Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

BACKGROUND: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. METHODS: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. RESULTS: Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15-30] and 30 days [18-30], respectively; median absolute difference of - 0.0 days, 95% CI - 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5-28] versus 6 days [2-13], p = 0.02). CONCLUSIONS: In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment.

BACKGROUND: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. METHODS: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). RESULTS: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. CONCLUSIONS: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530 .

Time course of fluid responsiveness in sepsis: the fluid challenge revisiting (FCREV) study.

BACKGROUND: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC. METHODS: This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20 min (T30) after the end of FC. RESULTS: From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43-63], median SOFA score 10 [8-12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI = [37-60]), and 39 (51%, 95%CI = [38-62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI = [1.9-15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. CONCLUSIONS: This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014.

Driving pressure and acute respiratory distress syndrome in critically ill patients.

BACKGROUND AND OBJECTIVE: Elevated driving pressure (ΔP) may be associated with increased risk of acute respiratory distress syndrome (ARDS) in patients admitted via the emergency department and with post-operative pulmonary complications in surgical patients. This study investigated the association of higher ΔP with the onset of ARDS in a high-risk, intensive care unit (ICU) population. METHODS: This is a secondary analysis of a prospective multicentre observational study. Data for this ancillary study were obtained from intubated adult patients with at least one ARDS risk factor upon ICU admission enrolled in a previous multicentre observational study. Patients were followed up for the development of ARDS within 7 days (primary outcome). Univariate and multivariate analyses tested the association between ΔP (measured at ICU admission (baseline) or 24 h later (day 1)) and the development of ARDS. RESULTS: A total of 221 patients were included in this study, among whom 34 (15%) developed ARDS within 7 days. These patients had higher baseline ΔP than those who did not (mean ± SD: 12.5 ± 3.1 vs 9.8 ± 3.4 cm H2 O, respectively, P = 0.0001). The association between baseline ΔP and the risk of developing ARDS was robust to adjustment for baseline tidal volume, positive-end expiratory pressure, illness severity, serum lactate and sepsis, pneumonia, severe trauma and shock as primary ARDS risk factors (odds ratio: 1.20; 95% CI: 1.03-1.41; P = 0.02). The same results were found with day 1 ΔP. CONCLUSION: Among at-risk ICU patients, higher ΔP may identify those who are more likely to develop ARDS.

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. © RSNA, 2017.

Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study.

RATIONALE: Sevoflurane improves gas exchange, and reduces alveolar edema and inflammation in preclinical studies of lung injury, but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS). OBJECTIVES: To assess whether sevoflurane would improve gas exchange and inflammation in ARDS. METHODS: We did a parallel, open-label single-center randomized controlled trial at three intensive care units from a French university hospital between April 2014 and February 2016. Adult patients were randomized within 24 hours of moderate-to-severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end-products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane. CONCLUSIONS: In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam. Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).

Cost assessment of a new oral care program in the intensive care unit to prevent ventilator-associated pneumonia.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is the most frequent hospital-acquired infections in intensive care units (ICU). In the bundle of care to prevent the VAP, the oral care is very important strategies, to decrease the oropharyngeal bacterial colonization and presence of causative bacteria of VAP. In view of the paucity of medical economics studies, our objective was to determine the cost of implementing this oral care program for preventing VAP. MATERIALS AND METHODS: In five ICUs, during period 1, caregivers used a foam stick for oral care and, during period 2, a stick and tooth brushing with aspiration. Budgetary effect of the new program from the hospital's point of view was analyzed for both periods. The costs avoided were calculated from the incidence density of VAP (cases per 1000 days of intubation). The cost study included device cost, benefit lost, and ICU cost (medication, employer and employee contributions, blood sample analysis…). RESULTS: A total of 2030 intubated patients admitted to the ICUs benefited from oral care. The cost of implementing the study protocol was estimated to be €11,500 per year. VAP rates decreased significantly between the two periods (p1 = 12.8% and p2 = 8.5%, p = 0.002). The VAP revenue was ranged from €28,000 to €45,000 and the average cost from €39,906 to €42,332. The total cost assessment calculated was thus around €1.9 million in favor of the new oral care program. CONCLUSION AND CLINICAL RELEVANCE: Our study showed that the implementation of a simple strategy improved the quality of patient care is economically viable. TRIAL REGISTRATION: NCT02400294.

Extubation Failure in Brain-injured Patients: Risk Factors and Development of a Prediction Score in a Preliminary Prospective Cohort Study.

BACKGROUND: The decision to extubate brain-injured patients with residual impaired consciousness holds a high degree of uncertainty of success. The authors developed a pragmatic clinical score predictive of extubation failure in brain-injured patients. METHODS: One hundred and forty brain-injured patients were prospectively included after the first spontaneous breathing trial success. Assessment of multiparametric hemodynamic, respiratory, and neurologic functions was performed just before extubation. Extubation failure was defined as the need for ventilatory support during intensive care unit stay. Extubation failure within 48 h was also analyzed. Neurologic outcomes were recorded at 6 months. RESULTS: Extubation failure occurred in 43 (31%) patients with 31 (24%) within 48 h. Predictors of extubation failure consisted of upper-airway functions (cough, gag reflex, and deglutition) and neurologic status (Coma Recovery Scale-Revised visual subscale). From the odds ratios, a four-item predictive score was developed (area under the curve, 0.85; 95% CI, 0.77 to 0.92) and internally validated by bootstrap. Cutoff was determined with sensitivity of 92%, specificity of 50%, positive predictive value of 82%, and negative predictive value of 70% for extubation failure. Failure before and beyond 48 h shared similar risk factors. Low consciousness level patients were extubated with 85% probability of success providing the presence of at least two operating airway functions. CONCLUSIONS: A simplified clinical pragmatic score assessing cough, deglutition, gag reflex, and neurologic status was developed in a preliminary prospective cohort of brain-injured patients and was internally validated (bootstrapping). Extubation appears possible, providing functioning upper airways and irrespective of neurologic status. Clinical practice generalizability urgently needs external validation.

Impact of the anesthetic conserving device on respiratory parameters and work of breathing in critically ill patients under light sedation with sevoflurane.

BACKGROUND: Sevoflurane sedation in the intensive care unit is possible with a special heat and moisture exchanger called the Anesthetic Conserving Device (ACD) (AnaConDa; Sedana Medical AB, Uppsala, Sweden). The ACD, however, may corrupt ventilatory mechanics when used during the weaning process of intensive care unit patients. The authors compared the ventilatory effects of light-sedation with sevoflurane administered with the ACD and those of classic management, consisting of a heated humidifier and intravenous sedation, in intensive care unit patients receiving pressure-support ventilation. METHODS: Fifteen intensive care unit patients without chronic pulmonary disease were included. A target Richmond Agitation Sedation Scale level of -1/-2 was obtained with intravenous remifentanil (baseline 1-condition). Two successive interventions were tested: replacement of the heated humidifier by the ACD without sedation change (ACD-condition) and sevoflurane with the ACD with an identical target level (ACD-sevoflurane-condition). Patients finally returned to baseline (baseline 2-condition). Work of breathing, ventilatory patterns, blood gases, and tolerance were recorded. A steady state of 30 min was achieved for each experimental condition. RESULTS: ACD alone worsened ventilatory parameters, with significant increases in work of breathing (from 1.7 ± 1.1 to 2.3 ± 1.2 J/l), minute ventilation, P0,1, intrinsic positive end-expiratory pressure (from 1.3 ± 2.6 to 4.7 ± 4.2 cm H2O), inspiratory pressure swings, and decreased patient comfort. Sevoflurane normalized work of breathing (from 2.3 ± 1.2 to 1.8 ± 1 J/l), intrinsic positive end-expiratory pressure (from 4.7 ± 4.2 to 1.8 ± 2 cm H2O), inspiratory pressure swings, other ventilatory parameters, and patient tolerance. CONCLUSIONS: ACD increases work of breathing and worsens ventilatory parameters. Sevoflurane use via the ACD (for a light-sedation target) normalizes respiratory parameters. In this patient's population, light-sedation with sevoflurane and the ACD may be possible during the weaning process.

Cost awareness among intensivists in their daily clinical practice: a prospective multicentre study.

BACKGROUND: Better cost-awareness is a prerogative in achieving the best benefit/risk/cost ratio in the care. We aimed to assess the cost-awareness of intensivists in their daily clinical practice and to identify factors associated with accurate estimate of cost (50-150% of the real cost). METHODS: We performed a prospective observational study in seven French ICUs. We compared the estimate of intensivists of the daily costs of caring with the real costs on a given day. The estimates covered five categories (drugs, laboratory tests, imaging modalities, medical devices, and waste) whose sum represented the overall cost. RESULTS: Of the 234 estimates made by 65 intensivists, 70 (29.9%) were accurate. The median overall cost estimate (€330 [170; 620]) was significantly higher than the real cost (€178 [124; 239], p < 0.001). This overestimation was found in four categories, in particular for waste (€40 [15; 100] vs. €1.1 [0.6; 2.3], p < 0.001). Only the laboratory tests were underestimated (€65 [30; 120] vs. €106 [79; 138], p < 0.001). Being aware of the financial impact of prescriptions was factor associated with accurate estimate (OR: 5.05, 95%CI:1.47-17.4, p = 0.01). However, feeling able to accurately perform estimation was factor negatively associated with accurate estimate (OR: 0.11, 95%CI: 0.02-0.71, p = 0.02). CONCLUSION: French intensivists have a poor awareness of costs in their daily clinical practice. Raising awareness of the financial impact of prescriptions, and of the cost of laboratory tests and waste are the main areas for improvement that could help achieve the objective of the best care at the best cost.

Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.

BACKGROUND: Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. METHODS: We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. FINDINGS: Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. INTERPRETATION: After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. FUNDING: The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.

Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke: The AMETIS Randomized Clinical Trial.

Importance: General anesthesia and procedural sedation are common practice for mechanical thrombectomy in acute ischemic stroke. However, risks and benefits of each strategy are unclear. Objective: To determine whether general anesthesia or procedural sedation for anterior circulation large-vessel occlusion acute ischemic stroke thrombectomy are associated with a difference in periprocedural complications and 3-month functional outcome. Design, Setting, and Participants: This open-label, blinded end point randomized clinical trial was conducted between August 2017 and February 2020, with final follow-up in May 2020, at 10 centers in France. Adults with occlusion of the intracranial internal carotid artery and/or the proximal middle cerebral artery treated with thrombectomy were enrolled. Interventions: Patients were assigned to receive general anesthesia with tracheal intubation (n = 135) or procedural sedation (n = 138). Main Outcomes and Measures: The prespecified primary composite outcome was functional independence (a score of 0 to 2 on the modified Rankin Scale, which ranges from 0 [no neurologic disability] to 6 [death]) at 90 days and absence of major periprocedural complications (procedure-related serious adverse events, pneumonia, myocardial infarction, cardiogenic acute pulmonary edema, or malignant stroke) at 7 days. Results: Among 273 patients evaluable for the primary outcome in the modified intention-to-treat population, 142 (52.0%) were women, and the mean (SD) age was 71.6 (13.8) years. The primary outcome occurred in 38 of 135 patients (28.2%) assigned to general anesthesia and in 50 of 138 patients (36.2%) assigned to procedural sedation (absolute difference, 8.1 percentage points; 95% CI, -2.3 to 19.1; P = .15). At 90 days, the rate of patients achieving functional independence was 33.3% (45 of 135) with general anesthesia and 39.1% (54 of 138) with procedural sedation (relative risk, 1.18; 95% CI, 0.86-1.61; P = .32). The rate of patients without major periprocedural complications at 7 days was 65.9% (89 of 135) with general anesthesia and 67.4% (93 of 138) with procedural sedation (relative risk, 1.02; 95% CI, 0.86-1.21; P = .80). Conclusions and Relevance: In patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke, general anesthesia and procedural sedation were associated with similar rates of functional independence and major periprocedural complications. Trial Registration: ClinicalTrials.gov Identifier: NCT03229148.

Effect of an individualized versus standard blood pressure management during mechanical thrombectomy for anterior ischemic stroke: the DETERMINE randomized controlled trial.

BACKGROUND: Hypotension and blood pressure (BP) variability during endovascular therapy (EVT) for acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO) is associated with worse outcomes. However, the optimal BP threshold during EVT is still unknown given the lack of randomized controlled evidence. We designed the DETERMINE trial to assess whether an individualized BP management during EVT could achieve better functional outcomes compared to a standard BP management. METHODS: The DETERMINE trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial (PROBE design). AIS patients with a proximal anterior LVO are randomly assigned, in a 1:1 ratio, to an experimental arm in which mean arterial pressure (MAP) is maintained within 10% of the first MAP measured before EVT, or a control arm in which systolic BP (SBP) is maintained within 140-180 mm Hg until reperfusion is achieved or artery closure in case of EVT failure. The primary outcome is the rate of favorable functional outcomes, defined by a modified Rankin Scale (mRS) between 0 and 2 at 90 days. Secondary outcomes include excellent outcome and ordinal analysis of the mRS at 90 days, early neurological improvement at 24 h (National Institutes of Health Stroke Scale), final infarct volume, symptomatic intracranial hemorrhage rates, and all-cause mortality at 90 days. Overall, 432 patients will be included. DISCUSSION: DETERMINE will assess the clinical relevance of an individualized BP management before reperfusion compared to the one size fits all approach currently recommended by international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04352296. Registered on 20th April 2020.

Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated: The AGATE Multicenter Randomized Controlled Study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination. RESEARCH QUESTION: Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma? STUDY DESIGN AND METHODS: In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants. RESULTS: A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted. INTERPRETATION: Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.

Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Anaesthesia and haemodynamic management of acute ischaemic stroke patients before, during and after endovascular therapy.

Endovascular therapy (EVT) is now standard of care for eligible patients with acute ischaemic stroke caused by large vessel occlusion in the anterior circulation. EVT can be performed with general anaesthesia (GA) or with monitored anaesthesia care, involving local anaesthesia with or without conscious sedation (LA/CS). Controversies remain regarding the optimal choice of anaesthetic strategy and observational studies suggested poorer functional outcome and higher mortality in patients treated under GA, essentially because of its haemodynamic consequences and the delay to put patients under GA. However, these studies are limited by selection bias, the most severe patients being more likely to receive GA and recent randomised trials and meta-analysis showed that protocol-based GA compared with LA/CS is significantly associated with less disability at 3 months. Unlike for intravenous thrombolysis, few data exist to guide management of blood pressure (BP) before and during EVT, but arterial hypotension should be avoided as long as the occlusion persists. BP targets following EVT should probably be adapted to the degree of recanalisation and the extent of ischaemia. Lower BP levels may be warranted to prevent reperfusion injuries even if prospective haemodynamic management evaluations after EVT are lacking.

Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements.

BACKGROUND: Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV. STUDY DESIGN AND METHODS: This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015. RESULTS: Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P < 0.0001), flail chest (P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P < 0.001), and noninvasive ventilation (P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7. CONCLUSIONS: EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.

Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol.

INTRODUCTION: Endovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS. METHODS AND ANALYSIS: Anesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0-2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7. ETHICS AND DISSEMINATION: The AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT03229148.