discrepancies included: adaptation to ideal body weight (0/9), protein target achievement (6/18), absence of complementary PN, lack of traceability of nutrition interruption (5/18), mismatch between either location or diameter of feeding tube (11/18), wrong or incomplete bedside EN identification (18/18). Major contributions resulted in weekly theoretical and practical training sessions, digital tools for ICU providers, updated and standardized procedures for nutrition support initiation and follow up in various patient profile. Second audit is taking place during February 2022.

**Conclusion:** Nutrition brings ICU caregivers in a continuous improvement program. It favours interprofessional interactions for direct patients benefit and proved importance and performance of multidisciplinary approach for quality improvement. Preliminary data issued from second audit are encouraging but sustaining efforts are required for long lasting results. Other areas of ICU management may be eligible according to the same model.

**Reference 1:** D. Hurel, J. Y. Lefrant, N.J. Cano, C. Ichai, J. C. Preiser, F. Tamion. Nutrition artificielle en réanimation. Réanimation (2014) 23:332-350.

**Reference 2:** P. Singer, A.R. Blaser, M.M. Berger, W. Alhazzani, P.C. Calder, M. Casaer, M. Hiesmayr, K. Mayer, J.C. Montejo, C. Pichard, J.-C. Preiser, A.R.H. van Zanten, S. Oczkowski, W. Szczeklik, S.C. Bischoff. ESPEN guideline on clinical nutrition in the intensive care.

**Compliance with ethics regulations:** N/A.

## FC-012

### Assessment of nutritional support in a medical ICU

PERRIN Clémence¹, CIDERON Cédrick¹, LABRO Guylaine¹, DUREAU Anne
Florence¹, KUTEIFAN Khaldoun¹

¹GHRMSA, Mulhouse, France

**Correspondence:** Clémence PERRIN (clemenceperrin@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-012

**Rationale:** According to the recommendations, for all patients admitted to intensive care and likely to stay longer than 48 h nutrition must be quickly introduced. Lack of access to indirect calorimetry requires calculating the necessary nutritional intake according to the weight and the duration of hospitalization in ICU. Our objective is to assess caloric intake (nutritional and non-nutritional) in our medical intensive care unit.

**Patients and methods/Materials and methods:** This study is descriptive and retrospective. All patients admitted between July 1 and September 30, 2021 and hospitalized more than 3 days, were included. We collected daily nutritional and non-nutritional caloric intake during the whole hospitalization. The weight used for calculation was the one measured at the admission (BMI < 30 kg/m²) or the adjusted weight (BMI ≥ 30 kg/m²).

**Results:** 180 patients were admitted and 140 were included. The average age was 59.7 years (± 12), 61% were male. The average of SOFA score was 7.8 (± 4.3) and the average of SAPS II score was 45 (± 19.4). The average length of ICU stay was 8.1 days (± 5.9) and the mortality rate was 23.8%. At 48 h, 62 patients (44.3%) received nutrition. Among these patients, 49 received oral nutrition and 13 received enteral artificial nutrition. None of them received a parenteral artificial nutrition. From 140 patients, excluding 49 patients with an unquantifiable oral diet, the average caloric intake was 5.9 kcal/kg/day (± 2.8) for 91 patients. This caloric intake was distributed as follows: 49% from glucose solutions, 26.4% from lipids contained in propofol, 25.1% from artificial nutrition. At 7 days, 54 patients still hospitalized in ICU and 39 patients (72%) received an enteral nutrition. The caloric intake was 18.4 (± 7.4) kcal/kg/day.

**Discussion:** At 48 h, most of patients fed received a standard oral nutrition with an unknown number of calories ingested. During the first 3 days, if patients did not eat in the standard way, they had little or no nutritional support. Most of the calories ingested during the first 3 days of resuscitation are provided by therapies such as propofol and glucose. These therapies are administered either for sedation, or as a carrier or solvent, or for hydration, but not for nutritional purpose. The caloric intake targets were not reached according to the

recommendations in force. However, the mortality rate is average according to the SAPS score.

**Conclusion:** In our department, patients caloric intake was lower than recommended. Many of caloric intake was brought by non-nutritional caloric intake in acute phase.

**Reference 1:** Guidelines for Nutrition Support in Critically Ill Patient, Réanimation (2014) 23:332-350.

**Reference 2:** ESPEN guideline on clinical nutrition in the intensive care unit. Singer P, et al. Clin Nutr. 2019.

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

<figure><img src="image_44.png" /><figcaption>Daily caloric intake</figcaption></figure>

## FC-013

### Obese tool box evaluation

MAYENCO CARDENAL Nicolas¹, SZTRYMF Benjamin¹

¹Hôpital Antoine Béclère, Clamart, France

**Correspondence:** Nicolas MAYENCO CARDENAL (nmayencocardenal@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-013

**Rationale:** Obese patients are more and more frequent in the Intensive Care Units (ICU). This group of patients has unique pathophysiological features involving all organs. They raise special challenges about their management in ICUs. Aspects like mechanical ventilation, artificial nutrition, thromboprophylaxis or antibiotic dosing can be difficult. Guidelines and clinical data are available about obese patient care, but their application in every day's practice is uncertain. In the ICU in Antoine Beclère's hospital (Clamart), we have created a clinical decision support system that brings the existing guidelines about those four features to the physicians in a friendly-user interface. In this study we have assessed the impact of this support system on the physician's prescriptions.

**Patients and methods/Materials and methods:** In this retrospective study we have collected data about prescriptions and outcomes of obese patients during two periods, before and after the support system was made available. The endpoint was the number of prescriptions following the existing guidelines. We have also assessed the physician's satisfaction through a survey.

**Results:** Over a 3-year period, 39 patients have been included (23 before and 15 after the availability of the support system). They represent 500 days of ICU admission. Patients were comparable in the two groups. They had a mean age of 62.35 years, mean BMI of 39.13 kg/m² and SOFA score of 4.71. For patients in the second group, prescribed tidal volume was lower (6.57 ml/kg of ideal body weight vs. 7.03 ml/kg; p < 0.001). Less overfeeding was observed (26.64 kcal/kg of adjusted body weight vs. 28.32 kcal/kg; p = 0.03) without improving protein intake. Thromboprophylaxis prescriptions were more frequently in accordance with guidelines (74.8% vs 57.7%; p = 0.001). No difference was observed in antibiotic prescription or plasmatic concentration measurements. Surveyed physicians considered thromboprophylaxis and nutrition advice the most useful. They have used the support system several times when caring for an obese patient.
**Conclusion:** In our UCI, the availability of a computer clinical decision support system for prescription in obese patients brought physician's prescriptions closer to existing guidelines. Physicians thought the system was useful and user-friendly, especially for nutrition and thromboprophylaxis aspects.

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

## FC-014

### Non thyroidal illness syndrome in critically ill patients with SARS-CoV-2 infection

TURKI Olfa¹, SMAOUI Ayoub¹, CHTARA Kamilia¹, BRADAI Sabrine¹, BAHLOUL Mabrouk¹, BOUAZIZ Mounir¹

¹CHU Habib Bourguiba Sfax, Sfax, Tunisie

**Correspondence:** Olfa TURKI (olfa.turki.rea@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-014

**Rationale:** "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (FT3). The relationship between thyroid hormones levels and mortality is well known. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our purpose was to investigate the incidence of this endocrinal perturbation in COVID-19 infected patients and the relationship between thyroid function and severity of this infection.

**Patients and methods/Materials and methods:** We prospectively considered patients admitted in SARS-CoV2 ICU Unit within 2 months. The SARS-CoV-2 infection was confirmed in all patients by PCR testing. Blood samples were collected within 48 h of admission and prior to any treatment that may affect thyroid hormone, on the third day and on the seventh day of ICU stay. NTIS was defined as serum FT3 levels <2 pg/ml, FT4 and TSH levels within or below the normal reference ranges.

**Results:** We enrolled 57 patients. The average age was 64 ± 11.7 years with a sex ratio at 1.28. The average ICU stay was 7 days (2-31 days). Only 16 (28%) patients had normal thyroid hormone levels while 41 (72%) had developed NTIS. Thirty-one patients (54.4%) developed NTIS on admission. On the third day, 42% of ICU patients developed NTIS and they were 14 of 21 patients (66.6%) who developed this thyroid perturbation on the seventh day. Overall, troponin, cortisol-level, severe ARDS, ventilation and septic shock predicted disease severity and death. Patients with NTIS had worse symptomatology, worse profiles of inflammatory and tissue injury markers. But neither the NTIS, nor the Rt3 level predicted poor issue in our cohort.

**Conclusion:** NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. Thus, understanding the pathophysiology and evolution of NTIS is crucial even though it rarely require specific treatment. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients and it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase.

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

## FC-015

### Diabetic ketoacidosis in intensive care unit: epidemiological, clinical and evolutionary features

GUISSOUMA Jihene¹,², ALLOUCHE Hend¹,², BEN ALI Hana², ABDOU Ghada¹,², TRABELSI Insaf¹,², GHADHOUNE Hatem¹,²

¹Faculté de médecine de Tunis, Bizerte, Tunisie; ²Université Tunis El Manar, Tunis, Tunisie

**Correspondence:** Jihene GUISSOUMA (guissouma.jihene@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-015

**Rationale:** Diabetic ketoacidosis (DKA) is a serious metabolic complication of diabetes. It is a potentially life-threatening condition and usually requires intensive care unit (ICU) hospitalization. We aimed to describe the epidemiological, clinical and evolutionary features of DKA managed in ICU.

**Patients and methods/Materials and methods:** A 7-year retrospective, descriptive and longitudinal single-center study including all patients admitted to a 6-bed ICU for DKA. Statistical analysis was performed using SPSS 23.

**Results:** Sixty-two patients were enrolled. The mean age was 36±16 years with a female predominance (sex ratio 0.55). The most common type of diabetes was type 1 (60%), followed by type2 (21%) and inaugural diabetes (19%). The mean duration of diabetes was 9±8 years. The most common comorbidities were hypertension (28%) and chronic renal failure (23%). The mean duration of symptoms before hospitalization was 20±8 h. The most common were asthenia (92%) and nausea, vomiting with abdominal pain (69%). Confusion or less alertness and increase in polydipsia and polyuria were noted in 37% and 32% of cases respectively. On admission, 47% of patients had dehydration, 22% shock and 16% were comatose. Fifty percent had acute kidney injury. The mean capillary blood glucose measurement was 5.8±1.6 g. The average levels of pH and bicarbonates were 7.12±0.14 and 6±4 respectively. DKA was severe, moderate and mild in 84%, 11% and 5% of cases respectively. The mean IGS II and APACHE II were 22±18 and 13±10 respectively. Infection was the predominant precipitating factor (50%) followed by non-compliance to treatment (30%). The symptoms regressed after restoration of fluid deficits, electrolyte replacement and continuous intravenous insulin therapy. Vasopressors and mechanical ventilation (MV) were imperative in 19% and 11% of cases respectively. Only 8% required hemodialysis. DKA resolved within 20 h (extremes 5 and 33 h). The mean length of stay in ICU was 5±3 days and mortality rate was 13%. In univariate analysis: IGS II (p < 10⁻³), APACHE II (p < 10⁻³), GCS (p < 10⁻³), shock on admission (p = 0.01) and MV (p < 10⁻³) were all predictors of mortality. Besides APACHE II (p = 0.03) and MV (p = 0.009) were the two independent prognostic factors in multivariate analysis.

**Conclusion:** DKA occurs mainly in type1 diabetes. Although it was severe in most cases, it resolved within a few hours. However, mortality was relatively high in this study and was significantly associated to high APACHE II and need of mechanical ventilation. Adequate follow up and better diabetes education are necessary to avoid this serious metabolic complication.

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

## FC-016

### Early-onset acute kidney injury in COVID-19 critically ill patients, a monocentric retrospective analysis (SARCOV-AKI)

RUAULT Alice¹, DUPUIS Claire¹, EVRARD Bertrand¹, CALVET Laure¹, THOUY François¹, GRAPIN Kévin¹, GUIDO Olivia¹, HERNANDEZ Gilles¹, DOPEUX Loïc¹, MASCLE Olivier¹, BOUZGARROU Radhia¹, ADDA Mireille¹, BONNET Benjamin¹, SAPIN Vincent¹, PHILIPPONNET Carole¹, SOUWEINE Bertrand¹
¹CHU Gabriel Montpied, CHU Clermont Ferrand, Clermont Ferrand, France

**Correspondence:** Claire DUPUIS (dupuis1@chu-clermontferrand.fr)

*Annals of Intensive Care* 2022, **12**(1):FC-016

**Rationale:** The aim of the study was to assess the epidemiology of early-onset Acute kidney injury (EO-AKI) in COVID-19 pneumonia patients admitted to ICU.

**Patients and Methods/Materials and Methods:** This study, approved by the ethical committee of the French Intensive Care Society (CE-SRLF20-20), was a prospective single center study, performed in the medical ICU of the university hospital of Clermont-Ferrand France. All consecutive adult patients aged ≥ 18 years, admitted between March 20th, 2020 and August 31th, 2021 for COVID-19 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and ICU length of stay (LOS) ≤ 72 h were excluded. Baseline patients' characteristics, variables recorded regarding ICU admission, organ support and main laboratory features during ICU stay and outcomes were collected. Biological testing on admission included mHLADR, plasma cytokines (IL-6, CXCL8, IFN-alpha, IL-10 and IL1Ra); and AKI urinary (L-FABP, PODXL, TIMP-2IGFP7) and serum biomarkers (s-Rage, SuPAR). AKI was defined according to the KDIGO classification and classified according to the timing of their recovery as transient,
persistent and acute kidney disease (AKD) (ref 1). EO-AKI was defined as the first episode of AKI occurring within 7 days of ICU admission. MAKE (Major Adverse Kidney Events) including death or new RRT or no renal recovery during the first 90 days after ICU admission were recorded. Uni and multivariate analyses were performed to determine factors associated with the presence of AKI and predictors of MAKE.

**Results:** 264 patients were included in this study. Patients' characteristics are described in Table 1. EO-AKI occurred in 87 patients (33%), including 43, 17 and 27 patients with EO-AKI stage 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 31 (35.6%), 14 (16%) and 42 (48.2%) patients, respectively. The median ICU LOS was 8 days [5;13]. The ICU mortality was 30.4% (N=80), and increased with EO-AKI occurrence and severity: 15.8%, 46.5%, 64.7% and 77.8% in patients without AKI, and with EO-AKI stage 1, 2 or 3, respectively (P < 0.001). ICU mortality in patients with transient, persistent AKI and AKD were 50%, 50% and 77.4%, respectively and was significantly lower in patients with EO-AKI not developing AKD than in patients developing (P < 0.01).

**Conclusion:** In this single center study, EO-AKI developed in 30% of COVID patients admitted to ICU. EO-AKI stage 3 or AKD was associated with a fatal outcome in ≥ 77% of cases. Preventing EO-AKI occurrence and achieving EO-AKI recovery is of paramount importance in COVID-19 patients.

**Reference 1:** Darmon, ICM, 2018.

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

<table><thead><tr><th>Variables (Median (IQR)/ N (%))</th><th>All</th><th>No AKI</th><th>AKI</th><th>Pvalue</th></tr></thead><tbody><tr><td>Number of patients</td><td>264</td><td>177</td><td>87</td><td></td></tr><tr><td>Delay before ICU admission</td><td>9 [6.6; 11.6]</td><td>10 [8; 12]</td><td>9 [5; 11]</td><td>&lt;0.01</td></tr><tr><td>Age</td><td>68.8 [60.6; 75]</td><td>67 [59.5; 73.5]</td><td>73 [65.8; 76.4]</td><td>&lt;0.01</td></tr><tr><td>Sex (male)</td><td>186 (70.4)</td><td>125 (70.6)</td><td>61 (70.1)</td><td>0.93</td></tr><tr><td>BMI &gt; 30</td><td>116 (44)</td><td>75 (42.4)</td><td>41 (47.1)</td><td>0.46</td></tr><tr><td>Chronic cardiovascular disease</td><td>49 (18.6)</td><td>27 (15.3)</td><td>22 (25.3)</td><td>0.05</td></tr><tr><td>Chronic respiratory disease</td><td>15 (5.6)</td><td>14 (7.9)</td><td>1 (1.1)</td><td>0.03</td></tr><tr><td>Chronic renal disease</td><td>9 (3.4)</td><td>1 (0.6)</td><td>8 (9.2)</td><td>&lt;0.01</td></tr><tr><td>Chronic liver disease</td><td>7 (2.6)</td><td>4 (2.3)</td><td>3 (3.4)</td><td>0.57</td></tr><tr><td>Immunosuppression</td><td>41 (15.6)</td><td>22 (12.4)</td><td>19 (21.8)</td><td>0.05</td></tr><tr><td>Diabetes mellitus</td><td>42 (16)</td><td>23 (13)</td><td>19 (21.8)</td><td>0.06</td></tr><tr><td>Charlson score</td><td>2 [0; 3]</td><td>1 [0; 3]</td><td>3 [1; 4]</td><td>&lt;0.01</td></tr><tr><td>On admission</td><td></td><td></td><td></td><td></td></tr><tr><td>SAPS</td><td>36 [29; 45]</td><td>34 [28; 41]</td><td>42 [34; 50]</td><td>&lt;0.01</td></tr><tr><td>SOFA</td><td>4 [3; 6]</td><td>4 [3; 5]</td><td>5 [4; 9]</td><td>&lt;0.01</td></tr><tr><td>PAO2/FiO2</td><td>88 [67; 128.4]</td><td>91.5 [70.9; 128.2]</td><td>84 [65; 130]</td><td>0.39</td></tr><tr><td>Invasive mechanical ventilation</td><td>34 (12.8)</td><td>9 (5.1)</td><td>25 (28.7)</td><td>&lt;0.01</td></tr><tr><td>Vasopressors</td><td>28 (11.4)</td><td>3 (1.8)</td><td>25 (30.5)</td><td>&lt;0.01</td></tr><tr><td>Steroids</td><td>212 (84.2)</td><td>143 (85.1)</td><td>69 (82.1)</td><td>0.54</td></tr><tr><td>Tocilizumab</td><td>29 (11.6)</td><td>24 (14.3)</td><td>5 (6)</td><td>0.05</td></tr><tr><td>Laboratory features</td><td></td><td></td><td></td><td></td></tr><tr><td>HLA DR/II-6, CXCL8, INF-alpha -II10, IIIRa*</td><td></td><td></td><td></td><td></td></tr><tr><td>L-FABP, PODXL, TIMP-2IGFP7*</td><td></td><td></td><td></td><td></td></tr><tr><td>s-RAGE, SuPAR*</td><td></td><td></td><td></td><td></td></tr><tr><td>During ICU stay</td><td></td><td></td><td></td><td></td></tr><tr><td>Vasopressors</td><td>73 (29)</td><td>22 (13.1)</td><td>51 (60.7)</td><td>&lt;0.01</td></tr><tr><td>Invasive mechanical ventilation</td><td>89 (33.8)</td><td>31 (17.5)</td><td>58 (66.7)</td><td>&lt;0.01</td></tr><tr><td>ECMO</td><td>3 (1.2)</td><td>2 (1.2)</td><td>1 (1.2)</td><td>1.00</td></tr><tr><td>Limitation of care</td><td>30 (12)</td><td>14 (8.3)</td><td>16 (19)</td><td>0.01</td></tr><tr><td>Renal Replacement Therapy</td><td>31 (12.4)</td><td>8 (4.8)</td><td>23 (27.4)</td><td>&lt;0.01</td></tr><tr><td>Kidney function</td><td></td><td></td><td></td><td></td></tr><tr><td>During the 1st 7 days after ICU admission</td><td></td><td></td><td></td><td></td></tr><tr><td>KDIGO 0</td><td>177 (67)</td><td>177 (100)</td><td>0 (0)</td><td>&lt;0.01</td></tr><tr><td>KDIGO 1</td><td>43 (16.2)</td><td>0 (0)</td><td>43 (49.4)</td><td>-</td></tr><tr><td>KDIGO 2</td><td>17 (6.4)</td><td>0 (0)</td><td>17 (19.5)</td><td>-</td></tr><tr><td>KDIGO 3</td><td>27 (10.2)</td><td>0 (0)</td><td>27 (31)</td><td>-</td></tr><tr><td>Recovery of AKI</td><td></td><td>177 (100)</td><td>0 (0)</td><td>&lt;0.01</td></tr><tr><td>Transient</td><td>31 (35.6)</td><td>0 (0)</td><td>42 (48.3)</td><td>-</td></tr><tr><td>Persistent</td><td>14 (16)</td><td>0 (0)</td><td>14 (16.1)</td><td>-</td></tr><tr><td>Acute Kidney Disease</td><td>42 (48.2)</td><td>0 (0)</td><td>31 (35.6)</td><td>-</td></tr><tr><td>Outcomes</td><td></td><td></td><td></td><td></td></tr><tr><td>ICU LOS</td><td>8 [5; 13]</td><td>6 [4; 9]</td><td>11 [7; 18]</td><td>&lt;0.01</td></tr><tr><td>Hospital LOS</td><td>14 [10; 22]</td><td>14 [10; 22]</td><td>15 [9; 25]</td><td>0.24</td></tr><tr><td>ICU Death</td><td>80 (30.4)</td><td>28 (15.8)</td><td>52 (59.8)</td><td>&lt;0.01</td></tr></tbody><tfoot><tr><td colspan="5">*Results not available at the time of abstract submission</td></tr></tfoot></table>

Characteristics and comparisons of COVID-19 ICU patients with and without Early Onset AKI

### FC-017

#### Acute kidney injury in critically ill COVID-19 patients: clinical features

BEN MILED Cherifa¹, SOUILHI Jawhar¹, DRIDI Amira¹, NAIMI Skander¹, FITOUHI Nizar¹, QUERGHI Sonia¹, MESTIRI Tahar¹

¹Hôpital Abderrahman Mami- Ariana, Tunis, Tunisie

**Correspondence:** Cherifa BEN MILED (cherifa.bm@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-017

**Rationale:** Acute kidney injury is a frequent complication in critically ill COVID-19 patients and is associated with severe outcomes. This study aims to describe the clinical characteristics of this Acute kidney injury and to assess its incidence.

**Patients and methods/Materials and methods:** A retrospective and descriptive study was conducted including all covid-19 patients admitted in our ICU who presented an acute kidney injury defined by the KDIGO criteria, during a 6-month period. We collected demographic and anthropometric parameters, underlying comorbidities, nephrotoxic medicine prescription, clinical features of the acute renal failure with the KDIGO grade, mechanical ventilation characteristics, requirement of kidney replacement therapy and outcomes. Data analysis was performed using SPSS 28.0 software.

**Results:** During our study period, 147 patients were admitted in our ICU. AKI incidence was 52.2% (71 patients out of 147). According to KDIGO criteria, 16.9% were staged KDIGO 1, 35.2% KDIGO 2 and 47.8% KDIGO 3. The mean age was 61 years, ranged from 27 to 93 years. 38% were considered as elderly (> 65 years old). The main comorbidities were arterial hypertension (66%), diabetes mellitus (54.9%), atrial fibrillation (28.1%) and obesity (22.5%). Acute kidney injury occurred mainly around the 6th day of ICU and resolved after 7 days. For 18.3% of the patients, the AKI was transient, defined as a return to the baseline serum creatinine levels or its decrease of 50% or more within the 72 h after the onset of the AKI. Most of the patients were intubated (87%) and 96% were ventilated with a high PEEP (> 12 cmH₂O). AKI occurred after the intubation in 73.2% of the cases, 2 days after on average. In 25.4% of the cases, AKI was associated with septic shock. Prescription of nephrotoxic drugs was identified in 77.4% of cases. 12 patients (16.9%) required a replacement kidney therapy, but only 2 of them had a dialysis session, due to the lack of dialysis facilities in our ICU. The 28-day mortality rate was 84,5%.

**Conclusion:** The incidence of Acute kidney injury in our ICU was 52.2% and occurred mainly in elderly patients with underlying comorbidities. Most patients required a mechanical ventilation with high levels of PEEP. The 28-day mortality was 84,5%.

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

### FC-018

#### Clinical features and outcomes of Acute Kidney Injury in severe to critical COVID-19 patients

BOUGUEZZI Nabil¹, BEN SAIDA Imen¹,², TOUMI Radhouane¹,², MAATOUK Iyed¹, ZGHIDI Maroua¹, ZOUARI Hajer¹, MEDDEB Khaoula¹,², BOUSSARSAR Mohamed¹,²

¹Farhat Hached University Hospital, Sousse, Tunisie; ²Research Laboratory N° LR12SP09. Heart Failure. Farhat Hached University Hospital, Sousse, Tunisie

**Correspondence:** Nabil BOUGUEZZI (dr_nabil@live.fr)

Annals of Intensive Care 2022, **12**(1):FC-018

**Rationale:** Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by an emerged virus SARS-CoV-2. An alarming number of patients with SARS-CoV-2 infection especially severe cases have been reported to develop Acute Kidney Injury (AKI). Our study is aimed to investigate features, outcomes and risk factors for Acute Kidney Injury in Critically Ill COVID-19 patients.

**Patients and methods/Materials and methods:** It is a retrospective observational study conducted from March 2020 to October 2021, in a Medical ICU. Information regarding demographic, clinical characteristics and outcomes of Critically Ill COVID-19 patients was obtained from medical records. AKI was defined according to the Kidney Disease
Improving Global Outcomes (KDIGO) clinical practice Guideline. Multi-variate analysis was performed to evaluate risk factors for AKI.

**Results:** 442 critically ill COVID-19 patients were admitted to ICU during the study period. Median age, 64 [54–71] years; 279(63.1) were males. Hypertension, 197(44.6); diabetes mellitus, 187(42.3) and chronic kidney disease 36(8,1). Median SAPS II, 28 [22–35]. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. 215(48.6) patients required invasive mechanical ventilation (IMV) and 195(44) received a vasoactive drug. 209(47,2) developed AKI during hospitalization. Among the 209 patients with AKI, 31(14.8), 22(10.5) and 156(74.6) had stage 1, 2, and 3, respectively. AKI occurred within a median of 5[1–24] days of hospitalization. 37(21,0) patients received renal replacement therapy, with a total of 117 sessions. The causes of acute kidney injury can be divided into two categories, hypoxic acute tubular necrosis in 177(84) and type 1 cardiorenal syndrome in 31(14.8) patients. The mortality was significantly higher in AKI group compared to those without (54% vs 43%, p 0.01). The mortality rate was 6.6% (n=14), 3.8% (n=8), and 42% (n=89) among those with AKI stages 1, 2, and 3, respectively. On univariate analysis, the factors predicting AKI were mechanical ventilation(p=0.05), cardiogenic shock (p = 0.001), positive fluid balance (p = 0.000), vasopressors use (p = 0,019); Multivariate regression model identified the following factors as independently associated to AKI, cardiogenic shock, (OR, 2.59; 95% CI, [1.5–4.3]; p = 0.000); positive fluid balance, (OR, 1.76; 95% CI, [1.3–2.2]); p = 0.000).

**Conclusion:** AKI among patients with severe to critical COVID-19 was common. Several factors were shown to contribute to its occurrence. This complication was highly associated with mortality.

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

FC-019

**Incidence and risk factors of acute kidney injury in critical forms of COVID-19**

GUISSOUMA Jihene<sup>1,2</sup>, BEN ALI Hana<sup>2</sup>, TRABELSI Insaf<sup>1,2</sup>, ALLOUCHE Hend<sup>1,2</sup>, SAMET Mohamed<sup>2</sup>, BRAHMI Habib<sup>2</sup>, GHADHOUNE Hatem<sup>1,2</sup>

**Correspondence:** Jihene GUISSOUMA (guissouma.jihene@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-019

**Rationale:** Acute kidney injury (AKI) is a common metabolic complication in the COVID-19 particularly among critical forms. Besides the viral tropism the pathogenesis of AKI is likely multifactorial. We aimed to describe the epidemiological, clinical and biological features of patients admitted to intensive care unit (ICU) for critical forms of COVID-19 in order to deduce the risk factors of AKI.

**Patients and methods/Materials and methods:** A 16-month prospective analytic study (September 2020–December 2021) including all patients (without a chronic kidney failure history) admitted to ICU for critical forms of COVID-19. The patients were divided into two groups: -Group 1: patients who developed AKI during ICU stay. -Group 2: patients who have maintained normal kidney function. The KDIGO classification was adopted to stratify the AKI. The statistical analysis was performed using SPSS 23.

**Results:** Overall 140 patients were included. Twenty-three per cent developed AKI (33 cases in group 1 and 107 in group 2). The mean age was 58±13 with male predominance (sex ratio 1.2). The most common comorbidities were hypertension (64%) and diabetes (62%). The mean IGS II and APACHE II were 40±13 and 13±6 respectively. The mean base creatinine level was 79±22 mmol/l. The mean creatinine level at the onset of AKI was 295±201 mmol/l. According to the KDIGO criteria the group 1 patients were staged class I (4 cases), class II (11 cases) or class III (18 cases). The mean period for developing AKI was 8 days. Sepsis and hypotension were the two predominant precipitating factors of the AKI (45% and 33% of cases of group 1). Hemodialysis was indicated in 40% of cases. The AKI was irreversible in 72% of the cases. In univariate analysis, there were no significant differences between the two groups in gender, comorbidities, IGS II and ICU length of stay. However, age (p = 0.007), Apache II (p = 0.01) and septic shock (p < 10-3) were the main risk factors of AKI. Only septic

shock (p < 10-3) was an independent factor in multivariate analysis. Besides group 1 patients required more invasive ventilation (p = 0.001) and developed much more healthcare-associated infections (p < 10-3). Overall mortality rate was 69%. It was higher in group 1 (87%) compared to group 2 (63%) with a significant difference (p = 0.029).

**Conclusion:** The occurrence of AKI in critical forms of COVID-19 was frequent in our study and was associated to a higher mortality. Septic shock was the main risk factor of AKI. These results need to be confirmed by further larger studies.

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

FC-020

**Impact of dexamethasone and inhaled nitric oxide on severe acute kidney injury in critically ill patients with COVID-19**

BOBOT Mickaël<sup>1,2,7</sup>, TONON David<sup>5</sup>, PERES Noémie<sup>7</sup>, GUERVILLY Christophe<sup>2</sup>, LEFÉVRE Flora<sup>1</sup>, MAX Howard<sup>4</sup>, BOMMEL Youri<sup>4</sup>, VOLFF Maxime<sup>4</sup>, LEONE Marc<sup>5</sup>, LOPEZ Alexandre<sup>5</sup>, SIMEONE Pierre<sup>4</sup>, CARVELLI Julien<sup>6</sup>, HRAIECH Sami<sup>2</sup>, PAPAZIAN Laurent<sup>2</sup>, VELLY Lionel<sup>4</sup>, BOURRENNE Jérémy<sup>6</sup>, FOREL Jean-Marie<sup>2</sup>

**Correspondence:** Mickaël BOBOT (mickaël.bobot@ap-hm.fr)

Annals of Intensive Care 2022, **12**(1):FC-020

**Rationale:** Kidney failure is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe acute kidney injury (AKI) in critically ill COVID-19 patients.

**Patients and methods/Materials and methods:** In our cohort study, we retrospectively analysed a database of consecutive patients hospitalized in 6 ICUs for COVID-19. The incidence and severity of AKI were monitored during the entire ICU stay. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring mechanical ventilation were included.

**Results:** 164 patients were included in the final analysis, 97 (59.1%) displayed AKI, of which 39 (23.8%) severe stage 3 AKI and 21 (12.8%) requiring renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with Angiotensin Converting Enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307–13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044–1.241), p = 0.003) and iNO (OR: 5.694 (1.953–16.606), p = 0.001). Protective factors were prone positioning (OR: 0.234 (0.057–0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053–0.713), p = 0.014).

**Discussion:** Our study confirms the negative impact of AKI on mortality in COVID-19 in critically ill patients, and then the need to be careful about risk factors of AKI and to implement strategies to limit nephrotoxicity in the ICU. We report for the first time an independent association of iNO with both severe AKI and the need for RRT in severe COVID-19 patients. In our study, iNO did not improve mortality rates or the duration of MV and was associated with AKI and RRT. Thus, we suggest against its using in COVID-19-related ARDS, when other therapeutic strategies are available. Dexamethasone could decrease glomerular and interstitial inflammation observed in kidneys, decreasing the risk of AKI during severe COVID-19, which may have contributed

<footnote n="1"><sup>1</sup>Faculté de médecine de Tunis, Bizerte, Tunisie; <sup>2</sup>Université Tunis El Manar, Tunis, Tunisie</footnote>

<footnote n="1"><sup>1</sup>Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, AP-HM, Aix-Marseille Université, Marseille, France; <sup>2</sup>Service de Médecine Intensive Réanimation, Hôpital Nord, AP-HM, Aix-Marseille Université, Marseille, France; <sup>3</sup>Département d'Anesthésie Réanimation, Hôpital de la Conception, AP-HM, Aix-Marseille Université, Marseille, France; <sup>4</sup>Département d'Anesthésie Réanimation, Hôpital de la Timone, AP-HM, Aix-Marseille Université, Marseille, France; <sup>5</sup>Service d'Anesthésie Réanimation, Hôpital Nord, AP-HM, Aix-Marseille Université, Marseille, France; <sup>6</sup>Service de Réanimation et Surveillance Continue, Hôpital de la Timone, AP-HM, Aix-Marseille Université, Marseille, France; <sup>7</sup>C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France</footnote>
to a decrease in the AKI rate between the first and the second wave of COVID pandemics.

**Conclusion:** Dexamethasone was associated with a prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19; iNO should be used with caution in COVID-19 related ARDS.

**Reference 1:** Orieux A et al. Impact of dexamethasone use to prevent from severe COVID-19-induced acute kidney injury. Crit Care Lond Engl. 2021 Jul 16;25(1):249.

**Reference 2:** Ruan SY et al. Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. Crit Care. 2015 Dec;19(1):137.

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

<figure><img src="image_45.png" /><figcaption>Figure 1: Flow chart of the study AKI: Acute Kidney Injury, ESRD: End-stage renal disease, ICU: Intensive Care Unit, RRT: Renal replacement therapy</figcaption></figure>

FC-021

Is hyponatremia associated with poor outcome in critically ill COVID-19 patients?

SDIRI Ines¹, JARRAYA Fatma¹, RACHDI Emna¹, JAMOUSSI Amira¹, AYED Samia¹, BEN KHELIL Jalila¹

¹H'ôpital Abderrahmane Mami, Ariana, Tunisie

**Correspondence:** Fatma JARRAYA (fatma.jarraya8@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-021

**Rationale:** Patients with COVID-19 have multiple clinical conditions that may cause electrolyte imbalances. Hyponatremia is a prevalent metabolic disorder that could be involved with adverse outcomes in critically ill COVID-19 patients. The aim of this study was to describe the impact of hyponatremia on outcomes of COVID-19 patients, including mortality.

**Patients and methods/Materials and methods:** This was retrospective observational cohort study included all consecutive COVID-19 patients admitted to the intensive care unit from March 2020 to September 2021. All COVID-19 patients in whom serum sodium was measured at admission were included. Patients were divided into two groups: GI patients without hyponatremia; G II patients with hyponatremia (serum sodium < 135 mmol/L). Outcomes such as mortality, need for invasive mechanical ventilation (IMV), sepsis, and acute kidney injury (AKI) were assessed.

**Results:** During the study period, 520 patients were collected and divided into two groups (G I n = 394; G II n = 126). The median age was 61 years [52-69] with a gender ratio (H/F) of 1.65. The mean of the SAPS II score was 27.9 ± 10. The most common comorbidities were hypertension (38.2%) and diabetes (36.5%). The mean body mass index was 30.79. The incidence of hyponatremia at admission was 23.4% and it was generally mild (n = 100; 79%). Demographic characteristics were similar between the two groups. Transit disorders particularly emesis prior to admission were more common in the hyponatremia group (21% vs 13.3%; p = 0.055). Pulmonary bacterial co-infection occurred more in GII (14.3% vs 7.8%; p = 0.030). Hyponatremic patients had

higher ferritin levels (1500 µg/l [205-1500] vs 401 µg/l [250-1030]; p = 0.05). Hyponatremia was not associated with increased risk of AKI (48.3% vs 41.8%; p = 0.403) or sepsis (35.8% vs 26.1%; p = 0.140). IMV and death were not significantly more frequent in hyponatremic patients compared with normonatremic patients (61.1% vs 55.3%; p = 0.257; 59.5% vs 52.3%; p = 0.156, respectively).

**Conclusion:** Mild hyponatremia at admission is common but is not associated with poor outcomes in patients with critical COVID-19.

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

FC-022

Hypokalemia in critically ill COVID-19 patients

HADDED Amina¹, ALILA Ilef¹, KHARRAT Sana¹, BRADAI Sabrine¹, BAHLOUL Mabrouk¹, BOUAZIZ Mounir¹

¹hôpital Habib Bourguiba Sfax, Sfax, Tunisie

**Correspondence:** Ilef ALILA (ilefalila1323@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-022

**Rationale:** Patients with COVID-19 have multiple clinical conditions that can cause electrolyte imbalances, including hypokalemia. This study aimed to estimate the prevalence and outcomes of hypokalemia in patients with COVID-19 admitted to intensive care units (ICU).

**Patients and methods/Materials and methods:** We conducted a retrospective study in an ICU over a period of 16 months [September 2020–December 2021] including patients with SARS-COV2 infection.

**Results:** During the study period, 586 patients were included with a mean age of 59.5 ± 14.7 years and a sex ratio of 1.6. The median SAPS-II and SOFA score were respectively of 29 ± 14.8 and 4 ± 2.6. Most patients had comorbidities, including hypertension (36%), obesity (32.1%) and diabetes mellitus (36.2%). A total of 52 patients (9%) had hypokalemia. Severe ARDS was observed in 63% of the first group versus 72% of the second group (p = 0.109). No significant difference was found in terms of use of NIV (59.6% versus 65%; p = 0.4) and invasive mechanical ventilation (75% versus 72.8%; p = 0.73). The mean duration of mechanical ventilation was longer in the hypokalemia group: 7.7 days versus 4.4 days in the second group (p < 0.001). Similarly, the average length of stay in the intensive care unit was higher in the first group than in the second group: 9.3 days versus 7.3 days (p = 0.021). Mortality was higher in patients with hypokalemia but the difference was not significant 59.6% versus 47.9% (p = 0.108). The use of diuretics and corticosteroids was comparable between two groups.

**Conclusion:** Hypokalemia in patients with covid-19 admitted to the ICU is associated with prolonged duration of mechanical ventilation and ICU stay but does not influence mortality.

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

FC-023

Hyponatremia in critically ill COVID-19 patients

HADDED Amina¹, KHARRAT Sana¹, ALILA Ilef¹, AMMAR Rania¹, BEN KHALIFA Atraa¹, BAHLOUL Mabrouk¹, BOUAZIZ Mounir¹

¹hôpital Habib Bourguiba Sfax, Sfax, Tunisie **Correspondence:** Ilef ALILA (ilefalila1323@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-023

**Rationale:** Dysnatremia is common in patients hospitalized in the intensive care units, often worsening the prognosis of lung disease and severe illness. The main objective of this study is to assess the prevalence of hyponatremia in patients with COVID-19 admitted to the ICU and to evaluate the impact of hyponatremia on severity and outcomes in COVID-19 patients.

**Patients and Methods/Materials and methods:** We conducted a retrospective study including all COVID-19 patients hospitalized in an intensive care unit during a period of 16 months. We compared two groups of patients: the first (G1) group of patients with hyponatremia and the second (G2) group of patients with normal natremia.

**Results:** A total of 126 patients (21.5%) developed hyponatremia in our study. There were more male patients in hyponatremia group 91 (72.2%) versus 269 (58.5%) (p = 0.005). The average age was comparable between the two groups (59.1 year in G1 versus 60.9 year in G2;
p=0.24). Pulmonary lesions on chest CT performed during hospitalization were significantly more extensive in the first group (p=0.023). The prevalence of renal failure was higher in the hyponatremia group with a significant difference (49.2% versus 38.5%; p=0.03). Regarding the use of invasive ventilation, the two groups were comparable (p=0.96) and there was no significant difference in terms of duration of mechanical ventilation (p=0.6). Hyponatremia was a risk factor for prolonged stay in intensive care units 8.9 days i versus 7.1 days (p=0.03). Mortality was higher in the hyponatremia group but the difference was not significant 52.4% versus 48% (p=0.38).

**Conclusion:** Hyponatremia had poor outcome in our study. It was associated with more extensive parenchymal damage, an increased prevalence of renal failure and a longer stay in ICU.

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

FC-024

Incidence, characteristics, and long-term outcomes of new-onset atrial fibrillation in a medical intensive care unit

DOYEN Denis¹, LABBAOUI Mohamed¹, SQUARA Fabien¹, HYVERNAT Hervé¹, BERNARDIN Gilles¹, JOZWIAK Mathieu¹, DELLAMONICA Jean¹
¹Centre Hospitalier Universitaire de Nice, Nice, France

**Correspondence:** Denis DOYEN (doyen.d@chu-nice.fr)

*Annals of Intensive Care* 2022, **12**(1):FC-024

**Rationale:** Atrial fibrillation is the most common acquired arrhythmia in the intensive care unit (ICU) and is associated with increased morbidity and mortality. However, patient characteristics, particularly echocardiographic features of new-onset atrial fibrillation (New-AF), are scarce. In addition, little is known about the long-term outcomes of patients with New-AF.

**Patients and methods/Materials and methods:** We conducted a single-center prospective observational study in a medical intensive care unit. All consecutive patients admitted were included. Continuous electrocardiogram monitoring was checked daily for New-AF. Patients were divided into the following groups: New-AF patients, patients with a history of AF, and No-AF patients when no AF was previously diagnosed or documented during hospitalization. Transthoracic echocardiography, electrocardiogram, and blood analysis were performed at admission and in case of New-AF. The following outcomes were collected 6 months after ICU discharge: re-hospitalizations, strokes or other thromboembolism, and mortality.

**Results:** Over a 5-month period, 110 patients were included: 21% (23) New-AF patients, 13% (14) with a history of AF, and 66% (73) No-AF patients. New-AF patients were predominantly male (61%), were significantly older (70 versus 58 years, p < 0.01), and had more comorbidities than patients without AF. Patients with New-AF had higher levels of high-sensitivity troponin I, B-type natriuretic peptide and protein C reactive than No-AF patients (respectively 73 vs 18 ng/L, 408 vs 55 pg/L, and 114 vs 32 mg/L; p < 0.01). At the time of AF onset in the New-AF group, kalemia was lower than at admission (3.5 vs 4.4 mmol/L, p < 0.01). In New-AF patients, TTE showed more left ventricular systolic and diastolic dysfunction, right ventricular systolic dysfunction, pulmonary hypertension and more enlarged left atrial and left ventricular index volumes than in No-AF patients. New-AF patients had more acute pulmonary edema and cardiogenic shock than No-AF patients (respectively 48% versus 6% and 26% versus 4%; p < 0.01). New-AF was significantly associated with greater use of inotropic or vasopressor drugs, mechanical ventilation, and renal replacement, and had higher in-hospital mortality (44% vs 12%, p < 0.01) than No-AF patients. During follow-up, there was no difference in re-hospitalizations, thromboembolism, or mortality between all groups (42% versus 36%, 8% versus 2%, and 15% versus 10%, respectively, between patients with AF and No-AF patients; p > 0.05).

**Conclusion:** In a medical intensive care unit, the incidence of New-AF was 21%. New-AF patients had more echocardiographic abnormalities, organ failure, and higher in-hospital mortality than No-AF patients. No difference in outcomes was observed 6 months after ICU discharge between all groups.

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

FC-025

Lactate/Pyruvate ratio as a marker of tissue hypoxia in cardiac surgery

KOLSI Hichem¹, JAWADI Wael¹, KAMMOUN Anas¹, SELLAMI Bouthaina¹, FOURATI Mahdi¹, KETATA Salma¹, CHEIKHROUHOU Hichem¹, TRIKI Zied¹, ZOUARI Dhouha¹, JALLOULI Dana¹, NAIFAR Manel¹, AYADI Fatma¹
¹Centre hospitalo-universitaire Habib Bourguiba, Sfax, Sfax, Tunisie

**Correspondence:** Hichem KOLSI (hichem.kolsi17@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-025

**Rationale:** Cardiac surgery with cardiopulmonary bypass (CPB) has a high risk to induce tissue hypoperfusion and oxygenation impairment. This can lead to complications and organ failure. Blood lactate elevation is a classic marker of anaerobic metabolism and hypoperfusion. But lactate increasing can result from aerobic glycolysis acceleration or impaired clearance. Lactate/Pyruvate ratio (L/P) was studied in septic shock and seems to have a better specificity of anaerobic metabolism. The aim of this study is to assess whether the L/P is associated with adverse outcome after cardiac surgery.

**Patients and methods/Materials and methods:** This is a prospective, observational, monocentric clinical study being performed. We included 26 patients over 18 years undergoing cardiac surgery with CPB, from October 2021. We have an objective of 80 patients. We did not include patients with severe hepatocellular impairment, preoperative hemodynamic instability, or severe renal failure. We have excluded patients who have died during surgery, patients who can only leave the operating room with a circulatory assistance technique. Arterial blood lactate and pyruvate were collected, lactate in sodium fluoride tube, pyruvate in perchloric acid tube. The samples were transported at 4 °C, and then analyzed by enzymatic colorimetric reaction for lactate and spectrophotometry for pyruvate. We have analyzed receiving operating curve (ROC) of L/P for complications occurring. We tested then the correlation of the variables with prognosis interest to L/P by Spearman test.

**Results:** Complications rate was 46.2%. Mortality rate was 26.9%. Mean age was 61.96 ± 9.34. Median Euroscore II was 1.5 (1.09; 2.13). 23 patients have lactate level > 2 mmol/l. Only 18 (78.26%) of these patients have L/P > 16 (a cutoff used previously in septic shock). L/P was predictive of complications with area under ROC 0.857, higher than area under ROC of lactate which was 0.777. Best threshold was 20.34. LP median was significantly higher in group with complications and in non survivor group. We found that L/P is correlated to Euroscore II, duration of CPB and SAPSII at one and two days postoperative.

**Conclusion:** We conclude that L/P is associated with poor outcome after cardiac surgery. L/P is more efficient than lactate to predict postoperative complications. L/P could be used as an additional tool to identify patients with high risk of adverse outcome after cardiac surgery. Nevertheless, these results should be confirmed in larger multicentric studies. A randomized trial comparing a standard therapy strategy with a strategy based on L/P is needed to allow clinicians to make a therapy decision using LP.

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

FC-026

Phenotypic heterogeneity of covid-19-related myocarditis in adults

BARHOUM Petra¹, PINETON DE CHAMBRUN Marc¹, DORGHAM Karim¹, KERNEIS Mathieu¹, BURREL Sonia¹, QUENTRIC Paul¹, PARIZOT Christophe¹, CHOMMELOUX Juliette¹, BRECHOT Nicolas¹, LEBRETON Guillaume¹, BOUSSOUAR Samia¹, SCHMIDT Matthieu¹, YSSEL Hans¹, LEFEVRE Lucie¹, MIYARA Makoto¹, CHARUEL Jean-Luc¹, MAROT Stephane¹, LUYT Charles-Edouard¹, LEPRINCE Pascal¹, AMOURA Zahir¹, MONTALESCOT Gilles¹, REDHEUIL Alban¹, COMBES Alain¹, GOROCHOV Guy¹, HEKIMIAN Guillaume¹

¹GROUPE HOSPITALIER PITIE SALPETRIERE, Paris, France

**Correspondence:** Petra BARHOUM (pbarhoum@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-026
**Rationale:** Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes of COVID-19 related myocarditis. The objective of this study was to compare the characteristics and clinical outcome between patients with COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A-).

**Patients and methods/Materials and methods:** We retrospectively reviewed the prospectively constituted database of our 26-bed ICU between March 2020 and June 2021, and included all patients admitted for suspected myocarditis with proven SARS-CoV-2 infection, without vaccination against COVID-19. The primary endpoint was in-hospital mortality. The secondary outcomes included left ventricle ejection fraction (LVEF) evolution, and long-term survival.

**Results:** Between March 2020 and June 2021, 38 patients required ICU admission (male: 66%; mean age: $32 \pm 15$ years) for suspected COVID-19-related myocarditis. All had positive SARS-CoV-2 RT-PCR (37%) or serology (68%). In-ICU treatment for organ failures included dobutamine (79%), norepinephrine (60%), mechanical ventilation (50%), VA-ECMO (42%) and renal replacement therapy (29%). In-hospital mortality was 13%. Twenty-five (66%) patients met the MIS-A criteria. MIS-A- compared to MIS-A+ patients were characterized by a shorter time lapse between the first COVID-19 symptoms and myocarditis (3 vs. 8 days, $p=0.04$), a lower left ventricle ejection fraction (LVEF 10 vs. 30%, $p=0.01$; LVOT-VTI 5 vs.13 cm, $p<0.0001$), as well as higher in-ICU organ failure, need for mechanical circulatory support with VA-ECMO (92% vs.16%, $p<0.0001$), and in-hospital mortality (31% vs. 4%, $p=0.04$). The main differences between the phenotypes of MIS-A+ and MIS-A- patients are summarized in the Central Illustration. Median LVEF at ICU and hospital discharge was 42% [30–54] and 60% [50–64] respectively. At the last follow-up (median [IQR] 235 [155–359] days), 32 patients were alive, all but one with normal LVEF, and one was lost of follow-up. The main differences between the phenotypes of MIS-A+ and MIS-A- patients are summarized in the Central Illustration.

**Conclusion:** MIS-A+ and MIS-A- COVID-19-related myocarditis patients have two distinct phenotypes in term of clinical presentation, timing, prognosis, and immunological profile. This study differentiated for the first time these two phenotypes, and it seems relevant for patients' management and further understanding of their pathophysiology.

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

<figure><img src="image_46.png" /><figcaption>Main phenotypic differences between (MIS-A+) and (MIS-A-) COVID-19-related myocarditis.</figcaption></figure>

FC-027
Impaired microvascular endothelial reactivity in critically ill COVID-19 patients

RAIA Lisa¹, URBINA Tomas¹, GABARRE Paul¹, BONNY Vincent¹, HARRI Geoffroy¹, ERHMINGER Sébastien¹, BIGÉ Naike¹, BAUDEL Jean-Luc¹, GUIDET Bertrand¹, MAURY Eric¹, JOFFRE Jérémie¹, AIT-OUFELLA Hafid¹
¹Hôpital Saint Antoine, Paris, France

**Correspondence:** Lisa RAIA (lr.lisa.raia@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-027

**Rationale:** The COVID-19 outbreak, caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2), has affected unprecedentedly all regions of the world. Critically ill COVID-19 patients exhibit inflammatory syndrome and frequent arterial and venous thrombosis affecting large vessels and microcirculation. Plus, clinical and histological studies have reported that SARS-CoV2 infection may damage the endothelium. However, the impact of this virus on endothelial function in vivo remains poorly characterized. This prospective observational study aimed to compare skin microvascular endothelial reactivity in critically-ill COVID-19 to patients admitted in the ICU for non-COVID-19 bacterial pneumonia (NCBP).

**Patients and methods/Materials and methods:** We conducted a prospective observational study in an 18-bed ICU. We included consecutive COVID-19 adult patients and patients with non-COVID-19 bacterial pneumonia admitted to our ICU for acute respiratory failure. Microvascular endothelial reactivity was assessed in the forearm skin area within the first 24 h of admission using acetylcholine iontophoresis coupled with Laser doppler. This non-invasive technique allows transdermal diffusion of acetylcholine across the skin to subcutaneous capillaries which results in endothelium-dependent vasodilatation and increased blood flow. The endothelial reactivity was quantified by the area under the curve (AUC) of the blood flow curve within a standardized 10-min recording. Hemodynamic and tissue perfusion parameters were also recorded.

**Results:** During 3 consecutive months, 32 COVID-19 patients and 11 control NCBP patients with acute respiratory failure were included. The median age was 59 [50–68] and 69 [57–75] years in COVID-19 and NCBP groups, respectively ($P=0.11$). No significant difference in comorbidities or medications was observed between the two groups, except for body mass index, which was higher in COVID-19 patients. NCBP patients had higher SAPS II score compared to COVID-19 patients [46 [32–51] vs. 23 [18-30], $P<0.0001$] but SOFA score was not different between groups [4 [3–4] vs 4 [2–5.3], $P=0.51$]. Global hemodynamic and peripheral tissue perfusion parameters were not different between groups. COVID-19 patients had significant lower skin basal blood flow compared to NCBP patients (7.9 [5.5–9.9] vs. 10.4 [9.4–12.1] UI, $P=0.02$). In addition, endothelium-dependent microvascular reactivity was threefold lower in COVID-19 patients compared to NCBP patients (AUC 3911 [1725–6318] vs. 14280 [5038–19743], $P=0.008$) (Fig. 1).

**Conclusion:** In critically ill COVID-19 patients, we evidenced a drastically impaired skin microvascular endothelium-dependent vasoreactivity at the early phase of the disease compared to non-COVID-19 bacterial pneumonia patients. This result supports the hypothesis of a singular and clinically relevant SARS-CoV 2-associated endotheliopathy.

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

<figure><img src="image_47.png" /><figcaption>Figure 1. A. Skin microvascular blood flow in response to three stimulation of acetylcholine (arrows) in NCBP patients (grey) and in COVID-19 patients (red), represented as mean+/SEM every seconds for 10 min after the first electric stimulation. B.</figcaption></figure>
FC-028

**Venous Thromboembolism events in critically ill COVID-19 patients**

ALILA Ilef¹, HADDED Amina¹, KHARRAT Sana¹, CHTARA Kamilia¹, BAHLOUL Mabrouk¹, BOUAZIZ Mounir¹

¹hôpital Habib Bourguiba Sfax, Sfax, Tunisie

**Correspondence:** Ilef ALILA (ilefalila1323@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-028

**Rationale:** There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (1). The aim of this study was to determine the incidence of PE in patients with COVID-19, risk factors and its prediction of outcome in critically ill COVID19 patients.

**Patients and methods/Materials and methods:** We conducted a retrospective study in a medical ICU over a period of 16 months [September 2020–December 2021] including patients with SARS-COV2 infection.

**Results:** During the study period, 586 patients were included with a mean age of 59.5 ± 14.7 and a gender ratio of 1.6. The median SAPSII and SOFA score were respectively of 29 ± 14.8 and 4 ± 2.6. Most patients had comorbidities, including hypertension (36%), obesity (32.1%) and diabetes (36.2%). 509 (87%) patients received therapeutic anticoagulation on admission versus only 77 (13%) received prophylactic anticoagulation. Twenty-eight (4.7%) patients had venous thromboembolic events: PE was diagnosed through CT pulmonary angiography in 22 (3.8%) of 586 hospitalized patients with COVID-19 and deep venous thrombosis was diagnosed in 10 (1.7%) patients through doppler ultrasound of lower limb. Four patients had both complications. The comparison between 2 groups with or without thromboembolic (TE) complications showed that the risk factors usually associated the development of thromboembolic complications were not significantly different (high blood pressure in 7 (25%) vs 204 (36.6%) p = 0.2, diabetes in 9 (32.1%) vs 203 (36.4%) p = 0.8, obesity in 13 (46.4%) vs 175 (31.3%) p = 0.09, smoking in 6 (21.4%) vs 125 (22.4) p = 0.9). Invasive mechanical ventilation was required in 264 (45.1%) patients, 20 (71.4%) in the group with TE complications and 244 (43.7%) in the other group, p = 0.004. Mortality was similar between the 2 groups (15 (53.5%) vs 272 (48.7%); P = 0.6).

**Conclusion:** TE complications were rare in our cohort. These complications are associated with higher use of mechanical ventilation but not with higher mortality.

**Reference 1:** (1) Pompilio Faggiano, Andrea Bonelli, Sara Paris, Giuseppe Milesi, Stefano Bisegna, Nicola Bernardi, Antonio Curnis, Eustachio Agricola, Roberto Maroldi: Acute pulmonary embolism in COVID-19 disease: Preliminary report on seven patients.

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

FC-029

**Anti-RNA-polymerase III autoantibodies-associated fulminant myocarditis**

PINETON DE CHAMBRUN Marc¹, CHARUEL Jean-Luc¹, DORGHAM Karim¹, QUENTRIC Paul¹, KERNEIS Mathieu¹, LEBRETON Guillaume¹, MIYARA Makoto¹, SCHMIDT Matthieu¹, LUYT Charles-Edouard¹, LIFERMANN Francois², MELKI Isabelle³, AMOURA Zahir¹, GOROCHOV Guy¹, HEKIMIAN Guillaume¹, COMBES Alain¹

¹Hôpital La Pitié-Salpêtrière, Paris, France; ²CH DAX, Dax, France; ³Hôpital Robert Debré, Paris, France

**Correspondence:** Marc PINETON DE CHAMBRUN (marc.dechambrun@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-029

**Rationale:** Anti-RNA-polymerase III autoantibodies (RNApol3)-associated fulminant myocarditis is a recently discovered entity associating recurrent viral (mostly influenzae)-induced fulminant myocarditis and/or severe pericarditis in patients with RNApol3 but no overt systemic sclerosis. It is a serious condition owing the severity of myocarditis episodes and the risk of relapse. The pathophysiology of the disease is unknown. We conducted this study to better delineate the clinical characteristics and the outcome of these patients.

**Patients and methods/Materials and methods:** Retrospective, monocenter study between January 2013 and January 2022 including every patients admitted to a 26-bed intensive care unit for myocarditis and/or severe pericarditis in the presence of RNApol3.

**Results:** Twenty-five patients (women 80%, mean age at first episode 35 ± 11.4 years) were included in the study. Seven (28%) patients died after a median follow-up 39 [6–50] months: during a first myocarditis episode (n = 2), a relapse (n = 4) or from other cause (n = 1). The mean number of episodes per patients was 1.6 ± 0.9 and 40% patients had at least one relapse. Every patient was admitted at least once in critical care for a median duration of 9 [5–14] days. The lowest left ventricle ejection fraction value was 5 [5–10] % and the highest troponin value 82 [19–370] fold over ULN. Pericardial effusion was reported in 94% cases, requiring drainage in 40% cases. Inflammatory parameters were mildly elevated: C-reactive protein 7 [5–14] mg/L, procalcitonin 0.1 [0.06–0.4] ng/mL and fibrinogen 3 [2.4–3.4] g/L. Conduction and rhythm disorders were infrequent: 3 and 7% respectively. In-ICU organ-failure treatment frequencies were: dobutamine 83%, VA-ECMO 77%, vasopressors 70%, mechanical ventilation 67% and renal replacement therapy 30%. Two patients received cardiac transplantation because of unrecovering cardiac failure while all survivors could be weaned from ECMO and recovered normal cardiac function at distant follow-up. The etiology of myocarditis were: influenza 52%, COVID-19 44%, unknown viral infection 12% and other virus 4%. Four patients had a myocarditis episode on the occasion of both influenzae virus infection and COVID-19. RNApol3 were confirmed on distant follow-up in every patient (n = 17) after a mean duration of 8 [2.5–16.5] months. Two patients only had systemic sclerosis classification score ≥ 9 without visceral involvement.

**Conclusion:** RNApol3-associated fulminant myocarditis is a new severe entity. Our study shows that both influenza and COVID-19 are responsible for myocarditis in these patients. A significant number of patients have been diagnosed on the occasion of COVID-19 pandemic. The pathophysiology of this disease needs further investigation.

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

FC-030

**Safety, diagnostic yield and therapeutical consequences of myocardial biopsy in unexplained acute heart failure requiring extracorporeal life support**

PINETON DE CHAMBRUN Marc¹, YANN Marquet¹, ROUVIER Philippe¹, KERNEIS Mathieu¹, BRECHOT Nicolas¹, SCHMIDT Matthieu¹, CHOMMELOUX Juliette¹, MOYON Quentin¹, BARHOUM Petra¹, LEFEVRE Lucie¹, SAURA Ouriel¹, LEVY David¹, ASSOULINE Benjamin¹, LUYT Charles-Edouard¹, COMBES Alain¹, HEKIMIAN Guillaume¹

¹Hôpital La Pitié-Salpêtrière, Paris, France

**Correspondence:** Marc PINETON DE CHAMBRUN (marc.dechambrun@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-030

**Rationale:** Myocardial biopsy is strongly recommended in patients with unexplained acute heart failure, especially in case of cardiogenic shock, despite a very low level of evidence. The safety, the diagnostic yield and the therapeutical consequences of myocardial biopsy in patients requiring extracorporeal life support (ECLS) is poorly investigated.

**Patients and methods/Materials and methods:** Retrospective, monocenter study between January 2002 and January 2018 including every patients admitted to a 26-bed intensive care unit undergoing a myocardial biopsy (surgical or endomyocardial) for unexplained acute heart failure while being under ECLS. All patients had a myocardial biopsy altogether with a comprehensive noninvasive diagnosis work-up. The primary endpoint was the rate of therapeutical modifications as a direct consequence of myocardial biopsy results.

**Results:** Forty-seven patients (women 53%, mean age at admission 39 ± 11 years) were included in the study. Forty-two (89%) received veno-arterial extracorporeal membrane oxygenation (VA-ECMO), requiring centralization in 26 (62%) and 15 (32%) were given ventricle assist device. Twenty-six (55%) patients died in hospital, 16 (34%)
could be weaned from ECLS and 7 (15%) required cardiac transplantation. According the Bonaca myocarditis classification, 75% had definite and 25% probable myocarditis. Biopsy was endomyocardial in 17 (36%) patients and surgical in other cases. Organ failure treatments on biopsy-day were: ECLS 100%, inotropes/vasopressors 96%, mechanical ventilation 75% and renal replacement therapy 30%. Endomyocardial and surgical biopsy was followed by tamponade in 29% and 10% cases respectively. One patient undergoing endomyocardial biopsy died as a direct consequence of the procedure. The biopsy-based and the noninvasive heart failure mechanism diagnosis work-up resulted in the following diagnosis respectively: myocarditis 51 and 13%; none 45 and 57% and alternated diagnosis 4 and 30%. The biopsy-based and the noninvasive etiology diagnosis work-up led to a diagnosis in 25 and 47% cases respectively. The biopsy-based and the noninvasive diagnosis work-up results in a therapeutic modification in 13 and 19% patients respectively (Fig. 1). Among the 6 patients whose biopsy led to a treatment change, 2 survived to hospital discharge, including one whose etiological diagnosis was also given by the noninvasive work-up.

**Conclusion:** Myocardial biopsy in patients with acute heart failure of unknown etiology requiring ECLS has low diagnostic yield and therapeutic consequences and is associated with significant adverse events. The benefit/risk ratio of this procedure should be carefully weighted in these patients.

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

<figure><img src="image_48.png" /><figcaption>Figure 1. Diagnosis and therapeutic consequences according to biopsy-based or noninvasive diagnosis work-up</figcaption></figure>

FC-031

Stent thrombosis in cardiac arrest patients: prevalence, risk factors and long-term outcome

BOIS Antoine¹

¹Hôpital Henri Mondor, Villejuif, France

**Correspondence:** Antoine BOIS (antoinebois01@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-031

**Rationale:** Ischemic heart disease is the leading cause of cardiac arrest (CA) and stent thrombosis (ST) is ten times more frequent when acute coronary syndrome is initially associated with CA. Data are missing about impact and risk factors of this complication.

**Patients and Methods/Materials and Methods:** We conducted a monocenter and retrospective study from January 2010 to September 2019 including all patients hospitalized after a CA who were treated by stent and had a second coronary angiography in the 3 following months. Demographics and characteristics of patient care were

compared according to ST. Long-term follow-up was provided using the French National Healthcare Insurance database.

**Results:** 22 patients met the inclusion criteria during the study period. The incidence of ST was 50%. Stent length was associated with ST occurrence (26.8 mm vs 17.0 mm, p=0.023), whereas there was no significant difference on age, gender, coronary lesion features, type of stent or drugs used. Long-term follow-up of 7 patients, including 6 cases of ST, revealed no major adverse cardiac event.

**Conclusion:** Stent thrombosis is a frequent complication after CA and appears to be associated to stent's length. Larger prospective studies, are needed to define the prognosis and risk factors of ST.

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

<figure><img src="image_49.png" /><figcaption>Kaplan-Meier plot of probability of MACE occurrence according to the presence of ST</figcaption></figure>

FC-032

SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest

BENGHANEM Sarah¹,², NGUYEN Lee Son¹, GAVARET Martine², MIRA Jean Paul¹, PENE Frederic¹, CHARPENTIER Julien¹, MARCHI Angela², CARIOU Alain¹

¹Hôpital Cochin APHP, Paris, France; ²Unité INSERM 1266 Institut de Psychiatrie et Neurosciences Paris IPNP, Hopital Sainte Anne, Paris, France

**Correspondence:** Sarah BENGHANEM (sarah.benghanem@aphp.fr)

Annals of Intensive Care 2022, **12**(1):FC-032

**Rationale:** Background: To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely N20-baseline (N20-b) and N20-P25, are predictive of neurological outcome.

**Patients and methods/Materials and Methods:** Methods: Monocenter prospective study in a tertiary cardiac center between November 2019 and July 2021. All patients comatose at 72 h after CA with at least one SEP recorded were included. The N20-b and N20-P25 amplitudes were automatically measured in microvolts (µV), along with other recommended prognostic markers (status myoclonus, neuron-specific enolase levels at 2 and 3 days, and EEG pattern). We assessed the predictive value of SEP for neurologic outcome using the best Cerebral Performance Categories (CPC 1 or 2 as good outcome) at 3 months (main endpoint) and 6 months (secondary
endpoint). Specificity and sensitivity of different thresholds of SSEP amplitudes, alone or in combination with other prognostic markers, were calculated.

**Results:** Results: Among 82 patients, a poor outcome (CPC 3-5) was observed in 78% of patients at 3 months. The median time to SSEP recording was 3(2-4) days after CA, with a pattern "bilaterally absent" in 19 patients, "unilaterally present" in 4, and "bilaterally present" in 59 patients. The median N20-b amplitudes were different between patients with poor and good outcomes, i.e., 0.93 [0-2.05] µV vs 1.56 [1.24-2.75] µV respectively (p < 0.0001), as the median N20-P25 amplitudes (0.57 [0-1.43] µV in poor outcome vs 2.64 [1.39-3.80] µV in good outcome patients p < 0.0001). A N20-b > 2 µV predicted good outcome with a specificity of 73% and a moderate sensitivity of 39%, although a N20-P25 > 3.2 µV was 93% specific and only 30% sensitive. A low voltage N20-b < 0.88 µV and N20-P25 < 1 µV predicted poor outcome with a high specificity (specificity of 94% and 93% respectively) and a moderate sensitivity (sensitivity of 50% and 66% respectively). Association of "bilaterally absent or low voltage SSEP" patterns increased the sensitivity significantly as compared to "bilaterally absent" SSEP alone (58 vs 30%, p = 0.002) for prediction of poor outcome.

**Conclusion:** Conclusion: In comatose patient after CA, both N20-b and N20-P25 amplitudes could predict both good and poor outcomes with high specificity but low sensitivity. Our results suggest that SSEP amplitudes are inversely related to the severity of neurological injury, although this indicator should be combined with other indicators in a multimodal approach for prognostication.

**Reference 1:** Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med 2021;47:369-421.

**Reference 2:** Scarpino M, Lolli F, Lanzo G, Carrai R, Spalletti M, Valzania F, et al. SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study. Resuscitation 2021;163:162

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

<figure><img src="image_50.png" /></figure>

Presence of the cortical responses
N20 and P25

<figure><img src="image_51.png" /></figure>

Presence of the N20 and P25
components with a reduced amplitudes

<figure><img src="image_52.png" /></figure>

Absence of the N20 and P25
components

In a normal SSEP (panel 1), the channels show the cortical responses N20 and P25, the spinal component (N13) and the peripheral component (N9). In the panel 2, N20 and P25 were presented but amplitudes were reduced. In the panel 3, N20 and P25 were absent

FC-033

Head-up position reduces intra-cranial pressure
during extracorporeal resuscitation following refractory cardiac
arrest in swine

LEVY Yael¹, HUTIN Alice², POLGE Nicolas³, LIDOUREN Fanny³, FERNANDEZ Rocio³, KOHLHAUER Matthias³, LEGER Pierre-Louis¹, DEBATY Guillaume⁴, LURIE Keith⁵, LAMHAUT Lionel², GHALEH Bijan³, TISSIER Renaud³

¹CHU Armand Trousseau, Paris, France; ²CHU Necker, Paris, France; ³Ecole Nationale Vétérinaire d'Alfort, Maison-Alfort, France; ⁴CHU de Grenoble, Grenoble, France; ⁵Hennepin Healthcare Research Institute, Minneapolis, Etats-Unis

**Correspondence:** Yael LEVY (yael.levy@aphp.fr)

Annals of Intensive Care 2022, 12(1):FC-033

**Rationale:** Head-up position was shown to mitigate cerebral alterations and improve cerebral perfusion pressure during conventional cardiopulmonary resuscitation. Since extracorporeal cardiopulmonary resuscitation (E-CPR) is more and more used for the management of refractory cardiac arrest, we aimed at determining whether head-up position could also modify cerebral hemodynamics during E-CPR. Accordingly, we compared this hemodynamics in swine submitted to E-CPR in flat position as compared to head position (head-up position at 30 °C). Hypothesis: Our goal was to determine whether a standardized head-up could improve intracranial pressure (ICP) and cerebral autoregulation during E-CPR in a swine model of cardiac arrest.

**Patients and methods/Materials and methods:** Pigs were anesthetized and instrumented for the continuous evaluation of carotid blood flow, intracranial pressure (ICP), cerebral perfusion pressure, pressure reactivity index (PRx) and systemic hemodynamics. They were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until resumption of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. Epinephrine was delivered to achieve a mean arterial pressure ≥ 65 mmHg. An automated head-up position device (over two minutes, 30°) was used in head-up group. Animals were followed during 120-min after ROSC.

**Results:** Six animals were included in both groups. Cerebral hemodynamic parameters are illustrated in Figure. During E-CPR and ROSC, ICP decreased in head-up vs flat position and cerebral perfusion pressure tended to be improved at the end of the follow-up (NS). Cerebral oxygen saturation, carotid blood flow and PRx, which is the correlation coefficient between arterial blood pressure and ICP, were not different among groups.

**Conclusion:** During E-CPR, head-up is associated with lower ICP with a trend toward higher cerebral perfusion pressure. This study supports the need for further investigations to confirm that the early decrease in ICP could be associated with an improvement in neurological outcome after E-CPR.

**Compliance with ethics regulations:** Yes in animal testing.

<figure><img src="image_53.png" /></figure>

<figure><img src="image_54.png" /></figure>

<figure><img src="image_55.png" /></figure>

<figure><img src="image_56.png" /></figure>

Cerebral hemodynamic parameters after cardiac arrest

FC-034

Targeted temperature management after in-hospital cardiac
arrest: an ancillary analysis of hyperion trial data

BLANC Alexiane¹, COLIN Gwenhaël², CARIOU Alain³,⁴, MERDJI Hamid⁵,⁶, GRILLET Guillaume⁷, GIRARDIE Patrick⁸, COUPEZ Elisabeth⁹, DEQUIN Pierre-François¹⁰,¹¹, BOULAIN Thierry¹², FRAT Jean-Pierre¹³,¹⁴,¹⁵, ASFAR Pierre¹⁶, PICHON Nicolas¹⁷,¹⁸, LANDAIS Mickael¹⁹, PLANTEFEVE Gaëtan²⁰, QUENOT Jean-Pierre²¹, CHAKARIAN Jean-Charles²², SIRODOT Michel²³, LEGRIEL Stéphane²⁴, MASSART Nicolas²⁵, THEVENIN Didier²⁶, DESACHY
Arnaud²⁷, DELAHAYE Arnaud²⁸, BOTOC Vlad²⁹, VIMEUX Sylvie³⁰, MARTINO Frederic³¹, REIGNIER Jean¹, TACCONE Fabio Silvio³², LASCARROU Jean-Baptiste¹,³

¹Centre Hospitalier Universitaire de Nantes, Médecine intensive réanimation, Nantes, France; ²Centre Hospitalier Départemental de La Roche-sur-Yon, La Roche-Sur-Yon, France; ³Centre de recherche cardiovasculaire INSERM U970, Paris, France; ⁴Centre Hospitalier Universitaire de Cochin, Médecine intensive réanimation, Paris, France; ⁵Hôpitaux universitaires de Strasbourg, Nouvel Hôpital Civil, Médecine intensive réanimation, Strasbourg, France; ⁶Fédération de Médecine Translationnelle de Strasbourg UMR 1260, Strasbourg, France; ⁷Centre hospitalier de Bretagne sud Lorient, Médecine intensive réanimation, Lorient, France; ⁸Centre Hospitalier Universitaire de Lille, Médecine intensive réanimation, Lille, France; ⁹Centre Hospitalier Universitaire de Clermont-Ferrand, Médecine intensive réanimation, Clermont-Ferrand, France; ¹⁰Centre Hospitalier Universitaire de Tours, Médecine intensive réanimation, Tours, France; ¹¹Centre d'Etude des Pathologies Respiratoires, Université de Tours, Tours, France; ¹²Centre Hospitalier Régional d'Orléans, Médecine intensive réanimation, Orléans, France; ¹³Centre Hospitalier Universitaire de Poitiers, Médecine intensive réanimation, Poitiers, France; ¹⁴INSERM, CIC-1402, Poitiers, France; ¹⁵Faculté de Médecine et de Pharmacie de l'Université de Poitiers, Poitiers, France; ¹⁶Centre Hospitalier Universitaire d'Angers, Médecine intensive réanimation, Angers, France; ¹⁷Centre Hospitalier Universitaire de Limoges, Service de Réanimation Polyvalente, Limoges, France; ¹⁸Centre Hospitalier Universitaire de Limoges, CIC 1435, Limoges, France; ¹⁹Centre Hospitalier du Mans, Service de réanimation, Le Mans, France; ²⁰Centre Hospitalier d'Argenteuil, Service de réanimation, Argenteuil, France; ²¹Centre Hospitalier Universitaire de Dijon, Médecine intensive réanimation, Dijon, France; ²²Centre Hospitalier de Roanne, Service de réanimation, Roanne, France; ²³Centre Hospitalier d'Annecy, Service de réanimation, Annecy, France; ²⁴Centre Hospitalier de Versailles, Service de réanimation, Versailles, France; ²⁵Centre Hospitalier de Saint Brieuc, Service de réanimation, Saint Brieuc, France; ²⁶Centre Hospitalier de Lens, Service de réanimation, Lens, France; ²⁷Centre Hospitalier d'Angoulême, Service de réanimation, Angoulême, France; ²⁸Centre Hospitalier de Rodez, Service de réanimation, Rodez, France; ²⁹Centre Hospitalier de Saint Malo, Service de réanimation, Saint Malo, France; ³⁰Centre Hospitalier de Montauban, Service de réanimation, Montauban, France; ³¹Centre Hospitalier Universitaire de Pointe-à-Pitre, Médecine intensive réanimation, Pointe-à-Pitre, France; ³²Centre Hospitalier Universitaire Erasmus, Université de Bruxelles, Bruxelles, Belgique

**Correspondence:** Alexiane BLANC (alexiane.blanc@hotmail.fr)

Annals of Intensive Care 2022, **12**(1):FC-034

**Rationale:** Targeted temperature management (TTM) is currently the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest remains unclear. Is hypothermia at 33 °C associated with better neurological outcomes after in-hospital cardiac arrest in a non-shockable rhythm, compared to targeted normothermia at 37 °C?

**Patients and methods/Materials and methods:** We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm (HYPE-RION) randomized controlled trial in 584 patients. We included the 159 patients with in-hospital cardiac arrest; 73 were randomized to 33 °C and 86 to 37 °C. The primary outcome was survival with a good neurological outcome (Cerebral Performance Category [CPC] score 1 or 2) at day 90. Mixed multivariable adjusted logistic regression analysis was performed to determine whether survival with CPC 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization.

**Results:** Compared to targeted normothermia for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurological outcomes at day 90 (16.4% vs. 5.8%; P = 0.03). Day-90 mortality was not significantly different between the two groups (68.5% vs. 76.7%; P = 0.24). By mixed

multivariable analysis adjusted on the CAHP score and circulatory shock, hypothermia was significantly associated with good day-90 neurological outcomes (2.40 [1.17;13.03]; P = 0.03).

**Conclusion:** Hypothermia at 33 °C was associated with better day-90 neurological outcomes after in-hospital cardiac arrest in a non-shockable rhythm, compared to targeted normothermia. However, our limited sample size resulted in wide confidence intervals. Further studies of patients after cardiac arrest from any cause, including in-hospital cardiac arrest, are needed.

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

## FC-035

### Impact of Methylene Blue for post resuscitation syndrome in a pig model of refractory cardiac arrest resuscitated with veno-arterial ECMO

PEQUIGNOT Benjamin¹, LESCROART Mickael¹, ALBUISSON Eliane¹, ORLOWSKI Sophie¹, PINA Héloïse¹, TRAN Nguyen¹, GRANDMOugin Daniel¹, LEVY Bruno¹

¹CHRU de Nancy, Vandœuvre-Lès-Nancy, France

**Correspondence:** Benjamin PEQUIGNOT (b.pequignot@chru-nancy.fr)

Annals of Intensive Care 2022, **12**(1):FC-035

**Rationale:** Selected patients with a refractory cardiac arrest could benefit from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as rescue with good prognosis. Circulatory flow recovery with ECMO is associated with vasoplegia and vasopressor need. The aim of the present work is to assess the interest of Methylene Blue perfusion in a pig model of ischemic refractory cardiac arrest implanted by VA-ECMO.

**Patients and methods/Materials and methods:** Ischemic refractory cardiac arrest was performed in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and pigs were randomly assigned to standard care group (norepinephrine + crystalloids) or methylene blue group (IV methylene blue + standard care). Macrocirculatory and metabolic parameters were assessed by lactate clearance. Microcirculatory parameters were assessed by sublingual microcirculation with Side-stream Dark Field (SDF). Pulmonary oedema was evaluated by measuring lung wet/dry weight ratio. Severity of ischemic digestive lesions were assessed by Chiu/Park scale.

**Results:** 18 pigs were included in statistical analyses. There was no significant difference between the groups with regard to lactate clearance levels (29.16 [12.5–39.32], 46.10 [22.61–64.54] % for control and methylene blue group). There was no significant difference between the groups regarding sublingual capillary microvascular parameters assessed by SDF. Total crystalloid load was significantly reduced with Methylene Blue infusion (5000 [6000–8000] mL vs. 17000 [10000–19000] mL p = 0.007, Methylene Blue versus control group). Methylene blue infusion significantly reduced catecholamine requirements (0.31 [0.14–0.44] µg.kg1.min⁻¹ vs. 2.32 [1.17–5.55] µg.kg1.min⁻¹, methylene blue versus control group p = 0.004). The was not difference in Chiu/Park scale and Lung wet/dry weight ratio between groups.

**Discussion:** The main result of this study is that in an experimental pig model of refractory cardiac arrest resuscitated with veno-arterial ECMO, the use of methylene blue infusion was not associated with a faster lactate clearance. Importantly, the adjunction of methylene blue was associated with sharp reduction of crystalloid fluid load and catecholamine perfusion. There were also some limitations: no return of spontaneous circulation was achieved for any animal of the experiment. The study time over a 6-h period represents a major limitation as it could be mis-scaled to assess benefits and drawbacks of catecholamine or fluid restriction.

**Conclusion:** Methylene blue infusion was efficient for catecholamine and fluid restriction respectively but failed to improve lactate clearance in a pig model of post resuscitation syndrome after refractory cardiac arrest treated with VA-ECMO.

**Compliance with ethics regulations:** Yes in animal testing.
<figure><img src="image_57.png" /><figcaption>Lactate clearance, Volume and cathecolamine dose between groups</figcaption></figure>

FC-036

Right ventricular changes before and after veno-venous ECMO
implantation in refractory COVID-19 ARDS

LEVY David¹, DESNOS Cyrielle¹,³, THÉRY Guillaume¹,², SCHMIDT Matthieu¹,
BRECHOT Nicolas¹, PINETON DE CHAMBRUN Marc¹, CHOMMELOUX
Juliette¹, COMBES Alain¹, HEKIMIAN Guillaume¹

¹Pitié-Salpêtrière, Paris, France; ²CHU de Reims, Reims, France; ³Hôpital Tenon, Paris, France

**Correspondence:** David LEVY (dlevy88@gmail.com)

Annals of Intensive Care 2022, 12(1):FC-036

**Rationale:** Right ventricular (RV) failure is a common complication during acute respiratory distress syndrome (ARDS). Veno-venous ECMO (VV-ECMO) is considered in refractory ARDS and might be responsible for RV function changes. Our objective was to describe RV function before and after VV-ECMO course in refractory ARDS COVID-19 patients.

**Patients and methods/Materials and methods:** This retrospective observational single-center study was performed between April 2020 and April 2021. Patients included were refractory ARDS secondary to SARS-CoV-2 infection and required VV-ECMO according to EOLIA criteria. Patients underwent serial echocardiographic examinations (Philips, CX-50) before and after VV-ECMO implantation.

**Results:** 15 patients were included. Median age was 54 years (46–62), 9/15 (60%) were male. Before ECMO cannulation, median PaO₂/FiO₂ was 60 (56–72) mmHg, delay between ventilation and cannulation was 6 (4–11) days. SAPS-II at cannulation was 46 (30–55). Inhaled nitric oxide and norepinephrine were used in 8/15 patients (53.3%) before ECMO. Fractional area change of RV (FAC-RV) was greater after ECMO implantation, (36 [20–44] % before ECMO, 42 [35–45] % at day 1 and 42 [40–46] % at day 3, p = 0.008). Estimated systolic pulmonary pressure (sPAP) decreased over time (47 [40–55] mmHg before, 40 [36.3–40.1] mmHg at day 1 and 37 [34–45] mmHg at day 3, p = 0.048). PCO₂ was higher before ECMO implantation (56 [49–63] mmHg versus 44 [39–47] mmHg at day 1 and 41 [39–44] mmHg at day 3, p = 0.001). FAC-RV/sPAP increased after ECMO cannulation (0.68 [0.31–0.97] before vs. 1 [0.74–1.2] at day 1 and 1.1 [0.96–1.3] at day 3, p = 0.027). Tricuspid valve systolic velocity (S'wave) and TAPSE were similar before and after ECMO implantation (S'wave, 17 [13–20] vs. 15 [12–20] cm/sec at day 1 and 14 [11–26] cm/sec at day 3, p = 0.28; TAPSE, 21 [19–27] mm before ECMO, 21 [17–26.5] mm at day 1 and 23 [19–25] mm at day 3, p = 0.44). Arterial blood lactate level decreased after cannulation (2 [1.6–2] mmol/L before vs. 1.7 [1.5–2.3] mmol/L at day 1 and 1.6 [1.6–1.7] mmol/L at day 3, p = 0.006). Also, inotropic score tended to be lower (40.7 [24.5–75.8] before ECMO vs. 4.9 [0–20.8] at day 1 and 0 at day 3, p = 0.05). Median time of VV-ECMO course was 20 (15–41) days and 7/15 (46.6%) were alive at ICU discharge.

**Conclusion:** Based on this small-sample study in refractory ARDS, VV-ECMO could be responsible for RV systolic function improvements while decreasing sPAP, and could provide hemodynamic stability through right ventricular-pulmonary artery coupling.

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

<figure><img src="image_58.png" /><figcaption>Right ventricular metrics and hemodynamic changes before and after VV-ECMO implantation</figcaption></figure>

FC-037

Interest of albumin infusion for post resuscitation syndrome
in a porcine model of refractory cardiac arrest resuscitated
with veno-arterial ECMO

LESCROART Mickael¹,², PEQUIGNOT Benjamin¹,², GRANDMOUGIN Daniel¹,², TRAN N'Guyen², ALBUISSON Eliane¹, LEVY Bruno¹,²

¹CHRU Nancy, Vandoeuvre, France; ²Université de Lorraine, Nancy, France

**Correspondence:** Mickael LESCROART (dr.lescroart@gmail.com)

Annals of Intensive Care 2022, 12(1):FC-037

**Rationale:** Hemodynamic instability is common in post resuscitation syndrome and could worsen survival and neurological outcomes. The myocardial and vascular dysfunction may be exacerbated by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implanted as a rescue therapy for refractory cardiac arrest. Standard care of haemodynamic management after VA-ECMO initiation are based on norepinephrine and crystalloids. The aim of the present work is to assess the interest on haemodynamics of albumin perfusion in a swine model of ischemic refractory cardiac arrest implanted by VA-ECMO.

**Patients and methods/Materials and methods:** Ischemic refractory cardiac arrest was performed in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and pigs were randomly assigned to standard care group (norepinephrine + crystalloids) or albumin group (10 ml/kg of 20% albumin + standard care). Hemodynamical assessment was performed over the 6 h of the experiment

**Results:** 18 pigs were included in statistical analyses. There was no significant difference between groups with regard to lactate clearance (29.16% [12.5–39.32] and 10.09% [6.78–29.36] for control and albumin group respectively). Blood albumin concentration rapidly decreased after ECMO priming in the sham group while it remained stable in the albumin group. Total crystalloid load was significantly reduced with albumin infusion (1000 [1000–2278] mL vs. 17000 [10000–19000] mL, albumin versus control group respectively, p < 0.001).

**Conclusion:** This is the first study assessing albumin for fluid resuscitation in post resuscitation syndrome rescued by VA-ECMO. Albumin infusion did not improve lactate clearance but was highly efficient to reduce fluid loading in a porcine model of post resuscitation syndrome after refractory cardiac arrest treated with VA-ECMO.

**Compliance with ethics regulations:** Yes in animal testing.
<figure><img src="image_59.png" /></figure>

Panel A: experimental protocol. Panel B: albumin concentration over time (in hours). Panel C: Lactate clearance 6 h after initial resuscitation. Panel D: fluid loading over a 6 h resuscitation. ALB: albumin group. CTL: control group.

FC-038

Clinical characteristic, injuries pattern and management of pediatric polytraumatized patients: an experience of an emergency departement

MALLEK Mariam<fnref n="1" />, KARRAY Rim<fnref n="1" />, BEN ALI Hana<fnref n="1" />, ZOUARI Alaeddine<fnref n="1" />, BEN SALEM Imen<fnref n="1" />, KSENTINI Hana<fnref n="1" />, NASRI Abdennour<fnref n="1" />, CHAKROUN Olfa<fnref n="1" />, REKIK Noureddine<fnref n="1" />

**Correspondence:** Rim KARRAY (karray_rim@medecinesfax.org)

Annals of Intensive Care 2022, **12**(1):FC-038

**Rationale:** Caring for pediatric trauma patient requires an understanding of the distinct anatomy and pathophysiology of the pediatric population compared with adult. As a result, the degree of awarding towards polytraumatized children must be higher. The aim of our study is to identify clinical and therapeutic aspects of pediatric polytraumatized patients.

**Patients and methods/Materials and methods:** A 5-month prospective study including polytraumatized children admitted to ICU of Emergency Department. Demographic clinical and radiological data are described. Management and outcomes of patients are also reported.

**Results:** We enrolled 20 pediatric polytraumatized patients. Fifty percent of them were boys. Road traffic was the main cause of pediatric trauma in 75% of cases. Half of the polytraumatized patients were conscious and 20% of children had a severe traumatic brain injury with a Glasgow coma scale under 8. In the majority of cases, pupils were normodilated. Convulsion and agitation were reported in 15% of patients. The most frequent brain injury was brain contusion in 55% of cases. Extradural, subdural hematoma and subarachnoid hemorrhage were present in 25% of cases. Chest trauma was present in 40% of cases and the main chest injury was thoracic contusion in 35% of cases. One in four children had an abdominal trauma with abdominal hemorrhage in 15% of cases, hepatic contusion in 10% and splenic contusion in 5% of cases. Pelvic fracture was present in 15% of cases. Airway management was performed in 35% of cases for neurological distress. Fluid administration was performed only in 15% of cases and transfusion in 30% of cases. A brain surgery was necessary in 20% of patients. No children died and only 10% referred to home after a stay in the emergency department. Overall, 85% of patients were transferred: 30% to the intensive care unit, 40% to neurosurgery service and 10% to a surgical pediatric unit.

**Conclusion:** Trauma is the cause of more than 45% of deaths in children aged 1 to 14 years. Since multiple injuries are common in children, the emergency physician must assess all organs of a child with high-energy injuries, regardless of the mechanism of the trauma.

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

FC-039

Impact of pre-hospital intubation on the outcome of polytraumatic patients

MALLEK Mariam<fnref n="1" />, KARRAY Rim<fnref n="1" />, BEN ALI Hana<fnref n="1" />, MZOUGHI Faten<fnref n="1" />, BEN SALEM Imen<fnref n="1" />, CHAARI Leila<fnref n="1" />, CHAKROUN Olfa<fnref n="1" />, CHAARI Adel<fnref n="1" />, REKIK Noureddine<fnref n="1" />

**Correspondence:** Rim KARRAY (karray_rim@medecinesfax.org)

Annals of Intensive Care 2022, **12**(1):FC-039

**Rationale:** Polytrauma is a leading cause of mortality and disability all over the world. Respiratory, hemodynamic and neurological distress are very frequent and correlated with high mortality. Therefore, an early energetic therapy controlling these distresses, by pharmacological methods and airway management can improve the outcome of polytraumatized patients. The aim of our study is to evaluate the impact of an early airway management on patient prognosis of patient in terms of length of stay in emergency department, mortality and neurological outcomes.

**Patients and methods/Materials and methods:** In this prospective study, only intubated patients were enrolled. The enrolled patients were randomly assigned into two groups: group A: intubated in pre-hospital phase and group B: intubated in hospital phase. Basic characteristics of injury, length of stay in emergency department, mortality and neurological outcomes according to the GOS score at one month (GOS1: death, GOS2: vegetative state, GOS3: severe state, GOS4: moderate state, GOS5: good recovery) Iwere compared.

**Results:** During the study period, we enrolled 116 polytraumatized patients and 54 patients were intubated. The main indication of airway management was coma with a Glasgow coma scale <8 in almost half of the population and cardiac arrest in 12% of cases. Seven percent and 3% of patients were intubated for hemodynamic and respiratory distress respectively. The two groups did not differ regarding to injury severity assessed by the 'Injury severity score' (p < 0.001). The mean length of stay in the emergency department was 23 ± 2 h in group B vs 20 ± 2 h in group A. There was no difference in terms of transfer to an intensive care between the two groups (94% in each group). Two patients (10%) in group A and six patients (17%) in group B died. There was no difference in terms of neurological outcome: in Group A, 55% of patients had a GOS 5, 20% a GOS 3 and 10% a GOS 2. In Group B, 40% of patients had a GOS 5, 18% a GOS 3 and 12% a GOS 2 (p > 0.05 for each one).

**Conclusion:** Prehospital intubation reduces the length of stay in emergency department and mortality but has no influence on the orientation of patient or on their neurological evolution. However, ambulance practitioner should be familiar with airway management and should be trained in such a challenging treatment that could worsen the prognosis of polytraumatized patients if not performed correctly.

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

FC-040

Chest trauma in children: a monocenter study

CHAARI Zied<fnref n="1" />, BEN AYED Aymen<fnref n="1" />, KAMMOUN Jaweher<fnref n="1" />, ABID Walid<fnref n="1" />, BEN AYED Ahmed<fnref n="1" />, HENTATI Abdessalem<fnref n="1" />, FRIKHA Imed<fnref n="1" />

**Correspondence:** Zied CHAARI (chaari.zied1@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-040

**Rationale:** Children are vulnerable to injuries most often occurring following a road accident. As part of polytrauma, pediatric thoracic trauma often requires special care.

**Patients and methods/Materials and methods:** This is a retrospective and analytical study including all children aged under 17 years of age, victims of thoracic trauma (whether open or closed), and hospitalized in our department (after or without admission in intensive care

<footnote n="1">¹Service des Urgences et SAMU 04 CHU Habib Bourguiba Sfax Tunisie, Sfax, Tunisie</footnote>

<footnote n="1">¹service des Urgences et SAMU 04 CHU Habib Bourguiba Sfax Tunisie, Sfax, Tunisie</footnote>

<footnote n="1">¹Université de Sfax - CHU Habib Bourguiba, Sfax, Tunisie</footnote>
or pediatric resuscitation unit) between January 2015 and December 2021.

**Results:** During the study period, 25 children were admitted to our department following severe chest trauma with an average age of 9.7±5.3 years (2–16 years) and a male predominance (88%). Road accidents (48%), domestic accidents (28%), and assaults (16%) were the most frequently reported circumstances. Seven children (28%) presented a penetrating thoracic trauma including 2 (28%) of ballistic origin. The most common lesions were pneumothorax (44%), cerebral contusions (43%), pulmonary contusions (40%), intra-abdominal lesions (36%), rib fractures (32%), pneumothorax (20%) and pneumomediastinum (12%). Cranial, peripheral, or pelvic fractures were associated in 28%, 16%, and 4% of patients respectively. The median length of stay in our service was 2 days (1–38 days). Urgent surgery was necessary for 6 children (24%) divided into 2 abdominal, 2 pulmonary, one pleural, and one cardiac surgery. The follow-up was favorable for the majority of patients (60%). Complications were mainly observed in patients who underwent surgery or were intubated for more than 4 days. No deaths were noted in our series.

**Conclusion:** The management of thoracic trauma in children must be multidisciplinary involving clinicians, emergency physicians, intensivists, as well as surgeons. Associated peripheral and cranial lesions influence the prognosis.

**Compliance with ethics regulations:** N/A.

## FC-041

### Value of early thoracic computed tomography in severe blunt chest trauma

BOUGDAL Dalila¹, SADAT Souhila¹, ZEGHDOUD Dalila¹

¹Etablissement Salim Zemirli, Alger, Algerie

**Correspondence:** Dalila BOUGDAL (bouqdalila@yahoo.fr)

*Annals of Intensive Care* 2022, **12**(1):FC-041

**Rationale:** Blunt chest trauma is common. Severe chest trauma can be life-threatening immediately or secondarily after a period of apparent calm. The objective of this study is to determine the contribution of early injury assessment to the morbidity and mortality of patients with severe blunt chest trauma.

**Patients and methods/Materials and methods:** prospective, observational study including 90 patients with severe blunt chest trauma, hospitalized in the ICU during the period March 2015–March 2017. We studied the lesion mechanism, the severity scores, we collected the pleuro-pulmonary lesions, their treatment and the future of the patients. We noted the hourly delays between the accident and the realization of the thoracic computed tomography (CT), as well as the delay between the admission to the hospital and the realization of the thoracic CT. We investigated the impact of thoracic CT on morbidity and mortality. The data were entered with the EPIINFO 7 software and analyzed using the SPSS statistics 23 software. The statistical tests are significant from $p \le 0.05$

**Results:** The mean age of the patients was 33.6±17.9 years with a male predominance (sex-ratio = 4M/1F). 98.8% were polytraumatized. The mean ISS score was 34.5±8.9; 68% of patients arrived with at least one vital distress. The delay between the thoracic radiological assessment and the time of the accident was less than 6 h in 73% of the patients. Furthermore, early assessment of injuries improved mortality ($p = 0.02$).

**Conclusion:** Early thoracic CT in severe blunt chest trauma allows an exhaustive diagnosis of thoracic lesions and improves mortality.

**Keywords:** Severe blunt chest trauma, Early chest CT.

**Compliance with ethics regulations:** N/A.

## FC-042

### Flail chest: what are the associated morbidity and mortality risk factors?

CHAARI Zied¹, BEN AYED Aymen¹, KAMMOUN Jaweher¹, BEN AYED Ahmed¹, ABID Walid¹, HENTATI Abdessalem¹, FRIKHA Imed¹

¹Université de Sfax - CHU Habib Bourguiba, Sfax, Tunisie

**Correspondence:** Zied CHAARI (chaari.zied1@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-042

**Rationale:** Rib fractures are frequently observed in patients with chest or multiple trauma. Flail chest represents a particular entity in terms of prognosis and management. Rare are the studies that have focused on the search for morbidity and mortality associated factors for patients with traumatic flail chest.

**Patients and methods/Materials and methods:** This was a retrospective and analytical study including all patients hospitalized in our department for a flail chest (with or without going through an intensive care or resuscitation unit) between January 1987 and December 2021.

**Results:** During the study period, 2342 patients were admitted to our department for chest trauma including 159 patients with confirmed flail chest (7%). The mean age was 53±16 years (11–90 years) and a male predominance was noted (sex ratio = 6.22). The mean number of rib fractures was 12.9±4.9 fractures (6–22 fractures). An intensive care unit hospitalization was necessary for 66% of patients. Conservative treatment (thoracic drainage, analgesia, nebulization and respiratory physiotherapy) was performed in the majority of cases (95%), and surgical treatment was necessary for only 8 patients (5%). During hospital stay we have reported complications for 56 patients (35%) and 7 patients died (hospital mortality of 4%). The mean injury severity score (ISS) was 20 (13–50). The factors associated with high morbidity rates were: ISS score > 25, hospitalization in intensive care unit, the need for intubation, and length of hospitalization > 7 days. For all possible mortality-studied factors, only an ISS score > 25 was associated with an increase in mortality rates.

**Conclusion:** Flail chest are associated with several factors influencing vital prognosis, as well as post-traumatic consequences during hospital or intensive care unit stays. A good knowledge of these factors would make it possible to better manage patients and improve subsequent follow-up.

**Compliance with ethics regulations:** N/A.

## FC-043

### Antivenoms to treat Bothrops genus snakebite envenoming in the French Territories in the Americas: comparative experimental studies

FLORENTIN Jonathan, RESIERE Dabor¹, KALLEL Hatem², FLORENTIN Jonathan¹, GUTIÉRREZ José Maria³, MEHDAOUI Hossein¹, NEVIERE Remi⁴, MEGARBANE Bruno⁵

¹Critical Care Unit, University Hospital of Martinique (French West Indies), Fort-De-France, Martinique; ²Intensive Care Unit, Cayenne General Hospital, Cayenne, Guyana; ³Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; ⁴Department of cardiovascular surgery, University Hospital of Martinique, Fort-De-France, Martinique; ⁵Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris University, INSERM UMRS1144, Paris, France

**Correspondence:** Dabor RESIERE (dabor.resiere@chu-martinique.fr)

*Annals of Intensive Care* 2022, **12**(1):FC-043

**Rationale:** In the French Territories in the Americas, *Bothrops* snakebite envenoming represent a public health issue. In Martinique, *Bothrops lanceolatus* is the only snake responsible for envenoming with thrombotic complications. In French Guiana, *Bothrops atrox* is responsible for most envenomings. The first antivenom specific to *Bothrops lanceolatus*, *Bothrofav®*1, produced in 1991, reduced complications. However, in 2004, an upsurge in cases of ischemic stroke despite early antivenom infusion, suggested a decline in its effectiveness. A new antivenom, *Bothrofav®*2 was produced in 2011 and manufactured in France. However, its marketing should be stopped in 2022. Polival-ICP® (manufactured in Costa Rica) and Antivipmyn Tri® (manufactured in Mexico) are successfully used to treat *Bothrops atrox* envenoming in French Guiana. We compared the effectiveness of all three antivenoms on *Bothrops lanceolatus* and *B. atrox* venoms using an experimental bench protocol.

**Patients and methods/Materials and methods:** We conducted third-generation antivenomics quantitative analyses, in vivo mouse and in vitro assays comparing *Bothrofav®*2, Polival-ICP® and Antivipmyn Tri® on *Bothrops lanceolatus* and *B. atrox* venoms.
**Results:** Bothrofav®2 immunocaptured all major *Bothrops lanceolatus* venom protein components, underscoring its high neutralizing efficacy (Table 1). Our in vivo and in vitro assays demonstrated its effectiveness in the neutralization of lethal, local and systemic haemorrhagic, oedema forming, myotoxic, thrombocytopenic, proteinase and phospholipase A2 activities, showing a higher preclinical efficacy as compared to previous batch used in the past. Regarding the neutralization of *B. atrox* venom, Polival-ICP® has higher neutralizing activity than Antivipmyn Tri® against lethal, haemorrhagic and in vitro coagulant activities. Antivipmyn Tri® and Polival-ICP® antivenoms similarly neutralized the venom-induced myotoxic effects of *B. atrox* venom, while Antivipmyn Tri® did not neutralize the lethal activity at the highest antivenom level tested.

**Conclusion:** Based on preclinical investigations, Bothrofav2® was highly effective in the neutralization of the venom of *B. lanceolatus*, whereas Polival-ICP® and Antivipmyn Tri® neutralized the venom of *B. atrox*, albeit with different efficacies.

**Compliance with ethics regulations:** Yes in animal testing.

FC-044

**Association between healthcare trajectories before critical illness and 1-year survival among elderly patients hospitalized in ICU for acute respiratory infection—To predict the future, you need to know the past**

TCHATAT WANGUEU Lionel¹, GABORIT Christophe¹, LAURENT Emeline¹, GRAMMATICO-GUILLON Leslie¹, GUILLON Antoine¹

¹CHRU Tours, Tours, France

**Correspondence:** Lionel TCHATAT WANGUEU (tchatatlegrand@outlook.fr).

*Annals of Intensive Care* 2022, **12**(1):FC-044

**Rationale:** Intensive care unit (ICU) hospitalizations of elderly patients with acute respiratory infection (ARI) have increased; however, we observed an important mortality during the ICU stay and in the first year of hospital discharge. Yet many physicians have doubts as to whether elderly patients benefit from ICU admission. Our hypothesis is that healthcare trajectories before critical illness might be used as surrogate of frailty that can be useful for the decision-making. The aim of this study was to assess whether the healthcare trajectories in the 3 months preceding ICU admission were associated with 1-year survival in elderly patients with ARI.

**Patients and methods/Materials and methods:** A national population-based cohort study was performed from hospital discharge databases (2013–2017) and included ICU patients ≥ 80 years old with an ARI. Patient characteristics were collected as well as ICU procedures and their healthcare trajectories before and after discharge from ICU. Healthcare trajectories before critical illness were evaluated by the number of emergency room visits and the number of cumulative days of hospitalization 3 months before admission in ICU. Mortality refers to mortality at hospital or 1 year after discharge, during the follow-up period. The vital status of patients was assessed during at least 3-year follow-up. Logistic regression was used to find prehospital factors associated with mortality. Odd ratios (OR) and 95% confidence intervals (95% CI) were calculated. Results are in median (IQR).

**Results:** 40 327 patients aged 80 years or older were hospitalized in ICU for ARI during the studied period. Among them, 35 666 (88%) had a known vital status at 1 year of which 19 379 (54%) died during ICU stay or the first year of discharge. Patient characteristics were: age 84 [82–87] years old, male 19 708 (55.2%), SAPS II 30 [20; 44], invasive mechanical ventilation 9241 (26%). During the 3-month period preceding the ICU-admission, ≥ 1 day of hospitalization or ≥ 1 visit to the emergency room were independently associated with increased 1-year mortality: OR 1.27 [1.19–1.35] and 1.13 [1.06–1.20], respectively.

Other independent factors associated with a worse outcome were: age (OR 1.05 [1.04–1.06]), male sex (OR 1.40 [1.34–1.46]), ≥ 3 comorbidities (OR 1.10 [1.03–1.18]) and frailty score ≥ 5 (OR 1.17 [1.11–1.25]).

**Conclusion:** Healthcare consumption 3 months prior to ICU was associated with 1-year mortality among elderly patients hospitalized for ARI. Healthcare consumption is an objective and easy-to-obtain information that may be used to implement a clinical score designed to help the decision-making for ICU admission of elderly with ARI.

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

FC-045

**Evaluation of preoperative frailty in cardiac surgery patients using the Edmonton Frail Scale. "Frail heart" study, a preliminary analysis**

NTWALI Francis¹, MOMENI Mona¹, JACQUET Luc¹, VANCAENEGEM Olivier¹, LATERRE Pierre-François¹, DECHAMPS Melanie¹

¹UCLouvain, Bruxelles, Belgique

**Correspondence:** Francis NTWALI (francisntwali@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-045

**Rationale:** Frailty is a state of increased vulnerability to a stressor event, resulting in a poor resolution of homeostasis which increases the risk of adverse outcome. Recent studies have shown association between pre-operative frailty in older patients and mortality after cardiac surgery. The Edmonton Frail Scale (EFS) is a valid, quick to use tool which allows bedside assessment of preoperative frailty without the need of any special training. Frailty is usually assessed for patients aged 65 years and older, but prevalence in younger patients admitted to hospital is significant and is associated with adverse outcome. The primary objective of this study is to assess the association between frailty and intensive care unit (ICU) length-of-stay, hospital discharge after 30 days and one-year mortality in patients undergoing cardiac surgery, independently of age.

**Patients and methods/Materials and methods:** This is a prospective, monocenter and observational study in a tertiary care academic hospital. The study has been approved by the ethics comity of the hospital and all patients signed an informed consent. Overall, 233 consecutive patients who met the inclusion criteria (18 years old and older undergoing any cardiac surgery under cardiopulmonary bypass) and agreed with the study protocol were included between 25th April 2019 and 24th February 2020 and were evaluated preoperatively by EFS. Exclusion criteria were salvage surgery and patients with cirrhosis CHILD B or C.

**Results:** 191 (82%) patients were not frail, 42 (18%) were vulnerable or frail. The mean age of the entire cohort was 66.88 ± 12.01 years old. 80 patients were under 65 years old and 10 (12.5%) of them were vulnerable or frail. 153 were 65 years old or more and 32 (20.9%) of them were vulnerable or frail. Functional independence was the frailty domain with the strongest correlation with the overall EFS score. Prealbumin was the biological value with the strongest correlation with frailty (r = − 0.40, p < 0.05). In the non-frail group, 184 patients (96.3%) were discharged at day 30 compared to 34 (80.9%) in the frail group. The mean ICU length of stay was 3.38 ± 2.17 days in the non-frail group and 8.26 ± 14.95 days in the frail group. One year after surgery, 4 (2.3%) patients died in the non-frail group and 7 (21.9%) died in the frail group (p < 0.05).

**Conclusion:** Frailty significantly affects patients undergoing cardiac surgery, even under the age of 65, and is associated with significantly longer ICU length-of-stay, lower discharge at 30 days and higher one-year mortality.

**Compliance with ethics regulations:** Yes in clinical research.
<figure><img src="image_60.png" /></figure>

Results

FC-046

Community peritonitis in the elderly

JARIR Ibtissam¹, KHALLEQ Khalid¹, BAZA Sanaa¹, HARRAR Rachid¹,
BOUHOURI Mohamed Amine¹, HATTABI Khalid¹
¹CHU IBN ROCHD, Casablanca, Maroc

**Correspondence:** Ibtissam JARIR (ibtissamjarir30@gmail.com)

Annals of Intensive Care 2022, 12(1):FC-046

**Rationale:** Community peritonitis in the elderly is a medical-surgical emergency, acquired by the patient in an extra hospital environment. The diagnosis is usually late due to the heterogeneity of clinical signs, this leads to a delay in management. The objective of our study is to evaluate the prognostic factors of an epidemiological, clinical, para-clinical, etiological, therapeutic and evolutionary order of the community peritonitis in the elderly in our context.

**Patients and methods/Materials and methods:** We conducted an analytical descriptive retrospective study of 50 cases of community peritonitis hospitalized in the surgical emergency resuscitation department over a period from January 2018 to June 2020. All patients over 65 years of age who were admitted for community peritonitis and who received medical and surgical care were included in this study. The parameters studied are demographic data, clinical and paraclinical signs, management and patient evolution. The Statistical analysis was performed using SPSS software, the evaluation of prognostic factors using a univariate and multivariate analysis.

**Results:** The study showed that the mean age was 70.08 ± 6.07 years, with a sex ratio of 2.12. The medical history was dominated by smoking (38%), the extra-abdominal signs (hemodynamic failure (70%), renal failure (68%), hematological disorders (48%), respiratory disorders (34%) and neurological disorders (32%)). Therapeutic management was based on perioperative resuscitation, treatment of organ failure, probabilistic antibiotic therapy and median laparotomy surgery. The main etiologies of community peritonitis were: peptic ulcer perforation (44%), intestinal perforation (22%), intestinal necrosis (12%), cholecystitis (4%). The bacteriological samples carried out in per operative allowed to have the following bacteriological profile: predominance of Gram-negative bacteria (61%) dominated by *E. coli* (39%), the average length of hospitalization was 6.32 ± 5.25 days. The mortality rate was 68%. The main prognostic factors identified in our univariate analysis study were: high blood pressure, organ failure, increased gravity scores, site of intervention, duration of intervention, use of catecholamines, development of septic shock, as well as duration of mechanical ventilation and duration of stay in intensive care unit. Multivariate analysis showed a statistically significant association between high blood pressure and the development of hemodynamic failure, creatinine > 13 mg/L, C-reactive protein > 150 mg/L, Occlusion,

norepinephrine + epinephrine, duration of ventilation > 2.5 days and mortality.

**Conclusion:** Community peritonitis in the elderly is a serious condition, fraught with high mortality. The improvement of its prognosis is based on a screening of risk factors, and an updating of medical—surgical protocols.

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

FC-047

COVID-19 and elderly population

CHOUCHÊNE Salma¹, FATHALLAH Ines¹, FAZZENI Hayfa¹, MAHMOUD Jihene², KOURAICHI Nadia¹

¹Hôpital régional de Ben Arous, Ben Arous, Tunisie; ²hopital Sahloul, Sousse, Tunisie

**Correspondence:** Salma CHOUCHÊNE (Zamitisalma92@gmail.com)

Annals of Intensive Care 2022, 12(1):FC-047

**Rationale:** To describe the clinical and prognostic particularities of COVID-19 infection in elderly patients hospitalized for a SARSCOV 2 infection.

**Patients and methods/Materials and methods:** Descriptive and comparative retrospective study conducted from September 2020 to September 2021. We included all patients admitted to intensive care with a serious SARSCOV2 infection. The infection was confirmed by RT-PCR, a rapid test or a typical chest CT scan. Elderly patients were defined as whom aged over 65 years old.

**Results:** We included 217 patients, 93 (42%) of whom were elderly subjects. The gender ratio was 1.11. The average IGSII score was 38 ± 14. For the past history, hypertension (56%) was at the top of the list followed by diabetes (43%). Twenty-eight patients were treated at home, 9 of whom required oxygen therapy. The first clinical examination showed anxiety and agitation in 17 (18%) and 18 (19%) patients respectively. Mechanical ventilation (MV) was used in 55 patients (59%) with prone positioning in 41 of cases (44%). Acute renal failure was noted in 46 (51%) patients and six (7%) patients required dialysis. Forty-one patients presented septic shock, 10 trophic disorders and five resuscitation delirium. The median durations of MV and intensive care unit (ICU) stay were respectively 7 [2;14] and 10 [6;16] days. The overall mortality was 53%. In the young population, more agitation (p = 0.033) and anxiety (p = 0.04) were noted with a longer duration of ventilation (11 vs 7 days (p = 0.004)). Elderly subjects were more severe on admission [IGSII score 37 vs 29 (p < 0.001)] and they developed more acute renal failure (51 vs 28%. (p < 0.001)). There was no significant difference between the two groups (old and young subjects) in terms of intubation time and mortality.

**Conclusion:** The elderly population was more severe on admission and the ICU stay was complicated by more acute renal failure. There was no difference in terms of mortality between young and old subjects.

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

FC-048

Utilization of automated oxygen titration in patients managed at the emergency department for suspected or confirmed COVID-19

DALLAIRE Léa¹, GUIROY Antoine¹, BOUCHARD Pierre-Alexandre ¹, LELLOUCHE Francois¹

¹Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Canada

**Correspondence:** Francois LELLOUCHE (francois.lelouche@criucpq.ulaval.ca)

Annals of Intensive Care 2022, 12(1):FC-048

**Rationale:** During the COVID-19 pandemic, automated oxygen titration has been implemented at the emergency department (ED) to maintain the patients within the oxygenation targets and to reduce the interventions from healthcare workers. We report here our experience to manage patients with suspected or confirmed COVID-19 at the ED.
**Patients and methods/Materials and methods:** We retrospectively collected data from the automated oxygen titration device (SpO₂ target, respiratory rate and heart rate) in patients managed at the ED between April 2021 and February 2022. We analyzed the time within the SpO₂ target (set SpO₂ ± 2%), with hypoxemia (SpO₂ < target - 5%), with hyperoxemia (SpO₂ > target + 5%). We analyzed the whole population and the subgroup of patients with confirmed COVID-19. We evaluated the number of patients with oxygen weaning during the management. We evaluated separately the impact of the SpO₂ target on oxygen flow when the target was modified by the clinicians by 2% or more. In this subgroup of patients, we evaluated the mean oxygen flowrate 15 min before and after the modification of the SpO₂ target.

**Results:** We included 98 patients (mean age 72 ± 16 years, 57% were men) admitted to the ED with acute respiratory distress and suspected (n = 77) or confirmed (n = 21) COVID-19 requiring oxygen therapy. The mean duration of utilization of automated oxygen titration device was 14.3 ± 4.7 h. A SpO₂ signal was present 91.9% of the time. Main SpO₂ targets set by the clinicians were 90% (43%), 88% (27%), 92% (20%), 94% (4%). Oxygen weaning was possible in 35/98 patients (36%). For the whole population/COVID-19 patients, the time in the SpO₂ target was 78/81%, time with hypoxemia was 3/3%, time with hyperoxemia was 2/0.6%. In a subgroup of 11 patients, the effect of modifying the SpO₂ target was evaluated. The mean initial SpO₂ target was 91.9% and the mean final target was 89.5%. The mean initial and final oxygen flow were 3.3 ± 0.6 and 1.9 ± 0.6 L/min respectively, P = 0.0076.

**Conclusion:** In patients with acute respiratory failure, the utilization of automated oxygen therapy was feasible to manage patients with suspected or confirmed COVID-19 with potential benefits. Similarly to other studies with automated oxygen therapy, the time in the oxygenation target was high, and oxygen weaning was potential in 1/3 of the patients. SpO₂ target has a significant impact on oxygen flow rates and is a useful tool with this new device.

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

<figure><img src="image_61.png" /></figure>

impact of the SpO₂ target on oxygen flowrate in a subgroup of 11 patients with modified target. With high SpO₂ target (mean 91.9%) reduced to low SpO₂ target (mean 89.5%), oxygen flow was significantly reduced from 3.3 to 1.9 L/min.

FC-049

**Acute heart failure in the emergency department: prognosis value of PaO₂/FiO₂ ratio**

GHABARA Racha¹, BAHRI Badra¹, SEDGHIANI Ines¹, KHIARI Saoussen¹, DOGHRI Hamdi¹, TOUJ Hager¹, ZAGHDOUDI Imen¹, FALFOUL Nebiha¹

¹Hospital Habib Thameur, Tunis, Tunisie

**Correspondence:** Racha GHABARA (Rsha993@gmail.com)
Annals of Intensive Care 2022, **12**(1):FC-049

**Rationale:** Heart failure is a common presentation in the emergency department. Searching for risk factors is a challenging step in the emergency physicians. The purpose of our study was to search for prognosis values of ratio PaO₂/FiO₂ in patients admitted to the emergency department for acute heart failure.

**Patients and methods/Materials and methods:** Prospective mono-center observational study, conducted between November 2021 and January 2022. We included patients over the age of 18, we established diagnosis of heart failure on clinical grounds. We performed blood gases at admission. The primary endpoint was in-hospital mortality.

**Results:** We included 100 patients. Average age: 73 ± 11 years and sex ratio M/F = 51/49. The most common comorbidities were hypertension: 81(82%), diabetes 46 (47%), coronary artery disease 47(47%) patients; 68% had a left ventricular ejection fraction (LVEF) more than 40%, with an average pro-BNP of 9,440 pg/mL; 37% of patients had permanent atrial fibrillation. 24% returned in < 30 days with an average of readmissions/year of 1.75(± 0.96). Seventy-two patients (76%) required ventilatory support, 5% required the use of invasive mechanical ventilation. The mortality rate was 12%. There was no significant difference in terms of comorbidity between the group of deceased and surviving patients. However, deceased patients had a higher SOFA score (4 vs 2; p = 0.001), a lower LVEF (43% vs 25%; p = 0.18). D-dimers and CRP were higher in the deceased patients, with a median value of 3636 vs 1385 µg/L (p = 0.001) and 98 vs 56 mg/L (p = 0.08) respectively. The PaO₂/FiO₂ ratio in admission was 195 in the deceased patients vs 298 in the surviving patients (p = 0.01). The PaO₂/FiO₂ ratio was as an independent mortality factor (OR = 0.99, CI [0.98; 1.00], p = 0.05). Using the ROC curve, the best cut-off for the PaO₂/FiO₂ ratio was 160. A PaO₂/FiO₂ ratio ≤ 160 was predictive of mortality with an area under curve of 0.74, a sensitivity of 86% and a specificity of 76%.

**Conclusion:** A PaO₂/FiO₂ ratio ≤ 160 is an independent factor of death in patients admitted to the emergency department with acute heart failure.

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

FC-050

**Care prognosis and outcomes in elderly patients admitted to the intensive care unit**

JERBI Mouna¹, GHORBEL Rezk¹, REKIK Akraf¹, BEN JEDDOU Kais¹, GHARBI Emna¹, BEN AMAR Boutheina¹, CHAKROUN Olfa¹, REKIK Noureddine¹

¹Centre Hospitalo-universitaire Habib Bourguiba sfax, Sfax, Tunisie

**Correspondence:** Rezk GHORBEL (rezkghorbel3@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-050

**Rationale:** To describe the medical histories, demographic characteristics and analyze the standardized geriatric assessment in elderly patients admitted to emergency department intensive care unit (EDUCI). To determine the pathologies found in these patients as well as the therapeutic and outcomes.

**Patients and methods/Materials and methods:** This is a prospective descriptive study carried out at the EDUCI of the Habib Bourguiba University Hospital, during a period of four months. We included all people aged 65 and older admitted to our intensive care unit. We observed their therapeutic management as well as their demographic and evolutionary characteristics. We also calculated the ADL score for all patients and followed their evolution at discharge from the emergency room.

**Results:** Our study involved 262 patients during the enrollment period. The average age was 77 ± 8 years with a sex ratio of 1.1. From pathological medical history was noted in most patients (82%) dominated by hypertension and diabetes mellitus. The majority of patients (74%) are polymedicated. The history of hospitalization was found in 42% of cases. Data anamnestics have shown the presence of cognitive disorders and Alzheimer's disease in 21% and 7% of cases, respectively. The ADL score showed a loss of autonomy for 39% of the population. The reasons of hospitalizations were mainly medical and, to a lesser extent, traumatic and visceral reasons while the deterioration of the general state was involved in 5% cases. Overall, 11% of patients required mechanical ventilation and 9% of patients required a blood transfusion. The average length of hospital stay was 3 ± 4 days. The evolution was favorable in the majority of cases (75%). Among
home leavers (41%), a quarter sustained moderate or severe sequelae. These sequelae were essentially neurological deficit, resuscitation neuromyopathy and/or pressure sores. The evolution has been fatal in 17% of cases, in the EDICU. The main causes of death were cerebral suffering (8%), septic shock and hypoxemia.

**Conclusion:** The admission of geriatric patients to the ICU is increasing. Frailty assessment may play an important role in the clinical evaluation of such individuals for triage, but should not be considered a priori as an exclusion criterion for admission. Physicians are aware of the difficulties faced with such patients and the need to promote short admission pathways.

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

## FC-051

### French translation and validation of the Healthy Aging Brain Care-Monitor, Hybrid Version (HABC-M-HV): a new tool for remote post-intensive care syndrome screening

BOUGARD Laurine¹, BEAUDART Charlotte¹, COLSON Camille¹, HORLAIT Geoffrey², BORNHEIM Stephen³, BRUYERE Olivier¹,³, MISSET Benoit¹, ROUSSEAU Anne-Françoise¹

¹CHU Liège, Liège, Belgique; ²CHU UCL Namur, Namur, Belgique; ³University of Liège, Liège, Belgique

**Correspondence:** Laurine BOUGARD (laurine_bougard@hotmail.com)

Annals of Intensive Care 2022, **12**(1):FC-051

**Rationale:** Patients surviving a stay in an intensive care unit (ICU) may experience new or worsening disorders that have been labeled as "post-intensive care Syndrome" (PICS). PICS includes physical weakness, mental disorders and neurocognitive impairments that can affect the patient's quality of life. Authors of the Healthy Aging Brain Care Monitor have developed a hybrid version (HABC-M-HV) suited to the daily needs of their post-ICU follow-up clinic. This is a 30-item questionnaire with 4 subscales for cognitive, functional, psychological and quality of life assessment. The hybrid version of the HABC-M questionnaire (HABC-M-HV) has not yet been validated in its English version. Using rigorous methodologies, the objectives of this cross-sectional observational study were to translate the HABC-M-HV questionnaire into French (HABC-M-HV-F, Fig. 1) and to evaluate the main measurement properties of this new version.

**Patients and methods/Materials and methods:** The questionnaire was translated following a five-stage validated method for the translation and cross-cultural adaptation of questionnaires. A convenience sample of ICU survivors was recruited in our follow-up clinic to validate the questionnaire. The HABC-M-HV-F was administered by phone. The measurement performances of the questionnaire were tested using internal consistency, test-retest reliability, standard error of measurement (SEM) and smallest detectable change (SDC) calculation, floor and ceiling effect measurement and construct validity.

**Results:** A total of 51 patients with 14/51 (27.5%) women were recruited between February and September 2021. Their median age was 63 [55–71] years. The internal consistency was very good (Cronbach's alpha coefficient 0.79). The intra- and inter-examiner reliabilities were excellent (Intraclass Coefficient Correlation = 0.99 and 0.97, respectively). Total scores of the HABC-M-HV-F were very similar between test and retest with the same examiner, respectively 9 [4–15] and 8 [4–16], as well as with two examiners, respectively 12 [6–24] and 12 [4–23]. The SEM was 0.62 and the SDC was 1.72. No floor nor ceiling effects were observed. The convergent validity was almost entirely confirmed with 71.4% of our hypothesis confirmed.

**Conclusion:** The HABC-M-HV-F has been shown to be a valid and reliable tool for standardized PICS screening and follow-up among French-speaking ICU survivors. A remote administration by phone is feasible, making it an advantageous alternative in the growing context of telemedicine.

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

<table><thead><tr><th></th><th>Pas du tout (pendant 0 ou 1 jour)</th><th>Durant quelques jours (pendant 2 à 6 jours)</th><th>Plus de la moitié du temps (pendant 7 à 11 jours)</th><th>Tous les jours ou presque (12-14 jours)</th></tr></thead><tbody><tr><td colspan="5"><strong>Healthy Aging Brain Care-Monitor-Hybrid version - French (HABC-M-HV-F)</strong><br>Quand vous complétez cette évaluation, merci de garder à l'esprit que votre réponse doit être votre première réaction à la question. Il n'y a pas de définition formelle pour les symptômes que l'on vous demande d'évaluer. C'est pourquoi des exemples sont parfois inclus.</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, avez-vous eu des problèmes pour</strong></td></tr><tr><td>Prendre une décision, porter un jugement</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Apprendre à utiliser un outil, un appareil, un accessoire ou un gadget</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Vous souvenir du mois ou de l'année en cours</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Gérer votre argent: équilibrer le budget, payer vos factures, gérer les impôts etc.</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Vous rappeler de vos rendez-vous</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Penser ou vous rémemorer</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, avez-vous</strong></td></tr><tr><td>Eu moins d'intérêt ou de plaisir à faire des choses, des loisirs ou des activités</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Répété les mêmes choses encore et encore, comme des questions ou des histoires</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, avez-vous eu des problèmes pour</strong></td></tr><tr><td>Programmer, préparer ou servir les repas</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Prendre vos médicaments à la bonne dose ou au bon moment</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Marcher ou vous déplacer</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Vous laver</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Faire vos courses (alimentaires)</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Conduire</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Faire les tâches ménagères</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, êtes-vous</strong></td></tr><tr><td>Tombé ou avez-vous trébuché</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, avez-vous vécu les situations suivantes ?</strong></td></tr><tr><td>Se montrer mal, déprime ou désespéré</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Se sentir seul</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Rejoiter l'aide des autres ou se sentir irrité</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Se sentir anxieux, nerveux, tendu, effrayé ou paniqué</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Croire que les autres veulent vous voler ou vous faire du mal</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Entendre des voix, voir des choses ou parler à des gens qui ne sont pas présents</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Avoir trop peu ou trop d'appétit</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Tomber endormi, avoir du mal à se lever ou trop dormir</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Agrir de manière impulsive, sans penser aux conséquences de vos actes</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Error, faire les cent pas ou faire des choses de manière répétitive</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="5"><strong>Au cours des deux dernières semaines, avez-vous été prê occupé par :</strong></td></tr><tr><td>Votre qualité de vie</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Votre avenir financier</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Votre santé mentale</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td>Votre santé physique</td><td>0</td><td>1</td><td>2</td><td>3</td></tr><tr><td colspan="4"><strong>Total des colonnes</strong></td><td></td></tr><tr><td colspan="4"><strong>Score</strong></td><td></td></tr></tbody></table>

### Healthy Aging Brain Care Monitor Hybrid Version in French

## FC-052

### Ceftolozane/Tazobactam use for the treatment of bacterial infections in France: focus on patients with abnormal renal functions

RUIMY Raymond¹, AKRICH Brune², BOURGE Xavier², BOUTOILLE David³, BRASSAC Isabelle², CASTAN Bernard⁹, LORIEAU-THIBAULT Raphaèle², MACKOSSO Carole², MONTEIRO TAVARES Linsay⁵, MOOTIEN Joy⁶, RUIZ Fabrice⁵, TIMSIT Jean-François⁷

¹CHU Nice, Nice, France; ²MSD France, Puteaux, France; ³CHU Nantes, Nantes, France; ⁴CH Périgueux, Périgueux, France; ⁵ClinSearch, Malakoff, France; ⁶CHU Mulhouse, Mulhouse, France; ⁷AP-HP Bichat, Paris, France

**Correspondence:** Gabriella PASSONI (gabriella.passoni@clinsearch.net)

Annals of Intensive Care 2022, **12**(1):FC-052

**Rationale:** The Conduct study was initiated following a request from the French Health Authorities, to describe the use of Ceftolozane/Tazobactam (C/T) in current clinical practice.

**Patients and methods/Materials and methods:** This was an observational, prospective, multicenter, French study. Any patient having received at least one dose of C/T was eligible to participate and
followed-up upon inclusion until stop of C/T. This analysis aims to examine C/T outcomes relative to renal functions, in patients with pneumonia, or treated for complicated intra-abdominal (cIAI) or urinary tract infections (cUTI) and pyelonephritis (other indications). Current recommended daily C/T doses are 6 g/3 g for pneumonia treatment (indication approved in August 2019), and 3 g/1.5 g for the other indications, with decreased daily doses recommended in patients with renal impairment. Normal renal functions were defined as creatinine clearance (CLCR) between 50-150 mL/min, augmented renal clearance (ARC) was defined as CLCR > 150 mL/min, and renal impairment (RI) as CLCR < 50 mL/min.

**Results:** Between October 2018 and December 2019, 260 patients were enrolled and data on renal functions were available for 240. Of these, 133 (55.4%) presented with pneumonia (of whom, 30.8% [N=41/133] included after the approved indication), and 50 (20.8%) received C/T for the three other approved indications (the remaining 57 received C/T for another indication—data not shown). Baseline demographic and clinical characteristics are presented in Table 1. Among patients treated for pneumonia and included after the indication was approved, all RI patients received a dose adaptation (less than 6 g/3 g). On the other hand, 3/5 (60%) of ARC patients and 10/29 (34.5%) of patients with normal renal functions received doses lower than 6 g/3 g. For the other indications, the majority of ARC and normal renal function patients received the standard dose (57.1% [N=4/7] and 71% [22/31], respectively); 42.8% of ARC patients and 22.6% with normal renal function received higher doses (between 4 g/2 g and 6 g/3 g). Among RI patients, dose adaptation was not strictly followed (8/12 received 3 g/1.5 g, and one patient received 4.5 g/2.25 g). In both groups, the most commonly reported reasons for treatment termination were complete or partial cure (100%, 93.1%, 85.7%, for ARC, normal renal functions, and RI pneumonia patients respectively, and 57.1%, 71%, 66.6%, for the same subgroups in patients with other indications).

**Conclusion:** These results suggest that C/T dose adaptation is followed by most clinicians, and provides important cure rates among all renal function groups.

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

<table><thead><tr><th rowspan="2">Pneumonia Patients (included after approval of 6g/3g dose – August 2019)</th><th colspan="2">CLCR</th><th rowspan="2">CLCR<br/>&lt; 50 mL/min</th></tr><tr><th>&gt; 150 mL/min</th><th>50-150 mL/min</th></tr></thead><tbody><tr><td></td><td>N=5</td><td>N=29</td><td>N=7</td></tr><tr><td>Age, mean (SD)*</td><td>52.6 (15.3)</td><td>48.8 (20.4)</td><td>61.1 (18.9)</td></tr><tr><td>Sex, Men (%)</td><td>5 (100%)</td><td>13 (44.8%)</td><td>5 (71.4%)</td></tr><tr><td>Charlson Comorbidity Index &gt; 5 (%)</td><td>1 (20%)</td><td>4 (13.8%)</td><td>5 (71.4%)</td></tr><tr><td>Patients with prior medical conditions, N (%)</td><td>4 (80%)</td><td>25 (86.2%)</td><td>7 (100%)</td></tr><tr><td colspan="4">Most frequent medical conditions</td></tr><tr><td>Chronic pulmonary disease</td><td>2 (40%)</td><td>23 (79.3%)</td><td>5 (71.4%)</td></tr><tr><td>Diabetes</td><td>1 (20%)</td><td>6 (20.7%)</td><td>2 (28.6%)</td></tr><tr><td>Renal insufficiency</td><td>0</td><td>0</td><td>3 (42.9%)</td></tr><tr><td>Duration of C/T treatment, Mean (SD)</td><td>16.4 (7.2)</td><td>15.9 (8.2)</td><td>12.9 (7.2)</td></tr></tbody></table><table><thead><tr><th rowspan="2">Other Indications (cIAI<sup>a</sup>, cUTI<sup>b</sup>, Pyelonephritis)</th><th colspan="2">CLCR</th><th rowspan="2">CLCR<br/>&lt; 50 mL/min</th></tr><tr><th>&gt; 150 mL/min</th><th>50-150 mL/min</th></tr></thead><tbody><tr><td></td><td>N=7</td><td>N=31</td><td>N=12</td></tr><tr><td>Age, mean (SD)</td><td>53.1 (18.1)</td><td>63.1 (14.4)</td><td>67.0 (13.6)</td></tr><tr><td>Sex, Men (%)</td><td>5 (71.4%)</td><td>24 (77.4%)</td><td>9 (75%)</td></tr><tr><td>Charlson Comorbidity Index &gt; 5 (%)</td><td>2 (28.6%)</td><td>16 (51.6%)</td><td>9 (75%)</td></tr><tr><td>Patients with prior medical conditions, N (%)</td><td>5 (71.4%)</td><td>26 (83.9%)</td><td>11 (91.7%)</td></tr><tr><td colspan="4">Most frequent medical conditions</td></tr><tr><td>Diabetes</td><td>0</td><td>12 (38.7%)</td><td>4 (33.3%)</td></tr><tr><td>Renal insufficiency</td><td>0</td><td>7 (22.6%)</td><td>8 (66.7%)</td></tr><tr><td>Peripheral vascular disease</td><td>2 (28.6%)</td><td>4 (12.9%)</td><td>5 (41.7%)</td></tr><tr><td colspan="4">Distribution of index infection £</td></tr><tr><td>cIAI</td><td>3 (42.9%)</td><td>15 (48.4%)</td><td>2 (16.7%)</td></tr><tr><td>cUTI</td><td>3 (42.9%)</td><td>12 (38.7%)</td><td>6 (50%)</td></tr><tr><td>Pyelonephritis</td><td>1 (14.3%)</td><td>5 (16.1%)</td><td>4 (33.3%)</td></tr><tr><td>Duration of C/T treatment, Mean (SD)</td><td>13.1 (5.9)</td><td>13.4 (10.2)</td><td>11.0 (7.4)</td></tr></tbody></table>

<caption>Table 1</caption>

### FC-053

#### Does the cefepime plasma concentration at steady-state in critical ill patients frequently exceed the maximum target assumed to be neurotoxic?

JEAN-MICHEL Vanessa¹, HOMEY Corentin¹, CAULIER Thomas¹, DELANNOY Pierre-Yves¹, BOUSSEKEY Nicolas¹, GEORGES Hugues¹

¹CH TOURCOING, Tourcoing, France

**Correspondence:** Vanessa JEAN-MICHEL (vanessa.jeanmichel@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-053

**Rationale:** Cefepime (CEF) is one of antimicrobials commonly prescribed for nosocomial infections in intensive care unit (ICU). Neurotoxicity of cefepime can occur for plasma concentration > 35 mg/L, when administered by continuous infusion [1,2]. We aimed to assess the risk factors of plasma CEF concentration at steady state above 35 mg/L. We also determined the relationship between neurotoxicity, CEF concentration and general co-morbidities.

**Patients and methods/Materials and methods:** We performed a retrospective study of adult ICU patients treated with CEF for at least 48 h between January 2019 and September 2021.

**Results:** Fifty-seven patients were included. Twenty-one patients had a renal clearance < 60 mL/min/1.73 m² before CEF initiation. The mean starting daily dose of CEF was 5.4 (1.3) g. The mean time to first CEF monitoring was 2.9 (1.7) days and the incidence of CEF concentration above 35 mg/L was 46/57 (80.7%) patients. Factors independently associated with CEF concentration above 35 mg/L were age upper to 65 years old [OR= 4.1 (95% CI 1.1–62.1), p= 0.04] and initial daily delivery of 6 g of CEF [OR= 2.7 (95% CI 1.2–68.9); p= 0.03]. Presumed CEF neurotoxicity was 12/57 (21.1%) patients. Mean CEF concentration was higher for patients who developed neurotoxicity: 85 (31.2) mg/L vs 50.9 (23.4) mg/L; p = 0.001. No patient with neurotoxicity had a CEF concentration of 35 mg/L or less. The mean treatment duration was 5.4 (2.6) days. The mean time to develop neurotoxicity related to CEF was 4.8 (1.8) days. Seventeen patients were not neurologically assessable due to deep sedation. The mean time from CEF change to neurological improvement was 2.8 (1.6) days. CEF concentration above 40 mg/L (p= 0.01) was more frequently associated with neurotoxicity in univariate analysis but did not appear to be an independent factor. The only independent factor for presumed CEF neurotoxicity was estimated glomerular filtration rate below 60 mL/min/1.73 m² at initiation of treatment [OR= 8.6 (95% CI 1.4–51.9); p= 0.02].

**Conclusion:** CEF concentration above 35 mg/L is frequent and therefore should be systematically investigated to prevent neurotoxicity.

**Reference 1:** Guilhaumou R, Benaboud S, Bennis Y, Dahyot-Fizelier C, Dailly E, Gandia P, et al. Optimization of the treatment with beta-lactam antibiotics in critically ill patients. Crit Care Lond Engl. 2019;23:104.

**Reference 2:** Huwyler T, Lenggenhager L, Abbas M, Ing Lorenzini K, Hughes S, Huttner B, et al. Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study. Clin Microbiol Infect. 2017 Jul;23(7):454–9.

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

### FC-054

#### Population pharmacokinetics of fluconazole and dosing simulations in critically ill patients

VASSAL Olivia¹, MATUSIK Elodie²,³, FERRY Tristan⁴,⁵, MILLET Aurelien⁶, BOHE Julien¹, GUITTON Jerome⁶, FRIGGERI Arnaud¹,⁵, GOUTELLE Sylvain²,³

¹Service Anesthésie Reanimation Medecine Intensive, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Benite, France; ²Service Pharmacie/Pharmacologie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; ³CNRS UMR 5558 LBBE, Université Lyon 1, Lyon, France; ⁴Service des maladies infectieuses et tropicales, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; ⁵Inserm U111, CNRS UMR 5308, Centre International de Recherche en Infectiologie, Lyon, France; ⁶Laboratoire de Pharmacologie toxicologie, Groupement

<footnote>*CLCR = Creatinine clearance. $^{a}$SD = Standard Deviation. $^{b}$cIAI = complicated intra-Abdominal infection. $^{c}$cUTI = complicated Urinary Tract infection.</footnote>

<footnote>£ patients presenting with at least one of the three infections (cIAI, cUTI, or pyelonephritis)</footnote>

<footnote>■ data missing for one patient</footnote>
Hospitalier Sud, Hospices Civils de Lyon, Lyon, France.

**Correspondence:** Olivia VASSAL (Oliviavassal@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-054

**Rationale:** Fluconazole pharmacokinetics (PK) may be altered in critically ill patients, but changes and implications for drug dosing remain unclear. We aimed to describe the PK and dosage requirements of fluconazole in intensive care unit (ICU) patients.

**Patients and methods/Materials and methods:** This was a PK study performed in an ICU over 1 year. All patients who were prescribed fluconazole with at least two measured concentrations were included. A second dataset from a medical unit was also analyzed for comparison. Population PK modelling was performed by with Monolix software. Classical criteria were used for model evaluation including goodness-of-fit and simulation-based diagnostics. Patient covariates were investigated. Dosing simulations were performed with the final model with Simulx software. Various loading (LD) and maintenance doses (MD) were evaluated, and probability of target attainment (PTA) was computed in simulated patients (n = 1000). PK targets were set as a trough concentration (Cmin) of 15 mg/L and a daily AUC of 400 mg.h/L.

**Results:** A total of 202 plasma concentrations were available. They were 33 men and 19 women with mean age of 61 ± 16 years and mean initial weight of 72 ± 21 kg. 59% of patients had proven invasive candidiasis (C. albicans 35%, C. tropicalis 8%) and 4% has cryptococcosis. In ICU patients, a LD of 800 mg was administered in 83% of patients. Data were best described with by a one-compartment model with first-order elimination. The mean (CV%) of body clearance (CL) and volume of distribution (Vd) parameters were as follows: 0.46 L/h (56%) and 40.72 L (10%). ICU hospitalization was associated with a 80% increase in CL. The optimal dosage regimen was based on a LD of 800 mg q12h over the first 24 h followed by a MD of 600 mg/24 h. This dosage was associated with median [percentiles 5th–95th] Cmin of 29.5 mg/L [19.2–37.3] at 24 h and 30.9 mg/L [8,6–62,8] at 120 h and a median AUC of 583.7 mg.h/L [461.4–706.5] at 24 h and 895.0 mg.h/L [356.8–1597.0] at 120 h. PTA at 24 h and 120 h were as follows 98.7% and 99.9% for Cmin; 99.2% and 93.4% for AUC, respectively. Only 6% of patients had a concentration over 80 mg/L after 5 days.

**Discussion:** We identified increased fluconazole clearance in ICU patients. LD and MD higher than currently recommended are necessary to achieve PK/PD targets in most patients.

**Conclusion:** This study confirms interindividual variability of fluconazole PK and the need for higher dosage in ICU patients. Early therapeutic drug monitoring may be useful for dosage individualization.

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

FC-055

Factors associated with failure to achieve meropenem plasma concentration target in critically ill patients

TOURNAYRE Sarah¹, MATHIEU Olivier¹, VILLIET Maxime¹, KLOUCHE Kada¹, LARCHER Romaric²

¹CHU MONTPELLIER, Montpellier, France; ²CHU NIMES, Nimes, France

**Correspondence:** Sarah TOURNAYRE (tournayresarah@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-055

**Rationale:** Optimal management of septic shock requires prompt and adequate administration of broad-spectrum antibiotic therapy, ensuring that effective therapeutic levels are achieved. We aimed to determine factors associated with failure to achieve meropenem plasma concentration target in critically ill patients.

**Patients and methods/Materials and methods:** Between January 2019 and March 2020, charts of all patients admitted in medical intensive care unit (ICU) for septic shock and treated with meropenem and who had at least one meropenem plasma concentration measurement were reviewed. Adequate target meropenem plasma concentration was ranged from 10 to 50 mg/L. Factors associated with meropenem plasma concentration target non-attainment were assessed by multi-variable logistic regression (R software version 4.1.2).

**Results:** 117 meropenem plasma concentrations were measured 3 days after initiation of meropenem or change on its dosage regimen, in 70 ICU patients. Meropenem was administered by prolonged

intermittent infusion in 34 patients and by continuous infusion in 36. Factors independently associated with failure to achieve 10 mg/L of meropenem plasma concentration were female sex, age < 65 years old, prolonged intermittent rather than continuous infusion and low daily doses of meropenem (Fig. 1). Factors associated with plasma concentrations above 50 mg/L were low body weight, renal clearance < 25 ml/min and higher daily doses of meropenem. Of note, only 3 patients had neurotoxicity.

**Conclusion:** In ICU patients, age < 65 years old, female sex, prolonged intermittent infusion and low dose of meropenem were significantly associated with failure to achieve meropenem plasma concentration target. Some patients experienced a high meropenem plasma concentration but few of them had clinical signs of toxicity. Our results suggest to prefer continuous infusion of meropenem over 24 h rather than prolonged intermittent infusion, particularly in patients with normal or increased renal clearance.

**Reference 1:** Abdul-Aziz, M.H., Alfenaar, JW.C., Bassetti, M. et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper#. Intensive Care Med 46, 1127–1153 (2020).

**Reference 2:** Li C, Du X, Kuti JL, Nicolau DP. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother 51:1725–1730 (2007).

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

<figure><img src="image_62.png" /></figure>

Meropenem concentration after different daily dose among patients with different renal clearance. Group 1 = CrCl < 25 ml/min, Group 2 = CrCl 25–50 ml/min or CRRT, Group 3 = CrCl 50–90 ml/min, Group 4 = CrCl 90–130 ml/min, Group 5 = CrCl > 130 ml/min.

FC-056

Optimisation of piperacillin-tazobactam dosing regimen for critically-ill patient with sepsis: the OPT-TAZ population pharmacokinetics study

SARFATI Sacha¹, WILS Julien¹, CARPENTIER Dorothée¹, NILES Christopher², GOUIN Philippe¹, BRAULT Clément³, IMBERT Laurent¹, GAËTAN Béduneau¹, NSEIR Saad², DAHYOT Sandrine¹, MISSET Benoit⁴, LAMOUREUX Fabien¹

¹CHU de Rouen, Rouen, France; ²CHRU de Lille, Lille, France; ³CHU d'Amiens, Amiens, France; ⁴CHU de Liège, Liège, Belgique

**Correspondence:** Sacha SARFATI (sacha.sarfati@gmail.com)

*Annals of Intensive Care* 2022, **12**(1):FC-056

**Rationale:** In critically-ill patient with sepsis, the piperacillin-tazobactam (pip-taz) combination is one of the most used antibiotics. Although pharmacokinetics of pip-taz exhibits very high inter-individual variability mainly based on volume of distribution, renal clearance, patient's weight and serum albumin level, a standard dosing protocol is generally used (1). Moreover, these covariates are highly variable in sepsis and predictive algorithms based on clinical and biological parameters may help to optimize dosing and improve outcomes. The aim of the study is to use a population pharmacokinetics study to build a Bayesian model predicting the optimal dosing regimen of pip-taz in sepsis patients.

**Patients and methods/Materials and methods:** The OPT-TAZ (optimisation of pip-taz) study is a prospective multicenter open-label non-comparative cohort study designed with a 60-patient learning cohort
and a 30-patient validation cohort. Patients will be included prospectively in 4 ICUs in France. The protocol plan to analyze pharmacokinetics of 60 patients then development of a predictive model validated on 30 patients. We present here the analysis of the 60 first patients. Standard dosing of pip-taz 4 g/0,5 g each 6 h (group 1) or 8 h (group 2) in 3 h infusion has been chosen according to clinician choice. Serum concentration of piperacillin and tazobactam has been measured at H0, 1,5, 3, 4, 5 (G1) or 6 (G2), 6 (G1) or 8 (G1), 12 (G1) or 16 (G2), 24, 48 and 120 with a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

**Results:** In our cohort, we showed that pharmacokinetics of pip-taz present a very high inter-individual variability. Residual concentration was lower than recommended target concentration in more than 50% of cases. Dosing of 4 g/0.5 g every 8 h and augmented renal clearance were risk factor for failure of PK/PD target attainment. PK of piperacillin-lin and tazobactam show a strong association and tazobactam concentration was of the order of 10% of piperacillin concentration.

**Conclusion:** In conclusion, pip-taz dosing regimen must be adapted to patient characteristics. Creatinine clearance is one of the most important covariates to take into consideration for dose adaptation. The dose of 4 g/0.5 g each 8 h must be considered of high risk of failure of PK/PD attainment in patient with no impaired renal function. Therapeutic drug monitoring is an essential tool to assess the match of dosing regimen with PK/PD target.

**Reference 1:** (1) Huttner A, Harbarth S, Hope WW, Lipman J, Roberts JA. Therapeutic drug monitoring of the ?-lactam antibiotics: what is the evidence and which patients should we be using it for? *J Antimicrob Chemother* 2015;70(12):3178-83.

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

<figure><img src="image_63.png" /></figure>

Residual concentration of piperacillin over time in group 1 (4 g each 6 h) and group 2 (4 each 8 h) compared to different level of PK/PD target.

FC-057

**Should we really ban 3rd generation cephalosporin (C3G) use for the treatment of Enterobacter cloacae infection in ICU patients?**

BERNIER Juliette¹, TANKOVIC Jacques¹, VILLA Antoine¹, URBINA Tomas¹, BONNY Vincent¹, GABARRE Paul¹, AIT OUFELLA Hafid¹, MAURY Eric¹
¹CHU Saint Antoine, Paris, France

**Correspondence:** Juliette BERNIER (j.bernier1505@laposte.net)

*Annals of Intensive Care* 2022, **12**(1):FC-057

**Rationale:** Limiting the ecological impact of antibiotics through accurate prescription is one of the major goals of antibiotic stewardship policy. However, an antibiotic-sparing strategy must not have a potential deleterious impact on patient's prognosis. Group 3 Enterobacteriaceae possess the AmpC gene encoding a cephalosporinase. Antibiotic therapy with a 3rd generation cephalosporin (C3Gs) might lead to treatment failure when cephalosporinase hyperproducing mutants (Hcase) emergence occurs making them resistant to all penicillins and C3Gs. Thus, expert recommendations advise against the use of C3Gs as monotherapy in this case (1). This risk would be increased for Enterobacter cloacae species. This statement, based on old studies,

is now being debated (2). This study aimed at evaluating mutants Hcase emergence when treating Enterobacter cloacae complex wild-type infections in ICU patients with C3Gs.

**Patients and methods/Materials and methods:** Methods: We performed a multicenter retrospective study including microbiological files of patients more than 18, admitted to intensive care unit, between January 2015 and August 2021, and who were treated for wild-type Enterobacter cloacae infection and assessed mutants emergence defined by a subsequent sample finding mutants Hcase emergence whatever clinical evolution.

**Results:** Among the 5275 Enterobacter cloacae species found from the microbiology files during the study period, 373 were associated to infections occurring in ICU patients and finally 165 ICU patients infected with C3Gs susceptible E cloacae were included in the analysis. C3Gs resistance emergence was observed in 19 cases (11.5%), 13 being related to Hcase mechanism and 6 to extended spectrum beta-lactamase (ESBL) production. C3G were used in 56 cases (35%) before identification (n=12), after identification (n=18) or exclusively (n=26). Cefepime was used in 67 cases (41%) before identification (n=11), after identification (n=28), exclusively (n=21), or combined with a fluoroquinolone (n=3), an aminoglycoside (n=3) or sulfamethoxazole (n=1). Mutants Hcase emergence occurred most often after an exclusive treatment by cefotaxime (n=5), cefepime (n=2), tazocillin (n=3). Three were observed following tazocillin/aminoglycoside association (n=1), tazocillin followed by sulfamethoxazole (n=1) or cefepime/fluoroquinolone association (n=1). None was observed after carbapenem use. Considering patients receiving monotherapy following identification, mutants Hcase emergence was more frequent in the C3G group than in the cefepime group (11,4 vs 4% respectively, (p=0.3).

**Conclusion:** Enterobacter cloacae mutants Hcase emergence could be more frequent following C3G use than cefepime. The data reported here are not significantly different but are obtained on a limited population. A prospective study would be necessary to answer this question.

**Reference 1:** 1. 2021. CASFM / EUCAST AVRIL 2021 V1.0. Société Française de Microbiologie. https://www.sfm-microbiologie.org/2021/04/23/casfm-avril-2021-v1-0/. Retrieved 23 January 2022.

**Reference 2:** 2. Mizrahi A, Delerue T, Morel H, Le Monnier A, Carbonnelle E, Pilmis B, Zahar JR. 2020. Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review. *International Journal of Antimicrob.*

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

FC-058

**Anticoagulation, thromboembolic and bleeding events in COVID-19 VV-ECMO patients in the French Territories in the Americas**

DAOUD Laura¹, VALLY Shazima¹, KALLEL Hatem², CHAPLAIN Agathe¹, FLORENTIN Jonathan¹, MEGARBANE Bruno³, MEHDAOUI Hossein¹, VALENTINO Ruddy¹, RESIERE Dabor¹

¹Centre Hospitalier Universitaire, Fort-De-France, Martinique; ²Cayenne General Hospital, French Guiana, Cayenne, Guyane Française; ³Lariboisière Hospital, Paris University; Paris, France

**Correspondence:** Dabor RESIERE (dabor.resiere@chu-martinique.fr)

*Annals of Intensive Care* 2022, **12**(1):FC-058

**Rationale:** Since December 2019, COVID-19 has affected more than 400 million people and caused more than 5 million deaths, causing a truly global pandemic. While most people with COVID-19 will have a minor or moderate form of the disease, some people will develop severe acute respiratory distress syndrome (ARDS), requiring admission to intensive care and the use of mechanical ventilation (VM) and sometimes venovenous extracorporeal membrane oxygenation (VV-ECMO). However, COVID-19 has been associated with an increased risk of thromboembolic and bleeding events, and heparin resistance during VV-ECMO treatment in critically ill patients admitted to the intensive care unit (ICU). The therapeutic target for anticoagulation under VV-ECMO is not really known. The anticoagulant treatment of choice
according to the ELSO recommendations is unfractionated heparin with anti-Xa targets between 0.2 and 0.4. The objective of this cohort study was to evaluate the association between severe COVID-19 infection and the occurrence of thromboembolic and bleeding complications following VV-ECMO.

**Patients and methods/Materials and methods:** We conducted a monocenter retrospective observational study in the ICU department of the University Hospital of Martinique from January 2020 to December 2021. Our center has an on-call ECMO mobile unit (UMAC) which includes a cardiothoracic surgeon and a perfusionist nurse. Requests for VV-ECMO French West Indies (Guadeloupe, Martinique, and French Guyana) are regulated by the intensivist on duty at the Martinique University Hospital.

**Results:** We included the records of 40 patients with 25 COVID-19 patients and 15 non-COVID-19 patients over the period January 2020 to December 2021. Six non-COVID-19 patients were excluded: 3 for deaths within 24 h, one patient with acute myeloid leukemia type 3, and 2 patients with a contraindication to heparin therapy. The median age was 46 years old for COVID-19 patients et 49 year old for non-COVID-19 patients. COVID-19 patients experienced thromboembolic complications in 55% of cases (11) and non-COVID-19 patients in 24% of cases (2), p = 0.1

**Conclusion:** Our study confirms that the management of anticoagulation in VV-ECMO represents a particular challenge in COVID-19 patients who appear to be at increased risk of thromboembolic risk complications without sparing the bleeding consequences of the assistance. On the other hand, the difference in thromboembolic and hemorrhagic complications in our two groups was not significant.

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

## FC-059

### Bilateral acral ischemia in COVID-19 patients: a peculiar symptom and treatment options

SGHAIER Ameni<fnref n="1" />, RHAIEM Sirine<fnref n="1" />, JAMOUSSI Amira<fnref n="1" />, AYED Samia<fnref n="1" />, RACHDI Emna<fnref n="1" />, JARRAYA Fatma<fnref n="1" />, BESBES Mohamed<fnref n="1" />, BEN KHELIL Jalila<fnref n="1" />

**Correspondence:** Ameni SGHAIER (sghaier.ameni@caramail.com)

*Annals of Intensive Care 2022, 12(1):FC-059*

**Rationale:** Although primarily a respiratory virus, SARS-CoV-2 has shown clear impact on hemostasis, often resulting in hypercoagulability state. Deep vein thrombosis, pulmonary embolism and arterial occlusion have all been increasingly reported and investigated during the COVID-19 pandemic. Few studies have however focused on the occurrence of bilateral acral ischemia (BAI). The aim of our study was to examine the characteristics of COVID-19 patients who developed BAI, as well as the various therapy options that might be offered to them.

**Patients and methods/Materials and methods:** We conducted a retrospective study including patients admitted to our intensive-care unit for acute respiratory distress (ARDS) due to COVID-19 between January and August 2021. Clinical characteristics, laboratory findings and vasopressive treatment doses were recorded and used to compare between patients who developed BAI and those who did not. Fischer bilateral exact test and Mann-Whitney-u test were used for comparison between groups.

**Results:** During the study period, 398 patients were admitted; 238 male and 160 female. Of these patients, 8 developed BAI (7 men). Mean age was 67 years old. Medical history of diabetes was present in 7 patients, and hypertension in all 8 patients. All patients who developed BAI had severe ARDS. Only one patient remained on non-invasive ventilation support at the time of BAI occurrence and until discharge. The main affected sites of BAI were fingers and toes although ear lobules were also involved in 3 patients. The mean time to development of BAI starting from the day of admission was

4.9 days. Among patients who were intubated, the mean time of BAI occurrence after intubation was 1.2 days. 4 patients were not under any vasopressive treatment at the time of BAI development. The mean norepinephrine dose among the other 4 patients was 0.65 mg/h. When compared to the other group of patients, there was no statistically significant difference in gender (p = 0.12), median age (56 vs 67 years old; p = 0.054), baseline prothrombin time levels (p = 0.08), d-Dimer levels (p = 0.13), platelet count (p = 0.22) and blood fibrinogen levels (p = 0.061) when available. Survival rates between the two groups were not statistically significant (196 vs 1 patient; p = 0.068). Anticoagulant treatment using heparin was given to 4 patients, with only one patient improved over the course of 10 days. One patient received thrombolysis for subsequent pulmonary embolism with improvement in less than 2 days.

**Conclusion:** BAI has been increasingly reported in critically-ill COVID-19 patients with no apparent other risk factors to predict its occurrence and limited options for treatment and prevention.

**Compliance with ethics regulations:** N/A.

## FC-060

### Comparative profiles of routine and specialized biomarkers of coagulopathy and endotheliopathy in moderate and severe COVID-19 disease: a prospective observational study

BOUSQUET Giovanni<fnref n="1" />, LACROIX Romaric³, PAHUS Laurie<fnref n="1" />, VALERA Sabine<fnref n="1" />, HEZARD Nathalie<fnref n="2" />, ARNAUD Laurent³, ABDILI Evelyne³, BAUMSTARCK Karine⁴, CHANEZ Pascal<fnref n="1" />, DIGNAT-GEORGE Françoise³, PAPAZIAN Laurent<fnref n="1" />, FOREL Jean-Marie<fnref n="1" />, HRAIECH Sami<fnref n="1" />, MORANGE Pierre<fnref n="2" />, GUERVILLY Christophe<fnref n="1" />

**Correspondence:** Giovanni BOUSQUET (giovanni.bousquet@icloud.com)

*Annals of Intensive Care 2022, 12(1):FC-060*

**Rationale:** Endothelial injury and coagulation activation are prominent axis in coronavirus disease 19 (COVID-19) pathogenesis. However, few studies have compared comprehensive profiles of biomarkers of coagulopathy/endotheliopathy with regard to the initial severity of COVID-19 and the time course of the disease.

**Patients and methods/Materials and methods:** In a prospective longitudinal study, we explored coagulation and endothelial function biomarkers in two cohorts of severe and moderate COVID-19 patients and according to their respective outcomes.

**Results:** We found that Tissue factor pathway inhibition (TFPI), Extracellular vesicles—tissue factor (EV-TF), von Willebrand factor antigen (VWF:Ag) and soluble thrombomodulin (STM) at admission were associated with disease severity. With regard to outcome, d-dimers, TFPI, EV-TF, VWF:Ag/ADAMTS13 ratio and sTM at admission, at day 3 and at day 7 were associated with death and mechanical ventilation. TFPI with a cut-off value of 37.5 ng/mL had 87% sensitivity and 94% specificity and EV-TF with a cut-off value of 13 fM had 87% sensitivity and 83% specificity. ROC curves analysis for severe outcome was significant with AUC = 0.90 for TFPI and AUC = 0.88 for EV-TF (p < 0.001 for both).

**Conclusion:** We found a specific profile of specialized biomarkers of coagulopathy/endotheliopathy associated with the severe forms of COVID-19 and its clinical outcome. We identified TFPI and EV-TF to be of potential interest in stratifying patients' risk or to design specific treatment targeting coagulation pathways. Additional studies are warranted to confirm our results.

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

<footnote n="1">¹Hospital Abderrahman Mami, Ariana, Tunisie</footnote>

<footnote n="1">¹Centre Hospitalier Universitaire de Marseille - Nord, Marseille, France;</footnote>

<footnote n="2">²Centre Hospitalier Universitaire de Marseille - La Timone, Marseille, France; ³Centre Hospitalier Universitaire de Marseille - La Conception, Marseille, France; ⁴Faculté de Médecine de Marseille - La Timone, Marseille, France</footnote>
<figure><img src="image_64.png" /></figure>

ROC curves of specialized biomarkers at admission for severe outcome (death or mechanical ventilation) Definition of abbreviations: AUC, area under the curve; TFPI, tissue factor pathway inhibitor; EV-TF, extracellular vesicles—tissue factor; VWF, vo.

FC-061

Bedside ACT anticoagulation monitoring in patients infected with SARS-CoV-2 comparing to anti-Xa activity

MOUNIR Anass<fnref n="1" />, FALAHI Salma<fnref n="1" />, SAADAOUI Soufiane<fnref n="1" />, CHERKAB Rachid<fnref n="1" />, EL KETTANI Chafik<fnref n="1" />, BARROU Houcine<fnref n="1" />

**Correspondence:** Salma FALAHI (salmalafahi73@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-061

**Rationale:** Patients with coronavirus disease 2019 appear to be at high risk for thrombotic disease in both venous and arterial circulations due to excessive inflammation, platelet activation, endothelial dysfunction, and immobility. Anti-Xa and aPTT are prone to monitor therapeutic range of unfractionated heparin of patients with COVID-19 and severe illness. These biological parameters are certainly effective but are not momentary. Hence the idea of proposing ACT (Activated Clotting Time), as an element for monitoring anticoagulation in patients infected with SARS-CoV-2, given its multiple advantages: simple, fast, inexpensive, and which can be done at the bedside.

**Patients and methods/Materials and methods:** We performed a study comparing the results of anticoagulation monitoring by ACT with anti-Xa and TCA activity in 20 patients infected with COVID-19 and treated with curative anticoagulation (LMWH 0.8Ux2/day) over a one month-period. We excluded from the study patients with potentials that could interfere with TCA results: Hypofibrinogenemia, clotting factor deficiencies, haemodilution, Aprotinin, thrombocytopenia, qualitative platelet abnormalities, oral anticoagulants.

**Results:** Our results are shown in Table 1. The mean age of the population was 54 ± 10. 50% of the patients were diabetic, 25% were hypertensive, one patient was asthmatic, and one patient had dyslipidemia. 50% of patients had parenchymal involvement ≥ 75%. 35% of patients presented a high risk of thromboembolism. No agreement was found between ACT results and anti-Xa activity in our sample. In contrast, in 95% of cases, there was a linear trend between ACT and TCA results.

**Discussion:** The ACT is routinely used to monitor anticoagulation during cardiopulmonary bypass surgery and endovascular procedures. ACT is determined predominantly by the anti-ila activity of the anti-coagulant. Thus, ACT is higher with heparin or bivalirudin than with

LMWH for the same intensity of anticoagulation. However, ACT can be used to monitor LMWH anticoagulation with appropriate adjustments. Several studies have attempted to compare the concordance between ACT results with anti-Xa and TCA activity in patients on low-grade UFH anticoagulation. They have shown that In Intensive care unit patients, no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. All the studies that were found were in IV anticoagulation with UFH. The literature remains very limited about monitoring by ACT for anticoagulation by LMWH.

**Conclusion:** COVID-19 infection presents a problem with the management of anticoagulation. The biological monitoring parameters are effective but are not momentary. However, bedside ACT anticoagulation monitoring cannot be recommended in patients infected with SARS-CoV-2.

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

<figure><img src="image_65.png" /><figcaption>Table 1: Clinico-biological and radiological parameters of our patients.</figcaption></figure>

FC-062

Is there a place to sulodexide in COVID-19 critically ill patients?

DHIA Boudour<fnref n="1" />,⁴, BEN ISMAIL Khaoula<fnref n="1" />,⁴, ESSAFI Fatma<fnref n="1" />,⁴, TALIK Imen<fnref n="1" />,⁴, BAYOUDH Aida³,⁴, FESSI Ilhem³,⁴, CHKIRBENE Mariem², JERBI Tahany², MERHBENE Takoua<fnref n="1" />,⁴

¹Service de réanimation Médicale, Hôpital Régional de Zaghouan, Zaghouan, Tunisie; ²Département pharmacie, Hôpital Régional de Zaghouan, Zaghouan, Tunisie; ³Service de pneumologie, Hôpital Régional de Zaghouan, Zaghouan, Tunisie; ⁴Faculté de médecine de Tunis, Université Tunis El Manar, Tunis, Tunisie

**Correspondence:** Boudour DHIA (bidourabdbg2014@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-062

**Rationale:** Several studies have demonstrated that endothelitis is prominent in COVID-19. Sulodexide (glycosaminoglycan with endothelial protective, vascular anti-inflammatory and antithrombotic activities) was identified to be helpful in hypoxemic patients. The aim of this study was to assess the contribution of sulodexide addition in severe SARS-CoV-2 pneumonia and to determine its impact on prognosis.

**Patients and methods/Materials and methods:** Double-arm interventional clinical trial conducted at the medical intensive care unit (ICU) of the regional hospital of Zaghouan (Tunisia) from April 2021 to December 2021, after approval of the ethics committee. Consenting COVID-19 patients over 18 years were included. Two groups were identified: Group 1 (G1) interventional group and Group 2 (G2) control. Sulodexide (500 LSU) was administered from the first day of ICU hospitalization to discharge for a total of 21 days. Epidemiological and prognostic data were analyzed. The study was conducted anonymously. No conflict of interest to be declared.

<footnote n="1">¹Réanimation chirurgicale P17, CHU IBN ROCHD, Casablanca, Maroc.</footnote>
**Results:** During the study period, 149 patients were admitted with severe SARS-CoV-2 pneumonia. Seventy-two patients agreed to participate in the clinical trial (G1). The rest defined the control group. On admission, the two groups were comparable in terms of demographic characteristics, clinical presentation and initial severity. Comparison of outcome parameters showed that patients in group 1 had developed less thromboembolic complications (23.1% vs 39.6%, p = 0.016), need for invasive mechanical ventilation (16.8% vs 21.3%, p = 0.031), with lower mortality in G1 (19% vs 36%, p = 0.047). More intra-hospital cardiovascular complications were noted in G2 (37% vs 12% p = 0.03). There were no significant differences in terms of bleeding complications' occurrence, hemodynamic instability, incidence of healthcare-associated infections, barotrauma complications and length of ICU stay. Multivariate analysis showed that sulodexide use was an independent protective factor against thromboembolic events (OR = 0.57; 95% CI [0.6-0.8]; p = 0.04). Follow-up of patients after three months of discharge showed no difference in terms of cardiovascular complications or post-COVID effects.

**Conclusion:** In this preliminary study, it appears that sulodexide may reduce the risk of thromboembolic and cardiovascular complications in severe COVID-19 patients without affecting the final outcome. Further prospective, multicentre studies with endothelial function studies are needed to confirm this contribution.

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

## FC-063

### Impact of corticosteroids on coagulation profile of critically ill COVID-19 patients—a before-after study

GABARRE Paul¹, URBINA Tomas¹, CUNAT Sibylle², MERDJI Hamid ²,³, BONNY Vincent¹, LAVILLEGRAND Jean-Rémi¹,⁴, RAIA Lisa¹, BIGE Naike¹, BAUDEL Jean-Luc¹, MAURY Eric¹, GUIDET Bertrand¹, HELMS Julie²,³, AIT-OUFELLA Hafid ¹,⁴
¹Hôpital Saint Antoine, Paris, France; ²Hôpital civil, Strasbourg, France; ³INSERM, UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France; ⁴INSERM U970, Centre de Recherche Cardiovasculaire de Paris (PARCC), Paris, France.

**Correspondence:** Paul GABARRE (paulgabarre@hotmail.com)

Annals of Intensive Care 2022, **12**(1):FC-063

**Rationale:** Several studies have reported an increased risk of thrombotic events in COVID-19 patients, but the pathophysiology of this procoagulant phenotype remains poorly understood. In addition to direct virus-induced endothelial injury, systemic release of pro-inflammatory cytokines may be involved. We hypothesized that corticosteroids may attenuate this procoagulant state through their anti-inflammatory effects.

**Patients and methods/Materials and METHODS:** We conducted a before/after bi-centric cohort study among ICU patients hospitalized for severe COVID-19 and receiving therapeutic anticoagulation by unfractionated heparin (UFH). Before and after the standardized use of dexamethasone (DXM), we compared inflammatory and coagulation profiles, as well as the kinetics of heparin requirement, adjusted for weight and anti-Xa activity.

**Results:** Eighty-six patients were included, 35 in the no-DXM group, and 51 in the DXM group. At admission, CRP and fibrinogen levels were not different between groups, neither were UFH infusion rates. At day 3 after ICU admission, CRP (178 ± 94 mg/L vs 99 ± 68 mg/L, p < 0.0001) and fibrinogen (7.2 ± 1.4 g/L vs 6.1 ± 1.4 g/L, p = 0.0001) significantly decreased in the DXM group, but did not in the no-DXM group. From day 4, UFH infusion rates became lower in the DXM group (Day 4: 435 ± 190 vs 360 ± 96 UI/kg/24 h p = 0.038) without any significant difference in plasma anti-Xa activity. CRP variations correlated with heparin dose variations between Day 0 and Day 3 (r = 0.39, p = 0.009). Finally, the incidence of venous thromboembolic events during in-ICU stay was significantly reduced in the DXM group (4 vs 43%, p < 0.0001).

**Conclusion:** In this before-after bi-centric cohort of critically ill COVID-19 patients, dexamethasone use was associated with a decrease in both pro-inflammatory and procoagulant profile.

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

## FC-064

### Pulmonary embolism in patients with COVID-19 versus non COVID-19 pneumonia

TOUJ Hager¹, SAAD Soumaya¹, SEDGHIANI Ines¹, KDEYMI Henedi¹, AQUAINI Khalil¹, CHELBI Rym¹, BORSALI FALFOUL Nebiha¹

¹Hôpital Habib Thameur, Tunis, Tunisie

**Correspondence:** Hager TOUJ (hagertouj@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-064.

**Rationale:** We aim to compare epidemiological, clinical and prognostic characteristics of patients diagnosed with pulmonary embolism (PE) at the emergency department (ED), which we divided into two groups: patients with confirmed COVID-19 pneumonia versus those without it.

**Patients and methods/Materials and methods:** We conducted a single-centre, retrospective observational study in the period between April 2020 and February 2022. We included patients over 18 years admitted at the ED and diagnosed with PE following computed tomography pulmonary angiography (CTPA). SARS-CoV-2 pneumonia was confirmed by RT-PCR performed in all patients included in our study. Patients were divided into two groups: those affected with COVID-19 Pneumonia and those not affected by it. Patient's demographics, comorbidities, clinical state and prognosis were collected in both.

**Results:** 144 patients were included. The mean age was 68 ± 15 years with a sex-ratio of 0.9. 79 patients (55%) were diagnosed with confirmed COVID-19 pneumonia. The mean length of stay at ED was 7 days. The clinical characteristics of both groups are presented in Table 1. The intra-hospital mortality rate was 30%.

**Conclusion:** The association of SARS-CoV-2 pneumonia and PE leads to a higher morbidity. Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19.

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

<table><caption>Table 1 Baseline characteristics of findings in COVID-19 + group and COVID-19 - group</caption><thead><tr><th>Characteristics</th><th>COVID19 +<br>N=65 (45%)</th><th>COVID19 -<br>N=79 (55%)</th><th>P</th></tr></thead><tbody><tr><td>Age, mean ±SD</td><td>67 ± 14</td><td>68 ± 15</td><td>0,78</td></tr><tr><td>Female gender n (%)</td><td>34 (52,3)</td><td>40 (50,6)</td><td>0,88</td></tr><tr><td>Diabetes n(%)</td><td>27 (41,5)</td><td>20 (25,3)</td><td>0,03</td></tr><tr><td>History of VTED</td><td>4 (6,1)</td><td>11 (14)</td><td>0,17</td></tr><tr><td>Cancer</td><td>3 (0,5)</td><td>12 (1,5)</td><td>0,03</td></tr><tr><td>Dyspnea</td><td>56 (86,1)</td><td>52 (65,8)</td><td>0,005</td></tr><tr><td>Chest pain</td><td>5 (0,8)</td><td>16 (2)</td><td>0,03</td></tr><tr><td>SpO2, mean ±SD</td><td>84 ± 9</td><td>88 ± 10</td><td>0,02</td></tr><tr><td>Respiratory rate mean(c/min)±SD</td><td>27 ± 5</td><td>23 ± 6</td><td>0,02</td></tr><tr><td>Low clinical probability of PE n (%)</td><td>25 (38,4)</td><td>13 (16,4)</td><td>0,003</td></tr><tr><td>Wells score mean ±SD</td><td>2 ± 2</td><td>3 ± 2</td><td>&lt; 0,001</td></tr><tr><td>CRP, mean ±SD</td><td>166 ± 103</td><td>96 ± 94</td><td>&lt; 0,001</td></tr><tr><td>Invasive mechanical ventilation n(%)</td><td>16 (24,6)</td><td>5 (6,3)</td><td>0,002</td></tr><tr><td>ICU n(%)</td><td>25 (38,4)</td><td>10 (12,6)</td><td>&lt; 0,001</td></tr><tr><td>Death n (%)</td><td>24 (37)</td><td>19 (24)</td><td>0,10</td></tr></tbody></table>

SD: standard deviation; VTED: venous thromboembolic disease; PE: pulmonary embolism; CRP: C-reactive-protein; ICU: intensive care unit

<caption>Table 1 Baseline characteristics in COVID-19 + group and COVID-19 - group.</caption>

## FC-065

### Neutrophil phenotypes and microbicidal activity in SARS-CoV-2 associated ARDS patients

QUELVEN Quentin¹, GRÉGOIRE Murielle², COIRIER Valentin¹, ROUSSEL Mikael², TARTE Karin², TADIÉ Jean-Marc¹, LESOUHAITIER Mathieu¹

¹CHU Rennes, Pontchaillou, Rennes, France; ²Unitée de Microenvironment, Cell differentiation, iMmunology And Cancer (MICMAC), UMR INSERM 1236, Rennes, France

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

Annals of Intensive Care 2022, **12**(1):FC-065
**Rationale:** The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate, sharing clinical and biological features with sepsis-induced immune dysfunction. Since neutrophils play a critical role in host defense against infections, the aim of our study was to investigate phenotypic and functional alterations of neutrophils in patients with SARS-CoV-2 associated ARDS.

**Patients and methods/Materials and methods:** SARS-CoV-2 associated ARDS patients admitted to the ICU, without known immunosuppression, were included. Neutrophil phenotypic maturation and functions (migration, adhesion, Neutrophil Extracellular Trap (NET) release, Reactive Oxygen Species (ROS) production, bacteria/aspergillus killing and phagocytosis) were evaluated within 24 h of ICU admission and at day 7. Furthermore, in a second set of experiments, we investigated the effects of bronchoalveolar lavage (BAL) fluids from SARS-CoV-2 associated ARDS patients on neutrophils.

**Results:** Forty-nine patients were included (Table 1). We found that SARS-CoV-2 associated ARDS induced a systemic inflammation with an increase of circulating mature neutrophils. However, we found a significant decrease in CD66b expression (a marker of granulocyte activation involved in adhesion to endothelial cells, degranulation, and reactive oxygen species (ROS) production). Neutrophil antifungal activity against *Aspergillus fumigatus* was not impaired in patients with SARS-CoV-2 associated ARDS.

**Conclusion:** Although neutrophils ROS production from patients with SARS-CoV-2 associated ARDS was significantly decreased, our results do not support that the increased risk of invasive aspergillosis is linked to neutrophil dysfunction.

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

<table><thead><tr><td>Parameters (n=49)</td><td>Values</td></tr></thead><tbody><tr><td>Age (years)</td><td>61 (+/-11)</td></tr><tr><td>Sex ratio (H/F)</td><td>31/18</td></tr><tr><td>BMI</td><td>31 (+/-7)</td></tr><tr><td>IGS 2 at admission</td><td>40 +/- 14</td></tr><tr><td>PaO2/FiO2 at day 1</td><td>148 +/-64</td></tr><tr><td>PaO2/FiO2 at day 7</td><td>193 +/-54</td></tr><tr><td>Mechanical ventilation duration</td><td>16 +/-11</td></tr><tr><td>ICU acquired infection</td><td>51%</td></tr><tr><td>ICU mortality</td><td>10,2%</td></tr><tr><td>ICU stay duration</td><td>21+/-13</td></tr><tr><td>Hospital stay duration</td><td>34+/-20</td></tr></tbody></table>

Table: Demographic data and outcomes of patients admitted to intensive care for SARS-CoV-2 associated ARDS.

FC-066

**High plasma hyaluronate is associated with mortality in critically-ill patients with SARS-CoV-2 infections**

BONNY Vincent¹, URBINA Tomas¹, ELABBADI Alexandre², GABARRE Paul¹, MISSRI Louai¹, EHRMINGER Sebastien¹, DESNOS Cyrielle², GUIDET Bertrand¹, MAURY Eric¹, VOIRIOT Guillaume², CHANTRAN Yannick¹, MARIO Nathalie¹, JOFFRE Jérémie¹, AIT-OUFELLA Hafid¹

¹Hôpital Saint-Antoine, Paris, France; ²Hôpital Tenon, Paris, France

**Correspondence:** Vincent BONNY (vincent.bonny@aphp.fr)

Annals of Intensive Care 2022, **12**(1):FC-066

**Rationale:** SARS-CoV-2 infection could be responsible for life-threatening severe lung damage with inflammatory cell infiltration, increased vascular permeability and fluid leakage. Hyaluronic acid (HA) is an extracellular matrix polysaccharide, detected in large amounts in lung alveoli in lethal cases of COVID-19 patients. HA which is released by inflammatory cells may be involved in the pathophysiology of alveolar exudate formation through fluid retention. We aimed

to evaluate the relationship between plasma HA levels and the outcome of critically ill COVID-19 patients.

**Patients and methods/Materials and methods:** We performed an observational, bi-center study including patients admitted to intensive care unit with a confirmed laboratory SARS-CoV-2 infection, for acute respiratory failure between April 2020 and December 2020. Plasma level of hyaluronan was measured by ELISA.

**Results:** Overall, 120 patients were included in this study, median age was 62 [53–70] years, 25 patients (21%) were female, median SOFA score was 3 [2–6] at ICU admission. 76 patients (63%) required invasive mechanical ventilation. At admission, median PaO₂/FiO₂ ratio was 157 [112–221] mm Hg, mortality at day 28 was 20%. Median HA level was 177 [68–356] ng/mL at admission. HA levels were twofold higher in non-survivors (379 [90–914] vs 150 [62–283] ng/mL), p = 0.01) whereas CRP and fibrinogen were not different according to the outcome. HA levels correlated with PaO₂/FiO₂ (R = −0.22, p = 0.02, Pearson test) but did not correlate with CRP.

**Conclusion:** Plasma HA levels were associated with poor outcome in critically ill patients with SARS-CoV-2 infections.

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

FC-067

**Serum complement C3 and C4 prediction of mortality in critically ill COVID-19 patients**

MESSAOUD Linda¹, JAMOUSSI Amira¹, AYED Samia¹, RACHDI Enma¹, JARR AYA Fatma¹, YAALAQUI Sadok¹, BESBES Mohamed¹, BEN KHELIL Jalila¹

¹Hôpital Abderrahmen Mami, Ariana, Tunisie

**Correspondence:** Linda MESSAOUD (lyndamessaoud1991@gmail.com)

Annals of Intensive Care 2022, **12**(1):FC-067

**Rationale:** The complement system has many protective effects against infectious agents following activation during innate immunity, through the alternative and lectin pathways, and acquired immunity, through the classical pathway. However, adverse events were observed in COVID-19 following activation of the complement system by the prolonged release of pro-inflammatory mediators. We aimed to investigate ability of serum complement C3, C4 to predict mortality in patients with critical COVID-19.

**Patients and methods/Materials and methods:** Prospective study carried in respiratory medical intensive care unit of Abderrahmen Mami teaching hospital. It included critically ill patients diagnosed with COVID-19 between September 2020 and December 2021. Complement C3 and C4 were measured during the first 24 h of hospitalization. C3 and C4 complement deficiency was defined respectively by a concentration below 0.9 g/L and 0.16 g/L respectively. Association with ICU mortality was then analyzed.

**Results:** During the study period, we enrolled 34 patients. Mean age was 54 ± 13 years and gender ratio of 1.8. The most common comorbidities were diabetes (36%), obesity (35%) and hypertension (18%). Nineteen patients were transferred to general ward or discharged (survival group) and fifteen died in hospital (non-survival group). The condition of 9 of these patients (27%) degraded during hospitalization and needed invasive mechanical ventilation. The time from hospital admission to intubation varied from 1 to 8 days (median 1 day). During the first 24 h, median C3 was 1.72 g/L [0.6–2.61], and C4 was 0.38 g/L [0.06–0.73]. Six patients (19%) had a C3 deficit and 5 (16%) had a C4 deficit on admission. The overall mortality rate was 56% and the mean length of hospital stay was 10 days [6–17]. Patients who died had lower C3 concentrations in comparison to survivors (1.54 vs 1.85 g/L; p = 0.015). However, no significant difference was found in C4 concentrations (0.36 vs 0.40 g/L; p = 0.595). The level of complement C3 was also lower in patients who required invasive mechanical ventilation (1.42 vs 1.87 p = 0.016) compared to the non-invasive ventilation group.

**Conclusion:** Serum complement C3 and C4 deficiency can be observed in critical COVID-19 patients. C3 concentrations was significantly lower among non-survivors and invasively ventilated patients.

**Compliance with ethics regulations:** Yes in clinical research.
FC-068

Early decrease of CD4 and HLA-DR expression on monocytes
predicts the severity of COVID-19 pneumonia

ALLARDET-SERVENT Jerome¹, AIT BELKACEM Ines²,³, MILOUD Tewfik³,
BENAROUS Lucas¹, GALLAND Franck², HALFON Philippe¹, MEGE
Jean-Louis⁴, BUSNEL Jean-Marc³, MALERGUE Fabrice³

¹HOPITAL EUROPEEN MARSEILLE, Marseille, France; ²CENTRE
D'IMMUNOLOGIE MARSEILLE-LUMINY, Marseille, France; ³BECKMAN
COULTER IMMUNOTECH, Marseille, France; ⁴INSTITUT HOSPITALO-UNIVER-
SITAIRE DE MALADIES INFECTIEUSES, Marseille, France

**Correspondence:** Jerome ALLARDET-SERVENT (j.allardetservent@hopital-european.fr)

Annals of Intensive Care 2022, 12(1):FC-068

**Rationale:** Early prediction of COVID-19 pneumonia course remains challenging for physicians. Characterization of blood immune cell status may improve patient stratification¹. This study investigates the value of a rapid one-step flow cytometry method in patients hospitalized for moderate to severe COVID-19 pneumonia.

**Patients and methods/Materials and methods:** Thirty patients with laboratory confirmed COVID-19 pneumonia were prospectively included and compared to 19 healthy controls. End-points of interest were the need for intensive care unit (ICU) admission and mechanical ventilation (MV) initiation. Whole-blood immunophenotyping was performed within the first 48 h of hospital admission using three antibody panels (Beckman Coulter, Brea, USA) focusing on leucocytes (DURAClone IM Phenotyping Basic panel), granulocytes (DURAClone IM Granulocytes panel), and myeloid activation markers (IOTest Myeloid Activation Antibody Cocktail: CD169, CD64, HLA-DR). Leucocyte staining and lysis were performed following the one-step method². Comparisons were performed using Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was used to determine the area under the curve (AUC) of factors associated with ICU admission and MV requirement. Continuous data are presented as median and interquartile.

**Results:** COVID-19 patients were mostly male (87%), aged 61 [50,71] years, and 12 (40%) were obese. Nine COVID-19 patients (30%) received standard oxygen therapy in the ward while 21 (70%) required ICU admission. Among ICU patients, 7 (23%) received high flow oxygen therapy and 14 (47%) required MV of whom 3 also received extracorporeal membrane oxygenation. Four patients (13%) deceased. We confirmed a COVID-19 signature including: 1) a reduction of HLA-DR expression; 2) decreased basophils, eosinophils, T-cells, NK cells, and non-classical monocyte count; and 3) an upregulation of CD169, CD64, the adhesion/migration markers (CD62L and CD11b), and the checkpoint inhibitor CD274. COVID-19 patients requiring MV presented significantly lower expression of HLA-DR and CD4 on monocytes, as well as reduced CD8+ T-cell count. These three parameters predicted MV requirement with respective AUC of 0.87, 0.87 and 0.79 but their combination increased the AUC up to 0.991 (Fig. 1). Similarly, ICU admission was best predicted by the combination of HLA-DR and CD4 on monocytes with CD4+ T-cell count, yielding an AUC of 0.947.

**Discussion:** This study further describes the immunophenotypic alterations associated with COVID-19, emphasizes the role of monocytes, and strengthens the clinical potential of a rapid, one-step, flow cytometry method.

**Conclusion:** HLA-DR and CD4 expression on monocytes, when combined to CD4+ and CD8+ T-cells count, may facilitate the early prediction of ICU admission and MV initiation in hospitalized patients with COVID-19 pneumonia.

**Reference 1:** Chevrier, S et al. A Distinct Innate Immune Signature Marks Progression from Mild to Severe COVID-19. Cell Rep Med 2021, 2 (1), 100166.

**Reference 2:** Ait Belkacem, I et al. One-Step White Blood Cell Extracellu-
lular Staining Method for Flow Cytometry. Bio-protocol 2021, 11 (16),
e4135–e4135.

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

<figure><img src="image_66.png" /></figure>

Immune parameters at hospital admission in COVID-19 patients. A-D: Comparison of HLA-DR and CD4 expression on monocytes and CD4+ and CD8+ T cell count according to MV or ICU admission. B-D: Individual and combined ROC curves of the three best discriminant.

FC-069

Lymphocytic alveolitis in severe COVID-19 pneumonia

REYNAUD Faustine¹, RODRIGUEZ Maeva¹, ARRIVE François¹, VEINSTEIN
Anne¹, CHATELLIER Delphine¹, BOISSIER Florence¹, FRAT Jean-Pierre¹,
COUDROY Rémi¹, THILLE Arnaud W.¹

¹CHU de Poitiers, Poitiers, France

**Correspondence:** Faustine REYNAUD (faust.reynaud@gmail.com)

Annals of Intensive Care 2022, 12(1):FC-069

**Rationale:** Neutrophil alveolitis has been reported in the early course of mechanically ventilated patients with COVID-19¹,². Whereas lymphocytic alveolitis is described in organizing pneumonia, whether this pattern occurs during the course of COVID-19-related respiratory failure is unknown.

**Patients and methods/Materials and methods:** Retrospective observational cohort study performed in a single-center. All patients with COVID-19-related respiratory failure admitted to our ICU between September 2020 and June 2021 (second and third wave) and who had broncho-alveolar lavage (BAL) were included. BAL was performed for secondary worsening or lack of improvement after excluding ventilator-associated pneumonia or pulmonary embolism. Secondary worsening was defined as a one-point increase on the World Health Organization 7-point Clinical Progression Scale (WHO-CPS) occurring after steroid discontinuation and after a first step of improvement (at least one-point drop on the WHO-CPS). Lack of improvement was defined as no point-drop on WHO-CPS after ten days of steroids. The primary outcome was the prevalence of lymphocytic alveolitis defined by a lymphocyte count at least 20% of total cellular count.

**Results:** Among the 182 patients admitted for COVID-19-related respiratory failure over the study-period, BAL was performed in 20 patients with secondary worsening (n = 12) or lack of improvement (n = 8). As compared to the others, patients who underwent BAL were more likely to be intubated (18 of 20 patients, 90% vs. 76 of 162 patients, 47%; p < 0.001), and had longer duration mechanical ventilation (24 days in median [14–39] vs. 10 days [8–15]; p < 0.001). Among the 20 patients who underwent BAL, 10 (50%) had lymphocytic alveolitis including 50% of patients who had BAL for secondary worsening (6 out of 12 patients), and 50% of patients who had BAL for lack of improvement (4 out of 8 patients). All patients with lymphocytic alveolitis received a second course of steroid therapy after BAL. Mortality was 75% in patients with lack of improvement (3 of 4 patients) and 17% (1 of 6 patients) in those with secondary worsening.

**Conclusion:** Lymphocytic alveolitis was found in half of patients who underwent BAL for secondary worsening or lack of improvement and was associated with good outcomes when a second regimen of steroid was administered to patients with secondary worsening.

**Reference 1:** Baron A, Hachem M, Tran Van Nhieu J, Botterel F, Fourati S, Carteaux G, De Prost N, Maitre B, Mekontso-Dessap A, Schlemmer F. Bronchoalveolar lavage in patients with COVID-19 with invasive mechanical ventilation for acute respiratory distress syndrome. An.