Publications by authors named "Bruno Megarbane"

375 Publications

Extracorporeal Kidney-Replacement Therapy for Acute Kidney Injury.

N Engl J Med 2022 06;386(23):2250

Université Paris Cité, Paris, France

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc2204453DOI Listing
June 2022

A two-decade review of butane toxicity as a substance of abuse.

Basic Clin Pharmacol Toxicol 2022 Jun 5. Epub 2022 Jun 5.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, INSERM UMRS-1144, Paris, France.

Butane, an aliphatic hydrocarbon with explosive and flammable properties, is widely misused especially by young people. Acting as an asphyxiant gas, butane mainly targets the central nervous and cardiovascular systems. We aimed to review butane-attributed toxicities due to its harmful use or misuse reported in a two-decade period. We searched English-language publications reporting butane toxicities from 2000 up to 2021 and collected data on age, gender, route and source of exposure, country of origin, clinical presentation and outcome. Among 54 butane's harmful use/misuse cases identified in the literature, there were 11 survivors successfully discharged from the hospital. Patients were predominantly males with a mean age ± SD of 23 ± 13 years. The main route of exposure was inhalation. Manifestations were mainly cardiac and neurological. Majority of the cases were reported from Europe and Japan. To conclude, butane exposure is at risk of severe central nervous system and cardiac toxicities, which may result in a fatal outcome. Therefore, in the event of a sudden or suspicious death in a young individual, our findings suggest that butane's harmful use/misuse should be considered as a potential differential diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcpt.13760DOI Listing
June 2022

[Severe hypoglycemia with cardiac arrest after massive tramadol ingestion - a case report].

Therapie 2022 Apr 27. Epub 2022 Apr 27.

Réanimation médicale et toxicologique, hôpital Lariboisière, fédération de toxicologie AP-HP, Inserm ULRS-1144, université de Paris Centre, 75010 Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.therap.2022.04.002DOI Listing
April 2022

Extracorporeal life support as a bridge to lung transplantation strategy in anti-MDA5+ rapidly progressive interstitial lung disease is life-saving but with persistent difficulties at the bedside.

Eur Respir J 2022 May 20. Epub 2022 May 20.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université de Paris Cité, INSERM UMRS-1144, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00817-2022DOI Listing
May 2022

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Proc Natl Acad Sci U S A 2022 05 16;119(21):e2200413119. Epub 2022 May 16.

Hospices Civils de Lyon, 69002 Lyon, France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2200413119DOI Listing
May 2022

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

Am J Respir Crit Care Med 2022 May 9. Epub 2022 May 9.

Service de Medecine Intensive Reanimation Pitie Salpetrière hospital , Pairs, France;

Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.

Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables.

Main Results: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients.

Conclusions: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202111-2495OCDOI Listing
May 2022

Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial.

JMIR Res Protoc 2022 May 9;11(5):e30496. Epub 2022 May 9.

GHU-Paris Psychiatrie & Neurosciences, Sainte-Anne Hospital, Université de Paris, Paris, France.

Background: Critically ill patients are at risk of developing a postintensive care syndrome (PICS), which is characterized by physical, psychological, and cognitive impairments and which dramatically impacts the patient's quality of life (QoL). No intervention has been shown to improve QoL. We hypothesized that a medical, psychological, and social follow-up would improve QoL by mitigating the PICS.

Objective: This multicenter, randomized controlled trial (SUIVI-REA) aims to compare a multidisciplinary follow-up with a standard postintensive care unit (ICU) follow-up.

Methods: Patients were randomized to the control or intervention arm. In the intervention arm, multidisciplinary follow-up involved medical, psychological, and social evaluation at ICU discharge and at 3, 6, and 12 months thereafter. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. Baseline characteristics at ICU discharge were collected for all patients. The primary outcome was QoL at 1 year, assessed using the Euro Quality of Life-5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological, and functional status; social and professional reintegration; and the rate of rehospitalization and outpatient consultations at 1 year.

Results: The study was funded by the Ministry of Health in June 2010. It was approved by the Ethics Committee on July 8, 2011. The first and last patient were randomized on December 20, 2012, and September 1, 2017, respectively. A total of 546 patients were enrolled across 11 ICUs. At present, data management is ongoing, and all parties involved in the trial remain blinded.

Conclusions: The SUVI-REA multicenter randomized controlled trial aims to assess whether a post-ICU multidisciplinary follow-up improves QoL at 1 year.

Trial Registration: Clinicaltrials.gov NCT01796509; https://clinicaltrials.gov/ct2/show/NCT01796509.

International Registered Report Identifier (irrid): DERR1-10.2196/30496.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/30496DOI Listing
May 2022

Massive tramadol ingestion resulting in fatal brain injury - a pharmacokinetic study with discussion on the involved mechanisms of toxicity.

Clin Toxicol (Phila) 2022 May 4:1-4. Epub 2022 May 4.

Université de Paris, Inserm UMRS, Paris, France.

Background: Tramadol-attributed toxicity may involve opioid-like, serotoninergic, and noradrenergic mechanisms. We investigated the mechanisms of toxicity in a massive tramadol ingestion case by examining serial clinical, imaging, electroencephalography, pharmacokinetics, and genotyping data.

Case Report: A 32-year-old female who presumably ingested 9000 mg sustained-release tramadol was found comatose without hypoglycemia, bradypnea, hypotension, marked hypoxemia or seizures. She developed eyelid myoclonus and non-reactive mydriasis. Electroencephalogram showed non-reactive encephalopathy. MRI showed extensive brain injury. Despite supportive care and ventricular derivation, brain death occurred on day 12.

Methods: Plasma concentrations of tramadol and metabolites were measured using a liquid chromatography-tandem mass spectrometry assay. Genotyping for the presence of metabolizing cytochrome P450 (CYP) gene polymorphisms was performed.

Results: Plasma concentrations of tramadol and metabolites were extremely high (∼70-fold the therapeutic concentrations) and slowly decreased during the first ∼146 h post-admission, possibly due to prolonged gastrointestinal absorption. Elimination half-lives were 2-3-fold longer than usual values. The patient was an intermediate CYP2D6 metabolizer with decreased CYP3A4 and CYP2B6 activities. Clinical and electroencephalographic data did not support the hypotheses of opioid or serotoninergic toxicity nor prolonged/repeated seizures. Based on serial imaging showing progressive extension of ischemic edema in the context of prolonged high plasma concentrations, we hypothesized a cerebral vasospasm as mechanism of injury.

Conclusion: Massive tramadol ingestion with prolonged high plasma concentrations can result in severe brain injury, possibly involving vasospasm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2071286DOI Listing
May 2022

Poisoning-related cardiac arrest: Why prognosis should be better?

Resuscitation 2022 06 27;175:77-80. Epub 2022 Apr 27.

Réanimation Médicale et Toxicologique, Hôpital Lariboisière, Assistance Publique - Hôpitaux de Paris, Paris, France; INSERM UMRS-942, MASCOT, Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resuscitation.2022.04.022DOI Listing
June 2022

Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19: protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial.

BMJ Open 2022 04 26;12(4):e059383. Epub 2022 Apr 26.

Université Paris Est, Groupe de Recherche Clinique GR05 CARMAS, Institut Mondor de recherche biomédicale, INSERM, Créteil, France.

Introduction: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely.

Methods And Analysis: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90.

Ethics And Dissemination: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT04808882.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-059383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044512PMC
April 2022

Factors associated with prolonged intensive care stay among self-poisoned patients.

Clin Toxicol (Phila) 2022 Apr 22:1-9. Epub 2022 Apr 22.

Department of Medical and Toxicological Critical Care, Lariboisière hospital, Federation of Toxicology, APHP, Paris, France.

Context: Since recovery or death is generally observed within a few days after intensive care unit (ICU) admission of self-poisoned patients in the developed countries, reasons for the prolonged ICU stay are of interest as they have been poorly investigated. We aimed to identify the characteristics, risk factors, outcome, and predictors of death in self-poisoned patients requiring prolonged ICU management.

Methods: We conducted an eight-year single-center cohort study including all self-poisoned patients who stayed at least seven days in the ICU. Patients admitted with drug adverse events and chronic overdoses were excluded. Using multivariate analyses, we investigated risk factors for prolonged ICU stay in comparison with a group of similar size of self-poisoned patients with <7day-ICU stay and studied risk factors for death.

Results: Among 2,963 poisoned patients admitted in the ICU during the study period, the number who stayed beyond seven days was small (398/2,963, 13.1%), including 239 self-poisoned patients (125 F/114M; age, 51 years [38-65] (median [25th-75th percentiles]); SAPSII, 56 [43-69]). Involved toxicants included psychotropic drugs (59%), cardiotoxicants (31%), opioids (15%) and street drugs (13%). When compared with patients who stayed <7days in the ICU, acute kidney injury (odds ratio (OR), 3.15; 95% confidence interval (1.36-7.39);  = .008), multiorgan failure (OR, 8.06 (3.43-19.9);  < .001), aspiration pneumonia (OR, 8.48 (4.28-17.3);  < .001), and delayed awakening related to the persistent toxicant effects, hypoxic encephalopathy and/or oversedation (OR, 8.64 (2.58-40.7);  = .002) were independently associated with prolonged ICU stay. In-hospital mortality rate was 9%. Cardiac arrest occurring in the prehospital setting and during the first hours of ICU management (OR, 27.31 (8.99-158.76);  < .001) and delayed awakening (OR, 14.94 (6.27-117.44);  < .001) were independently associated with increased risk of death, whereas exposure to psychotropic drugs (OR, 0.08 (0.02-0.36);  = .002) was independently associated with reduced risk of death.

Conclusion: Self-poisoned patients with prolonged ICU stay of ≥7days are characterized by concerning high rates of morbidities and poisoning-attributed complications. Acute kidney injury, multiorgan failure, aspiration pneumonia, and delayed awakening are associated with ICU stay prolongation. Cardiac arrest occurrence and delayed awakening are predictive of death. Further studies should focus on the role of early goal-directed therapy and patient-targeted sedation in reducing ICU length of stay among self-poisoned patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2064870DOI Listing
April 2022

Intravenous Lipid Emulsion for treating Tramadol-Induced Seizures: Surprising but Worth Considering for Future Studies; a Letter to Editor.

Arch Acad Emerg Med 2022 9;10(1):e14. Epub 2022 Feb 9.

National Egyptian Center for Toxicological Researches, Faculty of Medicine, University of Cairo, Cairo, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22037/aaem.v10i1.1541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986489PMC
February 2022

Erythema nodosum triggered by BNT162b2 mRNA COVID-19 vaccine.

Vaccine 2022 04 28;40(19):2650-2651. Epub 2022 Mar 28.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris University, INSERM UMRS-1144 Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2022.03.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958097PMC
April 2022

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group.

EClinicalMedicine 2022 Apr 25;46:101362. Epub 2022 Mar 25.

Service de maladies infectieuses, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial.

Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979.

Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively.

Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn.

Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2022.101362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949640PMC
April 2022

Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review.

Clin Toxicol (Phila) 2022 Mar 21:1-14. Epub 2022 Mar 21.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, University of Montreal, Montreal, QC, Canada.

Context: Ethylene glycol is metabolized to toxic metabolites that cause acute kidney injury, metabolic acidemia, and death. The treatment of patients with ethylene glycol poisoning includes competitively inhibiting alcohol dehydrogenase with ethanol or fomepizole to prevent the formation of toxic metabolites, and extracorporeal treatments such as hemodialysis to remove ethylene glycol and its metabolites. In the absence of significant metabolic acidemia or kidney injury, it is hypothesized that extracorporeal treatments may be obviated without adverse outcomes to the patient if alcohol dehydrogenase inhibitors are used.

Objectives: The objectives of this study are to: (1) identify indicators predicting ADH inhibitor failure in patients with ethylene glycol poisoning treated with either ethanol or fomepizole for whom extracorporeal treatment was not performed (aside from rescue therapy, see below) (), and (2) validate if the anion gap, shown in a previous study to be the best surrogate for the glycolate concentration, is associated with acute kidney injury and mortality ().

Methods: We conducted a systematic review to identify all reported patients with ethylene glycol poisoning treated without extracorporeal treatments but with either fomepizole () or ethanol (). Analyses were performed using both one case per patient and all cases (if multiple events were reported for a single patient). Data were compiled regarding poisoning, biochemistry, and outcomes. Treatment failure was defined as mortality, worsening of acid-base status, extracorporeal treatments used as rescue, or a worsening of kidney or neurological function after alcohol dehydrogenase inhibition was initiated. Also, we performed an analysis of previously described anion gap thresholds to determine if they were associated with outcomes such as acute kidney injury and mortality.

Results: Of 115 publications identified, 96 contained case-level data. A total of 180 cases were identified with ethanol monotherapy, and 231 with fomepizole monotherapy. Therapy failure was noted mostly when marked acidemia and/or acute kidney injury were present prior to therapy, although there were cases of failed ethanol monotherapy with minimal acidemia (suggesting that ethanol dosing and/or monitoring may not have been optimal). Ethylene glycol dose and ethylene glycol concentration were predictive of monotherapy failure for ethanol, but not for fomepizole. In the anion gap study (207 cases), death and progression of acute kidney injury were almost nonexistent when the anion gap was less than 24 mmol/L and mostly observed when the anion gap was greater than 28 mmol/L.

Conclusion: This review suggests that in patients with minimal metabolic acidemia (anion gap <28 mmol/L), fomepizole monotherapy without extracorporeal treatments is safe and effective regardless of the ethylene glycol concentration. Treatment failures were observed with ethanol monotherapy which may relate to transient subtherapeutic ethanol concentrations or very high ethylene glycol concentrations. The results are limited by the retrospective nature of the case reports and series reviewed in this study and require prospective validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2049810DOI Listing
March 2022

Cytological patterns of bronchoalveolar lavage fluid in mechanically ventilated COVID-19 patients on extracorporeal membrane oxygenation.

Clin Respir J 2022 Apr 11;16(4):329-334. Epub 2022 Mar 11.

Réanimation Médicale et Toxicologique, INSERM UMRS1144, AP-HP, Hôpital Lariboisière, Université de Paris, Paris, France.

Introduction: Coronavirus disease-2019 (COVID-19) may lead to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO). Patterns of inflammatory bronchoalveolar cells in COVID-19 patients treated with ECMO are not well described.

Objective: We aimed to describe inflammatory cell subpopulations in blood and bronchoalveolar lavages (BALs) obtained in critically ill COVID-19 patients shortly after ECMO implementation.

Methods: BAL was performed in the middle lobe in 12 consecutive ECMO-treated COVID-19 patients. Trained cytologists analyzed peripheral blood and BAL cells using flow cytometry and routine staining, respectively. Data were interpreted in relation to dexamethasone administration and weaning from ECMO and ventilator.

Results: High neutrophil proportions (66% to 88% of total cells) were observed in the absence of bacterial superinfection and more frequently in dexamethasone-free patients (83% [82-85] vs. 29% [8-68], P = 0.006), suggesting that viral infection could be responsible of predominantly neutrophilic lung inflammation. Successful weaning from ECMO/ventilator could not be predicted by the peripheral white blood and BAL cell pattern.

Conclusion: High neutrophil proportions can be observed in critically ill COVID-19 patients despite the lack of microbiological evidence on BAL of bacterial superinfection. Dexamethasone was associated with lower neutrophil proportions in BAL. Our study was probably underpowered to provide BAL cell pattern helpful to predict weaning from ECMO/ventilator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/crj.13481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060052PMC
April 2022

Cumulative Radiation Exposure in Covid-19 Patients Admitted to the Intensive Care Unit.

Radiat Res 2022 06;197(6):605-612

Department of Skeletal and Visceral Radiology, Lariboisière Hospital, APHP, Paris University, Paris, France.

Medical imaging plays a major role in coronavirus disease-2019 (COVID-19) patient diagnosis and management. However, the radiation dose received from medical procedures by these patients has been poorly investigated. We aimed to estimate the cumulative effective dose (CED) related to medical exposure in COVID-19 patients admitted to the intensive care unit (ICU) in comparison to the usual critically ill patients. We designed a descriptive cohort study including 90 successive ICU COVID-19 patients admitted between March and May 2020 and 90 successive non-COVID-19 patients admitted between March and May 2019. In this study, the CED resulting from all radiological examinations was calculated and clinical characteristics predictive of higher exposure risk identified. The number of radiological examinations was 12.0 (5.0-26.0) [median (interquartile range) in COVID-19 vs. 4.0 (2.0-8.0) in non-COVID-19 patient (P < 0.001)]. The CED during a four-month period was 4.2 mSv (1.9-11.2) in the COVID-19 vs. 1.2 mSv (0.13-6.19) in the non-COVID-19 patients (P < 0.001). In the survivors, the CED in COVID-19 vs. non-COVID-19 patients was ≥100 mSv in 3% vs. 0%, 10-100 mSv in 23% vs. 15%, 1-10 mSv in 56% vs. 30% and <1 mSv in 18% vs. 55%. The CED (P < 0.001) and CED per ICU hospitalization day (P = 0.004) were significantly higher in COVID-19 than non-COVID-19 patients. The CED correlated significantly with the hospitalization duration (r = 0.45, P < 0.001) and the number of conventional radiological examinations (r = 0.8, P < 0.001). To conclude, more radiological examinations were performed in critically ill COVID-19 patients than non-COVID-19 patients resulting in higher CED. In COVID-19 patients, contribution of strategies to limit CED should be investigated in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1667/RADE-21-00203.1DOI Listing
June 2022

The Time Has Come to Understand the Mechanisms by Which Comorbidities Contribute to COVID-19 Severity.

Authors:
Bruno Mégarbane

J Pers Med 2022 Jan 18;12(2). Epub 2022 Jan 18.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, INSERM UMRS-1144, Paris-University, 75010 Paris, France.

A new coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been responsible for a worldwide pandemic for two years, resulting in almost 280 million infections and 5 [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm12020123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878418PMC
January 2022

Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial.

Crit Care 2022 02 21;26(1):48. Epub 2022 Feb 21.

APHP, Hôpital Saint-Louis, Unité de Thérapie Cellulaire, Centre d'Investigation Clinique en Biothérapies CBT501, INSERM, Université de Paris, Paris, France.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS.

Methods: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO/FiO)-ratio change between baseline (day (D) 0) and D7.

Results: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO/FiO changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment.

Conclusions: D0-to-D7 PaO/FiO changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context.

Trial Registration: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-022-03930-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860258PMC
February 2022

Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge.

JAMA 2022 Mar;327(11):1042-1050

Famirea Study Group, Medical Intensive Care Unit, APHP, Saint Louis University Hospital, Paris, France.

Importance: Persistent physical and mental disorders are frequent in survivors of COVID-19-related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce.

Objective: To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)-related symptoms in family members.

Design, Setting, And Participants: Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled.

Exposures: Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes.

Main Outcomes And Measures: The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes.

Results: Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient's death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non-COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]).

Conclusions And Relevance: Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge.

Trial Registration: ClinicalTrials.gov Identifier: NCT04341519.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2022.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924722PMC
March 2022

Exposure to immediate-release tramadol in children 6 years and under - a nationwide French poison control center study.

Clin Toxicol (Phila) 2022 06 18;60(6):750-758. Epub 2022 Feb 18.

Centre antipoison de Paris, Assistance Publique - Hôpitaux de Paris, Hôpital Fernand Widal, Paris, France.

Introduction: Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population.

Methods: Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003-2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity.

Results: We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time ( < .0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3-11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2-PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS ( < .0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92;  < .001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85-100]; specificity, 73% [95% CI, 64-80]; predictive positive value, 39% [95% CI, 35-57]; negative predictive value, 100% [95% CI, 96-100]). Children who ingested <7.4 mg/kg IR-tramadol developed no ( = 68) or minor ( = 22) neurological symptoms.

Conclusions: Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2033257DOI Listing
June 2022

Critical pathways for controlled donation after circulatory death in France.

Anaesth Crit Care Pain Med 2022 04 1;41(2):101029. Epub 2022 Feb 1.

Agence de la biomédecine, Medical and Scientific Department, 1, avenue du stade de France, 93212 Saint-Denis, France.

Introduction: In 2015, France authorised controlled donation after circulatory death (cDCD) according to a nationally approved protocol. The aim of this study is to provide an overview from the perspective of critical care specialists of cDCD. The primary objective is to assess how the organ donation procedure affects the withdrawal of life-sustaining therapies (WLST) process. The secondary objective is to assess the impact of cDCD donors' diagnoses on the whole process.

Material And Methods: This 2015-2019 prospective observational multicentre study evaluated the WLST process in all potential cDCD donors identified nationwide, comparing 2 different sets of subgroups: 1- those whose WLST began after organ donation was ruled out vs. while it was still under consideration; 2- those with a main diagnosis of post-anoxic brain injury (PABI) vs. primary brain injury (PBI) at the time of the WLST decision.

Results: The study analysed 908 potential cDCD donors. Organ donation remained under consideration at WLST initiation for 54.5% of them with longer intervals between their WLST decision and its initiation (2 [1-4] vs. 1 [1-2] days, P < 0.01). Overall, 60% had post-anoxic brain injury. Time from ICU admission to WLST decision was longer for primary brain injury donors (10 [4-21] vs. 6 [4-9] days, P < 0.01). Median time to death (agonal phase) was 15 [15-20] min.

Conclusions: French cDCD donors are mostly related to post-anoxic brain injury. The organ donation process does not accelerate WLST decision but increases the interval between the WLST decision and its initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.accpm.2022.101029DOI Listing
April 2022

L-carnitine does not improve valproic acid poisoning management: a cohort study with toxicokinetics and concentration/effect relationships.

Ann Intensive Care 2022 Jan 29;12(1). Epub 2022 Jan 29.

Department of Medical and Toxicological Critical Care, Federation of Toxicology APHP, Lariboisière Hospital, 2 Rue Ambroise Paré, 75010, Paris, France.

Background: Valproic acid (VPA) poisoning is responsible for life-threatening neurological and metabolic impairments. Despite only low-level evidence of effectiveness, L-carnitine has been used for years to prevent or reverse VPA-related toxicity. We aimed to evaluate the effects of L-carnitine used to treat acute VPA poisoning on the time-course of plasma VPA concentrations and VPA-related toxicity. We designed a single-center cohort study including all VPA-poisoned patients admitted to the intensive care unit. We studied VPA toxicokinetics using a nonlinear mixed-effects model-based population approach and modeled individual plasma VPA/blood lactate concentration relationships. Then, we evaluated L-carnitine-attributed effects by comparing VPA elimination half-lives and time-courses of blood lactate levels and organ dysfunction [assessed by the Sequential Organ Failure Assessment (SOFA) score] between matched L-carnitine-treated and non-treated patients using a multivariate analysis including a propensity score.

Results: Sixty-nine VPA-poisoned patients (40F/29 M; age, 41 years [32-47]) (median [25th-75th percentiles]; SOFA score, 4 [1-6]) were included. The presumed VPA ingested dose was 15 g [10-32]. Plasma VPA concentration on admission was 231 mg/L [147-415]. The most common manifestations were coma (70%), hyperlactatemia (3.9 mmol/L [2.7-4.9]) and hyperammonemia (127 mmol/L [92-159]). VPA toxicokinetics well fitted a one-compartment linear model with a mean elimination half-life of 22.9 h (coefficient of variation, 28.1%). Plasma VPA (C)/blood lactate concentration (E) relationships were well described by an exponential growth equation [[Formula: see text]; with baseline E = 1.3 mmol/L (43.9%) and rate constant of the effect, k = 0.003 L/mg (59.5%)]. Based on a multivariate analysis, peak blood lactate concentration was the only factor independently associated with L-carnitine administration (odds ratio, 1.9, 95% confidence interval, 1.2-2.8; P = 0.004). We found no significant contribution of L-carnitine to enhancing VPA elimination, accelerating blood lactate level normalization and/or preventing organ dysfunction.

Conclusions: VPA poisoning results in severe toxicity. While L-carnitine does not contribute to enhancing VPA clearance, its impact on accelerating blood lactate level normalization and/or preventing organ dysfunction remains uncertain. Investigating VPA toxicokinetics and concentration/effect relationships may help understanding how to improve VPA-poisoned patient management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-022-00984-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800998PMC
January 2022

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

Res Sq 2022 Jan 14. Epub 2022 Jan 14.

Hospices Civils de Lyon.

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21203/rs.3.rs-1225906/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764723PMC
January 2022

Case series of massive direct oral anticoagulant ingestion-Treatment and pharmacokinetics data.

Eur J Clin Invest 2022 Jun 12;52(6):e13746. Epub 2022 Jan 12.

Department of Medical and Toxicological Critical Care, AP-HP Lariboisière Hospital, Paris, France.

Background: Direct oral anticoagulants (DOAC) are widely used due to favourable benefit/risk ratio. However, consequences of massive ingestion have been poorly investigated.

Objectives: We aimed to report outcome and pharmacokinetic parameters in patients who massively ingested DOACs.

Methods: We conducted a 5-year cohort study including consecutive massive DOAC ingestion patients admitted to two critical care departments. Patients were managed in accordance with standards of care. We collected the main history, clinical, laboratory, management and outcome data. The time-course of plasma DOAC concentrations measured using specific assays was modelled.

Results: Twelve patients (3F/9M; age, 55 years [41-63], median [25th-75th percentiles]) were included. Ingestions involved rivaroxaban (n = 7), apixaban (n = 3) and dabigatran (n = 2), with presumed doses of 9.4-fold [5.0-22.0] the full daily dose. Six patients received activated charcoal but no antidote nor blood-derived product. No bleeding was observed. One patient died due to refractory cardiogenic shock related to bisoprolol co-intoxication. Highest observed peak plasma concentrations were 1720 ng/ml (rivaroxaban), 750 ng/ml (apixaban) and 644 ng/ml (dabigatran). Times to reach DOAC concentration below 50 ng/ml were ~20-45 h (rivaroxaban), ~125 h (apixaban) and ~30-50 h (dabigatran). Elimination half-lives were 2.5-25.5 h (rivaroxaban), 22.0 and 36.5 h (apixaban), and 5.8 and 15.5 h (dabigatran), with substantial interindividual variability and prolongation in case of cardiovascular failure related to co-intoxicants. Charcoal administration, even if delayed, may have contributed to limit toxicity, possibly by reducing absorption and/or enteroenteric recycling.

Conclusion: No bleeding was observed in this series of massive DOAC ingestions despite elevated plasma concentrations. No patient required specific haemostatic agents. Charcoal administration should be considered to limit toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.13746DOI Listing
June 2022

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

J Clin Microbiol 2022 Mar 5;60(3):e0216921. Epub 2022 Jan 5.

Institut Pasteurgrid.428999.7, Université de Paris, CNRS, Unité de Mycologie Moléculaire, UMR-2000, Paris, France.

Diagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients ( = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (-qPCR), and galactomannan testing were performed on all respiratory samples ( = 350). Serum galactomannan, β-d-glucan, and plasma -qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test,  = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) ( < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. -qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.02169-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8925884PMC
March 2022

Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study.

Crit Care 2022 01 4;26(1):11. Epub 2022 Jan 4.

Service de Médecine Intensive-Réanimation et Pneumologie, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients.

Objectives: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients.

Methods: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event.

Results: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53-7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88-5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization.

Conclusions: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-021-03874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724752PMC
January 2022

Outcome of Critically Ill COVID-19 Patients According to the Setting of Corticosteroid Initiation-A Retrospective Observational Cohort Study.

J Pers Med 2021 Dec 13;11(12). Epub 2021 Dec 13.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, INSERM UMRS-1144, Paris-University, 75010 Paris, France.

(1) Background: Corticosteroids lower 28-day all-cause mortality in critically ill COVID-19 patients. However, the outcome of COVID-19 patients referred to the intensive care unit (ICU) for respiratory deterioration despite corticosteroids initiated during hospitalization before ICU admission has been poorly investigated. Our objective was to determine survival according to corticosteroid initiation setting. (2) Methods: We conducted a cohort study including all successive critically ill COVID-19 patients treated with corticosteroids and managed in our ICU. We compared survival, whether corticosteroids were initiated before (Cb-group) or after ICU admission (Ca-group), using a propensity score matching. (3) Results: Overall, 228 patients (67 years (56-74); 168M/60F; invasive mechanical ventilation on admission, 17%) were included with 63 patients in the Cb-group and 165 patients in the Ca-group. Survival to hospital discharge was 43% versus 69%, respectively ( = 0.001). In a multivariable analysis, factors associated with death were age (odds ratio, 1.07; 95%-confidence interval, (1.04-1.11); < 0.0001), the sequential organ failure assessment (SOFA) score on ICU admission (1.30 (1.14-1.50); = 0.0001) and corticosteroid initiation before ICU admission (2.64 (1.30-5.43); = 0.007). No significant differences in outcome related to corticosteroid regimen were found. (4) Conclusions: Critically ill COVID-19 patients transferred to the ICU with deterioration despite corticosteroids initiated before admission have a less favorable outcome than patients receiving corticosteroids initiated after ICU admission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11121359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706060PMC
December 2021
-->