Multicentric investigations of the role in the disease severity of accelerated phospholipid changes in COVID-19 patient airway.

CONTEXT: The changes in host membrane phospholipids are crucial in airway infection pathogenesis. Phospholipase A2 hydrolyzes host cell membranes, producing lyso-phospholipids and free fatty acids, including arachidonic acid (AA), which contributes significantly to lung inflammation. AIM: Follow these changes and their evolution from day 1, day 3 to day 7 in airway aspirates of 89 patients with COVID-19-associated acute respiratory distress syndrome and examine whether they correlate with the severity of the disease. The patients were recruited in three French intensive care units. The analysis was conducted from admission to the intensive care unit until the end of the first week of mechanical ventilation. RESULTS: In the airway aspirates, we found significant increases in the levels of host cell phospholipids, including phosphatidyl-serine and phosphatidyl-ethanolamine, and their corresponding lyso-phospholipids. This was accompanied by increased levels of AA and its inflammatory metabolite prostaglandin E2 (PGE2). Additionally, enhanced levels of ceramides, sphingomyelin, and free cholesterol were observed in these aspirates. These lipids are known to be involved in cell death and/or apoptosis, whereas free cholesterol plays a role in virus entry and replication in host cells. However, there were no significant changes in the levels of dipalmitoyl-phosphatidylcholine, the major surfactant phospholipid. A correlation analysis revealed an association between mortality risk and levels of AA and PGE2, as well as host cell phospholipids. CONCLUSION: Our findings indicate a correlation between heightened cellular phospholipid modifications and variations in AA and PGE2 with the severity of the disease in patients. Nevertheless, there is no indication of surfactant alteration in the initial phases of the illness.

Respiratory Infection Triggering Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Background: Data are scarce on respiratory infections during severe acute exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to investigate respiratory infection patterns in the intensive care unit (ICU) and identify variables associated with infection type and patient outcome. Methods: A retrospective, single-centre cohort study. All patients admitted (2015-2021) to our ICU for severe acute exacerbation of COPD were included. Logistic multivariable regression analysis was performed to predict factors associated with infection and assess the association between infection and outcome. Results: We included 473 patients: 288 (60.9%) had respiratory infection and 139 (29.4%) required invasive mechanical ventilation. Eighty-nine (30.9%) had viral, 81 (28.1%) bacterial, 34 (11.8%) mixed, and 84 (29.2%) undocumented infections. Forty-seven (9.9%) patients died in the ICU and 67 (14.2%) in hospital. Factors associated with respiratory infection were temperature (odds ratio [+1°C]=1.43, P=0.008) and blood neutrophils (1.07, P=0.002). Male sex (2.21, P=0.02) and blood neutrophils were associated with bacterial infection (1.06, P=0.04). In a multivariable analysis, pneumonia (cause-specific hazard=1.75, P=0.005), respiratory rate (1.17, P=0.04), arterial partial pressure of carbon-dioxide (1.08, P=0.04), and lactate (1.14, P=0.02) were associated with the need for invasive MV. Age (1.03, P=0.03), immunodeficiency (1.96, P=0.02), and altered performance status (1.78, P=0.002) were associated with hospital mortality. Conclusions: Respiratory infections, 39.9% of which were bacterial, were the main cause of severe acute exacerbation of COPD. Body temperature and blood neutrophils were single markers of infection. Pneumonia was associated with the need for invasive mechanical ventilation but not with hospital mortality, as opposed to age, immunodeficiency, and altered performance status.

Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial.

INTRODUCTION: Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever. METHODS AND ANALYSIS: SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients. ETHICS AND DISSEMINATION: The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04494074.

Patient-reported outcomes in adults after status epilepticus: A systematic review.

Impairments after status epilepticus have generally been assessed by physicians, using generic scales. Patient-reported outcomes (PROs) directly reflect each patient's experience and are therefore recommended to improve patient-centered care. The objective of this systematic review was to compile the available information on patient-reported outcomes of adults after status epilepticus. We used Medical Subject Headings terms to search PubMed, Embase, and the Cochrane Library from database inception to February 2023. We excluded reviews, case reports, abstract-only reports, editorials, and publications in languages other than English or French. Studies reporting PROs in adults after SE were eligible. Bias in included studies was assessed using the Newcastle-Ottawa Scale (NOS). Given the heterogeneity in assessment tools and outcomes, most of the results are presented separately for each included study. Only three studies met our criteria. All used an observational cohort design. Two were retrospective and one prospective. Of the 141 patients (76 males and 65 females, mean age 43-63 years), 105 (74.4 %) had a history of epilepsy before status epilepticus. The studies used four epilepsy-specific and five generic tools to assess five patient-reported outcomes: quality of life (n = 141), mental health (depression, n = 81, or anxiety, n = 49), physical health including fatigue (n = 130), return to work (n = 49), and side effects of antiepileptic drugs (n = 81). A single study (n = 81) was of good methodological quality. Health-related quality of life (HRQOL) and mental health were the most extensively studied outcomes, and both were impaired. HRQOL scores ranged from 41.7 ±â€¯11.5 to 48.3 ±â€¯24.5. The prevalence of depression and anxiety varied from 30 % to 36 %, and from 22 % to 62 %, respectively. However, data were not collected before the status epilepticus episode, and the possible impact of this last on the outcomes cannot therefore be assessed. Information on PROs of adults after status epilepticus is extremely scant. Patient-reported outcomes should be collected more widely in adults after status epilepticus.

Clinician-Reported Physical and Cognitive Impairments After Convulsive Status Epilepticus: Post Hoc Study of a Randomized Controlled Trial.

BACKGROUND: Clinician-reported outcome (ClinRO) measures are emerging as useful contributors to assessments of treatment benefits. The objective of this study was to collect ClinRO measures of physical and cognitive impairments after convulsive status epilepticus (CSE) requiring intensive care unit admission. METHODS: We conducted a post hoc analysis of the data from HYBERNATUS, a multicenter open-label controlled trial that randomized 270 critically ill patients with CSE requiring mechanical ventilation in 11 French intensive care units to therapeutic hypothermia (32-34 °C for 24 h) plus standard care or standard care alone. We included all patients who attended a day 90 in-person neurologist visit with measurement of the functional independence measure (FIM) score (range from 18 [total assistance] to 126 [total independence]), Mini-Mental State Examination (MMSE) score (range 0-30), and Glasgow outcome scale (GOS) score (1, death; 2, vegetative state; 3, severe disability; 4, moderate disability; and 5, mild or no disability). These three scores were compared across groups defined by several patient and CSE characteristics. RESULTS: Of 229 patients with GOS scores ≥ 3 on day 90 (male sex, 58.2%; median age, 56 years [47-67]), 67 (29%) attended an in-person neurologist visit. Twenty-nine (43%) patients had a previous history of epilepsy, and 16 (24%) patients had a primary brain insult. CSE was refractory in 22 (33%) patients. On day 90 after CSE onset, median FIM and MMSE scores were 121 (112-125) and 26.0 (24.0-28.8), respectively. The GOS score was 3 in 16 (33.8%) patients, 4 in 9 (13.4%) patients, and 5 in 42 (62.7%) patients. Worse GOS score values were significantly associated with worse FIM and MMSE scores. CONCLUSIONS: In patients attending the in-person neurologist visit on day 90 after CSE onset, ClinRO measures indicated that the main impairments were cognitive. FIM and MMSE scores were associated with GOS scores. Further studies are needed to evaluate the possible impact of neuroprotective and rehabilitation strategies on disability and cognitive impairments in survivors of CSE. Clinical trial registration NCT01359332.

Prospective comparison of prognostic scores for prediction of outcome after out-of-hospital cardiac arrest: results of the AfterROSC1 multicentric study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. METHODS: We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. RESULTS: During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76-0.83], whereas AUROCs from other scores varied from 0.79 [0.75-0.83] to 0.88 [0.86-0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. CONCLUSIONS: In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891.

Long-term heart function in cardiac-arrest survivors.

Purpose: To assess outcomes and predictors of long-term myocardial dysfunction after cardiac arrest (CA) of cardiac origin. Methods: We retrospectively included consecutive, single-center, prospective-registry patients who survived to hospital discharge for adult out-of-hospital and in-hospital CA of cardiac origin in 2005-2019. The primary objective was to collect the 1-year New York Heart Association Functional Class (NYHA-FC) and major adverse cardiovascular events (MACE). Results: Of 135 patients, 94 (72%) had their NYHA-FC determined after 1 year, including 75 (75/94, 80%) who were I, 17 (17/94, 18%) II, 2 (2/94, 2%) III, and none IV. The echocardiographic left ventricular ejection fraction was abnormal in 87/130 (67%) patients on day 1, 52/123 (42%) at hospital discharge, and 17/52 (33%) at 6 months. During the median follow-up of 796 [283-1975] days, 38/119 (32%) patients experienced a MACE. These events were predominantly related to acute heart failure (13/38) or ischemic cardiovascular events (16/38), with acute coronary syndrome being the most prevalent among them (8/16). Pre-CA cardiovascular disease was a risk factor for 1-year NYHA-FC > I (P = 0.01), absence of bystander cardiopulmonary resuscitation was significantly associated with NYHA-FC > I at 1 year. Conclusion: Most patients had no heart-failure symptoms a year after adult out-of hospital or in-hospital CA of cardiac origin, and absence of bystander cardiopulmonary resuscitation was the only treatment component significantly associated with NYHA-FC > I at 1 year. Nearly a third experienced MACE and the most common types of MACE were ischemic cardiovascular events and acute heart failure. Early left ventricular dysfunction recovered within 6 months in half the patients with available values.

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

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.

Unchanged Characteristics and Survival among Critically Ill COVID-19 Patients during First, Second, and Third Waves: A Prospective Observational Cohort.

BACKGROUND: This study was carried out to compare characteristics and outcomes in patients with acute respiratory failure related to COVID-19 during first, second, and third waves. METHODS: We included consecutive adults admitted to the intensive care unit between March 2020 and July 2021. We compared three groups defined by the epidemic intake phase: waves 1 (W1), 2 (W2), and 3 (W3). RESULTS: We included 289 patients. Two hundred and eight (72%) patients were men with a median age of 63 years (IQR: 54-72), of whom 68 (23.6%) died in hospital. High-flow nasal oxygen (HFNO) was inversely associated with the need for invasive mechanical ventilation (MV) in multivariate analysis (p = 0.003) but not dexamethasone (p = 0.25). The day-90 mortality rate did not vary from W1 (27.4%) to W2 (23.9%) and W3 (22%), p = 0.67. By multivariate analysis, older age (odds ratio [OR]: 0.94/year, p < 0.001), immunodeficiency (OR: 0.33, p = 0.04), acute kidney injury (OR: 0.26, p < 0.001), and invasive MV (OR: 0.13, p < 0.001) were inversely associated with higher day-90 survival as opposed to the use of intermediate heparin thromboprophylaxis dose (OR: 3.21, p = 0.006). HFNO use and dexamethasone were not associated with higher day-90 survival (p = 0.24 and p = 0.56, respectively). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, survival did not change between first, second, and third waves while the use of invasive MV decreased. HFNO or intravenous steroids were not associated with better outcomes, whereas the use of intermediate dose of heparin for thromboprophylaxis was associated with higher day-90 survival. Larger multicentric studies are needed to confirm our findings.

Association between the Cardiac Arrest Hospital Prognosis (CAHP) score and reason for death after successfully resuscitated cardiac arrest.

Individualize treatment after cardiac arrest could potentiate future clinical trials selecting patients most likely to benefit from interventions. We assessed the Cardiac Arrest Hospital Prognosis (CAHP) score for predicting reason for death to improve patient selection. Consecutive patients in two cardiac arrest databases were studied between 2007 and 2017. Reasons for death were categorised as refractory post-resuscitation shock (RPRS), hypoxic-ischaemic brain injury (HIBI) and other. We computed the CAHP score, which relies on age, location at OHCA, initial cardiac rhythm, no-flow and low-flow times, arterial pH, and epinephrine dose. We performed survival analyses using the Kaplan-Meier failure function and competing-risks regression. Of 1543 included patients, 987 (64%) died in the ICU, 447 (45%) from HIBI, 291 (30%) from RPRS, and 247 (25%) from other reasons. The proportion of deaths from RPRS increased with CAHP score deciles; the sub-hazard ratio for the tenth decile was 30.8 (9.8-96.5; p < 0.0001). The sub-hazard ratio of the CAHP score for predicting death from HIBI was below 5. Higher CAHP score values were associated with a higher proportion of deaths due to RPRS. This score may help to constitute uniform patient populations likely to benefit from interventions assessed in future randomised controlled trials.

Outcomes in Patients With COVID-19 With Acute Encephalopathy and Coma: An International Prospective Study.

BACKGROUND AND OBJECTIVES: To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes. METHODS: Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability). RESULTS: Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83). DISCUSSION: In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology. TRIAL REGISTRATION INFORMATION: The study is registered with ClinicalTrials.gov, number NCT04320472.

An Esophagopleural Fistula Related to Cardiopulmonary Resuscitation.

We describe a previously unreported and potentially fatal complication of esophageal perforation following cardiopulmonary resuscitation in a 74-year-old man with cardiac arrest subsequent to ventricular tachycardia caused by ischemic heart disease. We discuss the importance of searching for severe traumatic complications. This description emphasizes presenting complaints, early recognition, and management strategies of such cases (Level of Difficulty: Intermediate).

Predicting neurological outcome after cardiac arrest by combining computational parameters extracted from standard and deviant responses from auditory evoked potentials.

Background: Despite multimodal assessment (clinical examination, biology, brain MRI, electroencephalography, somatosensory evoked potentials, mismatch negativity at auditory evoked potentials), coma prognostic evaluation remains challenging. Methods: We present here a method to predict the return to consciousness and good neurological outcome based on classification of auditory evoked potentials obtained during an oddball paradigm. Data from event-related potentials (ERPs) were recorded noninvasively using four surface electroencephalography (EEG) electrodes in a cohort of 29 post-cardiac arrest comatose patients (between day 3 and day 6 following admission). We extracted retrospectively several EEG features (standard deviation and similarity for standard auditory stimulations and number of extrema and oscillations for deviant auditory stimulations) from the time responses in a window of few hundreds of milliseconds. The responses to the standard and the deviant auditory stimulations were thus considered independently. By combining these features, based on machine learning, we built a two-dimensional map to evaluate possible group clustering. Results: Analysis in two-dimensions of the present data revealed two separated clusters of patients with good versus bad neurological outcome. When favoring the highest specificity of our mathematical algorithms (0.91), we found a sensitivity of 0.83 and an accuracy of 0.90, maintained when calculation was performed using data from only one central electrode. Using Gaussian, K-neighborhood and SVM classifiers, we could predict the neurological outcome of post-anoxic comatose patients, the validity of the method being tested by a cross-validation procedure. Moreover, the same results were obtained with one single electrode (Cz). Conclusion: statistics of standard and deviant responses considered separately provide complementary and confirmatory predictions of the outcome of anoxic comatose patients, better assessed when combining these features on a two-dimensional statistical map. The benefit of this method compared to classical EEG and ERP predictors should be tested in a large prospective cohort. If validated, this method could provide an alternative tool to intensivists, to better evaluate neurological outcome and improve patient management, without neurophysiologist assistance.

Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial.

BACKGROUND: Patients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.

Management and outcomes of critically ill adult patients with convulsive status epilepticus and preadmission functional impairments.

OBJECTIVE: Functional status is among the criteria relevant to decisions about intensive care unit (ICU) admission and level of care. Our main objective was to describe the characteristics and outcomes of adult patients requiring ICU admission for Convulsive Status Epilepticus (CSE) according to whether their functional status was previously impaired. METHODS: We retrospectively analyzed data from consecutive adults who were admitted to two French ICUs for CSE between 2005 and 2018 and then included them retrospectively in the Ictal Registry. Pre-existing functional impairment was defined as a Glasgow Outcome Scale (GOS) score of 3 before admission. The primary outcome measure was a loss of ≥1 GOS score point at 1 year. Multivariate analysis was used to identify factors associated with this measure. RESULTS: The 206 women and 293 men had a median age of 59 years [47-70 years]. The preadmission GOS score was 3 in 56 (11.2%) patients and 4 or 5 in 443 patients. Compared to the GOS-4/5 group, the GOS-3 group was characterized by a higher frequency of treatment-limitation decisions (35.7% vs. 12%, P < 0.0001), similar ICU mortality (19.6 vs. 13.1, P = 0.22), higher 1-year mortality (39.3% vs. 25.6%, P < 0.01), and a similar proportion of patients with no worsening of the GOS score at 1 year (42.9 vs. 44.1, P = 0.89). By multivariate analysis, not achieving a favorable 1-year outcome was associated with age above 59 years (OR, 2.36; 95%CI, 1.55-3.58, P < 0.0001), preexisting ultimately fatal comorbidity (OR, 2.92; 95%CI, 1.71-4.98, P = 0.0001), refractory CSE (OR, 2.19; 95%CI, 1.43-3.36, P = 0.0004), cerebral insult as the cause of CSE (OR, 2.75; 95%CI, 1.75-4.27, P < 0.0001), and Logistic Organ Dysfunction score ≥ 3 at ICU admission (OR, 2.08; 95%CI, 1.37-3.15, P = 0.0006). A preadmission GOS score of 3 was not associated with a functional decline during the first year (OR, 0.61; 95%CI, 0.31-1.22, P = 0.17). SIGNIFICANCE: Preadmission functional status in adult patients with CSE is not independently associated with a functional decline during the first postadmission year. This finding may help physicians make ICU admission decisions and adult patients write advance directives. STUDY REGISTRATION: #NCT03457831.

Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry.

OBJECTIVES: To describe early electrocardiogram (ECG) abnormalities after status epilepticus (SE) and evaluate their association with 90-day neurological outcomes. DESIGN: Retrospective analysis of a multicenter, national prospective registry between February 2018 and June 2020. SETTING: Sixteen ICUs in France, IctalGroup Research Network. PATIENTS: Adults with available ECG performed less than or equal to 24 hours after the onset of SE and less than or equal to 12 hours after its resolution. INTERVENTION: Double-blinded review of all ECGs was performed by two independent cardiologists. ECGs were categorized as normal/abnormal and then with minor/major early ECG abnormalities according to the Novacode ECG Classification system. MEASUREMENTS AND MAIN RESULTS: Among 155 critically ill patients with SE, early ECG abnormalities were encountered in 145 (93.5%), categorized as major in 91 of 145 (62.8%). In addition to sinus tachycardia, the main abnormalities were in the ST segment (elevation [16.6%] or depression [17.9%]) or negative T waves (42.1%). Major early ECG abnormalities were significantly associated with respiratory distress and sinus tachycardia at the scene and hyperlactatemia at ICU admission. By multivariable analysis, three variables were significantly associated with 90-day poor outcome: age, preexisting ultimately fatal comorbidity, and cerebral insult as the cause of SE. Early major ECG abnormalities were not independently associated with 90-day functional outcome. CONCLUSIONS: In our study, early ECG abnormalities in the acute phase of SE were frequent, often unrecognized and were associated with clinical and biological stigma of hypoxemia. Although they were not independently associated with 90-day functional outcome, ECG changes at the early stage of SE should be systematically evaluated. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03457831 .