Autoimmune and inflammatory neurological disorders in the intensive care unit.

PURPOSE OF REVIEW: The present review summarizes the diagnostic approach to autoimmune encephalitis (AE) in the intensive care unit (ICU) and provides practical guidance on therapeutic management. RECENT FINDINGS: Autoimmune encephalitis represents a group of immune-mediated brain diseases associated with antibodies that are pathogenic against central nervous system proteins. Recent findings suggests that the diagnosis of AE requires a multidisciplinary approach including appropriate recognition of common clinical syndromes, brain imaging and electroencephalography to confirm focal pathology, and cerebrospinal fluid and serum tests to rule out common brain infections, and to detect autoantibodies. ICU admission may be necessary at AE onset because of altered mental status, refractory seizures, and/or dysautonomia. Early management in ICU includes prompt initiation of immunotherapy, detection and treatment of seizures, and supportive care with neuromonitoring. In parallel, screening for neoplasm should be systematically performed. Despite severe presentation, epidemiological studies suggest that functional recovery is likely under appropriate therapy, even after prolonged ICU stays. CONCLUSION: AE and related disorders are increasingly recognized in the ICU population. Critical care physicians should be aware of these conditions and consider them early in the differential diagnosis of patients presenting with unexplained encephalopathy. A multidisciplinary approach is mandatory for diagnosis, ICU management, specific therapy, and prognostication.

Prognostic value of early EEG abnormalities in severe stroke patients requiring mechanical ventilation: a pre-planned analysis of the SPICE prospective multicenter study.

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.

One-Year Mental and Physical Health Assessment in Survivors after Extracorporeal Membrane Oxygenation for COVID-19-related Acute Respiratory Distress Syndrome.

Rationale: Long-term outcomes of patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome treated with extracorporeal membrane oxygenation (ECMO) are unknown. Objectives: To assess physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorder and quality of life at 6 and 12 months after ECMO onset. Methods: Multicenter, prospective study in patients who received ECMO for COVID-19 acute respiratory distress syndrome from March to June 2020 and survived hospital discharge. Measurements and Main Results: Of 80 eligible patients, 62 were enrolled in seven French ICUs. ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive, but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at 1 year. Pulmonary function tests were almost normal at 6 months, except for DlCO, which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared with patients receiving ECMO who did not have COVID-19. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms, and 21/50 (42%) were at risk for post-traumatic stress disorders. Conclusions: Despite the partial recovery of the lung function tests at 1 year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of patients receiving ECMO who did not have COVID-19, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation.

Femoro-axillary versus femoro-femoral veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock: A monocentric retrospective study.

RATIONALE: For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF. METHODS: Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis. RESULTS: VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest (n = 77 (14%)) and those supported by multiple VA-ECMO (n = 92, (17%)) were excluded. Out of the 333 patients studied (n = 209 Vf-Aa; n = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, n = 109), dilated cardiomyopathy (20%, n = 66), post-cardiac transplantation (15%, n = 50), acute myocardial infarction (14%, n = 46) and other etiologies (18%, n = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% (n = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation. CONCLUSION: Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.

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.

Neurological complications of critically ill COVID-19 patients.

PURPOSE OF REVIEW: COVID-19 and systemic critical illness are both associated with neurological complications. We provide an update on the diagnosis and critical care management of adult patients with neurological complications of COVID-19. RECENT FINDINGS: Large prospective multicentre studies conducted in the adult population over the last 18 months improved current knowledge on severe neurological complications of COVID-19. In COVID-19 patients presenting with neurological symptoms, a multimodal diagnostic workup (including CSF analysis, brain MRI, and EEG) may identify different syndromes associated with distinct trajectories and outcomes. Acute encephalopathy, which represents the most common neurological presentation of COVID-19, is associated with hypoxemia, toxic/metabolic derangements, and systemic inflammation. Other less frequent complications include cerebrovascular events, acute inflammatory syndromes, and seizures, which may be linked to more complex pathophysiological processes. Neuroimaging findings include infarction, haemorrhagic stroke, encephalitis, microhaemorrhages and leukoencephalopathy. In the absence of structural brain injury, prolonged unconsciousness is usually fully reversible, warranting a cautious approach for prognostication. Advanced quantitative MRI may provide useful insights into the extent and pathophysiology of the consequences of COVID-19 infection including atrophy and functional imaging changes in the chronic phase. SUMMARY: Our review highlights the importance of a multimodal approach for the accurate diagnosis and management of complications of COVID-19, both at the acute phase and in the long-term.

Severe meningoencephalitis: epidemiology and outcomes.

PURPOSE OF REVIEW: This article aims to provide an updated review on the epidemiology and outcomes of severe meningoencephalitis. RECENT FINDINGS: Meningoencephalitis is a critical medical condition characterized by inflammation in both the meninges and brain parenchyma. Bacterial, viral, or fungal infections are common causes, although noninfectious factors, such as autoimmune causes, can also contribute. In patients requiring intensive care, meningoencephalitis is associated with a severe prognosis, including mortality rates ranging from 11 to 25% and functional disability in 15-25% of survivors. Recent multicenter studies have identified several parameters linked to poor outcomes, including older age, immunocompromised status, focal neurologic signs, abnormal brain imaging, and delayed administration of antimicrobials. The use of new multiplex PCR techniques for diagnosis has generated debate based on recent data. Investigation is still needed to determine the effectiveness of adjunctive therapies, including seizure prophylaxis, and adjunctive steroids for nonbacterial causes. SUMMARY: Recent multicenter studies have enhanced our understanding of the current epidemiology and outcomes of severe meningoencephalitis in adult patients.

The spectrum of sepsis-associated encephalopathy: a clinical perspective.

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient's mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients.

Skin biopsy in adult patients with meningococcal purpura fulminans: a multicenter retrospective cohort study.

BACKGROUND: Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. METHODS: A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. RESULTS: Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. CONCLUSIONS: Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes. CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Brain abscess in immunocompetent patients: recent findings.

PURPOSE OF REVIEW: We conducted a systematic review of the literature to update findings on the epidemiology and the management of cerebral abscesses in immunocompetent patients. RECENT FINDINGS: Observational studies suggest that the overall prognosis has improved over the last decades but mortality rates remain high. Several parameters may contribute to a better prognosis, including the identification of common risk factors for brain abscess, the systematic use of brain MRI at diagnosis, the implementation of appropriate neurosurgical and microbiological techniques for diagnosis, the optimization of the antibacterial treatment based on epidemiology and pharmacokinetic/pharmacodynamic studies, and a long-term follow-up for detection of secondary complications. Outcome research on brain abscess is mainly based on observational studies. Randomized controlled trials have yet to be performed to identify clinically relevant interventions associated with improved patient-centered outcomes. SUMMARY: Our review highlights the importance of a multidisciplinary approach to optimize brain abscess management both at the acute phase and in the long-term. Randomized controlled studies are urgently needed to identify interventions associated with improved outcomes.

Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact.

OBJECTIVES: To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. DESIGN: Retrospective multicenter study from 2007 to 2017. SETTING: Forty-seven French ICUs. PATIENTS: Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). CONCLUSIONS: In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation.

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU. DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020). SETTING: Two academic hospital ICUs, Paris, France. PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge. INTERVENTIONS: Follow-up by face-to-face neurologic consultation. MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome. CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

Critical care management of meningitis and encephalitis: an update.

PURPOSE OF REVIEW: Meningitis and encephalitis represent severe neurological syndromes associated with encephalopathy, seizures, focal deficits, and neurological sequelae in survivors. We update on the critical care management of adult patients with severe meningitis and encephalitis. RECENT FINDINGS: Large multicenter studies conducted in the adult population improved current knowledge on the epidemiology and outcomes of patients with severe meningitis and encephalitis. An early multimodal diagnostic workup (including CSF analysis, brain MRI, EEG, and serum studies) is mandatory for diagnosis and prognostication in those patients.New diagnostic methods, including multiplex PCR and next-generation sequencing techniques, allow for a faster differential diagnosis of infectious causes that may require specific antimicrobial therapy. Autoimmune causes of encephalitis, which may require urgent immunotherapy, are also increasingly recognized in the ICU setting. Although observational data suggest that early combined immunotherapy is associated with better neurological outcomes in patients with autoimmune encephalitis, randomized clinical trials have yet to be performed. SUMMARY: Our review highlights the importance of an early multimodal approach for diagnosing severe meningitis and encephalitis. Randomized clinical trials are needed to identify pharmacological interventions that may improve patients' outcomes.

Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults.

BACKGROUND: The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic pathogens (such as Enterococcus) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking. METHODS: We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90. RESULTS: From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2 (SAPS 2) at admission was 33 [24; 50] and a Sequential Organ Failure Assessment score (SOFA score) at 6 [4; 8]. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of Enterococcus spp., Staphylococcus aureus and Candida spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in Enterococcus spp., S. aureus and Candida spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death. CONCLUSION: We found that elevated oropharyngeal/intestinal Enterococcus spp. S. aureus and Candida spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

BACKGROUND: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. METHODS: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. RESULTS: Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45-2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06-1.46). CONCLUSIONS: Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration ( NCT01367093 ; Registered 6 June 2011).

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

Association of Standard Electroencephalography Findings With Mortality and Command Following in Mechanically Ventilated Patients Remaining Unresponsive After Sedation Interruption.

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.