Publications by authors named "Sami Hraiech"

75 Publications

Identifying Clinical Phenotypes in Moderate to Severe Acute Respiratory Distress Syndrome Related to COVID-19: The COVADIS Study.

Front Med (Lausanne) 2021 11;8:632933. Epub 2021 Mar 11.

Soins Intensifs, Hôpital Erasme, Universite Libre Bruxelles, Bruxelles, Belgium.

Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19. We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes. We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2. In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.
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http://dx.doi.org/10.3389/fmed.2021.632933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991403PMC
March 2021

Oesophageal pressure as a surrogate of pleural pressure in mechanically ventilated patients.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Mar 8.

Médecine Intensive Réanimation, Hôpital Nord, AP-HM, Marseille, France.

Background: Oesophageal pressure () is used to approximate pleural pressure () and therefore to estimate transpulmonary pressure (). We aimed to compare oesophageal and regional pleural pressures and to calculate transpulmonary pressures in a prospective physiological study on lung transplant recipients during their stay in the intensive care unit of a tertiary university hospital.

Methods: Lung transplant recipients receiving invasive mechanical ventilation and monitored by oesophageal manometry and dependent and nondependent pleural catheters were investigated during the post-operative period. We performed simultaneous short-time measurements and recordings of oesophageal manometry and pleural pressures. Expiratory and inspiratory were computed by subtracting regional or from airway pressure; inspiratory was also calculated with the elastance ratio method.

Results: 16 patients were included. Among them, 14 were analysed. Oesophageal pressures correlated with dependent and nondependent pleural pressures during expiration (R=0.71, p=0.005 and R=0.77, p=0.001, respectively) and during inspiration (R=0.66 for both, p=0.01 and p=0.014, respectively). values calculated using were close to those obtained from the dependent pleural catheter but higher than those obtained from the nondependent pleural catheter both during expiration and inspiration.

Conclusions: In ventilated lung transplant recipients, oesophageal manometry is well correlated with pleural pressure. The absolute value of is higher than of nondependent lung regions and could therefore underestimate the highest level of lung stress in those at high risk of overinflation.
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http://dx.doi.org/10.1183/23120541.00646-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938048PMC
January 2021

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

Ann Intensive Care 2021 Feb 11;11(1):33. Epub 2021 Feb 11.

Sorbonne Université, INSERM, Médecine Intensive Réanimation, Institut de Cardiologie, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.

Methods: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37).

Results: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups.

Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.
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http://dx.doi.org/10.1186/s13613-020-00793-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876264PMC
February 2021

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

Crit Care 2021 02 8;25(1):52. Epub 2021 Feb 8.

Soins Intensifs, Hôpital Erasme, ULB, Route de Lennik 808, 1070, Bruxelles, Belgium.

Background: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14.

Methods: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation.

Results: The mean Crs in 372 patients was 37.6 ± 13 mL/cmHO, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO/FiO ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmHO vs 37.8 ± 11.4 mL/cmHO, p < 0.001). The decrease in Crs was not associated with day-28 outcome.

Conclusion: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmHO and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.
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http://dx.doi.org/10.1186/s13054-020-03433-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868865PMC
February 2021

Prevalence of pressure injuries among critically ill patients and factors associated with their occurrence in the intensive care unit: The PRESSURE study.

Aust Crit Care 2021 Jan 19. Epub 2021 Jan 19.

CERC, SRLF, France. Electronic address:

Background: The prevalence of pressure injuries (PIs) in critically ill patients has been extensively studied, but there is uncertainty regarding the risk factors. The main objective of this study was to describe the prevalence of PIs in critically ill patients. Secondary objectives were to describe PI, use of preventive measures for PI, and factors associated with occurrence of PI in the intensive care unit (ICU).

Material And Methods: This was a 1-day point-prevalence study performed on a weekday in June 2017 in ICUs in France. On the same day, we noted the presence or absence of PI in all hospitalised patients of the participating ICUs, data on the ICUs, and the characteristics of patients and of PI.

Results: Eighty-six participating ICUs allowed the inclusion of 1228 patients. The prevalence of PI on the study day was 18.7% (95% confidence interval: 16.6-21.0). PIs acquired in the ICU were observed in 12.5% (95% confidence interval: 10.6-14.3) of critically ill patients on the study day. The most frequent locations of PI were the sacrum (57.4%), heel (35.2%), and face (8.7%). Severe forms of PI accounted for 40.8% of all PIs. Antiulcer mattresses were used in 91.5% of the patients, and active and/or passive mobilisation was performed for all the patients. Multiple logistic regression analysis identified longer length of stay in the ICU, a higher Simplified Acute Physiology Score, higher body weight, motor neurological disorder, high-dose steroids, and absence of oral nutrition on the study day as factors independently associated with occurrence of PI in the ICU.

Conclusion: This large point-prevalence study shows that PIs are found in about one of five critically ill patients despite extensive use of devices for preventing PI. Acquisition of PI in the ICU is strongly related to the patient's severity of illness on admission to the ICU and length of stay in the ICU.
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http://dx.doi.org/10.1016/j.aucc.2020.12.001DOI Listing
January 2021

Bedside POCUS during ward emergencies is associated with improved diagnosis and outcome: an observational, prospective, controlled study.

Crit Care 2021 01 22;25(1):34. Epub 2021 Jan 22.

Assistance Publique Hôpitaux de Marseille, Department of Anesthesiology and Intensive Care, Hôpital Nord, Aix Marseille University, 13015, Marseille, France.

Background: Rapid response teams are intended to improve early diagnosis and intervention in ward patients who develop acute respiratory or circulatory failure. A management protocol including the use of a handheld ultrasound device for immediate point-of-care ultrasound (POCUS) examination at the bedside may improve team performance. The main objective of the study was to assess the impact of implementing such a POCUS-guided management on the proportion of adequate immediate diagnoses in two groups. Secondary endpoints included time to treatment and patient outcomes.

Methods: A prospective, observational, controlled study was conducted in a single university hospital. Two teams alternated every other day for managing in-hospital ward patients developing acute respiratory and/or circulatory failures. Only one of the team used an ultrasound device (POCUS group).

Results: We included 165 patients (POCUS group 83, control group 82). Proportion of adequate immediate diagnoses was 94% in the POCUS group and 80% in the control group (p = 0.009). Time to first treatment/intervention was shorter in the POCUS group (15 [10-25] min vs. 34 [15-40] min, p < 0.001). In-hospital mortality rates were 17% in the POCUS group and 35% in the control group (p = 0.007), but this difference was not confirmed in the propensity score sample (29% vs. 34%, p = 0.53).

Conclusion: Our study suggests that protocolized use of a handheld POCUS device at the bedside in the ward may improve the proportion of adequate diagnosis, the time to initial treatment and perhaps also survival of ward patients developing acute respiratory or circulatory failure. Clinical Trial Registration NCT02967809. Registered 18 November 2016, https://clinicaltrials.gov/ct2/show/NCT02967809 .
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http://dx.doi.org/10.1186/s13054-021-03466-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825196PMC
January 2021

National incidence rate and related mortality for acute respiratory distress syndrome in France.

Anaesth Crit Care Pain Med 2021 02 24;40(1):100795. Epub 2020 Dec 24.

Aix-Marseille Université, Faculté de Médecine, Centre d'Études et de Recherches sur les Services de Santé et qualité de vie EA 3279, 13005 Marseille, France; Unité d'Aide Méthodologique à la Recherche Clinique, Assistance Publique, Hôpitaux de Marseille, 13015 Marseille, France.

Introduction: Despite many efforts to improve mechanical ventilation strategies and the use of rescue strategies, ARDS-related mortality remains high. The primary objective of this study was to determine the incidence and 90-day mortality of ARDS patients admitted to all French ICUs following the introduction of the Berlin definition of ARDS.

Patients And Methods: The data source for this nationwide cohort study was the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)), which systematically collects administrative and medical information related to all patients hospitalised and hospital stays. Patient-level data were obtained from the PMSI database for all patients admitted to an ICU from the 1 of January 2017, through the 31 of December 2017. The inclusion criteria were as follows: ICU patients ≥ 18 years old with at least one International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) diagnosis code of J80 (ARDS), either as a primary diagnosis or a secondary diagnosis, during their ICU stay.

Results: A total of 12,846 ICU adult patients with ARDS were included. The crude incidence of ARDS was 24.6 per 100,000 person-years, varying with age from 6.7 per 100,000 person-years for those 18 through 40 years of age to 51.9 per 100,000 person-years for those 68 through 76 years of age. The in-hospital mortality rate was 51.1%. Day-90 mortality (day-1 being the ICU admission) was 51.2% and increased with age from 29.0% for patients 18 through 40 years of age to 69.3% for patients 77 years of age or older (p < 0.001). Only 53.9% of the survivors were transferred home directly after hospital discharge.

Conclusions: The incidence and mortality of ARDS in adults in France are higher than that generally reported in other countries.
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http://dx.doi.org/10.1016/j.accpm.2020.100795DOI Listing
February 2021

Migrants in the intensive care unit: time to show we care.

Intensive Care Med 2021 Apr 24;47(4):473-475. Epub 2020 Nov 24.

Service de Médecine Intensive Et Réanimation, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.

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http://dx.doi.org/10.1007/s00134-020-06318-6DOI Listing
April 2021

Adverse Events in Intensive Care and Continuing Care Units During Bed-Bath Procedures: The Prospective Observational NURSIng during critical carE (NURSIE) Study.

Crit Care Med 2021 01;49(1):e20-e30

Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire, Chemin des Bourrely, Marseille, France.

Objectives: Standard nursing interventions, especially bed-baths, in ICUs can lead to complications or adverse events defined as a physiologic change that can be life-threatening or that prolongs hospitalization. However, the frequency and type of these adverse events are rarely reported in the literature. The primary objective of our study was to describe the proportion of patients experiencing at least one serious adverse event during bed-bath. The secondary objectives were to determine the incidence of each type of serious adverse event and identify risk factors for these serious adverse events.

Design: Prospective multicenter observational study.

Setting: Twenty-four ICUs in France, Belgium, and Luxembourg.

Patients: The patients included in this study had been admitted to an ICU for less than 72 hours and required at least one of the following treatments: invasive ventilation, vasopressors, noninvasive ventilation, high-flow oxygen therapy. Serious adverse events were defined as cardiac arrest, accidental extubation, desaturation and/or mucus plugging/inhalation, hypotension and/or arrhythmia and/or agitation requiring therapeutic intervention, acute pain, accidental disconnection or dysfunction of equipment, and patient fall requiring additional assistance.

Interventions: None.

Measurements And Main Results: The study included 253 patients from May 1, 2018, to July 31, 2018 in 24 ICUs, representing 1,529 nursing procedures. The mean Simplified Acute Physiology Score II was 54 ± 19. Nursing care was administered by an average of 2 ± 1 caregivers and lasted between 11 and 20 minutes. Of the 253 patients included, 142 (56%) experienced at least one serious adverse event. Of the 1,529 nursing procedures, 295 (19%) were complicated by at least one serious adverse event. In multivariate analysis, the factors associated with serious adverse event were as follows: presence of a specific protocol (p = 0.011); tracheostomy (p = 0.032); administration of opioids (p = 0.007); presence of a physician (p = 0.0004); duration of nursing care between 6 and 10 minutes (p = 0.003), duration of nursing care between 11 and 20 minutes (p = 0.005), duration of nursing care greater than 40 minutes (p = 0.04) with a reference duration of nursing care between 20 and 40 minutes.

Conclusions: Serious adverse events were observed in one-half of patients and concerned one-fifth of nurses, confirming the need for caution. Further studies are needed to test systematic serious adverse event prevention strategies.
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http://dx.doi.org/10.1097/CCM.0000000000004745DOI Listing
January 2021

Myorelaxants in ARDS patients.

Intensive Care Med 2020 Dec 7;46(12):2357-2372. Epub 2020 Nov 7.

Assistance Publique - Hôpitaux de Marseille, Hôpital Nord, Médecine Intensive Réanimation, 13015, Marseille, France.

Neuromuscular blocking agents (NMBAs) inhibit patient-initiated active breath and the risk of high tidal volumes and consequent high transpulmonary pressure swings, and minimize patient/ ventilator asynchrony in acute respiratory distress syndrome (ARDS). Minimization of volutrauma and ventilator-induced lung injury (VILI) results in a lower incidence of barotrauma, improved oxygenation and a decrease in circulating proinflammatory markers. Recent randomized clinical trials did not reveal harmful muscular effects during a short course of NMBAs. The use of NMBAs should be considered during the early phase of severe ARDS for patients to facilitate lung protective ventilation or prone positioning only after optimising mechanical ventilation and sedation. The use of NMBAs should be integrated in a global strategy including the reduction of tidal volume, the rational use of PEEP, prone positioning and the use of a ventilatory mode allowing spontaneous ventilation as soon as possible. Partial neuromuscular blockade should be evaluated in future trials.
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http://dx.doi.org/10.1007/s00134-020-06297-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648542PMC
December 2020

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

J Clin Med 2020 Oct 22;9(11). Epub 2020 Oct 22.

Cardiology Department, APHM, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Centre for CardioVascular and Nutrition Research (C2VN), Aix-Marseille Univ, INSERM 1263, INRA 1260, Hopital Nord, 13015 Marseille, France.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895-2277) vs. 2622 (2264-2993) dynes-s·cm·m ( = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88-2.18) vs. 1.78 (1.65-1.96) L·min·m ( = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.
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http://dx.doi.org/10.3390/jcm9113384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690259PMC
October 2020

Management of lung transplantation in the COVID-19 era-An international survey.

Am J Transplant 2021 04 5;21(4):1586-1596. Epub 2020 Nov 5.

Department of Internal Medicine V - Pneumology, Allergology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.
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http://dx.doi.org/10.1111/ajt.16368DOI Listing
April 2021

Characteristics and outcomes of acute respiratory distress syndrome related to COVID-19 in Belgian and French intensive care units according to antiviral strategies: the COVADIS multicentre observational study.

Ann Intensive Care 2020 Oct 6;10(1):131. Epub 2020 Oct 6.

CRICS-TriggerSEP research network, Tours, France.

Background: Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS).

Methods: Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into "patients still ventilated or dead at day 28" versus "patients weaned and alive at day 28".

Results: We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0-13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO/FiO ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18-1.25); OR 0.96 (0.47-2.02) and OR 1.43 (0.53-4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16-5.59).

Conclusion: In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT.
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http://dx.doi.org/10.1186/s13613-020-00751-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537971PMC
October 2020

Transpulmonary pressures in obese and non-obese COVID-19 ARDS.

Ann Intensive Care 2020 Oct 1;10(1):129. Epub 2020 Oct 1.

Assistance Publique - Hôpitaux de Marseille, Hôpital Nord, Médecine Intensive Réanimation, Chemin Des Bourrely, 13015, Marseille, France.

Background: Data on respiratory mechanics of COVID-19 ARDS patients are scarce. Respiratory mechanics and response to positive expiratory pressure (PEEP) may be different in obese and non-obese patients.

Methods: We investigated esophageal pressure allowing determination of transpulmonary pressures (PL ) and elastances (EL) during a decremental PEEP trial from 20 to 6 cm HO in a cohort of COVID-19 ARDS patients.

Results: Fifteen patients were investigated, 8 obese and 7 non-obese patients. PEEP ≥ 16 cm HO for obese patients and PEEP ≥10 cm HO for non-obese patients were necessary to obtain positive expiratory P. Change of PEEP did not alter significantly ΔP or elastances in obese patients. However, in non-obese patients lung EL  and ΔP increased significantly with PEEP increase. Chest wall EL was not affected by PEEP variations in both groups.
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http://dx.doi.org/10.1186/s13613-020-00745-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527784PMC
October 2020

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Science 2020 10 24;370(6515). Epub 2020 Sep 24.

Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
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http://dx.doi.org/10.1126/science.abd4570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857407PMC
October 2020

Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19.

J Infect Dis 2020 Nov;222(11):1789-1793

Aix-Marseille University, INSERM 1263, INRAE, C2VN, Marseille, France.

Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.
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http://dx.doi.org/10.1093/infdis/jiaa528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454721PMC
November 2020

Factors Associated With Pulmonary Embolism Among Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: A Multicenter Study Among 375 Patients.

Crit Care Explor 2020 Jul 25;2(7):e0166. Epub 2020 Jun 25.

Service de Réanimation Médicale, CHU Besançon, Besançon, France.

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France ( = 12) and Belgium ( = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339309PMC
July 2020

Critical illness-associated cerebral microbleeds in COVID-19 acute respiratory distress syndrome.

Neurology 2020 09 29;95(11):498-499. Epub 2020 Jul 29.

From Médecine Intensive Réanimation (O.C., S.H.) and Service de Neurochirurgie, Pôle de Neurosciences Cliniques (L.M.-A.), Hôpital Nord, Assistance Publique-Hôpitaux de Marseille; and Centre d'Etudes et de Recherches sur les Services de Santé et Qualité de vie EA 3279 (O.C., S.H.), Faculté de Médecine, Aix-Marseille Université, Marseille, France.

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http://dx.doi.org/10.1212/WNL.0000000000010537DOI Listing
September 2020

Venous Thromboembolism Events Following Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome Coronavirus 2 Based on CT Scans.

Crit Care Med 2020 10;48(10):e971-e975

Médecine Intensive Réanimation Détresses Respiratoires et Infection Sévères, AP-HM, CHU Nord, Marseille, France.

Objectives: The main objective of the study was to determine the prevalence of venous thromboembolism events in patients infected with severe acute respiratory syndrome coronavirus 2 requiring venovenous extracorporeal membrane oxygenation. The secondary objective was to compare venous thromboembolism events and coagulation variables in patients requiring venovenous extracorporeal membrane oxygenation according to the pathogen.

Design: Retrospective observational analysis at a single center.

Setting: Tertiary referral university teaching hospital.

Patients: Patients with severe acute respiratory syndrome coronavirus 2-related severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation therapy with an injected CT scan performed after extracorporeal membrane oxygenation retrieval.

Interventions: None.

Measurements And Main Results: We included 13 severe acute respiratory syndrome coronavirus 2 patients requiring venovenous extracorporeal membrane oxygenation. All of these patients experienced venous thromboembolism: 10 patients (76.9%) had isolated cannula-associated deep vein thrombosis, two patients (15.4%) had isolated pulmonary embolism, and one patient (7.7%) had both cannula-associated deep vein thrombosis and pulmonary embolism. Eleven patients (84.6%) had cannula-associated deep vein thrombosis. A jugular associated cannula-associated deep vein thrombosis was identified in seven patients (53.8%), a femoral associated cannula-associated deep vein thrombosis was identified in 10 patients (76.9%), and six patients (46.2%) had both femoral and jugular cannula-associated deep vein thrombosis. A pulmonary embolism was found in three patients (23.1%). No patient had central venous catheter-related deep vein thrombosis. One patient had thrombotic occlusion of the centrifugal pump, and one had oxygenator thrombosis requiring circuit replacement. Three patients (23.1%) had significant bleeding. Three patients (23.1%) had laboratory-confirmed heparin-induced thrombocytopenia, and all of them developed cannula-associated deep vein thrombosis. These three patients had femoral cannula-associated deep vein thrombosis, and two had an oxygenator or pump thrombosis. The mean activated partial thromboplastin time ratio was higher in the severe acute respiratory syndrome coronavirus 2 group than in the influenza group and the community-acquired pneumonia group (1.91 vs 1.48 vs 1.53; p = 0.001), which was also found in regard to the percentage of patients with an activated partial thromboplastin time ratio greater than 1.8 (47.8% vs 20% vs 20.9%; p = 0.003) and the mean prothrombin ratio (86.3 vs 61.6 vs 67.1; p = 0.003). There was no difference in baseline characteristics or venous thromboembolism events.

Conclusions: We report a 100% occurrence of venous thromboembolism in critically ill patients supported by venovenous extracorporeal membrane oxygenation for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome using CT scan imaging despite a high target and close monitoring of anticoagulation.
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http://dx.doi.org/10.1097/CCM.0000000000004504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328443PMC
October 2020

Worldwide clinical practices in perioperative antibiotic therapy for lung transplantation.

BMC Pulm Med 2020 Apr 29;20(1):109. Epub 2020 Apr 29.

Aix Marseille University, APHM, Hôpital Nord, Intensive Care Unit, Marseille, France.

Background: Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices.

Methods: We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period.

Results: We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%).

Conclusion: Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.
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http://dx.doi.org/10.1186/s12890-020-1151-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191774PMC
April 2020

Response to Huang et al. "Herpesviridae reactivation for poor outcome in ARDS patients with ECMO: criminal or witness?"

Ann Intensive Care 2020 Jan 21;10(1). Epub 2020 Jan 21.

Service de Médecine Intensive-Réanimation, APHM, Hôpital Nord, Marseille, France.

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http://dx.doi.org/10.1186/s13613-020-0627-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973884PMC
January 2020

Prevalence and Risk Factors for Thrombotic Complications Following Venovenous Extracorporeal Membrane Oxygenation: A CT Scan Study.

Crit Care Med 2020 02;48(2):192-199

Médecine Intensive Réanimation Détresses Respiratoires et Infection Sévères, AP-HM, CHU Nord, Marseille, France.

Objectives: The aims of this study were to: 1) analyze the cannula-associated deep vein thrombosis frequency after venovenous extracorporeal membrane oxygenation using a CT scan and 2) identify the associated risk factors for cannula-associated deep vein thrombosis.

Design: Retrospective observational analysis at a single center.

Setting: Tertiary referral university teaching hospital.

Patients: Patients under venovenous extracorporeal membrane oxygenation with a femorofemoral or femorojugular cannulation admitted for acute respiratory distress syndrome or primary graft dysfunction after pulmonary transplantation. CT scan was performed within 4 days after decannulation.

Interventions: None.

Measurements And Main Results: We included 105 of 228 patients screened. Bacterial pneumonia was the main indication of venovenous extracorporeal membrane oxygenation (46.7%). CT scans were performed at a median of 2 days (1-3 d) after decannulation. Cannula-associated deep vein thrombosis was found in 75 patients (71.4%) despite it having a mean activated partial thromboplastin time ratio of 1.60 ± 0.31. Femorofemoral cannulation induced femoral cannula-associated deep vein thrombosis more frequently than femorojugular cannulation (69.2% vs 63.1%, respectively; p = 0.04). Seventeen of the 105 patients (16.2%) had a pulmonary embolism. Multivariate logistic regression analysis showed that higher the percentage of thrombocytopenia less than 100 G/L during extracorporeal membrane oxygenation period, lower the risk for developing cannula-associated deep vein thrombosis (hazard ratio, 0.98; 95% CI, 0.98-1.00; p = 0.02).

Conclusions: Cannula-associated deep vein thrombosis after venovenous extracorporeal membrane oxygenation is a frequent complication. This plead for a systematic vascular axis imaging after venovenous extracorporeal membrane oxygenation. Thrombocytopenia is associated with a reduction in the occurrence of thrombotic events.
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http://dx.doi.org/10.1097/CCM.0000000000004129DOI Listing
February 2020

Herpes simplex virus and Cytomegalovirus reactivation among severe ARDS patients under veno-venous ECMO.

Ann Intensive Care 2019 Dec 23;9(1):142. Epub 2019 Dec 23.

Service de Médecine Intensive - Réanimation, APHM, Hôpital Nord, Marseille, France.

Background: Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS). However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO). We tried to determine the frequency of Herpesviridae reactivation and its impact on patients' prognosis during ECMO for severe ARDS.

Results: During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a veno-venous ECMO were included. Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone). HSV reactivation occurred earlier than CMV after the beginning of MV [(6-15) vs. 19 (13-29) days; p < 0.01] and after ECMO implementation [(2-8) vs. 14 (10-20) days; p < 0.01]. In univariate analysis, HSV/CMV reactivation was associated with a longer duration of mechanical ventilation [(22-52.5) vs. 17.5 (9-28) days; p < 0.01], a longer duration of ECMO [15 (10-22.5) vs. 9 (5-14) days; p < 0.01], and a prolonged ICU [29 (19.5-47.5) vs. 16 (9-30) days; p < 0.01] and hospital stay [44 (29-63.5) vs. 24 (11-43) days; p < 0.01] as compared to non-reactivated patients. However, in multivariate analysis, viral reactivation remained associated with prolonged MV only. When considered separately, both HSV and CMV reactivation were associated with a longer duration of MV as compared to non-reactivation patients [29 (19.5-41) and 28 (20.5-37), respectively, vs. 17.5 (9-28) days; p < 0.05]. Co-reactivation patients had a longer duration of MV [58.5 (38-72.3); p < 0.05] and ICU stay [51.5 (32.5-69) vs. 27.5 (17.75-35.5) and 29 (20-30.5), respectively] as compared to patients with HSV or CMV reactivation alone. In multivariate analysis, HSV reactivation remained independently associated with a longer duration of MV and hospital length of stay.

Conclusions: Herpesviridae reactivation is frequent among patients with severe ARDS under veno-venous ECMO and is associated with a longer duration of mechanical ventilation. The direct causative link between HSV and CMV reactivation and respiratory function worsening under ECMO remains to be confirmed.
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http://dx.doi.org/10.1186/s13613-019-0616-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928167PMC
December 2019

Thyroid Storm in the ICU: A Retrospective Multicenter Study.

Crit Care Med 2020 01;48(1):83-90

Medical Intensive Care Unit, Hôpital Pontchaillou, CHU de Rennes, France.

Objectives: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission.

Design: Retrospective, multicenter, national study over an 18-year period (2000-2017).

Setting: Thirty-one French ICUs.

Patients: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure.

Measurements And Main Results: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality.

Conclusions: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.
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http://dx.doi.org/10.1097/CCM.0000000000004078DOI Listing
January 2020

Neuromuscular blocking agents as part of lung-protective strategy in severe ARDS patients.

Anaesth Crit Care Pain Med 2019 08;38(4):311-313

Marseille Public University Hospital System, North Hospital, Service de Médecine Intensive et Réanimation, 13015 Marseille, France; University of Aix-Marseille, Faculty of Medicine, Centre d'Études et de Recherches sur les Services de Santé et qualité de vie EA 3279, 13005 Marseille, France.

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http://dx.doi.org/10.1016/j.accpm.2019.07.002DOI Listing
August 2019

Chest CT scan and alveolar procollagen III to predict lung fibroproliferation in acute respiratory distress syndrome.

Ann Intensive Care 2019 Mar 27;9(1):42. Epub 2019 Mar 27.

Médecine Intensive Réanimation Détresses Respiratoires et Infection Sévères, AP-HM, CHU Nord, chemin des Bourrely, 13015, Marseille, France.

Background: Lung fibroproliferation in ARDS patients is associated with mortality. Alveolar procollagen III (NT-PCP-III) is a validated biomarker of lung fibroproliferation. A chest CT scan could be useful for the diagnosis of lung fibroproliferation. The aim of this study was to identify lung fibroproliferative CT scan aspects in ARDS patients with high levels of NT-PCP-III.

Results: This retrospective study included ARDS patients who had at least one assessment of alveolar NT-PCP-III and a chest CT scan within 3 days before or after NT-PCP-III determination. An alveolar level of NT-PCP-III > 9 µG/L indicated fibroproliferation. The CT scan was scored on interstitial and alveolar abnormalities. Each lobe was scored from 0 to 5 according to the severity of the abnormalities. The crude score and the corrected score (related to the number of scored lobes in cases of important lobar condensation or lobectomy) were used. One hundred ninety-two patients were included, for a total of 228 alveolar NT-PCP-III level and CT scan 'couples'. Crude and corrected CT scan fibrosis scores were higher in the fibroproliferation group compared with the no fibroproliferation group (crude score: 12 [9-17] vs 14 [11-12], p = 0.002; corrected score: 2.8 [2.2-4.0] vs 3.4 [2.5-4.7], p < 0.001). CT scan fibrosis scores and NT-PCP-III levels were significantly but weakly correlated (crude score: ρ = 0.178, p = 0.007; corrected score: ρ = 0.184, p = 0.005).

Conclusions: When the alveolar level of NT-PCP-III was used as a surrogate marker of histological lung fibroproliferation, the CT scan fibrosis score was significantly higher in patients with active lung fibroproliferation. Pulmonary condensation is the main limitation to diagnosing fibroproliferation during ARDS.
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http://dx.doi.org/10.1186/s13613-019-0516-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437222PMC
March 2019