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Introduction: Prognostication of outcome in severe stroke patients necessitating invasive mechanical ventilation poses significant challenges. The objective of this study was to assess the prognostic significance and prevalence of early electroencephalogram (EEG) abnormalities in adult stroke patients receiving mechanical ventilation., Methods: This study is a pre-planned ancillary investigation within the prospective multicenter SPICE cohort study (2017-2019), conducted in 33 intensive care units (ICUs) in the Paris area, France. We included adult stroke patients requiring invasive mechanical ventilation, who underwent at least one intermittent EEG examination during their ICU stay. The primary endpoint was the functional neurological outcome at one year, determined using the modified Rankin scale (mRS), and dichotomized as unfavorable (mRS 4-6, indicating severe disability or death) or favorable (mRS 0-3). Multivariable regression analyses were employed to identify EEG abnormalities associated with functional outcomes., Results: Of the 364 patients enrolled in the SPICE study, 153 patients (49 ischemic strokes, 52 intracranial hemorrhages, and 52 subarachnoid hemorrhages) underwent at least one EEG at a median time of 4 (interquartile range 2-7) days post-stroke. Rates of diffuse slowing (70% vs. 63%, p = 0.37), focal slowing (38% vs. 32%, p = 0.15), periodic discharges (2.3% vs. 3.7%, p = 0.9), and electrographic seizures (4.5% vs. 3.7%, p = 0.4) were comparable between patients with unfavorable and favorable outcomes. Following adjustment for potential confounders, an unreactive EEG background to auditory and pain stimulations (OR 6.02, 95% CI 2.27-15.99) was independently associated with unfavorable outcomes. An unreactive EEG predicted unfavorable outcome with a specificity of 48% (95% CI 40-56), sensitivity of 79% (95% CI 72-85), and positive predictive value (PPV) of 74% (95% CI 67-81). Conversely, a benign EEG (defined as continuous and reactive background activity without seizure, periodic discharges, triphasic waves, or burst suppression) predicted favorable outcome with a specificity of 89% (95% CI 84-94), and a sensitivity of 37% (95% CI 30-45)., Conclusion: The absence of EEG reactivity independently predicts unfavorable outcomes at one year in severe stroke patients requiring mechanical ventilation in the ICU, although its prognostic value remains limited. Conversely, a benign EEG pattern was associated with a favorable outcome., (© 2024. The Author(s).)

Background: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU)., Methods: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors., Results: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors., Conclusions: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03335995., Competing Interests: Disclosures Dr Sonneville reports grants from the French Ministry of Health, outside the submitted work. Dr Mazighi reports compensation from Novo Nordisk for consultant services; compensation from Boerhinger-Ingelheim for consultant services; and compensation from Acticor Biotech for consultant services. Dr Cortier reports employment by Foch. Dr Geri reports compensation from BARD for consultant services. Dr Demoule reports compensation from Agence Européenne Informatique for other services; compensation from Fisher and Paykel Healthcare Limited for other services; compensation from Baxter Healthcare for other services; compensation from Lowenstein for other services; compensation from Getinge for other services; travel support from Lowenstein; compensation from AstraZeneca for other services; compensation from Lungpacer for other services; compensation from Liberate Medical for other services; compensation from Respinor for other services; and compensation from Mindray DS USA Inc. for other services. Dr Timsit reports grants from Merck; compensation from BD Biosciences for consultant services; and grants from Pfizer. The other authors report no conflicts.

Context: Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation., Objectives: We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting., Design, Setting, and Patients: In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients' outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography., Measurements and Main Results: Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1-4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16-0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings., Conclusions: In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following., Competing Interests: Dr. Sonneville received grants from the French Ministry of Health, the French Society of Intensive Care Medicine, and the European Society of Intensive Care Medicine, and lecture fees from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Spontaneous breathing trial (SBT) using a T-piece remains the most frequently performed trial before extubation in ICUs., Research Question: We aimed at determining whether initial SBT using pressure-support ventilation (PSV) could increase successful extubation rates among patients at high risk of extubation failure., Study Design and Methods: Post hoc analysis of a multicenter trial focusing on reintubation in patients at high-risk of extubation failure. The initial SBT was performed using PSV or T-piece according to the physician/center decision. The primary outcome was the proportion of patients successfully extubated 72 hours after initial SBT, that is, extubated after initial SBT and not reintubated within the following 72 hours., Results: Among the 641 patients included in the original study, initial SBT was performed using PSV (7.0 cm H 2 O in median without positive end-expiratory pressure) in 243 patients (38%) and using a T-piece in 398 patients (62%). The proportion of patients successfully extubated 72 hours after initial SBT was 67% (162/243) using PSV and 56% (223/398) using T-piece (absolute difference 10.6%; 95% CI, 2.8 to 28.1; P = .0076). The proportion of patients extubated after initial SBT was 77% (186/283) using PSV and 63% (249/398) using T-piece (P = .0002), whereas reintubation rates within the following 72 hours did not significantly differ (13% vs 10%, respectively; P = .4259). Performing an initial SBT using PSV was independently associated with successful extubation (adjusted OR, 1.60; 95% CI, 1.30 to 2.18; P = .0061)., Interpretation: In patients at high risk of extubation failure in the ICU, performing an initial SBT using PSV may hasten extubation without an increased risk of reintubation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir., Objectives: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir., Patients and Methods: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored., Results: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735)., Conclusions: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Care pathways and long-term outcomes of acute stroke patients requiring mechanical ventilation have not been thoroughly studied., Methods and Results: Stroke Prognosis in Intensive Care (SPICE) is a prospective multicenter cohort study which will be conducted in 34 intensive care units (ICUs) in the Paris, France area. Patients will be eligible if they meet all of the following inclusion criteria: (1) age of 18 years or older; (2) acute stroke (i.e., ischemic stroke, intracranial hemorrhage, or subarachnoid hemorrhage) diagnosed on neuroimaging; (3) ICU admission within 7 days before or after stroke onset; and (4) need for mechanical ventilation for a duration of at least 24 h. Patients will be excluded if they meet any of the following: (1) stroke of traumatic origin; (2) refusal to participate; and (3) privation of liberty by administrative or judicial decision. The primary endpoint is poor functional outcome at 1 year, defined by a score of 4 to 6 on the modified Rankin scale (mRS), indicating severe disability or death. Main secondary endpoints will include decisions to withhold or withdraw care, mRS scores at 3 and 6 months, and health-related quality of life at 1 year., Conclusions: The SPICE multicenter study will investigate 1-year outcomes, ethical issues, as well as care pathways of acute stroke patients requiring invasive ventilation in the ICU. Gathered data will delineate human resources and facilities needs for adequate management. The identification of prognostic factors at the acute phase will help to identify patients who may benefit from prolonged intensive care and rehabilitation., Trial Registration: NCT03335995.

Objectives: To describe the epidemiology and prognostic impact of pneumonia in acute ischemic stroke patients requiring invasive mechanical ventilation., Methods: Retrospective analysis from a prospective multicenter cohort study of critically ill patients with acute ischemic stroke requiring invasive mechanical ventilation at admission. Impact of pneumonia was investigated using Cox regression for 1-year mortality, and competing risk survival models for ICU mortality censored at 30-days., Results: We included 195 patients. Stroke was supratentorial in 62% and 64% of patients had a Glasgow coma scale score <8 on admission. Mortality at day-30 and 1 year were 56%, and 70%, respectively. Post-stroke pneumonia was identified in 78 (40%) patients, of which 46/78 (59%) episodes were present at ICU admission. Post-stroke pneumonia was associated with an increase in 1-year mortality (adjusted HR 1.49, 95%CI [1.01-2.20]). Post-stroke pneumonia was not associated with ICU mortality but was associated with a 1.6-fold increase in ICU length of stay (CSHR 0.62 [0.39-0.99], p = 0.06)., Conclusions: In ischemic stroke patients requiring invasive ventilation, pneumonia occurred in 40% of cases and was associated with a 49% increase in 1-year mortality. Post-stroke pneumonia did not impact day-30 mortality but increased ICU length of stay., (Copyright © 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events, comprising ventilator-associated conditions and infection-related ventilator-associated complications. We assess 1) the current epidemiology of ventilator-associated event, 2) the relationship between ventilator-associated event and ventilator-associated pneumonia, and 3) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration., Design: Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1996-2012)., Patients: Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode, using slightly modified Centers for Disease Control and Prevention definitions., Intervention: None., Measurements and Main Results: Among the 3,028 patients, 2,331 patients (77%) had at least one ventilator-associated condition, and 869 patients (29%) had one infection-related ventilator-associated complication episode. Multiple causes, or the lack of identified cause, were frequent. The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%). Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection-related ventilator-associated complication, respectively. A good correlation was observed between ventilator-associated condition and infection-related ventilator-associated complication episodes, and ventilator-associated pneumonia occurrence: R = 0.69 and 0.82 (p < 0.0001). The median number of days alive without antibiotics and mechanical ventilation at day 28 was significantly higher in patients without any ventilator-associated event (p < 0.05). Ventilator-associated condition and infection-related ventilator-associated complication rates were closely correlated with antibiotic use within each ICU: R = 0.987 and 0.99, respectively (p < 0.0001)., Conclusions: Ventilator-associated event is very common in a population at risk and more importantly highly related to antimicrobial consumption and may serve as surrogate quality indicator for improvement programs.

Purpose: Few data are available about optimal nutrition modalities in mechanically ventilated patients with shock. Our objective was to assess associations linking early nutrition (<48 h after intubation), feeding route and calorie intake to mortality and risk of ventilator-associated pneumonia (VAP) in patients with invasive mechanical ventilation (IMV) and shock., Methods: In the prospective OutcomeRea database, we identified adults with IMV >72 h and shock (arterial systolic pressure <90 mmHg) within 48 h after intubation. A marginal structural Cox model was used to create a pseudo-population in which treatment was unconfounded by subject-specific characteristics., Results: We included 3,032 patients. Early nutrition was associated with lower day-28 mortality [HR 0.89, 95 % confidence interval (CI) 0.81-0.98, P = 0.01] and day-7 mortality (HR 0.76, CI 0.66-0.87, P < 0.001) but not with lower day-7 to day-28 mortality (HR 1.00, CI 0.89-1.12, P = 0.98). Early nutrition increased VAP risk over the 28 days (HR 1.08, CI 1.00-1.17, P = 0.046) and until day 7 (HR 7.17, CI 6.27-8.19, P < 0.001) but decreased VAP risk from days 7 to 28 (HR 0.85, CI 0.78-0.92, P < 0.001). Compared to parenteral feeding, enteral feeding was associated with a slightly increased VAP risk (HR 1.11, CI 1.00-1.22, P = 0.04) but not with mortality. Neither mortality nor VAP risk differed between early calorie intakes of ≥20 and <20 kcal/kg/day., Conclusion: In mechanically ventilated patients with shock, early nutrition was associated with reduced mortality. Neither feeding route nor early calorie intake was associated with mortality. Early nutrition and enteral feeding were associated with increased VAP risk.

Background: Pulmonary edema may alter alveolar bacterial clearance and infectivity. Manipulation of fluid balance aimed at reducing fluid overload may, therefore, influence ventilator-associated pneumonia (VAP) occurrence in intubated patients. The objective of the present study was to assess the impact of a depletive fluid-management strategy on ventilator-associated complication (VAC) and VAP occurrence during weaning from mechanical ventilation., Methods: We used data from the B-type Natriuretic Peptide for the Fluid Management of Weaning (BMW) randomized controlled trial performed in nine ICUs across Europe and America. We compared the cumulative incidence of VAC and VAP between the biomarker-driven, depletive fluid-management group and the usual-care group during the 14 days following randomization, using specific competing-risk methods (the Fine and Gray model)., Results: Among the 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the usual-care group vs 14 (9.2%) in the interventional group (P = .03). From the Fine and Gray model, the probabilities of VAC and VAP occurrence were both significantly reduced with the interventional strategy while adjusting for weaning outcome as a competing event (subhazard ratios [25th-75th percentiles], 0.44 [0.22-0.87], P = .02 and 0.50 [0.25-0.96], P = .03, respectively)., Conclusions: Using proper competing risk analyses, we found that a depletive fluid-management strategy, when initiating the weaning process, has the potential for lowering VAP risk in patients who are mechanically ventilated., Trial Registry: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov.