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 .

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

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

Automated vs. conventional ventilation in the ICU: a randomized controlled crossover trial comparing blood oxygen saturation during daily nursing procedures (I-NURSING).

BACKGROUND: Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen desaturation during DNPs remains unknown. METHODS: A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO2) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO2 ≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO2 in the acceptable range of 90-95% during the DNP. RESULTS: Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p <  0.001). The percentage of time spent with SpO2 in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO2 in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01). CONCLUSION: AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV. TRIAL REGISTRATION: This study was registered in clinical-trial.gov ( NCT03176329 ) in June 2017.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

BACKGROUND: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. METHODS: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. RESULTS: A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. CONCLUSIONS: In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

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.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

Return to work after out of hospital cardiac arrest, insights from a prospective multicentric French cohort.

RATIONALE: About 60 to 70% of out-of-hospital cardiac arrest (OHCA) survivors who worked before cardiac arrest return to work within one year but the precise conditions for this resumption of professional activity remain little known. The objective of this study was to assess components of return to work among OHCA survivors. PATIENTS AND METHODS: We used the French national multicentric cohort AfterRosc to include OHCA survivors admitted between April 1st 2021 and March 31st 2022, discharged alive from the Intensive Care Unit (ICU), and who were less than 65 years old. A phone-call interview was performed one year after OHCA to assess return to work, level of education, former level of occupation as well as neurological recovery. Geographic and socio-economic data from the patient's residential neighborhoods were also collected. Comparisons were performed between patients who returned to work and those who did not, using non-parametric tests. RESULTS: Of the 251 patients included in the registry, 86 were alive at ICU discharge and 31 patients that worked prior to the OHCA were included for analysis. Seventeen survivors returned to work after a median delay of 112 days [92-157] Among them, nine (53%) had required initial work adjustments. Overall, only 6 patients (19%) had returned to work ad integrum. Higher educational level, work which required higher competence-level, higher income, living in a better socio-economical neighborhood, as well as better scores on all three standardized MPAI-4 score components (abilities, adjustment and participation) were significantly associated with return to work. Participants that had not returned to work had a significant drop of income (p = 0.0025). CONCLUSION: In this prospective study regarding French OHCA survivors, return to work is associated with better socio-economical individual and environmental status, as well as better scores on all MPAI-4 components.

Early intravenous high-dose vitamin C in postcardiac arrest shock (VICEPAC): study protocol for a randomised, single-blind, open-label, multicentre, controlled trial.

INTRODUCTION: The high incidence of morbidity and mortality associated with the post-cardiac arrest (CA) period highlights the need for novel therapeutic interventions to improve the outcome of out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit (ICU). The aim of this study is to assess the ability of high-dose intravenous vitamin C (Vit-C) to improve post-CA shock. METHODS AND ANALYSIS: This is a single-blind, open-label, multicentre, randomised controlled trial, involving 234 OHCA patients with post-CA shock planned to be enrolled in 10 French ICUs. Patients will be randomised to receive standard-of-care (SOC) or SOC with early high-dose intravenous Vit-C administration (200 mg/kg per day, within 6 hours after return of spontaneous circulation, for 3 days). The primary endpoint is the cumulative incidence of vasopressor withdrawal at 72 hours after enrolment, with death considered as a competing event. The main secondary endpoints are neurological outcome, mortality due to refractory shock, vasopressor-free days and organ failure monitored by the sequential organ failure assessment score. ETHICS AND DISSEMINATION: The study protocol was approved by a French Ethics Committee (EC) on 21 February 2023 (Comité de Protection des Personnes Ile de France 1, Paris, France). Due to the short enrolment period to avoid any delay in treatment, the EC approved the study inclusion before informed consent was obtained. As soon as possible, patient and their relative will be asked for their deferred informed consent. The data from the study will be disseminated through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05817851.

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.

PURPOSE: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear. METHODS: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality. RESULTS: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048). CONCLUSION: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

Performance of the ERC/ESICM-recommendations for neuroprognostication after cardiac arrest: Insights from a prospective multicenter cohort.

AIM: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome. METHODS: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 h after resuscitation, we measured: (1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score ≥4 at 90 days), and (2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate. RESULTS: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, and the positive predictive value for an unfavourable outcome was 100% [98-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38]% sensitivity. CONCLUSION: All comatose resuscitated patients who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty.

Comparison of high-flow nasal therapy, noninvasive ventilation, and continuous positive airway pressure on outcomes in critically ill patients admitted for COVID-19 with acute respiratory failure.

BACKGROUND: The optimal first-line noninvasive respiratory support (NIRS) to improve outcome in patients affected by COVID-19 pneumonia admitted to ICU is still debated. METHODS: We conducted a retrospective study in seven French ICUs, including all adults admitted between July and December 2020 with documented SARS-CoV-2 acute respiratory failure (PaO2/FiO2<300 mmHg), and treated with either high-flow nasal therapy (HFNT) alone, noninvasive ventilation alone or in combination with HFNT (NIV), or continuous positive airway pressure alone or in combination with HFNT (CPAP). The primary outcome was NIRS failure at day 28, defined as the need for endotracheal intubation (ETI) or death without ETI. RESULTS: Among the 355 patients included, 160 (45%) were treated with HFNT alone, 115 (32%) with NIV and 80 (23%) with CPAP. The primary outcome occurred in 65 (41%), 69 (60%), and 25 (31%) patients among those treated with HFNT alone, NIV, and CPAP, respectively (P<0.001). After univariate analysis, patients treated with CPAP had a trend for a lower incidence of the primary outcome, whereas patients treated with NIV had a significant higher incidence of the primary outcome, both compared to those treated with HFNT alone (unadjusted Hazard ratio 0.67; 95% CI [0.42-1.06], and 1.58; 95% CI [1.12-2.22]; P=0.09 and 0.008, respectively). CONCLUSIONS: Among ICU patients admitted for severe COVID-19 pneumonia and managed with NIRS, the outcome seems to differ according to the initial chosen strategy. Prospective randomized controlled studies are warranted to identify the optimal strategy.

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

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

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

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

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.

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.

Incidence, clinical characteristics, and outcome after unexpected cardiac arrest among critically ill adults with COVID-19: insight from the multicenter prospective ACICOVID-19 registry.

BACKGROUND: Initial reports have described the poor outcome of unexpected cardiac arrest (CA) in intensive care unit (ICU) among COVID-19 patients in China and the USA. However, there are scarce data on characteristics and outcomes of such CA patients in Europe. METHODS: Prospective registry in 35 French ICUs, including all in-ICU CA in COVID-19 adult patients with cardiopulmonary resuscitation (CPR) attempt. Favorable outcome was defined as modified Rankin scale ranging from 0 to 3 at day 90 after CA. RESULTS: Among the 2425 COVID-19 patients admitted to ICU from March to June 2020, 186 (8%) experienced in-ICU CA, of whom 146/186 (78%) received CPR. Among these 146 patients, 117 (80%) had sustained return of spontaneous circulation, 102 (70%) died in the ICU, including 48 dying within the first day after CA occurrence and 21 after withdrawal of life-sustaining therapy. Most of CA were non-shockable rhythm (90%). At CA occurrence, 132 patients (90%) were mechanically ventilated, 83 (57%) received vasopressors and 75 (51%) had almost three organ failures. Thirty patients (21%) had a favorable outcome. Sepsis-related organ failure assessment score > 9 before CA occurrence was the single parameter constantly associated with unfavorable outcome in multivariate analysis. CONCLUSIONS: In-ICU CA incidence remains high among a large multicenter cohort of French critically ill adults with COVID-19. However, 21% of patients with CPR attempt remained alive at 3 months with good functional status. This contrasts with other recent reports showing poor outcome in such patients. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (NTC04373759) in April 2020 ( https://www.clinicaltrials.gov/ct2/show/NCT04373759?term=acicovid&draw=2&rank=1 ).

Sustained low-efficiency dialysis with regional citrate anticoagulation for patients with liver impairment in intensive care unit: A single-center experience.

Regional citrate anticoagulation (RCA) is a recommended method for extracorporeal circuit anticoagulation during renal replacement therapy (RRT). Increased risk of citrate accumulation by default of hepatic metabolism limits its use in liver failure patients. A Catot /Caion ratio ≥2.5 is established as an indirect control of plasma citrate poisoning. To investigate the safety of RCA in patients with liver impairment during sustained low-efficiency dialysis (SLED), we conducted a retrospective study of 41 patients with acute or chronic hepatocellular failure requiring RRT between January 2014 and June 2015 in the intensive care unit of the Groupe Hospitalier Sud Ile de France. Sixty-seven SLED sessions were performed. At admission, 32 (78%) patients had acute liver dysfunction and nine (22%) patients had cirrhosis with a median MELD score of 27 (IQR: 18.8, 42.0). Despite a majority of poor prognosis patients (SAPS-II (Simplified Acute Physiology Score II) score 71 [IQR: 58; 87]), with acute liver impairment as a part of multi-organ failure, no dosage of Catot /Caion ratio after SLED sessions exceeded the critical threshold of 2.5. Of the 63 complete sessions, neither dyscalcemia nor major dysnatremia, nor extracorporeal circuit thrombosis were noticed. Observed acid-base disturbances (16.4%) were not significantly correlated with the Catot /Caion ratio (P = .2155). In this retrospective study using RCA during intermittent RRT in ICU patients with severe liver dysfunction, we did not observe any citrate accumulation but monitoring of acid-base status and electrolytes remains necessary to ensure technique safety.

Association of systemic secondary brain insults and outcome in patients with convulsive status epilepticus: A post hoc study of a randomized controlled trial.

OBJECTIVE: To evaluate the association between systemic factors (mean arterial blood pressure, arterial partial pressures of carbon dioxide and oxygen, body temperature, natremia, and glycemia) on day 1 and neurologic outcomes 90 days after convulsive status epilepticus. METHODS: This was a post hoc analysis of the Evaluation of Therapeutic Hypothermia in Convulsive Status Epilepticus in Adults in Intensive Care (HYBERNATUS) multicenter open-label controlled trial, which randomized 270 critically ill patients with convulsive status epilepticus requiring mechanical ventilation to therapeutic hypothermia (32°C-34°C for 24 hours) plus standard care or standard care alone between March 2011 and January 2015. The primary endpoint was a Glasgow Outcome Scale score of 5, defining a favorable outcome, 90 days after convulsive status epilepticus. RESULTS: The 172 men and 93 women had a median age of 57 years (45-68 years). Among them, 130 (49%) had a history of epilepsy, and 59 (29%) had a primary brain insult. Convulsive status epilepticus was refractory in 86 (32%) patients, and total seizure duration was 67 minutes (35-120 minutes). The 90-day outcome was unfavorable in 126 (48%) patients. In multivariate analysis, none of the systemic secondary brain insults were associated with outcome; achieving an unfavorable outcome was associated with age >65 years (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.20-3.85; p = 0.01), refractory convulsive status epilepticus (OR 2.00, 95% CI 1.04-3.85; p = 0.04), primary brain insult (OR 2.00, 95% CI 1.02-4.00; p = 0.047), and no bystander-witnessed seizure onset (OR 2.49, 95% CI 1.05-5.59; p = 0.04). CONCLUSIONS: In our population, systemic secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus. CLINICALTRIALSGOV IDENTIFIER: NCT01359332.

OHCA (Out-of-Hospital Cardiac Arrest) and CAHP (Cardiac Arrest Hospital Prognosis) scores to predict outcome after in-hospital cardiac arrest: Insight from a multicentric registry.

AIM: We assessed the ability of the Out-of-Hospital Cardiac Arrest (OHCA) and the Cardiac Arrest Hospital Prognosis (CAHP) scores to predict neurological outcome following in-hospital cardiac arrest (IHCA). METHODS: Retrospective review of a seven-year French multicentric database including ten intensive care units. Primary endpoint was the outcome at hospital discharge using the Cerebral Performance Category score (CPC) in all IHCA patients. OHCA and CAHP scores, sequential organ failure assessment (SOFA) score and the simplified acute physiological score 2 (SAPS-2) were compared using area under ROC curves (AUROC) and Delong tests. RESULTS: Among 381 included patients, 125 (33%) were discharged alive with favourable outcome (CPC 1-2). Among 256 patients (77%) with unfavourable outcome (CPC 3-5), 10 were discharged alive with CPC 3 (4%), 130 died from withdrawal of life sustaining therapies because of severe neurological impairment (51%), 107 died from multiorgan failure (42%) and 9 died after discharge from complications and comorbidities (3%). OHCA and CAHP scores were independently associated with unfavourable outcome. The AUROCs to predict unfavourable outcome for OHCA, CAHP, SAPS-2 and SOFA scores were 0.76 [0.70-0.80], 0.74 [0.69-0.79], 0.72 [0.67-0.77], and 0.69 [0.64-0.74] respectively, with a significant difference observed only between OHCA and SOFA scores AUROCs (p = 0.04). CONCLUSION: In parallel with CAHP score, OHCA score could be used to early predict outcome at hospital discharge after IHCA. However, prediction accuracy for all scores remains modest, suggesting the use of other dedicated means to early predict IHCA patients' outcome.

Duration of prone position sessions: a prospective cohort study.

BACKGROUND: Prone position (PP) is highly recommended in moderate-to-severe ARDS. However, the optimal duration of PP sessions remains unclear. We searched to evaluate the time required to obtain the maximum physiological effect, and to search for parameters related to patient survival in PP. METHODS AND RESULTS: It was a prospective, monocentric, physiological study. We included in the study all prone-positioned patients in our ICU between June 2016 and January 2018. Pulmonary mechanics, data from volumetric capnography and arterial blood gas were recorded before prone positioning, 2 h after proning, before return to a supine position (SP) and 2 h after return to SP. Dynamic parameters were recorded before proning and every 30 min during the session until 24 h. 103 patients (ARDS 95%) were included performing 231 PP sessions with a mean length of 21.5 ± 5 h per session. They presented a significant increase in pH, static compliance and PaO2/FiO2 with a significant decrease in PaCO2, Pplat, phase 3 slope of the volumetric capnography, PetCO2, VD/VT-phy and ΔP. The beneficial physiological effects continued after 16 h of PP and at least up to 24 h in some patients. The evolution of the respiratory parameters during the first session and also during the pooled sessions did not find any predictor of response to PP, whether before, during or 2 h after the return in SP. CONCLUSIONS: PP sessions should be prolonged at least 24 h and be extended in the event that the PaO2/FiO2 ratio at 24 h remains below 150, especially since no criteria can predict which patient will benefit or not from it. Trial registration The trial has been registered on 28 June 2016 in ClinicalTrials.gov (NCT02816190) (https://clinicaltrials.gov/ct2/show/NCT02816190?term=propocap&rank=1).