Hence, 4671 patients were included in the final analysis. Median age of patients was 63 (54–70) years, and 26% were women. Eighty-two percent had at least one comorbidity and the median clinical frailty scale score was 2 (2–3). ARDS severity was mild, moderate and severe in 24%, 49% and 28% of patients, respectively, and invasive mechanical ventilation was initiated for 2866 patients (61%) during the first 24 h. All baseline characteristics of the study population are shown in Table 1.

### Modalities of LST withholding and withdrawal

LST limitation decisions during ICU stay occurred for 675 (period prevalence = 14.5%) patients, including a withholding decision in 656 (period prevalence = 14.0%) and a withdrawal decision in 297 (period prevalence = 6.4%) patients. A withdrawal decision was mostly preceded by an LST withholding decision (278/297 [93.6%]) (Table 1). LST withholding frequently included several modalities, with 82% percent of patients presenting two or more modalities of withholding (see Additional file 1: Data Supplement, tables E1 and E2). A do-not-resuscitate order was the most frequent modality of LST withholding (86.6%), followed by limitations of renal replacement therapy initiation (62.8%) and an initiation or increase of vasopressors (60.2%). At the time of LST withholding decisions, patients who had a further decision of

<figure><img src="image_2.png" /><figcaption>**Fig. 1** Flowchart of study population</figcaption></figure>
writing of the report, or the decision to submit for publication.

# Results

## Study population

Among the 4746 patients included in the study from February 25 to May 4, 2020, LST status recorded in the daily dataset report form was missing for 75 patients (Fig. 1). Hence, 4671 patients were included in the final analysis. Median age of patients was 63 (54–70) years, and 26% were women. Eighty-two percent had at least one comorbidity and the median clinical frailty scale score was 2 (2–3). ARDS severity was mild, moderate and severe in 24%, 49% and 28% of patients, respectively, and invasive mechanical ventilation was initiated for 2866 patients (61%) during the first 24 h. All baseline characteristics of the study population are shown in Table 1.

## Modalities of LST withholding and withdrawal

LST limitation decisions during ICU stay occurred for 675 (period prevalence = 14.5%) patients, including a withholding decision in 656 (period prevalence = 14.0%) and a withdrawal decision in 297 (period prevalence = 6.4%) patients. A withdrawal decision was mostly preceded by an LST withholding decision (278/297 [93.6%]) (Table 1). LST withholding frequently included several modalities, with 82% percent of patients presenting two or more modalities of withholding (see Additional file 1: Data Supplement, tables E1 and E2). A do-not-resuscitate order was the most frequent modality of LST withholding (86.6%), followed by limitations of renal replacement therapy initiation (62.8%) and an initiation or increase of vasopressors (60.2%). At the time of LST withholding decisions, patients who had a further decision of

<figure><img src="image_4.png" /><figcaption>**Fig. 1** Flowchart of study population</figcaption></figure>
<table><caption>**Table 1** Characteristics of the included study population according to LST withholding or withdrawing during ICU stay</caption><thead><tr><th>Variable</th><th>Missing</th><th>All (n=4671)</th><th>No limitation (n=3996)</th><th>LST withholding (n=378)</th><th>LST withdrawing (n=297)</th></tr></thead><tbody><tr><td>Age (years), median (IQR)</td><td>–</td><td>63 (54, 70)</td><td>61 (53, 69)</td><td>70 (63, 76)</td><td>71 (63, 78)</td></tr><tr><td>Female, n (%)</td><td>33</td><td>1191 (26)</td><td>1009 (25)</td><td>108 (29)</td><td>74 (25)</td></tr><tr><td>Healthcare worker, n (%)</td><td>83</td><td>160 (3)</td><td>149 (4)</td><td>7 (2)</td><td>4 (1)</td></tr><tr><td>Nursing home resident, n (%)</td><td>47</td><td>74 (2)</td><td>46 (1)</td><td>16 (4)</td><td>12 (4)</td></tr><tr><td>Obesity (BMI > 30 kg/m²), n (%)</td><td>336</td><td>1681 (39)</td><td>1457 (39)</td><td>134 (39)</td><td>90 (33)</td></tr><tr><td>SAPS II score, median (IQR)</td><td>403</td><td>37 (28, 50)</td><td>35 (27, 48)</td><td>44 (36, 56)</td><td>47 (35, 59)</td></tr><tr><td>SOFA score, median (IQR)</td><td>679</td><td>5 (3, 8)</td><td>4 (3, 8)</td><td>7 (4, 10)</td><td>7 (4, 10)</td></tr><tr><td>Hypertension, n (%)</td><td></td><td>2221 (48)</td><td>1831 (46)</td><td>224 (59)</td><td>166 (56)</td></tr><tr><td>Diabetes, n (%)</td><td></td><td>1271 (27)</td><td>1034 (26)</td><td>134 (35)</td><td>103 (35)</td></tr><tr><td>Coronary artery disease, n (%)</td><td></td><td>509 (11)</td><td>381 (10)</td><td>71 (19)</td><td>57 (19)</td></tr><tr><td>Chronic heart failure, n (%)</td><td></td><td>172 (4)</td><td>111 (3)</td><td>32 (8)</td><td>29 (10)</td></tr><tr><td>Chronic respiratory disease, n (%)</td><td>40</td><td>993 (21)</td><td>804 (20)</td><td>106 (28)</td><td>83 (28)</td></tr><tr><td>Immunodeficiency, n (%)</td><td>38</td><td>337 (7)</td><td>263 (7)</td><td>38 (10)</td><td>36 (12)</td></tr><tr><td>Chronic renal failure, n (%)</td><td>38</td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td></td><td>324 (7)</td><td>247 (6)</td><td>45 (12)</td><td>32 (11)</td></tr><tr><td>Chronic dialysis</td><td></td><td>112 (2)</td><td>88 (2)</td><td>15 (4)</td><td>9 (3)</td></tr><tr><td>Hematological malignancy, n (%)</td><td></td><td>129 (3)</td><td>93 (2)</td><td>17 (4)</td><td>19 (6)</td></tr><tr><td>Clinical frailty scale score</td><td>465</td><td>2 (2–3)</td><td>2 (2–3)</td><td>3 (2–4)</td><td>3 (2–4)</td></tr><tr><td>Date of ICU admission, n (%)</td><td>167</td><td></td><td></td><td></td><td></td></tr><tr><td>Before March 15, 2020</td><td></td><td>n=295</td><td>225 (76)</td><td>39 (13)</td><td>31 (11)</td></tr><tr><td>From March 16 to 31, 2020</td><td></td><td>n=2752</td><td>2343 (85)</td><td>227 (8)</td><td>182 (7)</td></tr><tr><td>From April 1 to 15, 2020</td><td></td><td>n=1214</td><td>1072 (88)</td><td>75 (6)</td><td>67 (6)</td></tr><tr><td>After April 16, 2020</td><td></td><td>n=243</td><td>208 (86)</td><td>22 (9)</td><td>13 (5)</td></tr><tr><td>Time between first symptoms and ICU admission</td><td>404</td><td></td><td></td><td></td><td></td></tr><tr><td>&lt; 4 days</td><td></td><td>n=421</td><td>327 (78)</td><td>50 (12)</td><td>44 (10)</td></tr><tr><td>4–7 days</td><td></td><td>n=1379</td><td>1138 (83)</td><td>134 (10)</td><td>107 (8)</td></tr><tr><td>≥ 8 days</td><td></td><td>n=2467</td><td>2200 (89)</td><td>151 (6)</td><td>116 (5)</td></tr><tr><td>During the first 24 h, n (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Standard oxygen therapy</td><td>94</td><td>1367 (29)</td><td>1202 (30)</td><td>103 (27)</td><td>62 (21)</td></tr><tr><td>Noninvasive ventilation</td><td>148</td><td>271 (6)</td><td>217 (5)</td><td>30 (8)</td><td>24 (8)</td></tr><tr><td>High-flow oxygen</td><td>162</td><td>873 (19)</td><td>767 (19)</td><td>67 (18)</td><td>39 (13)</td></tr><tr><td>Invasive mechanical ventilation</td><td>76</td><td>2866 (61)</td><td>2377 (60)</td><td>260 (69)</td><td>229 (77)</td></tr><tr><td>ARDS severity*, n (%)</td><td>412</td><td></td><td></td><td></td><td></td></tr><tr><td>Mild</td><td></td><td>580 (24)</td><td>488 (24)</td><td>43 (19)</td><td>49 (24)</td></tr><tr><td>Moderate</td><td></td><td>1197 (49)</td><td>1000 (49)</td><td>109 (47)</td><td>88 (44)</td></tr><tr><td>Severe</td><td></td><td>677 (28)</td><td>534 (26)</td><td>80 (34)</td><td>63 (32)</td></tr><tr><td>Static compliance, mL/cmH<sub>2</sub>O</td><td>341</td><td>35 (29–43)</td><td>35 (29–43)</td><td>33.6 (28–42)</td><td>33.3 (28–42)</td></tr></tbody></table>

LST life-sustaining treatment, IQR interquartile range, SAPS II simplified acute physiology score II, BMI body mass index, ICU intensive care unit, SOFA sequential organ failure assessment, ARDS acute respiratory distress syndrome

*Data reported for patients under invasive mechanical ventilation

LST withdrawal included more treatment restrictions. LST withdrawal involved predominantly vasopressors (53.2%), renal replacement therapy (41.1%), and mechanical ventilation (31.6%). Extubation was decided in 24.9%. Of note, among all patients with a withholding decision (656), only 59 (9%) patients had solely a

do-not-resuscitate order, and among these 59 patients, only 7 patients had finally a withdrawing.

At 28 and 90 days, the cumulative incidence of LST limitation in patients with complete date data (4549/4671) was 12.4% and 14.8%, respectively (Fig. 2A). Decisions on LST limitations were taken at a median of 8 days (range
<table><caption>**Table 1** Characteristics of the included study population according to LST withholding or withdrawing during ICU stay</caption><thead><tr><th>Variable</th><th>Missing</th><th>All (n=4671)</th><th>No limitation (n=3996)</th><th>LST withholding (n=378)</th><th>LST withdrawing (n=297)</th></tr></thead><tbody><tr><td>Age (years), median (IQR)</td><td>–</td><td>63 (54, 70)</td><td>61 (53, 69)</td><td>70 (63, 76)</td><td>71 (63, 78)</td></tr><tr><td>Female, n (%)</td><td>33</td><td>1191 (26)</td><td>1009 (25)</td><td>108 (29)</td><td>74 (25)</td></tr><tr><td>Healthcare worker, n (%)</td><td>83</td><td>160 (3)</td><td>149 (4)</td><td>7 (2)</td><td>4 (1)</td></tr><tr><td>Nursing home resident, n (%)</td><td>47</td><td>74 (2)</td><td>46 (1)</td><td>16 (4)</td><td>12 (4)</td></tr><tr><td>Obesity (BMI > 30 kg/m²), n (%)</td><td>336</td><td>1681 (39)</td><td>1457 (39)</td><td>134 (39)</td><td>90 (33)</td></tr><tr><td>SAPS II score, median (IQR)</td><td>403</td><td>37 (28, 50)</td><td>35 (27, 48)</td><td>44 (36, 56)</td><td>47 (35, 59)</td></tr><tr><td>SOFA score, median (IQR)</td><td>679</td><td>5 (3, 8)</td><td>4 (3, 8)</td><td>7 (4, 10)</td><td>7 (4, 10)</td></tr><tr><td>Hypertension, n (%)</td><td></td><td>2221 (48)</td><td>1831 (46)</td><td>224 (59)</td><td>166 (56)</td></tr><tr><td>Diabetes, n (%)</td><td></td><td>1271 (27)</td><td>1034 (26)</td><td>134 (35)</td><td>103 (35)</td></tr><tr><td>Coronary artery disease, n (%)</td><td></td><td>509 (11)</td><td>381 (10)</td><td>71 (19)</td><td>57 (19)</td></tr><tr><td>Chronic heart failure, n (%)</td><td></td><td>172 (4)</td><td>111 (3)</td><td>32 (8)</td><td>29 (10)</td></tr><tr><td>Chronic respiratory disease, n (%)</td><td>40</td><td>993 (21)</td><td>804 (20)</td><td>106 (28)</td><td>83 (28)</td></tr><tr><td>Immunodeficiency, n (%)</td><td>38</td><td>337 (7)</td><td>263 (7)</td><td>38 (10)</td><td>36 (12)</td></tr><tr><td>Chronic renal failure, n (%)</td><td>38</td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td></td><td>324 (7)</td><td>247 (6)</td><td>45 (12)</td><td>32 (11)</td></tr><tr><td>Chronic dialysis</td><td></td><td>112 (2)</td><td>88 (2)</td><td>15 (4)</td><td>9 (3)</td></tr><tr><td>Hematological malignancy, n (%)</td><td></td><td>129 (3)</td><td>93 (2)</td><td>17 (4)</td><td>19 (6)</td></tr><tr><td>Clinical frailty scale score</td><td>465</td><td>2 (2–3)</td><td>2 (2–3)</td><td>3 (2–4)</td><td>3 (2–4)</td></tr><tr><td>Date of ICU admission, n (%)</td><td>167</td><td></td><td></td><td></td><td></td></tr><tr><td>Before March 15, 2020</td><td></td><td>n=295</td><td>225 (76)</td><td>39 (13)</td><td>31 (11)</td></tr><tr><td>From March 16 to 31, 2020</td><td></td><td>n=2752</td><td>2343 (85)</td><td>227 (8)</td><td>182 (7)</td></tr><tr><td>From April 1 to 15, 2020</td><td></td><td>n=1214</td><td>1072 (88)</td><td>75 (6)</td><td>67 (6)</td></tr><tr><td>After April 16, 2020</td><td></td><td>n=243</td><td>208 (86)</td><td>22 (9)</td><td>13 (5)</td></tr><tr><td>Time between first symptoms and ICU admission</td><td>404</td><td></td><td></td><td></td><td></td></tr><tr><td>&lt; 4 days</td><td></td><td>n=421</td><td>327 (78)</td><td>50 (12)</td><td>44 (10)</td></tr><tr><td>4–7 days</td><td></td><td>n=1379</td><td>1138 (83)</td><td>134 (10)</td><td>107 (8)</td></tr><tr><td>≥ 8 days</td><td></td><td>n=2467</td><td>2200 (89)</td><td>151 (6)</td><td>116 (5)</td></tr><tr><td>During the first 24 h, n (%)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Standard oxygen therapy</td><td>94</td><td>1367 (29)</td><td>1202 (30)</td><td>103 (27)</td><td>62 (21)</td></tr><tr><td>Noninvasive ventilation</td><td>148</td><td>271 (6)</td><td>217 (5)</td><td>30 (8)</td><td>24 (8)</td></tr><tr><td>High-flow oxygen</td><td>162</td><td>873 (19)</td><td>767 (19)</td><td>67 (18)</td><td>39 (13)</td></tr><tr><td>Invasive mechanical ventilation</td><td>76</td><td>2866 (61)</td><td>2377 (60)</td><td>260 (69)</td><td>229 (77)</td></tr><tr><td>ARDS severity*, n (%)</td><td>412</td><td></td><td></td><td></td><td></td></tr><tr><td>Mild</td><td></td><td>580 (24)</td><td>488 (24)</td><td>43 (19)</td><td>49 (24)</td></tr><tr><td>Moderate</td><td></td><td>1197 (49)</td><td>1000 (49)</td><td>109 (47)</td><td>88 (44)</td></tr><tr><td>Severe</td><td></td><td>677 (28)</td><td>534 (26)</td><td>80 (34)</td><td>63 (32)</td></tr><tr><td>Static compliance, mL/cmH<sub>2</sub>O</td><td>341</td><td>35 (29–43)</td><td>35 (29–43)</td><td>33.6 (28–42)</td><td>33.3 (28–42)</td></tr></tbody></table>

LST life-sustaining treatment, IQR interquartile range, SAPS II simplified acute physiology score II, BMI body mass index, ICU intensive care unit, SOFA sequential organ failure assessment, ARDS acute respiratory distress syndrome

*Data reported for patients under invasive mechanical ventilation

LST withdrawal included more treatment restrictions. LST withdrawal involved predominantly vasopressors (53.2%), renal replacement therapy (41.1%), and mechanical ventilation (31.6%). Extubation was decided in 24.9%. Of note, among all patients with a withholding decision (656), only 59 (9%) patients had solely a

do-not-resuscitate order, and among these 59 patients, only 7 patients had finally a withdrawing.

At 28 and 90 days, the cumulative incidence of LST limitation in patients with complete date data (4549/4671) was 12.4% and 14.8%, respectively (Fig. 2A). Decisions on LST limitations were taken at a median of 8 days (range
<table><caption>**Table 2** Patient characteristics associated with LST limitations</caption><thead><tr><th>Factor</th><th>Crude odds ratio (95% confidence interval)</th><th>Adjusted odds ratio (95% confidence interval)</th><th>P value</th></tr></thead><tbody><tr><td>Age (years)</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>[16-65]</td><td>-</td><td>-</td><td></td></tr><tr><td>[65-75]</td><td>2.50 (1.93 to 3.23)</td><td>2.00 (1.51 to 2.65)</td><td>&lt;0.001</td></tr><tr><td>[75-91]</td><td>10.19 (7.64 to 13.59)</td><td>8.28 (5.94 to 11.54)</td><td>&lt;0.001</td></tr><tr><td>Female</td><td>1.07 (0.85 to 1.35)</td><td>0.91 (0.69 to 1.20)</td><td>0.507</td></tr><tr><td>Nursing home resident</td><td>3.86 (2.11 to 7.06)</td><td>1.41 (0.65 to 3.07)</td><td>0.381</td></tr><tr><td>Clinical frailty scale score</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>[1-3]</td><td>-</td><td>-</td><td></td></tr><tr><td>(3-4)</td><td>3.28 (2.42 to 4.45)</td><td>1.61 (1.11 to 2.32)</td><td>0.012</td></tr><tr><td>(4-10)</td><td>6.21 (4.27 to 9.03)</td><td>3.03 (1.89 to 4.83)</td><td>&lt;0.001</td></tr><tr><td>Body mass index ≥ 30 kg/m<sup>-2</sup></td><td>0.88 (0.71 to 1.09)</td><td>0.92 (0.71 to 1.19)</td><td>0.529</td></tr><tr><td>Hypertension</td><td>1.81 (1.47 to 2.23)</td><td>1.06 (0.82 to 1.37)</td><td>0.647</td></tr><tr><td>Diabetes</td><td>1.64 (1.32 to 2.04)</td><td>1.39 (1.06 to 1.81)</td><td>0.016</td></tr><tr><td>Coronary artery disease</td><td>2.59 (1.96 to 3.41)</td><td>1.31 (0.93 to 1.85)</td><td>0.119</td></tr><tr><td>Chronic heart failure</td><td>4.25 (2.85 to 6.33)</td><td>1.80 (1.11 to 2.91)</td><td>0.016</td></tr><tr><td>Chronic respiratory disease</td><td>1.65 (1.31 to 2.09)</td><td>1.26 (0.95 to 1.65)</td><td>0.105</td></tr><tr><td>Immunodeficiency</td><td>1.61 (1.13 to 2.30)</td><td>1.44 (0.95 to 2.19)</td><td>0.086</td></tr><tr><td>Chronic renal failure</td><td></td><td></td><td>0.573</td></tr><tr><td>None</td><td>-</td><td>-</td><td></td></tr><tr><td>Yes w/o dialysis</td><td>2.32 (1.65 to 3.24)</td><td>1.13 (0.74 to 1.73)</td><td>0.578</td></tr><tr><td>Chronic dialysis</td><td>2.21 (1.27 to 3.86)</td><td>1.43 (0.72 to 2.86)</td><td>0.311</td></tr><tr><td>Hematological malignancy</td><td>1.99 (1.32 to 3.01)</td><td>1.77 (1.09 to 2.88)</td><td>0.020</td></tr><tr><td>Period of admission</td><td></td><td></td><td>0.106</td></tr><tr><td>Before March 15, 2020</td><td>-</td><td>-</td><td></td></tr><tr><td>March 16 to 31, 2020</td><td>0.51 (0.35 to 0.73)</td><td>0.73 (0.47 to 1.14)</td><td>0.164</td></tr><tr><td>April 1 to 15, 2020</td><td>0.36 (0.24 to 0.55)</td><td>0.55 (0.33 to 0.92)</td><td>0.021</td></tr><tr><td>After April 16, 2020</td><td>0.47 (0.26 to 0.83)</td><td>0.58 (0.29 to 1.13)</td><td>0.110</td></tr><tr><td>Time since 1st symptom</td><td></td><td></td><td>0.003</td></tr><tr><td>&lt;4 days</td><td>-</td><td>-</td><td></td></tr><tr><td>4-7 days</td><td>0.78 (0.56 to 1.08)</td><td>1.02 (0.70 to 1.50)</td><td>0.902</td></tr><tr><td>≥ 8 days</td><td>0.42 (0.30 to 0.58)</td><td>0.67 (0.46 to 0.98)</td><td>0.041</td></tr><tr><td>ICU load (%)</td><td></td><td></td><td>0.010</td></tr><tr><td>≤ 100</td><td>-</td><td>-</td><td></td></tr><tr><td>(100-150]</td><td>0.58 (0.43 to 0.78)</td><td>0.70 (0.50 to 0.99)</td><td>0.042</td></tr><tr><td>(150-200]</td><td>0.47 (0.34 to 0.63)</td><td>0.63 (0.44 to 0.91)</td><td>0.014</td></tr><tr><td>&gt; 200</td><td>0.57 (0.41 to 0.80)</td><td>1.14 (0.75 to 1.73)</td><td>0.533</td></tr><tr><td>First 24-h respiratory failure severity</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>Not intubated</td><td>-</td><td>-</td><td></td></tr><tr><td>Mild ARDS PF (200-600]</td><td>1.64 (1.21 to 2.23)</td><td>1.89 (1.27 to 2.81)</td><td>0.002</td></tr><tr><td>Moderate ARDS PF (100-200]</td><td>1.80 (1.37 to 2.37)</td><td>2.03 (1.40 to 2.94)</td><td>&lt;0.001</td></tr><tr><td>Severe ARDS PF (0-100]</td><td>3.23 (2.37 to 4.41)</td><td>3.61 (2.42 to 5.37)</td><td>&lt;0.001</td></tr><tr><td>SOFA cardiovascular ≥ 3</td><td>1.84 (1.49 to 2.27)</td><td>1.11 (0.83 to 1.48)</td><td>0.499</td></tr><tr><td>SOFA renal ≥ 3</td><td>1.97 (1.39 to 2.80)</td><td>1.39 (0.90 to 2.17)</td><td>0.141</td></tr></tbody></table>

LST life-sustaining treatment, ICU intensive care unit, SOFA sequential organ failure assessment, ARDS acute respiratory distress syndrome
<table><caption>**Table 2** Patient characteristics associated with LST limitations</caption><thead><tr><th>Factor</th><th>Crude odds ratio (95% confidence interval)</th><th>Adjusted odds ratio (95% confidence interval)</th><th>P value</th></tr></thead><tbody><tr><td>Age (years)</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>[16-65]</td><td>-</td><td>-</td><td></td></tr><tr><td>[65-75]</td><td>2.50 (1.93 to 3.23)</td><td>2.00 (1.51 to 2.65)</td><td>&lt;0.001</td></tr><tr><td>[75-91]</td><td>10.19 (7.64 to 13.59)</td><td>8.28 (5.94 to 11.54)</td><td>&lt;0.001</td></tr><tr><td>Female</td><td>1.07 (0.85 to 1.35)</td><td>0.91 (0.69 to 1.20)</td><td>0.507</td></tr><tr><td>Nursing home resident</td><td>3.86 (2.11 to 7.06)</td><td>1.41 (0.65 to 3.07)</td><td>0.381</td></tr><tr><td>Clinical frailty scale score</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>[1-3]</td><td>-</td><td>-</td><td></td></tr><tr><td>(3-4)</td><td>3.28 (2.42 to 4.45)</td><td>1.61 (1.11 to 2.32)</td><td>0.012</td></tr><tr><td>(4-10)</td><td>6.21 (4.27 to 9.03)</td><td>3.03 (1.89 to 4.83)</td><td>&lt;0.001</td></tr><tr><td>Body mass index ≥ 30 kg/m<sup>-2</sup></td><td>0.88 (0.71 to 1.09)</td><td>0.92 (0.71 to 1.19)</td><td>0.529</td></tr><tr><td>Hypertension</td><td>1.81 (1.47 to 2.23)</td><td>1.06 (0.82 to 1.37)</td><td>0.647</td></tr><tr><td>Diabetes</td><td>1.64 (1.32 to 2.04)</td><td>1.39 (1.06 to 1.81)</td><td>0.016</td></tr><tr><td>Coronary artery disease</td><td>2.59 (1.96 to 3.41)</td><td>1.31 (0.93 to 1.85)</td><td>0.119</td></tr><tr><td>Chronic heart failure</td><td>4.25 (2.85 to 6.33)</td><td>1.80 (1.11 to 2.91)</td><td>0.016</td></tr><tr><td>Chronic respiratory disease</td><td>1.65 (1.31 to 2.09)</td><td>1.26 (0.95 to 1.65)</td><td>0.105</td></tr><tr><td>Immunodeficiency</td><td>1.61 (1.13 to 2.30)</td><td>1.44 (0.95 to 2.19)</td><td>0.086</td></tr><tr><td>Chronic renal failure</td><td></td><td></td><td>0.573</td></tr><tr><td>None</td><td>-</td><td>-</td><td></td></tr><tr><td>Yes w/o dialysis</td><td>2.32 (1.65 to 3.24)</td><td>1.13 (0.74 to 1.73)</td><td>0.578</td></tr><tr><td>Chronic dialysis</td><td>2.21 (1.27 to 3.86)</td><td>1.43 (0.72 to 2.86)</td><td>0.311</td></tr><tr><td>Hematological malignancy</td><td>1.99 (1.32 to 3.01)</td><td>1.77 (1.09 to 2.88)</td><td>0.020</td></tr><tr><td>Period of admission</td><td></td><td></td><td>0.106</td></tr><tr><td>Before March 15, 2020</td><td>-</td><td>-</td><td></td></tr><tr><td>March 16 to 31, 2020</td><td>0.51 (0.35 to 0.73)</td><td>0.73 (0.47 to 1.14)</td><td>0.164</td></tr><tr><td>April 1 to 15, 2020</td><td>0.36 (0.24 to 0.55)</td><td>0.55 (0.33 to 0.92)</td><td>0.021</td></tr><tr><td>After April 16, 2020</td><td>0.47 (0.26 to 0.83)</td><td>0.58 (0.29 to 1.13)</td><td>0.110</td></tr><tr><td>Time since 1st symptom</td><td></td><td></td><td>0.003</td></tr><tr><td>&lt;4 days</td><td>-</td><td>-</td><td></td></tr><tr><td>4-7 days</td><td>0.78 (0.56 to 1.08)</td><td>1.02 (0.70 to 1.50)</td><td>0.902</td></tr><tr><td>≥ 8 days</td><td>0.42 (0.30 to 0.58)</td><td>0.67 (0.46 to 0.98)</td><td>0.041</td></tr><tr><td>ICU load (%)</td><td></td><td></td><td>0.010</td></tr><tr><td>≤ 100</td><td>-</td><td>-</td><td></td></tr><tr><td>(100-150]</td><td>0.58 (0.43 to 0.78)</td><td>0.70 (0.50 to 0.99)</td><td>0.042</td></tr><tr><td>(150-200]</td><td>0.47 (0.34 to 0.63)</td><td>0.63 (0.44 to 0.91)</td><td>0.014</td></tr><tr><td>&gt; 200</td><td>0.57 (0.41 to 0.80)</td><td>1.14 (0.75 to 1.73)</td><td>0.533</td></tr><tr><td>First 24-h respiratory failure severity</td><td></td><td></td><td>&lt;0.001</td></tr><tr><td>Not intubated</td><td>-</td><td>-</td><td></td></tr><tr><td>Mild ARDS PF (200-600]</td><td>1.64 (1.21 to 2.23)</td><td>1.89 (1.27 to 2.81)</td><td>0.002</td></tr><tr><td>Moderate ARDS PF (100-200]</td><td>1.80 (1.37 to 2.37)</td><td>2.03 (1.40 to 2.94)</td><td>&lt;0.001</td></tr><tr><td>Severe ARDS PF (0-100]</td><td>3.23 (2.37 to 4.41)</td><td>3.61 (2.42 to 5.37)</td><td>&lt;0.001</td></tr><tr><td>SOFA cardiovascular ≥ 3</td><td>1.84 (1.49 to 2.27)</td><td>1.11 (0.83 to 1.48)</td><td>0.499</td></tr><tr><td>SOFA renal ≥ 3</td><td>1.97 (1.39 to 2.80)</td><td>1.39 (0.90 to 2.17)</td><td>0.141</td></tr></tbody></table>

LST life-sustaining treatment, ICU intensive care unit, SOFA sequential organ failure assessment, ARDS acute respiratory distress syndrome
<figure><img src="image_3.png" /><figcaption>**Fig. 2** A Cumulative incidence plot of time from ICU admission to first LST limitation decision, and B survival probability after LST withholding or withdrawing decisions within 14 days after ICU admission</figcaption></figure>

3–21) after ICU admission. The cumulative incidence of LST limitation in patients with complete data for all variables (3051/4671) is shown in Figure E1 (see Additional file 1: Data Supplement). The results were similar between these two cohorts.

## Factors associated with LST limitations

Median ICU load was 126% (range 71–187). ICU load distribution at the patient level and according to LST categories are presented in Figures E2 and E3 (see Additional file 1: Online Data Supplement). The multivariable model included 3051 patients (Table 2). Age, clinical frailty scale score, and first 24-h respiratory failure severity were independently associated with a decision of LST limitation. Importantly, the odds ratios of the age categories ≥ 65 and ≤ 75 years and ≥ 75 years were 2.00 (1.51–2.64) and 8.30 (5.95–11.6), respectively, compared to patients aged < 65 years (*p* < 0.001). The decision of LST limitation was significantly associated with pre-frail and frail status compared to non-frail patients, with odds ratios of 1.61 (1.11–2.32) and 3.02 (1.89–4.82), respectively (*p* < 0.001). By contrast, an ICU load over 100% was associated with a decreased probability of LST limitation, but time to LST decision did not differ according to ICU load category. A sensitivity analysis yielded similar results when omitting centres including < 10 patients (data not shown).

Centre characteristics, adjunct measures during ICU stay according to LST limitation status, and time to LST decision according to ICU load category are presented in Tables E3, E4 and E5, respectively (see Additional file 1: Online Data Supplement).

## Variability of LST limitations between centres

Of the 163 participating centres, 121 included 10 patients or more, representing a total of 4492 patients. The estimated overall proportion of patients with an LST limitation was 12.5% (95% CI 11.0–14.2; Fig. 3). There was a significant heterogeneity between centres, with a tau of 0.539 (likelihood-ratio test *p* value < 0.001). Hence, it was expected that the prevalence of LST limitations in 95% of centres would lie within 4.7% and 29.1%. Similar results were observed in the subpopulation of patients aged ≥ 75 years and regardless to the number of patients included per centre (see Additional file 1: Tables E6, E7, Figure E4).

## Outcomes

Overall, 1347 patients (29%) died within 90 days of follow-up after ICU admission. An LST withholding or withdrawal decision during ICU stay preceded death in 561 patients (42%). Of the 675 patients who experienced treatment limitation during their ICU stay, 561 (83%) died within 90 days of follow-up. In-ICU death occurred for 279 (74%) and 282 (95%) patients, respectively, after
<figure><img src="image_5.png" /><figcaption>**Fig. 2** A Cumulative incidence plot of time from ICU admission to first LST limitation decision, and B survival probability after LST withholding or withdrawing decisions within 14 days after ICU admission</figcaption></figure>

3–21) after ICU admission. The cumulative incidence of LST limitation in patients with complete data for all variables (3051/4671) is shown in Figure E1 (see Additional file 1: Data Supplement). The results were similar between these two cohorts.

## Factors associated with LST limitations

Median ICU load was 126% (range 71–187). ICU load distribution at the patient level and according to LST categories are presented in Figures E2 and E3 (see Additional file 1: Online Data Supplement). The multivariable model included 3051 patients (Table 2). Age, clinical frailty scale score, and first 24-h respiratory failure severity were independently associated with a decision of LST limitation. Importantly, the odds ratios of the age categories ≥ 65 and ≤ 75 years and ≥ 75 years were 2.00 (1.51–2.64) and 8.30 (5.95–11.6), respectively, compared to patients aged < 65 years (p < 0.001). The decision of LST limitation was significantly associated with pre-frail and frail status compared to non-frail patients, with odds ratios of 1.61 (1.11–2.32) and 3.02 (1.89–4.82), respectively (p < 0.001). By contrast, an ICU load over 100% was associated with a decreased probability of LST limitation, but time to LST decision did not differ according to ICU load category. A sensitivity analysis yielded similar results when omitting centres including < 10 patients (data not shown).

Centre characteristics, adjunct measures during ICU stay according to LST limitation status, and time to LST decision according to ICU load category are presented in Tables E3, E4 and E5, respectively (see Additional file 1: Online Data Supplement).

## Variability of LST limitations between centres

Of the 163 participating centres, 121 included 10 patients or more, representing a total of 4492 patients. The estimated overall proportion of patients with an LST limitation was 12.5% (95% CI 11.0–14.2; Fig. 3). There was a significant heterogeneity between centres, with a tau of 0.539 (likelihood-ratio test *p* value < 0.001). Hence, it was expected that the prevalence of LST limitations in 95% of centres would lie within 4.7% and 29.1%. Similar results were observed in the subpopulation of patients aged ≥ 75 years and regardless to the number of patients included per centre (see Additional file 1: Tables E6, E7, Figure E4).

## Outcomes

Overall, 1347 patients (29%) died within 90 days of follow-up after ICU admission. An LST withholding or withdrawal decision during ICU stay preceded death in 561 patients (42%). Of the 675 patients who experienced treatment limitation during their ICU stay, 561 (83%) died within 90 days of follow-up. In-ICU death occurred for 279 (74%) and 282 (95%) patients, respectively, after
<figure><img src="image_4.png" /><figcaption>**Fig. 3** Distribution of estimated prevalence of life-sustaining treatment limitations according to centres</figcaption></figure>

LST withholding and withdrawal. Survival time after the first treatment limitation decision was evaluated in patients with an LST decision within 14 days after ICU admission. Median survival time was 3 days (range 1–11), with a 28- and 60-day survival after a first limitation of 15.7% (95% CI 12.8–19.4) and 14.2% (95% CI 11.4–17.7), respectively (Fig. 2B).

Discussion

This European multicentre study of 4671 patients provides the most exhaustive descriptive analysis to date on LST limitations in patients admitted to the ICU during the first surge of the COVID-19 pandemic. The global period prevalence of in-ICU LST limitation decisions was 14.5%, with an important variability between centres. However, this variability was not related to the patient and/or centre characteristics analyzed in the study. Age, clinical frailty scale score, and respiratory severity were the patient characteristics most associated with decisions of LST limitations. Interestingly, while ICU load reflected an overwhelming surge of COVID-19 patients admitted to the ICU, the strain on ICU capacities was associated with a decreased probability of LST limitation. Not unexpectedly, decisions of LST withholding and withdrawal were followed by high short-term mortality and frequently preceded in-ICU death.

With regards to previously published data on LST limitations in the ICU [10, 14, 15], our findings reflected a similar incidence rate and patient characteristics taken into account for ethical decision-making. A 14.5% prevalence of LST limitations is consistent with the recently reported incidence of 11.8% of all-cause ICU admissions reported in the worldwide Ethicus-2 study [10]. Older age and illness severity at ICU admission was associated with limitations of LST as already demonstrated in a general population of critically ill patients [14]. However, the frailty score was only found to be associated with decisions of LST limitations in the ICU in the very elderly (≥ 80 years) [13]. To the best of our knowledge, this is the first time that factors associated with LST limitations in a setting of an overwhelming surge of critically ill patients or in a subpopulation of acute hypoxic respiratory failure patients have been identified.

The important (up to six-fold) variability of the prevalence of LST limitations observed between centres in a homogeneous population of severe COVID-19 patients represents a significant and original result of our study. Interestingly, this variability was not explained by patient or organizational characteristics of the centres. Indeed, between-ICU variability in ethical decision-making in the same range has already been reported in nationwide and
<figure><img src="image_6.png" /><figcaption>**Fig. 3** Distribution of estimated prevalence of life-sustaining treatment limitations according to centres</figcaption></figure>

LST withholding and withdrawal. Survival time after the first treatment limitation decision was evaluated in patients with an LST decision within 14 days after ICU admission. Median survival time was 3 days (range 1–11), with a 28- and 60-day survival after a first limitation of 15.7% (95% CI 12.8–19.4) and 14.2% (95% CI 11.4–17.7), respectively (Fig. 2B).

Discussion

This European multicentre study of 4671 patients provides the most exhaustive descriptive analysis to date on LST limitations in patients admitted to the ICU during the first surge of the COVID-19 pandemic. The global period prevalence of in-ICU LST limitation decisions was 14.5%, with an important variability between centres. However, this variability was not related to the patient and/or centre characteristics analyzed in the study. Age, clinical frailty scale score, and respiratory severity were the patient characteristics most associated with decisions of LST limitations. Interestingly, while ICU load reflected an overwhelming surge of COVID-19 patients admitted to the ICU, the strain on ICU capacities was associated with a decreased probability of LST limitation. Not unexpectedly, decisions of LST withholding and withdrawal were followed by high short-term mortality and frequently preceded in-ICU death.

With regards to previously published data on LST limitations in the ICU [10, 14, 15], our findings reflected a similar incidence rate and patient characteristics taken into account for ethical decision-making. A 14.5% prevalence of LST limitations is consistent with the recently reported incidence of 11.8% of all-cause ICU admissions reported in the worldwide Ethicus-2 study [10]. Older age and illness severity at ICU admission was associated with limitations of LST as already demonstrated in a general population of critically ill patients [14]. However, the frailty score was only found to be associated with decisions of LST limitations in the ICU in the very elderly (≥ 80 years) [13]. To the best of our knowledge, this is the first time that factors associated with LST limitations in a setting of an overwhelming surge of critically ill patients or in a subpopulation of acute hypoxic respiratory failure patients have been identified.

The important (up to six-fold) variability of the prevalence of LST limitations observed between centres in a homogeneous population of severe COVID-19 patients represents a significant and original result of our study. Interestingly, this variability was not explained by patient or organizational characteristics of the centres. Indeed, between-ICU variability in ethical decision-making in the same range has already been reported in nationwide and
international studies [10, 16, 25]. Some factors unrelated to individual characteristics have been identified as associated with this variability. For example, the frequency of LST limitations is higher in countries with a high gross domestic product and lower in countries where religion is important [13]. In addition, there is currently no uniform approach to the LST limitation decision-making process that could take into account all individual, relatives and social determinants, particularly in a new disease. Therefore, variability between ICUs possibly reflects differences in institutional policies [25].

A significant variability in mortality rates was reported in several nationwide studies during the COVID-19 pandemic, with some highlighting an increased mortality rate when ICU resources were strained, but without any clear explanation of the mechanism involved [2-7]. A retrospective study of 9891 patients who died in the ICU suggested the positive association of strain on ICU capacities and a shorter time to end-of-life decision-making [19]. In the context of important ethical discussions regarding the allocation of critical care resources during the first surge of the pandemic, it appeared important to investigate the effect of ICU load on LST limitation decisions. Using the parameter proposed by Bravata et al.,[4] we were able to calculate this marker reflecting strain on regional ICU resources from pre-pandemic baseline capacities and daily ICU bed occupancy data at the patient level. Despite an increased median of 126%, ICU load was associated with a lower treatment limitation probability. However, we were unable to investigate if this result was due to triage before ICU admission. Another unexplored hypothesis to explain the increased mortality in regions of high ICU strain could be related to understaffing leading to suboptimal practices, with an impact on adverse events [18].

Of note, there are few data on LST limitations in the literature reporting an epidemiological analysis of severe COVID-19 patients during the pandemic [26], apart from the COVID European study, which described the characteristics of elderly patients admitted to ICUs [27]. The latter study reported a higher incidence rate of LST limitation at day 30 in COVID-19 patients compared to non-COVID-19 patients. LST limitation was associated with the frailty scale score[28] and the COVID-19 incidence rate [29], thus suggesting that decisions of LST limitations could potentially be influenced by pressure on the healthcare system. Unfortunately, the authors did not explicitly investigate the relationship of LST limitations with strain on ICU resources.

The high mortality following decisions of LST withholding and withdrawal in our cohort of severe COVID-19 patients is similar to rates reported in the

pre-pandemic literature [10]. However, when added to the prevalence of LST limitations observed and the unexplained variability across centres, these results emphasize the need to improve the reporting of LST limitations in randomized, controlled trials of COVID-19 patients managed in the ICU. Indeed, knowledge of LST decisions is of importance when assessing mortality or short-term endpoints, such as organ support-free days or duration, as both the modality and timing of LST limitations undoubtedly impact on mortality. Messika et al. demonstrated that LST limitations were rarely reported in randomized, controlled trials in critical care and that an imbalance between two groups concerning the proportion of LST decisions may affect results, particularly in open design trials [30]. To date, no randomized, controlled trial including COVID-19 patients in the ICU setting has reported rates and timing of LST limitations or proposed the standardization of treatment limitation decisions.

The strength of our study lies in the detailed description of decisions of LST limitations in the ICU during the first surge of the COVID-19 pandemic. However, the study has several limitations. First, we focused on decisions of LST limitation during ICU stay, but we are not able to provide data on triage before ICU admission. Second, our analysis was restricted to patients admitted to the ICU during the first surge. Considering likely changes of ICU practices after the first wave and a steep learning curve in the context of this new disease, we cannot exclude a subsequent different prevalence of LST limitations. However, some of our findings in the particular context of COVID-19 confirmed previous reports in a general ICU patient population. Third, as reported in the tables, some variables have missing data due to an important workload for intensivists during the first surge of the pandemic, which prevented the completion of research case report forms. Fourth, we did not investigate the variability of the timing of LST limitations between centres. Finally, we recognize that the method used to calculate the ICU load parameter over the entire patient ICU stay may have underestimated the exact load of care on a given day. Considering that all LST limitation decisions have been made during the ICU stay, we believe that this approach has limited the temporal delay between ICU load and LST limitation decision. In addition, we made the assumption that ICU load was the best parameter to assess ICU strain, with the hypothesis that the COVID-19-related ICU load was inferior to 100% of baseline ICU bed occupancy in France and Belgium before March 19, 2020, which is the date from when daily ICU occupancy data were communicated.
international studies [10, 16, 25]. Some factors unrelated to individual characteristics have been identified as associated with this variability. For example, the frequency of LST limitations is higher in countries with a high gross domestic product and lower in countries where religion is important [13]. In addition, there is currently no uniform approach to the LST limitation decision-making process that could take into account all individual, relatives and social determinants, particularly in a new disease. Therefore, variability between ICUs possibly reflects differences in institutional policies [25].

A significant variability in mortality rates was reported in several nationwide studies during the COVID-19 pandemic, with some highlighting an increased mortality rate when ICU resources were strained, but without any clear explanation of the mechanism involved [2-7]. A retrospective study of 9891 patients who died in the ICU suggested the positive association of strain on ICU capacities and a shorter time to end-of-life decision-making [19]. In the context of important ethical discussions regarding the allocation of critical care resources during the first surge of the pandemic, it appeared important to investigate the effect of ICU load on LST limitation decisions. Using the parameter proposed by Bravata et al.,[4] we were able to calculate this marker reflecting strain on regional ICU resources from pre-pandemic baseline capacities and daily ICU bed occupancy data at the patient level. Despite an increased median of 126%, ICU load was associated with a lower treatment limitation probability. However, we were unable to investigate if this result was due to triage before ICU admission. Another unexplored hypothesis to explain the increased mortality in regions of high ICU strain could be related to understaffing leading to suboptimal practices, with an impact on adverse events [18].

Of note, there are few data on LST limitations in the literature reporting an epidemiological analysis of severe COVID-19 patients during the pandemic [26], apart from the COVID European study, which described the characteristics of elderly patients admitted to ICUs [27]. The latter study reported a higher incidence rate of LST limitation at day 30 in COVID-19 patients compared to non-COVID-19 patients. LST limitation was associated with the frailty scale score[28] and the COVID-19 incidence rate [29], thus suggesting that decisions of LST limitations could potentially be influenced by pressure on the healthcare system. Unfortunately, the authors did not explicitly investigate the relationship of LST limitations with strain on ICU resources.

The high mortality following decisions of LST withholding and withdrawal in our cohort of severe COVID-19 patients is similar to rates reported in the

pre-pandemic literature [10]. However, when added to the prevalence of LST limitations observed and the unexplained variability across centres, these results emphasize the need to improve the reporting of LST limitations in randomized, controlled trials of COVID-19 patients managed in the ICU. Indeed, knowledge of LST decisions is of importance when assessing mortality or short-term endpoints, such as organ support-free days or duration, as both the modality and timing of LST limitations undoubtedly impact on mortality. Messika et al. demonstrated that LST limitations were rarely reported in randomized, controlled trials in critical care and that an imbalance between two groups concerning the proportion of LST decisions may affect results, particularly in open design trials [30]. To date, no randomized, controlled trial including COVID-19 patients in the ICU setting has reported rates and timing of LST limitations or proposed the standardization of treatment limitation decisions.

The strength of our study lies in the detailed description of decisions of LST limitations in the ICU during the first surge of the COVID-19 pandemic. However, the study has several limitations. First, we focused on decisions of LST limitation during ICU stay, but we are not able to provide data on triage before ICU admission. Second, our analysis was restricted to patients admitted to the ICU during the first surge. Considering likely changes of ICU practices after the first wave and a steep learning curve in the context of this new disease, we cannot exclude a subsequent different prevalence of LST limitations. However, some of our findings in the particular context of COVID-19 confirmed previous reports in a general ICU patient population. Third, as reported in the tables, some variables have missing data due to an important workload for intensivists during the first surge of the pandemic, which prevented the completion of research case report forms. Fourth, we did not investigate the variability of the timing of LST limitations between centres. Finally, we recognize that the method used to calculate the ICU load parameter over the entire patient ICU stay may have underestimated the exact load of care on a given day. Considering that all LST limitation decisions have been made during the ICU stay, we believe that this approach has limited the temporal delay between ICU load and LST limitation decision. In addition, we made the assumption that ICU load was the best parameter to assess ICU strain, with the hypothesis that the COVID-19-related ICU load was inferior to 100% of baseline ICU bed occupancy in France and Belgium before March 19, 2020, which is the date from when daily ICU occupancy data were communicated.
## Conclusions

In this multicentre observational study, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations. Our results did not support the association between ICU load and higher mortality. Importantly, our results showed very significant differences in LST limitation rates between centres. LST limitations frequently preceded death, with a major impact on time of death, and this should be reported in future studies evaluating ICU mortality with severe COVID-19 or critically ill patients.

## Abbreviations

**ARDS** Acute respiratory distress syndrome

**ICU** Intensive care unit

**IQR** Interquartile range

**LST** Life-sustaining therapies

**REVA** Réseau Européen de recherche en Ventilation Artificielle

**SAPS-II** Simplified acute physiology score II

**SOFA** Sequential organ failure assessment

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13054-023-04349-1.

**Additional file 1.** Data collection. Epidemiological data used for ICU load calculation. Definitions of withholding and withdrawal of life-sustaining therapies (LST). Statistical analysis: multivariable model and list of the variables included in the model. **Table E1.** Modalities of LST withholding and withdrawal in the study population. **Table E2.** Modalities of LST withholding according to a further (or not) LST withdrawal decision. **Table E3.** Centre characteristics at the patient level. **Table E4.** Adjunct measures during ICU stay according to LST limitation status. **Table E5.** Time to LST decision from ICU admission according to ICU load category. **Figure E1.** (A) Cumulative incidence plot of time from ICU admission to first LST limitation decision, and (B) Survival probability after LST withholding or withdrawing decisions within 14 days after ICU admission involving only patients with complete data (3051 patients). **Figure E2.** Distribution of ICU load at the patient level. **Figure E3.** ICU load (%) according to LST categories. Subgroup analysis by centre size, and in patients aged ≥75 years. **Table E6.** Expected prevalences estimated by the multivariate model according to the number of patients in the centre. **Table E7.** Prevalence of decisions of LST limitations in patients aged ≥ 75 years. **Figure E4.** Forest plot of prevalences of decisions of LST limitations in the 15 centres with ≥ 10 patients aged ≥75 years.

**Additional file 2.** Participating Sites and COVID-ICU Investigators.

## Acknowledgements

This study was funded by the Assistance Publique Hôpitaux de Paris Foundation through the programme "Alliance Tous Unis Contre le Virus", Clinical Research and Development Department, French Ministry of Health, and the Private Foundation of Geneva University Hospitals. The Reseau European de recherche en Ventilation Artificielle (REVA) network received a Euro75,000 research grant from Air Liquide Healthcare. We thank all physicians and ICU staff for their dedication in the care of our patients. We acknowledge the contributions of the Clinical Research Centre, Geneva University Hospitals and Faculty of Medicine (Isabelle Semac, Véronique Ménoni, Emmanuelle Lelong-Favre, Sophie Longchamp and Isabelle Mercier). We also acknowledge with gratitude all the French and Belgian clinical research centres, medical students, students of the Polytechnic University, and all the volunteers for their amazing help in data collection. We thank Rosemary Sudan for editorial assistance. Participating Sites and COVID-ICU Investigators; CHU Angers,

Angers, France (Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle), APHP - Hôpital Bicêtre, Le Kremlin-Bicêtre, France (Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard), APHP - Hôpital Pitié Salpêtrière, Paris, France (Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton), CHU Caen Normandie - Hôpital Côte de Nacre, Caen, France, (Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron), APHP - Hôpital Cochin, Paris, France (Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert), APHP - Hôpital Tenon, Paris, France, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau), CHRU de Brest - La Cavale Blanche, Brest, France (Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere), Centre Hospitalier de Cholet, Cholet, France (Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni), CHU Dijon Bourgogne, Dijon, France (Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère), CHU Lille - Hôpital Roger Salengero, Lille, France (Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu), Groupe Hospitalier Nord Essonne, Longjumeau, France (Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault), APHM - Hôpital Nord, Marseille, France (Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre), Hôpital de Melun-Sénart, Melun, France (Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi), Élément Militaire de Réanimation du SSA, Mulhouse, France (Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier), CHU Nantes - Hôpital Hotel Dieu, Nantes, France (Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet), CHU Nice - Hôpital Archet, Nice, France (Jean Dellammonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit), Centre Hospitalier d'Orléans, Orléans, France (Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge), Centre Hospitalier Universitaire de la Guadeloupe, Pointe-à-Pitre, France (Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles), Hôpital de la Milétrie, Poitiers, France (Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez), Centre Hospitalier Roanne, Roanne, France (Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin), CHU Rouen - Hôpital Charles Nicolle, Rouen, France (Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau), CHRU Tours - Hôpital Bréttonne, Tours, France (Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djalil Elaroussi), Centre Hospitalier Bretagne Atlantique, Vannes, France (Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas), CHU Liège, Liège, Belgique (Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont), Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France (Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent), Centre Hospitalier Du Mans, Le Mans, France (Christophe Guitton, Nicolas Chateau, Mickaël Landais, Cédric Darreau), Centre Hospitalier de Versailles, Le Chesnay, France (Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel), Hôpital Foch, Suresnes, France (Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot), Hôpital Claude Galien, Quincy sous Senart, France (Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine), GHR Mulhouse Sud-Alsace, Mulhouse, France (Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien), APHP - Hôpital Antoine Béclère, Clamart, France (Charles Damoisel, Benjamin Sztrymf), APHP - Hôpital Pitié- Salpêtrière, Paris, France (Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt), Hôpital Intercommunal de Créteil, Créteil, France (Frédérique Schortgen, Leon Rusel, Camille Jung), Hospices Civils de Lyon - Hôpital Neurologique, Lyon, France (Florent Gobert), APHP - Hôpital Necker, Paris, France (Damien Vimpere, Lionel Lamhaut), Centre Hospitalier Public du Cotentin - Hôpital Pasteur, Cherbourg-en-cotentin, France (Bertrand Sauneuf, Liliane Charrier, Julien Calus, Isabelle Desmeules), CHU Rennes - Hôpital du Pontchaillou, Rennes, France (Benoît Painvin, Jean-Marc Tadie), CHU Strasbourg - Hôpital Haute-pierre, Strasbourg, France (Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini), APHP - Hôpital Pitié Salpêtrière, Paris, France (Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut), Centre Hospitalier Territorial Gaston-Bourret, Nouméa, France (Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadaud, Mathieu Série), Centre Hospitalier Compiègne-Noyon, Compiègne, France (Nica Alexandru), Groupe Hospitalier Saint-Joseph, Paris, France (Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler), Centre hospitalier mémorial de Saint-Lô, Saint-Lô, France (Maxime Leclerc, Michel Ramakers), Grand Hôpital de l'Est Francilien, Jossigny, France (Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen), Gustave Roussy, Villejuif, France (Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin), Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-sous-Bois, France (Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome), Hospices Civiles de Lyon - Hôpital Edouard Herriot, Lyon, France (Paul
## Conclusions

In this multicentre observational study, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations. Our results did not support the association between ICU load and higher mortality. Importantly, our results showed very significant differences in LST limitation rates between centres. LST limitations frequently preceded death, with a major impact on time of death, and this should be reported in future studies evaluating ICU mortality with severe COVID-19 or critically ill patients.

## Abbreviations

**ARDS** Acute respiratory distress syndrome

**ICU** Intensive care unit

**IQR** Interquartile range

**LST** Life-sustaining therapies

**REVA** Réseau Européen de recherche en Ventilation Artificielle

**SAPS-II** Simplified acute physiology score II

**SOFA** Sequential organ failure assessment

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13054-023-04349-1.

**Additional file 1.** Data collection. Epidemiological data used for ICU load calculation. Definitions of withholding and withdrawal of life-sustaining therapies (LST). Statistical analysis: multivariable model and list of the variables included in the model. **Table E1.** Modalities of LST withholding and withdrawal in the study population. **Table E2.** Modalities of LST withholding according to a further (or not) LST withdrawal decision. **Table E3.** Centre characteristics at the patient level. **Table E4.** Adjunct measures during ICU stay according to LST limitation status. **Table E5.** Time to LST decision from ICU admission according to ICU load category. **Figure E1.** (A) Cumulative incidence plot of time from ICU admission to first LST limitation decision, and (B) Survival probability after LST withholding or withdrawing decisions within 14 days after ICU admission involving only patients with complete data (3051 patients). **Figure E2.** Distribution of ICU load at the patient level. **Figure E3.** ICU load (%) according to LST categories. Subgroup analysis by centre size, and in patients aged ≥75 years. **Table E6.** Expected prevalences estimated by the multivariate model according to the number of patients in the centre. **Table E7.** Prevalence of decisions of LST limitations in patients aged ≥ 75 years. **Figure E4.** Forest plot of prevalences of decisions of LST limitations in the 15 centres with ≥ 10 patients aged ≥75 years.

**Additional file 2.** Participating Sites and COVID-ICU Investigators.

## Acknowledgements

This study was funded by the Assistance Publique Hôpitaux de Paris Foundation through the programme "Alliance Tous Unis Contre le Virus", Clinical Research and Development Department, French Ministry of Health, and the Private Foundation of Geneva University Hospitals. The Reseau European de recherche en Ventilation Artificielle (REVA) network received a Euro75,000 research grant from Air Liquide Healthcare. We thank all physicians and ICU staff for their dedication in the care of our patients. We acknowledge the contributions of the Clinical Research Centre, Geneva University Hospitals and Faculty of Medicine (Isabelle Semac, Véronique Ménoni, Emmanuelle Lelong-Favre, Sophie Longchamp and Isabelle Mercier). We also acknowledge with gratitude all the French and Belgian clinical research centres, medical students, students of the Polytechnic University, and all the volunteers for their amazing help in data collection. We thank Rosemary Sudan for editorial assistance. Participating Sites and COVID-ICU Investigators; CHU Angers,

Angers, France (Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle), APHP - Hôpital Bicêtre, Le Kremlin-Bicêtre, France (Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard), APHP - Hôpital Pitié Salpêtrière, Paris, France (Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton), CHU Caen Normandie - Hôpital Côte de Nacre, Caen, France, (Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron), APHP - Hôpital Cochin, Paris, France (Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert), APHP - Hôpital Tenon, Paris, France, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau), CHRU de Brest - La Cavale Blanche, Brest, France (Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere), Centre Hospitalier de Cholet, Cholet, France (Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni), CHU Dijon Bourgogne, Dijon, France (Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère), CHU Lille - Hôpital Roger Salengero, Lille, France (Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu), Groupe Hospitalier Nord Essonne, Longjumeau, France (Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault), APHM - Hôpital Nord, Marseille, France (Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre), Hôpital de Melun-Sénart, Melun, France (Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi), Élément Militaire de Réanimation du SSA, Mulhouse, France (Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier), CHU Nantes - Hôpital Hotel Dieu, Nantes, France (Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet), CHU Nice - Hôpital Archet, Nice, France (Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit), Centre Hospitalier d'Orléans, Orléans, France (Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge), Centre Hospitalier Universitaire de la Guadeloupe, Pointe-à-Pitre, France (Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles), Hôpital de la Milétrie, Poitiers, France (Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez), Centre Hospitalier Roanne, Roanne, France (Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin), CHU Rouen - Hôpital Charles Nicolle, Rouen, France (Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau), CHRU Tours - Hôpital Bréttonne, Tours, France (Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djali Elaroussi), Centre Hospitalier Bretagne Atlantique, Vannes, France (Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas), CHU Liège, Liège, Belgique (Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont), Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France (Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent), Centre Hospitalier Du Mans, Le Mans, France (Christophe Guitton, Nicolas Chateau, Mickaël Landais, Cédric Darreau), Centre Hospitalier de Versailles, Le Chesnay, France (Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel), Hôpital Foch, Suresnes, France (Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot), Hôpital Claude Galien, Quincy sous Senart, France (Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine), GHR Mulhouse Sud-Alsace, Mulhouse, France (Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien), APHP - Hôpital Antoine Béclère, Clamart, France (Charles Damoisel, Benjamin Sztrymf), APHP - Hôpital Pitié- Salpêtrière, Paris, France (Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt), Hôpital Intercommunal de Créteil, Créteil, France (Frédérique Schortgen, Leon Rusel, Camille Jung), Hospices Civils de Lyon - Hôpital Neurologique, Lyon, France (Florent Gobert), APHP - Hôpital Necker, Paris, France (Damien Vimpere, Lionel Lamhaut), Centre Hospitalier Public du Cotentin - Hôpital Pasteur, Cherbourg-en-cotentin, France (Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules), CHU Rennes - Hôpital du Pontchaillou, Rennes, France (Benoît Painvin, Jean-Marc Tadie), CHU Strasbourg - Hôpital Haute-pierre, Strasbourg, France (Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini), APHP - Hôpital Pitié Salpêtrière, Paris, France (Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut), Centre Hospitalier Territorial Gaston-Bourret, Nouméa, France (Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadaud, Mathieu Série), Centre Hospitalier Compiègne-Noyon, Compiègne, France (Nica Alexandru), Groupe Hospitalier Saint-Joseph, Paris, France (Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler), Centre hospitalier mémorial de Saint-Lô, Saint-Lô, France (Maxime Leclerc, Michel Ramakers), Grand Hôpital de l'Est Francilien, Jossigny, France (Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen), Gustave Roussy, Villejuif, France (Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin), Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-sous-Bois, France (Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome), Hospices Civiles de Lyon - Hôpital Edouard Herriot, Lyon, France (Paul
Abraham, Céline Monard, Julien Textoris, Thomas Rimmele), Centre Hospitalier d'Avignon, Avignon, France (Florent Montini), Groupe Hospitalier Diaconesses - Croix Saint Simon, Paris, France (Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi), CHU Clermont-Ferrand - Hôpital Gabriel Montpied, Clermont Ferrand, France (Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy), Hôpital d'Instruction des Armées Percy, Clamart, France (Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot), CHU Nancy - Hôpital Brabois, Vandoeuvre-les-Mâles, France (Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy), Centre Hospitalier de Vichy, Vichy, France (Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux), Hôpital Pierre Bérégovoy, Nevers, France (Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey), Centre Hospitalier de Tarbes, Tarbes, France (Jermy Castanera, Philippe Tupe, Benjamin Madeux), Hôpitaux Civils de Colmar - Hôpital Louis pasteur, Colmar, France (Otto Hartman), CHU Charleroi - Hôpital Marie Curie, Bruxelles, Belgique (Michael Piagnerelli, Anne Joosten, Cindereла Noel, Patrick Biston), Centre hospitalier de Verdun Saint Mihiel, Saint Mihiel, France (Thibaut Noel), CH Eure-Seine - Hôpital d'Evreux-Vernon, Evreux, France (Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet), Hôpital René Dubos, Pontoise, France (Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour), APHP - Hôpital Lariboisière, Paris, France (Buno Mégarbane, Sébastien Voicu, Nicolas Deye, Isabelle Malissin), Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France (François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre), Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France (Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol), HIA Sainte Anne, Toulon, France (Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale), Grand Hôpital de l'Est Francilien, Meaux, France (Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo), HIA Robert Picqué, Villenave d'Ornon, France (David Tran-Van, Patrick Avargues, Lisa Carengo), Centre Hospitalier Fontainebleau, Fontainebleau, France (Nicolas Robin, Alexandre Ouali, Lucie Houdou), Hôpital Universitaire de Genève, Genève, Suisse (Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérôme Pugin), APHP - Hôpital Beaujon, Cliché, France (Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz), Groupe Hospitalier Bretage Sud, Lorient, France (Béatrice La Combe, Rolland Smonig, Jade Vieilleau, Pauline Cailliez), Centre Hospitalier Intercommunal Toulon, La Seyne sur Mer, France (Jonathan Chelly), Centre Hospitalier de Dieppe, Dieppe, France (Antoine Marchalot, Cécile Saladin, Christelle Bigot), CHU de Martinique, Fort-de-France, France (Pierre-Marie Fayolle, Jules Fatsés, Amr Ibrahim, Dabor Resiere), Hôpital Fondation Adolpe de Rothchild, Paris, France (Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler), APHP - Bichat Claude Bernard, Paris, France (Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh), APHP - Hôpital Universitaire Paris Sud, Bicêtre, France (Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner), APHP - Hôpital Européen Georges Pompidou, Paris, France (Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue), APHP, GHU Henri Mondor, Créteil, France (Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost), APHP - Hôpitaux Universitaires Henri Mondor, Créteil, France (Nicolas Mongardon, Meriam Lamraoui, Claire Alessandri, Quentin de Roux), APHP - Hôpital Lariboisière, Paris, France (Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazza, Etienne Gayat), APHP - Hôpital Saint-Antoine, Paris, France (Marc Garnier, Emmanuel Pardo, LeaSatre-Buisson, Christophe Gutton), APHP Hôpital Saint-Louis, Paris, France (Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon), APHP - Hôpital Saint-Antoine, Paris, France (Hafid Ait Oufella, Geoffroy Hiriri, Tomas Urbina, Sandie Mazerand), APHP - Hôpital Raymond Pointcarré, Garches, France (Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Anane), APHP - Hôpital Pitié Salpêtrière, Paris, France (Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot), Centre Hospitalier Victor Dupouy, Argenteuil, France (Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot), CHU Toulouse - Hôpital Rangueil, Toulouse, France (Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier), Centre Hospitalier de Poissy, Poissy, France (Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin), APHP - Hôpital Saint-Louis, Paris, France (François Dépret, Maxime Coutrot, Maître Chaussard, Lucie Guillemet), Clinique du MontLégia, CHC Groupe-Santé, Liège, Belgique (Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot), CHU Saint-Denis, La Réunion, France (Romain Persichini), Centre Hospitalier de Tourcoing, Tourcoing, France (Vanessa Jean-Michel, Hugues Georges, Thomas Caulier), Centre Hospitalier Henri Mondor d'Aurillac, Aurillac, France (Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud), Centre Hospitalier Saint Joseph Saint Luc, Lyon, France (Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian

Pommier) Centre Hospitalier de Polynésie Française, Polynésie, France (Marc Vinclair, Simon Poignant, Sandrine Mons), Ramsay Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France (Wulfran Bougouin), Centre Hospitalier Alpes Léman, Contamine sur Arve, France (Franklin Bruna, Quentin Maestraggi, Christian Roth), Hospices Civils de Lyon - Hôpital de la Croix Rousse, Lyon, France (Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli), Centre Biologique du Nord, Saint-Denis, France (Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan), GHU - Hôpital Saint-Anne, Paris, France (Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar) CHR Metz - Hôpital Mercy, Metz, France (Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaume Louis), APHP - Hôpital Paul Brousse, Villejuif, France (Sophie-Caroline Sacleux, Marie-Amélie Ordan), CHRU Nancy - Hôpital Central, Nancy, France (Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot), Centre Hospitalier d'Ajaccio, Ajaccio, France (Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti), Centre Hospitalier de Bourges, Bourges, France (Marie-Catherine Besse, Anna Bourreau), Centre hospitalier de la Côte Basque, Bayonne, France (Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux), Hospices Civils de Lyon - Hôpital de la Croix Rousse, Lyon, France (Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun), CH Saint-Malo, Saint-Malo (Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin), Centre Hospitalier de Mulhouse, Mulhouse, France (Samuel Degoul), Centre Hospitalier de Briançon, Briançon, France (Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lasan spre), CHU Nice, Hôpital Pasteur 2, Nice, France (Hervé Quintard, Eve Marie Maiziere), Centre Hospitalier des Pays de Morlaix, Morlaix, France (Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel), Centre Hospitalier Valence, Valence, France (Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison), Centre Hospitalier Niort, Niort, France (Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera), APHP - Hôpital Pitié Salpêtrière, Paris, France (Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel), Clinique du Val d'Or, Saint Cloud, France (Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet), Centre Hospitalier de Béthune, Béthune, France (Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahman), Groupe Hospitalier Intercommunal de la Haute-Saône, Vesoul, France (Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette), Clinique Saint-Martin, Caen, France (Benoît Her, Jennifer Brunet), Ramsay Générale de Santé, Clinique Convert, Bourg en Bresse, France (Mathieu Page, Fabienne Boiste, Anthony Collin), Hôpital Victor Jousselin, Dreux, France (Florent Bavozet, Aude Garin, Mohamed Laola, Kais Mhamdi), Centre Hospitalier de Troye, Troye, France, (Bassem Beilouny, Alexandra Lavalard, Severine Perez), CHU de ROUEN-Hôpital Charles Nicolle, Rouen, France (Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamazc), Centre Hospitalier Agen-Nérac, Agen, France (Fabienne Plouvain, Bertrand P Delaborde, Aissa Kherchache, Amina Chaalal), APHP - Hôpital Louis Mourier, Colombes, France (Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux), APHP - Hôpital Pitié-Salpêtrière, Paris, France (Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves), Institut Mutualiste Montsouris, Paris, France (Florian Prevost, Christian Lamer, Ruifying Shi, Lyes Knani), CHU Besançon - Hôpital Jean Minjoz, Besançon, France (Sébastien Pili Floury, Lucie Vettoretti), APHP - Hôpital Universitaire Robert-Debré, Paris, France (Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon), CHU Besançon - Hôpital Jean Minjoz, Besançon, France, (Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier) ; Médipôle Lyon-Villeurbanne, Vileurbanne, France, (Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Tao), APHP - Ambroise Paré, Boulogne-Billancourt, France (Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron), CHU Amiens Picardie, Amiens, France (Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinar d, Pierre-Yves Macq), Hôpital Nord-Ouest, Villefranche-sur-Saône, France (Kevin Chaulier, Sylvie Goutte), CH de Châlons en Champagne, Châlons en Champagne, France (Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau), CHU Angers, Angers, France (Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie), CHU Grenoble Alpes, Grenoble, France (Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau), APHP - Hôpital Européen Georges Pompidou, Paris, France (Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot), Hôpital Privé d'Antony, Antony, France (Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont), Institut Arnault Tzanck, Saint Laurent du Var, France (Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle) ; Centre Hospitalier d'Angoulême, Angoulême, France (Christophe Cracco, Stéphane Rouleau, David Schnell) ;
Abraham, Céline Monard, Julien Textoris, Thomas Rimmele), Centre Hospitalier d'Avignon, Avignon, France (Florent Montini), Groupe Hospitalier Diaconesses - Croix Saint Simon, Paris, France (Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi), CHU Clermont-Ferrand - Hôpital Gabriel Montpied, Clermont Ferrand, France (Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy), Hôpital d'Instruction des Armées Percy, Clamart, France (Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot), CHU Nancy - Hôpital Brabois, Vandoeuvre-les-Mâles, France (Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy), Centre Hospitalier de Vichy, Vichy, France (Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux), Hôpital Pierre Bérégovoy, Nevers, France (Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey), Centre Hospitalier de Tarbes, Tarbes, France (Jermy Castanera, Philippe Tupe, Benjamin Madeux), Hôpitaux Civils de Colmar - Hôpital Louis pasteur, Colmar, France (Otto Hartman), CHU Charleroi - Hôpital Marie Curie, Bruxelles, Belgique (Michael Piagnerelli, Anne Joosten, Cindereла Noel, Patrick Biston), Centre hospitalier de Verdun Saint Mihiel, Saint Mihiel, France (Thibaut Noel), CH Eure-Seine - Hôpital d'Evreux-Vernon, Evreux, France (Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet), Hôpital René Dubos, Pontoise, France (Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour), APHP - Hôpital Lariboisière, Paris, France (Buno Mégarbane, Sébastien Voicu, Nicolas Deye, Isabelle Malissin), Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France (François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre), Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France (Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol), HIA Sainte Anne, Toulon, France (Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale), Grand Hôpital de l'Est Francilien, Meaux, France (Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo), HIA Robert Picqué, Villenave d'Ornon, France (David Tran-Van, Patrick Avargues, Lisa Carengo), Centre Hospitalier Fontainebleau, Fontainebleau, France (Nicolas Robin, Alexandre Ouali, Lucie Houdou), Hôpital Universitaire de Genève, Genève, Suisse (Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérôme Pugin), APHP - Hôpital Beauxjon, Cliché, France (Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz), Groupe Hospitalier Bretage Sud, Lorient, France (Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez), Centre Hospitalier Intercommunal Toulon, La Seyne sur Mer, France (Jonathan Chelly), Centre Hospitalier de Dieppe, Dieppe, France (Antoine Marchalot, Cécile Saladin, Christelle Bigot), CHU de Martinique, Fort-de-France, France (Pierre-Marie Fayolle, Jules Fatsés, Amr Ibrahim, Dabor Resiere), Hôpital Fondation Adolpe de Rothchild, Paris, France (Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler), APHP - Bichat Claude Bernard, Paris, France (Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh), APHP - Hôpital Universitaire Paris Sud, Bicêtre, France (Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner), APHP - Hôpital Européen Georges Pompidou, Paris, France (Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue), APHP, GHU Henri Mondor, Créteil, France (Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost), APHP - Hôpitaux Universitaires Henri Mondor, Créteil, France (Nicolas Mongardon, Meriam Lamraoui, Claire Alessandri, Quentin de Roux), APHP - Hôpital Lariboisière, Paris, France (Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazza, Etienne Gayat), APHP - Hôpital Saint-Antoine, Paris, France (Marc Garnier, Emmanuel Pardo, LeaSatre-Buisson, Christophe Gutton), APHP Hôpital Saint-Louis, Paris, France (Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon), APHP - Hôpital Saint-Antoine, Paris, France (Hafid Ait Oufella, Geoffroy Hiriri, Tomas Urbina, Sandie Mazerand), APHP - Hôpital Raymond Pointcarré, Garches, France (Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Anane), APHP - Hôpital Pitié Salpêtrière, Paris, France (Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot), Centre Hospitalier Victor Dupouy, Argenteuil, France (Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot), CHU Toulouse - Hôpital Rangueil, Toulouse, France (Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier), Centre Hospitalier de Poissy, Poissy, France (Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin), APHP - Hôpital Saint-Louis, Paris, France (François Dépret, Maxime Coutrot, Maître Chaussard, Lucie Guillemet), Clinique du MontLégia, CHC Groupe-Santé, Liège, Belgique (Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot), CHU Saint-Denis, La Réunion, France (Romain Persichini), Centre Hospitalier de Tourcoing, Tourcoing, France (Vanessa Jean-Michel, Hugues Georges, Thomas Caulier), Centre Hospitalier Henri Mondor d'Aurillac, Aurillac, France (Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud), Centre Hospitalier Saint Joseph Saint Luc, Lyon, France (Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian

Pommier) Centre Hospitalier de Polynésie Française, Polynésie, France (Marc Vinclair, Simon Poignant, Sandrine Mons), Ramsay Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France (Wulfran Bougouin), Centre Hospitalier Alpes Léman, Contamine sur Arve, France (Franklin Bruna, Quentin Maestraggi, Christian Roth), Hospices Civils de Lyon - Hôpital de la Croix Rousse, Lyon, France (Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli), Centre Biologique du Nord, Saint-Denis, France (Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan), GHU - Hôpital Saint-Anne, Paris, France (Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar) CHR Metz - Hôpital Mercy, Metz, France (Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaume Louis), APHP - Hôpital Paul Brousse, Villejuif, France (Sophie-Caroline Sacleux, Marie-Amélie Ordan), CHRU Nancy - Hôpital Central, Nancy, France (Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot), Centre Hospitalier d'Ajaccio, Ajaccio, France (Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti), Centre Hospitalier de Bourges, Bourges, France (Marie-Catherine Besse, Anna Bourreau), Centre hospitalier de la Côte Basque, Bayonne, France (Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux), Hospices Civils de Lyon - Hôpital de la Croix Rousse, Lyon, France (Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun), CH Saint-Malo, Saint-Malo (Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin), Centre Hospitalier de Mulhouse, Mulhouse, France (Samuel Degoul), Centre Hospitalier de Briançon, Briançon, France (Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lasan spre), CHU Nice, Hôpital Pasteur 2, Nice, France (Hervé Quintard, Eve Marie Maiziere), Centre Hospitalier des Pays de Morlaix, Morlaix, France (Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel), Centre Hospitalier Valence, Valence, France (Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison), Centre Hospitalier Niort, Niort, France (Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera), APHP - Hôpital Pitié Salpêtrière, Paris, France (Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel), Clinique du Val d'Or, Saint Cloud, France (Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet), Centre Hospitalier de Béthune, Béthune, France (Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahman), Groupe Hospitalier Intercommunal de la Haute-Saône, Vesoul, France (Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette), Clinique Saint-Martin, Caen, France (Benoît Her, Jennifer Brunet), Ramsay Générale de Santé, Clinique Convert, Bourg en Bresse, France (Mathieu Page, Fabienne Boiste, Anthony Collin), Hôpital Victor Jousselin, Dreux, France (Florent Bavozet, Aude Garin, Mohamed Laola, Kais Mhamdi), Centre Hospitalier de Troye, Troye, France, (Bassem Beilouny, Alexandra Lavalard, Severine Perez), CHU de ROUEN-Hôpital Charles Nicolle, Rouen, France (Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamazc), Centre Hospitalier Agen-Nérac, Agen, France (Fabienne Plouvain, Bertrand P Delaborde, Aissa Kherchache, Amina Chaalal), APHP - Hôpital Louis Mourier, Colombes, France (Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux), APHP - Hôpital Pitié-Salpêtrière, Paris, France (Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves), Institut Mutualiste Montsouris, Paris, France (Florian Prevost, Christian Lamer, Ruifying Shi, Lyes Knani), CHU Besançon - Hôpital Jean Minjoz, Besançon, France (Sébastien Pili Floury, Lucie Vettoretti), APHP - Hôpital Universitaire Robert-Debré, Paris, France (Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon), CHU Besançon - Hôpital Jean Minjoz, Besançon, France, (Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier) ; Médipôle Lyon-Villeurbanne, Vileurbanne, France, (Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Tao), APHP - Ambroise Paré, Boulogne-Billancourt, France (Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron), CHU Amiens Picardie, Amiens, France (Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinar d, Pierre-Yves Macq), Hôpital Nord-Ouest, Villefranche-sur-Saône, France (Kevin Chaulier, Sylvie Goutte), CH de Châlons en Champagne, Châlons en Champagne, France (Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau), CHU Angers, Angers, France (Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie), CHU Grenoble Alpes, Grenoble, France (Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau), APHP - Hôpital Européen Georges Pompidou, Paris, France (Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot), Hôpital Privé d'Antony, Antony, France (Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont), Institut Arnault Tzanck, Saint Laurent du Var, France (Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle) ; Centre Hospitalier d'Angoulême, Angoulême, France (Christophe Cracco, Stéphane Rouleau, David Schnell) ;
Centre Hospitalier de Cahors, Cahors, France (Camille Foucault), Centre hospitalier de Carcassonne, Carcassonne, France (Cécile Lory); CHU Nice - Hôpital L'Archet 2, Nice, France (Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdilazize Sahraoui); Hôpital Privé du Vert Galant, Tremblay-en- France, France (Nathalie Abbosh, Caroline Bornstain, Pierre Pernet); Centre Hospitalier de Rambouillet, Rambouillet, France (Florent Poirson, Ahmed Pasem, Philippe Karoubi); Hopitaux du Léman, Thonon les Bains, France (Virginie Poirpinel, Caroline Gauthier, François Bouniol, Philippe Feuchere), Centre Hospitalier Victor Jousselin, Dreux, France (Florent Bazovet, Anne Heron), Hôpital Sainte Camille, Brie sur Marne, France (Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli), Hôpital d'instruction des armées Clermont-Tonnerre, Brest, France (Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill), APHP - Hôpital Pitié Salpêtrière, Paris, France (Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage); APHP - Hôpital Avicenne, Bobigny, France (Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen); Groupement Hospitalier la Rochelle Ré Amis, La Rochelle, France (Julie Noublanche, Olivier Lesieur); Centre Hospitalier Intercommunal de Mont de Marsan et du Pays des Sources, Mont de Marsan, France (Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma); Centre Hospitalier Départemental de Vendée, La- Roche-Sur-Yon, France (Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau); Pôle Anesthésie-Réanimation, CHU Grenoble (Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-François Payen).

## Author contributions

S.B., A.P., M.G., and C.L.T. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: S.B., A.P., M.G. and C.L.T. Methodology: S.B., A.P., M.G. and C.L.T. Acquisition, analysis, or interpretation of data: S.B., A.P., M.G. and C.L.T. Drafting of the manuscript: S.B., A.P., M.G. and C.L.T. Critical revision of the manuscript for important intellectual content: S.B., C.L.T., M.G., E.W., J.P., B.G., J.P.Q., J.P.R. and B.G. Statistical analysis: A.P. Supervision: S.B., J.P. and E.W. Obtained funding: J.P., C.L.T. and S.B. All authors had full access to all the data in the study, read and approved the final manuscript and had final responsibility for the decision to submit for publication. All authors read and approved the final manuscript.

## Funding

Open access funding provided by University of Geneva. This study was funded by the Assistance Publique Hôpitaux de Paris Foundation through the programme "Alliance Tous Unis Contre le Virus", Clinical Research and Development Department, French Ministry of Health, and the Private Foundation of Geneva University Hospitals. The Reseau European de recherche en Ventilation Artificielle (REVA) network received a Euro75,000 research grant from Air Liquide Healthcare. The funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication.

## Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

## Declarations

### Ethics approval and consent to participate

The ethics committees of the French Intensive Care Society (CE-SRLF 20-23), Belgium (2020-294), and Switzerland (BASEC #2020-00704) approved the study according to regulations for each participating country.

### Consent for publication

Not applicable.

### Competing interests

The authors declare that they have no competing interests.

## Author details

¹Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Paris, France. ²Centre de Recherche des Cordeliers, Université Paris Cité, Inserm, Laboratoire ETREs, Sorbonne Université, Paris, France. ³Division of Intensive Care, Geneva University Hospitals, Faculty

of Medicine, University of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland. ⁴Clinical Research Centre, Faculty of Medicine, University of Geneva, Geneva, Switzerland. ⁵Division of Clinical Epidemiology, Department of Health and Community Medicine, University Hospitals of Geneva, Geneva, Switzerland. ⁶Service de Réanimation Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France. ⁷Réanimation Polyvalente, Centre Hospitalier de Dieppe, Dieppe, France. ⁸Department of Intensive Care, François Mitterrand University Hospital, Dijon, France. ⁹Unité Fonctionnelle d'Ethique Médicale, Hôpital Necker-Enfants Malades, APHP, Paris, France. ¹⁰CHU Angers, Angers, France. ¹¹APHP - Hôpital Bicêtre, Le Kremlin-Bicêtre, France. ¹²APHP - Hôpital Pitié Salpêtrière, Paris, France. ¹³CHU Caen Normandie - Hôpital Côte de Nacre, Caen, France. ¹⁴APHP - Hôpital Cochin, Paris, France. ¹⁵APHP - Hôpital Tenon, Paris, France. ¹⁶CHRU de Brest - La Cavale Blanche, Brest, France. ¹⁷Centre Hospitalier de Cholot, Cholot, France. ¹⁸CHU Dijon Bourgogne, Dijon, France. ¹⁹CHU Lille - Hôpital Roger Salengero, Lille, France. ²⁰Groupe Hospitalier Nord Essonne, Longjumeau, France. ²¹APHM - Hôpital Nord, Marseille, France. ²²Hôpital de Melun-Sénart, Melun, France. ²³Élément Militaire de Réanimation du SSA, Mulhouse, France. ²⁴CHU Nantes - Hôpital Hotel Dieu, Nantes, France. ²⁵CHU Nice - Hôpital Archet, Nice, France. ²⁶Centre Hospitalier d'Orléans, Orléans, France. ²⁷Centre Hospitalier Universitaire de La Guadeloupe, Pointe-a-Pitre, France. ²⁸Hôpital de La Milétrie, Poitiers, France. ²⁹Centre Hospitalier Roanne, Roanne, France. ³⁰CHU Rouen - Hôpital Charles Nicolle, Rouen, France. ³¹CHU Tours - Hôpital Bretonneau, Tours, France. ³²Centre Hospitalier Bretagne Atlantique, Vannes, France. ³³CHU Liège, Liège, Belgium. ³⁴Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France. ³⁵Centre Hospitalier du Mans, Le Mans, France. ³⁶Centre Hospitalier de Versailles, Le Chesnay, France. ³⁷Hôpital Foch, Suresnes, France. ³⁸Hôpital Claude Galien, Quincy Sous Senart, France. ³⁹GHR Mulhouse Sud-Alsace, Mulhouse, France. ⁴⁰APHP - Hôpital Antoine Béclère, Clamart, France. ⁴¹APHP - Hôpital Pitié-Salpêtrière, Paris, France. ⁴²Hôpital Intercommunal de Créteil, Créteil, France. ⁴³Hospices Civils de Lyon - Hôpital Neurologique, Lyon, France. ⁴⁴APHP - Hôpital Necker, Paris, France. ⁴⁵Centre Hospitalier Public du Cotentin - Hôpital Pasteur, Cherbourg-en-Cotentin, France. ⁴⁶CHU Rennes - Hôpital du Pontchaillou, Rennes, France. ⁴⁷CHU Strasbourg - Hôpital Hautepierre, Strasbourg, France. ⁴⁸Centre Hospitalier Territorial Gaston-Bourré, Nouméa, France. ⁴⁹Centre Hospitalier Compiegne-Noyon, Compiegne, France. ⁵⁰Groupe Hospitalier Saint-Joseph, Paris, France. ⁵¹Centre Hospitalier Mémorial de Saint-Lô, Saint-Lô, France. ⁵²Grand Hôpital de l'Est Francilien, Jossigny, France. ⁵³Gustave Roussy, Villejuif, France. ⁵⁴Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-Sous-Bois, France. ⁵⁵Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France. ⁵⁶Centre Hospitalier d'Avignon, Avignon, France. ⁵⁷Groupe Hospitalier Diaconesses - Croix Saint Simon, Paris, France. ⁵⁸CHU Clermont-Ferrand - Hôpital Gabriel Montpied, Clermont Ferrand, France. ⁵⁹Hôpital d'Instruction Des Armées Percy, Clamart, France. ⁶⁰CHU Nancy - Hôpital Brabois, Vandoeuvre-Les-Nancy, France. ⁶¹Centre Hospitalier de Vichy, Vichy, France. ⁶²Hôpital Pierre Bérégovoy, Nevers, France. ⁶³Centre Hospitalier de Tarbes, Tarbes, France. ⁶⁴Hôpitaux Civils de Colmar - Hôpital Louis pasteur, Colmar, France. ⁶⁵CHU Charleroi - Hôpital Marie Curie, Brussels, Belgium. ⁶⁶Centre Hospitalier de Verdun Saint Mihiel, Saint Mihiel, France. ⁶⁷CH Eure-Seine - Hôpital d'Evreux-Vernon, Evreux, France. ⁶⁸Hôpital René Dubos, Pontoise, France. ⁶⁹APHP - Hôpital Lariboisière, Paris, France. ⁷⁰Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France. ⁷¹Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France. ⁷²HIA Sainte Anne, Toulon, France. ⁷³Grand Hôpital de L'Est Francilien, Meaux, France. ⁷⁴HIA Robert Picqué, Villenave d'Ornon, France. ⁷⁵Centre Hospitalier Fontainebleau, Fontainebleau, France. ⁷⁶Hôpital Universitaire de Genève, Geneva, Switzerland. ⁷⁷APHP - Hôpital Beaujon, Clichy, France. ⁷⁸Groupe Hospitalier Bretage Sud, Lorient, France. ⁷⁹Centre Hospitalier Intercommunal Toulon, La Seyne Sur Mer, France. ⁸⁰Centre Hospitalier de Dieppe, Dieppe, France. ⁸¹CHU de Martinique, Fort-de-France, France. ⁸²Hôpital Fondation Adolphe de Rothchild, Paris, France. ⁸³APHP - Bichat Claude Bernard, Paris, France. ⁸⁴APHP - Hôpital Universitaire Paris Sud, Bicêtre, France. ⁸⁵APHP - Hôpital Européen Georges Pompidou, Paris, France. ⁸⁶APHP, GHU Henri Mondor, Créteil, France. ⁸⁷APHP - Hôpitaux Universitaires Henri Mondor, Créteil, France. ⁸⁸APHP - Hôpital Saint-Antoine, Paris, France. ⁸⁹APHP Hôpital Saint-Louis, Paris, France. ⁹⁰APHP - Hôpital Saint-Antoine, Paris, France. ⁹¹APHP - Hôpital Raymond Pointcarré, Garches, France. ⁹²Centre Hospitalier Victor Dupouy, Argenteuil, France. ⁹³CHU Toulouse - Hôpital Rangueil, Toulouse, France. ⁹⁴Centre Hospitalier de Poissy, Poissy, France. ⁹⁵APHP - Hôpital Saint-Louis, Paris, France. ⁹⁶Clinique du MontLégia, CHC Groupe-Santé, Liège, Belgium. ⁹⁷CHU Saint-Denis, La Réunion, France. ⁹⁸Centre Hospitalier de Tourcoing, Tourcoing, France. ⁹⁹Centre
Centre Hospitalier de Cahors, Cahors, France (Camille Foucault), Centre hospitalier de Carcassonne, Carcassonne, France (Cécile Lory); CHU Nice - Hôpital L'Archet 2, Nice, France (Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdilazize Sahraoui); Hôpital Privé du Vert Galant, Tremblay-en- France, France (Nathalie Abbosh, Caroline Bornstain, Pierre Pernet); Centre Hospitalier de Rambouillet, Rambouillet, France (Florent Poirson, Ahmed Pasem, Philippe Karoubi); Hopitaux du Léman, Thonon les Bains, France (Virginie Poirpinel, Caroline Gauthier, François Bouniol, Philippe Feuchere), Centre Hospitalier Victor Jousselin, Dreux, France (Florent Bazovet, Anne Heron), Hôpital Sainte Camille, Brie sur Marne, France (Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli), Hôpital d'instruction des armées Clermont-Tonnerre, Brest, France (Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill), APHP - Hôpital Pitié Salpêtrière, Paris, France (Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage); APHP - Hôpital Avicenne, Bobigny, France (Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen); Groupement Hospitalier la Rochelle Ré Amis, La Rochelle, France (Julie Noublanche, Olivier Lesieur); Centre Hospitalier Intercommunal de Mont de Marsan et du Pays des Sources, Mont de Marsan, France (Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma); Centre Hospitalier Départemental de Vendée, La- Roche-Sur-Yon, France (Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau); Pôle Anesthésie-Réanimation, CHU Grenoble (Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-François Payen).

## Author contributions

S.B., A.P., M.G., and C.L.T. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: S.B., A.P., M.G. and C.L.T. Methodology: S.B., A.P., M.G. and C.L.T. Acquisition, analysis, or interpretation of data: S.B., A.P., M.G. and C.L.T. Drafting of the manuscript: S.B., A.P., M.G. and C.L.T. Critical revision of the manuscript for important intellectual content: S.B., C.L.T., M.G., E.W., J.P., B.G., J.P.Q., J.P.R. and B.G. Statistical analysis: A.P. Supervision: S.B., J.P. and E.W. Obtained funding: J.P., C.L.T. and S.B. All authors had full access to all the data in the study, read and approved the final manuscript and had final responsibility for the decision to submit for publication. All authors read and approved the final manuscript.

## Funding

Open access funding provided by University of Geneva. This study was funded by the Assistance Publique Hôpitaux de Paris Foundation through the programme "Alliance Tous Unis Contre le Virus", Clinical Research and Development Department, French Ministry of Health, and the Private Foundation of Geneva University Hospitals. The Reseau European de recherche en Ventilation Artificielle (REVA) network received a Euro75,000 research grant from Air Liquide Healthcare. The funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication.

## Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

## Declarations

### Ethics approval and consent to participate

The ethics committees of the French Intensive Care Society (CE-SRLF 20-23), Belgium (2020-294), and Switzerland (BASEC #2020-00704) approved the study according to regulations for each participating country.

### Consent for publication

Not applicable.

### Competing interests

The authors declare that they have no competing interests.

## Author details

¹Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Paris, France. ²Centre de Recherche des Cordeliers, Université Paris Cité, Inserm, Laboratoire ETREs, Sorbonne Université, Paris, France. ³Division of Intensive Care, Geneva University Hospitals, Faculty

of Medicine, University of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland. ⁴Clinical Research Centre, Faculty of Medicine, University of Geneva, Geneva, Switzerland. ⁵Division of Clinical Epidemiology, Department of Health and Community Medicine, University Hospitals of Geneva, Geneva, Switzerland. ⁶Service de Réanimation Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France. ⁷Réanimation Polyvalente, Centre Hospitalier de Dieppe, Dieppe, France. ⁸Department of Intensive Care, François Mitterrand University Hospital, Dijon, France. ⁹Unité Fonctionnelle d'Ethique Médicale, Hôpital Necker-Enfants Malades, APHP, Paris, France. ¹⁰CHU Angers, Angers, France. ¹¹APHP - Hôpital Bicêtre, Le Kremlin-Bicêtre, France. ¹²APHP - Hôpital Pitié Salpêtrière, Paris, France. ¹³CHU Caen Normandie - Hôpital Côte de Nacre, Caen, France. ¹⁴APHP - Hôpital Cochin, Paris, France. ¹⁵APHP - Hôpital Tenon, Paris, France. ¹⁶CHRU de Brest - La Cavale Blanche, Brest, France. ¹⁷Centre Hospitalier de Cholot, Cholot, France. ¹⁸CHU Dijon Bourgogne, Dijon, France. ¹⁹CHU Lille - Hôpital Roger Salengero, Lille, France. ²⁰Groupe Hospitalier Nord Essonne, Longjumeau, France. ²¹APHM - Hôpital Nord, Marseille, France. ²²Hôpital de Melun-Sénart, Melun, France. ²³Élément Militaire de Réanimation du SSA, Mulhouse, France. ²⁴CHU Nantes - Hôpital Hotel Dieu, Nantes, France. ²⁵CHU Nice - Hôpital Archet, Nice, France. ²⁶Centre Hospitalier d'Orléans, Orléans, France. ²⁷Centre Hospitalier Universitaire de La Guadeloupe, Pointe-a-Pitre, France. ²⁸Hôpital de La Milétrie, Poitiers, France. ²⁹Centre Hospitalier Roanne, Roanne, France. ³⁰CHU Rouen - Hôpital Charles Nicolle, Rouen, France. ³¹CHU Tours - Hôpital Bretonneau, Tours, France. ³²Centre Hospitalier Bretagne Atlantique, Vannes, France. ³³CHU Liège, Liège, Belgium. ³⁴Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France. ³⁵Centre Hospitalier du Mans, Le Mans, France. ³⁶Centre Hospitalier de Versailles, Le Chesnay, France. ³⁷Hôpital Foch, Suresnes, France. ³⁸Hôpital Claude Galien, Quincy Sous Senart, France. ³⁹GHR Mulhouse Sud-Alsace, Mulhouse, France. ⁴⁰APHP - Hôpital Antoine Béclère, Clamart, France. ⁴¹APHP - Hôpital Pitié-Salpêtrière, Paris, France. ⁴²Hôpital Intercommunal de Créteil, Créteil, France. ⁴³Hospices Civils de Lyon - Hôpital Neurologique, Lyon, France. ⁴⁴APHP - Hôpital Necker, Paris, France. ⁴⁵Centre Hospitalier Public du Cotentin - Hôpital Pasteur, Cherbourg-en-Cotentin, France. ⁴⁶CHU Rennes - Hôpital du Pontchaillou, Rennes, France. ⁴⁷CHU Strasbourg - Hôpital Hautepierre, Strasbourg, France. ⁴⁸Centre Hospitalier Territorial Gaston-Bourré, Nouméa, France. ⁴⁹Centre Hospitalier Compiègne-Noyon, Compiègne, France. ⁵⁰Groupe Hospitalier Saint-Joseph, Paris, France. ⁵¹Centre Hospitalier Mémorial de Saint-Lô, Saint-Lô, France. ⁵²Grand Hôpital de l'Est Francilien, Jossigny, France. ⁵³Gustave Roussy, Villejuif, France. ⁵⁴Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-Sous-Bois, France. ⁵⁵Hospices Civils de Lyon - Hôpital Edouard Herriot, Lyon, France. ⁵⁶Centre Hospitalier d'Avignon, Avignon, France. ⁵⁷Groupe Hospitalier Diaconesses - Croix Saint Simon, Paris, France. ⁵⁸CHU Clermont-Ferrand - Hôpital Gabriel Montpied, Clermont Ferrand, France. ⁵⁹Hôpital d'Instruction Des Armées Percy, Clamart, France. ⁶⁰CHU Nancy - Hôpital Brabois, Vandoeuvre-Les-Nancy, France. ⁶¹Centre Hospitalier de Vichy, Vichy, France. ⁶²Hôpital Pierre Bérégovoy, Nevers, France. ⁶³Centre Hospitalier de Tarbes, Tarbes, France. ⁶⁴Hôpitaux Civils de Colmar - Hôpital Louis pasteur, Colmar, France. ⁶⁵CHU Charleroi - Hôpital Marie Curie, Brussels, Belgium. ⁶⁶Centre Hospitalier de Verdun Saint Mihiel, Saint Mihiel, France. ⁶⁷CH Eure-Seine - Hôpital d'Evreux-Vernon, Evreux, France. ⁶⁸Hôpital René Dubos, Pontoise, France. ⁶⁹APHP - Hôpital Lariboisière, Paris, France. ⁷⁰Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France. ⁷¹Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France. ⁷²HIA Sainte Anne, Toulon, France. ⁷³Grand Hôpital de L'Est Francilien, Meaux, France. ⁷⁴HIA Robert Picqué, Villenave d'Ornon, France. ⁷⁵Centre Hospitalier Fontainebleau, Fontainebleau, France. ⁷⁶Hôpital Universitaire de Genève, Geneva, Switzerland. ⁷⁷APHP - Hôpital Beaujon, Clichy, France. ⁷⁸Groupe Hospitalier Bretage Sud, Lorient, France. ⁷⁹Centre Hospitalier Intercommunal Toulon, La Seyne Sur Mer, France. ⁸⁰Centre Hospitalier de Dieppe, Dieppe, France. ⁸¹CHU de Martinique, Fort-de-France, France. ⁸²Hôpital Fondation Adolphe de Rothchild, Paris, France. ⁸³APHP - Bichat Claude Bernard, Paris, France. ⁸⁴APHP - Hôpital Universitaire Paris Sud, Bicêtre, France. ⁸⁵APHP - Hôpital Européen Georges Pompidou, Paris, France. ⁸⁶APHP, GHU Henri Mondor, Créteil, France. ⁸⁷APHP - Hôpitaux Universitaires Henri Mondor, Créteil, France. ⁸⁸APHP - Hôpital Saint-Antoine, Paris, France. ⁸⁹APHP Hôpital Saint-Louis, Paris, France. ⁹⁰APHP - Hôpital Saint-Antoine, Paris, France. ⁹¹APHP - Hôpital Raymond Pointcarré, Garches, France. ⁹²Centre Hospitalier Victor Dupouy, Argenteuil, France. ⁹³CHU Toulouse - Hôpital Rangueil, Toulouse, France. ⁹⁴Centre Hospitalier de Poissy, Poissy, France. ⁹⁵APHP - Hôpital Saint-Louis, Paris, France. ⁹⁶Clinique du MontLégia, CHC Groupe-Santé, Liège, Belgium. ⁹⁷CHU Saint-Denis, La Réunion, France. ⁹⁸Centre Hospitalier de Tourcoing, Tourcoing, France. ⁹⁹Centre
Hospitalier Henri Mondor d'Aurillac, Aurillac, France. ¹⁰⁰Centre Hospitalier Saint Joseph Saint Luc, Lyon, France. ¹⁰¹Centre Hospitalier de Polynésie Française, Polynésie, France. ¹⁰²Ramsay Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France. ¹⁰³Centre Hospitalier Alpes Léman, Contamine Sur Arve, France. ¹⁰⁴Hospices Civils de Lyon - Hôpital de La Croix Rousse, Lyon, France. ¹⁰⁵Centre Cardiologique du Nord, Saint-Denis, France. ¹⁰⁶GHU - Hôpital Saint-Anne, Paris, France. ¹⁰⁷CHR Metz - Hôpital Mercy, Metz, France. ¹⁰⁸APHP - Hôpital Paul Brousse, Villejuif, France. ¹⁰⁹CHRU Nancy - Hôpital Central, Nancy, France. ¹¹⁰Centre Hospitalier d'Ajaccio, Ajaccio, France. ¹¹¹Centre Hospitalier de Bourges, Bourges, France. ¹¹²Centre Hospitalier de La Côte Basque, Bayonne, France. ¹¹³CH Saint-Malo, Saint-Malo, France. ¹¹⁴Centre Hospitalier de Mulhouse, Mulhouse, France. ¹¹⁵Centre Hospitalier de Briançon, Briançon, France. ¹¹⁶CHU Nice, Hôpital Pasteur 2, Nice, France. ¹¹⁷Centre Hospitalier Des Pays de Morlaix, Morlaix, France. ¹¹⁸Centre Hospitalier Valence, Valence, France. ¹¹⁹Centre Hospitalier Niort, Niort, France. ¹²⁰Clinique du Val d'Or, Saint Cloud, France. ¹²¹Centre Hospitalier de Béthune, Béthune, France. ¹²²Groupe Hospitalier Intercommunal de La Haute-Saône, Vesoul, France. ¹²³Clinique Saint-Martin, Caen, France. ¹²⁴Ramsay Générale de Santé, Clinique Convert, Bourg en Bresse, France. ¹²⁵Hôpital Victor Jousselin, Dreux, France. ¹²⁶Centre Hospitalier de Troye, Troye, France. ¹²⁷CHU de ROUEN-Hôpital Charles Nicolle, Rouen, France. ¹²⁸Centre Hospitalier Agen-Nérac, Agen, France. ¹²⁹APHP - Hôpital Louis Mourier, Colombes, France. ¹³⁰APHP - Hôpital Pitié-Salpêtrière, Paris, France. ¹³¹Institut Mutualiste Montsouris, Paris, France. ¹³²CHU Besançon - Hôpital Jean Minjoz, Besançon, France. ¹³³APHP - Hôpital Universitaire Robert-Debré, Paris, France. ¹³⁴Médipôle Lyon-Villeurbanne, Vileurbanne, France. ¹³⁵APHP - Ambroise Paré, Boulogne-Billancourt, France. ¹³⁶CHU Amiens Picardie, Amiens, France. ¹³⁷Hôpital Nord-Ouest, Villefranche-Sur-Saône, France. ¹³⁸CH de Châlons en Champagne, Châlons en Champagne, France. ¹³⁹CHU Grenoble Alpes, Grenoble, France. ¹⁴⁰Hôpital Privé d'Antony, Antony, France. ¹⁴¹Institut Arnault Tzanck, Saint Laurent du Var, France. ¹⁴²Centre Hospitalier d'Angoulême, Angoulême, France. ¹⁴³Centre Hospitalier de Cahors, Cahors, France. ¹⁴⁴Centre Hospitalier de Carcassonne, Carcassonne, France. ¹⁴⁵CHU Nice - Hôpital L'Archet 2, Nice, France. ¹⁴⁶Hôpital Privé du Vert Galant, Tremblay-en-France, France. ¹⁴⁷Centre Hospitalier de Rambouillet, Rambouillet, France. ¹⁴⁸Hopitaux du Léman, Thonon Les Bains, France. ¹⁴⁹Centre Hospitalier Victor Jousselin, Dreux, France. ¹⁵⁰Hôpital Sainte Camille, Brie Sur Marne, France. ¹⁵¹Hôpital d'instruction Des Armées Clermont-Tonnerre, Brest, France. ¹⁵²APHP - Hôpital Avicenne, Bobigny, France. ¹⁵³Groupement Hospitalier La Rochelle Ré Amis, La Rochelle, France. ¹⁵⁴Centre Hospitalier Intercommunal de Mont de Marsan Et du Pays Des Sources, Mont de Marsan, France. ¹⁵⁵Centre Hospitalier Départemental de Vendée, La-Roche-Sur-Yon, France. ¹⁵⁶Pôle Anesthésie-Réanimation, CHU Grenoble, La Tronche, France.

Received: 31 October 2022 Accepted: 6 February 2023

Published online: 11 March 2023

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12. Orban J-C, Walrave Y, Mongardon N, Allaouchiche B, Argaud L, Aubrun F, et al. Causes and characteristics of death in intensive care units a prospective multicenter study. Anesthes. 2017;126:882-9.

13. Guidet B, Flaatten H, Boumendil A, Morandi A, Andersen FH, Artigas A, et al. Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit. Intensive Care Med. 2018;44:1027-38.

14. Sprung CL, Cohen SL, Sjokvist P, Baras M, Bulow H-H, Hovilehto S, et al. End-of-life practices in european intensive care units: the ethicus study. JAMA. 2003;290:790-7.

15. Wunsch H, Harrison DA, Harvey S, Rowan K. End-of-life decisions: a cohort study of the withdrawal of all active treatment in intensive care units in the United Kingdom. Intensive Care Med. 2005;31:823-31.

16. Mark NM, Rayner SG, Lee NJ, Curtis JR. Global variability in withholding and withdrawal of life-sustaining treatment in the intensive care unit: a systematic review. Intensive Care Med. 2015;41:1572-85.

17. Gabler NB, Ratcliffe SJ, Wagner J, Asch DA, Rubenfeld GD, Angus DC, et al. Mortality among patients admitted to strained intensive care units. Am J Respir Crit Care Med. 2013;188:800-6.

18. Neuraz A, Guérin C, Payet C, Polazzi S, Aubrun F, Dailler F, et al. Patient mortality is associated with staff resources and workload in the ICU: a multicenter observational study. Crit Care Med. 2015;43:1587-94.

19. Hua M, Halpern SD, Gabler NB, Wunsch H. Effect of ICU strain on timing of limitations in life-sustaining therapy and on death. Intensive Care Med. 2016;42:987-94.

20. von Elm E, Altman DG, Egger M, Pocock SJ, Götzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453-7.

21. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957-63.

22. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707-10.

23. Juma S, Taabazuing M-M, Montero-Odasso M. Clinical frailty scale in an acute medicine unit: a simple tool that predicts length of stay. Can Geriatr J. 2016;19:34-9.

24. Borenstein M, Hedges LV, Higgins JPT. Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97-111.

25. Quill CM, Ratcliffe SJ, Harhay MO, Halpern SD. Variation in decisions to forgo life-sustaining therapies in US ICUs. Chest. 2014;146:573-82.

26. Flaatten H, Guidet B, de Lange DW, Beil M, Leaver SK, Fjølner J, et al. The importance of revealing data on limitation of life sustaining therapy in critical ill elderly Covid-19 patients. J Crit Care. 2022;67:147-8.

27. Guidet B, Jung C, Flaatten H, Fjølner J, Artigas A, Pinto BB, et al. Increased 30-day mortality in very old ICU patients with COVID-19 compared to patients with respiratory failure without COVID-19. Intensive Care Med. 2022;48:435-47.

28. Jung C, Fjølner J, Bruno RR, Wernly B, Artigas A, Bollen Pinto B, et al. Differences in mortality in critically ill elderly patients during the second COVID-19 surge in Europe. Crit Care. 2021;25:344.
Hospitalier Henri Mondor d'Aurillac, Aurillac, France. ¹⁰⁰Centre Hospitalier Saint Joseph Saint Luc, Lyon, France. ¹⁰¹Centre Hospitalier de Polynésie Française, Polynésie, France. ¹⁰²Ramsay Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France. ¹⁰³Centre Hospitalier Alpes Léman, Contamine Sur Arve, France. ¹⁰⁴Hospices Civils de Lyon - Hôpital de La Croix Rousse, Lyon, France. ¹⁰⁵Centre Cardiologique du Nord, Saint-Denis, France. ¹⁰⁶GHU - Hôpital Saint-Anne, Paris, France. ¹⁰⁷CHR Metz - Hôpital Mercy, Metz, France. ¹⁰⁸APHP - Hôpital Paul Brousse, Villejuif, France. ¹⁰⁹CHRU Nancy - Hôpital Central, Nancy, France. ¹¹⁰Centre Hospitalier d'Ajaccio, Ajaccio, France. ¹¹¹Centre Hospitalier de Bourges, Bourges, France. ¹¹²Centre Hospitalier de La Côte Basque, Bayonne, France. ¹¹³CH Saint-Malo, Saint-Malo, France. ¹¹⁴Centre Hospitalier de Mulhouse, Mulhouse, France. ¹¹⁵Centre Hospitalier de Briançon, Briançon, France. ¹¹⁶CHU Nice, Hôpital Pasteur 2, Nice, France. ¹¹⁷Centre Hospitalier Des Pays de Morlaix, Morlaix, France. ¹¹⁸Centre Hospitalier Valence, Valence, France. ¹¹⁹Centre Hospitalier Niort, Niort, France. ¹²⁰Clinique du Val d'Or, Saint Cloud, France. ¹²¹Centre Hospitalier de Béthune, Béthune, France. ¹²²Groupe Hospitalier Intercommunal de La Haute-Saône, Vesoul, France. ¹²³Clinique Saint-Martin, Caen, France. ¹²⁴Ramsay Générale de Santé, Clinique Convert, Bourg en Bresse, France. ¹²⁵Hôpital Victor Jousselin, Dreux, France. ¹²⁶Centre Hospitalier de Troye, Troye, France. ¹²⁷CHU de ROUEN-Hôpital Charles Nicolle, Rouen, France. ¹²⁸Centre Hospitalier Agen-Nérac, Agen, France. ¹²⁹APHP - Hôpital Louis Mourier, Colombes, France. ¹³⁰APHP - Hôpital Pitié-Salpêtrière, Paris, France. ¹³¹Institut Mutualiste Montsouris, Paris, France. ¹³²CHU Besançon - Hôpital Jean Minjoz, Besançon, France. ¹³³APHP - Hôpital Universitaire Robert-Debré, Paris, France. ¹³⁴Médipôle Lyon-Villeurbanne, Vileurbanne, France. ¹³⁵APHP - Ambroise Paré, Boulogne-Billancourt, France. ¹³⁶CHU Amiens Picardie, Amiens, France. ¹³⁷Hôpital Nord-Ouest, Villefranche-Sur-Saône, France. ¹³⁸CH de Châlons en Champagne, Châlons en Champagne, France. ¹³⁹CHU Grenoble Alpes, Grenoble, France. ¹⁴⁰Hôpital Privé d'Antony, Antony, France. ¹⁴¹Institut Arnault Tzanck, Saint Laurent du Var, France. ¹⁴²Centre Hospitalier d'Angoulême, Angoulême, France. ¹⁴³Centre Hospitalier de Cahors, Cahors, France. ¹⁴⁴Centre Hospitalier de Carcassonne, Carcassonne, France. ¹⁴⁵CHU Nice - Hôpital L'Archet 2, Nice, France. ¹⁴⁶Hôpital Privé du Vert Galant, Tremblay-en-France, France. ¹⁴⁷Centre Hospitalier de Rambouillet, Rambouillet, France. ¹⁴⁸Hopitaux du Léman, Thonon Les Bains, France. ¹⁴⁹Centre Hospitalier Victor Jousselin, Dreux, France. ¹⁵⁰Hôpital Sainte Camille, Brie Sur Marne, France. ¹⁵¹Hôpital d'instruction Des Armées Clermont-Tonnerre, Brest, France. ¹⁵²APHP - Hôpital Avicenne, Bobigny, France. ¹⁵³Groupement Hospitalier La Rochelle Ré Amis, La Rochelle, France. ¹⁵⁴Centre Hospitalier Intercommunal de Mont de Marsan Et du Pays Des Sources, Mont de Marsan, France. ¹⁵⁵Centre Hospitalier Départemental de Vendée, La-Roche-Sur-Yon, France. ¹⁵⁶Pôle Anesthésie-Réanimation, CHU Grenoble, La Tronche, France.

Received: 31 October 2022 Accepted: 6 February 2023

Published online: 11 March 2023

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2. Qian Z, Alaa AM, van der Schaar M, Ercole A. Between-centre differences for COVID-19 ICU mortality from early data in England. Intensive Care Med. 2020;46:1779-80.

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9. DeJong C, Chen AH, Lo B. An ethical framework for allocating scarce inpatient medications for COVID-19 in the US. JAMA. 2020;323:2367-8.

10. Avidan A, Sprung CL, Schefold JC, Ricou B, Hartog CS, Nates JL, et al. Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study. Lancet Respir Med. 2021;9:1101-10.

11. Lautrette A, Garrouste-Orgeas M, Bertrand P-M, Goldgran-Toledano D, Jamali S, Laurent V, et al. Respective impact of no escalation of treatment, withholding and withdrawal of life-sustaining treatment on ICU patients' prognosis: a multicenter study of the Outcomerea Research Group. Intensive Care Med. 2015;41:1763-72.

12. Orban J-C, Walrave Y, Mongardon N, Allaouchiche B, Argaud L, Aubrun F, et al. Causes and characteristics of death in intensive care units a prospective multicenter study. Anesthes. 2017;126:882-9.

13. Guidet B, Flaatten H, Boumendil A, Morandi A, Andersen FH, Artigas A, et al. Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit. Intensive Care Med. 2018;44:1027-38.

14. Sprung CL, Cohen SL, Sjokvist P, Baras M, Bulow H-H, Hovilehto S, et al. End-of-life practices in european intensive care units: the ethicus study. JAMA. 2003;290:790-7.

15. Wunsch H, Harrison DA, Harvey S, Rowan K. End-of-life decisions: a cohort study of the withdrawal of all active treatment in intensive care units in the United Kingdom. Intensive Care Med. 2005;31:823-31.

16. Mark NM, Rayner SG, Lee NJ, Curtis JR. Global variability in withholding and withdrawal of life-sustaining treatment in the intensive care unit: a systematic review. Intensive Care Med. 2015;41:1572-85.

17. Gabler NB, Ratcliffe SJ, Wagner J, Asch DA, Rubenfeld GD, Angus DC, et al. Mortality among patients admitted to strained intensive care units. Am J Respir Crit Care Med. 2013;188:800-6.

18. Neuraz A, Guérin C, Payet C, Polazzi S, Aubrun F, Dailler F, et al. Patient mortality is associated with staff resources and workload in the ICU: a multicenter observational study. Crit Care Med. 2015;43:1587-94.

19. Hua M, Halpern SD, Gabler NB, Wunsch H. Effect of ICU strain on timing of limitations in life-sustaining therapy and on death. Intensive Care Med. 2016;42:987-94.

20. von Elm E, Altman DG, Egger M, Pocock SJ, Götzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453-7.

21. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957-63.

22. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707-10.

23. Juma S, Taabazuing M-M, Montero-Odasso M. Clinical frailty scale in an acute medicine unit: a simple tool that predicts length of stay. Can Geriatr J. 2016;19:34-9.

24. Borenstein M, Hedges LV, Higgins JPT. Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97-111.

25. Quill CM, Ratcliffe SJ, Harhay MO, Halpern SD. Variation in decisions to forgo life-sustaining therapies in US ICUs. Chest. 2014;146:573-82.

26. Flaatten H, Guidet B, de Lange DW, Beil M, Leaver SK, Fjølner J, et al. The importance of revealing data on limitation of life sustaining therapy in critical ill elderly Covid-19 patients. J Crit Care. 2022;67:147-8.

27. Guidet B, Jung C, Flaatten H, Fjølner J, Artigas A, Pinto BB, et al. Increased 30-day mortality in very old ICU patients with COVID-19 compared to patients with respiratory failure without COVID-19. Intensive Care Med. 2022;48:435-47.

28. Jung C, Fjølner J, Bruno RR, Wernly B, Artigas A, Bollen Pinto B, et al. Differences in mortality in critically ill elderly patients during the second COVID-19 surge in Europe. Crit Care. 2021;25:344.
29. Jung C, Flaatten H, de Lange D, Beil M, Guidet B. The relationship between treatment limitations and pressure on intensive care units in elderly patients. Intensive Care Med. 2022;48:124–5.

30. Messika J, Gaudry S, Tubach F, Guillo S, Dreyfuss D, Hajage D, et al. Under-reporting of end-of-life decisions in critical care trials: a call to modify the consolidated standards of reporting trials statement. Am J Respir Crit Care Med. 2017;197:263–6.

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29. Jung C, Flaatten H, de Lange D, Beil M, Guidet B. The relationship between treatment limitations and pressure on intensive care units in elderly patients. Intensive Care Med. 2022;48:124–5.

30. Messika J, Gaudry S, Tubach F, Guillo S, Dreyfuss D, Hajage D, et al. Under-reporting of end-of-life decisions in critical care trials: a call to modify the consolidated standards of reporting trials statement. Am J Respir Crit Care Med. 2017;197:263–6.

**Publisher's Note**

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ready to submit your research? Choose BMC and benefit from:

* fast, convenient online submission

* thorough peer review by experienced researchers in your field

* rapid publication on acceptance

* support for research data, including large and complex data types

* gold Open Access which fosters wider collaboration and increased citations

* maximum visibility for your research: over 100M website views per year

At BMC, research is always in progress.

Learn more biomedcentral.com/submissions

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