Continuous and deep sedation until death after a decision to withdraw life-sustaining therapies in intensive care units: A national survey.

BACKGROUND: Continuous and deep sedation until death is a much highly debated end-of-life practice. France is unique in having a regulatory framework for it. However, there are no data on its practice in intensive care units (ICUs). AIM: The aim is to describe continuous and deep sedation in relation to the framework in the specific context of withdrawal of life-sustaining therapies in ICUs, that is, its decision-making process and its practice compared to other end-of-life practices in this setting. DESIGN AND SETTING: French multicenter observational study. Consecutive ICU patients who died after a decision to withdraw life-sustaining therapies. RESULTS: A total of 343 patients in 57 ICUs, 208 (60%) with continuous and deep sedation. A formalized procedure for continuous and deep sedation was available in 32% of the ICUs. Continuous and deep sedation was not the result of a collegial decision-making process in 17% of cases, and did not involve consultation with an external physician in 29% of cases. The most commonly used sedative medicines were midazolam (10 [5-18] mg h-1) and propofol (200 [120-250] mg h -1). The Richmond Agitation Sedation Scale (RASS) was -5 in 60% of cases. Analgesia was associated with sedation in 94% of cases. Compared with other end-of-life sedative practices (n = 98), medicines doses were higher with no difference in the depth of sedation. CONCLUSIONS: This study shows a poor compliance with the framework for continuous and deep sedation. It highlights the need to formalize it to improve the decision-making process and the match between the intent, the practice and the actual effect.

Body-weight support gait training in neurological intensive care: safety, feasibility, and delays before walking with or without suspension.

BACKGROUND: Early Mobilization in Intensive Care Units (ICUs) enhances patients' evolution, but has been rarely studied in neurological ICUs. The aim of this study was to assess gait training with body-weight support (BWS) in neuroICU, and to report on its safety, feasibility and on delays before walking with and without BWS. METHODS: This study was an observational one-year single-center study. Inclusion criteria were adults with a neurological injury requiring mechanical ventilation. Exclusion criteria were early death or ICU transfer. After weaning from ventilation, patients were screened for indications of BWS walking using predefined criteria. RESULTS: Patients' conditions were mostly brain injuries: 32% subarachnoid hemorrhages, 42% focal strokes, and 12% traumatic brain injuries. Out of 272 admissions, 136 patients were excluded, 78 were eligible, and 33 performed BWS walking. Among non-eligible patients, 36 walked unsuspended upon ventilation weaning, 17 presented too severe impairments. Among the 45 eligible patients who did not receive BWS training, main reasons were workload and weekends (31%), medical barriers (29%), and early ICU discharge (22%). 78 BWS sessions were performed on the 33 beneficiaries (median sessions per patient 2, max 10). Pre-session, most patients had inadequate response to pain, orders, or simple orientation questions. Sitting without support was impossible for 74%. Most pre-post changes in hemodynamic, respiratory, and pain parameters were small, and recovered spontaneously after the session. Eight sessions were interrupted; reasons were pain, fatigue or major imbalance (4), syncope (1), occurrence of stool (2), and battery failure (1). None of these adverse events required medical intervention, patients recovered upon session interruption. Median session duration was 31 min, patients walked on median 17 m. First BWS session occurred on median 3 days after ventilation weaning, and 11 days before patients were able to walk unsuspended. CONCLUSIONS: Verticalization and walking using a suspension device in patients in neuroICU allows early gait training, despite challenging neurological impairments. It is safe and generally well tolerated. TRIAL REGISTRATION: ClinicalTrials database (ID: NCT04300491).

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Pectoral Nerve Blocks for Breast Augmentation Surgery: A Randomized, Double-blind, Dual-centered Controlled Trial.

BACKGROUND: Pectoral nerve blocks have been proposed for analgesia during and after breast cancer surgery, but data are conflicted in aesthetic breast surgery. This trial tested the primary hypothesis that adding a preincisional pectoral nerve block is superior to systemic multimodal analgesic regimen alone for pain control after breast augmentation surgery. A second hypothesis is that rescue opioid consumption would be decreased with a long-lasting effect for both outcomes during the following days. METHODS: Seventy-three adult female patients undergoing aesthetic breast augmentation surgery under general anesthesia were randomly allocated to receive a pectoral nerve block versus no block. Both groups received standard care with protocolized multimodal analgesia alone including systematic acetaminophen and nonsteroidal anti-inflammatory drugs. The primary outcome measure was the maximal numerical rating scale in the first 6 h after extubation. Secondary outcomes included intraoperative remifentanil consumption and from extubation to day 5: maximal numerical rating scale, postoperative cumulative opioid consumption and postoperative opioid side effects, and patient satisfaction recorded at day 5. RESULTS: The maximal numerical rating scale score in the first 6 h was lower in the pectoral nerve block group compared with the control group (3.9 ± 2.5 vs. 5.2 ± 2.2; difference: -1.2 [95% CI, -2.3 to -0.1]; P = 0.036). The pectoral nerve block group had a lower maximal numerical rating scale between days 1 and 5 (2.2 ± 1.9 vs. 3.2 ± 1.7; P = 0.032). The cumulative amount of overall opioids consumption (oral morphine equivalent) was lower for the pectoral nerve block group from hour 6 to day 1 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 31.5] mg, P = 0.006) and from days 1 to 5 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 51] mg, P = 0.002). CONCLUSIONS: Pectoral nerve block in conjunction with multimodal analgesia provides effective perioperative pain relief after aesthetic breast surgery and is associated with reduced opioid consumption over the first 5 postoperative days.

Macintosh Videolaryngoscope for Intubation in the Operating Room: A Comparative Quality Improvement Project.

BACKGROUND: "Macintosh"-videolaryngoscopes (VLs) are VLs that allow both direct and indirect laryngoscopy for intubation. We describe the decision-making and implementation-processes that our hospital used regarding the choice of device. We compared the performances of 4 Macintosh-VLs both in direct and indirect laryngoscopy. METHODS: A quality-improvement-project for airway management aiming at implementing Macintosh-VL for all intubation procedures performed in the operating room, involving 4 Macintosh-VLs (McGrath-Mac, C-MAC-S, C-MAC-S-Pocket-Monitor [PM], and APA). Three consecutive steps were described: (1) direct laryngoscopy with Macintosh-VL, (2) indirect laryngoscopy with Macintosh-VL (intubation attempt with Macintosh-style blade in case of Cormack I or II), (3) intubation attempt with hyperangulated blade in case of Cormack III/IV or failure of Macintosh-style blade. The main end point was the need to move to step III and use a hyperangulated blade. A mixed-effects multivariable logistic regression analysis was performed to compare devices on the main end point while considering site as a random effect. Comparison of means was performed using analysis of variance and Tukey's test for multiple comparisons (number of laryngoscopy attempts, numeric rate scale [NRS] difficulty of intubation and NRS user-friendliness). Comparison of percentages was performed using a χ2 test for the need to move to step III and a Kruskal-Wallis test for the quality of image (bad, passable, good, very good, excellent). A P value ≤.008 was considered statistically significant. RESULTS: From May to September 2017, 589 patients were included. Using the McGrath-Mac (22/180 [12%]) was associated with less use of hyperangulated blade than using the C-MAC-S (39/132 [30%], odds ratio [OR] [99.2% confidence interval {CI}] 0.34 [0.16-0.77], P = .0005), the APA (35/138 [25%], OR [99.2% CI] 0.42 [0.19-0.93]; P = .004), but not the C-MAC-S-PM (29/139 [21%], OR [99.2% CI] 0.53 [0.23-1.2]; P = .04).Overall, the number of intubation attempts was significantly lower using the McGrath Mac than the C-MAC-S or the C-MAC-S-PMVLs. Subjective appreciation of intubation difficulty and user-friendliness of the devices showed respectively lower and higher NRS scores for the McGrath-Mac compared to the other devices, whereas subjective assessment of image quality showed higher quality for the C-MAC-S and C-MAC-S-PM compared to the APA or McGrath-Mac. CONCLUSIONS: Among 4 single-use Macintosh-VLs, glottic visualization in direct and indirect laryngoscopy with the Macintosh-style blade was significantly improved with the McGrath-Mac compared to other Macintosh-VLs, leading to a less frequent need to resort to the hyperangulated blade and reduced overall number of intubation attempts.

Optimal intracranial pressure in patients with aneurysmal subarachnoid hemorrhage treated with coiling and requiring external ventricular drainage.

Optimal management of intracranial pressure (ICP) among aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) is controversial. To analyze predictors of delayed cerebral ischemia (DCI)-related cerebral infarction after aSAH and the influence of ICP values on DCI, we prospectively collected consecutive patients with aSAH receiving coiling and requiring EVD. Predictors of DCI-related cerebral infarction (new CT hypodensities developed within the first 3 weeks not related to other causes) were studied. Vasospasm and brain hypoperfusion were studied with CT angiography and CT perfusion (RAPID-software). Among 50 aSAH patients requiring EVD, 21 (42%) developed DCI-related cerebral infarction, while 27 (54%) presented vasospasm. Mean ICP ranged between 2 and 19 mmHg. On the multivariate analysis, the mean ICP (OR = 2, 95%CI = 1.01-3.9, p = 0.042) and the mean hypoperfusion volume on Tmax delay > 6 (OR = 1.2, 95%CI = 1.01-1.3, p = 0.025) were independent predictors of DCI. To predict DCI-related cerebral infarction, Tmax delay > 6 s presented the highest AUC (0.956, SE = 0.025), with a cutoff value of 18 ml showing sensitivity, specificity, PPV, NPV, and accuracy of 90.5% (95%CI = 69-98.8%), 86.2% (95%CI = 68.4-96%), 82.6% (95%CI = 65.4-92%), 92.5% (95%CI = 77-98%), and 88% (95%CI = 75-95%), respectively. The AUC of the mean ICP was 0.825 (SE = 0.057), and the best cutoff value was 6.7 mmHg providing sensitivity, specificity, PPV, NPV, and accuracy of 71.4% (95%CI = 48-89%), 62% (95%CI = 42-79%), 58% (95%CI = 44-70%), 75% (95%CI = 59-86%), and 66% (95%CI = 51-79%) for the prediction of DCI-related cerebral infarction, respectively. Among aSAH patients receiving coiling and EVD, lower ICP (< 6.7 mmHg in our study) could potentially be beneficial in decreasing DCI-related cerebral infarction. Brain hypoperfusion with a volume > 18 ml at Tmax delay > 6 s presents a high sensibility and specificity in prediction of DCI-related cerebral infarction.

The Frontal Bone Window for Transcranial Doppler Ultrasonography in Critically Ill Patients: Validation of a New Approach in the ICU.

BACKGROUND AND OBJECTIVE: The temporal bone window (TBW) for transcranial Doppler (TCD) often fails to insonate the anterior cerebral artery (ACA). The frontal bone window (FBW) has never been evaluated in intensive care units (ICU). The main objective was to determine the ability of the FBW to assess ACA velocities in critically ill patients. METHODS: A prospective study was conducted in two ICUs of the Montpellier University Hospital (France), between November 2014 and September 2016. Adult patients admitted to ICU for brain injury, with a Glasgow Coma Scale score ≤ 13, were enrolled within 3 days after admission. A first TCD examination was carried out bilaterally through the TBW and FBW by an intensivist expert in TCD, repeated by the same examiner, and 15 min later by an intensivist certified in TCD, designated as non-expert, blinded. The success of the FBW examinations was defined by the ability to measure the ACA velocities. Intra- and interobserver agreements were analyzed according to the Bland and Altman method. RESULTS: A total of 147 patients were analyzed. The FBW succeeded in insonating the ACA in 66 patients [45%, CI (37-53)], 45 bilaterally and 21 unilaterally. For 16 patients (11%), the FBW was the only way to measure ACA velocities. By combining the two techniques, the ACA success rate increased from 62% CI (54-70) to 73% CI (65-79) (P = 0.05). Intra- and interobserver mean biases and 95% limits of agreement for ACA systolic velocity measurements through the FBW were 1 (- 33 to 35) and 2 (- 34 to 38) cm s-1, respectively. For paired TBW and FBW measures of ACA velocities, mean biases (± SD) for ACA systolic, and mean and diastolic velocities were relatively close to zero, but negatives (- 7 ± 33, - 2 ± 19, - 1 ± 15 cm s-1, respectively), highlighting that ACA velocities were lower with the FBW (A2 segment) than TBW (A1 segment). The correlation coefficient for ACA systolic velocities measured by the FBW and TBW was R = 0.47, CI (0.28-0.62). No risk factors for failure of the FBW were identified. CONCLUSIONS: In ICU, the FBW was able to insonate the ACA in 45% of patients admitted for brain injury, without the use of contrast agents. The FBW could improve the detection of ACA vasospasms.

Deep brain stimulation treated dystonia-trajectory via status dystonicus.

BACKGROUND: Status dystonicus (SD) is a life-threatening condition. OBJECTIVE AND METHODS: In a dystonia cohort who developed status dystonicus, we analyzed demographics, background dystonia phenomenology and complexity, trajectory previous to-, via status dystonicus episodes, and evolution following them. RESULTS: Over 20 years, 40 of 328 dystonia patients who were receiving DBS developed 58 status dystonicus episodes. Dystonia was of pediatric onset (95%), frequently complex, and had additional cognitive and pyramidal impairment (62%) and MRI alterations (82.5%); 40% of episodes occured in adults. Mean disease duration preceding status dystonicus was 10.3 ± 8 years. Evolution time to status dystonicus varied from days to weeks; however, 37.5% of patients exhibited progressive worsening over years. Overall, DBS was efficient in resolving 90% of episodes. CONCLUSION: Status dystonicus is potentially reversible and a result of heterogeneous conditions with nonuniform underlying physiology. Recognition of the complex phenomenology, morphological alterations, and distinct patterns of evolution, before and after status dystonicus, will help our understanding of these conditions. © 2018 International Parkinson and Movement Disorder Society.

Patient factors and outcomes associated with the withdrawal or withholding of life-sustaining therapies in mechanically ventilated brain-injured patients: An observational multicentre study.

BACKGROUND: Knowledge of the factors associated with the decision to withdraw or withhold life support (WWLS) in brain-injured patients is limited. However, most deaths in these patients may involve such a decision. OBJECTIVES: To identify factors associated with the decision to WWLS in brain-injured patients requiring mechanical ventilation who survive the first 24 h in the ICU, and to analyse the outcomes and time to death. DESIGN: A retrospective observational multicentre study. SETTINGS: Twenty French ICUs in 18 university hospitals. PATIENTS: A total of 793 mechanically ventilated brain-injured adult patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Decision to WWLS within 3 months of ICU admission, and death or Glasgow Outcome Scale (GOS) score at day 90. RESULTS: A decision to WWLS was made in 171 patients (22%), of whom 89% were dead at day 90. Out of the 247 deaths recorded at day 90, 153 (62%) were observed after a decision to WWLS. The median time between admission and death when a decision to WWLS was made was 10 (5 to 20) days vs. 10 (5 to 26) days when no end-of-life decision was made (P < 0.924). Among the 18 patients with a decision to WWLS who were still alive at day 90, three patients (2%) had a GOS score of 2, nine patients (5%) had a GOS score of 3 and five patients (3%) a GOS score of 4. Older age, presence of one nonreactive and dilated pupil, Glasgow Coma Scale less than 7, barbiturate use, acute respiratory distress syndrome and worsening lesions on computed tomography scans were each independently associated with decisions to WWLS. CONCLUSION: Using a nationwide cohort of brain-injured patients, we observed a high proportion of deaths associated with an end-of-life decision. Older age and several disease severity factors were associated with the decision to WWLS.

Association between continuous hyperosmolar therapy and survival in patients with traumatic brain injury - a multicentre prospective cohort study and systematic review.

BACKGROUND: Intracranial hypertension (ICH) is a major cause of death after traumatic brain injury (TBI). Continuous hyperosmolar therapy (CHT) has been proposed for the treatment of ICH, but its effectiveness is controversial. We compared the mortality and outcomes in patients with TBI with ICH treated or not with CHT. METHODS: We included patients with TBI (Glasgow Coma Scale ≤ 12 and trauma-associated lesion on brain computed tomography (CT) scan) from the databases of the prospective multicentre trials Corti-TC, BI-VILI and ATLANREA. CHT consisted of an intravenous infusion of NaCl 20% for 24 hours or more. The primary outcome was the risk of survival at day 90, adjusted for predefined covariates and baseline differences, allowing us to reduce the bias resulting from confounding factors in observational studies. A systematic review was conducted including studies published from 1966 to December 2016. RESULTS: Among the 1086 included patients, 545 (51.7%) developed ICH (143 treated and 402 not treated with CHT). In patients with ICH, the relative risk of survival at day 90 with CHT was 1.43 (95% CI, 0.99-2.06, p = 0.05). The adjusted hazard ratio for survival was 1.74 (95% CI, 1.36-2.23, p < 0.001) in propensity-score-adjusted analysis. At day 90, favourable outcomes (Glasgow Outcome Scale 4-5) occurred in 45.2% of treated patients with ICH and in 35.8% of patients with ICH not treated with CHT (p = 0.06). A review of the literature including 1304 patients from eight studies suggests that CHT is associated with a reduction of in-ICU mortality (intervention, 112/474 deaths (23.6%) vs. control, 244/781 deaths (31.2%); OR 1.42 (95% CI, 1.04-1.95), p = 0.03, I 2 = 15%). CONCLUSIONS: CHT for the treatment of posttraumatic ICH was associated with improved adjusted 90-day survival. This result was strengthened by a review of the literature.

Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial.

BACKGROUND: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). OBJECTIVE: To determine whether MARS improves survival in ALF. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705). SETTING: 16 French liver transplantation centers. PATIENTS: 102 patients with ALF. INTERVENTION: Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. MEASUREMENTS: 6-month survival and secondary end points, including adverse events. RESULTS: 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. LIMITATION: The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. CONCLUSION: This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. PRIMARY FUNDING SOURCE: Assistance Publique-Hôpitaux de Paris.

CT perfusion-guided administration of IV milrinone is associated with a reduction in delayed cerebral infarction after subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The "before" period included 277 patients, and the "after" one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the "after" period. Conversely, the occurrence of DCIn was reduced with the "after" management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, p = 0.001 ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, p < 0.001 ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.

Tension between continuous and deep sedation and assistance in dying: a national survey of intensive care professionals' perceptions.

INTRODUCTION: The situation in France is unique, having a legal framework for continuous and deep sedation (CDS). However, its use in intensive care units (ICU), combined with the withdrawal of life-sustaining therapies, still raises ethical issues, particularly its potential to hasten death. The legalization of assistance in dying, i.e., assisted suicide or euthanasia at the patient's request, is currently under discussion in France. The objectives of this national survey were first, to assess whether ICU professionals perceive CDS administered to ICU patients as a practice that hastens death, in addition to relieving unbearable suffering, and second, to assess ICU professionals' perceptions of assistance in dying. METHODS: A national survey with online questionnaires for ICU physicians and nursesaddressed through the French Society of Anesthesiology and Critical Care Medicine. RESULTS: A total of 956 ICU professionals responded to the survey (38% physicians and 62% nurses). Of these, 22% of physicians and 12% of nurses (p < 0.001) felt that the purpose of CDS was to hasten death. For 20% of physicians, CDS combined with terminal extubation was considered an assistance in dying. For 52% of ICU professionals, the current framework did not sufficiently cover the range of situations that occur in the ICU. A favorable opinion on the potential legalization of assistance in dying was observed in 83% of nurses and 71% of physicians (p < 0.001), with no preference between assisted suicide and euthanasia. CONCLUSION: Our findings highlight the tension between CDS and assisted suicide/euthanasia in the specific context of intensive care and suggest that ICU professionals would be supportive of a legislative evolution.

Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

BACKGROUND: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. METHODS: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406. FINDINGS: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. INTERPRETATION: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. FUNDING: French Ministry of Social Affairs and Health.

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.

Rescue, combined, and stand-alone thrombectomy in the management of large vessel occlusion stroke using the solitaire device: a prospective 50-patient single-center study: timing, safety, and efficacy.

BACKGROUND AND PURPOSE: Large vessel occlusion in ischemic stroke is associated with a high degree of morbidity. When intravenous thrombolysis fails, mechanical thrombectomy can provide an alternative and synergistic method for flow restoration. In this study we evaluate the safety and efficacy of our stroke management protocol (RECOST study). METHODS: Fifty consecutive ischemic stroke patients with large vessel occlusion were included. After clinical and MRI imaging assessment, 3 treatment strategies were selected according to time of symptom onset and location of vessel occlusion: rescue therapy; combined therapy; and stand-alone thrombectomy (RECOST study). MRI ASPECT score <5 was the main exclusion criterion. Mechanical thrombectomy was performed exclusively with the Solitaire flow restoration device. Clinical outcome was assessed after treatment, on day 1, and at discharge. RESULTS: Mean patient age was 67.6 years, mean NIHSS score was 14.7, and mean ASPECT score was 6 on presentation. Vessel occlusions were in the middle cerebral artery (40%), the internal carotid artery (28%), and the basilar artery (32%). Rescue treatment represented 24%, combined therapy represented 56%, and stand-alone thrombectomy represented 20%. Mean recanalization time from symptoms onset was 377 minutes, with overall recanalization rate TICI 3 of 84%. NIHSS score at discharge was 6.5, with 60% of patients demonstrating NIHSS score 0 to 1 or an improvement of >9 points. Symptomatic complication rate was 10%. At 3 months, 54% of patients had a modififed Rankin scale score of 0 to 2, with an overall mortality rate of 12%. CONCLUSIONS: The present integrated stroke management protocol (RECOST study) demonstrated rapid, safe, and effective recanalization. We postulate that the Solitaire device contributed to high recanalization and patient selection using MRI ASPECT score to low and complication rates, therefore avoiding futile and dangerous interventions.

Long-term outcome in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation.

BACKGROUND: Patients affected with aneurysmal subarachnoid hemorrhage (aSAH) often require intensive care, and then present distinctive outcome from less severe patients. We aimed to specify their long-term outcome and to identify factors associated with poor outcome. METHODS: We conducted a retrospective study in a French university hospital intensive care unit. Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. At least one year after initial bleeding, survival and degree of disability were assessed using the modified Rankin Scale (mRS) via telephone interviews. A multivariable logistic regression analysis was performed to determine independent factors associated with poor outcome defined as mRS≥3. RESULTS: Two-hundred thirty-six patients were included. Among them, 7 were lost to follow-up, and 229 were analyzed: 73 patients (32%) had a good outcome (mRS<3), and 156 (68%) had a poor outcome (mRS≥3). The estimated 1-year survival rate was 63%. One-hundred sixty-three patients patients (71%) suffered from early brain injuries (EBI), 33 (14%) from rebleeding, 80 (35%) from vasospasm and 63 (27%) from delayed cerebral ischemia (DCI). Multivariable logistic regression identified independent factors associated with poor outcome including delay between aSAH diagnosis and mRS assessment (OR, 0.96; 95% CI, 0.95-0.98; p<.0001), age (OR per 10 points, 1.57; 95% CI, 1.12-2.19; p = 0.008), WFNS V versus WFNS III (OR, 5.71; 95% CI 1.51-21.61; p = 0.004), subarachnoid rebleeding (OR, 6.47; 95% CI 1.16-36.06; p = 0.033), EBI (OR, 4.52; 95% CI 1.81-11.29; p = 0.001) and DCI (OR, 4.73; 95% CI, 1.66-13.49; p = 0.004). CONCLUSION: Among aSAH patients requiring assisted ventilation, two-third of them survived at one year, and one-third showed good long-term outcome. As it appears as an independant factor associated with poor outcome, DCI shoud retain particular attention in future studies beyond angiographic vasospasm.

Transcranial sonographic assessment of the third ventricle in neuro-ICU patients to detect hydrocephalus: a diagnostic reliability pilot study.

BACKGROUND: Transcranial sonography is a point-of-care tool recommended in intensive care units (ICU) to monitor brain injured patients. Objectives of the study was to assess feasibility and reliability of the third ventricle (V3) diameter measurement using transcranial sonography (TCS) compared to brain computed-tomography (CT), the gold standard measurement, and to measure the TCS learning curve. DESIGN: prospective study, in a 16-bed neurological ICU in an academic hospital. Every consecutive brain injured adult patient, who required a brain CT and TCS monitoring were included. The V3 diameter was blindly measured by TCS and CT. Intraclass correlation coefficient (ICC) and Bland-Altman plot were used to assess the reliability and agreement between TCS and CT V3 measurements. Diagnosis performance of the V3 diameter using TCS to detect hydrocephalus was measured. Absolute difference between V3 measurement by residents and experts was measured consecutively to assess the learning curve. RESULTS: Among the 100 patients included in the study, V3 diameter could be assessed in 87 patients (87%) from at least one side of the skull. Both temporal windows were available in 70 patients (70%). The ICC between V3 diameter measured by TCS and CT was 0.90 [95% CI 0.84-0.93] on the right side, and 0.92 [0.88-0.95] on the left side. In Bland-Altman analysis, mean difference, standard deviation, 95% limits of agreement were 0.36, 1.52, - 2.7 to 3.3 mm, respectively, on the right side; 0.25, 1.47, - 2.7 to 3.1 mm, respectively, on the left side. Among the 35 patients with hydrocephalus, V3 diameters could be measured by TCS in 31 patients (89%) from at least one side. Hydrocephalus was, respectively, excluded, confirmed, or inconclusive using TCS in 35 (40%), 25 (29%) and 27 (31%) of the 87 assessable patients. After 5 measurements, every resident reached a satisfactory measurement compared to the expert operator. CONCLUSION: TCS allows rapid, simple and reliable V3 diameter measurement compared with the gold standard in neuro-ICU patients. Aside from sparing irradiating procedures and transfers to the radiology department, it may especially increase close patient monitoring to detect clinically occult hydrocephalus earlier. Further studies are needed to measure the potential clinical benefit of this method. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02830269.