"It's all about setting the stage." The nurse facilitator trial: perceived outcomes and implementation issues. A qualitative study among ICU clinicians and nurse facilitators.

PURPOSE: For the first time in France, a randomised controlled trial was conducted to evaluate the impact of a nurse facilitator on family psychological symptoms. We sought to explore the implementation of the intervention, how it was experienced by clinicians, as well as the barriers and facilitators to implementing the change. METHODS: We conducted qualitative semi-structured interviews with intensive care unit (ICU) clinicians and facilitators involved in the trial. Interview questions focused on participants' perceptions of the intervention and its outcomes, including the effect of the intervention on patients, families and the health care team, and barriers and facilitators to its implementation. Interviews were conducted by two social science researchers, audio recorded, transcribed, and analyzed using thematic content analysis. RESULTS: Twenty-three clinicians were interviewed from the five participating ICUs. Three themes emerged, capturing clinicians' perspectives on implementing the intervention: (1) improved communication and enhanced care for families and the ICU team, albeit with some associated risks; (2) active listening and support, both for families and ICU clinicians but with certain limitations; (3) barriers to implementation including lack of organizational readiness, exclusion of under-represented groups, and facilitator challenges including role ambiguity and the need for role support. CONCLUSION: Participants believed the facilitator intervention potentially improved families' experience. However, they also highlighted emotional difficulties and tensions with some members of the participating teams, due to competing territories and ambiguous role definitions. Facilitators' failure to affect decision-making suggests their role in enhancing goal-concordant care was inadequate within the setting.

Prospective multi-center evaluation of the incidence of unplanned extubation and its outcomes in French intensive care units. The Safe-ICU study.

BACKGROUND: We aimed to determine the epidemiology and outcomes of unplanned extubation (UE), both accidental and self-extubation, in ICU. METHODS: A multicentre prospective cohort study was conducted in 47 French ICUs. The number of mechanical ventilation (MV) days, and planned and unplanned extubation were recorded in each center over a minimum period of three consecutive months to evaluate UE incidence. Patient characteristics, UE environmental factors, and outcomes were compared based on the UE mechanism (accidental or self-extubation). Self-extubation outcomes were compared with planned extubation using a propensity-matched population. Finally, risk factors for extubation failure (re-intubation before day 7) were determined following self-extubation. RESULTS: During the 12-month inclusion period, we found a pooled UE incidence of 1.0 per 100 MV days. UE accounted for 9% of all endotracheal removals. Of the 605 UE, 88% were self-extubation and 12% were accidental-extubations. The latter had a worse prognosis than self-extubation (34%vs. 8% ICU-mortality, p < 0.001). Self-extubation did not increase mortality compared with planned extubation (8 vs. 11%, p = 0.075). Regardless of the type of extubation, planned or unplanned, extubation failure was independently associated with a poor outcome. Cancer, higher respiratory rate, lower PaO2/FiO2 at the time of extubation, weaning process not-ongoing, and immediate post-extubation respiratory failure were independent predictors of failed self-extubation. CONCLUSION: Unplanned extubation, mostly represented by self-extubation, is common in ICU and accounts for 9% of all endotracheal extubations. While accidental extubations are a serious and infrequent adverse event, self-extubation does not increase mortality compared to planned extubation.

Predictive Models of Long-Term Outcome in Patients with Moderate to Severe Traumatic Brain Injury are Biased Toward Mortality Prediction.

BACKGROUND: The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability. METHODS: We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. RESULTS: Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model. CONCLUSIONS: We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.

Continuous non-invasive vs. invasive arterial blood pressure monitoring during neuroradiological procedure: a comparative, prospective, monocentric, observational study.

BACKGROUND: In the perioperative setting, the most accurate way to continuously measure arterial blood pressure (ABP) is using an arterial catheter. Surrogate methods such as finger cuff have been developed to allow non-invasive measurements and are increasingly used, but need further evaluation. The aim of this study is to evaluate the accuracy and clinical concordance between two devices for the measurement of ABP during neuroradiological procedure. METHODS: This is a prospective, monocentric, observational study. All consecutive patients undergoing a neuroradiological procedure were eligible. Patients who needed arterial catheter for blood pressure measurement were included. During neuroradiological procedure, ABP (systolic, mean and diatolic blood pressure) was measured with two different technologies: radial artery catheter and Nexfin. Bland-Altman and error grid analyses were performed to evaluate the accuracy and clinical concordance between devices. RESULTS: From March 2022 to November 2022, we included 50 patients, mostly ASA 3 (60%) and required a cerebral embolization (94%) under general anaesthesia (96%). Error grid analysis showed that 99% of non-invasive ABP measures obtained with the Nexfin were located in the risk zone A or B. However, 65.7% of hypertension events and 41% of hypotensive events were respectively not detected by Nexfin. Compared to the artery catheter, a significant relationship was found for SAP (r2 = 0.78) and MAP (r2 = 0.80) with the Nexfin (p < 0.001). Bias and limits of agreement (LOA) were respectively 9.6 mmHg (- 15.6 to 34.8 mmHg) and - 0.8 mmHg (- 17.2 to 15.6 mmHg), for SAP and MAP. CONCLUSIONS: Nexfin is not strictly interchangeable with artery catheter for ABP measuring. Further studies are needed to define its clinical use during neuroradiological procedure. TRIAL REGISTRATION: Clinicaltrials.gov, registration number: NCT05283824.

A randomised controlled trial of a nurse facilitator to promote communication for family members of critically ill patients.

PURPOSE: Suboptimal communication with clinicians, fragmented care and failure to align with patients' preferences are determinants of post intensive care unit (ICU) burden in family members. Our aim was to evaluate the impact of a nurse facilitator on family psychological burden. METHODS: We carried out a randomised controlled trial in five ICUs in France comparing standard communication by ICU clinicians to additional communication and support by nurse facilitators. We included patients > 18 years, with expected ICU length of stay > 2 days, chronic life-limiting illness, and their family members. Facilitators were trained to help families to secure care in line with patient's goals, beginning in ICU and continuing for 3 months. Assessments were made at baseline and 1, 3 and 6 months post-randomisation. Primary outcome was the evolution of family symptoms of depression over 6 months using a linear mixed effects model on the depression subscale of the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included HADS-Anxiety, Impact of Event Scale-6, goal-concordant care and experience of serious illness (QUAL-E). RESULTS: 385 patients and family members were enrolled. Follow-up at 1-, 3- and 6-month was completed by 284 (74%), 264 (68.6%) and 260 (67.5%) family members respectively. The intervention was associated with significantly more formal meetings between the ICU team and the family (1 [1-3] vs 2 [1-4]; p < 0.001). There was no significant difference between the intervention and control groups in evolution of symptoms of depression over 6 months (p = 0.91), nor in symptoms of depression at 6 months [0.53 95% CI (- 0.48; 1.55)]. There were no significant differences in secondary outcomes. CONCLUSION: This study does not support the use of facilitators for family members of ICU patients.

Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Moderate Exercise Modulates Inflammatory Responses and Improves Survival in a Murine Model of Acute Pneumonia.

OBJECTIVES: An association between physical inactivity and worse outcome during infectious disease has been reported. The effect of moderate exercise preconditioning on the immune response during an acute pneumonia in a murine model was evaluated. SETTING: Laboratory experiments. SUBJECTS: C57BL6/j male mice. INTERVENTIONS: Six-week-old C57BL/6J mice were divided in two groups: an exercise group and a control group. In the exercise group, a moderate, progressive, and standardized physical exercise was applied for 8 weeks. It consisted in a daily treadmill training lasting 60 minutes and with an intensity of 65% of the maximal theoretical oxygen uptake. Usual housing recommendation were applied in the control group during the same period. After 8 weeks, pneumonia was induced in both groups by intratracheal instillation of a fixed concentration of a Klebsiella pneumoniae (5 × 103 colony-forming unit) solution. MEASUREMENTS AND MAIN RESULTS: Mice preconditioned by physical exercise had a less sever onset of pneumonia as shown by a significant decrease of the Mouse Clinical Assessment Severity Score and had a significantly lower mortality compared with the control group (27% vs. 83%; p = 0.019). In the exercise group, we observed a significantly earlier but transient recruitment of inflammatory immune cells with a significant increase of neutrophils, CD4+ cells and interstitial macrophages counts compared with control group. Lung tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 were significantly decreased at 48 hours after pneumonia induction in the exercise group compared with the control group. CONCLUSIONS: In our model, preconditioning by moderate physical exercise improves outcome by reducing the severity of acute pneumonia with an increased but transient activation of the innate immune response.

Secondary Neurologic Deterioration After Moderate Traumatic Brain Injury: Development of a Multivariable Prediction Model and Proposition of a Simple Triage Score.

BACKGROUND: Identifying patients at risk of secondary neurologic deterioration (SND) after moderate traumatic brain injury (moTBI) is a challenge, as such patients will need specific care. No simple scoring system has been evaluated to date. This study aimed to determine clinical and radiological factors associated with SND after moTBI and to propose a triage score. METHODS: All adults admitted in our academic trauma center between January 2016 and January 2019 for moTBI (Glasgow Coma Scale [GCS] score, 9-13) were eligible. SND during the first week was defined either by a decrease in GCS score of >2 points from the admission GCS in the absence of pharmacologic sedation or by a deterioration in neurologic status associated with an intervention, such as mechanical ventilation, sedation, osmotherapy, transfer to the intensive care unit (ICU), or neurosurgical intervention (for intracranial mass lesions or depressed skull fracture). Clinical, biological, and radiological independent predictors of SND were identified by logistic regression (LR). An internal validation was performed using a bootstrap technique. A weighted score was defined based on beta (ß) coefficients of the LR. RESULTS: A total of 142 patients were included. Forty-six patients (32%) showed SND, and 14-day mortality rate was 18.4%. Independent variables associated with SND were age above 60 years (odds ratio [OR], 3.45 [95% confidence interval {CI}, 1.45-8.48]; P = .005), brain frontal contusion (OR, 3.22 [95% CI, 1.31-8.49]; P = .01), prehospital or admission arterial hypotension (OR, 4.86 [95% CI, 2.03-12.60]; P = .006), and a Marshall computed tomography (CT) score of 6 (OR, 3.25 [95% CI, 1.31-8.20]; P = .01). The SND score was defined with a range from 0 to 10. The score included the following variables: age >60 years (3 points), prehospital or admission arterial hypotension (3 points), frontal contusion (2 points), and Marshall CT score of 6 (2 points). The score was able to detect patients at risk of SND, with an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI, 0.65-0.82). A score of 3 had a sensitivity of 85%, a specificity of 50%, a VPN of 87%, and a VPP of 44 % to predict SND. CONCLUSIONS: In this study, we demonstrate that moTBI patients have a significant risk of SND. A simple weighted score at hospital admission could be able to detect patients at risk of SND. The use of the score may enable optimization of care resources for these patients.

Prophylactic platelet transfusion response in critically ill patients: a prospective multicentre observational study.

BACKGROUND: Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes. METHODS: This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18-24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy. RESULTS: Poor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 [95% confidence interval (CI) 0.7-0.89]) and body mass index (BMI) (OR: 0.93 [0.89-0.98]) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 [1.09-3.43]), sepsis as primary ICU admission diagnosis (OR: 2.81 [1.57-5.03]), SOFA score (OR 1.10 [1.03; 1.17]) and maximum storage duration of platelet (OR: 1.24 [1.02-1.52]) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy. CONCLUSIONS: In this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention. Trial registration in October 2017: ClinicalTrials.gov: NCT03325140.

Guidelines on perioperative optimization protocol for the adult patient 2023.

OBJECTIVE: The French Society of Anesthesiology and Intensive Care Medicine [Société Française d'Anesthésie et de Réanimation (SFAR)] aimed at providing guidelines for the implementation of perioperative optimization programs. DESIGN: A consensus committee of 29 experts from the SFAR was convened. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Four fields were defined: 1) Generalities on perioperative optimization programs; 2) Preoperative measures; 3) Intraoperative measures and; 4) Postoperative measures. For each field, the objective of the recommendations was to answer a number of questions formulated according to the PICO model (population, intervention, comparison, and outcomes). Based on these questions, an extensive bibliographic search was carried out using predefined keywords according to PRISMA guidelines and analyzed using the GRADE® methodology. The recommendations were formulated according to the GRADE® methodology and then voted on by all the experts according to the GRADE grid method. As the GRADE® methodology could have been fully applied for the vast majority of questions, the recommendations were formulated using a "formalized expert recommendations" format. RESULTS: The experts' work on synthesis and application of the GRADE® method resulted in 30 recommendations. Among the formalized recommendations, 19 were found to have a high level of evidence (GRADE 1±) and ten a low level of evidence (GRADE 2±). For one recommendation, the GRADE methodology could not be fully applied, resulting in an expert opinion. Two questions did not find any response in the literature. After two rounds of rating and several amendments, strong agreement was reached for all the recommendations. CONCLUSIONS: Strong agreement among the experts was obtained to provide 30 recommendations for the elaboration and/or implementation of perioperative optimization programs in the highest number of surgical fields.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Anxiety and depression symptoms in relatives of moderate-to-severe traumatic brain injury survivors - A multicentre cohort.

INTRODUCTION: The prevalence and risk factors of anxiety and depression symptoms in relatives of moderate to severe traumatic brain injury (TBI) survivors have not been thoroughly investigated. METHODS: Ancillary study of a multicentric prospective randomized-controlled trial in nine university hospitals in 370 moderate-to-severe TBI patients. TBI survivor-relative dyads were included in the 6th month of follow-up. Relatives responded to the Hospital Anxiety and Depression Scale (HADS). The primary endpoints were the prevalence of severe symptoms of anxiety (HADS-Anxiety ≥ 11) and depression (HADS-Depression ≥ 11) in relatives. We explored the risk factors of severe anxiety and depression symptoms. RESULTS: Relatives were predominantly women (80.7%), spouse-husband (47.7%), or parents (39%). Out of the 171 dyads included, 83 (50.6%) and 59 (34.9%) relatives displayed severe symptoms of anxiety and depression, respectively. Severe anxiety symptoms in relatives were independently associated with the patient's discharge at home (OR 2.57, 95%CI [1.04-6.37]) and the patient's higher SF-36 Mental Health domain scores (OR 1.03 95%CI [1.01-1.05]). Severe depression symptoms were independently associated with a lower SF-36 Mental Health domain score (OR = 0.98 95%CI [0.96-1.00]). No ICU organization characteristics were associated with psychological symptoms in relatives. DISCUSSION: There is a high prevalence of anxiety and depression symptoms among relatives of moderate-to-severe TBI survivors at 6 months. Anxiety and depression were inversely correlated with the patient's mental health status at 6 months. CONCLUSIONS: Long-term follow-up must provide psychological care to relatives after TBI.

Postoperative transfusion hemoglobin threshold and functional recovery after high-risk oncologic surgery: A randomized controlled pilot study.

BACKGROUND: Robust evidence to inform best transfusion management after major oncologic surgery, where postoperative recovery might impact treatment regimens for cancer, is lacking. We conducted a study to validate the feasibility of a larger trial comparing liberal versus restrictive red blood cells (RBC) transfusion strategies after major oncologic surgery. STUDY DESIGN AND METHODS: This was a two-center, randomized, controlled, study of patients admitted to the intensive care unit after major oncologic surgery. Patients whose hemoglobin level dropped below 9.5 g/dL, were randomly assigned to immediately receive a 1-unit RBC transfusion (liberal) or delayed until the hemoglobin level dropped below 7.5 g/dL (restrictive). The primary outcome was the median hemoglobin level between randomization to day 30 post-surgery. Disability-free survival was evaluated by the WHODAS 2.0 questionnaire. RESULTS: 30 patients were randomized (15 patients/group) in 15 months with a mean recruitment rate of 1.8 patients per month. The median hemoglobin level was significantly higher in the liberal group than in the restrictive group: 10.1 g/dL (IQR 9.6-10.5) versus 8.8 g/dL (IQR 8.3-9.4), p < .001, and RBC transfusion rates were 100% versus 66.7%, p = .04. The disability-free survival was similar between groups: 26.7% versus 20%, p = 1. DISCUSSION: Our results support the feasibility of a phase 3 randomized controlled trial comparing the impact of liberal versus restrictive transfusion strategies on the functional recovery of critically ill patients following major oncologic surgery.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial.

BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Impact of continuous hypertonic (NaCl 20%) saline solution on renal outcomes after traumatic brain injury (TBI): a post hoc analysis of the COBI trial.

BACKGROUND: To evaluate if the increase in chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) compared to standard of care in traumatic brain injury patients. METHODS: In this post hoc analysis of the COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level between 150 and 155 mmol/L for at least 48 h. Patients enrolled in the control arm were treated as recommended by the latest Brain Trauma foundation guidelines. The primary outcome of this study was the occurrence of AKI within 28 days after enrollment. AKI was defined by stages 2 or 3 according to KDIGO criteria. RESULTS: After exclusion of missing data, 322 patients were included in this post hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p < 0.001) and had higher blood chloride levels at day 4 (117.9 ± 10.7 mmol/L vs. 111.6 ± 9 mmol/L, respectively, p < 0.001). The incidence of AKI was not statistically different between the intervention and the control group (24.5% vs. 28.9%, respectively; p = 0.45). CONCLUSIONS: Despite a significant increase in chloride intake, a continuous infusion of HSS was not associated with AKI in moderate-to-severe TBI patients. Our study does not confirm the potentially detrimental effect of chloride load on kidney function in ICU patients. TRIAL REGISTRATION: The COBI trial was registered on clinicaltrial.gov (Trial registration number: NCT03143751, date of registration: 8 May 2017).

Characteristics and outcomes of SARS-COV 2 critically ill patients after emergence of the variant of concern 20H/501Y.V2: A comparative cohort study.

There are currently no data regarding characteristics of critically ill patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean). Consecutive patients with Covid-19 and over 18 years admitted in the unique intensive care unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a LR comparing wave 1 and wave 2 as outcomes. To complete analysis, we built a Random Forest model (RF), that is, a machine learning classification tool- using the same variable set as that of the LR. We included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% confidence interval (CI) 1.89-14.48, p = .001) and a lower simplified acute physiology score (SAPS II) (aOR 0.95, 95% CI 0.91-0.99, p = .007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98-12.51, p = .055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98-0.99, p = .03). Patients in wave 2 had also an increased risk of ventilator-associated pneumonia (VAP) (aOR 4.64, 95% CI 1.54-13.93, p = .006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model. Our data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.

Management of urgent invasive procedures in patients treated with direct oral anticoagulants: An observational registry analysis.

BACKGROUND: Patients treated with direct oral anticoagulants (DOACs) may require urgent procedures. Managing these patients is challenging due to different bleeding risks and may include laboratory testing, procedural delays, or haemostatic/reversal agent administration. OBJECTIVE: We evaluated management strategies and outcomes of urgent, non-haemostatic invasive procedures in patients treated with DOACs. METHODS AND RESULTS: In a descriptive cohort study, we prospectively evaluated 478 patients in the GIHP-NACO registry, from June 2013 to November 2015. Hospitalised patients receiving dabigatran (n = 160), rivaroxaban (n = 274), or apixaban (n = 44) requiring urgent, procedural interventions were evaluated, of which 384/478 (80 %) were surgical procedures. Orthopaedic surgery included 216/384 patients (56 %), while gastrointestinal surgery included 75/384 (20 %) patients. On admission, the median age was 79 (70-85), and creatinine clearance was <60 mL·min-1 in 316/478 (66 %) patients. DOAC concentration was determined in 277 (58 %) patients and was 85 ng·mL-1 (median; range 0-764), 61 ng·mL-1 (3-541), and 81 ng·mL-1 (26-354) for dabigatran, rivaroxaban, and apixaban, respectively. Procedures were delayed in 194/455 (43 %) of the cases. Excessive bleeding was observed in 62/478 (13 %) procedures, and haemostatic agents were administered in 76/478 (16 %) procedures. By day 30, major cerebral and cardiovascular events were observed in 38/478 (7.9 %) patients, and mortality was 28/478 (5.9 %). CONCLUSIONS: In the GIHP-NACO registry, before specific antidotes were available, DOAC treated patients undergoing urgent invasive procedures were delayed in nearly half of the cases, and showed a low rate of excessive bleeding, suggesting that most urgent procedures can be performed safely without DOAC reversal. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov. Identifier: NCT02185027.