Stroke on ECG: a cerebral T-wave change secondary to acute carbon monoxide poisoning.

In clinical management of carbon monoxide (CO) poisoning, serum cardiac enzyme biomarkers and electrocardiogram (ECG) are both highly recommended emergency check-ups to evaluate myocardial injuries. Medical imaging - including head CT or MRI - are not routine for CO poisoning emergency management. We herein report on a comatose patient who was diagnosed with cerebral infarction secondary to 24 hours previous acute CO poisoning, warned by a typical cerebral-type T waves on ECG in advance, and confirmed by a head MRI. Fortunately, the patient made a full recovery based on a timely treatment with medications and hyperbaric oxygen (HBO2) therapy. We would like to propose that a vital, stable, conscious CO poisoning patient who remains a higher risk for hemorrhagic or ischemic stroke should be closely monitored for potential neurological abnormalities, and a continuous ECG monitoring should be reinforced throughout the treatment. A head MRI or CT is a priority in evaluating the secondary cerebral stroke and should be arranged immediately in the event of an abnormal ECG or if unusual new symptoms are apparent.

[Separation/Conversion Disorders in Functional Coma With Pseudocataplexy: Report of One Case and Literature Review].

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.

Mild therapeutic hypothermia after cardiac arrest - effect on survival with good neurological outcome outside of randomised controlled trials: A registry-based analysis.

BACKGROUND: For nearly 20 years, in international guidelines, mild therapeutic hypothermia (MTH) was an important component of postresuscitation care. However, recent randomised controlled trials have questioned its benefits. At present, international guidelines only recommend actively preventing fever, but there are ongoing discussions about whether the majority of cardiac arrest patients could benefit from MTH treatment. OBJECTIVE: The aim of this study was to compare the outcome of adult patients treated with and without MTH after cardiac arrest. DESIGN: Observational cohort study. SETTING: German Resuscitation Registry covering more than 31 million inhabitants of Germany and Austria. PATIENTS: All adult patients between 2006 and 2022 with out-of-hospital or in-hospital cardiac arrest and comatose on admission. MAIN OUTCOME MEASURES: Primary endpoint: hospital discharge with good neurological outcome [cerebral performance categories (CPC) 1 or 2]. Secondary endpoint: hospital discharge. We used a multivariate binary logistic regression analysis to identify the effects on outcome of all known influencing variables. RESULTS: We analysed 33 933 patients (10 034 treated with MTH, 23 899 without MTH). The multivariate regression model revealed that MTH was an independent predictor of CPC 1/2 survival and of hospital discharge with odds ratio (95% confidence intervals) of 1.60 (1.49 to 1.72), P < 0.001 and 1.89 (1.76 to 2.02), P < 0.001, respectively. CONCLUSION: Our data indicate the existence of a positive association between MTH and a favourable neurological outcome after cardiac arrest. It therefore seems premature to refrain from giving MTH treatment for the entire spectrum of patients after cardiac arrest. Further prospective studies are needed.

Explaining recovery from coma with multimodal neuroimaging.

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients' neurological recovery after coma. 32 patients (18-76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient's hospitalization were used to derive cortical glucose metabolism (18F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p < .001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = - 0.74, p < 0.001, 95% CI: - 0.46, - 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R2 = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R2 = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R2 = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury.

Validating quantitative pupillometry thresholds for neuroprognostication after out-of-hospital cardiac arrest. A predefined substudy of the Blood Pressure and Oxygenations Targets After Cardiac Arrest (BOX)-trial.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) survivors face significant risks of complications and death from hypoxic-ischemic brain injury leading to withdrawal of life-sustaining treatment (WLST). Accurate multimodal neuroprognostication, including automated pupillometry, is essential to avoid inappropriate WLST. However, inconsistent study results hinder standardized threshold recommendations. We aimed to validate proposed pupillometry thresholds with no false predictions of unfavorable outcomes in comatose OHCA survivors. METHODS: In the multi-center BOX-trial, quantitative measurements of automated pupillometry (quantitatively assessed pupillary light reflex [qPLR] and Neurological Pupil index [NPi]) were obtained at admission (0 h) and after 24, 48, and 72 h in comatose patients resuscitated from OHCA. We aimed to validate qPLR < 4% and NPi ≤ 2, predicting unfavorable neurological conditions defined as Cerebral Performance Category 3-5 at follow-up. Combined with 48-h neuron-specific enolase (NSE) > 60 µg/L, pupillometry was evaluated for multimodal neuroprognostication in comatose patients with Glasgow Motor Score (M) ≤ 3 at ≥ 72 h. RESULTS: From March 2017 to December 2021, we consecutively enrolled 710 OHCA survivors (mean age: 63 ± 14 years; 82% males), and 266 (37%) patients had unfavorable neurological outcomes. An NPi ≤ 2 predicted outcome with 0% false-positive rate (FPR) at all time points (0-72 h), and qPLR < 4% at 24-72 h. In patients with M ≤ 3 at ≥ 72 h, pupillometry thresholds significantly increased the sensitivity of NSE, from 42% (35-51%) to 55% (47-63%) for qPLR and 50% (42-58%) for NPi, maintaining 0% (0-0%) FPR. CONCLUSION: Quantitative pupillometry thresholds predict unfavorable neurological outcomes in comatose OHCA survivors and increase the sensitivity of NSE in a multimodal approach at ≥ 72 h.

A practical magnetic-resonance imaging score for outcome prediction in comatose cardiac arrest survivors.

AIM: Magnetic Resonance Imaging (MRI) is an important prognostic tool in cardiac arrest (CA) survivors given its sensitivity for detecting hypoxic-ischemic brain injury (HIBI), however, it is limited by poorly defined objective thresholds. To address this limitation, we evaluated a qualitative MRI score for predicting neurological outcome in CA survivors. METHODS: Adult comatose CA survivors who underwent MRI were retrospectively identified at a single academic medical center. Two blinded neurointensivists qualitatively scored HIBI amongst 12 MRI brain regions. Scores were summated to form four distinct score groups: cortex, deep grey nuclei (DGN), cortex-DGN combined, and total (cortex, DGN, brainstem, and cerebellum). Poor neurological outcome was defined as Cerebral Performance Category (CPC) score 3-5 at hospital discharge. Inter-rater reliability was tested using intra-class correlation (ICC) and discrimination of poor neurological outcome assessed using area under the receiver operating curve (AUC). RESULTS: Our cohort included 219 patients with median time to MRI of 96 (IQR 81-110) hours. ICC (95% CI) was good to excellent across all MRI scores: cortex 0.92 (0.89-0.94), DGN 0.88 (0.80-0.92), cortex-DGN 0.94 (0.92-0.95), and total 0.93 (0.91-0.95). AUC (95% CI) for poor outcome was good across all MRI scores: cortex 0.84 (0.78-0.90), DGN 0.83 (0.77-0.89), cortex-DGN 0.83 (0.77-0.89), and total 0.83 (0.77-0.88). CONCLUSION: A simplified, qualitative MRI score had excellent reliability and good discrimination for poor neurologic outcome. Further work is necessary to externally validate our findings in an independent, ideally prospective, cohort.

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.

Prognosis of patients with prolonged disorders of consciousness after brain injury: a longitudinal cohort study.

Background: The findings regarding the prognosis of prolonged disorders of consciousness (PDOC) vary widely among different studies. This study aims to investigate the mortality, consciousness recovery and disabilities of patients with PDOC after brain injury. Methods: A total of 204 patients with PDOC were included in a longitudinal cohort study, including 129 males and 75 females. There were 112 cases of traumatic brain injury (TBI), 62 cases of cerebral hemorrhage (CH), 13 cases of cerebral infarction (CI) and 17 cases of ischemic hypoxic encephalopathy (IHE). The status of consciousness at 1, 2, 3, 6, 12, 18, 24, 36, 48 months of the disease course was assessed or followed up using the Revised Coma Recovery Scale (CRS-R). If the patients were conscious, the disability Rating Scale (DRS) was also performed. The prognosis of different PDOC including coma, vegetative state (VS) and minimal conscious state (MCS) was analyzed. The survival patients were screened for variables and included in multivariate binary Logistic regression to screen the factors affecting the recovery of consciousness. Results: The mortality rates at 12, 24, 36, and 48 months were 10.7, 23.4, 38.9, and 68.4%, respectively. The median time of death was 18 months (8.75, 29). The probability of MCS regaining consciousness was higher than VS (p < 0.05), with the degree of disability left lower than VS (p < 0.05). There was no significant difference between MCS- and MCS+ groups in terms of the probability of regaining consciousness, the extent of residual disability, and mortality rates (p > 0.05). The mortality rate of coma was higher than that of other PDOC (p < 0.05). The mortality rate of MCS was lower than that of VS, but the difference was not statistically significant (p > 0.05). The probability of consciousness recovery after TBI was the highest and the mortality rate was the lowest. The possibility of consciousness recovery in IHE was the least, and the mortality rate of CI was the highest. The cause of brain injury and initial CRS-R score were the factors affecting the consciousness recovery of patients (p < 0.05). Conclusion: The prognosis of MCS is more favorable than VS, with comparable outcomes between MCS- and MCS+, while comatose patients was the poorest. TBI has the best prognosis and IHE has the worst prognosis.

Complementary therapy with Chinese aromatic herbs to promote awakening in a comatose patient: A case report.

RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.

Alteration in early resting­state functional MRI activity in comatose survivors of cardiac arrest: a prospective cohort study.

BACKGROUND: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs). METHODS: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow-Pittsburgh cerebral performance category (CPC) scale at 3 months after CA. RESULTS: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001). CONCLUSIONS: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses. TRIAL REGISTRATION: NCT05966389 (Registered July 27, 2023).

Rationalising the dose threshold for severe carbamazepine toxicity: a retrospective series.

INTRODUCTION: Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. METHODS: This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). RESULTS: There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71-151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). DISCUSSION: Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. CONCLUSION: Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series.

Longitudinal associations of plasma amino acid levels with recovery from malarial coma.

BACKGROUND: Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations. METHODS: In a prospective observational study, 42 children with CM were enrolled. Amino acid levels were measured at entry and at frequent intervals thereafter and consciousness was assessed by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. Logistic regression was employed using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. RESULTS: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analysed at each sampling time. CONCLUSION: Longitudinal data is provided for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation and may contribute to CM pathogenesis.

Coma After Droperidol Administration: A Case Report.

In Switzerland, approximately 32,000 patients are hospitalized annually due to adverse drug reactions (ADRs), representing 2.3% of all hospitalizations. During the perioperative period, the administration of a variety of drugs from different classes over a relatively short period of time increases the risk of ADR. Here, we describe the case of a 32-year-old woman who was administered droperidol to treat nausea in the recovery room after a myomectomy and who subsequently became comatose. Correctable metabolic, respiratory, and cerebrovascular disorders were ruled out. Six hours after the event, she was extubated without residual effects. We discuss potential ADR for droperidol.

Markers of Mitochondrial Injury and Neurological Outcomes of Comatose Patients after Cardiac Arrest.

Background and Objectives: Most patients who are successfully resuscitated from cardiac arrest remain comatose, and only half regain consciousness 72 h after the arrest. Neuroprognostication methods can be complex and even inconclusive. As mitochondrial components have been identified as markers of post-cardiac-arrest injury and associated with survival, we aimed to investigate cytochrome c and mtDNA in comatose patients after cardiac arrest to compare neurological outcomes and to evaluate the markers' neuroprognostic value. Materials and Methods: This prospective observational study included 86 comatose post-cardiac-arrest patients and 10 healthy controls. Cytochrome c and mtDNA were determined at admission. Neuron-specific enolase (NSE) was measured after 72 h. Additional neuroprognostication methods were performed when patients remained unconscious. Cerebral performance category (CPC) was determined. Results: Cytochrome c was elevated in patients compared to healthy controls (2.029 [0.85-4.97] ng/mL vs. 0 [0.0-0.16], p < 0.001) but not mtDNA (95,228 [52,566-194,060] vs. 41,466 [28,199-104,708] copies/µL, p = 0.074). Compared to patients with CPC 1-2, patients with CPC 3-5 had higher cytochrome c (1.735 [0.717-3.40] vs. 4.109 [1.149-8.457] ng/mL, p = 0.011), with no differences in mtDNA (87,855 [47,598-172,464] vs. 126,452 [69,447-260,334] copies/µL, p = 0.208). Patients with CPC 1-2 and CPC 3-5 differed in all neuroprognostication methods. In patients with good vs. poor neurological outcome, ROC AUC was 0.664 (p = 0.011) for cytochrome c, 0.582 (p = 0.208) for mtDNA, and 0.860 (p < 0.001) for NSE. The correlation between NSE and cytochrome c was moderate, with a coefficient of 0.576 (p < 0.001). Conclusions: Cytochrome c was higher in comatose patients after cardiac arrest compared to healthy controls and higher in post-cardiac-arrest patients with poor neurological outcomes. Although cytochrome c correlated with NSE, its neuroprognostic value was poor. We found no differences in mtDNA.

Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study.

AIMS: To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension. METHODS AND RESULTS: A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P < 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67). CONCLUSION: Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

NCSE-coma in older adults: Clinical data, initial EEG, and hospital outcome.

INTRODUCTION: The clinical-EEG profile and prognosis in nonconvulsive status epilepticus (NCSE-coma) - with preceding SE and without preceding SE - have not been fully established yet. OBJECTIVE: To evaluate the initial EEG, clinical characteristics, and hospital outcome of older adults with NCSE-coma. METHODOLOGY: Clinical variables, immediate prognosis, initial EEG data, and scores on the Status Epilepticus Severity Score (STESS) and the SACE score were evaluated according to the type of NCSE-coma (with and without preceding seizure/SE) in 51 older adult patients treated in the emergency department. RESULTS: The mean age of the participants was 72.2 years. In 23 cases, the diagnosis was NCSE-coma with preceding seizure/SE, and in 28 cases the diagnosis was NCSE-coma without preceding seizure/SE. Previous history of seizures/epilepsy occurred in 11 cases (21.5 %), and was more frequent in NCSE-coma with preceding seizure/SE. The most common etiology was acute. Death within 30 days occurred in 21 cases (41.1 %), but there was no difference between types of NCSE-coma. The predominant EEG finding was the presence of epileptiform discharges/rhythmic delta activity showing morphological/spatial/temporal evolution (classified as A2 in the Salzburg Consensus Criteria [SCC]). There was a significant difference in EEG findings according to the type of NCSE-coma. Total SACE scores averaged 0.9 ± 0.8; on the STESS, it was 4.7 ± 0.4. In the SACE score, the highest total score and a more significant occurrence of scores ≥ 3 (indicating a better prognosis) were observed in NCSE-coma with preceding seizure/SE. CONCLUSION: In older adults, the types of NCSE-coma presented different clinical aspects and patterns on initial EEG. The mortality rates were elevated. The most prevalent EEG findings encompass criteria A2 of the SCC. A history of previous seizures/epilepsy and a more favorable prognosis in the SACE score occurred in NCSE-coma with preceding seizure/SE.