Influence of ICU-bed availability on ICU admission decisions

BACKGROUND: The potential influence of bed availability on triage to intensive care unit (ICU) admission is among the factors that may influence the ideal ratio of ICU beds to population: thus, high bed availability (HBA) may result in the admission of patients too well or too sick to benefit, whereas bed scarcity may result in refusal of patients likely to benefit from ICU admission. METHODS: Characteristics and outcomes of patient admitted in four ICUs with usual HBA, defined by admission refusal rate less than 11 % because of bed unavailability, were compared to patients admitted in six ICUs with usual low bed availability (LBA), i.e., an admission refusal rate higher than 10 % during a 90-day period. RESULTS: Over the 90 days, the mean number of days with no bed available was 30 ± 16 in HBA units versus 48 ± 21 in LBA units (p < 0.01). The proportion of admitted patients was significantly higher in the HBA (80.1 %; n = 659/823) than in the LBA units [61.6 %: n = 480/779; (p < 0.0001)]. The proportion of patients deemed too sick to benefit from admission was higher in LBA (9.0 %; n = 70) than in the HBA (6.3 %; n = 52) units (p < 0.05). The HBA group had a significantly greater proportion of patients younger than 40 years of age (22.5 %; n = 148 versus 14 %; n = 67 in LBA group; p < 0.001) and higher proportions of patients with either high or low simplified acute physiologic score II values. CONCLUSIONS: Bed availability affected triage decisions. Units with HBA trend to admit patients too sick or too well to benefit

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

A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock

International audienceINTRODUCTION: We aimed to establish whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during evolving bacterial community-acquired infection in adults is associated with severe sepsis or septic shock. METHODS: We conducted a multicentre case-control study in eight intensive care units. Cases were all adult patients admitted for severe sepsis or septic shock due to a bacterial community-acquired infection. Control individuals were patients hospitalized with a mild community-acquired infection. Each case was matched to one control for age, presence of diabetes and site of infection. RESULTS: The main outcome measures were the proportions of cases and controls exposed to NSAIDs or aspirin during the period of observation. In all, 152 matched pairs were analyzed. The use of NSAIDs or aspirin during the observation period did not differ between cases and controls (27% versus 28; odds ratio = 0.93, 95% confidence interval [CI] = 0.52 to 1.64). If aspirin was not considered or if a distinction was made between acute and chronic drug treatment, there remained no difference between groups. However, the median time to prescription of effective antibiotic therapy was longer for NSAID users (6 days, 95% CI = 3 to 7 days) than for nonusers (3 days, 95% CI = 2 to 3 days; P = 0.02). CONCLUSIONS: In this study, the use of NSAIDs or aspirin during evolving bacterial infection was frequent and occurred in one-quarter of the patients with such infection. Although the use of NSAIDs by patients with severe sepsis or septic shock did not differ from their use by those with mild infection at the same infected site, we observed a longer median time to prescription of effective antibiotic therapy in NSAID users

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)

Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co-Condensation of Wnt Signalodroplets

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells

Morphometric MRI findings in patients with suspected autoimmune psychosis spectrum syndromes and association with EEG slowing, CSF changes, and psychometric/neuropsychological findings

IntroductionPatients with autoimmune encephalitis – who often have accompanying psychiatric symptoms – frequently have electroencephalography (EEG) changes and normal conventional magnetic resonance imaging (MRI) findings. The aim of this paper was to analyze automated EEG and morphometric MRI findings in psychiatric patients with suspected autoimmune psychosis (AP) spectrum syndromes versus controls and the correlation of MRI measures with EEG, cerebrospinal fluid (CSF), and psychometric/neuropsychological findings.Participants and methodsIn total, forty patients were included. Suspected AP spectrum syndromes were defined broadly based on the autoimmune psychiatric syndrome concept. All patients showed signs of an autoimmune process. That is, upon further diagnostic testing, they tested at least positive for well-characterized neuronal antibodies, novel central nervous system antibodies, or well-characterized systemic antibodies with brain involvement. For EEG, thirty-seven matched patient-control pairs, and for structural MRI, thirty-five patients and matched controls, were available. EEG analysis for intermittent rhythmic delta/theta activity (IRDA/IRTA) was performed using independent component analysis. MRI scans were analyzed using FreeSurfer (7.2) for the subcortical measures and CAT12 for cortical thickness and global volumes.ResultsPatients did not show significantly increased IRDA/IRTA rates. Regarding brain volumes, there was a significant decrease in grey matter volume/total intracranial volume (TIV) (p=0.027) and a significant increase in CSF/TIV (p=0.027), which remained significant after correction for multiple comparisons. Further differences with lower white matter volume/TIV, reduced cortical thickness in the left parahippocampal and transversotemporal gyri and an increase in the volume of the left lateral ventricle of patients did not remain significant after correcting for multiple testing. White blood cell counts in the CSF of the whole patient group correlated positively with increased hippocampal volumes. Brain volumes did not correlate with psychometric scales, but with several neuropsychological scores.DiscussionAutoantibody-associated suspected AP spectrum syndromes seem to be associated with slight global grey matter volume reductions and secondary increased CSF volumes. Associations between hippocampal volume increases and inflammatory CSF markers could, in contrast, reflect edematous swelling within the limbic system. Further multimodal imaging studies of more homogeneous AP groups might be promising to detect morphometric correlates

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

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/)

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