# Plasma exchange are not associated with better outcome in MDA5 rapidly-progressive interstitial lung disease

Pierre Bay, Marc Pineton de Chambrun, Vincent Rothstein, Matthieu Mahevas, Nicolas de Prost, Antoine Roux, Benjamin Zuber, Dominique Israel Biet, Baptiste Hervier, Abdellatif Tazi, et al.

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## To cite this version:

Pierre Bay, Marc Pineton de Chambrun, Vincent Rothstein, Matthieu Mahevas, Nicolas de Prost, et al. Plasma exchange are not associated with better outcome in MDA5 rapidly-progressive interstitial lung disease. French Intensive Care Society International Congress 2022, 2022, Paris, France. pp.54, 10.1186/s13613-022-01016-6. hal-03831253

HAL Id: hal-03831253

https://hal.science/hal-03831253

Submitted on 6 Jun 2023

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## MEETING ABSTRACT

Open Access

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# Proceedings of Reanimation 2022, the French Intensive Care Society International Congress

*From Reanimation 2022*

Paris, France. 22-24 June 2022

Published: 22 June 2022

## Acknowledgements

This abstract report was edited and corrected by the members of the Congress Committee of the French Intensive Care Society Laetitia BODET-CONTENTIN¹, Emmanuel CANET², Guillaume CARTEAUX³, Jean-Pierre FRAT⁴, Guillaume GERI⁵, Olfa HAMZAOUI⁶, Julie HELMS⁷, Mathieu JOZWIAK⁸, Saad NSEIR⁹, Mehdi OUALHA¹⁰, Frédéric PÈNE¹¹, Nicolas WEISS¹²

¹CHU de Tours, Tours, France; ²CHU de Nantes, Nantes, France; ³Hôpital Henri Mondor, Assistance-Publique des Hôpitaux de Paris (AP-HP), Créteil, France; ⁴CHU de Poitiers, Poitiers, France; ⁵Clinique Ambroise Paré, Neuilly s/Seine, France; ⁶Hôpital Antoine Béclère, AP-HP Université Paris-Saclay, Clamart, France; ⁷CHU de Strasbourg, Strasbourg, France; ⁸CHU de Nice, Nice, France; ⁹CHU de Lille, Lille, France; ¹⁰Hôpital Necker-Enfants Malades, AP-HP, Paris, France; ¹¹Hôpital Cochin, AP-HP, Centre, Université Paris Cité, Paris, France; ¹²Sorbonne Université, Groupe Hospitalier AP-HP. Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France

## Oral communications

### CO-01

**Platelet transfusion efficacy in intensive care unit: a prospective multicenter observational**

REIZINE Florian¹, LE MAREC Sarah², LE MEUR Anthony³, CONSIGNY Maëlys², BERTEAU Florian¹, GESLAIN Marie², LE NIGER Catherine², HUNTZINGER Julien⁵, SEGUIN Philippe¹, THIBERT Jean-Baptiste⁶, REIGNIER Jean³, EGRETEAU Pierre-Yves⁴, TADIE Jean-Marc¹, HUET Olivier¹, ASFAR Pierre⁷, EHRMANN Stephan⁸, AUBRON Cécile²

¹CHU de Rennes, Rennes, France; ²CHU de Brest, Brest, France; ³CHU de Nantes, Nantes, France; ⁴CH de Morlaix, Morlaix, France; ⁵CH de Vannes, Vannes, France; ⁶Etablissement français du sang Bretagne, Rennes, France; ⁷CHU d'Angers, Angers, France; ⁸CHU de Tours, Tours, France

**Correspondence:** Florian REIZINE (florian.reizine@gmail.com)

*Annals of Intensive Care 2022, 12(1):CO-01*

**Rationale:** Up to 15% of critically ill patients receive platelets in intensive care units (ICU) (1). Both preventive and therapeutic platelet transfusions (PT) are not fully supported by high levels of evidence and the benefits of platelet transfusion remain subject to debates in some settings. This study aims to describe the efficacy of PT in ICU, and its impact on patients' outcomes.

**Patients and methods/Materials and methods:** From June 2018 to November 2019, we conducted a prospective multicenter observational study recruiting patients that received at least one PT in one of the 9 participating ICUs. Inefficacy of preventive PT was defined as a Corrected Count Increment (CCI, that adjusts for the transfused platelet dose and the body weight) <7 at 18 to 24 h after PT. Factors associated with transfusion inefficacy were assessed by performing an univariate analysis and in a mixed effect model.

**Results:** Of the 310 included patients, 119 patients (38.4%) received curative PT while 191 patients (61.6%) were treated preventively. Of the 975 transfusion episodes, 765 were given in prevention of bleeding because of low platelet count and 210 in treatment of active bleeding. PT efficacy according to the CCI was assessed in 679 preventive transfusion. Inefficacy criteria were met in 297 episodes (43.7%). Demographic and baseline characteristics associated with preventive PT inefficacy in the univariate analysis were younger age (57.7 years [Interquartile range (IQR) 44.5–66.6] versus 62.5 [53.1–69.5]; p=0.01); immunosuppression (69.9% versus 51.8%; p=0.025) and lower haemoglobin (8.5 g/dL [7.4–10] versus 9.7 g/dL [7.8–11.5]; p=0.0028). Among clinical features, PT inefficacy was associated with higher heart pulse (106 [92–120] versus 99 [86–114]; p<0.0001) and higher temperature prior to PT (37.2 [36.5–37.9] versus 37 [36.4–37.6]; p=0.016), both possible surrogate of sepsis. Interestingly, ABO compatibility did not affect PT efficacy. The mixed effect model identified haemoglobin (Estimate (E): 1.83 [Confidence Interval 95% (CI) 0.56–3.11]; p=0.0051), heart pulse before transfusion (Estimate: − 0.17 [− 0.3 to − 0.03]; p=0.016), curative anticoagulation (E: 14.1 [4.36; 23.77]; p=0.008), chronic kidney injury (E: 20.12 [0.86; 39.37]; p=0.008) and mean age of platelet transfused (E: − 3.21 [− 5.61; − 0.81]; p=0.009) being independently associated with the CCI.

**Conclusion:** Almost half of preventive PT in ICU do not meet efficacy criteria based on the CCI. Further research is warranted to investigate whether changes in the identified independent risk factors for PT inefficacy improve patients' outcomes.

**Reference 1:** Arnold DM, Crowther MA, Cook RJ, et al. (2006) Utilization of platelet transfusions in the intensive care unit: indications, transfusion triggers, and platelet count responses. Transfusion 46:1286–1291. https://doi.org/10.1111/j.1537-2995.2006.00892.x

Compliance with ethics regulations: Yes in clinical research.

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## CO-02

**Platelet transfusion in ICU: are we applying guidelines?**

LE MAREC Sarah<fnref n="1" />, REIZINE Florian², LE MEUR Anthony³, CONSIGNY Maëlys<fnref n="1" />, BODENES Laetitia<fnref n="1" />, BERTEAU Florian⁴, GESLAIN Marie<fnref n="1" />, LE NIGER Catherine<fnref n="1" />, HUNTZINGER Julien⁵, SEGUIN Philippe², THIBERT Jean-Baptiste<fnref n="6" />, REIGNIER Jean³, EGRETEAU Pierre-Yves⁴, TADIÉ Jean-Marc², HUET Olivier<fnref n="1" />, ASFAR Pierre⁷, EHRMANN Stephan⁸, AUBRON Cécile<fnref n="1" />
¹CHU de Brest, Brest, France; ²CHU de Rennes, Rennes, France; ³CHU de Nantes, Nantes, France; ⁴CH de Morlaix, Morlaix, France; ⁵CH de Vannes, Vannes, France; ⁶Etablissement français du sang Bretagne, Rennes, France; ⁷CHU d'Angers, Angers, France; ⁸CHU de Tours, Tours, France

**Correspondence:** Florian REIZINE (florian.reizine@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-02

**Rationale:** National and international guidelines for platelet transfusion in ICU are mostly based on studies conducted in non-critically ill patients or on low level of evidence leading to the potential risk of non-conformity to those recommendations. We study the conformity to both, French guidelines performed by High Health Authority (HHA) and American guidelines by the American Association of Blood Banks (AABB).

**Patients and methods/Materials and methods:** This is a prospective multicenter observational study conducted in 9 French ICU over a 18-month period. Indications and conformity of platelet transfusion (PT) to national and international guidelines were analyzed by two independent investigators and by a third one in case of disagreement between those 2 investigators. Parameters associated with PT conformity and the impact of non-conformity to 28-day mortality were identified.

**Results:** Of the 975 platelet transfusion episodes given to 310 patients, 210 (21.5%) were transfused to treat major bleeding, 407 (41.7%) to prevent bleeding because of low platelet count, 192 (19.8%) before an invasive procedure or surgery and 166 (17%) in treatments for minor bleeding. Among them, 80% (IC 95% 77-82) were conform to the French HHA guidelines, and 62% (IC 95% 59-65) to theABB. The factors independently associated with non-conformity to the French guidelines were preventive PT in patients with low platelet count (OR 5.28; IC 95% 3.66-7.63, p < 0.0001), and ongoing curative anticoagulation (OR 2.21; IC 95% 1.30-3.77, p = 0.0034). There was no difference in mortality between patients receiving conform and non-conform PT.

**Conclusion:** Around 20% and 40% of PT were non-conform to the national and the international guidelines, respectively. Independent risk factors for non-conformity were preventive PT for low platelet count, and ongoing curative anticoagulation. Our results highlight the need for further research to better define PT indications in ICU.

Compliance with ethics regulations: Yes in clinical research.

## CO-03

**Prognostic factors of renal function in critically ill patients with hemolytic and uremic syndrome: a 6-year retrospective multicenter study**

QUELVEN Quentin<fnref n="1" />, COIRIER Valentin<fnref n="1" />, DELAMAIRE Flora<fnref n="1" />, MARIOTTE Eric², FILLATRE Pierre⁴, DELBOVE Agathe³, GUILLOT Pauline<fnref n="1" />, GACOUIN Arnaud<fnref n="1" />, TADIÉ Jean-Marc<fnref n="1" />, CAMUS Christophe<fnref n="1" />, MAAMAR Adel<fnref n="1" />
¹CHU Rennes, Pontchaillou, Rennes, France; ²Hopital Saint Louis, Paris, France; ³CH Bretagne Atlantique, Vannes, France; ⁴CH Yves Le Foll, Saint Brieuc, France

**Correspondence:** Quentin QUELVEN (quentinquelven@hotmail.fr)

Annals of Intensive Care 2022, **12**(1):CO-03

**Rationale:** Hemolytic and uremic syndrome (HUS) is a field of heterogeneous pathologies whose diagnostic and therapeutic management remain difficult. We aimed to describe clinical and biological features of critically ill patients admitted to intensive care unit (ICU) for HUS and assess the impact of common therapeutics on renal function.

**Patients and methods/Materials and methods:** We performed a 6-year retrospective multicenter study from 2014 to 2019 of patients admitted for a proven HUS in four French ICU. HUS was defined by the presence of anemia with arguments in favor of a hemolytic origin and

non-autoimmune origin, associated with thrombocytopenia, or with histologic evidence of thrombotic microangiopathy. Clinical features, biological features and therapeutics initiated during the ICU stay were retrospectively collected. Glomerular filtration rate (GFR) was assessed by the Chronic Kidney Disease Epidemiology Collaboration at day-30, 90 and 180. We also assessed 30-day mortality. A repeated-measures analysis of variance was employed to assess the changes in GFR with the use of plasma exchange, Eculizumab and extra renal replacement therapy (RRT) during the ICU stay.

**Results:** We included 103 patients (median age 54 [32-65], males 48 (47%)). Twenty-seven (26%) had STEC-HUS, 13 (13%) aHUS and 59 (57%) secondary HUS. Among these patients, 71 (69%) received plasma exchange, 18 (18%) received eculizumab and 46 (45%) received renal replacement therapy (RRT) during their ICU stay. Ninety-two (89%) survived in ICU and 78 (86%) were alive at day 30. At day-180, 13 (12.6%) still required RRT. Renal function at six months was not significantly different between the patients who received plasma exchange (69 [41-91] versus 43 [23-50] mL/mn/1.73 m², p = 0.17), Eculizumab (55 [50-73] versus 69 [31-91] mL/min/1.73 m², p = 0.57) or RRT (49 [31-69] versus 69 [36-91] mL/mn/1.73 m², p = 0.40). Moreover, ICU and hospital lengths of stay were significantly longer for patients who received plasma exchange and they had a longer duration of RRT. Finally, multivariate analysis shows that RRT in ICU is a prognosis factor independently associated with RRT at day-180.

**Conclusion:** Plasma exchange, eculizumab and RRT were not associated with an improvement of day-180 renal function in our multicenter study. Further studies are still needed to define the best therapeutic management of these patients.

**Reference 1:** Pène F, Vigneau C, Auburtin M, Moreau D, Zahar J-R, Coste J, et al. Outcome of severe adult thrombotic microangiopathies in the intensive care unit. Intensive Care Med. janv 2005;31(1):71-8

**Compliance with ethics regulations:** Yes in clinical research.

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**Figure:** Evolution of renal function estimated by CKD-EPI depending on whether they received specific treatment or not.

## CO-04

**Epidemiology, clinical presentation, evolution and prognostic factors for survival of patients with eosinophilia in intensive care: retrospective national multicenter cohort study "REO"**

GAILLET Antoine⁷, BAY Pierre², PÉJU Edwige⁸, FAGUER Steven⁴, ASMA Mabrouki¹⁰, AZOULAY Elie¹⁰, PÈNE Frédéric⁸, TANDJAOUI-LAMBIOTTE Yacine¹¹, COHEN Yves¹¹, GERI Guillaume¹², VIEILLARD-BARON Antoine¹², PINETON DE CHAMBRUN Marc⁵, BENCHABANE Nacim⁵, LARCHER Romaric⁵, GRANGE Steven⁹, QUENOT Jean-Pierre¹⁴, AIT OUFELLA Hafid¹³, TIMSIT Jean-Francois³, MEKONTSO DESSAP Armand⁷, KAHN Jean-Emmanuel¹², DARGENT Auguste<fnref n="6" />, HERAULT Antoine⁹, GROH Matthieu<fnref n="1" />

<footnote n="1">¹Foch, Suresnes, France; ²Pitié Salpêtrière, Paris, France; ³Bichat, Paris, France; ⁴Rangueil, Toulouse, France; ⁵Lapeyronie, Montpellier, France;</footnote>

<footnote n="6">⁶Edouard Herriot, Lyon, France; ⁷Henri Mondor, Créteil, France; ⁸Cochin,</footnote>
Paris, France; ⁹CHU Rouen, Rouen, France; ¹⁰Saint Louis, Paris, France; ¹¹Avicenne, Bobigny, France; ¹²Ambroise Paré, Boulogne-Billancourt, France; ¹³Saint Antoine, Paris, France; ¹⁴François Mitterrand, Dijon, France
**Correspondence:** Antoine GAILLET (gaillet.antoine75@gmail.com)
*Annals of Intensive Care* 2022, **12**(1):CO-04

**Rationale:** The objectives of the "REO" study are to describe the epidemiological characteristics of situations associated with eosinophilia in intensive care units (ICU) and to identify predictors of mortality in this situation.

**Patients and methods/Materials and methods:** Retrospective, national, multicenter cohort (14 centers), including adult patients (≥ 18 years old) who presented, from 01/01/2013 to 12/31/2018, eosinophilia ≥ 1000/mm³ on two samples (not necessarily consecutive) performed from the day before admission to the end of the stay in ICU.

**Results:** 620 patients were included (i.e. approximately 1.2% of all stays over the period and participating centers): 248 (40%) with early eosinophilia (occurring within the first 24 h of admission, ICU-Eo1 group) and 348 (56%) with delayed eosinophilia (> 24 h after admission, ICU-Eo2 group), 24 patients with no reported time to onset of eosinophilia. In the ICU-Eo1 group, eosinophilia was mostly non-idipathic (with a high incidence of onco-haematological pathologies: 26% vs. 4% in the ICU-Eo2 group, p < 0.001), most often symptomatic (59% vs 25% for ICU-Eo2, p < 0.001), especially with respiratory involvement. Eosinophilia in patients in the ICU-Eo2 group was most often idiopathic or related to drug hypersensitivity (85% vs. 47% in patients in the ICU-Eo1 group, p < 0.001), and visceral skin involvement was at first plan (72% of visceral damage in ICU-Eo2 vs. 32% in the ICU-Eo1 group). Nevertheless, in 14% of ICU-Eo2 patients, an "unexpected" etiology (particularly parasitic, onco-haematological) was identified, especially when the patient had a prior history of eosinophilic disease, was admitted for acute respiratory distress or had an eosinophilia peak > 5000/mm³ during ICU stay. The risk factors for mortality at day 60 highlighted in multivariate analysis for the ICU-Eo1 group were age > 65 years (HR 1.78 95% CI [1.02; 3.13] p = 0.044), current immunosuppressant therapy at ICU admission (HR 2.32 95% CI [1.18; 4.54] p = 0.014), SOFA score > 8 (HR 2.26 95% CI [1.17; 4.39] p = 0.015), admission for acute respiratory distress (HR 2.43 IC95% [1.06; 5.60] p = 0.037) or for shock (HR 3.08 95% CI [1.15; 8.29] p = 0.026) and finally that the current eosinophilia is of onco-haematological origin (HR 4.41 [2.47; 7.90] p < 0.001). About the ICU-Eo2 group, only the use of invasive ventilation during the stay was associated with poor prognosis (HR 5.54 [1.32; 23.35] p = 0.019).

**Conclusion:** In ICU, two distinct populations of eosinophilia seem to be defined according to the time of onset of this one. When eosinophilia is present on admission, the onco-haematological origin particularly affects the prognosis.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-05

### Etoposide-containing regimens for the treatment of critically ill patients with hematological malignancy-related hemophagocytic lymphohistiocytosis

LE STANG Valentine¹, VIGNERON Clara², DECRQOCQ Justine², PÉJU Edwige², BURRONI Barbara², CHAPUIS Nicolas², CHARPENTIER Julien², PÈNE Frédéric²

¹La Pitié Salpétrière, Paris, France; ²Hôpital Cochin, Paris, France

**Correspondence:** Valentine LE STANG (vavaw_100@hotmail.fr)
*Annals of Intensive Care* 2022, **12**(1):CO-05

**Rationale:** Hemophagocytic lymphohistiocytosis (HLH) related to hematological malignancies is a rare condition likely responsible for life-threatening multiple organ failure. Etoposide is often used as a first-line treatment in this setting but its impact on the course of HLH-defining criteria and organ failures has not been investigated.

**Patients and methods/Materials and methods:** We conducted an 8-year (2013–2020) single-center retrospective study in a medical ICU

of a tertiary-care center, including adult patients with severe hematological malignancy-related HLH treated with etoposide.

**Results:** Twenty-four patients were analyzed, including 17 with lymphoma. Median H-score was 253.0 [226.3–287.0] and 16 patients fulfilled at least five HLH-2004 diagnostic criteria. All patients received first-line etoposide treatment, combined with corticosteroids in 21 patients, followed by combination chemotherapy in 16 patients after a median of 4 days [1.5–7.0]. Following etoposide initiation, body temperature decreased from 38.9 °C [38.0–39.5] to 37.6 °C [36.8–39.0] within 24 h (p = 0.01) (Fig. 1) and ferritin levels decreased by 59.8 ± 28.9% within 7 days. Lactate level decreased from 3.0 mmol/L [1.5–4.3] to 2.1 mmol/L [1.6–3.0] (p = 0.02) within 24 h from etoposide (Fig. 1). Patients exhibited early and transient deterioration in non-platelet SOFA score (npSOFA) that significantly increased from 5 [1.3–10] at etoposide initiation to 9.5 [2–15] at day 1, and thereafter improved to npSOFA value of 7 [1–11] at day 2 (Fig. 1). In-ICU, in-hospital and 1-year mortality were 45.8%, 54.2% and 66.7%, respectively.

**Conclusion:** Etoposide as single treatment or as part of sequential combination regimen was able to rapidly dampen some dynamic HLH-defining variables and to eventually improve organ failures.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-06

### Clinical significance of thrombocytopenia in patients with septic shock

PÉJU Edwige¹, FOUQUÉ Gaëlle¹, CHARPENTIER Julien¹, VIGNERON Clara¹, JOZWIAK Mathieu², MIRA Jean-Paul¹, CARIOU Alain¹, JAMME Matthieu³, PÈNE Frédéric¹

¹APHP/Hôpital Cochin, Paris, France; ²CHU de Nice/Hôpital l'Archet, Nice, France; ³Hôpital CHI Poissy/Saint-Germain-en-Laye, Paris, France

**Correspondence:** Edwige PÉJU (edwigepeju@gmail.com)
*Annals of Intensive Care* 2022, **12**(1):CO-06

**Rationale:** Thrombocytopenia is a common disorder in critically ill patients and is known to be associated with poor prognosis. Whether thrombocytopenia accounts for a bystander of severity or may drive specific complications is unclear. With respect to the various immune and procoagulant functions of platelets, the aim of this study is to address the impact of thrombocytopenia on the development of ICU-acquired infections, bleeding and ischemic events in high-risk patients with septic shock.

**Patients and methods/Materials and methods:** This was a single-center retrospective study conducted in a medical ICU over a 12-year period (2008–2019). Patients admitted for septic shock (Sepsis-2 definition) were included if still alive in the ICU after 48 h, to retain patients at risk of further ICU-acquired complications. Morning platelet counts were collected daily. Groups of patients were defined according to 7-day platelet count trajectories estimated using latent class mixed model. Outcomes were ICU mortality and ICU-acquired complications including infections, severe bleeding events (WHO grade 3–4) and thrombotic events.

**Results:** The cohort comprised 1024 48-h survivors. Among them, 39% were immunocompromised, including one third with hematological malignancies. Upon admission, 153 patients (15%) had profound thrombocytopenia with platelet count below 50 G/L. The in-ICU mortality rate was 27% (n = 281). ICU-acquired infections, severe bleeding events and thrombotic events occurred in 28%, 13% and 12% of patients, respectively. The latent class model identified five subgroups with consistent 7-day platelet count trajectories. The subgroup of patients with initial low and sustained thrombocytopenia (n = 224) was associated with high prevalence (39%) of hematologic malignancies and displayed increased mortality when compared to patients with alternative platelet trajectories (49% vs. 13%, 21%, 30%, 24%, p < 0.001). In multivariate analysis, initial low and sustained thrombocytopenia (cause-specific hazard (CSH) = 2.96 [95% CI 2.16–4.06], p < 0.001) and initial normal with fast decrease in platelet count (CSH = 2.21 [1.19–4.12], p = 0.01) were independently associated with
mortality. Sustained profound thrombocytopenia was independently associated with increased risk of bleeding (CSH = 1.57 [1.02–2.65], p = 0.004). Platelet count trajectories were not significantly associated with the development of ICU-acquired infections and thrombotic events.

**Conclusion:** Patterns of thrombocytopenia are associated with outcomes in septic shock. Sustained profound thrombocytopenia and fast relative thrombocytopenia were both independent determinants of ICU mortality. Sustained profound thrombocytopenia was associated with an increased risk of severe bleeding. Platelet count trajectories did not impact on the risk of ICU-acquired infections or thrombotic events.

**Compliance with ethics regulations:** Yes in clinical research.

CO-07

Reliability of peak inspiratory pressure to estimate plateau pressure in infants with severe virus airway infection

ROTAVA BURATTI Cecília¹,²,³, JOUVET Philippe³, ANDREOLIO Cinara¹,²,
BRUNO Francisco¹,², ANDRADE Lívia², MARCON Mônica¹, NAVARRO
Nádia¹,², PIVA Jefferson¹,²

¹Hospital de Clínicas de Porto Alegre, Porto Alegre, Bresil; ²Postgraduate program in child and adolescent health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ³Sainte Justine Research Center, Montreal, Canada

**Correspondence:** Rotava Buratti CECÍLIA (ceciliaburatti@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-07

**Rationale:** Peak inspiratory pressure (PIP) measured in decelerating-flow mode (PIPdc), i.e. pressure modes, is close to plateau pressure (Pplat) in children with pediatric acute respiratory distress syndrome¹. Since one third of children admitted to the PICU are less than 1 year old and that bronchiolitis is the leading cause of hospitalization in this age group², our aim was to evaluate the reliability of PIPdc to estimate Pplat in volume control (VC) in infants with severe respiratory virus infection (SRVI), which is characterized by increased airway resistance.

**Patients and methods/Materials and methods:** A retrospective observational study was developed including infants diagnosed as SRVI, mechanically ventilated, and with respiratory mechanics measurements taken between 2017 and 2021. Measurements were taken during inspiratory and expiratory pauses after switching ventilatory mode from pressure control to volume control in patients without respiratory effort. Statistical analysis included paired t-test, Pearson correlation (r) and coefficient of determination (R²).

**Results:** Thirty-seven patients were included with a median age of 3 months (2–5), a *Pediatric Index of Mortality-2* of 0.2% (0.2–0.6) and a mean oxygen saturation index of 4.3 ± 1. Inspiratory (Rlaw) and expiratory airway resistance (REaw) were 136 ± 43 and 168 ± 66 cmH₂O/L/s, respectively, and static compliance: 0.75 ± 0.30 ml/kg/cmH₂O. PIPdc was lower than PIP in VC, but still higher than measured Pplat (33 ± 3, 36 ± 5 and 26 ± 5 cmH₂O respectively, p = 0.01 between PIP and Pplat). PIPdc overestimates Pplat with a moderate correlation (r = 0.57, p < 0.001 and R² = 0.33, p < 0.001) and a mean difference of 7.3 ± 4 cmH₂O (Figure).

**Conclusion:** A large difference between PIP and Pplat can be observed in infants with a significant increase in airway resistance. In the absence of Pplat measurement in a static condition, any estimation of Pplat from PIP needs to consider the resistive component of respiratory system.

**Reference 1:** Patel B et al.: Agreement Between Peak Inspiratory Pressure in Decelerating-Flow Ventilation and Plateau Pressure in Square-Flow Ventilation in Pediatric Acute Respiratory Distress Syndrome. Pediatr Crit Care Med 2022.

**Reference 2:** Fujiogi M et al.: Trends in bronchiolitis hospitalizations in the United States: 2000–2016. Pediatrics 2019.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_7.png" /></figure>

Difference between positive inspiratory pressure in decelerating-flow modes (PIPdc) and plateau pressure (Pplat) in volume control according to time constant, in mechanically ventilated children.

**Figure Legend:** Difference between positive inspiratory pressure in decelerating-flow modes (PIPdc) and plateau pressure (Pplat) in volume control according to time constant, in mechanically ventilated children. **Panel A:** cohort of Patel et al.¹, patients with pediatric acute respiratory distress syndrome n = 52, median age 8.6 yo. And from our sample it has been shown **Panel B, C and D. Panel B:** patients with severe respiratory virus infection (SRVI) n = 9, median age 4 mo, Rlaw 50–100 cmH₂O/L/s; **Panel C:** patients with SRVI n = 13, median age 3 mo, Rlaw 100–150 cmH₂O/L/s; **Panel D:** patients with SRVI n = 15, median age 3 mo, Rlaw 150–200 cmH₂O/L/s. Rlaw: inspiratory airway resistance; REaw: expiratory airway resistance.

CO-08

Predictive factors of high flow nasal canula (HFNC) short term failure in severe acute bronchiolitis

ZINI Justine¹, VAUGIER Isabelle¹, BERGOUNIOUX Jean¹

¹CHU Raymond Poincaré, Garches, France

**Correspondence:** Justine ZINI (justine.zini@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-08

**Rationale:** High flow oxygen nasal cannula therapy (HFNC) is a non-invasive respiratory support increasingly used to treat bronchiolitis induced respiratory failure. HFNC utilisation spread in pediatric emergency department because of its affordable material and ease of use. However, regular monitoring and clinical assessment of the HFNC treated child by emergency physicians and nurses is needed. Its use has been shown to avoid transfers to intensive care that is a limited resource in epidemic period. However, at the early time of its implementation, it is difficult and yet critical for the security of the patient to predict its efficiency in treating the bronchiolitis induced respiratory failure.

**Objective:** The aim of this study was to identify factors predicting early failure of HFNC once it has been implemented in a pediatric emergency department to treat bronchiolitis induced respiratory failure.

**Patients and methods/Materials and methods:** This is a retrospective multicenter study in 4 Ile-de-France region hospitals (France), comparing biometric, anamnestic, clinical, biological and radiological patient data before and until 12 h HFNC treatment. Patients included
were aged 0 to 12 months, admitted to the pediatric emergency department and diagnosed with acute bronchiolitis with initiation of high-flow oxygen therapy within 12 h of arrival in the pediatric emergency department.

**Results:** 160 patients were included with 52 HFNC failures. Abnormal consciousness and apneas during the use of high-flow oxygen therapy were a predictor of early high-flow oxygen therapy failure (p = 0.0001). We showed a correlation of lower the pH, higher PCO₂ and bicarbonate levels with early HFNC failure (p < 0.001). Similarly, lack of improvement in pH (p = 0.03), PCO₂ (p = 0.017), and bicarbonate levels (p = 0.0005) shortly HFNC implementation are predictors of high-flow oxygen therapy failure. Chest X-ray atelectasis was a predictive factor for failure of OHD (p = 0.003). Wheezing heard before and during HFNC was associated with success (p = 0.01).

**Conclusion:** Our results showed that blood gases before and after HFNC implementation were a major predictive element for success or failure in the very first hours of HFNC treatment but that blood gases bicarbonate blood levels were also strongly correlated to HFNC success. Several clinical criteria were also associated with success such as the presence of wheezing sound, atelectasia, hypoxemia before HFNC. We believe that those results may help pediatric emergency physicians to anticipate HFNC success or failure in infant with acute bronchiolitis presenting to the pediatric emergency department.

**Reference 1:** The New England Journal of Medicine 2018 "A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis" Donna Franklin.

**Reference 2:** Eur Respir J 2020 "A randomised trial of high-flow nasal cannula in infants with moderate bronchiolitis" Philippe Durand.

**Compliance with ethics regulations:** Yes in clinical research.

<table><caption>Table 1. Analyze data before introduction of HFNC treatment, by collecting anamnestic, clinical and gases characteristics (pH, pCO₂, bicarbonates), between two groups (HFNC therapy success vs HFNC therapy failure). HFNC: High flow nasal cannula. n and (%)</caption><thead><tr><th></th><th>Overall, n = 160<sup>1</sup></th><th>Failure, n = 52<sup>1</sup></th><th>Success, n = 100<sup>2</sup></th><th>p-value<sup>3</sup></th></tr></thead><tbody><tr><td colspan="5"><strong>Characteristics neonatal</strong></td></tr><tr><td>Age (weeks)</td><td>92 (58%)</td><td>33 (63%)</td><td>59 (55%)</td><td>0.319</td></tr><tr><td>Tempe (SA)</td><td>37.94 (2.76)</td><td>37.80 (3.17)</td><td>38.01 (2.55)</td><td>0.685</td></tr><tr><td>Premature birth</td><td>27 (18%)</td><td>12 (24%)</td><td>15 (15%)</td><td>0.177</td></tr><tr><td>Weight birth (kg)</td><td>3.08 (0.73)</td><td>2.97 (0.75)</td><td>3.13 (0.71)</td><td>0.220</td></tr><tr><td>Twin</td><td>8 (5.0%)</td><td>6 (12%)</td><td>2 (1.9%)</td><td>0.015</td></tr><tr><td>Cardio-pulmonary disease</td><td>15 (9.4%)</td><td>9 (17%)</td><td>6 (5.6%)</td><td>0.022</td></tr><tr><td>CPAP support</td><td>14 (8.8%)</td><td>9 (17%)</td><td>5 (4.6%)</td><td>0.014</td></tr><tr><td>Invasive ventilation</td><td>2 (1.2%)</td><td>1 (1.9%)</td><td>1 (0.9%)</td><td>0.546</td></tr><tr><td colspan="5"><strong>Characteristics admission at the emergency and before HFNC introduction</strong></td></tr><tr><td>Age (weeks)</td><td>11 (10)</td><td>8 (10)</td><td>12 (9)</td><td>0.033</td></tr><tr><td>Age corrected (weeks)</td><td>9 (10)</td><td>6 (10)</td><td>10 (9)</td><td>0.009</td></tr><tr><td>Weight (kg)</td><td>5.13 (1.63)</td><td>4.62 (1.61)</td><td>5.36 (1.59)</td><td>0.009</td></tr><tr><td>Rate respiratory (breaths/min)</td><td>61 (14)</td><td>60 (16)</td><td>62 (13)</td><td>0.586</td></tr><tr><td>Heart rate (beats/min)</td><td>168 (18)</td><td>168 (16)</td><td>168 (18)</td><td>0.971</td></tr><tr><td>Transcutaneous oxygen saturation (%)</td><td>96 (4)</td><td>96 (5)</td><td>96 (4)</td><td>0.005</td></tr><tr><td>Transcutaneous oxygen saturation &lt;90%</td><td>38 (24%)</td><td>18 (35%)</td><td>20 (19%)</td><td>0.021</td></tr><tr><td>Atpnea</td><td>22 (14%)</td><td>9 (17%)</td><td>13 (12%)</td><td>0.365</td></tr><tr><td>Markling</td><td>24 (15%)</td><td>7 (13%)</td><td>17 (16%)</td><td>0.705</td></tr><tr><td>Neurologic disease</td><td>38 (24%)</td><td>9 (17%)</td><td>29 (27%)</td><td>0.184</td></tr><tr><td>Expiratory brake</td><td>56 (35%)</td><td>19 (37%)</td><td>37 (34%)</td><td>0.777</td></tr><tr><td>Thoraco-abdominal balance</td><td>106 (66%)</td><td>40 (77%)</td><td>66 (61%)</td><td>0.048</td></tr><tr><td>Intercostal indrawing</td><td>311 (19%)</td><td>35 (67%)</td><td>76 (70%)</td><td>0.694</td></tr><tr><td>Sus-tertial indrawing</td><td>95 (59%)</td><td>32 (62%)</td><td>63 (58%)</td><td>0.699</td></tr><tr><td>Cracking auscultation</td><td>47 (29%)</td><td>17 (33%)</td><td>30 (28%)</td><td>0.523</td></tr><tr><td>Wizing on auscultation</td><td>74 (44%)</td><td>16 (31%)</td><td>58 (54%)</td><td>0.006</td></tr><tr><td>Atelectasia</td><td>16 (10%)</td><td>11 (21%)</td><td>5 (4.6%)</td><td>0.001</td></tr><tr><td colspan="5"><strong>pCO₂ and bicarbonate blood gases before HFNC introduction</strong></td></tr><tr><td>Gases</td><td></td><td></td><td></td><td></td></tr><tr><td>pH</td><td>7.33 (0.06)</td><td>7.31 (0.05)</td><td>7.34 (0.05)</td><td>&lt;0.001</td></tr><tr><td>pO<sub>2</sub> - 7,34</td><td>32 (30%)</td><td>19 (45%)</td><td>13 (20%)</td><td>0.005</td></tr><tr><td>pCO₂ (mmHg)</td><td>53 (10)</td><td>59 (11)</td><td>49 (9)</td><td>&lt;0.001</td></tr><tr><td>pCO₂ &gt; 50 mmHg</td><td>57 (53%)</td><td>32 (76%)</td><td>25 (38%)</td><td>&lt;0.001</td></tr><tr><td>Bicarbonate (mmol/l)</td><td>26.8 (3.6)</td><td>28.2 (3.7)</td><td>25.8 (3.2)</td><td>0.001</td></tr><tr><td>Bicarbonate &gt; 26 mmol/l</td><td>46 (46%)</td><td>27 (68%)</td><td>19 (32%)</td><td>&lt;0.001</td></tr><tr><td colspan="5"><strong>Score 0 to 3 abnormally parametric gases blood gases</strong></td></tr><tr><td>Numbers of abnormally parametric gases among pH, pCO₂ or Bicarbonate</td><td></td><td></td><td></td><td></td></tr><tr><td>0</td><td>42 (39%)</td><td>7 (17%)</td><td>35 (53%)</td><td>&lt;0.001</td></tr><tr><td>1</td><td>14 (13%)</td><td>5 (12%)</td><td>9 (14%)</td><td></td></tr><tr><td>2</td><td>35 (32%)</td><td>17 (40%)</td><td>18 (27%)</td><td></td></tr><tr><td>3</td><td>17 (16%)</td><td>13 (31%)</td><td>4 (6.1%)</td><td></td></tr></tbody></table>

<caption>Table 1. Analyze data before introduction of HFNC treatment, by collecting anamnestic, clinical and blood gas characteristics (pH, pCO₂, bicarbonates), between two groups (HFNC therapy success vs HFNC therapy failure). HFNC: High flow nasal cannula. n and (%)</caption>

CO-09

Mechanical ventilator settings during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome: An European observational study

RAMBAUD Jerome<fnref n="1" />, BROMAN Lars<fnref n="2" />, VISCONTI Federico⁶, LEGER Pierre Louis<fnref n="1" />, BUTRAGUEÑO LAISECA Laura⁵, PILOQUER Jean Eudes⁴, DINARDO Matteo³

¹Armand-Trousseau, Paris, France; ²Karolinska Institute, Stockholm, Suede;

³Ospedale Pediatrico Bambino Gesù, Rome, Italie; ⁴Nantes universitary hospital, Nantes, France; ⁵Hospital General Universitario Gregorio Marañón, Madrid, Espagne; ⁶University Hospital of Padova, Padoue, Italie

**Correspondence:** Jerome RAMBAUD (jerome.rambaud@aphp.fr)

Annals of Intensive Care 2022, **12**(1):CO-09

**Rationale:** The main objective of the study was to first describe which settings are used for mechanical ventilation during ECMO for pediatric acute respiratory distress syndrome. The secondary objective of this study is to identify risk factors associated with poor prognosis or uncomplete recovery.

**Patients and methods/Materials and methods:** A retrospective observational study in five European centers. All children aged 1 month—18 years supported by ECMO for refractory P-ARDS from January 2009 to December 2019 were included. Collected data were pre-ECMO clinical score invasive ventilation parameters before ECMO and at day 1, 3, 7 and 14 of assistance (positive end-expiratory pressure, mean pressure, plateau pressure, driving pressure), adjunctive therapies during ECMO (prone positioning, steroids, tracheostomy, bronchoscopy and cross-sectional imaging). Finally, we gathered outcomes parameters (survival rate, length of ECMO and invasive ventilation).

**Results:** We included 256 patients. Median oxygenation index and oxygenation saturation index were 37 and 24.7, respectively. Half of the P-ARDS cases were viral pneumonia. Before ECMO implantation, prone positioning and neuromuscular blockers were used in 39% and 61% of the patients. Veno-venous ECMO was offered in 62%, and dual-lumen cannula was used in one quarter of VV ECMO cases. Preferential ventilator mode during ECMO was barometric setting during the whole study period. Positive end-expiratory pressure (PEEP) and mean airway pressure were significantly different between centers. Prone positioning (16%), recruitment maneuvers (2%), cross sectional imaging (8%), and tracheostomy (3%) during ECMO remained limited. Higher PEEP and higher mean airway pressure during the whole study period were associated with higher mortality.

**Conclusion:** Ventilatory setting during ECMO for acute respiratory distress syndrome are highly dependent on center. Associations between high PEEP and mean airway pressure with lower survival rate raise the question to define the best way to manage patients under ECMO for ARDS.

**Compliance with ethics regulations:** Yes in clinical research.

CO-10

Pediatric microcirculation monitoring during ECMO weaning

SUC Violette<fnref n="1" />, RAMBAUD Jerome<fnref n="1" />, STARCK Julie<fnref n="1" />, LEGER Pierre-Louis<fnref n="1" />

¹Hôpital Armand Trousseau, Paris, France

**Correspondence:** Violette SUC (violette.suc@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-10

**Rationale:** ECMO is an extracorporeal respiratory and circulatory support used in children for severe respiratory failure or refractory shock states. The usual monitoring of patient under ECMO makes it possible to understand the macrocirculatory system. Perfusion and tissue oxygenation are represented by microcirculation. It has been shown to be a powerful prognostic factor for survival in children in septic shock (reference 1). The duration of ECMO depends on the remission of the organs. Early and successful weaning from ECMO reduces morbidity and mortality of the technique. The aim of the study was to determine the relevance of the sublingual microcirculation to predict the risk of "difficult weaning" of ECMO in children, expressed by the occurrence of severe hemodynamic failure during the clamping of ECMO.

<footnote n="1">¹Mean (SD); n (%)</footnote>

<footnote n="2">²Welch Two Sample t-test; Pearson's Chi-squared test; Fisher's exact test</footnote>
**Patients and methods/Materials and methods:** A single-center prospective study on patients hospitalized in pediatric intensive care at Trousseau Hospital between March 2017 and December 2020. A video analysis in sidestream dark field was performed for all patients at the weaning time as well as an echocardiography and a blood gas. Patients were classified into two groups: "easy weaning" or "difficult weaning" depending on the outcome after ECMO clamping. Difficult weaning group was defined as patients with hemodynamic failure and need of restart ECMO within 24 h of the weaning, or patients who presented one of the following criteria: hemodynamic failure requiring introduction or increase of vasopressors, cardiac dysfunction requiring introduction or increase of inotropic drugs, pulmonary arterial hypertension requiring vasodilator treatment, ventilation increase (Pmax > 28–30 cmH₂O), refractory hypoxemia (SpO₂ < 94% with FiO₂ > 75%) or hypercapnic acidosis (pH < 7.30).

**Results:** 30 patients were included in the study (13 newborns, median age at admission 29 days [1–770]) including 18 (60%) in veino-arterial ECMO. 19 patients were classified in the "easy weaning" group and 11 in the "difficult weaning" group. The small vessel Microvascular Flow Index at weaning was high in both groups (median 2.3 [1.8-2.4] vs 2.3 [2.3-2.6], p = 0.24) without a significant difference (Table 1). There were no differences in macro-circulatory indices, nor by ECMO type or age. The microcirculation parameters were not a predictive factor of mortality.

**Conclusion:** Our study is the first pediatric study to present microcirculation data at the ECMO weaning time. The microcirculation parameters at the weaning time in ECMO don't seem to be predictive of success or failure of weaning. Post-clamping analysis may be relevant.

**Reference 1:** Top APC, Ince C, de Meij N, van Dijk M, Tibboel D. Persistent low microcirculatory vessel density in nonsurvivors of sepsis in pediatric intensive care. Crit Care Med. 2011.

**Compliance with ethics regulations:** Yes in clinical research

<table><thead><tr><th></th><th>"Easy weaning"<br>N = 19</th><th>"Difficult weaning"<br>N = 11</th><th>P Value</th></tr></thead><tbody><tr><td><strong>Detected Vessel Lenght</strong><br>(DVL, mm)</td><td>5.5 [4.5-6]</td><td>5.8 [5.2-6.4]</td><td>0.4</td></tr><tr><td><strong>Vessel Density</strong><br>(VD, mm/m2)</td><td>12.9 [10.8-14.8]</td><td>13.3 [12.5-14.7]</td><td>0.54</td></tr><tr><td><strong>Vessel surface</strong><br>(VS, mm/m2)</td><td>12.4 [10.5-14]</td><td>13.1 [11.8-14]</td><td>0.42</td></tr><tr><td><strong>Gride crossing</strong></td><td>30.9 [25.7-32]</td><td>31 [28-34]</td><td>0.38</td></tr><tr><td><strong>Gride length (mm)</strong></td><td>3.9 [3.9-3.9]</td><td>3.9 [3.8-3.89]</td><td>0.29</td></tr><tr><td><strong>De Backer score</strong><br>(1/mm3)</td><td>8 [6.6-8.3]</td><td>8.1[7.2-8.9]</td><td>0.41</td></tr><tr><td><strong>Total Vessel density</strong><br>(TVD, mm/m2)</td><td></td><td></td><td></td></tr><tr><td>Small</td><td>11.2 [9.3-13.6]</td><td>12.1 [11.2-13.9]</td><td>0.25</td></tr><tr><td>Other</td><td>1.4 [0.8-1.95]</td><td>1.3 [1-1.6]</td><td>0.89</td></tr><tr><td>All</td><td>12.9 [10.8-14.8]</td><td>13.9 [12.5-15.4]</td><td>0.41</td></tr><tr><td><strong>Microvascular Flow Index</strong><br>(MFI)</td><td></td><td></td><td></td></tr><tr><td>Small</td><td>2.3 [1.8-2.4]</td><td>2.3 [2.3-2.6]</td><td>0.24</td></tr><tr><td>Other</td><td>2.7 [3.3-3.8]</td><td>2.7 [2.5-2.8]</td><td>0.86</td></tr><tr><td>All</td><td>2.4 [2.3-2.7]</td><td>2.6 [2.4-2.7]</td><td>0.14</td></tr></tbody></table>

Microcirculatory parameters after one hour of weaning test

## CO-11

### Beta-lactam exposure of children on ECMO: are conventional dosing appropriate?

MARSAUX Alice¹, LÉGER Pierre-Louis², BILLE Emmanuel³, RENOLLEAU Sylvain³, TRELUYER Jean-Marc⁴, LORROT Mathie², GRIMAUD Marion³, TOUBIANA Julie³, BERANGER Agathe³, OUALHA Mehdi³

¹APHP, Paris, France; ²Hopital Trousseau, APHP, Paris, France; ³Hopital Necker, APHP, Paris, France; ⁴Hopital Cochin, APHP, Paris, France

**Correspondence:** Alice MARSAUX (alice.marsaux@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-11

**Rationale:** Children under Extracorporeal Membrane Oxygenation (ECMO) are at high risk of complications, particularly infectious ones, which may worsen their prognosis. However, recommendations for the use of antibiotics, particularly beta-lactams dosing which are frequently administered, are extrapolated from adult data and are not

adapted to the pharmacokinetic and pharmacodynamic (PK/PD) changes observed in children on ECMO. Therefore, there is a risk of inadequate exposure using the standard dosing. The objective of this study is to describe, for children undergoing ECMO, the exposure to beta-lactams at currently used dosing; and to identify factors associated with inadequate exposure.

**Patients and methods/Materials and methods:** This was an observational, retrospective, bicentric study conducted in 2 pediatric intensive care units, on 57 children undergoing veno-arterial or veno-venous ECMO. Plasma concentrations of beta-lactams used were measured and interpreted according to EUCAST, then to the minimum inhibitory concentration (MIC) found and according to the following PK/PD targets: serum concentration 4 times above the MIC throughout the dosing interval (100% fT > 4 × MIC).

**Results:** We included 57 patients (21 (36.8%)) died during our study), who received 11 types of beta-lactams (including 30 patients receiving piperacillin/ tazobactam) resulting in 226 concentrations analyzed. A total of 32 infections were documented. Based on the PK/PD target of 100% fT > 4 × MIC, for the highest MICs, 58.8% of concentrations were insufficient, mainly in young children (p = 0.035) with a low body-weight (p = 0.013), or in case of hypoalbuminemia (p = 0.011), reflecting the increase in volume of distribution, and also in case of increased renal clearance (p = 0.032). The risk of supra-therapeutic concentrations was 10.5% and was mainly associated with poor elimination (presence of renal impairment (p < 0.01)).

**Conclusion:** There is a non-negligible risk of under-exposure in children receiving conventional dosing of beta-lactam and ECMO support (mainly related to renal function and volume of distribution variations). Therapeutic drug monitoring combined with the application of specific PK/PD models would reduce this risk and ultimately improve the prognosis of these patients.

**Compliance with ethics regulations:** Yes in clinical research

<table><thead><tr><th rowspan="2">Variables</th><th colspan="4">All dosages</th><th colspan="2">Piperacillin/Tazobactam</th></tr><tr><th>Sub-therapeutic n=133</th><th>Optimal n=11</th><th>Super-therapeutic n=11</th><th>Sub-therapeutic n=11</th><th>Sub-therapeutic n=11</th><th>Super-therapeutic n=11</th></tr></thead><tbody><tr><td>Diuresis (mL/hour)</td><td>5</td><td>23</td><td>11</td><td>5</td><td>0.91</td><td>0.001 [0.004-0.005]</td></tr><tr><td>Infusion (mL/hour)</td><td>30 (27%)</td><td>30 (27%)</td><td>30 (27%)</td><td>30 (27%)</td><td>0.2</td><td>0.2 [0.1-0.3]</td></tr><tr><td>ECMO</td><td>40 (36%)</td><td>43 (37%)</td><td>43 (37%)</td><td>43 (37%)</td><td>0.80</td><td>0.80 [0.7-0.9]</td></tr><tr><td>ECMO mode</td><td>30 (27%)</td><td>23 (20%)</td><td>23 (20%)</td><td>23 (20%)</td><td>0.25</td><td>0.25 [0.1-0.3]</td></tr><tr><td>Gasparini</td><td>40 (37%)</td><td>40 (37%)</td><td>40 (37%)</td><td>40 (37%)</td><td>0.20</td><td>0.20 [0.1-0.3]</td></tr><tr><td>Sedation</td><td>25 (21%)</td><td>27 (24%)</td><td>27 (24%)</td><td>27 (24%)</td><td>0.20</td><td>0.20 [0.1-0.3]</td></tr><tr><td>Apnea</td><td>5 (4%)</td><td>3 (2%)</td><td>3 (2%)</td><td>3 (2%)</td><td>0.16</td><td>0.16 [0.08]</td></tr><tr><td>Diuresis (mL/hour)</td><td>508 (49%)</td><td>508 (49%)</td><td>508 (49%)</td><td>508 (49%)</td><td>0.33</td><td>0.33 [0.2-0.4]</td></tr><tr><td>Apnea (mL/hour)</td><td>209 (19%)</td><td>93 (81%)</td><td>93 (81%)</td><td>93 (81%)</td><td>0.51</td><td>0.51 [0.4-0.6]</td></tr><tr><td>Microvascular Flow Index</td><td>102 (94%)</td><td>102 (94%)</td><td>102 (94%)</td><td>102 (94%)</td><td>0.36</td><td>0.36 [0.2-0.4]</td></tr><tr><td>Microvascular Flow Index (MFI)</td><td>29.4 [28.6-31.5]</td><td>30.1 [28.5-34]</td><td>29 [28.6-32]</td><td>29 [28.6-32]</td><td>0.22</td><td>0.22 [0.1-0.3]</td></tr></tbody><tfoot><tr><td colspan="7"><sup>a</sup>ECMO (Circumferential) n=133; ECMO (Sub-therapeutic) n=11; ECMO (Sub-therapeutic) n=11; ECMO (Super-therapeutic) n=11; Sub-therapeutic n=11; Super-therapeutic n=11; p=0.001 [0.004-0.005]</td></tr></tfoot></table>

Association between clinical variables and the result of concentrations for all dosages and Piperacillin/Tazobactam (for an exposure assumption of serum concentration 4 times above the MIC throughout the dosing interval (100% fT > 4 × MIC))

## CO-12

### Anti-infective prescription practices in children undergoing renal replacement therapy: a multicenter survey

THY Michael¹,³, NAUDIN Jérôme⁴, GENUINI Mathieu⁴, LETEURTRE Stéphane⁵, OUALHA Mehdi²,³

¹Assistance Publique-Hôpitaux de Paris, Infectious and tropical diseases department, Bichat University Hospital, Université de Paris, Paris, France;

²Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France; ³EA 7323 - Pharmacology and Therapeutic Evaluation in Children and Pregnant Women, Université de Paris, France; ⁴Assistance Publique-Hôpitaux de Paris, Paediatric Intensive Care Unit, Robert-Debré University Hospital, Université de Paris, Paris, France; ⁵Pediatric Intensive Care Unit, CHU Lille, Lille, France

**Correspondence:** Michael THY (michael245thy@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-12

**Rationale:** The need of renal replacement therapy (RRT) in septic children may occur and add variability leading to unpredictable anti-infective concentrations with risks of treatment failure, toxicity and emergence of multidrug resistant bacteria. We aim to better
understand anti-infective prescription practices in children undergo-
ing RRT.

**Patients and methods/Materials and methods:** An online sur-
vey was sent via email to physicians working in pediatric intensive
care units (PICU) from the Groupe Francophone de Réanimation et
d'Urgences Pédiatiques (GFRUP). The survey form assessed the char-
acteristics of the PICU, practices of RRT, anti-infective prescription and
therapeutic drug monitoring. We excluded plasma exchanges and
adsorption techniques from the survey. When several respondents
from the same center answered, we selected the most complete form.

**Results:** From 10/04/2021 to 10/05/2021, 47 physicians answered the survey corresponding to 26 different centers including 21 French centers, corresponding to 88% of response rate for French PICU >4 beds. The median [IQR] number of ICU beds was 12 [8-16] and intermediate care beds was 5 [2-8]. Every PICU used continuous RRT with mainly Prismaflex® machine. Adaptation of anti-infective prescriptions to the presence of RRT were declared in 23 (89%) PICU according to the molecular weight in 6 (26%), to the molecule protein binding in 6 (26%), to the lipo/hydrophilic nature of the molecule in 4 (17%), to the elimination routes in 15 (65%). The anti-infective were adapted to the residual diuresis in 9 (41%) PICU, to the RRT flow in 6 (26%) and to the type of RRT used in 15 (65%). Most of the PICU declared no available guidelines (n = 20, 80%) but used VIDAL® in 12 (46%) or GPR® in 4 (15%). We noticed great variability even between the physicians from the same department. Adaptation of the anti-infective doses from the respondents are displayed on Fig. 1. Most of the centers (n = 20, 77%) used therapeutic drug monitoring under RRT and was systematically done for betalactams in 18 (69%) PICU, for aminoglycosides in 22 (92%), for glycopeptides in 21 (84%), for linezolid in 13 (54%), for antivirals in 16 (64%), for azoles 15 (60%), for candins in 12 (48%). Obstacles for monitoring were mainly (n = 11, 42%) the delay for the results and the absence of on-site laboratory (n = 8, 31%). Anti-infective stewardship was available with a specialist (pharmacologist or infectious-laboratory) in 11 (42%) PICU.

**Conclusion:** Our survey reported great variability of anti-infective pre-
scription practices in children undergoing RRT pointing out the need
for specific guidelines.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_8.png" /><figcaption>Figure 1: Adaptation of anti-infective doses in children under RRT</figcaption></figure>

**CO-13**
**High-flow nasal oxygen alone or alternating with noninvasive ventilation in critically ill immunocompromised patients with acute respiratory failure. A randomised controlled trial**

COUDROY Rémi¹, FRAT Jean-Pierre¹, EHRMANN Stephan², PÈNE Frédéric³,
DECAVELE Maxens⁴, TERZI Nicolas⁵, PRAT Gwenael⁶, GARRET Charlotte⁷,
CONTOU Damien⁸, GACOUIN Arnaud⁹, BOURENNE Jérémy¹⁰, GIRAULT
Christophe¹¹, VINSONNEAU Christophe¹², DELLAMONICA Jean¹³, LABRO
Guylaine¹⁴, JOCHMANS Sébastien¹⁵, HERBLAND Alexandre¹⁶, QUENOT
Jean-Pierre¹⁷, DEVAQUET Jérôme¹⁸, BENZEKRI Dalila²⁸, VIVIER Emmanuel¹⁹,
NSEIR Saad²⁰, COLIN Gwenahel²¹, THEVENIN Didier²², GRASSELLI
Giacomo²³, BOUGON David²⁴, ASSEFI Mona⁴, GUÉRIN Claude²⁵, LHERM
Thierry²⁶, KOUATCHET Achille²⁷, RAGOT Stéphanie¹, THILLE Arnaud W.¹
¹CHU de Poitiers, Poitiers, France; ²CHU de Tours, Tours, France; ³Hôpital
Cochin, Paris, France; ⁴Pitié-Salpêtrière, Paris, France; ⁵CHU Grenoble
Alpes, Grenoble, France; ⁶CHU de Brest, Brest, France; ⁷CHU de Nantes,
Nantes, France; ⁸Centre Hospitalier Victor Dupouy, Argenteuil, France;
⁹CHU de Rennes, Rennes, France; ¹⁰CHU La Timone 2, Marseille, France;

¹¹CHU de Rouen, Rouen, France; ¹²Centre hospitalier de Béthune, Beuvry, France; ¹³CHU de Nice, Nice, France; ¹⁴CHU de Besançon, Besançon, France; ¹⁵Centre hospitalier Sud-Ile-de France, Melun, France; ¹⁶Centre hospitalier Saint Louis, La Rochelle, France; ¹⁷CHU Dijon-Bourgogne, Dijon, France; ¹⁸Hôpital Foch, Suresnes, France; ¹⁹Hôpital Saint Joseph Saint Luc, Lyon, France; ²⁰CHU de Lille, Lille, France; ²¹Centre Hospitalier Départemental de Vendée, La Roche Sur Yon, France; ²²CH de Lens, Lens, France; ²³Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italie; ²⁴Centre Hospitalier Annecy Genevois, Annecy, France; ²⁵Hôpital de La Croix-Rousse, Lyon, France; ²⁶Hôpital de Chartres, Chartres, France; ²⁷CHU d'Angers, Angers, France; ²⁸CHR d'Orléans, Orléans, France

**Correspondence:** Rémi COUDROY (remi.coudroy@chu-poitiers.fr)

Annals of Intensive Care 2022, **12**(1):CO-13

**Rationale:** Whereas noninvasive ventilation is recommended for immu-
nocompromised patients with acute respiratory failure in the intensive
care unit (ICU), it may have deleterious effects in most severe patients.
High-flow nasal oxygen alone may be an alternative to reduce mortal-
ity. We aimed to determine whether high-flow nasal oxygen alone could
reduce the rate of mortality at day 28 compared to its alternation with
noninvasive ventilation in this setting.

**Patients and methods/Materials and methods:** The FLORALI-IM is a multicenter, open-label randomised clinical trial was conducted in 30 ICUs (29 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure defined as respiratory rate ≥ 25/min and a partial pressure of oxygen to inspired fraction of oxygen ≤ 300 mmHg were randomly assigned to high-flow nasal oxygen alone (n=154) or noninvasive ventilation alternating with high-flow nasal oxygen (n=145). The primary outcome was mortality at day 28. The trial is registered with ClinicalTrials.gov, number NCT02978300.

**Results:** Between January 2017 to March 2019, 299 patients were included in the intention-to-treat analysis. Mortality rate at day 28 was 36% (56/154) with high-flow nasal oxygen alone and 35% (51/145) with noninvasive ventilation alternating with high-flow nasal oxygen (absolute difference, 1.2% [95% CI, -9.6 to 11.9%], p=0.83). Intubation rate at day 28 was 51% (78/154) with high-flow nasal oxygen alone and 46% (67/145) with noninvasive ventilation alternating with high-flow nasal oxygen (difference, 4.4% [95% CI, -6.8 to 15.5%], p=0.44). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of high-flow nasal oxygen than with noninvasive ventilation (— 4 mm on visual analog scale [95 %CI, — 18 to 4] vs. 0 mm [95% CI, — 16 to 17], p=0.04).

**Conclusion:** In critically ill immunocompromised patients with acute res-
piratory failure, the mortality rate did not differ between high-flow nasal
oxygen alone and noninvasive ventilation alternating with high-flow
nasal oxygen.

**Compliance with ethics regulations:** Yes in clinical research.

CO-14
Lung histopathology of Covid-19 patients with acute respiratory distress syndrome: a French multicenter study

MORIN Jean¹, SAGAN Christine¹, PLANTEFEVRE Gaetan², CHELHA Riad³,
ASFAR Pierre⁴, SIRODOT Michel⁵, SIMON Georges⁶, FERRE Alexis⁷, KAMEL
Toufik⁸, PENE Frédéric⁹, DECAVELE Maxens¹⁰, BADIE Julio¹¹, BOYER
Alexandre¹², SOUWEINE Bertrand¹³, HRAIECH Sami¹⁴, DELBOVE Agathe¹⁵,
FOUCAULT Camille¹⁶, AUCHABIE Johann¹⁷, CHANAREILLE Paul-Marie¹⁸,
ARGAUD Laurent¹⁹, RICHARD Jean-Christophe²⁰, BEURET Pascal²¹,
GARÇON Pierre²², HAYON Jan²³, BONNY Vincent²⁴, LEGAY François²⁵, GERI
Guillaume²⁶, REIGNIER Jean¹, CANET Emmanuel¹

¹CHU de Nantes, Nantes, France; ²Centre Hospitalier Victor Dupouy, Argenteuil, France; ³Hôpital Privé Claude Galien, Quincy-Sous-Sénart, France; ⁴CHU Angers, Angers, France; ⁵Centre Hospitalier Annecy Genevois, Annecy, France; ⁶Centre Hospitalier de Troyes, Troyes, France; ⁷Hôpital de Versailles, Le Chesnay, France; ⁸CHR Orléans, Orléans, France; ⁹CHU Cochin, Paris, France; ¹⁰CHU Pitié Salpêtrière, Paris, France; ¹¹Hôpital Nord Franche-Comté, Belfort, France; ¹²CHU de Bordeaux, Bordeaux, France; ¹³CHU Clermont-Ferrand, Clermont-Ferrand, France; ¹⁴APHM CHU Nord, Marseille, France; ¹⁵CHBA Vannes-Auray, Vannes, France; ¹⁶CH Cahors - Hôpital Jean Rougier, Cahors, France; ¹⁷CH Cholet, Cholet,
France; ¹⁸GHPP Montélimar, Montélimar, France; ¹⁹CHU Edouard Herriot, Lyon, France; ²⁰CHU Hôpital Lyon Sud, Lyon, France; ²¹CH de Roanne, Roanne, France; ²²GHEF site de Marne-La-Vallée, Jossigny, France; ²³CHI Poissy-Saint-Germain-en-Laye, Poissy, France; ²⁴CHU Saint-Antoine, Paris, France; ²⁵CH de Saint-Brieuc, Saint-Brieuc, France; ²⁶CHU Ambroise Paré, Boulogne, France

**Correspondence:** Emmanuel CANET (emmanuel.canet@chu-nantes.fr)

Annals of Intensive Care 2022, **12**(1):CO-14

**Rationale:** COVID-19 is a viral pneumonia which may deteriorate into acute respiratory distress syndrome (ARDS). Analysis of the pathological features in the lung tissues of patients who have died from COVID-19-ARDS might help to understand the disease pathogenesis.

**Patients and methods/Materials and methods:** We conducted a multicenter study which involved 26 French ICUs. All Covid-19 patients who died from COVID-19-ARDS between February 1st 2020 and April 30th 2021 were eligible. The lung biopsies were performed by the intensivists immediately after the death following anatomical landmarks.

**Results:** Overall, 171 patients were included in the study. We report the results of the first 90 patients analyzed. Age was 70 [65–76] years-old, 62 (69%) patients were men, and 18 (20%) patients had a pre-existing pulmonary disease. Time from the onset of mechanical ventilation (MV) to death was 18 [10–31] days. The durations of moderate and severe ARDS were 6 [2–12] and 8 [3–15] days, respectively. The main causes of death were refractory shock and hypoxemia (42.2%), refractory hypoxemia (31.1%), and refractory shock (8.9%). Of the 90 biopsies performed, 85 (94%) had lung tissue available for pathological analysis. The most common primary lesions of the alveoli were: type-2 pneumocyte hyperplasia (84.7%), fibrin deposition (62.3%), plugs of fibroblastic tissue (36.4%), hyaline membranes (29.4%), fibrin balls (15.3%). The primary lesions identified in the septa were: proliferation of fibroblastic tissue (82.4%), lymphocytic infiltrate (20%), oedema (15.3%), and collagen deposition (8.2%). Microthrombi were identified in 7% of biopsies. Final pathological diagnosei were: late phase of proliferative diffuse alveolar damage (DAD) (38.8%), early phase of proliferative DAD (34.1%), unclassified interstitial pneumonia (29.4%), acute fibrinous and organizing pneumonia (AFOP) (12.9%), acute exsudative DAD (11.8%), and organizing pneumonia (OP) (7.1%). Early deaths (before day-10 of MV) were characterized by a high rate of acute exsudative DAD and early phase of proliferative DAD and the absence of collagen deposition. In contrast, late phase of proliferative DAD was the most common lesion encountered in late deaths (after day-30 of MV) with extensive proliferation of fibroblastic tissue. AFOP and OP were diagnosed in patients who died before day-30 of MV.

**Conclusion:** The predominant pattern of lung lesions in patients who died from Covid-19-ARDS is DAD. Fibroblastic tissue proliferation, AFOP, and OP were commonly reported while collagen fibrosis was rare. Our results support further evaluation of steroids in non-resolving ARDS Covid-19 given the significant proportion of potential steroid-sensitive patterns.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-15

### Management and outcomes of pregnant woman with severe pneumonia related to SARS-CoV-2 infection admitted in intensive care unit

PÉJU Edwige¹, BELICARD Félicie¹, STEIN Silva³⁰, HRAIECH Sami²⁴, TADIÉ Jean-Marc⁷, MULLER Grégoire¹⁹, THILLE Arnaud¹¹, GOURY Antoine¹⁸, GRIMALDI David²⁶, JUNG Boris²³, PITON Gael¹⁷, PIAGNERELLI Michael²⁷, GIBOT Sébastien¹⁴, THIERY Guillaume²⁰, LASCARROU Jean-Baptiste⁸, BOUHEMAD Belaid¹⁶, ARGAUD Laurent²², TERZI Nicolas³¹, TAMION Fabienne⁵, EHRMANN Stephan¹⁰, VIGNON Philippe¹⁹, BELONCLE François⁹, PUGIN Jérrôme²⁵, AUBRON Cécile⁶, BERTRAND Pierre-Marie²⁸, GUITTON Christophe¹², KAUDOMAR Michel²⁹, MAIZEL Julien³, MEZIANI Ferhat¹⁵, SOUWEINE Bertrand²¹, JOURDAIN Merce⁴, JOZWIAK Mathieu²

¹Hôpital Cochin - APHP, Paris, France; ²CHU de Nice, Nice, France; ³CHU de Amiens, Amiens, France; ⁴CHU de Lille, Lille, France; ⁵CHU de Rouen, Rouen, France; ⁶CHU de Brest, Brest, France; ⁷CHU de Rennes, Rennes, France; ⁸CHU de Nantes, Nantes, France; ⁹CHU de Angers, Angers, France; ¹⁰CHU de Tours, Tours, France; ¹¹CHU de Poitiers, Poitiers, France; ¹²Hôpital du Mans, Le Mans, France; ¹³CHR d'Orléans, Orléans, France; ¹⁴CHRU de Nancy, Nancy, France; ¹⁵CHRU de Strasbourg, Strasbourg, France; ¹⁶CHU de Dijon, Dijon, France; ¹⁷CHU de Besançon, Besançon, France; ¹⁸CHU de Reims, Reims, France; ¹⁹CHU de Limoges, Limoges, France; ²⁰CHU de Saint Etienne, Saint Etienne, France; ²¹CHU de Clermond-Ferrand, Clermond-Ferrand, France; ²²CHU de Lyon, Lyon, France; ²³CHU de Montpellier, Montpellier, France; ²⁴CHU de Marseille, Marseille, France; ²⁵CHU de Genève, Genève, Suisse; ²⁶Hôpital Erasme, Bruxelles, Belgique; ²⁷CHU de Charleroi, Charleroi, Belgique; ²⁸Hôpital de Cannes, Cannes, France; ²⁹CHI de Fréjus, Fréjus, France; ³⁰CHU de Toulouse, Toulouse, France; ³¹CHU de Grenoble, Grenoble, France

**Correspondence:** Edwige PÉJU (edwigepeju@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-15

**Rationale:** Pregnancy is a risk factor of developing a severe form of SARS-CoV-2 infection. So far, the management and outcomes of pregnant women with severe SARS-CoV-2 infection requiring intensive care unit (ICU) admission remain to be investigated.

**Patients and methods/Materials and methods:** This multicentric, retrospective and observational study was conducted in 31 ICUs in France, Belgium and Switzerland between March 2020 and December 2021. All patients admitted in ICU for severe pneumonia related to SARS-CoV-2 infection during pregnancy or just after fetal extraction were included. Maternal ventilatory and obstetrical management in ICU as well as maternal and fetal outcomes were collected and analyzed. Risk factors of intubation were also assessed.

**Results:** Overall, 165 patients were included with a median age of 34 [30–37] years old and a median gestation length of 29 [26–33] amenorrhea weeks. Among them, 61 (37%) had obesity, 10 (6%) had diabetes mellitus and 53 (32%) had pregnancy-related complications. The median time between the onset of symptoms and ICU admission was 8 [6–10] days. Corticosteroids and Tocilizumab were administered in 141 (85%) and 23 (14%) patients respectively. CT-Scan was performed in 120 (73%) patients and pulmonary embolism was found in 8 (5%) patients. Regarding ventilatory management, 107 (65%) patients were treated with high-flow nasal cannula oxygenation therapy, 40 (20%) with non-invasive ventilation, 74 (45%) required to be intubated, 20% of them prior to ICU admission, and 12 (7%) required veno-venous extracorporeal membrane oxygenation. Awake prone positioning was performed in 7 (4%) patients prior to any fetal extraction and in 2 (1%) after fetal extraction. In multivariate analysis, obesity (OR=3.22 [1.11–9.88], p=0.03), term (OR=1.14 [1.05–1.27], p=0.005), extent of CT-Scan abnormalities > 50% (OR=3.37 [1.17–10.13], p=0.03) and non-invasive ventilation use (OR=3.70 [1.20–12.24], p=0.03) were associated with intubation. Fetal extraction was performed prior to ICU admission in 19 (12%) patients and was required during ICU stay in 58 (35%) patients, always by cesarean section: 45 (78%) for maternal respiratory worsening and 7 (12%) for fetal suffering. The maternal ICU mortality rate was 1%. Main maternal complications were infection, thrombosis and hemorrhage (18%, 7%, 7%, respectively). The fetal mortality rate was 5% with 7 (4%) stillborns, 69 (40%) prematures including 55 (32%) requiring ICU admission and 103 (60%) born at term.

**Conclusion:** Despite low maternal and fetal mortality rates, half of pregnant women admitted in ICU for severe pneumonia related to SARS-CoV-2 infection required to be intubated and required fetal extraction. Risk factors of intubation were obesity, term, extent of
CT-Scan abnormalities > 50% and non-invasive ventilation use. Inclusions are still in progress.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-16

### Impact of obesity on survival in COVID-19 ARDS patients receiving ECMO: results from an ambispective observational cohort

DAVIET Florence¹,³, GUILLOUX Philippe², HRAIECH Sami¹,³, TONON David², VELLY Lionel², BOURENNE Jeremy⁴, PORTO Alizee⁵, GRAGUEB CHATTI Ines¹, BOBOT Mickaël¹, BAUMSTARCK Karine⁶, PAPAZIAN Laurent¹,³, COLLART Frederic⁵, FOREL Jean-Marie¹,³, GUERVILLY Christophe¹,³

¹Assistance Publique Hôpitaux de Marseille - Hôpital Nord- Medecine Intensive reanimation, Marseille, France; ²Assistance Publique Hôpitaux de Marseille- Hôpital de la Timone -Département d'Anesthésie-réanimation, Marseille, France; ³Aix-Marseille Université, Faculté de Médecine Centre d'Études et de Recherches sur les Services de Santé et qualité de vie EA 3279, Marseille, France; ⁴Assistance Publique Hôpitaux de Marseille- Hôpital de la Timone -Rénimation des Urgences, Marseille, France; ⁵Assistance Publique Hôpitaux de Marseille- Hôpital de la Timone -Département de chirurgie cardiaque, Marseille, France; ⁶Faculté de Médecine, Centre d'Études et de Recherches sur les Services de Santé et Qualité de Vie EA 3279, Marseille, France

**Correspondence:** Florence DAVIET (florence.daviet@ap-hm.fr)

*Annals of Intensive Care 2022, 12(1):CO-16*

**Rationale:** Since March 2020, healthcare systems were importantly affected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe Acute Respiratory Distress Syndrome (ARDS), requiring extracorporeal membrane oxygenation (ECMO).

**Patients and methods/Materials and methods:** We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival.

**Results:** Between March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3–10) days. At ECMO initiation, patients had a median PaO₂/FiO₂ ratio of 71 mmHg (IQR 62–81), median PaCO₂ of 58 mmHg (IQR 51–66) and a median arterial pH of 7.33 (IQR 7.25–7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were respectively 92, 62 and 51%. Factors associated with 90-day survival in univariate analysis were younger age, higher BMI and lower Charlson score. Of note, time from ICU admission to intubation (2 days (0–5) in survivors versus 4 days (1–7) in non survivors, p = 0.02) and time to ECMO cannulation (9 days (4–11) in survivors versus 11 (8–14) in non survivors, p = 0.02) were shorter in 90-day survivors. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival (Odds ratio (OR): 0.669 (0.506–0.886), p = 0.005) and 0.757 (0.632–0.907) respectively). Younger age was also associated with 90-day survival in one model (OR: 1.14 (1.007–1.292), p = 0.039). Kaplan–Meier cumulated survival curves according to the presence of obesity were significantly different (Fig. 1, p = 0.006), the survival was also different when comparing the different obesity grades (p = 0.003). Obese patients were ventilated with higher PEEP than non-obese patients (14 (10–15) vs. 10 (8–12) cm H₂O; p < 0.001) with comparable Pplat, (29 (25–31) vs. 28 (25–30) cm H₂O, respectively (p = 0.923)). There was a trend to higher compliance of respiratory system in obese patients as compared with non-obese patients, respectively 26.2 (21–39.1) and 23 (15.5–27.3) mL/cm H₂O (p = 0.07).

**Conclusion:** In this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_9.png" /></figure>

Kaplan–Meier cumulated survival curves at day 90 since ICU admission in obese (red curve) and non-obese patients (blue curve). Obesity was defined as a BMI > 30 kg/m².

## CO-17

### Management of acute exacerbations of chronic obstructive pulmonary disease in the intensive care unit: the Outcomerea database, 1997–2018

GALERNEAU Louis-Marie¹,², BAILLY Sébastien¹,², TERZI Nicolas¹,², RUCKLY Stéphane³, GARROUSTE-ORGEAS Maite⁴, COHEN Yves⁵, HONG TUAN HA Vivien⁶, GAINNIER Marc⁷, SIAMI Shidasp⁸, DUPUIS Claire⁹, DARMON Michael¹⁰, AZOULAY Elie¹⁰, FOREL Jean-Marie¹¹, RIGAULT Guillaume¹, ADRIE Christophe¹², GOLDGRAN-TOLEDANO Dany¹³, BRUNEEL Fabrice¹⁴, DE MONTMOLLIN Etienne¹⁵, ARGAUD Laurent¹⁶, REIGNIER Jean¹⁷, PEPIN Jean-Louis¹,², TIMSIT Jean-François¹⁵

¹CHU Grenoble Alpes, La Tronche, France; ²Université Grenoble Alpes, INSERM U1300 HP2, La Tronche, France; ³Département de biostatistiques, Outcomerea, Paris, France; ⁴Hopital Franco-Britanique, Levallois-Perret, France; ⁵AP-HP, Hôpital Avicenne, Paris, France; ⁶Grand Hôpital de l'Est Francilien, Meaux, France; ⁷Hôpital de la Timone, Marseille, France; ⁸Centre Hospitalier Sud Essonne, Etampes, France; ⁹CHU Gabriel-Montpied, Clermont-Ferrand, France; ¹⁰AP-HP, Hôpital Saint-Louis, Paris, France; ¹¹Hôpital Universitaire Marseille Nord, Marseille, France; ¹²Hôpital Delafontaine Hôpital, Saint-Denis, France; ¹³Groupe Hospitalier Intercommunal Le Raincy Montfermeil, Montfermeil, France; ¹⁴Centre Hospitalier de Versailles, Le Chesnay, France; ¹⁵AP-HP, Hôpital Bichat, Paris, France; ¹⁶Hospices civils de Lyon, Hôpital Edouard Herriot, Lyon, France; ¹⁷CHU de Nantes, Nantes, France

**Correspondence:** Louis-Marie GALERNEAU (Imgalerneau@chu-grenoble.fr)

*Annals of Intensive Care 2022, 12(1):CO-17*

**Rationale:** The natural history of COPD is punctuated by acute exacerbations of COPD (AECOPDs) leading to hospitalization in intensive care units (ICU) for the most severe cases. The daily practice of corticosteroids/antibiotics prescriptions and the respective proportions of invasive and non-invasive ventilation (NIV) have evolved over time in the ICU. These contextual changes might have implications regarding AECOPDs management and ICU outcomes such as length of stay, intubation rates and mortality. The aim of the current study was to assess
over 22 years the evolution of AECOPDs changes in the management practices and the impact on main outcomes including length of stay and mortality in ICU and in post-ICU stay.

**Patients and methods/Materials and methods:** 1,816 patients admitted for AECOPDs were included prospectively between 1997 and 2018 in the Outcomerea French database from 32 ICUs. Evaluation of time trends were performed with analysis of the evolution of these variables over time out using a mixed model. Time series analyses were performed to assess the relationship between mortality in ICU and use of corticosteroids, antibiotics and invasive mechanical ventilation, using a dynamic regression model.

**Results:** We observed limited changes in anthropometrics of AECOPD patients admitted to ICUs except a slight increase in body mass index (+0.32%/year, p=.01) and severity was greater at ICU admission (+0.6% of SAPS II score/year, p<.01). There was overtime a significant reduction in the prescription of corticosteroids (-4.7%/year, p<.01) and antibiotics (-5.8%/year, p<.01), without these changes being correlated with the evolution of mortality in ICU in a time series analysis. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (-3.7%/year, p=.01) with this time a significant correlation between variations of use of IMV and variations of deaths in ICU in the time series analysis (p<.01). Rate of NIV failures decreased over time (-6.2%/year, p<.01) with a diffusion of NIV for facilitating IMV weaning (+8.1%/year, p<.01). There was a significant shortening of length of stay in ICU (-3.2%/year, p<.01) and total duration of hospital stays (-2.6%/year, p<.01). We observed an improvement of the prognosis (-4.1%/year of deaths in ICU, p=0.03; -4.2%/year of deaths in hospital post-ICU stay, p=0.02 and -4.98%/ year of 90-day mortality, p=0.02).

**Conclusion:** Lengths of stay decreased with a better prognosis of AECOPD in ICU. The management of ventilatory support has improved. And if prescriptions for corticosteroids and antibiotics have been reduced, prescription strategies for these therapeutics in ICU have to be precised.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-18

**Weaning according to new definition: burden and long-term outcomes of WIND 2 and 3 survivors (WIND BLOWS) study**

BEDUNEAU Gaëtan¹, GILLIBERT André¹, DEMOULE Alexandre⁹, RICHARD Jean Christophe², MERCAT Alain², BROCHARD Laurent⁵, PHAM Tài³
¹CHU Rouen, Rouen, France; ²CHU Angers, Angers, France; ³CHU Tenon, Paris, France; ⁴CHU La Pitié, Paris, France; ⁵Hôp Universitaire Montréal, Montréal, Canada

**Correspondence:** Gaëtan BEDUNEAU (gaetan-beduneau@chu-rouen.fr)

Annals of Intensive Care 2022, 12(1):CO-18

**Rationale:** In order to analyze hospital burden and long-term outcomes of prolonged and difficult to wean patients we performed a follow-up of patients included in the WIND study.

**Patients and methods/Materials and methods:** Among the 2709 patients included in the WIND study (ref 1), 508 were classified either in group 2 (difficult weaning, n=273) or 3 (prolonged weaning, n=235), of whom 459 were included in France. The 339 patients of French centers alive at the end of the princeps study constituted the eligible population of our study. Each center investigator collected vital status, intercurrent hospitalization, life at home, need for oxygen therapy or home ventilation up to 8 years after the study participation.

**Results:** Data were obtained for 284 patients: 94 (33%) females, mean (standard deviation) age of 64 (14). The mean (SD) SAPS-II score at ICU admission was 50 (17) and 164 (58%) belonged to WIND group 2. We observed mortality rates of 27% at one year, 50% at 5 years and 60% at 8 years. Between 1 and 8 years, the standardized mortality ratio (SMR) compared to the general French population of the same age, sex and period distribution was estimated at 3.20 (95% CI 2.69 to 3.65). Overall mortality was higher for group 3 patients than group 2 patients (66% vs 55%, p=0.06, Fig. 1). At 1, 5 and 8 years, respectively 88%, 89% and 90% of alive patients had no oxygen or ventilation support and 89%, 93% and 92% lived at home. The estimated cumulative risks of having

at least one rehospitalization among survivors at 1, 5 and 8 years were respectively 51%, 71% and 76%.

**Conclusion:** Although the risk of death and readmission is high, especially in the first year following discharge, survivors at 8 years mostly live at home without oxygen or home ventilation.

**Reference 1:** AJRCCM Vol195, 772-783.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_10.png" /><figcaption>Probability of survival</figcaption></figure>

## CO-19

**HIV-infected patients hospitalized in intensive care from 1997 to 2020: analysis of the OUTCOMEREA multicenter cohort**

GAILLET Antoine¹, ELIE Azoulay², ETIENNE Demontmollin³, GARROUSTE Maïte⁴, COHEN Yves⁵, DUPUIS Claire⁶, SCHWEBEL Carole⁷, REIGNIER Jean⁸, SHIDASP Siami⁹, ARGAUD Laurent¹⁰, ADRIE Christophe¹⁴, MOURVILLIER Bruno¹², RUCKLY Stephane⁷, FOREL Jean-Marie¹³, TIMSIT Jean-François³
¹Henri Mondor, Créteil, France; ²Saint Louis, Paris, France; ³Bichat, Paris, France; ⁴Saint Joseph, Paris, France; ⁵Avicenne, Bobigny, France; ⁶Gabriel Montpied, Clermont Ferrand, France; ⁷Grenoble Alpes, Grenoble, France; ⁸CHU Nantes, Nantes, France; ⁹Sud Essone, Etampes, France; ¹⁰Edouard Herriot, Lyon, France; ¹¹Delafontaine, Saint Denis, France; ¹²CHU Reims, Reims, France; ¹³Hopital Nord, Marseille, France; ¹⁴Cochin, Paris, France

**Correspondence:** Antoine GAILLET (gaillet.antoine75@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-19

**Rationale:** Despite antiviral therapy (ARV), HIV infection is still responsible for 800,000 deaths per year. In parallel with the good virological control and the aging of this population, multiple comorbidities (HIV associated non-AIDS (HANA) conditions) have developed in this population. The objectives of the "VIHREA" study were to describe the phenotypic evolution of HIV patients admitted to intensive care unit (ICU) from 1997 to 2020 and then to identify risk factors for day-60 (D60) death.

**Patients and methods/Materials and methods:** Prospective, multicenter cohort (23 centers, OutcomeRea™), including HIV adult patients (≥ 18 years old) hospitalized in ICU from 01/01/1997 to 12/31/2020, with trend analysis through 3 periods dichotomized according to the integrase inhibitors appearance (2007) and WHO recommendation for systematic treatment of all HIV patients (2016). A survival model was used to study prognostic factors at D60.

**Results:** Of the 24,298 stays registered, 630 (2.6%) concerned first stays for a HIV patient. Throughout the 3 periods, the mean age increased (51.6 years in period 3 versus 44.2 years in period 1, p < 0.001), as did the level of comorbidity of the patients (diabetes, renal and respiratory
history, solid neoplasia). The proportion of HIV discovered on ICU admission decreased significantly (9.8% versus 28.4%, p < 0.001) while the median duration of HIV disease (18 years versus 5 years, p < 0.001) as well as the percentage of patients admitted on ARV (72% versus 47.6%, p < 0.001) increased. The main reasons for admission distribution remained stable over time (acute respiratory distress > shock > coma). Moreover, while we observed a significant drop in the rate of active opportunistic infections on admission (24% versus 36.2%, p = 0.007), pneumocystosis (9.2%) and tuberculosis (6.9%) being the most frequent, the rate of active hemopathy classifying AIDS increased non-significantly (p = 0.154) but was associated with a significant increase in the administration of chemotherapy in ICU (12.7% versus 1.4%, p < 0.001), non-Hodgkin's lymphoma being the majority (14.3%). Admissions for HANA (11.2%) or non-HIV (50.4%) reasons were stable over time, as were SOFA score on admission (p = 0.668), and the proportions of mechanically ventilated (49.4% versus 48.4%, p = 0.707) and dialysed patients (20.2% versus 14.9%, p = 0.128). In multivariate analysis, predictors of D60 mortality were advanced age, chronic liver disease, prior chemotherapy, SOFA score > 4 at admission, hospitalization time before admission to intensive care > 24 h, AIDS status, but not the period of admission.

**Conclusion:** The phenotype of HIV patients admitted to intensive care has evolved over time (HIV better controlled but more comorbidity associated). Mortality risk factors remain stable over time, including AIDS status.

**Compliance with ethics regulations:** Yes in clinical research.

<table><thead><tr><th rowspan="2">Variables</th><th colspan="2">At D60 (n=495)</th><th colspan="2">At D60 (n=135)</th><th colspan="2">Univariate</th><th colspan="2">Multivariate</th></tr><tr><th></th><th></th><th></th><th></th><th>HR, IIC 95%</th><th>p-value</th><th>HR, IIC 95%</th><th>p-value</th></tr></thead><tbody><tr><td>Age (years)</td><td>126 (25.5%)</td><td>29 (21.5%)</td><td>Ref.</td><td></td><td><strong>0.010</strong></td><td>Ref.</td><td></td><td><strong>0.029</strong></td></tr><tr><td>38 &lt; 54</td><td>249 (50.4%)</td><td>57 (42.2%)</td><td>0.96 (0.63, 1.50)</td><td></td><td></td><td>0.87 (0.54, 1.39)</td><td></td><td></td></tr><tr><td>&gt; 54</td><td>119 (24.1%)</td><td>49 (36.3%)</td><td>1.68 (1.06, 2.67)</td><td></td><td></td><td>1.47 (0.91, 2.36)</td><td></td><td></td></tr><tr><td>Age (years)</td><td>333 (74.4%)</td><td>107 (79.3%)</td><td>1.70 (1.31, 2.58)</td><td><strong>0.013</strong></td><td></td><td>1.53 (0.85, 2.07)</td><td></td><td><strong>0.206</strong></td></tr><tr><td>Chronic disease (KHALUS)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Hepatic</td><td>32 (6.5%)</td><td>15 (11.1%)</td><td>1.66 (0.97, 2.85)</td><td></td><td>0.066</td><td>2.07 (1.15, 3.73)</td><td></td><td><strong>0.015</strong></td></tr><tr><td>Cardiopulmonary</td><td>15 (3.2%)</td><td>10 (7.4%)</td><td>1.07 (0.56, 2.03)</td><td></td><td>0.846</td><td></td><td></td><td></td></tr><tr><td>Nephrological</td><td>29 (5.9%)</td><td>12 (8.9%)</td><td>1.59 (0.87, 2.88)</td><td></td><td>0.128</td><td></td><td></td><td></td></tr><tr><td>Respiratory</td><td>36 (7.3%)</td><td>7 (5.2%)</td><td>0.77 (0.36, 1.04)</td><td></td><td>0.507</td><td></td><td></td><td></td></tr><tr><td>Prior chemotherapy</td><td>52 (10.5%)</td><td>29 (28.9%)</td><td>3.09 (2.04, 4.68)</td><td><strong>&lt;0.001</strong></td><td></td><td>2.48 (1.54, 4.00)</td><td></td><td><strong>&lt;0.001</strong></td></tr><tr><td>Induction period:</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>1</td><td>167 (33.8%)</td><td>48 (35.6%)</td><td>Ref.</td><td></td><td>0.929</td><td></td><td></td><td></td></tr><tr><td>2</td><td>263 (53.2%)</td><td>72 (53.3%)</td><td>0.93 (0.63, 1.38)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>3</td><td>64 (13%)</td><td>15 (11.1%)</td><td>1.90 (0.55, 1.82)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>SOFA at admission &gt;4</td><td>262 (53%)</td><td>104 (77%)</td><td>2.60 (1.73, 3.88)</td><td><strong>&lt;0.001</strong></td><td></td><td>2.35 (1.56, 3.56)</td><td></td><td><strong>0.001</strong></td></tr><tr><td>Duration of hospitalization before ICU admission &gt;24 hours</td><td>172 (34.8%)</td><td>72 (53%)</td><td>1.92 (1.36, 2.70)</td><td><strong>&lt;0.001</strong></td><td></td><td>1.47 (1.03, 2.11)</td><td></td><td><strong>0.033</strong></td></tr><tr><td>AIDS status</td><td>355 (73.9%)</td><td>112 (83%)</td><td>1.77 (1.12, 2.80)</td><td><strong>0.014</strong></td><td></td><td>1.79 (1.11, 2.89)</td><td></td><td><strong>0.017</strong></td></tr><tr><td>Admission diagnoses according to HIV/AIDS</td><td>105 (24.9%)</td><td>29 (26.4%)</td><td>0.98 (0.65, 1.49)</td><td></td><td></td><td>1.39 (0.81, 2.39)</td><td></td><td></td></tr><tr><td>Opportunistic infections classifying AIDS</td><td>96 (22.8%)</td><td>50 (45.5%)</td><td>2.59 (1.68, 3.98)</td><td></td><td></td><td>1.52 (0.94, 2.46)</td><td></td><td></td></tr><tr><td>Active blood disease classifying AIDS</td><td>43 (10.2%)</td><td>16 (14.5%)</td><td>1.90 (1.06, 3.39)</td><td></td><td></td><td>1.49 (0.84, 2.64)</td><td></td><td></td></tr><tr><td>Affection classifying HANA</td><td>233 (53.3%)</td><td>41 (37.3%)</td><td>Ref.</td><td><strong>0.010</strong></td><td></td><td>Ref.</td><td></td><td>0.203</td></tr></tbody></table>

Predictors of death at D60 after ICU admission in the VIHREA cohort (Cox regression)

## CO-20

### Necrotizing soft tissue infections in neutropenic patients requiring ICU admission: a French multicenter retrospective cohort study

ARRESTIER Romain<sup>1,2,3</sup>, CHABA Anis<sup>4</sup>, MABROUKI Asma<sup>5</sup>, SACCHERI Clément<sup>6</sup>, CANET Emmanuel<sup>7</sup>, PINETON DE CHAMBRUN Marc<sup>8</sup>, STOCLIN Anabelle<sup>9</sup>, PICARD Muriel<sup>10</sup>, WALLET Florent<sup>11</sup>, PERIER François<sup>12</sup>, TURPIN Matthieu<sup>13</sup>, ARGAUD Laurent<sup>14</sup>, DECAVELE Maxens<sup>15</sup>, ISSA Nahema<sup>16</sup>, CADOZ Cyril<sup>17</sup>, KLOUCHE Kada<sup>18</sup>, COHEN Johana<sup>19</sup>, MOKART Djamel<sup>20</sup>, URBINA Tomas<sup>21</sup>, HUA Camille<sup>22</sup>, CHOSIDOW Olivier<sup>22</sup>, MEKONTSO-DESSAP Armand<sup>1,2,3</sup>, AZOULAY Elie<sup>5</sup>, DE PROST Nicolas<sup>1,2,3</sup> <sup>1</sup>Service de Médecine Intensive et Réanimation, APHP Hôpital Henri Mondor, Créteil, France; <sup>2</sup>Groupe de Recherche Clinique CARMAS, faculté de Santé de Créteil, UPEC, Créteil, France; <sup>3</sup>INSERM, IMRB, Université Paris Est Créteil, Créteil, France; <sup>4</sup>Service de médecine intensive et réanimation, APHP Hôpital Cochin, Paris, France; <sup>5</sup>Service de médecine intensive et réanimation, APHP Hôpital Saint-Louis, Paris, France; <sup>6</sup>Service de médecine intensive et réanimation, Hôpital Archet 1, Nice, France; <sup>7</sup>Service de médecine intensive et réanimation, Centre Hospitalier de Nantes, Nantes, France; <sup>8</sup>Service de médecine intensive et réanimation, APHP Hôpital La Pitié Salpêtrière, Paris, France; <sup>9</sup>Service de médecine intensive et réanimation, Institut Gustave Roussy, Villejuif, France; <sup>10</sup>Service de Réanimation

Polyvalente, Centre Hospitalier Universitaire de Toulouse, Oncopôle, Toulouse, France; <sup>1</sup>Service d'anesthésie, médecine intensive, réanimation, Hospices Civils de Lyon, Lyon, France; <sup>2</sup>Réanimation Médico-Chirurgicale, Hôpital André Mignot, Versailles, France; <sup>3</sup>Service de médecine intensive et réanimation, APHP, Hôpital Tenon, Paris, France; <sup>4</sup>Service de médecine intensive et réanimation, Hôpital Edouard Herriot, Lyon, France; <sup>5</sup>Service de Pneumologie, Médecine Intensive et Réanimation, APHP Hôpital La Pitié Salpêtrière, Paris, France; <sup>6</sup>Service de médecine intensive et réanimation, Hôpital Saint-André, CHU Bordeaux, Bordeaux, France; <sup>7</sup>Réanimation Polyvalente, CHR Metz-Thionville, Metz, France; <sup>8</sup>Service de médecine intensive et réanimation, CHU Montpellier, Montpellier, France; <sup>9</sup>Service de médecine intensive et réanimation, Groupe Hospitalier Intercommunal Le Raincy Montfermeil, Montfermeil, France; <sup>20</sup>Unité Traitement Soins Intensifs, Institut Paoli Calmettes, Marseille, France; <sup>21</sup>Service de médecine intensive et réanimation, APHP Hôpital Saint-Antoine, Paris, France; <sup>22</sup>Service de Dermatologie, APHP Hôpital Henri Mondor, Créteil, France

**Correspondence:** Romain ARRESTIER (romain.arrestier@aphp.fr)

Annals of Intensive Care 2022, 12(1):CO-20

**Rationale:** Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Immunocompromised patients have an increased risk of dying. Among them, neutropenic patients could have a particularly high risk of poor outcome but data are scarce. Our objectives are to describe the characteristics and the mortality of neutropenic patients with NSTI requiring intensive care unit (ICU) admission.

**Patients and methods/Materials and methods:** We conducted a retrospective multicenter cohort study in 18 French ICUs. Patients admitted in participating ICUs between 2011 and 2021 with either surgically confirmed NSTI or clinically suspected diagnosis of NSTI and neutropenia < 1.5 G/L at diagnosis were included. Characteristics and hospital mortality of patients with neutropenic NSTI were compared to a historical cohort of ICU patients with non-neutropenic NSTI. The factors associated with hospital mortality were identified using Cox regression.

**Results:** 83 neutropenic patients were included and compared to 129 historical non-neutropenic patients. Neutropenia was related to haematological malignancy in 64 (77.1%) patients and to solid cancer in 10 (12%) patients. Median time from neutropenia onset to NSTI was 4 [1-14] days. Other patients' characteristics are described in Table 1. As compared to non-neutropenic patients, neutropenic patients were younger [65 (56-75) vs 58 (46.5-64) years, p < 0.001], had less frequent lower limb (70.3% vs 42.2%, p < 0.01) and more abdomino-perineal NSTIs (25% vs 42.2%, p = 0.014). Neutropenic patients presented more frequent bacteraemia (58.5% vs 26.4%, p < 0.001). The most frequent bacteria isolated in neutropenic patients were *Enterobacteriaceae* (42.2%) and *Pseudomonas aeruginosa* (30.1%). In contrast, non-neutropenic patients were more frequently infected by *Streptococcus* species than neutropenic patients (68.2% (n = 88) vs 2.4% (n = 2), p < 0.001). Time from NSTI diagnosis to first surgery was shorter in non-neutropenic patients than in others (0 [0-0] days vs 1 [1-2] days, p < 0.001). 28-day and in-hospital mortality rates were significantly higher in neutropenic than in non-neutropenic patients (48.2% vs 25.6%, p = 0.001, and 54.2% vs 35.7%, p = 0.012). In multivariate analysis, factors associated with hospital mortality for neutropenic patients were age (adjusted Hazard Ratio (aHR) = 1.04 (1.02-1.06), p = 0.001) and SOFA score (aHR = 1.16 (1.08-1.25, p < 0.001), while treatment with G-CSF (aHR = 0.34 (0.17-0.66), p = 0.002) was protective.

**Conclusion:** NSTI in neutropenic patients presented different characteristics and higher mortality than in non-neutropenic patients requiring ICU. Treatment with G-CSF could be associated with better outcomes, although this finding should be interpreted with caution due to the presence of potential unadjusted confounding factors.

**Reference 1:** Urbina, T. et al. Early identification of patients at high risk of group A streptococcus-associated necrotizing skin and soft tissue infections: a retrospective cohort study. Crit Care 23, 417 (2019).

**Compliance with ethics regulations:** Yes in clinical research
<table><thead><tr><th></th><th>Neutropenic NSTI (n=83)</th><th>Non-neutropenic NSTI (n=129)</th><th>p-value*</th></tr></thead><tbody><tr><td colspan="4"><strong>General characteristics</strong></td></tr><tr><td>Age, years</td><td>58 (46.5-64)</td><td>65 (56-75)</td><td>&lt;0.001</td></tr><tr><td>Gender (male)</td><td>54 (65.1%)</td><td>75 (58.1%)</td><td>0.388</td></tr><tr><td>Obesity</td><td>15 (21.1%)</td><td>34 (26.4%)</td><td>0.515</td></tr><tr><td>BMI (kg/m²)</td><td>25.15 (22.35-28.6)</td><td>-</td><td>-</td></tr><tr><td>Hypertension</td><td>26 (31.3%)</td><td>-</td><td>-</td></tr><tr><td>Diabetes</td><td>11 (13.3%)</td><td>53 (41.1%)</td><td>&lt;0.001</td></tr><tr><td>Vasculopathy</td><td>3 (3.6%)</td><td>13 (10.1%)</td><td>0.141</td></tr><tr><td>Congestive heart failure</td><td>0 (0%)</td><td>-</td><td>-</td></tr><tr><td>COPD</td><td>8 (9.6%)</td><td>-</td><td>-</td></tr><tr><td>Chronic kidney disease</td><td>3 (3.6%)</td><td>-</td><td>-</td></tr><tr><td>ESRD requiring dialysis</td><td>1 (1.2%)</td><td>-</td><td>-</td></tr><tr><td>Cirrhosis</td><td>2 (2.4%)</td><td>8 (6.2%)</td><td>0.357</td></tr><tr><td>HIV infection</td><td>5 (6%)</td><td>8 (6.2%)</td><td>0.166</td></tr><tr><td>Hematological malignancy</td><td>64 (77.1%)</td><td>-</td><td>-</td></tr><tr><td>Solid tumor</td><td>10 (12%)</td><td>-</td><td>-</td></tr><tr><td colspan="4"><strong>NSTI description and management</strong></td></tr><tr><td>Nosocomial<br>Location</td><td>46 (55.4%)</td><td>34 (26.8%)</td><td>&lt;0.001</td></tr><tr><td>- Upper limbs</td><td>13 (15.7%)</td><td>9 (7%)</td><td>0.076</td></tr><tr><td>- Lower limbs</td><td>35 (42.2%)</td><td>90 (70.3%)</td><td>&lt;0.001</td></tr><tr><td>- Abdomino-perineal</td><td>35 (42.2%)</td><td>32 (25%)</td><td>0.014</td></tr><tr><td>- Cervical</td><td>8 (8.3%)</td><td>2 (1.6%)</td><td>0.018</td></tr><tr><td>- Trunk</td><td>4 (4.8%)</td><td>0</td><td>-</td></tr><tr><td>- Multifocal</td><td>10 (12%)</td><td>16 (12.5%)</td><td>&gt;0.99</td></tr><tr><td>Microbiological documentation</td><td></td><td></td><td></td></tr><tr><td>- Group A Streptococcus</td><td>0 (0%)</td><td>32 (24.8%)</td><td>&lt;0.001</td></tr><tr><td>- Other Streptococcus</td><td>2 (2.4%)</td><td>56 (43.4%)</td><td>&lt;0.001</td></tr><tr><td>- Staphylococcus aureus</td><td>2 (2.4%)</td><td>42 (32.6%)</td><td>&lt;0.001</td></tr><tr><td>- Coagulase negative<br>Staphylococcus</td><td>6 (7.2%)</td><td>0</td><td>-</td></tr><tr><td>- Enterobacteriaceae</td><td>35 (42.2%)</td><td>49 (38%)</td><td>0.643</td></tr><tr><td>- Non fermenting gram negative<br>bacillus</td><td>35 (42.2%)</td><td>26 (20.2%)</td><td>0.136</td></tr><tr><td>Costridium sp</td><td>4 (4.8%)</td><td>0</td><td>-</td></tr><tr><td>Other</td><td>12 (14.5%)</td><td>39 (30.2%)</td><td>0.009</td></tr><tr><td>No documentation</td><td>12 (14.5%)</td><td>7 (5.4%)</td><td>0.045</td></tr><tr><td>Bacteremia</td><td>48 (58.5%)</td><td>34 (26.4%)</td><td>&lt;0.001</td></tr><tr><td>Surgical treatment</td><td>56 (67.5%)</td><td>127 (98.4%)</td><td>&lt;0.001</td></tr><tr><td>Time from diagnosis to surgery (days)</td><td>1 [0.25-2]</td><td>0 [0-0]</td><td>&lt;0.001</td></tr><tr><td>IV-Ig</td><td>2 (2.4%)</td><td>5 (3.9%)</td><td>0.85</td></tr><tr><td>Hyperbaric oxygenotherapy</td><td>1 (1.2%)</td><td>0 (0%)</td><td>-</td></tr><tr><td colspan="4"><strong>Characteristics at ICU admission</strong></td></tr><tr><td>SAPS II</td><td>57 [45-74.25]</td><td>46 [30-75-60]</td><td>&lt;0.001</td></tr><tr><td>SOFa score</td><td>10 [6.5-13]</td><td>-</td><td>-</td></tr><tr><td>Shock</td><td>60 (72.3%)</td><td>86 (68.3%)</td><td>0.64</td></tr><tr><td>Mechanical ventilation</td><td>49 (59%)</td><td>-</td><td>-</td></tr><tr><td>ECMO</td><td>3 (3.6%)</td><td>-</td><td>-</td></tr><tr><td>AKI</td><td>60 (72.3%)</td><td>-</td><td>-</td></tr><tr><td>Lactate (mmol/L)</td><td>3.1 (1.7-6.1)</td><td>2.4 (1.3-4)</td><td>0.005</td></tr><tr><td>CPK (U/L)</td><td>145 [60-8-297.3]</td><td>60</td><td>-</td></tr><tr><td>Fibrinogen (g/L)</td><td>5 (3-6.8)</td><td>-</td><td>-</td></tr><tr><td>Platelets (G/L)</td><td>29 [13-51]</td><td>207 [131-350]</td><td>&lt;0.001</td></tr><tr><td colspan="4"><strong>Neutropenia characteristics</strong></td></tr><tr><td>Neutrophils at NSTI diagnosis (G/L)</td><td>0.04 [0-0.5]</td><td>-</td><td>-</td></tr><tr><td>Time from neutropenia to NSTI diagnosis<br>(days)</td><td>4 [1-14]</td><td>-</td><td>-</td></tr><tr><td>G-CSF injection</td><td>35 (42.2%)</td><td>-</td><td>-</td></tr><tr><td>Granulocytes transfusion</td><td>12 (14.5%)</td><td>-</td><td>-</td></tr><tr><td colspan="4"><strong>ICU outcomes</strong></td></tr><tr><td>Shock</td><td>67 (80.7%)</td><td>95 (73.6%)</td><td>0.308</td></tr><tr><td>Days of catecholamine</td><td>3 [2-6]</td><td>-</td><td>-</td></tr><tr><td>Mechanical ventilation</td><td>61 (73.5%)</td><td>84 (65.6%)</td><td>0.293</td></tr><tr><td>Days of mechanical ventilation</td><td>6 [2-14]</td><td>-</td><td>-</td></tr><tr><td>Renal replacement therapy</td><td>22 (26.5%)</td><td>-</td><td>-</td></tr><tr><td>ICU length of stay</td><td>7 [2.5-20]</td><td>-</td><td>-</td></tr><tr><td>Hospital length of stay</td><td>20 [7-42.5]</td><td>-</td><td>-</td></tr><tr><td>Death in ICU</td><td>40 (48.2%)</td><td>-</td><td>-</td></tr><tr><td>Death at 28 days</td><td>40 (48.2%)</td><td>33 (25.6%)</td><td>0.001</td></tr><tr><td>In-hospital death</td><td>45 (55.6%)</td><td>46 (35.7%)</td><td>0.012</td></tr></tbody></table>

Characteristics and ICU outcomes of neutropenic and non-neutropenic patients

## CO-21

### Critically ill patients with infective endocarditis, neurological failure and indication for cardiac surgery: a multicenter propensity-adjusted study

GROS Alexandre¹, GUETTARD Yves Olivier¹, SEGUY Benjamin¹, PILLOIS Xavier¹, PREVEL Renaud¹, ORIEUX Arthur¹, PREAU Sebastien², LAVIE-BADIE Yoan³, COUPEZ Elisabeth⁷, COUDROY Remi⁴, MAREST Delphine⁵, MARTINS

Raphael⁶, HIKARU Fukutomi¹, GRUSON Didier¹, TOURDIAS Thomas¹, BOYER Alexandre¹

¹CHU Bordeaux, Bordeaux, France; ²CHU Lille, Lille, France; ³CHU Toulouse, Toulouse, France; ⁴CHU Poitiers, Poitiers, France; ⁵CHU Nantes, Nantes, France; ⁶CHU Rennes, Rennes, France; ⁷CHU Clermont-Ferrand, Clermont-Ferrand, France

**Correspondence:** Alexandre BOYER (alexandre.boyer@chu-bordeaux.fr)

Annals of Intensive Care 2022, **12**(1):CO-21

**Rationale:** The benefit-risk balance and/or optimal timing of surgery for infective endocarditis (IE) with neurological events (ischemic or haemorrhagic stroke) remain debated, especially in critically ill patients. Our hypothesis is that these patients should still benefit from surgery. The main objective of this study was to compare their neurological functional outcome whether they received surgery or not.

**Patients and methods/Materials and methods:** We conducted a retrospective (2010–2017), French multi-center study of critically ill patients with acute IE. They were included if they met the following criteria: (i) left-sided IE according to the modified Duke criteria, (ii) with cerebral complications documented by cerebral imaging before cardiac surgery and (iii) with Sequential Organ Failure Assessment score (SOFA) ≥ 3; one of these justifying admission to ICU. Exclusion criteria were isolated right endocarditis, in-hospital acquired endocarditis and patients who developed cerebral complications only after cardiac surgery. All patients were explored with brain imaging before surgery. The primary analysis consisted in a propensity score adjusted logistic regression of surgery as an independent variable of the primary outcome, i.e. modified Rankin score (mRS) at 6 months. The 1-year mortality rate was the main secondary outcome.

**Results:** 192 patients were included whom 67 patients had medical treatment (35%) and 125 underwent cardiac surgery (65%). Delayed surgery according to theoretical recommended timing was decided in 62/125 (50%). Ischemic stroke was the most prevalent neurological complications (74.5%) followed by hemorrhagic lesion (15.6%). In the propensity score-adjusted logistic regression, the odds ratio (OR) for favorable 6-month functional outcome was 0.08 (95% CI 0.03–0.13) in favor of surgery. One-year mortality was strongly reduced with surgery in the fixed-effect propensity adjusted cox model (Hazard Ratio 0.23; 95% CI 0.14–0.36; p < 0.001). These effects remained whether the patients received delayed surgery or not and whether they were deeply comatose or not (Glasgow score > 10).

**Conclusion:** In this study of critically ill patients with simultaneous infectious endocarditis, indication for surgery and cerebral events, a better propensity-adjusted functional outcome was associated with surgery compared with medical treatment, whatever the deepness of coma. A delayed surgery should be considered in severe acute regurgitations. In the absence of randomized study precluded for ethical concerns, an individualized strategy remains highly suggested.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-22

### Predicting central venous catheter-tip colonization in the ICU: development and validation of a score in several randomized trials

IACHKINE Jeanne¹, BUETTI Niccolò², BRIANT Anaïs¹, MIMOZ Olivier³, MÉGARBANE Bruno⁵, MIRA Jean-Paul⁶, RUCKLY Stéphane⁸, SOUWEINE Bertrand⁴, DU CHEYRON Damien¹, TIMSIT Jean-François⁷, PARIENTI Jean-Jacques¹

¹CHU Caen, Caen, France; ²Hôpitaux universitaires de Genève, Genève, Suisse; ³CHU de Poitiers, Poitiers, France; ⁴CHU de Clermont-Ferrand, Clermont-Ferrand, France; ⁵Hôpital Lariboisière AP-HP, Paris, France; ⁶Hôpital Cochin AP-HP, Paris, France; ⁷Hôpital Bichat AP-HP, Paris, France; ⁸Université de Paris, Paris, France

**Correspondence:** Jeanne IACHKINE (jeanne.iachkine@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-22
**Rationale:** Catheter-related bloodstream infection (CRBSI) requires urgent removal of the central venous catheter (CVC). However, the majority of CVCs removed because of a suspicion of CRBSI proves sterile. We aimed to develop and validate a score predictive of catheter-tip colonization with pathogens other than Coagulase-negative Staphylococcus (CoNS).

**Patients and methods/Materials and methods:** We conducted a retrospective study based on databases from two multicenter randomized controlled trials investigating the effect of the catheter insertion site on intravascular complications (training cohort). Catheter colonization was defined as growth of $> = 10^3$ colony-forming units per milliliter from the catheter tip culture yielding to pathogens other than skin contaminants according to Brun-Buisson quantitative technique. Potential factors associated with catheter colonization were identified using a generalized linear model with binomial distribution to account for several CVCs per patients, in univariate and multivariate analyses. Internal validation of these risk factors was performed using bootstrap with 500 replications. Then, a score was computed from the adjusted Odds Ratio coefficients. Finally, external validation was performed in three other independent RCTs investigating the effect of different prevention strategies on the incidence of catheter-related infections (validation cohort). Discrimination was assessed by the Area Under the Curve (c-index).

**Results:** Among 3,681 CVCs and dialysis catheters included in the training cohort, 357 (9.7%) were colonized with microorganisms other than CoNS. Age, obesity, diabetes, site of insertion (jugular and femoral versus sub-clavian), type of catheter (dialysis versus CVC), catheterization duration, fever and local inflammation at removal were independently associated with colonization in multivariate analysis. Diabetes, site of insertion, type of catheter, catheterization duration, fever and local inflammation at removal were robust after internal validation and were computed in the score. Area under the ROC curve for the score was 0.70, 95% CI [0.68–0.73] in the training cohort (Hosmer and Lemeshow goodness of fit test: $p = 0.94$). The validating cohort included 6,299 dialysis catheters and CVCs, of which 262 (4.2%) were colonized. AUC for the score was 0.65, 95% CI [0.62–0.69] in the validation cohort (Hosmer and Lemeshow goodness of fit test: $p = 0.18$) (see Fig. 1). Among 1340 catheters removed for suspicion of CRBSI infection in the training and validating cohorts, 1168 (87.2%) were sterile.

**Conclusion:** This score had a moderate ability to discriminate central venous catheter colonization. Further research is needed to assess the clinical utility of this score for managing CVCs in the ICU, particular to help clinicians' decision facing a catheter-related infection suspicion.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_11.png" /><figcaption>**Figure 1** ROC curves for the score in (a) training (n=3,681) and (b) validating cohort (n=6,299). AUC, area under curve</figcaption></figure>

CO-23

Efficacy of carbapenem vs carbapenem-sparing therapy as empiric antimicrobial therapy in patients with extended-spectrum Beta-lactamase-producing Enterobacteriales urinary septic shock: a propensity-weighted multicenter cohort study (SCRUTIN study)

CARIOU Erwann¹, PREVEL Renaud¹, SILVA Stein², FAGUER Stanislas², SEGUIN Thierry², NSEIR Saadalla³, CANET Emmanuel¹, DESCLAUX Arnaud¹, SOUWEINE Bertrand⁶, KLOUCHE Kada⁵, GUISSET Olivier¹, PILLOT Jerome⁷, PICARD Walter⁸, SAGHI Tahar⁹, DELOBEL Pierre², GRUSON Didier¹, BOYER Alexandre¹

¹CHU de Bordeaux, Bordeaux, France; ²CHU de Toulouse, Toulouse, France; ³CHU de Lille, Lille, France; ⁴CHU de Nantes, Nantes, France; ⁵CHU de Montpellier, Montpellier, France; ⁶CHU de Clermont Ferrand, Clermont Ferrand, France; ⁷Ch de Bayonne, Bayonne, France; ⁸CH de Pau, Pau, France; ⁹Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France

**Correspondence:** Erwann CARIOU (erwann.ca@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-23

**Rationale:** Extended-spectrum beta-lactamase-producing Enterobacteriales (ESBL-E) is a serious health threat with $1.2 billion estimated attributable US healthcare costs in 2017. Their dissemination has led to a major increase in the use of carbapenems, last-resort antibiotics. The objective of this study was to assess the efficacy of carbapenem-sparing regimen as empiric therapy in extended-spectrum β-lactamase-producing Enterobacteriales (ESBL-E) urinary septic shock.

**Patients and methods/Materials and methods:** This retrospective propensity-weighted multicenter observational study conducted in 11 ICUs compared the outcomes of ESBL-E urinary septic shock patients treated with carbapenem or carbapenem-sparing regimen as empiric treatment (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd generation cephalosporin (3GC) + aminoglycosides). The primary outcome was Day-30 mortality. Secondary outcomes included in-ICU and Day-90 mortality rates, severity of illness, septic shock resolution, ICU and in-hospital length of stay and *Clostridium difficile* infection.

**Results:** Among 156 patients included in the study, 69 received a carbapenem and 87 received non-carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the 2 groups. Patients who received an empiric carbapenem-sparing therapy had similar Day-30 mortality (OR = 0.462 [0.173; 1.775] $p = 0.14$), illness severity, resolution of septic shock and ESBL-E infection recurrence rates than patients who received carbapenem. The rate of secondary infection with *C. difficile* was comparable.

**Conclusion:** In ESBL-E urinary septic shock, empiric treatment with carbapenem-sparing regimen was not associated with higher mortality, compared to a carbapenem regimen.

**Reference 1:** Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with *E. coli* or *Klebsiella pneumoniae* bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA 2018; 320:984–9.

**Reference 2:** Karaiskos I, Giamarellou H. Carbapenem-sparing strategies for ESBL producers: when and how. Antibiot Basel Switz 2020; 9:E61.

**Compliance with ethics regulations:** Yes in clinical research

<table><caption>Table 2. Outcomes</caption><thead><tr><th>Outcome</th><th>Total (n=156)</th><th>Carbapenem therapy (Ref.) (n=69)</th><th>Carbapenem-sparing therapy (n=87)</th><th>$</th><th>95% CI (β)</th><th>OR</th><th>95% CI (OR)</th><th>p-value</th></tr></thead><tbody><tr><td colspan="9"><strong>Primary outcome</strong></td></tr><tr><td>Day-30 mortality, n (%)</td><td>14 (10)</td><td>10 (15)</td><td>6 (7)</td><td></td><td></td><td>0.5</td><td>0.17;1.78</td><td>0.14</td></tr><tr><td colspan="9"><strong>Secondary outcome</strong></td></tr><tr><td>ICU mortality, n (%)</td><td>20 (13)</td><td>11 (15)</td><td>1 (15)</td><td></td><td></td><td>0.7</td><td>0.26;1.88</td><td>0.42</td></tr><tr><td>Day 90 mortality, n (%)</td><td>25 (16)</td><td>12 (17)</td><td>13 (15)</td><td></td><td></td><td>0.9</td><td>0.38;2.50</td><td>0.90</td></tr><tr><td>ICU length of stay (days), median (IQR)</td><td>3 (1,8)</td><td>3 (4,10)</td><td>4 (3,7.5)</td><td>-0.26</td><td>-4.52;4.44</td><td></td><td></td><td>0.90</td></tr><tr><td>Hospital length of stay (days), median (IQR)</td><td>15 (10,37.5)</td><td>15 (10,27)</td><td>15 (9,27)</td><td>-0.85</td><td>-7.75;6.85</td><td></td><td></td><td>0.82</td></tr><tr><td>Mechanical ventilation, n (%)</td><td>45 (30)</td><td>24 (35)</td><td>21 (24)</td><td></td><td></td><td>0.5</td><td>0.28;1.08</td><td>0.09</td></tr><tr><td>Renal replacement therapy, n (%)</td><td>25 (16)</td><td>14 (20)</td><td>11 (13)</td><td></td><td></td><td>0.5</td><td>0.22;1.51</td><td>0.10</td></tr><tr><td>Total duration norepinephrine (hours), mean</td><td>65</td><td>43</td><td>66</td><td>3.4</td><td>-11.34;22.11</td><td></td><td></td><td>0.52</td></tr><tr><td>Maximal dose norepinephrine (g/min/kg/min), mean</td><td>0.6</td><td>0.7</td><td>0.5</td><td>-0.17</td><td>-0.39;0.03</td><td></td><td></td><td>0.09</td></tr></tbody></table>

ICU intensive care unit; RRT Renal replacement therapy

For all secondary judgment criteria, the parameter estimates of the regression models were estimated by bootstrapping. The models by weighted based on the final propensity score. P-values are for comparison between carbapenem group and carbapenem-sparing group.
Outcomes.

**CO-24**

**Intravenous Interleukin-7 to restore absolute lymphocyte counts in patients with sepsis**

DAIX Thomas¹, JEANNET Robin¹, MATHONNET Armelle², MIRA Jean-Paul³,
DEQUIN Pierre-François⁴, MORRE Michel⁵, WALTON Andrew⁶, HOTCHKISS
Richard⁶, FRANÇOIS Bruno¹

¹CHU Dupuytren, Limoges, France; ²CHR Orléans, Orléans, France; ³Hôpital Cochin, AP-HP, Paris, France; ⁴CHRU de Tours, Tours, France; ⁵Revim-mune, Inc., Bethesda, Md, Etats-Unis; ⁶Washington University School of Medicine, St Louis, Mo, Etats-Unis

**Correspondence:** Thomas DAIX (thomas.daix@chu-limoges.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-24

**Rationale:** Sepsis leads to deep apoptosis-induced depletion of T-cells resulting in increased rate of secondary infection and late morbidity (1). Interleukin-7 (IL-7) is a pluripotent cytokine essential for lymphocyte proliferation and survival. By intra-muscular (IM) or subcutaneous route, IL-7 improved immunity by increasing T-cell count and reversed the marked loss of immune effector cells in lymphopenic patients with septic shock (2). Because IL-7 by IM route led to injection site reactions due to local lymphocytic infiltration, we designed a phase II study evaluating efficacy and safety of a potentially better tolerated route (intravenous).

**Patients and methods/Materials and methods:** Phase II prospective, randomized, double blind, placebo-controlled trial in 8 ICUs in France and 2 in the United States. Immunocompetent patients with vasopressor-dependent sepsis, two successive absolute lymphocyte counts (ALC) < 900 cells/mm³ and acute respiratory failure and/or acute kidney injury at 48 h after ICU admission were eligible. Forty patients were planned to be randomized 3:1 to receive IV administration of recombinant IL-7 (CYT107) at 10 µg/kg or placebo twice a week for 3 weeks. Primary objective was to determine if IV IL-7 induces an increased ALC at day 29 or hospital discharge. Secondary objective was to assess the safety and tolerability of CYT107.

**Results:** Between June 2019 and March 2020 21 patients (63.8 ± 15.8 y.o.; SOFA score = 8.8 ± 4.4, APACHE II = 17.5 ± 5.6) received CYT107 (n = 15) or placebo (n = 6). ALC was similar in both group at baseline (0.73 ± 0.38 G/L vs 0.70 ± 0.57 G/L). CYT107 tended to increase the ALC at day 29 or hospital discharge (1.71 ± 1.2 G/L in treatment groups vs 1.18 ± 0.79 G/L in control group; p = 0.17) (Figure). Patients in the treatment group had more organ support-free days (22.13 vs 7.7 days; p = 0.01) and slightly less secondary infections (26.7% vs 33%). Three patients developed fever, tachypnea and evidence of hypercytokinemia associated with IL-7 administration, which necessitated discontinuing therapy. Following the review of these events by the Data Safety Monitoring Board, a pharmacokinetic control was carried out and evidenced a higher concentration of CYT107 than expected (Cmax at 41,423 ± 8,548 ng/ml and an AUC at 273,772 ± 107,786 pg/ml·h) at time of adverse event.

**Conclusion:** While IV injection of IL-7 showed ability to reverse sepsis-related lymphopenia, safety issues related to this route led to favor IM or subcutaneous route for the next phase III trial.

**Reference 1:** Drewry AM, Samra N, Skruppy LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock. 2014;42(5):383-391.

**Reference 2:** Francois B, Jeannet R, Daix T, et al. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018;3(5):e98960.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_12.png" /></figure>

*Absolute Lymphocyte Count (ALC) at day 0 and day 29 (or hospital discharge). Blue dots represent placebo-treated patients and red squares CYT107-treated patients.*

**CO-25**

**Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial**

MAZERAUD Aurélien¹, JAMME Matthieu², LUCAS Bruno³, SYLLA Khaoussou¹, SHARSHAR Tarek¹

¹GHU Paris Psychiatrie et Neurosciences, Paris, France; ²CH Poissy Saint Germain en Laye, Poissy, France; ³Institut Cochin, INSERM, Paris, France

**Correspondence:** Aurélien MAZERAUD ( aurelien.mazeraud@gmail.com )

*Annals of Intensive Care* 2022, **12**(1):CO-25

**Rationale:** Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury.

**Patients and methods/Materials and methods:** In this multicentre, double-blind, placebo-controlled trial, done at 43 centers in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating center and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and > 24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimize the risk of adverse events, the IVIG administration was divided into four perfusions of 0.5 g/kg each administered over at least 8 h. Patients in the placebo group received an equivalent volume of sodium chloride 0.9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on [ClinicalTrials.gov](https://ClinicalTrials.gov). NCT04350580.

**Results:** Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0.0 [IQR 0.0-8.0]) and the placebo group (0.0 [0.0-6.0]; difference estimate 0.0 [0.0-0.0]; p = 0.21). Serious adverse events were
more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; $p=0.089$).

**Conclusion:** In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-26

**Unsupervised clustering in critically ill COVID-19 patients: corticosteroid therapy may not fit for all**

ZERBIB Yoann¹, CARPENTIER Mathieu¹, RICHECOEUR Jack², TAMION Fabienne³, CUGNART Cécile³, BONEF Olivier³, VANDERBECKEN Carla¹, MICHAUD Audrey¹, KONTAR Loay¹, SLAMA Michel¹, BRAULT Clément¹, MAIZEL Julien¹

¹CHU Amiens PICARDIE, Amiens, France; ²CH Simone Veil, Beauvais, France; ³CHU Rouen, Rouen, France; ⁴CH Saint Quentin, Saint Quentin, France

**Correspondence:** Yoann ZERBIB (zerbib.yoann@chu-amiens.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-26

**Rationale:** Since the beginning of the COVID-19 pandemic, corticosteroid therapy has become a standard treatment for critically ill patients. The aim of this study was to identify COVID-19 clusters and investigate therapeutic response among clusters.

**Patients and methods/Materials and methods:** We performed a multicenter observational retrospective study between March 2020 and December 2021. A hierarchical clustering on principal components (HCPC) was used to establish COVID-19 profiles based on standard laboratory tests. Demographic data, ICU management, mortality and therapeutic response were compared between clusters.

**Results:** During the period, 329 patients were included in the analysis. HCPC could identify 2 clusters. Patients of Cluster 2 were older (69 [61, 74] vs 64 [55, 71], $p=0.001$) and had more comorbidities (3.50 [2, 5] vs 2 [1, 4], $p<0.001$). These patients had a more severe organ failure. Requirement of invasive mechanical ventilation (69.9% (n=58) vs 56.5% (n=139); $p=0.033$) and renal replacement therapy (39.8% (n=33) vs 14.2% (n=31), $p<0.001$) were more frequent. In line with this, in-ICU mortality rate was 44.6% (n=37) while patients of Cluster 1 died in 27,2% of cases (n=67) ($p=0.004$). Corticosteroid therapy was associated with better outcome among patients of Cluster 1 (Relative Risk=0.66, 95% CI [0.45-1.001], $p=0.06$ and Log Rank test=0.035) while it was not associated with better survival among patients of Cluster 2 (Relative Risk = 1.51, 95% CI [0.94-2.2], $p=0.12$ and Log Rank test=0.12)

**Conclusion:** Based on HCPC, we could identify 2 distinct profiles with different severity and different outcome. More importantly, corticosteroid therapy was associated with a better outcome only in the less severe patients. This approach might help clinician to undertake personalized ICU management.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-27

**Relationship between corticosteroid adjuvant therapy and incidence of ventilator-associated lower respiratory tract infections: a planned ancillary analysis of the coVAPid cohort**

SAURA Ouriel¹, ROUZÉ Anahita¹, POVOA Pedro³, MARTIN-LOECHES Ignacio², MAKRIS Demosthenes⁴, ARTIGAS Antonio⁵, LABREUCHE Julien¹, NSEIR Saad¹

¹CHU Lille, Lille, France; ²St James Hospital, Dublin, Irlande; ³Hospital de Sao Francisco Xavier, Lisbonne, Portugal; ⁴University Hospital of Larissa, Larissa, Grece; ⁵Corporacion Sanitaria Universitaria Parc Tauli, CIBER Enferme dades Respiratorias, Sabadell, Espagne

**Correspondence:** Ouriel SAURA (ouriel.saura@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):CO-27

**Rationale:** Ventilator-associated lower respiratory tract infection (VA-LRTI) is a common and severe complication in patients admitted to the intensive care unit (ICU) for SARS-CoV-2 pneumonia. Corticosteroids are widely used to treat these patients although the impact of this adjuvant therapy on the incidence of VA-LRTI in this population is still unclear. We sought to determine the relationship between corticosteroid adjuvant therapy and the incidence of VA-LRTI in a large cohort of COVID-19 critically ill patients.

**Patients and methods/Materials and methods:** This is a planned ancillary analysis of the retrospective multicenter coVAPid study. Adult patients invasively ventilated for more than 48 h for a SARS-CoV-2 pneumonia during the first epidemic surge were consecutively included. VA-LRTI diagnosis required strict definition with clinical, radiological and microbiological documentation. We assessed the association between VA-LRTI and corticosteroid adjuvant therapy using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on prespecified confounders and with time stratification.

**Results:** 545 patients were included, 191 (35%) received corticosteroids. The incidence of VA-LRTI was not significantly different in the corticosteroid-treated versus non-treated patients ($p=0.068$ for the likelihood ratio in adjusted model). We found a significant time varying effect of corticosteroid on the incidence of VA-LRTI ($p=0.018$), with a non-significant increased risk of developing VA-LRTI after the 14th day following intubation (adjusted cHR 1.38 (95% CI 0.99 to 1.92)).

**Conclusion:** We found no significant association between corticosteroid adjuvant therapy and the incidence of VA-LRTI in a cohort of COVID-19 critically ill patients. We demonstrated a significant time-varying effect of corticosteroids on the risk of developing VA-LRTI all along the 28-day follow-up.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-28

**Impact of corticosteroid therapy on the incidence of ventilator-associated pneumonia in patients with COVID-19: retrospective multicenter observational study**

FORT Romain¹, VACHERON Charles Herve¹, BOHE Julien¹, RICHARD Jean Christophe², RIMMELE Thomas², LUKASZEWICZ Anne Claire², ARGAUD Laurent², DAILLER Frederic², AUBRUN Frederic², FELLAHI Jean Luc², ALLAOUCHICHE Bernard¹, BESTION Audrey², HODILLE Elisabeth², LEVRARD Melanie¹, GERBAUD COULAS Chloe¹, JOFFREDO Emilie¹, THIOLLIERE Fabrice¹, VASSAL Olivia¹, DE SEISSAN DE MARIGNAN Donatien¹, JAY Lucille¹, PIRIOU Vincent¹, FRIGGERI Arnaud¹, WALLET Florent¹

¹CHLS - HCL, Pierre-Bénite, France; ²HCL, Lyon, Gambie

**Correspondence:** Romain FORT (romain.fort@chu-lyon.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-28

**Rationale:** Several epidemic reports indicated a high incidence of ventilator-associated pneumonia (VAP) in patients with severe SARS-CoV2 pneumonia (1). Considering the common use of dexamethasone (DXM) since the 2nd wave, we conducted a large retrospective multicenter study to evaluate the influence of DXM exposure on the incidence of VAP.

**Patients and methods/Materials and methods:** 2088 patients with a diagnosis of COVID-19 admitted to the intensive care unit (ICU) between 27/02/20 and 30/05/21 were included. Among them 1080 (42.2%) had mechanical ventilation (MV) >48 h, and thus separated into 2 groups according to exposure or not to DXM (protocol defined in the RECOVERY trial): DXM+ (n=751) and DXM- (n=329). The diagnosis of VAP was based on clinical and microbiological arguments.

**Results:** The 2 groups were similar. Majority of patients were on MV within the first 24 h after admission; however, with a longer median time from admission to intubation in the DXM+ group (1 [0-3] vs 0 [0-1]; $p<0.001$). Patients exposed to DXM had also a longer duration of intubation: 15 days [8-28] vs 13 days [4-25], $p=0.003$. The
univariate analysis found a higher proportion of VAP in the DXM+ group (58.7%) compared with the DXM- group (51%) (p = 0.023). The overall incidence rate of VAP episodes was essentially the same in the 2 groups: 50.4‰ ventilator days [46.9–54.2] in the DXM+ group vs 49‰ [43.4–55.1] in the other group. Considering competing factors such as extubation and death, the cumulative incidence of the first episode of VAP was higher in the DXM+ group (p = 0.006) with respectively at 7 days: 37.1% [33.7–40.6] vs. 26.4% [21.7–31.2]; at 14 days: 52.7% [49.2–56.2] vs. 43.5% [38.2–48.7]; and at 28 days: 57.8% [54.3–61.2] vs. 49.9% [44.6–55.1] (Figure). But in multivariate analysis, DXM was not identified as an independent risk factor for VAP: HR = 1.08 [0.89–1.30]; p = 0.444. The microbiological distribution was approximately the same in both groups, most often with polymicrobial documentation represented essentially by gram-negative bacteria (GNB) with an overrepresentation of enterobacteria (45%) and non-fermenting GNB (20%). There was also no difference in terms of mortality.

**Discussion:** The incidence of VAP in our series is close to that found in Rouzé et al. study (2) of 1576 patients with the same diagnostic criteria for VAP.

**Conclusion:** In this large multicenter cohort of patients treated for severe SARS-CoV2 infection, there is no association between the incidence of VAP and the use of DXM.

**Reference 1:** Yang X, Yu Y, Xu J, et al.: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine 2020; 8:475–481.

**Reference 2:** Rouzé A, Martin-Loeches I, et al.: Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Medicine 2021; 47:188–198.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_13.png" /><figcaption>Cumulative incidence curve of the first episode of VAP in patients exposed and not exposed to DXM</figcaption></figure>

## CO-29
### Citrulline administration in COVID-19 associated ARDS patients: a randomized controlled trial

REIZINE Florian¹, LESOUHAITIER Mathieu¹, GREGOIRE Murielle¹, DULONG Joelle¹, LAUNEY Yoann¹, LEOUBIER Thomas¹, BENDAVID Claude¹, HAMON Catherine¹, LE PABIC Estelle¹, GACOUIN Arnaud¹, MAAMAR Adel¹, PAINVIN Benoit¹, ROUSSEL Mikael¹, PRONIER Charlotte¹, LE TULZO Yves¹, LAVIOLLE Bruno¹, COGNE Michel¹, TARTE Karin¹, TADIÉ Jean-Marc¹
¹CHU de Rennes, Rennes, France

**Correspondence:** Florian REIZINE (florian.reizine@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-29

**Rationale:** COVID-19 induces a sustained immunosuppression responsible for secondary infections acquisition and late mortality. We recently demonstrated that COVID-19 was responsible for T-cells dysfunction through arginine depletion. Several studies have found that supplementation with citrulline, which is converted in arginine through the activity of argininosuccinate synthetase and argininosuccinate lyase, was more efficient than arginine to increase plasma level of arginine. In the present study, we aimed to assess the effect of

citrulline supplementation in COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) patients as an adjuvant therapy with the goal to relieve immunosuppression and help virus clearance.

**Patients and methods/Materials and methods:** We performed a prospective randomized controlled trial. Patients with RT-PCR confirmed COVID-19 associated ARDS were randomized to receive enteral citrulline supplementation 7 g/day for 7 days or placebo. The primary endpoint was SOFA score on day 7. Secondary outcomes included SOFA score on day 14, Intensive Care Unit (ICU) length of stay (LOS), Day-28 mortality and SARS-CoV2 PCR positivity in tracheal aspirates at day 14 and plasma arginine concentration at day 7.

**Results:** A total of 32 patients were included (10 women, median age 66 years). SOFA score at day 7 were not statistically different between the two groups (4 (IQR: 3–6) versus 3.5 (3–4); p = 0.8) nor was the SOFA score at day 14 despite a trend towards a diminished SOFA score in the citrulline group (3(2.5–6.5) versus 2 (1–5); p = 0.068). Interestingly, a lower proportion of SARS-COV2 PCR positive respiratory samples was observed at day 14 in citrulline patients (30.8% versus 75%; p = 0.027). ICU LOS did not differ between the two groups (18.5 (13–28) versus 15.5 (10.5–25.5); p = 0.32. Arginine concentrations in patients treated by citrulline were higher at day 7 (51.9 (44.5–70.4) versus 77.7 (56.1–102.6), p = 0.026). Finally, Day-28, mortality was 0/16 in the citrulline group and 2/16 in the placebo group, log-rank test p = 0.2.

**Conclusion:** In this proof-of-concept study, citrulline supplementation among COVID-19 ARDS patients did not improve day-7 SOFA score. The higher viral clearance promoted by such treatment deserves further investigations.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-30
### Decontamination regimen in COVID-19 ICU patients

MASSART Nicolas¹, REIZINE Florian², FILLATRE Pierre¹, SEGUIN Philippe², LACOMBE Béatrice⁴, FREROU Aurélien⁵, EGRETEAU Pierre-Yves⁶, HOURMANT Baptiste⁷, KERGOAT Pierre⁸, LORBER Julien⁹, SOUCHARD Jerome², CANET Emmanuel¹⁰, RIEUL Guillaume³, FEDUN Yannick³, DELBOVE Agathe³, CAMUS Christophe²
¹CH Saint-Brieuc, Saint-Brieuc, France; ²CHU de Rennes, Rennes, France; ³CH de Vannes, Vannes, France; ⁴CH Bretagne SUD, Lorient, France; ⁵Centre Hospitalier de Saint-Malo, Saint-Malo, France; ⁶Centre Hospitalier de Morlaix, Morlaix, France; ⁷CHU de Brest, Brest, France; ⁸CH de QUIMPER, Quimper, France; ⁹CH de Saint-Nazaire, Saint-Nazaire, France; ¹⁰CHU de Nantes, Nantes, France

**Correspondence:** Nicola MASSART (nicolasmassart@hotmail.fr)

Annals of Intensive Care 2022, **12**(1):CO-30

**Rationale:** Critically ill patients admitted with SARS-COV 2 infectious disease (COVID-19) are at high risk of ventilator-associated infection (VAP) and ICU acquired bloodstream infection (BSI) with implications for outcomes. Among strategies that aimed to prevent both such acquired infections (AI), selective decontamination regimen has been poorly studied in COVID-19 setting.

**Patients and methods/Materials and methods:** We performed an ancillary analysis of the COCOREVAP study which is a multicenter retrospective observational study in 15 ICUs in western France. All adults admitted with COVID-19 from February 1st, 2020 until December 31st 2021 who required mechanical ventilation were eligible. In addition to standard care, 3 ICUs used a multiple-site decontamination regimen (MSD), a variant of selective digestive decontamination, which consists of the administration of topical antibiotics including an aminoglycoside (tobramycin or gentamicin), polymyxin and amphotericin B, four times daily in the oropharynx and the gastric tube, chlorhexidine body washing and a 5-day nasal mupirocin course in patients who had an expected intubation duration of 24 h or more. AI and death risk factors were estimated using logistic regression.

**Results:** During study period, 614 of 1158 COVID-19 patients admitted in our ICUs were intubated for at least 48 h. Due to missing data regarding AI in 153 patients, 461 patients were finally included. Baseline characteristics in both groups were similar at the exception of a lower age (62 years [55–71] vs 68 [61–73] p = 0.002), a lower body
mass index (27.46 [24.39–31.40] vs 28.76 [25.38–32.16] p = 0.026) and a lower proportion of patients admitted during fall 2020 (31.5% vs 48.1% p < 0.001) in the MSD group. Compared with the standard-care group, AI were less frequent in the MSD group with incidence rates of 30.6 per 1000 patients-days and 16.1 per 1000 patients-days (Incidence Rate Ratio = 0.53 95% CI [0.37–0.75] p < 0.001) respectively. In multivariate analysis, MSD administration was associated with a lower risk of AI (OR = 0.36, 95% CI [0.21–0.63]; p < 0.001). Regarding AI site, MSD remained independently associated with a significant lower risk of VAP (OR = 0.35, 95% CI [0.20–0.60]; p < 0.001) but not of BSI (OR = 0.54, 95% CI [0.57–1.31], p = 0.17). Hospital mortality was lower among patients receiving MSD (30.1% vs 16.9% p = 0.017) (Figure), with an independent protective effect (OR = 0.49, 95% CI [0.24–0.99]; p = 0.049).

**Conclusion:** MSD was associated with a lower incidence of AI among ventilated COVID-19 patients. These promising results deserve confirmation by randomized controlled trials.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_14.png" /><figcaption>Figure. Survival curves</figcaption></figure>

**CO-31**
The association of induced hypothermia at 33 °C and controlled normothermia at 37 °C with outcome in patients with shock on ICU admission after cardiac arrest in non-shockable rhythm: a post-hoc analysis of the HYPERION trial

ZIRIAT Ines¹, LE THUAUT Aurélie¹, LASCARROU Jean-Baptiste¹

¹CHU de Nantes, Nantes, France **Correspondence:** Ines ZIRIAT (ziriat.inesnaila@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):CO-31

**Rationale:** Last consensus of ERC-ESICM on temperature management indicates there was insufficient evidence to recommend for or against temperature control at 32–36 °C or early cooling after cardiac arrest. Post-resuscitation shock defined as need for vasopressors after return of spontaneous circulation is associated with high mortality and brain damage. A post-hoc analysis of TTM2 trial indicated a safety signal about higher mortality when 33 °C was chosen as target during TTM. We perform a post-hoc analysis of HYPERION trial to explore interaction between post-resuscitation shock status and temperature targeted after cardiac arrest.

**Patients and methods/Materials and methods:** Post-analysis of HYPERION trial which include patients with ROSC after cardiac arrest in non-shockable rhythm. Patients were divided according to presence

or absence of post-resuscitation shock after cardiac arrest. Impact of induced hypothermia (33 °C) or controlled normothermia (37 °C) on favorable functional outcome (defined as Cerebral Performance Category (CPC) 1 or 2 at day 90) was evaluated.

**Results:** We included, 581 patients: 339 with post-resuscitation shock and 242 without. Of patient with post-resuscitation shock, 159 received induced hypothermia and 180 controlled normothermia. On day 90, 14 of the 159 patients in the hypothermia group had a CPC score of 1 or 2, as compared with 10 of the 180 patients in the normothermia group, with no significant difference (8.81% vs 5.56%, p = 0.24) (Table 3). Patients in the hypothermia group and the normothermia groups did not differ in terms of mortality on day 90 (83% vs 86%, p = 0.43, Table 4, HR 0.92, 95% CI 0.73-1.16, p = 0.46, Fig. 2).

**Conclusion:** Presence of a post-resuscitation shock at ICU admission after cardiac arrest in non-shockable rhythm is a major determinant of day-90 functional outcome. There is no interaction between post-resuscitation shock presence and benefits of induced hypothermia provided for patients with cardiac arrest in non-shockable rhythm as compared to controlled normothermia.

**Compliance with ethics regulations:** Yes in clinical research.

**CO-32**
Organ donation after out-of-hospital cardiac arrest: a population-based study

RENAUDIER Marie¹,², BINOIS Yannick¹,², DUMAS Florence¹,², LAMHAUT Lionel²,³, BEGANTON Frankie², JOST Daniel²,⁴, CHARPENTIER Julien¹, LESIEUR Olivier⁵, MARIJON Eloi²,⁶, JOUVEN Xavier²,⁶, CARIOU Alain¹,², BOUGOUIN Wulfran²,⁷

¹Hôpital Cochin, Paris, France; ²Paris Sudden Death Expertise Center, Paris, France; ³Hôpital Necker Enfants-Malades, Paris, France; ⁴Brigade des Sapeurs Pompiers de Paris, Paris, France; ⁵Hôpital Saint-Louis, La Rochelle, France; ⁶Hôpital Européen Georges Pompidou, Paris, France; ⁷Hôpital Privé Jacques Cartier, Massy, France

**Correspondence:** Marie RENAUDIER (Mrenaudier@aol.com)

*Annals of Intensive Care* 2022, **12**(1):CO-32

**Rationale:** Organ shortage is a major public health issue, and patients who die after out-of-hospital cardiac arrest (OHCA) could be a valuable source of organs. Our objective was to identify factors associated with organ donation after brain death complicating OHCA, in unselected patients entered into a comprehensive real-life registry covering a well-defined geographic area.

**Patients and methods/Materials and methods:** We prospectively analyzed consecutive adults with OHCA who were successfully resuscitated but died in intensive care units in the Paris region in 2011–2018. The primary outcome was organ donation after brain death. Independent risk factors were identified using logistic regression analysis. A donation-likelihood score was established. One-year outcomes of transplants and transplant recipients were assessed using Cox and log-rank tests.

**Results:** Of the 3061 included patients, 136 (4.4%) became organ donors after brain death, i.e. 28% of the patients with brain death. Patients characteristics are described in the Table. An interaction between admission pH and post-resuscitation shock was identified. By multivariate analysis, in patients with post-resuscitation shock, predictors of organ donation were neurological cause of OHCA (odds ratio [OR], 14.5 [7.6–27.4], P < 0.001), higher pH (OR/0.1 increase, 1.3 [1.1–1.6], P < 0.001); older age predicted absence of donation (OR/10-year increase, 0.7 [0.6–0.8], P < 0.001). In patients without post-resuscitation shock, the only predictor was neurological cause of OHCA (OR, 6.9 [3.0–15.9], P < 0.001); higher pH (OR/0.1 increase, 0.8 [0.7–1.0], P = 0.04) and OHCA at home (OR, 0.4 [0.2–0.7], P = 0.006) predicted absence of donation. Organ donation occurred in 3% of patients with a prediction score < 0 and 34% of those with a score > 0. One-year outcomes of kidney transplants and their recipients did not differ according to Utstein characteristics of the donor.

**Conclusion:** Organ donation should be considered in every patient with OHCA due to a neurological cause, independently from presence of post-resuscitation shock and from Utstein characteristics.
**Compliance with ethics regulations:** Yes in clinical research.

<table><thead><tr><th></th><th>Organ donors (n=136)</th><th>Not organ donors (n=2925)</th><th>P value</th></tr></thead><tbody><tr><td>Age, years, median [IQR]</td><td>54 [48-64]</td><td>64 [54-75]</td><td>&lt;0.0001</td></tr><tr><td>Males, n (%)</td><td>82 (60)</td><td>1966 (67)</td><td>0.09</td></tr><tr><td>Neurological cause of OHCA, n (%)</td><td>53 (39)</td><td>132 (5)</td><td>&lt;0.001</td></tr><tr><td>OHCA at home, n (%)</td><td>80 (59)</td><td>1933 (66)</td><td>0.08</td></tr><tr><td>Bystander-witnessed, n (%)</td><td>119 (87)</td><td>2549 (87)</td><td>0.92</td></tr><tr><td>Bystander cardiopulmonary resuscitation n (%)</td><td>82 (69)</td><td>1775 (69)</td><td>0.91</td></tr><tr><td>Shockable rhythm, n (%)</td><td>38 (29)</td><td>1045 (38)</td><td>0.05</td></tr><tr><td>Epinephrine given, mg, median [IQR]</td><td>2 [1-4]</td><td>3 [1-5]</td><td>0.06</td></tr><tr><td>No-flow time, min, median [IQR]</td><td>5 [0-10]</td><td>5 [0-10]</td><td>0.64</td></tr><tr><td>Low-flow time, min, median [IQR]</td><td>27 [17-43]</td><td>26 [17-40]</td><td>0.86</td></tr><tr><td>Intensive care unit in transplant center, n (%)</td><td>111 (82)</td><td>2092 (71)</td><td>0.01</td></tr><tr><td>VA-ECMO for refractory OHCA, n (%)</td><td>22 (16)</td><td>372 (13)</td><td>0.24</td></tr><tr><td>Admission creatinine, µmol/L, median [IQR]</td><td>109 [88-125]</td><td>127 [99-165]</td><td>&lt;0.001</td></tr><tr><td>Admission pH, median [IQR]</td><td>7.18 [7.10-7.31]</td><td>7.16 [7.02-7.27]</td><td>&lt;0.001</td></tr><tr><td>Targeted temperature management, n (%)</td><td>61 (45)</td><td>1394 (48)</td><td>0.47</td></tr><tr><td>Post-resuscitation shock, n (%)</td><td>71 (61)</td><td>2041 (76)</td><td>&lt;0.001</td></tr></tbody></table>

Table: Utstein characteristics of patients with out-of-hospital cardiac arrest

CO-33

Factors associated with circulatory death after cardiac arrest: a population-based, clustering analysis

BINOIS Yannick¹,⁷, RENAUDIER Marie¹,⁷, DUMAS Florence³,⁷,⁸, YOUFFI Younès⁸,⁹, BEGANTON Frankie⁷,⁸, JOST Daniel⁵,⁷,⁸, LAMHAUT Lionel⁶,⁷,⁸, MARIJON Eloi⁴,⁷,⁸, JOUVEN Xavier⁴,⁷,⁸, CARIOU Alain¹,⁷,⁸, BOUGOUIN Wulfran²,⁷

¹Hôpital Cochin, ICU department, Paris, France; ²Hôpital Jacques Cartier, ICU department, Massy, France; ³Hôpital Cochin, Emergency department, Paris, France; ⁴Hôpital Georges Pompidou, Cardiology department, Paris, France; ⁵BSPP Paris, Paris, France; ⁶Hôpital Necker Enfants malades, ICU department, Paris, France; ⁷Université de Paris, INSERM U970 - PARCC, Paris, France; ⁸Paris Sudden Death Expertise Center, Paris, France; ⁹Center for Research in Economics and Statistics, Palaiseau, France

**Correspondence:** Yannick BINOIS (yannick.binois@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-33

**Rationale:** Out-of-hospital cardiac arrest (OHCA) is a common cause of death, with a very low survival rate. Early circulatory failure is the most common reason for death within the first 48 h after resuscitation. This study including intensive care unit (ICU) patients with OHCA was designed to identify and characterize clusters based on clinical and laboratory features and to determine the frequency of death from refractory post-resuscitation shock (RPRS) in each cluster.

**Patients and methods/Materials and methods:** We retrospectively identified adults who were admitted alive to ICUs after OHCA in 2011–2018 and recorded in a prospectively established registry for the Paris area (France). We identified patient clusters by performing an unsupervised hierarchical cluster analysis (without mode of death among the variables) based on Utstein clinical and laboratory variables. For each cluster, we used the Fine-and-Gray approach to estimate the hazard ratio (HRs) for RPRS (defined as post-resuscitation shock refractory to aggressive critical care). Inclusion was at ICU admission. The time-to-event analysis was censored on the date of death in the ICU or date of ICU discharge alive.

**Results:** Of the 4445 included patients, 1468 (33%) were discharged alive from the ICU and 2977 (67%) died in the ICU. We identified four clusters: initial shockable rhythm with short low-flow time (cluster 1), initial non-shockable rhythm with usual absence of ST-segment elevation (cluster 2), initial non-shockable rhythm with long no-flow time (cluster 3), and long low-flow time with high epinephrine dose (cluster 4). RPRS was significantly associated with this last cluster (HR, 5.51; 95% confidence interval, 4.51–6.74).

**Conclusion:** We identified patient clusters based on Utstein criteria, and one cluster was strongly associated with RPRS. This result may help to make decisions about using specific treatments after OHCA.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_15.png" /></figure>

Heatmap + PCA

CO-34

Effect of moderate hypothermia vs normothermia on 30-day mortality in patients with cardiogenic shock receiving venoarterial extracorporeal membrane oxygenation: a randomized clinical trial

LEVY Bruno¹, GIRERD Nicolas¹, QUATTARA Alexandre², COMBES Alain³

¹CHU Nancy, Vandoeuvre Les Nancy, France; ²CHU Bordeaux, Department Of Anaesthesia And Critical Care, Magellan Medico-Surgical Centre, France; ³APHP, Paris La Pitie Salpetriere, Mir, France

**Correspondence:** Bruno LEVY (blevy@sfr.fr)

Annals of Intensive Care 2022, 12(1):CO-34

**Rationale:** The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) during cardiogenic shock is uncertain.

**Patients and methods/Materials and methods:** To determine whether early use of moderate hypothermia (33–34 °C) compared to strict normothermia (36–37 °C) improves mortality in patients with cardiogenic shock receiving VA-ECMO. Multicenter, unblinded, parallel-group, randomized clinical trial in the intensive care units (ICU) of 20 French Cardiac Shock Care Centers Patients were eligible if they were endotracheally intubated and had been receiving VA-ECMO for cardiogenic shock for <6 h. Of 786 eligible patients, 374 were randomized. The primary outcome was mortality at 30 days. There were 21 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, cardiac transplant, stroke or escalation to left ventricular assist device (LVAD) at days 30, 60 and 180, ventilatory- and kidney replacement therapy-free days between inclusion and days 30, 60 and 180. Adverse events included rates of severe bleeding, sepsis and number of packed red blood cells transfused during VA-ECMO.

**Results:** 334 patients completed the trial (mean age, 57 [SD 12] years. At 30 days, 71 of the 168 patients (42%) in the moderate hypothermia group and 84 of the 166 patients (51%) in the normothermia group had died (adjusted odds-ratio = 0.71; 95% confidence interval 0.45–1.13, p = 0.15; risk difference -8.3% (–16.3 to –0.3%)). The odds-ratio of the composite outcome of death, cardiac transplant, escalation to LVAD and stroke in the hypothermia group, as compared with the control group, was 0.61 (95% CI 0.39–0.96, p = 0.03) at day 30 (risk
difference — 11.5% (— 23.2 to 0.2%)). Of the 27 secondary outcomes, 26 were inconclusive. The incidence of severe or moderate bleeding was 34% in the hypothermia group and 36% in the normothermia group. The incidence of infections was 52% in both groups.

**Conclusion:** In patients with refractory cardiogenic shock treated with VA-ECMO, early application of moderate hypothermia for 24 h did not significantly increase survival compared with normothermia. However, because the confidence interval was wide and included a potentially clinical important effect size, these findings should be considered inconclusive.

**Reference 1:** Levy B et al. JAMA. 2022 Feb 1;327(5):442-453. https://doi.org/10.1001/jama.2021.24776.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_16.png" /></figure>

Kaplan Meier survival estimates during the first 30 days of VA-ECMO patients treated with moderate hypothermia or normothermia. Median (IQR) of observation time was 8 (28, 30) days.

**CO-35**
**Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock**

FAGE Nicolas¹,², DEMISELLE Julien³,⁴, SEEGERS Valérie⁵, MERDJI Hamid³,⁴, GRELON Fabien⁶, MEGARBANE Bruno², ANGUEL Nadia⁸, MIRA Jean-Paul⁹, DEQUIN Pierre-François¹⁰, GERGAUD Soizic¹¹, WEISS Nicolas¹², LEGAY François¹³, LE TULZO Yves¹⁴, CONRAD Marie¹⁵, COUDROY Rémi¹⁶, GONZALEZ Frédéric¹⁷, GUITTON Christophe¹⁸, TAMION Fabienne¹⁹, TONNELIER Jean-Marie²⁰, BEDOS Jean Pierre²¹, VAN DER LINDEN Thierry²², VIEILLARD-BARON Antoine²³,²⁴, MARIOTTE Eric²⁵, PRADEL Gaël²⁶, LESIEUR Olivier²⁷, RICARD Jean-Damien²⁸, HERVE Fabien²⁹, DU CHEYRON Damien³⁰, GUERIN Claude³¹, MERCAT Alain¹, TEOUL Jean Louis⁸, RADERMACHER Peter³², ASFAR Pierre¹

¹Department of Medical Intensive Care, University Hospital of Angers, Angers, France; ²MITOVASC Laboratory UMR INSERM (French National Institute of Health and Medical Research), 1083 - CNRS 6015, University of Angers, Angers, France; ³Department of Intensive Care (Service de Médecine Intensive – Réanimation), Nouvel Hôpital Civil, University Hospital of Strasbourg, Strasbourg, France; ⁴INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France; ⁵Service de Biométrie, Institut de Cancérologie de l'Ouest, Centre Paul Papin, Angers, France; ⁶Medical and Surgical Intensive Care Unit, Le Mans Hospital, Le Mans, France; ⁷Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris University, INSERM UMRS-1144, Paris, France; ⁸Department

of Medical Intensive Care, Bicêtre University Hospital, AP-HP, Paris-Saclay University, Le Kremlin Bicêtre, France; ⁹Department of Medical Intensive Care, Cochin University Hospital, Paris, France; ¹⁰Department of Medical Intensive Care, Tours University Hospital, Tours, France; ¹¹Department of Surgical Intensive Care, University Hospital of Angers, Angers, France; ¹²Department of Medical Intensive Care, Georges Pompidou European Hospital, Assistance Publique - Hôpitaux de Paris, University of Paris, Paris, France; ¹³Medical and Surgical Intensive Care Unit, Saint Brieuc Hospital, Saint Brieuc, France; ¹⁴Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital, Rennes, France; ¹⁵Department of Medical Intensive Care, Nancy University Hospital, Nancy, France; ¹⁶Department of Medical Intensive Care, Université de Poitiers, CHU Poitiers, Poitiers, France; ¹⁷Department of Medical and Surgical Intensive Care, Avicenne Teaching Hospital, Bobigny, France; ¹⁸Department of Medical Intensive Care, Nantes University Hospital, Nantes, France; ¹⁹Department of Medical Intensive Care, Rouen University Hospital, Rouen, France; ²⁰Department of Medical Intensive Care, Brest University Hospital, Brest, France; ²¹Intensive Care Unit, Versailles Hospital, Le Chesnay, France; ²²Department of Intensive Care, Saint Philibert hospital, Catholic University of Lille, Lille, France; ²³Department of Medical Intensive Care, University Hospital of Ambroise Paré, Boulogne Billancourt, France; ²⁴Inserm U1018, Center for Research in Epidemiology and Population Health (CESP), Paris Saclay University, Villejuif, France; ²⁵Department of Intensive Care, Saint Louis Hospital, Paris, France; ²⁶Department of Intensive Care, Avignon Hospital, Avignon, France; ²⁷Department of Medical and Surgical Intensive Care, La Rochelle Saint Louis Hospital, La Rochelle, France; ²⁸Université de Paris, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive Réanimation, Colombes, France; ²⁹Department of Medical and Surgical Intensive Care, Quimper Hospital, Quimper, France; ³⁰Department of Medical Intensive Care, Caen University Hospital, Caen, France; ³¹Department of Medical Intensive Care, Edouard Herriot Hospital, Lyon, France; ³²Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, Ulm, Allemagne

**Correspondence:** Nicolas FAGE (fage.nicolas@gmail.com)

Annals of Intensive Care 2022, **12**(1):CO-35

**Rationale:** In patients with septic shock, the impact of mean arterial pressure (MAP) target on the course of mottling remains uncertain. We investigated whether a low-MAP (between 65 and 70 mm Hg) or a high-MAP target (between 80 and 85 mm Hg) would affect the course of mottling and arterial lactate in patients with septic shock.

**Patients and methods/Materials and methods:** For this post hoc analysis of the SESPSISPAM trial (1), we included patients with at least one available data regarding mottling. Data that concerned mottling were considered until the discontinuation of catecholamine or for a maximum of 5 days under vasopressors. The presence or absence of mottling was recorded every 2 h from 2 h after inclusion to the catecholamine weaning. We compared time course of mottling and arterial lactate between the two MAP target groups. We then evaluated the patient's outcome according to the presence or absence of mottling.

**Results:** We included 747 patients in this analysis: 374 were assigned to the low-MAP target group and 373 to the high-MAP target group. After adjustment for MAP target and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was significantly associated with a higher risk of death at day 90 [Hazard Ratio (HR) 2.28 (1.74–3.00), p < 0.0001]. As compared with low MAP target, a high MAP target did not alter mottling course (Fig. 1) and arterial lactate normalization. Our results were similar when considering only patients who reached the criteria of the SEPSIS-3 definition of septic shock. In addition, when compared to arterial lactate at inclusion, mottling duration appeared to be a better microcirculatory marker of mortality risk. Indeed, patients without mottling or mottling during less than 6 h and with arterial lactate ≥ 2 mmol/l has a lower mortality [HR 1.56 (1.10–2.20)] than patients with mottling during more than 6 h and with arterial lactate < 2 mmol/L [HR of 2.77 (1.80–4.30) (p = 0.005)].

**Conclusion:** In this large-scale study, we showed that a MAP target between 80 and 85 mm Hg, achieved through increased vasopressor doses, did not alter the course of mottling nor arterial lactate
normalization. In patients with septic shock, the presence of mottling ≥ 6 h was associated with higher mortality at day 28 and day 90. In addition, compared to arterial lactate at inclusion, mottling duration appears to be a stronger marker of mortality risk.

**Reference 1:** Asfar P, Meziani F, Hamel J-F et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 24 avr 2014;370(17):1583-93.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_17.png" /></figure>

Course of mottling in patients with septic shock according to the mean arterial pressure target. Horizontal line represents a patient follow-up. Solid line corresponds to a period with mottling; hatched line corresponds to period without mottling

CO-36

**Right ventricular failure is strongly associated with mortality in patients with moderate-to-severe COVID-19-related ARDS**

EVRARD Bruno¹, GOUDELIN Marine¹, GIRAUDEAU Bruno², BRIAT Charlotte¹, FEDOU Anne-Laure¹, DAIX Thomas¹, VAIDIE Julien¹, SANSON Amandine¹, FRANCOIS Bruno¹, VIGNON Philippe¹

¹CHU Limoges, Limoges, France; ²CHU de Tours, Tours, France

**Correspondence:** Bruno EVRARD (bruno.evrard@chu-limoges.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-36

**Rationale:** The incidence and prognostic value of new-onset right ventricular failure (RVF) in patients hospitalized in intensive care unit (ICU) for moderate-to-severe acute respiratory distress syndrome (ARDS) related to COVID-19 has been scarcely studied. Accordingly, the objective was to evaluate the association between the development of RVF during ICU stay and 90-day mortality in patients admitted for COVID-19 ARDS. Secondary objective was to evaluate the association between the new-onset RVF and variations of respiratory parameters.

**Patients and methods/Materials and methods:** In this single-center prospective observational study, ICU patients with COVID-19 moderate-to-severe ARDS were serially assessed using echocardiography. RVF was defined as the association of dilated RV (RV/left ventricular end-diastolic area > 0.6) and elevated central venous pressure (≥ 8 mmHg). Multivariate Cox model analysis accounting for new-onset RVF as time-dependent variable was used to identify parameters associated with mortality. In the subset of patients without RVF at baseline who subsequently developed RVF during the ICU stay, we compared respiratory parameters between the day of the RVF diagnosis and the day of the preceding CCE assessment using a Wilcoxon signed-rank test.

**Results:** Overall, 401 echocardiographic assessments were performed in 140 patients, 43 of whom died at day 90 (31%). RVF was identified within 72 h of ICU admission in 35 patients and secondarily in 40 patients. RVF was independently associated with 90-day mortality (adjusted hazard ratio: 8.17; 95% confidence intervals: 3.15-21.2; p < 0.001). Other independent risk factors were age (HR per 10 years:

1.84; 95% CI: 1.20-2.81; p = 0.005) and ischemic cardiomyopathy (HR: 2.26; 95% CI: 1.19-4.31; p = 0.013). Worsening of PaO₂/FiO₂ (median [quartiles]: 70 mmHg [57-126] vs. 96 mmHg [69-159]; p = 0.005), PaCO₂ (60 mmHg [46-65] vs. 51 mmHg [35-61]; p = 0.036), ventilatory ratio (2.73 [2.29-3.57] vs. 2.25 [1.51-2.92]; p = 0.004), and driving pressure (14 cm H₂O [13-19] vs. 13 cm H₂O [10-14]; p = 0.005) were associated with new-onset RVF.

**Conclusion:** The development of RVF during ICU stay was independently associated with a markedly higher risk of 90-days mortality and appeared associated with a worsening of respiratory parameters.

**Compliance with ethics regulations:** Yes in clinical research.

CO-37

**Sedation-analgesia in pediatric ICU: PEDIASLEEP study**

ALLARY Chloé¹, RONCIN César¹, MICHEL Fabrice¹

¹La Timone - Assistance Publique des Hôpitaux de Marseille, Marseille, France

**Correspondence:** Chloé ALLARY (chloe.allary@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):CO-37

**Rationale:** Sedation in pediatric intensive care units (PICU) is balancing between endangerment patient and the risk of tachyphylaxis, withdrawal syndrome and delirium (1). The main objective was to describe sedation-analgesia procedures in France. The secondary objectives was to specify the use of drugs without marketing authorization, and to observe the drugs associations.

**Patients and methods/Materials and methods:** We conducted a multicentric, descriptive and prospective study in France, between May and July 2021. PICU were joined by the PICURE network or by the chief of department. The referring doctors answered a first online survey describing their unit. They answered a second online survey about each sedated patient on the days of the study. The included patients were hospitalized in PICU; aged between 38 weeks of amenorrhea (WA) and 18 years old; received drugs for sedation or withdrawal syndrome. Excluded patients received painkillers against pure nociceptive pain, or palliative or terminal sedation.

**Results:** Thirty PICU were included, between 8 and 34 beds. Fourteen centers (47%) used protocols. Nurses were autonomous to set dose of sedation according to protocol in 13 centers. Four hundred and two questionnaires were filed. Twelve were excluded: 5 because of age < 38 WA, 7 because they received pure analgesia. Patients ages were: neonates 19%, infant 39%, 2-6 years old 17%, 6-10 years old 5%, 10-14 years old 8%, and 14-17 years old 11%. Forty eight percent patients were in postoperative care, including 30% post cardiotomy; 74% had invasive ventilation, 4% extra corporeal membrane oxygenation, 5% hemodialysis. Sedation was scored in 291 (74%) patients mainly by Comfort Behavior Scale (55%). Pain was scored in 314 (80%) patients, mainly using the Comfort Behavior Scale (50%). Withdrawal was scored in 214 patients (55%), mainly using the Withdrawal Assessment Tool 1. Sixteen per cent patients received no opioids; 42% received Morphine, and 36% Sufentanil. Non-opioid antalgics were: Acetaminophen (78%), NSAIDs, Nefopam, Nalbuphine. While 22% patients didn't received hypnotic, 57% received Midazolam, 34% alpha agonist, 18% Ketamine, 8,5% Propofol. Use of Pentothal, Levomepromazine and Sevoflurane was uncommon. Only 9% of patients received neuromuscular blocking agents, mainly Cisatracurium and Atracurium. Non-drug treatment was used in 77% cases: mainly parental presence, circadian rhythm observance, music therapy and cocooning.

**Conclusion:** The most frequent sedation includes an association between an opioid and a benzodiazepine. Non-drug cares are widely used. Though recommended, scores are not often used.

**Reference 1:** Harris et al. Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals, Intensive Care Med 2016 Jun;42(6):972-86.

**Compliance with ethics regulations:** Yes in clinical research.
CO-38

Retrospective study on prolonged sedation effects with inhaled agents in PICU

BERGER Léo¹, MIATELO Jordi², LÉGER Pierre-Louis¹

¹Hôpital Armand-Trousseau, Paris, France; ²Hôpital Bicêtre, Le Krem-
lin-Bicêtre, France

**Correspondence:** Léo BERGER (leo.berger@aphp.fr)

Annals of Intensive Care 2022, 12(1):CO-38

**Rationale:** In ICU, sedation-analgesia is a major therapeutic element to provide adequate comfort to the patient and to permit a good synchronization with the respirator. Currently, it is common to associate benzodiazepine with opioid. However, after prolonged sedation, effects of the sedative become exhausted, requiring an increase in doses, leading to an increased incidence of withdrawal syndrome, and delaying extubation. Since the beginning of the XXI century, there has been a growing interest in the use of halogenated gases in ICU, because of their hypnotic effects. Furthermore, there is little data on their use during prolonged sedation. Therefore, their efficacy and tolerance should be assessed. They could reduce the dosage of benzodiazepines and opioids, thereby reducing the incidence of withdrawal syndrome.

**Patients and methods/Materials and methods:** This is a retrospective, multicentric cohort study. 50 children (median age 2.2 years, [0.8–7.2]) admitted to PICU between January 2018 and December 2020 were included. All of them received multimodal prolonged sedation (> 72 h) for mechanical ventilation. They all benefited from volatile sedation (Isoflurane or Sevoflurane) for 24 h at least. The primary endpoint was a decrease superior to 20% in benzodiazepine dosages during the first 24 h after halogenated introduction. A 20% decrease in other hypnotics, NMBA, and opioids were also explored. The proportion of adverse events and withdrawal syndrome were collected.

**Results:** A statistically significant reduction in benzodiazepines dosages (µg/kg/h) was reported (118 [62.5; 200] vs 80.0 [32.5; 120], p < 0.01). The same results were found for other hypnotics (Ketamine: 2.00 [1.00; 2.00] vs 1.50 [1.00; 2.00], p = 0.036, mg/kg/h; Clonidine: 0.55 [0.35; 1.27] vs 0.20 [0.12; 0.43], p = 0.036, µg/kg/h). For opioids (µg/kg/h), only Sufentanil (0.80 [0.50; 1.00] vs 0.70 [0.35; 1.00]; p = 0.022) and Fentanyl (6.00 [4.00; 8.00] vs 5.75 [3.25; 6.00], p = 0.012) decreased significantly. No major adverse effects were reported. 26% of patients developed withdrawal syndrome.

**Conclusion:** Halogenated gases seem to be an interesting therapeutic to reduce dosages of different hypnotics and opioids used during multimodal prolonged sedations. Inhalation of halogenated gas via the ACD seems to be sure and easy to use. That appears to be a simple method for maintaining long-term sedation in PICU. Our results suggested IA sedation using the ACD to be an effective and safe alternative to the usual intravenous Propofol- or Midazolam-based regimen. Sevoflurane provided sedation quality comparable to Propofol and Midazolam, but with decreased wake-up and extubation times.

**Compliance with ethics regulations:** Yes in clinical research.

CO-39

3D and Thermography video research infrastructure
for multi-modal image acquisition in the Pediatric Intensive Care
Unit

SHCHERBAKOVA Monisha¹, BOIVIN Vincent², TIASSOU Edem¹, WILLGENSS
Priscilla², VAIL Mariane³, SAUTHIER Michael¹, JOUVET Philippe¹, NOUMEIR
Rita²

¹CHU Sainte Justine, Montreal, Canada; ²Ecole de technologie supérieure,
Montreal, Canada; ³HEC Montreal, Montreal, Canada

**Correspondence:** Monisha SHCHERBAKOVA (monisha.shcherbakova.

hsj@ssss.gouv.qc.ca

Annals of Intensive Care 2022, 12(1):CO-39

**Rationale:** Computer vision has promising potential for the diagnosis of vital distress in critically ill patients including neurological, respiratory and hemodynamic distress. For instance, measurement of respiratory rate using 3D videos in spontaneous breathing patients

and correlation between low cardiac output and thermal distribution using infrared (IR) images were reported in several studies. The aim of our research was to setup a multi-modal video infrastructure to create a clinical video research database and pave the way to real-time vital distress video monitoring within a pediatric intensive care unit (PICU).

**Patients and methods/Materials and methods:** The specifications of the infrastructure were developed by an interdisciplinary team including clinicians, computer scientists, and hospital information technology personnel. These specifications took into account the requirements of the research ethics board: (1) a multimodal video system (MMVS) that is able to capture color (RGB) videos for neurological distress analysis, 3D videos for respiratory distress analysis and thermal videos for hemodynamic analysis; (2) a MMVS in each room on the ceiling above the patient's bed; (3) security systems to only register videos of patients who have consented to the study; (4) automatic data storage on the hospital private servers; (5) synchronization of the videos with clinical data collected simultaneously; (6) data classification in a research database.

**Results:** The MMVS developed included a hardware and a software component (Fig. 1). The hardware component consisted of a NVIDIA Jetson Xavier NX mini-computer that has a built-in GPU (NVIDIA Corp, USA) connected to a Kinect Azure RGB-3D camera (Microsoft, USA) and a FLIR Lepton 3.5 thermal sensor (Teledyne FLIR, USA). Both cameras are pointed towards the patient and are placed in a 3D printed support. The software component included a web user interface for performing the acquisitions in the hospital intranet in a secure manner. The video research database currently includes more than 200 acquisitions and is being used in various studies to assess vital distress signs including facial expressions to estimate sedation level and consciousness using RGB videos, the refinement of tidal volume and respiratory rate measurements in patients using 3D videos, and estimation of the thermal gradient across various parts of the body using IR.

**Conclusion:** A multi-modal RGB 3D and thermography video infrastructure was successfully set up and a video research database of critically ill children was constructed and enabled algorithm development to assess various vital distress. This setup could be replicated in other PICUs.

**Compliance with ethics regulations:** Yes in clinical research.

CO-40

Volume per kg per transfusion of the first red blood cell (RBC) transfusion given to participants of the ABC-PICU randomized controlled trial, for the ABC-PICU Investigators, CCCTG, PALISI Network, BloodNet Network, and GFRUP

GALLAND Anne¹, DU PONT-THIDODEAU Geneviève¹, SPINELLA Philipp²,
LETEURTRE Stéphane³, DUCRUET Thierry⁴, LACROIX Jacques¹, TUCCI
Marisa¹

¹Division of Pediatric Critical Care Medicine, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Canada; ²Department of Surgery and Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Etats-Unis; ³Réanimation et Surveillance Continue Pédiatriques, Hôpital Jeanne de Flandre, CHRU Lille, Lille, France; ⁴Unité de recherches cliniques appliquées, Research Centre, CHU Sainte-Justine, Montreal, Canada

**Correspondence:** Jacques LACROIX (jlacroix052@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-40

**Rationale:** New et al¹ completed a national cohort study in the United Kingdom (UK); all hospitals were invited to participate. Hospitalized children—not only those in pediatric intensive care units (PICU)—<18 years old who received an RBC transfusion during a 3-month period in 2009 were eligible for inclusion. The median volume was 15.0 (IQR: 11.8–19.2) mL/kg per transfusion, with peaks of prescription volume at 10, 15 and 20 mL/kg. Almost no specific attention has been paid to the volume of RBC transfusion administered in PICU. We determined the volume/kg/transfusion of the first RBC transfusion given to participants in the Age of Blood in Children in PICU (ABC-PICU) trial.² The hypothesis was that we would find the same variability in the volume/kg administered to PICU patients than reported by New in hospitalized children.
**Patients and methods/Materials and methods:** Patients enrolled in ABC-PICU were allocated to receive either fresh (stored <7 days) or standard-issue RBC (delivery of oldest compatible unit available in the blood bank). The volume of RBC unit per transfusion was not controlled in ABC-PICU. Cardiac patients were randomized before surgery; other patients were randomized in PICU. In the former, data on RBC transfusion were collected in the operating room and PICU while data in the latter were collected only in PICU.

**Results:** 1538 patients across 50 centers (US, Canada, France, Italy, Israel) were randomized between February 2014 and August 2018; 1474, including 1263 non-cardiac patients, received at least one RBC transfusion. Figure 1 reports the number of participants to ABC-PICU per range of volume of the first RBC transfusion administered after randomization. Among the 1474 participants, 105 (7.1%) received >30 mL/kg/transfusion; most (82/105 = 78.1%) were cardiac patients who were first transfused while priming a cardio-pulmonary bypass. Among 1263 non-cardiac participants, 736 (58.3%) received between 9 and 16.99 mL/kg/transfusion; a significant proportion received <9 or >17 mL/kg/transfusion (286 or 22.6% and 241 or 19.1%, respectively).

**Conclusion:** There is an important variability in the volume/kg/transfusion given to participants in ABC-PICU. Data on bleeding status and on-site policy limiting volume per transfusion (e.g., not more than one unit per transfusion) were not collected in ABC-PICU, which limits the interpretation of the results reported in this abstract. Future studies taking into account patients' bleeding status and site-specific policy on volume per transfusion must investigate what are the causes and the clinical impact of the variability that we observed in ABC-PICU participants.

**Reference 1:** New HV, Grant-Casey J, Lowe D, Kelleher A, Hennem S, Stanworth SJ. Red blood cell transfusion practice in children: current status and areas for improvement? A study of the use of red blood cell transfusions in children and infants. Transfusion 2014;54.

**Reference 2:** Spinella PC, Tucci M, Fergusson DA, Lacroix J, Hébert PC, Leteurtre S, et al. The age of transfused blood in critically ill children. JAMA 2019;322:2179–90.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_18.png" /></figure>

Volume of first red cell transfusion given after randomization to 1263 non-cardiac and 211 cardiac participants to the ABC-PICU trial.

CO-41

**In situ simulation training for parental presence during critical situations in PICU: an observational study**

BORDESSOULE Alice¹, FELICE-CIVITILLO Cristina¹, GRAZIOLI Serge¹,
BARCOS Francisca¹, HADDAD Kevin¹, RIMENSBERGER Peter¹, POLITO
Angelo¹

¹HUG, Geneva, Suisse

**Correspondence:** Alice BORDESSOULE (alice.bordessoule@hcuge.ch)
Annals of Intensive Care 2022, **12**(1):CO-41

**Rationale:** Family presence during invasive procedures or cardiopulmonary resuscitation (CPR) is a part of the family-centered approach in pediatric intensive care units (PICUs). We established a simulation program aiming at providing communication tools to healthcare professionals. The goal of this study was to evaluate the impact of this program on the stress of PICU professionals and its acceptance.

**Patients and methods/Materials and methods:** An observational study of a simulation program, with questionnaire, was used to measure pre- and post-simulation stress and the degree of satisfaction of the participants. Setting: PICU of Geneva Children's Hospital, Switzerland. Forty simulations with four different simulation scenarios and various types of parental behavior, as imitated by professional actors, were completed during a 1-year period. Primary outcomes were the difference in perceived stress level before and after the simulation and the degree of satisfaction of healthcare professionals (nursing assistants, nurses, physicians). The impact of previous experience with family members during critical situations or CPR was evaluated by variation in perceived stress level.

**Results:** Overall, 201 questionnaires were analyzed. Perceived stress associated with parental presence decreased from a pre-simulation value of 6 (IQR, 4–7) to 4 (IQR, 2–5) post-simulation on a scale of 1–10. However, in 25.7% of cases, the individually perceived post-simulation stress level was higher than the pre-simulation one. Satisfaction of the participants was high with a median of 10 (IQR, 9–10) out of 10 (Fig. 1).

**Discussion:** Our study describes an in situ pediatric simulation program of critical situations in the presence of family members played by professional actors. The simulation program was explicitly aiming at the development of communication skills. The "in situ" setting and the possibility to debrief in the presence of a psychologist represent two innovative features of our study. The simulation generally, but not always, showed a reduction in healthcare professionals perceived stress caused by family presence during a critical situation in the PICU. To meet the demand of participants experiencing a high level of stress after the simulation, a pre-simulation video on potential benefits and pitfalls of family presence during critical situations as well as on ad-hoc communication tools is now available to all future participants.

**Conclusion:** A simulation program helps reduce PICU team emotional stress associated with the presence of family members during critical situations or CPR, and is welcomed by PICU team members.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_19.png" /></figure>

**Figure 1.** Box plot showing overall pediatric intensive care team stress related to family member presence during cardiopulmonary resuscitation or other major interventions in the pediatric intensive care unit, before and after the simulation.
CO-42

**Beta-lactam exposure and safety in intermittent or continuous
infusion in critically ill children**

DEBRAY Agathe³, CALLOT Delphine², HIRT Deborah², BILLE Emmanuelle¹,
RENOLLEAU Sylvain¹, CHOUCHANA Laurent², TRELUYER Jean-Marc¹,²,
OUALHA Mehdi¹, BERANGER Agathe¹

¹Necker enfants malades, Paris, France; ²cochin, Paris, France; ³trousseau,
Paris, France

**Correspondence:** Agathe BERANGER (agathe.beranger@gmail.com)

Annals of Intensive Care 2022, 12(1):CO-42

**Rationale:** To assess the pharmacokinetic (PK) efficacy and clinical toxicity for three beta-lactams: cefotaxime, piperacillin/tazobactam and meropenem, depending on two administration modalities: continuous or intermittent infusions in critically ill children.

**Patients and methods/Materials and methods:** This single center observational prospective study was conducted in a pediatric intensive care unit. All hospitalized children who had one measured plasma concentration of the investigated antibiotics were included. Plasma antibiotic concentrations were interpreted by a pharmacologist, using a Bayesian approach based on previously published population pharmacokinetic models. Exposure was considered optimal, low, or high according to the PK target 100% fT > 4 × MIC and a trough concentration below the toxic concentration (50 mg.L⁻¹ for cefotaxime, 150 mg. L⁻¹ for piperacillin and 44 mg.L⁻¹ for meropenem).

**Results:** Between May 2019 and January 2020, 80 patients were included and received 106 antibiotic courses: 74 (70%) were administered in intermittent infusion (II) and 32 (30%) in continuous infusion (CI). Compared to II, CI provided more optimal PK exposure (OR 1.2, 95% CI 1.01–1.5, p=0.04), less underexposure (OR 0.7, 95% CI 0.6–0.84, p<0.001) and more overexposure (OR 1.2, 95% CI 1.03–1.3, p=0.01) (Fig. 1). Five adverse events have been reported during the study period, although none have been attributed to beta-lactam treatment.

**Conclusion:** Continuous infusion provided a higher probability to attain an optimal PK target compared to intermittent infusion, but also a higher risk for overexposure. Regular therapeutic drug monitoring is recommended in critically ill children receiving beta-lactams, regardless of the administration modality.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_20.png" /></figure>

Description of the antibiotic exposure (underexposure, optimal exposure or overexposure) depending on the drug (A) or for the whole cohort (B), with respect to the administration route, intermittent infusion (II) or continuous infusion (CI).

CO-43

**Incidence and risk factors of weaning-induced cardiac
dysfunction: results from a multicenter, observational study**

SHI Rui¹, AYED Soufia¹, TEBOUL Jean-Louis¹, ANGUEL Nadia¹, OSMAN David¹, PHAM Tai¹, MORETTO Francesca¹, LAI Christopher¹, BEUZELIN Marie², PERSICHINI Romain³, LEGOUGE Marie⁴, DE VITA Nello⁵, LEVY Bruno⁶, BEURTON Alexandra⁷, MANGAL Kishore⁸, HULLIN Thomas⁹, LABBE Vincent¹⁰, GUILLOT Max¹¹, HARROIS Anatole¹², MONNET Xavier¹

¹Service de médecine intensive-réanimation, Université Paris-Saclay,
AP-HP, Hôpital de Bicêtre, DMU CORREVE, Inserm UMR S_999, FHU SEPSIS,
Groupe de recherche clinique CARMAS, Le Kremlin-Bicêtre, France;

²Service de réanimation polyvalente, Centre hospitalier de Dieppe,
Dieppe, France; ³Service de réanimation médicale, Hôpital Félix Guyon,
Saint-Denis-De-La-Réunion, France; ⁴Service de d'anesthésie-réanimation
adultes, Centre hospitalier d'Orléans, Orléans, France; ⁵Université del
Piemonte Orientale, Dipartimento di Medicina Traslazionale, Novara,
Italie; ⁶Service de réanimation médicale, Hôpital de Nancy-Brabois,
Vandoeuvre-Lès-Nancy, France; ⁷AP-HP, Groupe Hospitalier Universitaire
APHP-Sorbonne Université, site Pitié-Salpêtrière, Service de Pneumolo-
gie, Médecine intensive Réanimation (Département R3S), Paris, France;

⁸Department of Medicine and Critical Care, Eternal Hospital, Eternal Heart
Care Centre & Research Institute, Jaipur, Inde; ⁹Service de réanimation
polyvalente, Hôpital Sud-Essone, Etampes, France; ¹⁰Service de réanima-
tion, AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université,
site Tenon, Paris, France; ¹¹Service de réanimation médicale, Hôpital de
Strasbourg, Strasbourg, France; ¹²Service d'anesthésie-réanimation, Uni-
versité Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France

**Correspondence:** Rui SHI (rui.shi@u-psud.fr)

Annals of Intensive Care 2022, 12(1):CO-43

**Rationale:** Weaning-induced pulmonary edema (WiPO) is one of the main reasons for weaning failure. Nevertheless, the reported incidence of WiPO is variable mainly in monocentric studies with small sample size. We thus aimed to evaluate the incidence and risk factors of WiPO in a large mixed population of critically ill patients.

**Patients and methods/Materials and methods:** Adult critically ill patients receiving invasive ventilation were included once the attending physicians decided to perform a spontaneous breathing trial (SBT). Patients with tracheostomy were excluded. The duration and modalities of the SBT (T-tube/pressure support or others) were decided by attending physicians. The consensual diagnosis of WiPO was made a posteriori by five experts based on the patient characteristics, hemodynamic and echocardiographic variables, and biochemical results.

**Results:** From July 2019 to February 2021, 634 SBT performed in 500 patients (65 (55–74) y.o., 64% male) from twelve intensive care units, were prospectively included. The main indication for intubation was acute respiratory failure in 202 (40%) patients, neurological failure in 100 (20%) patients, interventional procedure in 74 (15%) patients, shock in 55 (11%) patients, resuscitated cardiac arrest in 10 (2%) patients, a mixture of previous reasons in 53 (11%) patients and miscellaneous reasons in 6 (1%) patients. SBT failed at 217 (34%) occurrences observed in 157 (31%) patients. WiPO was identified in 79 (36%) failed SBTs in 58 (37%) patients. We assessed WiPO according to the main indication for intubation, the prevalence of WiPO was 73% in patients intubated for acute respiratory failure/shock/sepsis, 13% in patients intubated for neurological failure, 9% in patients intubated after resuscitated cardiac arrest, and 5% in those intubated for an interventional procedure. Among 217
failed SBTs, WiPO occurred in 54 (25%) of SBTs performed with a T tube, 16 (7%) with pressure support ventilation, and 9 (4%) with other modalities. Compared to patients without WiPO (n = 98), patients with at least one WiPO (n = 58) had a higher prevalence of chronic obstructive pulmonary disease (COPD) (27% vs. 7%, respectively; p = 0.001), and previous cardiopathy (dilated and/or hypertrophic and/or valvular disease, 49% vs. 23%, respectively; p = 0.002). A logistic regression analysis found that, COPD (odds ratio (OR): 5.1, [95% confidence interval: 1.9–14.0]), and previous cardiopathy (OR: 2.9 [1.4–6.2]) were independent risk factors for developing WiPO.

**Conclusion:** In a large mixed population of critically ill patients, WiPO accounts for 36% of SBT failure. COPD and a previous cardiopathy were independent risk factors for developing WiPO.

**Compliance with ethics regulations:** Yes in clinical research.

CO-44

Plasma exchange are not associated with better outcome in MDA5 rapidly-progressive interstitial lung disease

BAY Pierre¹, PINETON DE CHAMBRUN Marc², ROTHSTEIN Vincent³,
MAHEVAS Matthieu¹, DE PROST Nicolas¹, ROUX Antoine⁴, ZUBER
Benjamin⁴, ISRAEL BIET Dominique⁵, HERVIER Baptiste⁶, TAZI Abdellatif⁶,
MOUTHON Luc⁷, MEKINIAN Arsene⁹, DELIGNY Christophe¹⁵, BORIE
Raphael⁸, MEURICE Jean Claude¹⁰, PRIOU Pascaline¹⁰, MEYER Alain¹²,
SAVALE Laurent¹⁴, DE SAINT MARTIN Luc¹³, BRILLIET Pierre-Yves³,
KHAFAGY Philippe³, BENVENISTE Olivier², NUNES Hilario³, ALLENBACH
Yves², UZUNHAN Yurdagul³

¹CHU Henri Mondor, Créteil, France; ²CHU Pitié Salpétrière, France, France; ³CHU Avicenne, Bobigny, France; ⁴Hôpital Foch, Suresnes, France; ⁵Hôpital Européen Georges Pompidou, Paris, France; ⁶CHU Saint Louis, Paris, France; ⁷CHU Cochin, Paris, France; ⁸CHU Bichat, Paris, France; ⁹CHU Saint Antoine, Paris, France; ¹⁰CHU Poitiers, Poitiers, France; ¹¹CHU Angers, Angers, France; ¹²CHU Strasbourg, Strasbourg, France; ¹³CHU Brest, Brest, France; ¹⁴CHU Bicetre, Le Kremlin Bicetre, France; ¹⁵CHU Martinique, Fort De France, France **Correspondence:** Pierre BAY (pierrebay53@yahoo.fr)

Annals of Intensive Care 2022, 12(1):CO-44

**Rationale:** Rapidly progressive interstitial lung disease (RP-ILD) is a frequent manifestation of anti-MDA5 dermatomyositis (DM) and is associated with a high mortality rate. The appropriate treatment regimen of anti-MDA5 RP-ILD is uncertain. A potential pathogenic role of MDA5 antibodies motivated plasma exchange (PLEX) but whether the effectiveness of this procedure is unknown. The aim of the study was to evaluate the outcome of patients undergoing PLEX for anti-MDA5 RP-ILD.

**Patients and methods/Materials and methods:** This French multicenter retrospective study was conducted from 2012 to 2021 in 18 hospitals and included all patients with anti-MDA5 RP-ILD. The primary endpoint was one-year mortality.

**Results:** 51 patients with anti-MDA5 RP-ILD (female 67%; mean age at disease onset: 51 ± 11.6 years) were included. 32 patients (62.7%) required mechanical ventilation. 25 patients (49%) received PLEX. Baseline characteristics were not different between PLEX+ and PLEX- patients. PLEX+ patients received more immunosuppressants and required more often mechanical ventilation (19 PLEX+ vs 13 PLEX−, p 0.05). One-year mortality rate for PLEX+ and PLEX− patients was 64% and 42.6%, respectively. The Kaplan–Meier estimated probabilities of one-year survival were similar for PLEX+ vs. PLEX− patients (Fig. 1).

**Conclusion:** Anti-MDA5 RP-ILD is associated with a high 1-year mortality rate. The use of PLEX was not associated with a favorable outcome. Further studies are needed to evaluate their efficacy.

**Compliance with ethics regulations:** Yes in clinical research.

<figure><img src="image_21.png" /></figure>

Kaplan–Meier Curves for the 1-year mortality status according to plasma exchange status.

CO-45

Spontaneous pneumomediastinum in critically ill COVID-19 patients

ELABBADI Alexandre¹, TOMAS Urbina², ENORA Berti³, CONTOU Damien ⁴,
QUINTANA Soulier², CARTEAU Guillaume³, VOIROT Guillaume¹, FARTOUKH
Muriel¹, GIBELIN Aude¹

¹Hôpital Tenon, APHP, Paris, France; ²Hôpital Saint-Antoine, APHP, Paris, France; ³Hôpital Henri Mondor, Créteil, France; ⁴Centre Hospitalier Victor Dupouy, Argenteuil, France

**Correspondence:** Alexandre ELABBADI (alexandre.elabbadi@aphp.fr)
Annals of Intensive Care 2022, 12(1):CO-45

**Rationale:** Spontaneous pneumomediastinum (SP), defined by the presence of air within the mediastinum without traumatic lesion, has been described during ARDS, even in the era of protective ventilation. It has been also described in case series of COVID-19 with severe pneumonia in the absence of use of invasive mechanical ventilation. We aimed at describing the prevalence of spontaneous pneumomediastinum during severe COVID-19 pneumonia, and at investigating its prognostic impact

**Patients and methods/Materials and methods:** We conducted a retrospective multicenter observational study in 4 French intensive care units (ICUs) between August 2020 and April 2021. All patients with laboratory-confirmed COVID-19 with severe pneumonia were included. Spontaneous pneumomediastinum was diagnosed either on chest X-ray or chest CT-scan. The primary endpoint was to estimate the prevalence of SP during COVID-19 with severe pneumonia. Secondary endpoints were to investigate the prognostic impact of SP, using a composite criterion named "complicated course" including mechanical ventilation or death at day-28.

**Results:** During the study period, 672 patients with COVID-19 with severe pneumonia were included. Thirty-two patients (5%) developed a SP after 9 days [4–13] of COVID-19 onset. A pneumothorax was associated in 10 patients (31%). Two-third of patients (n = 21; 66%) developed a SP after 6 days [4–12] of ICU admission, while they did not receive invasive mechanical ventilation (IMV). Finally, half of
these patients (n = 11/21) required IMV after 1 day [0-3] of SP diagnosis. Although the proportion of patients requiring IMV was similar, the time to tracheal intubation was longer in the patients with SP (6 days vs. 2 days; p < 0.01), with a significantly higher first-line use of high-flow nasal oxygen therapy or non-invasive ventilation, and more awake prone positioning sessions. Although there was no difference in "complicated course", the length of stay in the ICU was significantly higher in the SP group (18 vs 9 days, p = 0.01).

**Conclusion:** Prevalence of SP was not uncommon, affecting nearly 5% of all patients admitted to the ICU. Nearly two third of SP occur before or in the absence of IMV. This suggests that, barotrauma secondary to invasive mechanical ventilation, does not appear to be preponderant in the occurrence of pneumomediastinum in COVID-19. Mechanism is potentially carried-out by patient self-inflected lung injury and hyperinflation secondary to a prolonged respiratory failure, as underlined by a longer delay before invasive mechanical ventilation. Presence of a pneumomediastinum should alert the clinician in a spontaneously breathing patient to its tolerance and the need to use a more protective ventilation.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-46

### Attributable mortality and population attributable fraction of death of ventilator-associated pneumonia among pandemic non-COVID-19 patients, and pandemic COVID-19 patients

VACHERON Charles-Hervé¹, LEPAPE Alain¹, SAVEY Anne¹, MACHUT Anais¹, TIMSIT Jean-François², COURNO Gaelle⁴, VANHEMS Philippe⁵, LANDEL Verena⁵, LAVIGNE Thierry⁶, BAILLY Sebastien⁷, BETTEGA Francois⁷, COMPAROT Sylvie³, REA-REZO Study Group¹, MAUCORT-BOULCH Delphine⁵, FRIGGERI Arnaud⁵

¹CHU Lyon sud, Lyon, France; ²APHP, Paris, France; ³CH Avignon, Avignon, France; ⁴CH Toulon, Toulon, France; ⁵CHU Lyon, Lyon, France; ⁶CHU Strasbourg, Strasbourg, France; ⁷CHU Grenoble, Grenoble, France

**Correspondence:** Charles-Hervé VACHERON (charles-herve.vacheron@chu-lyon.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-46

**Rationale:** Patients with a SARS-CoV-2 infection are at higher risk of Ventilator-Associated Pneumonia (VAP) and may have an increased Attributable Mortality (AM) and Population Attributable Fraction (PAF) of mortality related to VAP.

**Patients and methods/Materials and methods:** Using the REA-REZO surveillance network, 3 groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of AM and PAF related to VAP in these patients. Using multi-state modeling with causal inference, the outcomes related to VAP were also evaluated.

**Results:** A total of 64816 patients were included in the control group, 7442 in the PandeCOV-, and 1687 in the PandeCOV+. The incidence of VAP was 14.2 (95% CI [13.9;14.6]), 18.3 (95% CI [17.3;19.4]), and 31.9 (95% CI [29.8;34.2]) VAP per 1000 ventilation-day, in each group, respectively. AM at 90 days was 3.15% (95% CI [2.04;3.43]), 2.91% (95% CI [− 0.21;5.02]), and 8.13% (95% CI [3.54–12.24]), and PAF of mortality at 90 days was 1.22% (95% CI [0.83;1.63]), 1.42% (95% CI [− 0.11–2.61]), and 9.17% (95% CI [3.54;12.24]) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing a VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (HR 0.62, 95% CI [0.52;0.74]) and tended to have a higher risk of death after acquiring VAP (HR 1.07, 95% CI [0.86;1.33]) compared to the control group.

**Conclusion:** Patients admitted in ICUs during the pandemic, even without a diagnosis of COVID-19, were at higher risk of VAP. VAP attributable mortality was higher for COVID-19 patients, with more than 9% of the overall mortality related to VAP.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-47

### FX06 to rescue acute respiratory distress syndrome during Covid-19 pneumonia. A randomized clinical trial

GUERIN Emmanuelle¹, FRANCHINEAU Guillaume², LE GUENNEC Loic¹, FRAPARD Thomas¹, LEFEVRE Lucie¹, LUYT Charles-Edouard¹, COMBES Alain¹, HAYON Jan², ASFAR Pierre³, BRECHOT Nicolas¹

¹CHU Pitié-Salpêtrière, Paris, France; ²CHI de POISSY, Saint-Germain-En-Laye, France; ³CHU d'ANGERS, Angers, France

**Correspondence:** Nicolas BRECHOT (nicolas.brechot@aphp.fr)

*Annals of Intensive Care* 2022, **12**(1):CO-47

**Rationale:** Vascular leakage is a major feature of SARS-CoV-2 induced acute respiratory distress syndrome (ARDS). Its levels are associated with mortality, which remains as high as 50%. FX06, a drug under development containing fibrin-derived peptide beta15-42, stabilizes cell-cell interactions, thereby reducing vascular leak and mortality in several animal models of ARDS. It was successfully used as a rescue therapy in a patient exhibiting a severe ARDS following EBOLA virus infection. The aim of this study was to evaluate the efficacy of FX06 in reducing vascular leakage during SARS-CoV-2 induced ARDS.

**Patients and methods/Materials and methods:** We conducted a double-blinded placebo-controlled multicenter trial. Patients receiving invasive mechanical ventilation for less than 5 days for a SARS-CoV-2 induced ARDS were randomized to receive intravenous FX06, 400 mg per day during 5 days, or its placebo, on the top of usual care. The primary endpoint was the reduction of pulmonary vascular leakage from day 1 to day 7, evaluated by transpulmonary thermodilution-derived extra-vascular lung water index (EVLWi). All analyses were conducted on an intent-to-treat basis.

**Results:** After one consent withdrawal, 49 patients were enrolled and randomized, 25 in the FX06 group and 24 in the placebo group. Patients were very severe, with a median SAPS-II score of 57 [IQR 39; 66], a median $PaO_2:FiO_2$ ratio of 104 [69; 165], and a median static pulmonary compliance of 28 ml/cm of water [19; 35]. One third of them were equipped with veno-venous ECMO. Although EVLWi was elevated at baseline (15.6 ml/kg [13.5; 18.5]), the primary endpoint of its reduction from day 1 to day 7 was comparable between groups (− 1.9 ml/kg [− 3.3; − 0.5] in the FX06 group vs. − 0.8 ml/kg [− 5.5; − 1.1] in the placebo group, estimated effect − 0.8 [− 3.1; 2.4], $p$=0.51). Cardiac index, pulmonary vascular permeability index, and fluid balance were also comparable between groups. $PaO_2:FiO_2$ ratio remained low and comparable between groups. Duration of mechanical ventilation and survival were also not affected by FX06 infusion, with 21 (84%) patients surviving at day 30 in the FX06 group and 17 (71%) in the placebo group ($p$=0.27). Adverse events rates were comparable between groups, although patients receiving the drug experienced more ventilator-associated pneumonia (16/25 vs. 6/24, $p$=0.009).

**Conclusion:** In this trial FX06 failed to reduce the level of SARS-CoV-2 induced pulmonary vascular leakage. Further studies are needed to evaluate its efficacy at earlier time points of the disease or using other dosing regimens.

**Compliance with ethics regulations:** Yes in clinical research.

## CO-48

### Quality of life and long-term assessment of survivors after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome due to COVID 19

CHOMMELOUX Juliette¹, VALENTIN Simon², ADDA Mélanie³, PINETON DE CHAMBRUN Marc¹, MOYON Quentin¹, MATHIAN Alexis¹, CAPELLIER Gilles⁴, GUERVILLY Christophe³, LEVY Bruno², JACQUET Pierre⁵, SONNEVILLE Romain⁵, VOIRIOT Guillaume⁶, DEMOULE Alexandre¹, BOUSSOUAR Samia¹, BRECHOT Nicolas¹, LEBRETON Guillaume¹, BARHOUM Pétra¹, LEFEVRE Lucie¹, HEKIMIAN Guillaume¹, LUYT Charles-Edouard¹, COMBES Alain¹, WINISZEWSKI Hadrien⁴, SCHMIDT Matthieu¹

¹Hôpital de la Pitié Salpêtrière, Paris, France; ²Centre Hospitalier Régional Universitaire de Nancy, Nancy, France; ³Hôpital Nord, Marseille, France;

⁴Centre Hospitalier Régional Universitaire de Besançon, Besançon, France;

⁵Hôpital Bichat, Paris, France; ⁶Hôpital Tenon, Paris, France