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.

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 .

Withholding and withdrawal of life-sustaining therapy in 8569 trauma patients: A multicentre, analytical registry study.

BACKGROUND: This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision. DESIGN: This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included. RESULTS: Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age: 62 versus 36, P  < 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P  < 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death. CONCLUSION: Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.

Multicentre observational status-epilepticus registry: protocol for ICTAL.

INTRODUCTION: Status epilepticus (SE) is a common life-threatening neurological emergency that can cause long-term impairments. Overall outcomes remain poor. Major efforts are required to clarify the epidemiology of SE and the determinants of outcomes, thereby identifying targets for improved management. METHODS AND ANALYSIS: ICTAL Registry is a multicentre open cohort of critically ill patients with convulsive, non-convulsive or psychogenic non-epileptic SE. Observational methods are applied to collect uniform data. The goal of the ICTAL Registry is to collect high-quality information on a large number of patients, thereby allowing elucidation of the pathophysiological mechanisms involved in mortality and morbidity. The registry structure is modular, with a large core data set and the opportunity for research teams to create satellite data sets for observational or interventional studies (eg, cohort multiple randomised controlled trials, cross-sectional studies and short-term and long-term longitudinal outcome studies). The availability of core data will hasten patient recruitment to studies, while also decreasing costs. Importantly, the vast amount of data from a large number of patients will allow valid subgroup analyses, which are expected to identify patient populations requiring specific treatment strategies. The results of the studies will have a broad spectrum of application, particularly given the multidisciplinary approach used by the IctalGroup research network. ETHICS AND DISSEMINATION: The ICTAL Registry protocol was approved by the ethics committee of the French Intensive Care Society (#CE_SRLF 19-68 and 19-68a). Patients or their relatives/proxies received written information to the use of the retrospectively collected and pseudonymised data, in compliance with French law. Prospectively included patients receive written consent form as soon as they recover decision-making competency; if they refuse consent, they are excluded from the registry. Data from the registry will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03457831.

ISS is not an appropriate tool to estimate overtriage.

PURPOSE: The aim of this work is to study a cohort of patients of ISS < 15 admitted to a TC, and to determine the number of patients that ultimately benefited from the skills and resources specific of a level 1 trauma center. METHODS: Retrospective study from a prospective cohort of patients admitted to TC (Beaujon Hospital, APHP) for suspected severe trauma from January 2011 to December 2017. The main outcome criterion was the use of surgery or interventional radiology within the first 24 h after admission of patients with ISS < 15. The secondary outcomes were stratified into severe (mortality, resuscitation care, length of stay in intensive care units) and non-severe criteria (mild head injury, hospital discharge or transfer within 24 h). RESULTS: Of 3035 patients admitted during the study period, 1409 with an ISS < 15 were included, corresponding to a theoretical overtriage rate of 46.4%. Among these, 611 patients (43.4%) underwent emergency intervention within the first 24 h (586 surgical interventions, 19 direct transfers to the operating theater and 6 acts of interventional radiology), 238 (16.9%) of patients presented with severe and 531 (38%) with non-severe outcome criteria. CONCLUSION: This work demonstrates that in a cohort of patients classified as ISS < 15 admitted to a TC, a considerable amount of TC-specific resources are required, and patients present with severe outcome criteria despite being classified as overtriaged. These results suggest that triage of trauma patients should be based on resource use and clinical outcome rather than anatomic criteria.

Teaching Important Basic EEG Patterns of Bedside Electroencephalography to Critical Care Staffs: A Prospective Multicenter Study.

BACKGROUND: Continuous electroencephalography (cEEG) is commonly recommended for neurocritical care patients. Routine implementation of such monitoring requires the specific training of professionals. The aim of this research was to evaluate the effectiveness of a training program on initiation of the basic interpretation of cEEG for critical care staff in a prospective multicenter study. METHODS: After completion of a pretest, participants (senior physicians, fellows, residents, medical students, and nurses) recruited in six French ICUs participated in a face-to-face electroencephalogram (EEG) training program followed by additional e-learning sessions at day 1 (post-course), day 15, day 30, and day 90, based on training tests followed by illustrated and commented answers. Each test was designed to evaluate knowledge and skills through correct recognition of ten predefined EEG sequences covering the most common normal and abnormal patterns. The primary objective was to achieve a success rate > 80% correct answers at day 90 by at least 75% of the participants. RESULTS: Among 250 participants, 77/108 (71.3%) who completed the full training program achieved at least 80% correct answers at day 90. Paired comparisons between the scores obtained at each evaluation showed an increase over time. The rate of correct answers at day 90 was > 80% for all common predefined EEG sequences, except for the recognition of periodic and burst-suppression patterns and reactivity, which were identified in only 42.6% (95% CI 36.4-48.8), 60.2% (54.1-66.3), and 70.4% (64.7-76.1) of the tests, respectively. CONCLUSIONS: A training strategy for the basic interpretation of EEG in ICUs, consisting of a face-to-face EEG course supplemented with reinforcement of knowledge by e-learning, was associated with significant resignation and an effectiveness of training allowing 71% of learners to accurately recognize important basic EEG patterns encountered in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03545776.

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

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

The Role of Secondary Brain Insults in Status Epilepticus: A Systematic Review.

(1) Background: Little is known about the impact of pathophysiological mechanisms that underlie the enhancement of excitotoxicity and the neuronal consequences of status epilepticus (SE), as well as the clinical consequences of secondary brain insults (SBI) in patients with SE on outcome; (2) Methods: Electronic searches were conducted in May 2020 using Medline via PubMed, Embase, and Google Scholar (#CRD42019139092). Experimental studies of animals or randomized, observational, controlled trials of patients with SE in indexed journals were included. There were no language or date restrictions for the published literature included in this review. Information was extracted on study design, sample size, SBI characteristics, and primary and secondary outcomes, including the timing of evaluation; (3) Results: Among the 2209 articles responding to our inclusion criteria, 56 were included in this systematic review. There are numerous experimental data reporting the deleterious effects associated with each of the SBI in animals exposed to SE. In humans, only the effect of target temperature management in hypothermia (32-34 °C) has been explored. (4) Conclusions: There is little experimental evidence that favors the control of secondary brain insult after SE. Further studies are required to assess the neuroprotective interest of secondary brain insult control after SE in humans.

Epileptic Seizures in Critically Ill Patients: Diagnosis, Management, and Outcomes.

Epileptic seizures in critically ill patients represent a major source of concern, because they are associated with significant mortality and morbidity rates. Despite recent advances that have enabled a better understanding of the global epidemiology of this entity, epileptic seizures in critically ill patients remain associated with a high degree of uncertainty and numerous questions remain unanswered. The present Special Issue aims to invite authors to contribute original research articles as well as review articles related to all aspects of epileptic seizures in critically ill patients, diagnosis, management, and outcomes.

Comparison of etomidate and sodium thiopental for induction during rapid sequence intubation in convulsive status epilepticus: A retrospective single-center study.

PURPOSE: Few outcome data are available about morbidity associated with endotracheal intubation modalities in critically ill patients with convulsive status epilepticus. We compared etomidate versus sodium thiopental for emergency rapid sequence intubation in patients with out-of-hospital convulsive status epilepticus. METHODS: Patients admitted to our intensive care unit in 2006-2015 were studied retrospectively. The main outcome measure was seizure and/or status epilepticus recurrence within 12 h after rapid sequence intubation. RESULTS: We included 97 patients (60% male; median age, 59 years [IQR, 48-70]). Median time from seizure onset to first antiepileptic drug was 60 min [IQR, 35-90]. Reasons for intubation were coma in 95 (98%), acute respiratory distress in 18 (19%), refractory convulsive status epilepticus in 9 (9%), and shock in 6 (6%) patients; 50 (52%) patients had more than one reason. The hypnotic drugs used were etomidate in 54 (56%) and sodium thiopental in 43 (44%) patients. Seizure and/or status epilepticus recurred in 13 (56%) patients in the etomidate group and 11 patients (44%) in the sodium thiopental group (adjusted common odds ratio [aOR], 0.98; 95%CI, 0.36-2.63; P = 0.97). The two groups were not significantly different for proportions of patients with hemodynamic instability after intubation (aOR, 0.60; 95%CI, 0.23-1.58; P = 0.30) or with difficult endotracheal intubation (OR, 1.28; 95% CI 0.23 to 7.21; P=0.77). CONCLUSIONS: Our findings argue against a difference in seizure and/or status epilepticus recurrences rates between critically ill patients with convulsive status epilepticus given etomidate vs. sodium thiopental as the induction agent for emergency intubation.

Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome.

OBJECTIVES: Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus-related cardiac arrest. DESIGN: Retrospective multicenter study. SETTING: Seventeen university or university affiliated participating ICUs in France and Belgium. PATIENTS: Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 49 cases with convulsive status epilepticus-cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5-85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03-7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27-13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67-34.69; p < 0.0001). Having at least one comorbidity among cardiac, respiratory, and neurologic (other than epilepsy) conditions predicted absence of cardiac arrest (odds ratio, 0.28; 95% CI, 0.10-0.80; p = 0.02). CONCLUSIONS: In patients managed for convulsive status epilepticus, relative hypoxemia, on-scene management complications, and drug poisoning as the cause of convulsive status epilepticus were strong early predictors of cardiac arrest, suggesting areas for improvement.