Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

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.

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.

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.

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.

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.

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.

Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults.

OBJECTIVE: Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care. DESIGN: Prospective, multicenter, cohort study from a national quality improvement collaborative. SETTING: 68 academic, community, and federal ICUs collected data during a 20-month period. PATIENTS: 15,226 adults with at least one ICU day. INTERVENTIONS: We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU and hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models were adjusted for a minimum of 18 a priori determined potential confounders. MEASUREMENTS AND RESULTS: Complete ABCDEF bundle performance was associated with lower likelihood of seven outcomes: hospital death within 7 days (adjusted hazard ratio, 0.32; CI, 0.17-0.62), next-day mechanical ventilation (adjusted odds ratio [AOR], 0.28; CI, 0.22-0.36), coma (AOR, 0.35; CI, 0.22-0.56), delirium (AOR, 0.60; CI, 0.49-0.72), physical restraint use (AOR, 0.37; CI, 0.30-0.46), ICU readmission (AOR, 0.54; CI, 0.37-0.79), and discharge to a facility other than home (AOR, 0.64; CI, 0.51-0.80). There was a consistent dose-response relationship between higher proportional bundle performance and improvements in each of the above-mentioned clinical outcomes (all p < 0.002). Significant pain was more frequently reported as bundle performance proportionally increased (p = 0.0001). CONCLUSIONS: ABCDEF bundle performance showed significant and clinically meaningful improvements in outcomes including survival, mechanical ventilation use, coma, delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition.

Early-SEPs' amplitude reduction is reliable for poor-outcome prediction after cardiac arrest?

OBJECTIVE: The bilateral absence of cortical Somatosensory Evoked Potentials (SEPs), after cardiac arrest (CA), is a high reliable predictor of poor outcome but it is present in no more than 40% of patients. An amplitude reduction of cortical SEPs was found in about 30% of subjects, but few papers analysed its prognostic significance. The aim of our study is to identify a value of SEP amplitude reduction below which all the CA patients had poor outcome and the relationship between SEP and Electroencephalogram (EEG) patterns. MATERIAL AND METHODS: We analysed comatose patients in whom SEPs and EEG were recorded at 6-12 hours after CA. We evaluated the sensitivity at specificity of 100% of SEP amplitude in predicting the non-recovery of consciousness by plotting Receiver Operating Characteristic (ROC) curves. We also analysed the relationship between SEP amplitude and EEG patterns. Outcome was evaluated at 6 months by Glasgow Outcome Scale. RESULTS: We analysed 119 subjects. According to the ROC analysis (area under the curve = 0.95/CI 0.91-0.99), all patients with a cortical SEP amplitude <0.65 µV did not recover consciousness (GOS 1-2), with a sensitivity of 71.8%. Severe EEG abnormalities (suppression and burst-suppression patterns) were also observed in all these patients. CONCLUSION: Not only the absence but also a bilateral amplitude reduction of cortical SEPs (<0.65 µV) is associated with ominous prognosis (death or non-recovery of consciousness) with a very high predictive value. However, we emphasize that great caution should be applied before adopting amplitude reduction as a criterion for the poor prognosis of CA patients.

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.

Validation of the Chinese version of the Coma Recovery Scale-Revised (CRS-R).

PRIMARY OBJECTIVE: This study aims to validate the Chinese version of the Coma Recovery Scale-Revised (CRS-R). METHODS: One hundred sixty-nine patients were assessed with both the CRS-R and the Glasgow Coma Scale (GCS), diagnosed as being in unresponsive wakefulness syndrome (UWS, formerly known as vegetative state), minimally conscious state (MCS), or emergence from MCS (EMCS). A subgroup of 50 patients has been assessed twice by the same rater, within 24 h. Patient outcome was documented six months after assessment. RESULTS: The internal consistency for the CRS-R total score was excellent (Cronbach's α = 0.84). Good test-retest reliability was obtained for CRS-R total score and subscale scores (intra-class correlation coefficient [ICC] = 0.87 and ICC = 0.66-0.84, respectively). Inter-rater reliability was high (ICC = 0.719; p < 0.01). Concurrent validity was good between CRS-R total scale and GCS total scale. Diagnostic validity was excellent compared with GCS (emerged from UWS: 24%; emerged from MCS: 28%). When considering patient outcome, diagnostic validity was good. In addition, false-positive rates have been detected for both diagnoses. CONCLUSION: The Chinese version of the CRS-R is a reliable and sensitive tool and can discriminate patients in UWS, MCS, and EMCS successfully.

Spontaneous Hyperventilation in Severe Traumatic Brain Injury: Incidence and Association with Poor Neurological Outcome.

BACKGROUND: Hypocapnia induces cerebral vasoconstriction leading to a decrease in cerebral blood flow, which might precipitate cerebral ischemia. Hypocapnia can be intentional to treat intracranial hypertension or unintentional due to a spontaneous hyperventilation (SHV). SHV is frequent after subarachnoid hemorrhage. However, it is understudied in patients with severe traumatic brain injury (TBI). The objective of this study was to describe the incidence and consequences on outcome of SHV after severe TBI. METHODS: We conducted a retrospective, observational study including all intubated TBI patients admitted in the trauma center and still comatose 24 h after the withdrawal of sedation. SHV was defined by the presence of at least one arterial blood gas (ABG) with both PaCO2 < 35 mmHg and pH > 7.45. Patient characteristics and outcome were extracted from a prospective registry of all intubated TBI admitted in the intensive care unit. ABG results were retrieved from patient files. A multivariable logistic regression model was developed to determine factors independently associated with unfavorable outcome (defined as a Glasgow Outcome Scale between 1 and 3) at 6-month follow-up. RESULTS: During 7 years, 110 patients fully respecting inclusion criteria were included. The overall incidence of SHV was 69.1% (95% CI [59.9-77]). Patients with SHV were more severely injured (median head AIS score (5 [4-5] vs. 4 [4-5]; p = 0.016)) and exhibited an elevated morbidity during their stay. The proportion of patients with an unfavorable functional neurologic outcome was significantly higher in patients with SHV: 40 (52.6%) versus 6 (17.6%), p = 0.0006. After adjusting for confounders, SHV remains an independent factor associated with unfavorable outcome at the 6-month follow-up (OR 4.1; 95% CI [1.2-14.4]). CONCLUSIONS: SHV is common in patients with a persistent coma after a severe TBI (overall rate: 69%) and was independently associated with unfavorable outcome at 6-month follow-up.

The electroclinical spectrum, etiologies, treatment and outcome of nonconvulsive status epilepticus in the elderly.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) in the elderly is particularly difficult to diagnose, mainly due to subtle clinical manifestations and associated comorbidities. The recently validated electroencephalography (EEG) diagnostic criteria for NCSE and the proposed operational classification of status epilepticus provide tools that can allow an earlier diagnosis and better management of NCSE in this age group, possibly contributing to reduce its high mortality. MATERIAL AND METHODS: we used these tools to identify and characterize a cohort of elderly (>60year-old) patients admitted at our institution in a 3-year period; the video-EEG and clinical files of the patients fulfilling EEG diagnostic criteria for NCSE were reviewed, being in this study described their electroclinical spectrum, etiologies, treatment, inhospital mortality, and status epilepticus severity score (STESS). RESULTS: Fourty patients (23 women; mean age 76.6years) were identified. Although dyscognitive NCSE associated with >2.5Hz of epileptiform discharges (ED) was the most frequent electroclinical phenotype, this was quite heterogeneous, ranging from patients with aura continua to patients in coma, associated with frequent ED or rhythmic slow activities. Acute symptomatic (45%) and multifactorial (27.5%) etiologies were the most common, and associated with the worst prognosis. There was a trend to use newer antiepileptic drugs in the early steps of NCSE treatment. The inhospital mortality was high (22.5%) and predicted by STESS scores ≥3. CONCLUSION: In the elderly, NCSE has heterogeneous electroclinical phenotypes and etiologies. In spite of the treatment limitations conditioned by the comorbidities, more aggressive treatments could be justified to reduce mortality in patients with high STESS scores.

Does semiology of status epilepticus have an impact on treatment response and outcome?

OBJECTIVE: This study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. METHOD: Two hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18-97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). RESULTS: The most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). CONCLUSION: Status epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE.

Association Between Transfusion of RBCs and Subsequent Development of Delirium in Critically Ill Children.

OBJECTIVES: To determine the temporal relationship between the transfusion of RBCs and the subsequent development of delirium in a cohort of critically ill children. DESIGN: Nested retrospective cohort study within prospective cohort study. SETTING: Urban academic tertiary care PICU. PATIENTS: All consecutive admissions from September 2014 through August 2015. INTERVENTIONS: Children were screened twice daily for delirium during their PICU admission. MEASUREMENTS AND MAIN RESULTS: Among 1,547 independent admissions screened for delirium, 166 (10.7%) were transfused RBCs. Children who were transfused RBCs were more than twice as likely to be delirious during their admission compared with children who were never transfused, after controlling for known predictors of delirium development (adjusted odds ratio, 2.16; 95% CI, 1.38-3.37; p = 0.001). Among transfused children, a temporal relationship was observed between receipt of RBCs and the subsequent development of delirium. For each additional 10 mL/kg of RBCs transfused, the recipients were 90% more likely to develop delirium or coma in the 72 hours following the transfusion, after controlling for confounders (adjusted odds ratio, 1.90; 95% CI, 1.14-3.17; p = 0.01). Anemia (represented by nadir hemoglobin prior to transfusion) was not associated with delirium development. CONCLUSIONS: In this cohort of critically ill children, there is an independent association between the receipt of an RBC transfusion and the subsequent development of delirium. Further prospective studies are warranted to replicate this finding and investigate possible pathophysiologic mechanisms for this association.

Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

RATIONALE: Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. OBJECTIVES: To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. METHODS: In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. MEASUREMENTS AND MAIN RESULTS: Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. CONCLUSIONS: Acute kidney injury is a risk factor for delirium and coma during critical illness.

Therapeutic monitoring of antiepileptic drugs in comatose patients.

OBJECTIVE: In this study, we aimed to analyze the trough plasmatic levels (C0) of the antiepileptic drugs (AED) administered by nasogastric tubes (NGT) in comatose patients and to draw up recommendations for therapeutic drug monitoring (TDM) and for the modalities of AED administration by NGT. METHODS: We conducted a retrospective study on comatose patients addressed over six years and 10 months in Clinical Pharmacology for C0 measurement of AED administered by NGT. RESULTS: In this study, the sex-ratio was 2.38 (44 patients). The patients' median age was 24 years. There was 14.5% of children (≤16 years). Among the 103 samples, C0 measurement concerned valproic acid in 57%, phenobarbital in 28 % and carbamazepine in 15%. Two AED or more were associated in 42% of patients. AED were associated to other drugs in 85% of cases. The AED C0 were subtherapeutic in 71% of cases. C0/Dp lower than recommanded in 65 %. In these samples, 55% presented at least one drug association with the concerned AED. In 45% of the cases, there was no drug association but a non-respect of modalities of AED administration by NGT in patients. CONCLUSION:   The drug monitoring is a useful tool to assess drug-drug interactions and to control modalities of AED administration in comatose patients.

Effectiveness and Safety of an Extended ICU Visitation Model for Delirium Prevention: A Before and After Study.

OBJECTIVES: To evaluate the effect of an extended visitation model compared with a restricted visitation model on the occurrence of delirium among ICU patients. DESIGN: Prospective single-center before and after study. SETTING: Thirty-one-bed medical-surgical ICU. PATIENTS: All patients greater than or equal to 18 years old with expected length of stay greater than or equal to 24 hours consecutively admitted to the ICU from May 2015 to November 2015. INTERVENTIONS: Change of visitation policy from a restricted visitation model (4.5 hr/d) to an extended visitation model (12 hr/d). MEASUREMENTS AND MAIN RESULTS: Two hundred eighty-six patients were enrolled (141 restricted visitation model, 145 extended visitation model). The primary outcome was the cumulative incidence of delirium, assessed bid using the confusion assessment method for the ICU. Predefined secondary outcomes included duration of delirium/coma; any ICU-acquired infection; ICU-acquired bloodstream infection, pneumonia, and urinary tract infection; all-cause ICU mortality; and length of ICU stay. The median duration of visits increased from 133 minutes (interquartile range, 97.7-162.0) in restricted visitation model to 245 minutes (interquartile range, 175.0-272.0) in extended visitation model (p < 0.001). Fourteen patients (9.6%) developed delirium in extended visitation model compared with 29 (20.5%) in restricted visitation model (adjusted relative risk, 0.50; 95% CI, 0.26-0.95). In comparison with restricted visitation model patients, extended visitation model patients had shorter length of delirium/coma (1.5 d [interquartile range, 1.0-3.0] vs 3.0 d [interquartile range, 2.5-5.0]; p = 0.03) and ICU stay (3.0 d [interquartile range, 2.0-4.0] vs 4.0 d [interquartile range, 2.0-6.0]; p = 0.04). The rate of ICU-acquired infections and all-cause ICU mortality did not differ significantly between the two study groups. CONCLUSIONS: In this medical-surgical ICU, an extended visitation model was associated with reduced occurrence of delirium and shorter length of delirium/coma and ICU stay.

Delirium in Critically Ill Children: An International Point Prevalence Study.

OBJECTIVES: To determine prevalence of delirium in critically ill children and explore associated risk factors. DESIGN: Multi-institutional point prevalence study. SETTING: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. PATIENTS: All children admitted to the pediatric critical care units on designated study days (n = 994). INTERVENTION: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. MEASUREMENTS AND MAIN RESULTS: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. CONCLUSIONS: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

Increase in Medical Emergency Calls and Calls for Central Nervous System Symptoms During a Severe Air Pollution Event, January 2013, Jinan City, China.

BACKGROUND: In January 2013, a continuous and severe haze event affected one third of the major cities in China, including Jinan. OBJECTIVES: We investigated whether medical emergency calls (for nonaccidental emergencies) and calls for Central Nervous System (CNS) syndromes increased during this episode compared with the previous winter months (January, February, and December) in 2011 and 2012. METHODS: Daily emergency calls were obtained from Jinan Medical Emergency Center. Sentinel CNS syndromes from nonaccidental emergency calls included seven symptoms: headache, dizziness, syncope, coma, convulsions, paralysis, and epilepsy. Particles with aerodynamic diameter <10 µm (PM10) were used as the indicator of air pollution. A generalized linear model based on quasi-Poisson regression was used to evaluate the effects on nonaccidental emergency calls and calls for CNS syndromes and each symptom, separately, during this episode. RESULTS: Markedly higher mean daily concentration, 332 µg/m of PM10, during this episode versus reference months was found. Obviously increased effects on nonaccidental emergency calls and calls for CNS syndromes were observed during this episode, with relative risk (RR) value 1.3 (95% CI = 1.2, 1.3) and 1.2 (95% CI = 1.1, 1.3). Four of seven CNS symptoms were also increased during this episode: RRs values for dizziness, convulsions, paralysis, and epilepsy were 1.4 (95% CI = 1.2, 1.7), 1.4 (95% CI = 1.1, 1.6), 1.6 (95% CI = 1.2, 2.1), and 1.5 (95% CI = 1.1, 2.0), respectively. CONCLUSIONS: A noticeable increase in medical emergency calls and calls for Central Nervous System syndromes were observed during a severe air pollution episode on January 2013, in a large Chinese city.