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 (β =  - 0.044 [95% CI - 0.085, - 0.003] days/wave day); more days of benzodiazepine infusion (β = 0.056 [95% CI 0.025, 0.088] days/wave day); and a higher maximum benzodiazepine infusion rate (β = 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.

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.
METHODS: Observational cohort study.
METHODS: German Resuscitation Registry covering more than 31 million inhabitants of Germany and Austria.
METHODS: All adult patients between 2006 and 2022 with out-of-hospital or in-hospital cardiac arrest and comatose on admission.
METHODS: 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.
CONCLUSIONS: 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.

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.
功能性昏迷伴假性猝倒发作的分离/转换障碍病例罕见。2021年12月9日山东第一医科大学第一附属医院神经内科收治1例分离/转换障碍青年女性患者,主要表现为发作性意识障碍、猝倒、小便失禁。完善实验室检查及颅脑MRI未见明显异常,行标准多导睡眠监测及多次睡眠潜伏期试验,患者小睡间期无法唤醒,行刺激试验,对压眶、大声呼叫、拍打无反应,但头部导联均为α节律,下颌肌电示肌张力增高,提示为清醒期。行24 h睡眠监测,患者夜间睡眠充足,早晨唤醒容易。行日间无限制睡眠及唤醒试验,患者上午及下午各小睡1次,在导联提示N3期进入N2期睡眠时对患者进行唤醒试验,此时患者可对周围环境进行反应并正确回答问题。检测脑脊液食欲素水平>110 pg/mL,可排除发作性睡病,考虑为伴假性猝倒发作的功能性昏迷。给予口服药物症状改善不明显,建议停口服药并调整作息、情绪,半年后随访,患者诉自行调整生活方式后未再发作,至今3年多次随访均未再出现类似症状。合并有猝倒样发作的功能性昏迷易误诊,需与真性昏迷及发作性睡病相鉴别。.

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.

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.

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.
METHODS: We collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020-2022 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 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.

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.

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.
CONCLUSIONS: 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.

暂无摘要。

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.