In-hospital catatonia, delirium, and coma and mortality: Results from the delirium and catatonia prospective cohort investigation.

BACKGROUND: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality. METHODS: We enrolled a convenience cohort of critically ill adults (N = 378) at an academic medical center. We assessed catatonia, delirium, and coma using the Bush-Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. We tested the associations between previous day brain dysfunction state occurrence with in-hospital and one-year mortality using multivariable time-dependent risk models. Additionally, we tested the association between brain dysfunction duration and one-year mortality. RESULTS: Catatonia was not associated with death on the day after diagnosis during hospitalization, and neither previous catatonia occurrence nor duration was associated with one-year mortality. Delirium was not associated with death on any day following diagnosis during hospitalization, and neither previous delirium occurrence nor duration was associated with one-year mortality. The occurrence of coma was associated with death on any day after diagnosis during hospitalization (HR 2.30,CI 1.19-4.44,p = 0.014), as well as through one year following hospital discharge (HR 1.68,CI 1.09-2.59,p = 0.02). CONCLUSIONS: Coma, but neither catatonia nor delirium, was associated with future day in-hospital and one-year mortality. More research is needed to understand catatonia's clinical impact. Delirium results differ from existing literature likely due to cohort demographics and size. Coma results highlight the prognostic significance of suppressed arousal while critically ill.

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.

Association of Incident Delirium With Short-term Mortality in Adults With Critical Illness Receiving Mechanical Ventilation.

Importance: Intensive care unit (ICU)-acquired delirium and/or coma have consequences for patient outcomes. However, contradictory findings exist, especially when considering short-term (ie, in-hospital) mortality and length of stay (LOS). Objective: To assess whether incident delirium, days of delirium, days of coma, and delirium- and coma-free days (DCFDs) are associated with 14-day mortality, in-hospital mortality, and hospital LOS among patients with critical illness receiving mechanical ventilation. Design, Setting, and Participants: This single-center prospective cohort study was conducted in 6 ICUs of a university-affiliated tertiary hospital in Taiwan. A total of 267 delirium-free patients (aged ≥20 years) with critical illness receiving mechanical ventilation were consecutively enrolled from August 14, 2018, to October 1, 2020. Exposures: Participants were assessed daily for the development of delirium and coma status over 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. Main Outcomes and Measures: Mortality rates (14-day and in-hospital) and hospital LOS using electronic health records. Results: Of 267 participants (median [IQR] age, 65.9 [57.4-75.1] years; 171 men [64.0%]; all of Taiwanese ethnicity), 149 patients (55.8%) developed delirium for a median (IQR) of 3.0 (1.0-5.0) days at some point during their first 14 days of ICU stay, and 105 patients (39.3%) had coma episodes also lasting for a median (IQR) of 3.0 (1.0-5.0) days. The 14-day and in-hospital mortality rates were 18.0% (48 patients) and 42.1% (112 of 266 patients [1 patient withdrew from the study]), respectively. The incidence and days of delirium were not associated with either 14-day mortality (incident delirium: adjusted hazard ratio [aHR], 1.37; 95% CI, 0.69-2.72; delirium by day: aHR, 1.00; 95% CI, 0.91-1.10) or in-hospital mortality (incident delirium: aHR, 1.00; 95% CI, 0.64-1.55; delirium by day: aHR, 1.02; 95% CI, 0.97-1.07), whereas days spent in coma were associated with an increased hazard of dying during a given 14-day period (aHR, 1.16; 95% CI, 1.10-1.22) and during hospitalization (aHR, 1.10; 95% CI, 1.06-1.14). The number of DCFDs was a protective factor; for each additional DCFD, the risk of dying during the 14-day period was reduced by 11% (aHR, 0.89; 95% CI, 0.84-0.94), and the risk of dying during hospitalization was reduced by 7% (aHR, 0.93; 95% CI, 0.90-0.97). Incident delirium was associated with longer hospital stays (adjusted ß = 10.80; 95% CI, 0.53-21.08) when compared with no incident delirium. Conclusions and Relevance: In this study, despite prolonged LOS, ICU delirium was not associated with short-term mortality. However, DCFDs were associated with a lower risk of dying, suggesting that future research and intervention implementation should refocus on maximizing DCFDs to potentially improve the survival of patients receiving mechanical ventilation.

The Curing Coma Campaign International Survey on Coma Epidemiology, Evaluation, and Therapy (COME TOGETHER).

BACKGROUND: Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis. METHODS: As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents. RESULTS: The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%). CONCLUSIONS: There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.

Prognostication of patients in coma after cardiac arrest: Public perspectives.

AIM: To elicit preferences for prognostic information, attitudes towards withdrawal of life-sustaining treatment (WLST) and perspectives on acceptable quality of life after post-anoxic coma within the adult general population of Germany, Italy, the Netherlands and the United States of America. METHODS: A web-based survey, consisting of questions on respondent characteristics, perspectives on quality of life, communication of prognostic information, and withdrawal of life-sustaining treatment, was taken by adult respondents recruited from four countries. Statistical analysis included descriptive analysis and chi2-tests for differences between countries. RESULTS: In total, 2012 respondents completed the survey. In each country, at least 84% indicated they would prefer to receive early prognostic information. If a poor outcome was predicted with some uncertainty, 37-54% of the respondents indicated that WLST was not to be allowed. A conscious state with severe physical and cognitive impairments was perceived as acceptable quality of life by 17-44% of the respondents. Clear differences between countries exist, including respondents from the U.S. being more likely to allow WLST than respondents from Germany (OR = 1.99, p < 0.001) or the Netherlands (OR = 1.74, p < 0.001) and preferring to stay alive in a conscious state with severe physical and cognitive impairments more than respondents from Italy (OR = 3.76, p < 0.001), Germany (OR = 2.21, p < 0.001), or the Netherlands (OR = 2.39, p < 0.001). CONCLUSIONS: Over one-third of the respondents considered WLST unacceptable when there is any remaining prognostic uncertainty. Respondents had a more positive perspective on acceptable quality of life after coma than what is currently considered acceptable in medical literature. This indicates a need for a closer look at the practice of WLST based on prognostic information, to ensure responsible use of novel prognostic tests.

Serious adverse events and 30-day hospital readmission rate following elective total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Elective total knee arthroplasty (TKA) is a common surgery which has evolved rapidly. However, there are no recent large systematic reviews of serious adverse event (SAE) rate and 30-day readmission rate (30-dRR) or an indication of whether surgical methods have improved. METHODS: To obtain a pooled estimate of SAE rate and 30-dRR following TKA, we searched Medline, Web of Science, Cochrane Library, and Google Scholar databases. Data were extracted by two authors following PRISMA guidelines. Eligibility criteria were defined prior to a comprehensive search. Studies were eligible if they were published in 2007 or later, described sequelae of TKA with patient N > 1000, and the SAE or 30-dRR rate could be calculated. SAEs included return to operating room, death or coma, venous thromboembolism (VTE), deep infection or sepsis, myocardial infarction, heart failure or cardiac arrest, stroke or cerebrovascular accident, or pneumonia. RESULTS: Of 248 references reviewed, 28 are included, involving 10,153,503 patients; this includes 9,483,387 patients with primary TKA (pTKA), and 670,116 patients with revision TKA (rTKA). For pTKA, the SAE rate was 5.7% (95% CI 4.4-7.2%, I2 = 100%), and the 30-dRR was 4.8% (95% CI 4.3-5.4%, I2 = 100%). For rTKA, the SAE rate was 8.5% (95% CI 8.3-8.7%, I2 = 77%), while the 30-dRR was 7.2% (95% CI 6.4-8.0%, I2 = 81%). Odds of 30-dRR following pTKA were about half that of rTKA (OR 0.57, 95% CI 0.53-0.62%, p < 0.001, I2 = 45%). Of patients who received pTKA, the commonest SAEs were VTE (1.22%; 95% CI 0.83-1.70%) and genitourinary complications including renal insufficiency or renal failure (1.22%; 95% CI 0.83-1.67%). There has been significant improvement in SAE rate and 30-dRR since 2010 (χ2 test < 0.001). CONCLUSIONS: TKA procedures have a relatively low complication rate, and there has been a significant improvement in SAE rate and 30-dRR over the past decade.

Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology COVID-19 Registry. / Encefalopatías y encefalitis durante la infección aguda por SARS-CoV2. Registro de la Sociedad Española de Neurología SEN COVID-19.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. PATIENTS AND METHODS: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. RESULTS: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. CONCLUSIONS: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study.

BACKGROUND: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. METHODS: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. FINDINGS: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. INTERPRETATION: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Impact of Videolaryngoscopy Expertise on First-Attempt Intubation Success in Critically Ill Patients.

OBJECTIVES: The use of a videolaryngoscope in the ICU on the first endotracheal intubation attempt and intubation-related complications is controversial. The objective of this study was to evaluate the first intubation attempt success rate in the ICU with the McGrath MAC videolaryngoscope (Medtronic, Minneapolis, MN) according to the operators' videolaryngoscope expertise and to describe its association with the occurrence of intubation-related complications. DESIGN: Observational study. SETTING: Medical ICU. SUBJECTS: Consecutive endotracheal intubations in critically ill patients. INTERVENTIONS: Systematic use of the videolaryngoscope. MEASUREMENTS AND MAIN OUTCOMES: We enrolled 202 consecutive endotracheal intubations. Overall first-attempt success rate was 126 of 202 (62%). Comorbidities, junior operator, cardiac arrest upon admission, and coma were associated with a lower first-attempt success rate. The first-attempt success rate was less than 50% in novice operators (1-5 previous experiences with videolaryngoscope, independently of airway expertise with direct laryngoscopies) and 87% in expert operators (> 15 previous experiences with videolaryngoscope). Multivariate analysis confirmed the association between specific skill training with videolaryngoscope and the first-attempt success rate. Severe hypoxemia and overall immediate intubation-related complications occurred more frequently in first-attempt failure intubations (24/76, 32%) than in first-attempt success intubations (14/126, 11%) (p < 0.001). CONCLUSIONS: We report for the first time in the critically ill that specific videolaryngoscopy skill training, assessed by the number of previous videolaryngoscopies performed, is an independent factor of first-attempt intubation success. Furthermore, we observed that specific skill training with the McGrath MAC videolaryngoscope was fast. Therefore, future trials evaluating videolaryngoscopy in ICUs should consider the specific skill training of operators in videolaryngoscopy.

Identification of distinct clinical phenotypes in mechanically ventilated patients with acute brain dysfunction using cluster analysis.

Acute brain dysfunction (ABD) is a frequent and severe syndrome occurring in critically ill patients and early identification of high-risk patients is paramount. In the present analysis, we propose a clinically applicable model for early phenotype identification of ABD at the bedside in mechanically ventilated patients, improving the recognition of patients with prolonged ABD.Prospective cohort with 629 mechanically ventilated patients in two medical-surgical intensive care units at academic centers. We applied cluster analysis to identify phenotypes using clinical and biological data. We then tested the association of phenotypes and its respective clinical outcomes. We performed a validation on a new cohort of patients select on subsequent patients admitted to the participants intensive care units.A model with 3 phenotypes best described the study population. A 4-variable model including medical admission, sepsis diagnosis, simplified acute physiologic score II and basal serum C-reactive protein (CRP) accurately classified each phenotype (area under curve 0.82; 95% CI, 0.79-0.86). Phenotype A had the shorter duration of ABD (median, 1 day), while phenotypes B and C had progressively longer duration of ABD (median, 3 and 6 days, respectively; P < .0001). There was an association between the duration of ABD and the baseline CRP levels and simplified acute physiology score II score (sensitivity and specificity of 80%). To increase the sensitivity of the model, we added CRP kinetics. By day 1, a CRP < 1.0 times the initial level was associated with a shorter duration of ABD (specificity 0.98).A model based on widely available clinical variables could provide phenotypes associated with the duration of ABD. Phenotypes with longer duration of ABD (phenotypes B and C) are characterized by more severe inflammation and by significantly worse clinical outcomes.

Epidemiology and Prognosis of Intensive Care Unit-Acquired Bloodstream Infection.

Intensive care unit-acquired bloodstream infections (ICU-BSI) are frequent and are associated with high morbidity and mortality rates. We conducted this study to describe the epidemiology and the prognosis of ICU-BSI in our ICU and to search for factors associated with mortality at 28 days. For this, we retrospectively studied ICU-BSI in the ICU of the Cayenne General Hospital, from January 2013 to June 2019. Intensive care unit-acquired bloodstream infections were diagnosed in 9.5% of admissions (10.3 ICU-BSI/1,000 days). The median delay to the first ICU-BSI was 9 days. The ICU-BSI was primitive in 44% of cases and secondary to ventilator-acquired pneumonia in 25% of cases. The main isolated microorganisms were Enterobacteriaceae in 67.7% of patients. They were extended-spectrum beta-lactamase (ESBL) producers in 27.6% of cases. Initial antibiotic therapy was appropriate in 65.1% of cases. Factors independently associated with ESBL-producing Enterobacteriaceae (ESBL-PE) as the causative microorganism of ICU-BSI were ESBL-PE carriage before ICU-BSI (odds ratio [OR]: 7.273; 95% CI: 2.876-18.392; P < 0.000) and prior exposure to fluoroquinolones (OR: 4.327; 95% CI: 1.120-16.728; P = 0.034). The sensitivity of ESBL-PE carriage to predict ESBL-PE as the causative microorganism of ICU-BSI was 64.9% and specificity was 81.2%. Mortality at 28 days was 20.6% in the general population. Factors independently associated with mortality at day 28 from the occurrence of ICU-BSI were traumatic category of admission (OR: 0.346; 95% CI: 0.134-0.894; P = 0.028) and septic shock on the day of ICU-BSI (OR: 3.317; 95% CI: 1.561-7.050; P = 0.002). Mortality rate was independent of the causative organism.

10 Years of Implementation of the "Glasgow 7" Quality Guarantee Program in the Mendoza Central Hospital: Epidemiology and Evolution of Neurocrytic Patients.

INTRODUCTION: In 2003, the Glasgow 7 Quality Guarantee Program was put into effect in Argentina with the objective of standardizing the donation and transplant process throughout the country, establishing the observation and registration of all neurocritical patients with a score on the Glasgow Coma Scale of 7 of 15 or less admitted to critical beds of selected establishments. MATERIALS AND METHODS: The following study is retrospective, observational, and cohort-based. It was developed in the Central Hospital of Mendoza, in the critical units, including guard, coronary, cardiovascular surgery recovery, and intensive care therapy. The inclusion criteria were admission to the institution with a score on the Glasgow Coma Scale of 7 or less with a structural cause of coma. Data collection was carried out in the national online database SINTRA. RESULTS: From January 1, 2008, to December 31, 2018, 1757 patients were enrolled at the Central Hospital of Mendoza, Argentina with Glasgow scores of 7 or less. The most frequent cause of coma was brain trauma (934 patients; 53%), followed by stroke (614 patients; 35%). Of those who scored 3 of 15 in the GCS upon admission, 65% progressed to brain death, whereas 72% of those who scored 7 were discharged. Of all these patients, 270 became donors, accounting for 43% of all brain deaths, whereas 187 had refused to become organ donors (30.6%). Of the total real donors, 55% were multiorganic (150 donors).

Comparison of Ketamine- Versus Nonketamine-Based Sedation on Delirium and Coma in the Intensive Care Unit.

BACKGROUND: At this time, there are no studies evaluating the risk of delirium or coma with the use of ketamine in mechanically ventilated adult patients, compared to conventional therapies such as propofol or dexmedetomidine. OBJECTIVE: The objective of this study was to evaluate the number of days alive without delirium or coma in mechanically ventilated patients in the intensive care unit receiving analgosedation infusions with ketamine versus without ketamine. METHODS: This was a retrospective cohort study conducted at an academic medical center in the United States. Consecutive mechanically ventilated adult patients between November 2015 and April 2017 were evaluated. Patients were divided into 2 groups based on the sedative regimen used: ketamine based or nonketamine based. The primary outcome was the number of days alive without delirium or coma. The secondary outcomes were incidence of delirium, incidence of coma, and ventilator-free days at day 28. RESULTS: The study cohort consisted of 79 patients, of which 39 received ketamine- and 40 received nonketamine-based sedation. The number of days alive without delirium or coma was 6 days (interquartile range [IQR]: 2-9 days) with ketamine and 4 days (IQR: 3-7 days) with nonketamine (P = .351). Delirium occurred in 29 (74%) of 39 patients with ketamine and 34 (85%) of 40 patients with nonketamine (P = .274). Coma occurred in 16 (41%) of 39 patients with ketamine and 6 (15%) of 40 patients with nonketamine (P = .013). The median ventilator-free days were 13 days (IQR: 0-23 days) with ketamine and 21 days (0-25 days) with nonketamine (P = .229). CONCLUSIONS: Sustained ketamine-based sedation in mechanically ventilated patients may be associated with a higher rate of observed coma but similar delirium- and coma-free days compared nonketamine-based regimens.

Biomarkers of Delirium Duration and Delirium Severity in the ICU.

OBJECTIVES: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. DESIGN: Observational study. SETTING: Three Indianapolis hospitals. PATIENTS: Three-hundred twenty-one critically ill delirious patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100ß lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100ß levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. CONCLUSIONS: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.

Causes of brain dysfunction in acute coma: a cohort study of 1027 patients in the emergency department.

BACKGROUND: Coma of unknown etiology (CUE) is a major challenge in emergency medicine. CUE is caused by a wide variety of pathologies that require immediate and targeted treatment. However, there is little empirical data guiding rational and efficient management of CUE. We present a detailed investigation on the causes of CUE in patients presenting to the ED of a university hospital. METHODS: One thousand twenty-seven consecutive ED patients with CUE were enrolled. Applying a retrospective observational study design, we analyzed all clinical, laboratory and imaging findings resulting from a standardized emergency work-up of each patient. Following a predefined protocol, we identified main and accessory coma-explaining pathologies and related these with (i.a.) GCS and in-hospital mortality. RESULTS: On admission, 854 of the 1027 patients presented with persistent CUE. Their main diagnoses were classified into acute primary brain lesions (39%), primary brain pathologies without acute lesions (25%) and pathologies that affected the brain secondarily (36%). In-hospital mortality associated with persistent CUE amounted to 25%. 33% of patients with persistent CUE presented with more than one coma-explaining pathology. In 173 of the 1027 patients, CUE had already resolved on admission. However, these patients showed a spectrum of main diagnoses similar to persistent CUE and a significant in-hospital mortality of 5%. CONCLUSION: The data from our cohort show that the spectrum of conditions underlying CUE is broad and may include a surprisingly high number of coincidences of multiple coma-explaining pathologies. This finding has not been reported so far. Thus, significant pathologies may be masked by initial findings and only appear at the end of the diagnostic work-up. Furthermore, even transient CUE showed a significant mortality, thus rendering GCS cutoffs for selection of high- and low-risk patients questionable. Taken together, our data advocate for a standardized diagnostic work-up that should be triggered by the emergency symptom CUE and not by any suspected diagnosis. This standardized routine should always be completed - even when initial coma-explaining diagnoses may seem evident.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Electroencephalographic reactivity as predictor of neurological outcome in postanoxic coma: A multicenter prospective cohort study.

OBJECTIVE: Outcome prediction in patients after cardiac arrest (CA) is challenging. Electroencephalographic reactivity (EEG-R) might be a reliable predictor. We aimed to determine the prognostic value of EEG-R using a standardized assessment. METHODS: In a prospective cohort study, a strictly defined EEG-R assessment protocol was executed twice per day in adult patients after CA. EEG-R was classified as present or absent by 3 EEG readers, blinded to patient characteristics. Uncertain reactivity was classified as present. Primary outcome was best Cerebral Performance Category score (CPC) in 6 months after CA, dichotomized as good (CPC = 1-2) or poor (CPC = 3-5). EEG-R was considered reliable for predicting poor outcome if specificity was ≥95%. For good outcome prediction, a specificity of ≥80% was used. Added value of EEG-R was the increase in specificity when combined with EEG background, neurological examination, and somatosensory evoked potentials (SSEPs). RESULTS: Of 160 patients enrolled, 149 were available for analyses. Absence of EEG-R for poor outcome prediction had a specificity of 82% and a sensitivity of 73%. For good outcome prediction, specificity was 73% and sensitivity 82%. Specificity for poor outcome prediction increased from 98% to 99% when EEG-R was added to a multimodal model. For good outcome prediction, specificity increased from 70% to 89%. INTERPRETATION: EEG-R testing in itself is not sufficiently reliable for outcome prediction in patients after CA. For poor outcome prediction, it has no substantial added value to EEG background, neurological examination, and SSEPs. For prediction of good outcome, EEG-R seems to have added value. ANN NEUROL 2019.

Death after awakening from post-anoxic coma: the "Best CPC" project.

BACKGROUND: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. METHODS: Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified. RESULTS: From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 [2.7%] vs. 114/1649 [6.9%]; p < 0.001). Median times from CA to awakening and from awakening to death were 2 [1-5] and 9 [3-18] days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome. CONCLUSIONS: In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.

Changes of clinical symptoms in patients with new psychoactive substance (NPS)-related disorders from fiscal year 2012 to 2014: A study in hospitals specializing in the treatment of addiction.

AIMS: The use of new psychoactive substances (NPS) has become increasingly widespread over the last decade, in Japan and internationally. NPS are associated with a range of increasingly serious clinical, public, and social issues. Political measures to ameliorate the effects of NPS in Japan have focused on tightening regulation rather than establishing treatment methods. The current study sought to compare the neuropsychiatric symptoms of patients with NPS-related disorders across several years. We examined patients who attended specialized hospitals for treating addiction, to elucidate the impacts of legal measures to control NPS. METHODS: Subjects (n = 864) were patients with NPS-related disorders who received medical treatment at eight specialized hospitals for treating addiction in Japan between April 2012 and March 2015. Clinical information was collected retrospectively from medical records. RESULTS: Among psychiatric symptoms, the ratio of hallucinations/delusions decreased over time across 3 years of study (first year vs second year vs third year: 40.1% vs 30.9% vs 31.7%, P = 0.037). Among neurological symptoms, the ratio of coma/syncope increased over the 3-year period (7.8% vs 11.0% vs 17.0%, P = 0.002), as did the ratio of convulsions (2.8% vs 4.3% vs 9.7%, P = 0.001). CONCLUSION: The symptoms associated with NPS were primarily psychiatric in the first year, while the prevalence of neurological symptoms increased each year. The risk of death and the severity of symptoms were greater in the third year compared with the first year, as regulation of NPS increased.