Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study.

BACKGROUND: Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. METHODS: This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. RESULTS: In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16-24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. CONCLUSIONS: In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.

Bordetella hinzii Pneumonia in Patient with SARS-CoV-2 Infection.

Patients infected with severe acute respiratory syndrome coronavirus 2 might have bacterial and fungal superinfections develop. We describe a clinical case of coronavirus disease with pulmonary aspergillosis associated with Bordetella hinzii pneumonia in an immunocompetent patient in France. B. hinzii infections are rare in humans and develop secondary to immunosuppression or debilitating diseases.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

BACKGROUND: The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS: In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS: At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2). CONCLUSIONS: Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .).

Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Dynamic properties of glucose complexity during the course of critical illness: a pilot study.

Methods to control the blood glucose (BG) levels of patients in intensive care units (ICU) improve the outcomes. The development of continuous BG levels monitoring devices has also permitted to optimize these processes. Recently it was shown that a complexity loss of the BG signal is linked to poor clinical outcomes. Thus, it becomes essential to decipher this relation to design efficient BG level control methods. In previous studies the BG signal complexity was calculated as a single index for the whole ICU stay. Although, these approaches did not grasp the potential variability of the BG signal complexity. Therefore, we setup this pilot study using a continuous monitoring of central venous BG levels in ten critically ill patients (EIRUS platform, Maquet Critical CARE AB, Solna, Sweden). Data were processed and the complexity was assessed by the detrended fluctuation analysis and multiscale entropy (MSE) methods. Finally, recordings were split into 24 h overlapping intervals and a MSE analysis was applied to each of them. The MSE analysis on time intervals revealed an entropy variation and allowed periodic BG signal complexity assessments. To highlight differences of MSE between each time interval we calculated the MSE complexity index defined as the area under the curve. This new approach could pave the way to future studies exploring new strategies aimed at restoring blood glucose complexity during the ICU stay.

Assessment of patients' self-perceived intensive care unit discomforts: Validation of the 18-item version of the IPREA.

BACKGROUND AND AIMS: We reported the validation of the 18-item version of the 'Inconforts des Patients de REAnimation (IPREA)' questionnaire that includes 2 new items exploring feeling depressed and shortness of breath during an intensive care unit (ICU) stay. METHODS: The validation process was integrated in a multicenter, cluster-randomized, controlled, two-parallel group study built to assess the effectiveness of a tailored multicomponent program for reducing self-perceived discomfort in the ICU. All patients aged 18 years or older who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Data collection included demographics (sex, age), type of admission (medical and surgical), health status scores at admission (Knaus score and McCabe index, Simplified Acute Physiology Score (SAPS) II), specific ICU therapeutics such as mechanical ventilation (MV), noninvasive ventilation (NIV), use of vasopressors, or renal replacement therapy (RRT), and ICU stay duration. RESULTS: A total of 994 patients were included. The initial structure of IPREA was confirmed using confirmatory factor analysis showing satisfactory fit (RMSEA at 0.042, CFI at 0.912). No multidimensional structure was identified, allowing the calculation of an overall discomfort score. The three highest discomforts were sleep deprivation, thirst, and perfusion lines and other devices, and the 3 lowest discomforts were limited visiting hours, hunger, and isolation. The overall discomfort score of the 18-item version of IPREA did not differ between men and women. Higher age was significantly correlated with a lower overall discomfort score. While MV was not linked to self-reported discomfort, patients treated by NIV reported higher overall discomfort scores than patients not treated by NIV. CONCLUSION: The 18-item version of IPREA is easy to use and possesses satisfactory psychometric properties. The availability of a reliable and valid French questionnaire asking about patients' self-perceived ICU discomforts enables feedback from the health care team to be incorporated in a continuous quality health care improvement strategy. TRIAL REGISTRATION: clinicaltrial.gov NCT02442934 (registration date: May 18, 2015, retrospectively registered).

Intravascular Complications of Central Venous Catheterization by Insertion Site.

BACKGROUND: Three anatomical sites are commonly used to insert central venous catheters, but insertion at each site has the potential for major complications. METHODS: In this multicenter trial, we randomly assigned nontunneled central venous catheterization in patients in the adult intensive care unit (ICU) to the subclavian, jugular, or femoral vein (in a 1:1:1 ratio if all three insertion sites were suitable [three-choice scheme] and in a 1:1 ratio if two sites were suitable [two-choice scheme]). The primary outcome measure was a composite of catheter-related bloodstream infection and symptomatic deep-vein thrombosis. RESULTS: A total of 3471 catheters were inserted in 3027 patients. In the three-choice comparison, there were 8, 20, and 22 primary outcome events in the subclavian, jugular, and femoral groups, respectively (1.5, 3.6, and 4.6 per 1000 catheter-days; P=0.02). In pairwise comparisons, the risk of the primary outcome was significantly higher in the femoral group than in the subclavian group (hazard ratio, 3.5; 95% confidence interval [CI], 1.5 to 7.8; P=0.003) and in the jugular group than in the subclavian group (hazard ratio, 2.1; 95% CI, 1.0 to 4.3; P=0.04), whereas the risk in the femoral group was similar to that in the jugular group (hazard ratio, 1.3; 95% CI, 0.8 to 2.1; P=0.30). In the three-choice comparison, pneumothorax requiring chest-tube insertion occurred in association with 13 (1.5%) of the subclavian-vein insertions and 4 (0.5%) of the jugular-vein insertions. CONCLUSIONS: In this trial, subclavian-vein catheterization was associated with a lower risk of bloodstream infection and symptomatic thrombosis and a higher risk of pneumothorax than jugular-vein or femoral-vein catheterization. (Funded by the Hospital Program for Clinical Research, French Ministry of Health; ClinicalTrials.gov number, NCT01479153.).

Improving glycemic control in critically ill patients: personalized care to mimic the endocrine pancreas.

There is considerable physiological and clinical evidence of harm and increased risk of death associated with dysglycemia in critical care. However, glycemic control (GC) currently leads to increased hypoglycemia, independently associated with a greater risk of death. Indeed, recent evidence suggests GC is difficult to safely and effectively achieve for all patients. In this review, leading experts in the field discuss this evidence and relevant data in diabetology, including the artificial pancreas, and suggest how safe, effective GC can be achieved in critically ill patients in ways seeking to mimic normal islet cell function. The review is structured around the specific clinical hurdles of: understanding the patient's metabolic state; designing GC to fit clinical practice, safety, efficacy, and workload; and the need for standardized metrics. These aspects are addressed by reviewing relevant recent advances in science and technology. Finally, we provide a set of concise recommendations to advance the safety, quality, consistency, and clinical uptake of GC in critical care. This review thus presents a roadmap toward better, more personalized metabolic care and improved patient outcomes.

Continuous glucose monitoring in the ICU: clinical considerations and consensus.

Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.

Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients.

INTRODUCTION: In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity. METHODS: We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement). RESULTS: A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality. CONCLUSION: In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.

Effects of tight computerized glucose control on neurological outcome in severely brain injured patients: a multicenter sub-group analysis of the randomized-controlled open-label CGAO-REA study.

INTRODUCTION: Hyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery. METHODS: A sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥ 48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L(-1)) and an IIT group (blood glucose target between 4.4 and 6 mmol.L(-1)). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale. RESULTS: A total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (± 4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L(-1) versus 6.5 (5.6 to 7.2) mmol.L(-1), P <0.001) in the first 5 days after ICU admission. The IIT group experienced more episodes of hypoglycemia (P < 0.0001). In the IIT group 24 (26.6%) patients had a favorable neurological outcome (good recovery or moderate disability) compared to 31 (31.6%) in the control group (P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome. CONCLUSIONS: In this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.

A randomized clinical trial to evaluate the effect of post-intensive care multidisciplinary consultations on mortality and the quality of life at 1 year.

PURPOSE: Critical illness is associated with long-term increased mortality and impaired quality of life (QoL). We assessed whether multidisciplinary consultations would improve outcome at 12 months (M12) after intensive care unit (ICU) discharge. METHODS: We performed an open, multicenter, parallel-group, randomized clinical trial. Eligible are patients discharged alive from ICU in 11 French hospitals between 2012 and 2018. The intervention group had a multidisciplinary face-to-face consultation involving an intensivist, a psychologist, and a social worker at ICU discharge and then at M3 and M6 (optional). The control group had standard post-ICU follow-up. A consultation was scheduled at M12 for all patients. The QoL was assessed using the EuroQol-5 Dimensions-5 Level (Euro-QoL-5D-5L) which includes five dimensions (mobility, self-care, usual activities, pain, and anxiety/depression), each ranging from 1 to 5 (1: no, 2: slight, 3: moderate, 4: severe, and 5: extreme problems). The primary endpoint was poor clinical outcome defined as death or severe-to-extreme impairment of at least one EuroQoL-5D-5L dimension at M12. The information was collected by a blinded investigator by phone. Secondary outcomes were functional, psychological, and cognitive status at M12 consultation. RESULTS: 540 patients were included (standard, n = 272; multidisciplinary, n = 268). The risk for a poor outcome was significantly greater in the multidisciplinary group than in the standard group [adjusted odds ratio 1.49 (95% confidence interval, (1.04-2.13)]. Seventy-two (13.3%) patients died at M12 (standard, n = 32; multidisciplinary, n = 40). The functional, psychological, and cognitive scores at M12 did not statistically differ between groups. CONCLUSIONS: A hospital-based, face-to-face, intensivist-led multidisciplinary consultation at ICU discharge then at 3 and 6 months was associated with poor outcome 1 year after ICU.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

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

[This corrects the article DOI: 10.2196/30496.].

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

OBJECTIVE: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. DATA SOURCES: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. METHODS: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. PRIMARY ENDPOINT: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. DISCUSSION: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?'Protocol version 0.4 - 06/26/2023PROSPERO registration:CRD42021278869.

Meta-analysis of subclavian insertion and nontunneled central venous catheter-associated infection risk reduction in critically ill adults.

OBJECTIVE: Catheter-associated infections are common, costly, and potentially lethal. The impact of catheter insertion site on infection risk remains controversial. We aimed to establish whether nontunneled central venous catheters inserted in the subclavian vein are associated with lower risk of catheter-associated infection compared to femoral or internal jugular vein insertion. DATA SOURCES: We searched MEDLINE (2000-2011), EMBASE (2000-2011), and Cochrane Library plus meta-analyses, gray literature, reference lists, and articles recommended by experts. STUDY SELECTION AND EXTRACTION: We selected peer-reviewed, randomized, or prospective cohort studies with systematic catheter culture using semiquantitative or quantitative catheter culture techniques and data available for catheter-associated infection by insertion site. Two reviewers independently performed study selection, assessed study quality, and extraction. Discrepancies were resolved by discussion and consensus. Outcomes were mean catheter duration and catheter-associated infection expressed as incidence density per 1000 catheter days. DATA SYNTHESIS: Ten studies (3250 subclavian, 3053 internal jugular, and 1554 femoral vein) met the inclusion criteria, one of which was randomized (136 subclavian vein and 134 femoral vein). Subclavian vein catheters were left in place significantly longer than alternative catheters (mean difference: 2 days, 95% confidence interval [0.9-3.1], I=92%, p<.001). The subclavian vein site was associated with fewer catheter-associated infections (1.3 compared to 2.7 per 1000 catheter days for alternative sites, incidence density ratio 0.50; 95% confidence interval [0.33- 0.74], I=0%, p<.001). The same was true when comparisons were stratified by alternative sites (subclavian vein vs. internal jugular vein, incidence density ratio 0.46; 95% confidence interval [0.30-0.70], I=0%; subclavian vein vs. femoral vein, incidence density ratio 0.27; 95% confidence interval [0.15-0.48], I=31%). CONCLUSION: Shortcomings in study design, including channeling, confounding bias, and study heterogeneity, may limit the interpretation of our preliminary study results. Our analysis suggests that the subclavian site may be associated with a lower risk of catheter-associated infection. However, a large, randomized, controlled trial comparing each catheter site complication is warranted before the subclavian site can be unequivocally recommended as a first choice for central venous catheter insertion.

Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because almitrine improves V/Q, it might reduce the risk for mechanical ventilation (MV) in such patients. Our primary objective was to determine the effect of almitrine on the need for MV at day 7. Methods: In a randomised double-blind placebo-controlled trial involving 15 ICUs, patients hospitalized for COVID-19 pneumonia and experiencing acute hypoxemic respiratory failure were randomly assigned to receive 5 days of intravenous low-dose (2 µg.kg-1.min-1) almitrine or placebo. The primary outcome was endotracheal intubation for MV or death within 7 days after randomisation. Secondary outcomes included in-hospital mortality, 28-day mortality, number of ventilator-free days, number of days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects. This trial was registered with ClinicalTrials.gov, NCT04357457. Findings: Between September 3, 2020 and September 25, 2021 181 patients were enrolled and randomly assigned to almitrine (n=89) or placebo (n=92). 179 patients (excluding two who withdrew from the study) were included in the intention-to-treat analysis (mean age: 60·1 years; 34% women) and analyzed. On day 7, the primary endpoint occurred in 32 patients assigned to almitrine (36%) and in 37 patients assigned to placebo (41%), for a difference of -4·3% (95% confidence interval: -18·7% to 10·2%). Secondary outcomes (28-day mortality, in-hospital mortality, ventilator-free days at day 28, days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects) did not differ between the two groups. Interpretation: In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7. Funding: Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge.

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

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.

Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

PURPOSE: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP). METHODS: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days. RESULTS: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. CONCLUSIONS: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.