Respiratory pulse pressure variation fails to predict fluid responsiveness in acute respiratory distress syndrome

International audienceIntroduction: Fluid responsiveness prediction is of utmost interest during acute respiratory distress syndrome (ARDS), but the performance of respiratory pulse pressure variation (Δ RESP PP) has scarcely been reported. In patients with ARDS, the pathophysiology of Δ RESP PP may differ from that of healthy lungs because of low tidal volume (Vt), high respiratory rate, decreased lung and sometimes chest wall compliance, which increase alveolar and/or pleural pressure. We aimed to assess Δ RESP PP in a large ARDS population. Methods: Our study population of nonarrhythmic ARDS patients without inspiratory effort were considered responders if their cardiac output increased by >10% after 500-ml volume expansion. Results: Among the 65 included patients (26 responders), the area under the receiver-operating curve (AUC) for Δ RESP PP was 0.75 (95% confidence interval (CI 95): 0.62 to 0.85), and a best cutoff of 5% yielded positive and negative likelihood ratios of 4.8 (CI 95 : 3.6 to 6.2) and 0.32 (CI 95 : 0.1 to 0.8), respectively. Adjusting Δ RESP PP for Vt, airway driving pressure or respiratory variations in pulmonary artery occlusion pressure (ΔPAOP), a surrogate for pleural pressure variations, in 33 Swan-Ganz catheter carriers did not markedly improve its predictive performance. In patients with ΔPAOP above its median value (4 mmHg), AUC for Δ RESP PP was 1 (CI 95 : 0.73 to 1) as compared with 0.79 (CI 95 : 0.52 to 0.94) otherwise (P = 0.07). A 300-ml volume expansion induced a ≥2 mmHg increase of central venous pressure, suggesting a change in cardiac preload, in 40 patients, but none of the 28 of 40 nonresponders responded to an additional 200-ml volume expansion. Conclusions: During protective mechanical ventilation for early ARDS, partly because of insufficient changes in pleural pressure, Δ RESP PP performance was poor. Careful fluid challenges may be a safe alternative

Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study

International audienceIntroduction: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI)

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

AANOXIE CEREBRALE APRES ARRET CARDIO-RESPIRATOIRE (QUESTIONNAIRE ETHIQUE AUPRES DE MEDECINS REANIMATEURS)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Influence des modalités d'oxygénothérapie et de nébulisation sur la fraction inspirée d'oxygène (Etude sur pièce anatomique)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Amikacine nébulisée à forte dose (étude pharmacocinétique de recherche de dose chez le volontaire sain sous ventilation mécanique non invasive)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de facteurs physiques et physiologiques influant sur la cinétique des aérosols médicamenteux

Nous avons étudié les paramètres permettant d'optimiser la nébulisation dans deux modèles : la mucoviscidose et la ventilation mécanique. Nous avons tout d'abord montré que le marquage isotopique d'un aérosol d'amikacine ne modifiait pas son comportement physique et permettait donc d'étudier son devenir dans l'organisme. In vivo, nous avons montré que la masse déposée dans le poumon était corrélée à la fraction inhalée et tendait à être inversement corrélée à la concentration en P. aeruginosa dans les sécrétions bronchiques, puis que la masse éliminée dans les urines était effectivement corrélée à celle déposée dans le poumon, ce qui suggère la possibilité d'évaluer de façon non invasive et non irradiante la masse d'aminoglycoside déposée dans le poumon par nébulisation. En modélisant in vitro des conditions de ventilation mécanique, nous avons montré que la rentabilité de la nébulisation de fénotérol était moins bonne que celle de l'administration par aérosol-doseur, suggérant un effet plateau dans la courbe dose-réponse au fénotérol en ventilation mécanique, l'effet global mesuré par ailleurs sur les résistances totales du système respiratoire étant d'amplitude comparable. Nous avons ensuite comparé, à FiO2 et volume courant identiques, l'influence d'un mélange air-oxygène et hélium-oxygène sur les caractéristiques d'un aérosol de salbutamol généré par deux nébuliseurs pneumatiques de type différent. Nous avons montré que la masse inhalable était influencée significativement par le type de nébuliseur, par la durée d'ouverture du système de nébulisation et, de façon plus marginale, par le type de gaz, l'hélium augmentant effectivement la masse inhalable avec le moins performant des nébuliseurs et pour un temps d'ouverture plus long. Le choix du nébuliseur s'est donc avéré dans ce modèle plus important que le gaz utilisé pour la ventilation.TOURS-BU Médecine (372612103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF