Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial.

INTRODUCTION: Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation. METHODS AND ANALYSIS: The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation. ETHICS AND DISSEMINATION: The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III-PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04273360.

Severe SARS-Cov2 pneumonia in vaccinated patients: a multicenter cohort study.

Vaccination reduces risk of infection, hospitalization, and death due to SARS-Cov2. Vaccinated patients may however experience severe SARS-Cov2 disease. The objective was to describe clinical features of vaccinated patients requiring intensive care unit (ICU) admission due to SARS-Cov2 infection and compare them to a published cohort of unvaccinated patients. We performed a multicenter cohort study of patients with severe SARS-Cov2 disease admitted to 15 ICUs in France between January and September 2021. 100 consecutive vaccinated patients (68 (68%) men, median age 64 [57-71]) were included. Immunosuppression was reported in 38 (38%) patients. Among available serologies at ICU admission, 64% exhibited an optimal antibody level. Median SOFA score at ICU admission was 4 [4-6.3] and median PaO2/FiO2 ratio was 84 [69-128] mmHg. A total of 79 (79%) and 18 (18%) patients received high flow nasal oxygen and non-invasive mechanical ventilation, respectively. Invasive mechanical ventilation (IMV) was initiated in 48 (48%) with a median duration of 11 [5-19] days. During a median ICU length-of-stay of 8 [4-20] days, 31 (31%) patients died. Age (OR per 5-years increment 1.38 CI95% [1.02-1.85], p = 0.035), and SOFA at ICU admission (OR 1.40 CI95% [1.14-1.72] per point, p = 0.002) were independently associated with mortality. When compared to a cohort of 1316 unvaccinated patients (72% men, median age 63 [53-71]), vaccinated patients exhibited less frequently diabetes (16 [16%] vs. 351 [27%], p = 0.029) but were more frequently immunosuppressed (38 [38%] vs. 109 (8.3%), p < 0.0001), had more frequently chronic kidney disease (24 [24%] vs. 89 (6.8%), p < 0.0001), chronic heart failure (16 [16%] vs. 58 [4.4%], p < 0.0001), and chronic liver disease (3 [3%] vs. 8 [0.6%], p = 0.037) compared to unvaccinated patients. Despite similar severity, vaccinated patients required less frequently IMV at ICU day 1 and during ICU stay (23 [23%] vs. 785 [59.7%], p < 0.0001, and 48 [48%] vs. 930 [70.7%], p < 0.0001, respectively). There was no difference concerning ICU mortality (31 [31%] vs. 379 [28.8%], p = 0.64). Severe SARS-Cov2 infection after vaccination occurs mainly in patients with immunosuppression, chronic kidney, heart or liver failure. Age and disease severity are independently associated with mortality.

Identification of bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome in critically ill COVID-19 patients.

The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30-4.41] vs. 9.53 [2.56-19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.

Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study.

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial.

PURPOSE: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN). METHODS: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis. RESULTS: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58-76] years, with 67% men, a SAPS II score of 59 [46-74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1-11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL. CONCLUSION: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.

Relationship Between Obesity and Ventilator-Associated Pneumonia: A Post Hoc Analysis of the NUTRIREA2 Trial.

BACKGROUND: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). RESEARCH QUESTION: Is obesity associated with an increased incidence of VAP? STUDY DESIGN AND METHODS: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. RESULTS: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. INTERPRETATION: Our results suggest that obesity has no significant impact on the incidence of VAP.

Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL.

INTRODUCTION: A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient's quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders. METHODS AND ANALYSIS: This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03673631.

Diagnosis and management of respiratory viruses in critically ill adult patients: an international survey of knowledge and practice among intensivists.

In this survey endorsed by the European Society of Intensive Care Medicine (ESICM), we aimed to describe the practice patterns of intensivists worldwide, regarding their diagnosis and management of respiratory viruses in lower respiratory tract infections. There were 229 respondents from 53 countries, mainly in Europe (78%). Our main findings are that a majority of intensivists (i) searched for respiratory viruses in case of severe community-acquired LRTI in adults, whatever the season and the medical history and clinical presentation; (ii) had access to large-panel respiratory mPCR; (iii) used them as first-line diagnostic test in routine practice; (iv) had some knowledge about the panel of the mPCR that they use, but markedly less about the cost. However, we observed strong heterogeneity regarding how intensivists took into account mPCR results for infection control (confinement measures) and patient care (antiviral treatment and antibiotics management).

An unusual community-acquired invasive and multi systemic infection due to ExoU-harboring Pseudomonas aeruginosa strain: Clinical disease and microbiological characteristics.

Community-acquired Pseudomonas aeruginosa infections are rare. Most cases involve patients either with underlying immunosuppression or structural chronic lung diseases. We report here an atypical case of a severe community-acquired invasive infection due to a hypervirulent ExoU-producing strain, in an immunocompetent patient.

Impact of the route of nutrition on gut mucosa in ventilated adults with shock: an ancillary of the NUTRIREA-2 trial.

PURPOSE: The effects of the route of nutrition on the gut mucosa of patients with shock are unclear. Plasma citrulline concentration is a marker of enterocyte mass, and plasma intestinal fatty acid binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to study the effect of the route of nutrition on plasma citrulline concentration measured at day 3 of nutrition. MATERIALS AND METHODS: Ancillary study of the NUTRIREA-2 trial. Ventilated adults with shock were randomly assigned to receive enteral or parenteral nutrition. Enterocyte biomarkers were measured at baseline, day 3, and day 8 of nutrition. RESULT: A total of 165 patients from 13 French ICUs were included in the study: 85 patients in the enteral group and 80 patients in the parenteral group. At baseline, plasma citrulline was low without difference between groups (12.2 µmol L-1 vs 13.3 µmol L-1). At day 3, plasma citrulline concentration was higher in the enteral group than in the parenteral group (18.7 µmol L-1 vs 15.3 µmol L-1, p = 0.01). Plasma I-FABP concentration was increased at baseline, without difference between groups (245 pg mL-1 vs 244 pg mL-1). Plasma I-FABP concentration was higher in the enteral group than in the parenteral group at day 3 and day 8 (158 pg mL-1 vs 50 pg mL-1, p = 0.005 and 225 pg mL-1 vs 50 pg mL-1, p = 0.03). CONCLUSION: Plasma citrulline concentration was higher after 3 days of enteral nutrition than after 3 days of parenteral nutrition. This result raises the question of the possibility that enteral nutrition is associated with a more rapid restoration of enterocyte mass than parenteral nutrition.

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. METHODS: Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. RESULTS: A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). CONCLUSIONS: Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.

Disparity of the "screen-and-isolate" policy for multidrug-resistant organisms: A national survey in French adult ICUs.

BACKGROUND: The prevalence of multidrug-resistant organisms (MDROs) has dramatically increased. The aim of this survey was to describe and analyze the different screening and isolation policies regarding MDROs in French adult intensive care units (ICUs). MATERIALS AND METHODS: A multicenter online survey was performed among French ICUs, including 63 questions distributed into 4 parts: characteristics of the unit, MDRO screening policy, policy regarding contact precautions, and ecology of the unit. RESULTS: From April 2015 to June 2016, 73 of 301 ICUs (24%) participated in the survey. MDRO screening was performed on admission in 96% of ICUs, for at least 1 MDRO (78%). MDRO screening was performed weekly during ICU stay in 83% of ICUs. Preemptive isolation was initiated on admission in 82% of ICUs, mostly in a targeted way (71%). Imported and acquired MDRO rates >10% were reported in 44% and 27% of ICUs, respectively. An MDRO outbreak had occurred within the past 3 years in 48% of cases. CONCLUSION: French ICUs have variable screening and isolation approaches for MDROs, as up to 10 combinations were met. Discrepancies with the 2009 national guidelines were observed. Very few ICUs practice without some form of screening and isolation of patients upon admission.

Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2).

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health.

Clinical Features of Patients with Diffuse Alveolar Hemorrhage due to Negative-Pressure Pulmonary Edema.

PURPOSE: Diffuse alveolar hemorrhage (DAH) with negative-pressure pulmonary edema (NPPE) is an uncommon yet life-threatening condition. We aimed at describing the circumstances, clinical, radiological, and bronchoscopic features, as well as the outcome of patients with NPPE-related DAH. METHODS: We performed a retrospective, observational cohort study, using data prospectively collected over 35 years in an intensive care unit (ICU). RESULTS: Of the 149 patients admitted for DAH, we identified 18 NPPE episodes in 15 patients, one admitted four times for recurrent NPPE-related DAH. The patients were primarily young, male, and athletic. The NPPE setting was postoperative (n = 12/18, 67%) or following generalized tonic-clonic seizures (n = 6/18, 33%). Hemoptysis was almost constant (n = 17/18, 94%), yet rarely massive (>200 cc, n = 1/18, 6%), with anemia observed in 10 (56%) episodes. The DAH triad (hemoptysis, anemia, and pulmonary infiltrates) was observed in 50% of episodes (n = 9/18), and acute respiratory failure in 94% (n = 17/18). Chest computed tomography revealed diffuse bilateral ground glass opacities (n = 10/10, 100%), while bronchoscopy detected bilateral hemorrhage (n = 12/12, 100%) and macroscopically bloody bronchoalveolar lavage, with siderophage absence in most (n = 7/8, 88%), indicating acute DAH. While one episode proved fatal, the other 17 recovered rapidly, with a mean ICU stay lasting 4.6 (2-15) days. Typically, the evolution was rapidly favorable under supportive care. CONCLUSION: NPPE-related DAH is a rare life-threatening condition occurring primarily after tonic-clonic generalized seizure or generalized anesthesia. Clinical circumstances are a key to its diagnosis. Early diagnosis and recognition likely allow for successful management of this potentially serious complication, whereas ictal-DAH appears ominous in epileptic patients.