Impact of healthcare system strain on the implementation of ICU sedation practices and encephalopathy burden during the early COVID-19 pandemic.

The COVID-19 pandemic posed unprecedented challenges to healthcare systems worldwide, particularly in managing critically ill patients requiring mechanical ventilation early in the pandemic. Surging patient volumes strained hospital resources and complicated the implementation of standard-of-care intensive care unit (ICU) practices, including sedation management. The objective of this study was to evaluate the impact of an evidence-based ICU sedation bundle during the early COVID-19 pandemic. The bundle was designed by a multi-disciplinary collaborative to reinforce best clinical practices related to ICU sedation. The bundle was implemented prospectively with retrospective analysis of electronic medical record data. The setting was the ICUs of a single-center tertiary hospital. The patients were the ICU patients requiring mechanical ventilation for confirmed COVID-19 between March and June 2020. A learning health collaborative developed a sedation bundle encouraging goal-directed sedation and use of adjunctive strategies to avoid excessive sedative administration. Implementation strategies included structured in-service training, audit and feedback, and continuous improvement. Sedative utilization and clinical outcomes were compared between patients admitted before and after the sedation bundle implementation. Quasi-experimental interrupted time-series analyses of pre and post intervention sedative utilization, hospital length of stay, and number of days free of delirium, coma, or death in 21 days (as a quantitative measure of encephalopathy burden). The analysis used the time duration between start of the COVID-19 wave and ICU admission to identify a "breakpoint" indicating a change in observed trends. A total of 183 patients (age 59.0 ± 15.9 years) were included, with 83 (45%) admitted before the intervention began. Benzodiazepine utilization increased for patients admitted after the bundle implementation, while agents intended to reduce benzodiazepine use showed no greater utilization. No "breakpoint" was identified to suggest the bundle impacted any endpoint measure. However, increasing time between COVID-19 wave start and ICU admission was associated with fewer delirium, coma, and death-free days (ß = - 0.044 [95% CI - 0.085, - 0.003] days/wave day); more days of benzodiazepine infusion (ß = 0.056 [95% CI 0.025, 0.088] days/wave day); and a higher maximum benzodiazepine infusion rate (ß = 0.079 [95% CI 0.037, 0.120] mg/h/wave day). The evidence-based practice bundle did not significantly alter sedation utilization patterns during the first COVID-19 wave. Sedation practices deteriorated and encephalopathy burden increased over time, highlighting that strategies to reinforce clinical practices may be hindered under conditions of extreme healthcare system strain.

Neurosurgical intervention in ultra-severe closed traumatic brain injury: Is it worth the effort?

Introduction: A subgroup of severe Traumatic Brain Injury (TBI) patients, known as ultra-severe (us-TBI), is most commonly defined as a post-resuscitation Glasgow Coma Scale (GCS) of 3-5. There is uncertainty on whether these critically injured patients can benefit from neurosurgical intervention. Research question: The available evidence regarding the decision-making and outcome following management of us-TBI patients is critically reviewed. Material and methods: Selected databases (PubMed, Google Scholar, Scopus and Cochrane Library) were searched from 1979 to May 2024 for publications on us-TBI patients, with a focus on treatment strategy, mortality and functional outcomes. Inclusion criteria were adult patients >18 years old with closed head trauma and admission post-resuscitation GCS 3-5. Studies were independently assessed for inclusion by two reviewers, and potential disagreements were solved by consensus. Results: Where such data could be extracted, mortality rate was 27-100%, and favorable outcome was observed in 4-30% of us-TBI patients. While early aggressive neurosurgical management was associated with decreased mortality, a high proportion of patients survived with unfavorable functional status. Discussion and conclusion: With supportive care only, outcome of patients with us-TBI is almost universally poor. Early and aggressive neurosurgical intervention in addition to best medical management can lead to favorable functional outcome in selected cases particularly in younger patients with an initial GCS>3 and traumatic mass lesions. There is insufficient data regarding the effectiveness of neurosurgical management on the outcome of us-TBI patients. and the decision to initiate treatment should be based on an individual basis.

[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.

The Development of Myxedema Coma in the Setting of Euthyroid Sick Syndrome: A Diagnostic Dilemma and Review of Management Strategies.

Euthyroid sick syndrome (ESS), also referred to as nonthyroidal illness syndrome, is an intriguing condition characterized by dysregulation of thyroid hormones despite normal thyroid gland function. It is diagnosed by low serum triiodothyronine levels, and, in some cases, other thyroid hormones such as thyroxine and thyroid-stimulating hormone may be affected. This condition arises via various physiologic mechanisms and is associated with intensive care unit (ICU) admissions, caloric deprivation, and severe illness. Myxedema coma (MC) is a rare medical emergency with a high mortality rate. It is caused by severe hypothyroidism, resulting in multiorgan failure with features including adrenal insufficiency, thermal dysregulation, and altered mentation. Generally, it is observed in untreated and poorly managed cases of hypothyroidism. However, stress from infections, surgical procedures, and medical comorbidities may precipitate this condition. It is particularly uncommon to see MC arise in the setting of ESS, especially in a patient with no history of thyroid disease, which makes this diagnosis easy to miss. In our case, a 36-year-old female presented with septic shock and was admitted to the ICU, where she subsequently developed ESS and features of MC. This case report aims to explore the risk factors, features, and diagnostic and therapeutic management of these conditions, as well as the diagnostic challenges that arise when these diseases present simultaneously.

The Role of Systemic Inflammation in the Pathogenesis of Spontaneous Intracranial Hemorrhage in the Presence or Absence of Effective Cerebral Blood Flow.

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1-3/5-8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood-brain barrier for tissue breakdown products and other neuroinflammatory factors.

Outcomes and Practices of Endotracheal Intubation Using the Glasgow Coma Scale in Acute Non-Traumatic Poisoning: A Systematic Review and Meta-Analysis of Proportions.

BACKGROUND: Acute poisoning often results in decreased consciousness, necessitating airway assessment and management. Existing literature in the trauma setting suggests the importance of airway protection in unconscious patients to prevent complications, including aspiration. Practices for endotracheal intubation in non-traumatic acute poisoning are poorly described and variable, particularly regarding the use of a Glasgow Coma Scale (GCS) ≤ 8 threshold for intubation. METHODS: A systematic review and meta-analysis of proportions was conducted to evaluate intubation rates and outcomes in patients presenting for acute non-traumatic poisoning. Studies were excluded if the primary indication for intubation was not airway protection. We analyzed rates of intubation, mortality, and aspiration by subgrouping patients into GCS ≤ 8, GCS 9-15, or mixed GCS. Common and random-effects analysis were used, supplemented by subgroup analyses. RESULTS: 39 studies were included in the analysis, involving 15,959 patients. Random-effects pooled intubation rates varied significantly across GCS categories: GCS ≤ 8 (30.0%, I2 = 92%, p < 0.01), GCS 9-15 (1.0%, I2 = 0%, p = 0.91), and mixed GCS (11.0%, I2 = 94%, p < 0.01), p-value <0.01 for subgroup difference. Aspiration rates also varied: GCS ≤ 8 (19.0%, I2 = 84%, p < 0.01), GCS 9-15 (4.0%, I2 = 78%, p < 0.01), and mixed group (5.0%, I2 = 72%, p < 0.01), p-value <0.01 for subgroup difference. Mortality rates remained low across all groups: GCS ≤ 8 (1.0%, I2 = 0%, p = 0.62), GCS 9-15 (1.0%, I2 = 0%, p = 0.99), and mixed group (2.0%, I2 = 68%, p < 0.01). CONCLUSION: The conventional "less than 8, intubate" approach may not be directly applicable to acute poisoning patients due to heterogeneity in patient presentation, intubation practices, and low mortality. Therefore, a nuanced approach is warranted to optimize airway management strategies tailored to individual patient needs.

Quantitative and Radiological Assessment of Post-cardiac-Arrest Comatose Patients with Diffusion-Weighted Magnetic Resonance Imaging.

BACKGROUND: Although magnetic resonance imaging, particularly diffusion-weighted imaging, has increasingly been used as part of a multimodal approach to prognostication in patients who are comatose after cardiac arrest, the performance of quantitative analysis of apparent diffusion coefficient (ADC) maps, as compared to standard radiologist impression, has not been well characterized. This retrospective study evaluated quantitative ADC analysis to the identification of anoxic brain injury by diffusion abnormalities on standard clinical magnetic resonance imaging reports. METHODS: The cohort included 204 previously described comatose patients after cardiac arrest. Clinical outcome was assessed by (1) 3-6 month post-cardiac-arrest cerebral performance category and (2) coma recovery to following commands. Radiological evaluation was obtained from clinical reports and characterized as diffuse, cortex only, deep gray matter structures only, or no anoxic injury. Quantitative analyses of ADC maps were obtained in specific regions of interest (ROIs), whole cortex, and whole brain. A subgroup analysis of 172 was performed after eliminating images with artifacts and preexisting lesions. RESULTS: Radiological assessment outperformed quantitative assessment over all evaluated regions (area under the curve [AUC] 0.80 for radiological interpretation and 0.70 for the occipital region, the best performing ROI, p = 0.011); agreement was substantial for all regions. Radiological assessment still outperformed quantitative analysis in the subgroup analysis, though by smaller margins and with substantial to near-perfect agreement. When assessing for coma recovery only, the difference was no longer significant (AUC 0.83 vs. 0.81 for the occipital region, p = 0.70). CONCLUSIONS: Although quantitative analysis eliminates interrater differences in the interpretation of abnormal diffusion imaging and avoids bias from other prediction modalities, clinical radiologist interpretation has a higher predictive value for outcome. Agreement between radiological and quantitative analysis improved when using high-quality scans and when assessing for coma recovery using following commands. Quantitative assessment may thus be more subject to variability in both clinical management and scan quality than radiological assessment.

Myxedema Coma: Recognition of a Rare Endocrine Emergency.

An 82-year-old patient with multiple comorbidities presented to the emergency department with progressive dyspnea, orthopnea, and anorexia. Despite initial treatment for community-acquired pneumonia and decompensated heart failure, her condition deteriorated, manifesting as severe hypotension, bradycardia, and refractory hypothermia. A detailed medical history and extensive systematic investigation led to the documentation of hypothyroidism complicated by myxedema coma, in the context of chronic amiodarone use and precipitated by sepsis. Treatment with intravenous levothyroxine and glucocorticoids resulted in significant clinical improvement, leading to eventual hospital discharge. This case highlights the complexity and diagnostic challenges of myxedema coma, emphasizing the importance of early recognition, appropriate application of diagnostic scoring systems, and describing key aspects of the proper management of this rare endocrine emergency, whose symptoms and clinical signs are nonspecific.

Comparison and combined use of NEWS2 and GCS scores in predicting mortality in stroke and traumatic brain injury: a multicenter retrospective study.

Objective: This study aims to assess the effectiveness of the National Early Warning Score 2 (NEWS2) versus Glasgow Coma Scale (GCS) in predicting hospital mortality among patients with stroke and traumatic brain injury (TBI). Location: This multicenter study was conducted at two anonymized tertiary care hospitals in distinct climatic regions of China, with a combined annual emergency admission exceeding 10,000 patients. Patients: The study included 2,276 adult emergency admissions diagnosed with stroke (n = 1,088) or TBI (n = 1,188) from January 2021 to December 2023, excluding those with chronic pulmonary disease, severe cardiac conditions, or a history of brain surgery. Measuring and main outcomes: The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to analyze the predictive accuracy of NEWS2 and GCS for hospital mortality at 24, 48, and 72 h post-admission and at discharge. Results: Out of 2,276 patients (mean age 61.4, 65.6% male), 1855 survived while 421 succumbed. NEWS2 demonstrated superior predictive accuracy (AUC = 0.962) over GCS (AUC = 0.854) for overall hospital mortality. Specifically, NEWS2 outperformed GCS in predicting mortality at 24 h (0.917 vs. 0.843), 48 h (0.893 vs. 0.803), and 72 h (0.902 vs. 0.763). Notably, despite a higher AUC for NEWS2 at predicting 24-h hospital mortality, the sensitivity and specificity of GCS were considerably lower (12 and 31%, respectively) compared to NEWS2 (sensitivity of 95% and specificity of 81%). Subgroup analysis showed NEWS2 outperforming GCS in predicting in-hospital mortality for TBI and stroke patients. For TBI patients (n = 260), NEWS2 had an AUC of 0.960 (95% CI: 0.948-0.973) vs. GCS's AUC of 0.811 (95% CI: 0.781-0.840). For stroke patients (n = 161), NEWS2 had an AUC of 0.930 (95% CI: 0.908-0.952) vs. GCS's AUC of 0.858 (95% CI, 0.823-0.892). NEWS2 showed greater sensitivity in both groups, highlighting its effectiveness in identifying high-risk neurological patients. Conclusion: NEWS2 scores are more precise and effective in predicting hospital mortality in stroke and TBI patients compared to GCS scores, although slightly less so within the first 24 h. Combining NEWS2 with GCS and clinical findings within the initial 24 h is recommended for a comprehensive prognosis evaluation.

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.

Topography-guided photorefractive keratectomy combined with accelerated corneal collagen cross-linking versus cross-linking alone for progressive keratoconus: a long-term prospective cohort study.

Purpose: To comprehensively compare the long-term outcome of the combined topography guided photorefractive keratectomy (TG-PRK) with accelerated corneal cross-linking (ACXL) and ACXL alone in eyes with progressive keratoconus. The analysis focused on the changes in the detailed corneal aberrometric values. Methods: This single-center, prospective cohort study included 28 patients (30 eyes) of the TG-PRK plus ACXL group and 14 patients (15 eyes) of the ACXL alone group. The mean duration of the follow-up was 44 ± 10.18 months (ranged from 31 to 65 months). The preoperative data and the postoperative measurement data at the last follow-up visit, including demographic data, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, corneal topography, pachymetry, aberrometry and densitometry were analyzed. Results: The CDVA significantly improved in the TG-PRK plus ACXL group at the last follow-up visit (p = 0.006), while no significant improvement was found in the ACXL alone group (p = 0.432). The maximal keratometry of the anterior corneal surface (Kmax) of both groups significantly decreased at the last follow-up visit (p < 0.05). Compared with the ACXL alone group, the Kmax of the TG-PRK plus ACXL group showed a greater decline (p = 0.008). The total corneal aberrations, the corneal lower-order aberrations (LOAs), the corneal higher order aberrations (HOAs), the vertical coma and the spherical aberration (SA) at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group significantly decreased at the last follow-up visit (all p < 0.05). The declines of the total corneal aberrations, the corneal LOAs, the corneal HOAs and the vertical coma at the 4.0 mm and 6.0 mm zone of the TG-PRK plus ACXL group were significantly higher than those in the ACXL alone group (p < 0.001). Conclusion: Compared with ACXL alone, combined TG-PRK with ACXL procedure had a significantly higher reduction in the corneal HOAs and better CDVA, while providing a similar long-term stability and safety. For progressive keratoconus patients with adequate corneal thickness, the combined procedure might be a recommended treatment option.

Non-motor role of the cerebellum: Cerebellar mutism syndrome in a child with a small hemorrhagic contusion in the dentate nucleus: A case report and literature review.

Key Clinical Message: Our case report highlights that Prompt recognition of cerebellar mutism syndrome (CMS) is critical in clinical practice, as it is often misdiagnosed as just being reduction in the level of consciousness, particularly in pediatrics trauma patients. Abstract: Cerebellar mutism syndrome is defined as transient mutism following posterior fossa surgery, hemorrhage or traumatic insults involving the cerebellum. Cerebellar mutism syndrome (CMS) is now recognized as a form of cerebellar cognitive affective syndrome (CCAS/Schmahmann syndrome). CMS following head injury is exceedingly rare with very few cases reported. Five years old boy with normal developmental milestones and no significant medical history, sustained closed head injury following road traffic accident, the clinical scenario in addition to the radiological findings led to the diagnosis of cerebellar mutism syndrome. CMS is defined as of neurologic and cognitive disorders, mainly speech disorder. Patient non-motor signs recovered in a period of few weeks from the mutism syndrome with remaining mild motor deficit. CMS is a set of neurologic and cognitive disorders, the most distinct of which is speech disorder (usually reversible), what is unique about this case is the selective site of the contusion at the region of the dentate nucleus and superior cerebellar peduncle. Such cases offer a better understanding to the function of the cerebellum and its role in cognition. Additionally, the knowledge of this aspect of cerebellar function helps in better predicting the clinical course of such lesions which in turn helps in communication and explanation to patient's families.

Prognostic Value of Dynamic Segmented Neutrophil to Monocyte (SeMo) Ratio Changes in Patients with Moderate to Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients, necessitating reliable prognostic tools. The segmented neutrophil-to-monocyte (SeMo) ratio, indicative of the inflammatory response, has emerged as a valuable biomarker. This study evaluates the prognostic value of dynamic changes in the SeMo ratio in predicting outcomes for patients with moderate to severe TBI. METHODS: A retrospective analysis was conducted on data from 1118 TBI patients admitted to the surgical intensive care unit at a level I trauma center between January 2009 and December 2020. Patients were selected based on an Abbreviated Injury Scale (AIS) score ≥ 3 in the head region. Initial and follow-up SeMo ratios were calculated upon admission and 48-72 h later, respectively. The dynamic SeMo ratio was defined as the difference between the second and initial SeMo ratios. Statistical analyses included receiver operating characteristic (ROC) curve analysis to determine the optimal threshold for mortality prediction, and comparative analysis of clinical outcomes. RESULTS: The study cohort included 121 deceased and 997 surviving patients. Deceased patients had significantly higher second SeMo ratios (20.9 ± 16.1 vs. 15.8 ± 17.2, p = 0.001) and dynamic SeMo ratios (2.4 ± 19.8 vs. -2.1 ± 19.5, p = 0.019) than those survival patients. In the multivariate analysis, the dynamic SeMo is a significant independent risk factor for in-hospital mortality (OR 1.01, 95%CI: 1.01-1.03, p = 0.031). The optimal cut-off for the dynamic SeMo ratio was 5.96, above which patients exhibited higher mortality (21.4% vs. 8.5%, p < 0.001), higher adjusted mortality (adjusted odds ratio: 2.98; 95% confidence interval: 1.95-4.56; p = 0.005), and longer hospital stays (23.6 days vs. 19.7 days, p = 0.005). DISCUSSION: Dynamic SeMo ratio changes serve as a prognostic marker for in-hospital mortality and hospital stay duration in moderate to severe TBI patients. A higher dynamic SeMo ratio indicates increased risk, highlighting the importance of early monitoring and intervention. Future prospective studies should validate these findings and explore integration with other biomarkers for enhanced prognostication.

Burst-Suppression EEG Reactivity to Photic Stimulation-A Translational Biomarker in Hypoxic-Ischemic Brain Injury.

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic-ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

High frequency oscillations may improve somatosensory evoked potential detection of good outcomes in disorders of consciousness secondary to acute neurologic injury.

BACKGROUND: Somatosensory evoked potentials (SEPs) are highly specific predictors of poor prognosis in hypoxic-ischemic coma when cortical responses (N20s) are absent. However, bilateral N20 presence is nonspecific for good outcomes. High-frequency oscillations (HFOs) in the SEP waveform predict neurologic recovery in animals, but clinical applications are poorly understood. We sought to develop a clinical measure of HFOs to potentially improve detection of good outcomes in coma. MATERIALS AND METHODS: We collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020 to 2022 at Johns Hopkins Hospital. We developed a novel measure - HFO evoked to spontaneous ratios (HFO-ESRs) - and applied this to those patients with bilaterally present N20s using both standard univariate classification and cubic kernal vector machine (SVM) models to predict the last documented in-hospital Glasgow Coma Scale (GCS) prior to discharge or death. RESULTS: Of 58 total patients, 34 (58.6%) had bilaterally present N20s. Of these, 14 had final GCS>=9, and 20 had final GCS<=8. Mean age was 52 (+/- 17) years, 20.1% female. Etiologies of coma were primarily global hypoxic-ischemic brain injury (79.4%), intracranial hemorrhage (11.8%), and traumatic brain injury (2.9%). In univariate classification, the addition of averaged HFO-ESRs to bilaterally present N20s predicted final GCS>=9 with 68% specificity. The SVM model further improved specificity to 85%. CONCLUSIONS: In this pilot investigation, we developed a novel clinical measure of SEP HFOs. Incorporation of this measure may improve the specificity of the SEP to predict in-hospital GCS outcomes in coma, but requires further validation in specific neurologic injuries and with longitudinal outcomes.

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.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Outcomes and Endpoints.

BACKGROUND: Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs. METHODS: The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms. RESULTS: Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children. CONCLUSIONS: The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges.

Functional near-infrared spectroscopy: A novel tool for detecting consciousness after acute severe brain injury.

Recent advancements in functional neuroimaging have demonstrated that some unresponsive patients in the intensive care unit retain a level of consciousness that is inconsistent with their behavioral diagnosis of awareness. Functional near-infrared spectroscopy (fNIRS) is a portable optical neuroimaging method that can be used to measure neural activity with good temporal and spatial resolution. However, the reliability of fNIRS for detecting the neural correlates of consciousness remains to be established. In a series of studies, we evaluated whether fNIRS can record sensory, perceptual, and command-driven neural processing in healthy participants and in behaviorally nonresponsive patients. At the individual healthy subject level, we demonstrate that fNIRS can detect commonly studied resting state networks, sensorimotor processing, speech-specific auditory processing, and volitional command-driven brain activity to a motor imagery task. We then tested fNIRS with three acutely brain injured patients and found that one could willfully modulate their brain activity when instructed to imagine playing a game of tennis-providing evidence of preserved consciousness despite no observable behavioral signs of awareness. The successful application of fNIRS for detecting preserved awareness among behaviorally nonresponsive patients highlights its potential as a valuable tool for uncovering hidden cognitive states in critical care settings.

Circulating soluble CD163 is associated with reduced Glasgow Coma Score and 1-year all-cause mortality in traumatized patients.

Soluble CD163 (sCD163) is a biomarker of macrophage activation, not previously investigated in the circulation of traumatized patients. A biobank of 398 adult trauma patients was analyzed. Patients with an Injury Severity Score (ISS) >8 served as trauma patients (n = 195) and those with ISS ≤8 as trauma controls (n = 203). Serum samples obtained upon admission, 15h and 72h after were analyzed for sCD163 using an in-house ELISA. Multiple linear regression was used to analyze the association between admission levels of sCD163 with, 1: overall trauma severity (ISS), and 2: severity of injury to specified organs using Abbreviated Injury Score (AIS) and Glasgow Coma Scale (GCS). The association between the peak level of sCD163 with 1-year all-cause mortality was analyzed by logistic regression analysis. Median admission levels of sCD163 were higher in trauma patients than trauma controls [2.32 (IQR 1.73 to 2.86) vs. 1.92 (IQR 1.41 to 2.51) mg/L, p < 0.01]. Worsening GCS score was associated with a 10.3% (95% CI: 17.0 to 3.1, p < 0.01) increase in sCD163. Increasing Head-AIS score was associated with a 5.1% (95% CI: -0.5 to 11.0, p = 0.07) increase in sCD163. The remaining AIS scores and ISS were not consistently associated with sCD163 admission levels. Each mg/L increase in sCD163 peak level had an odds ratio 1.34 (95%CI: 0.98 to 1.83), p = 0.06) after adjustment for age, sex, and GCS. Circulating sCD163 is increased in traumatized patients and associated with worsening GCS. Our findings suggest an association between circulating sCD163 levels with 1-year all-cause mortality.

Mismatch Negativity and P300 in the Diagnosis and Prognostic Assessment of Coma and Other Disorders of Consciousness.

BACKGROUND: The objective of this study was to investigate the value of mismatch negativity (MMN) and P300 event-related potentials for discriminating the consciousness state and predicting improvement of consciousness at 6 months in patients with coma and other disorders of consciousness (DOC). METHODS: We performed MMN and P300 on 42 patients with DOC with a mean onset time of 40.21 ± 19.43 days. These patients with DOC were categorized into coma, unresponsive wakefulness syndrome (UWS), minimal consciousness minus (MCS-), and minimal consciousness plus (MCS +) groups according to neurobehavioral assessment and the Coma Recovery Scale-Revised score. The primary outcome was the improvement of consciousness at 6 months in patients with DOC. We assessed the efficacy of MMN and P300 in quantitatively predicting the prognosis at 6 months and the capability of MMN and P300 parameters to differentiate between DOC. RESULTS: At least one significant difference in either MMN or P300 parameters was displayed among the DOC groups, but not between the MCS- and MCS+ groups (significance level: 0.05). Both MMN and P300 amplitudes showed desirable predictive accuracy at 6 months, with areas under the curve (AUCs) of 0.859 and 0.856, respectively. The optimal thresholds for MMN and P300 amplitudes were 2.044 and 1.095 µV. However, the combined MMN-P300 amplitude showed better 6-month predictive accuracy (AUC 0.934, 95% confidence interval 0.860-1.000), with a sensitivity of 85% and a specificity of 90.9%. CONCLUSIONS: MMN and P300 may help discriminate among coma, UWS, and MCS, but not between patients with MCS- and patients with MCS+ . The MMN amplitude, P300 amplitude, and especially combined MMN-P300 amplitude at 6 months may be interesting predictors of consciousness improvement at 6 months in patients with DOC. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier ChiCTR2400083798.