Early Coma Research Articles

Quantitative EEG and brain network analysis: predicting awakening from early coma after cardiopulmonary resuscitation

ABSTRACT Objective For patients in early coma after cardiopulmonary resuscitation (CPR), quantitative electroencephalogram (EEG) and brain network analysis was performed to identify relevant indicators of awakening. Methods A prospective cohort study was conducted on comatose patients after CPR in the neuro-critical care unit. The included patients received clinical evaluation. The bedside high-density (64-lead) EEG monitoring was performed for visual grading and calculation of power spectrum and brain network parameters. A 3-month prognostic assessment was performed and the patients were dichotomized into the awakening group and the unawakening group. Results A total of 25 patients were included. The awakening group had higher GCS score, more slow wave pattern and reactive EEG than the unawakening group (P = 0.003, P < 0.001, P < 0.001, respectively). Compared with the unawakening group, (1) the awakening group had significantly higher absolute and relative θ power and slow/fast band ratio of the whole brain (P < 0.05), (2) the awakening group had stronger connection based on coherence, phase synchronization, phase lag index and cross-correlation (P < 0.05), (3) the awakening group had higher small-worldness, clustering coefficient and average path length based on graph theory (P < 0.05). Conclusions The power spectrum and brain network characteristics in patients in early coma after CPR have predictive value for recovery.

Predictor of failed cancer resuscitation by expert agreement

Purpose: Cardiopulmonary resuscitation (CPR) in end-of-life and critical patients, specifically cancer in hospitals, often faces a dilemma between resuscitation or non-resuscitation. This study will determine the predictors of resuscitation failure for cancer patients by expert agreement. Materials and Methods: Predictor’s variables were collected from review 20 research journals based on cancer patients who expired and were not successfully resuscitated. From 20 research journal, we found only 11 articles that mentioned the variables involved in resuscitation failure and death in cancer patients. To find out which predictors occur the most in Indonesia, we asked 5 expert palliative anesthesiologists as an expert from a palliative center hospital in Indonesia to choose the predictor that relate to resuscitation failure. To measure the agreement, we use Fleiss–Kappa statistic method with SPSS software ver. 20. Results: Based on the agreement of the experts (k &gt;0.8), eight of 44 predictors were noted for cardiopulmonary resuscitation failure in cancer patients that are expected to occur in Indonesia, namely: AIDS (acquired immunodeficiency syndrome), CPR &gt; 15′, non-recovery of heart rate after CPR &gt;20 min, electrocardiogram (ECG) rhythm asystole, early coma, hepatic insufficiency, non-shockable heart rhythm, and pulseless electrical activity (PEA). Conclusions: Experts agree that AIDS, CPR &gt;15′, non-recovery of heart rate after CPR &gt;20 min, ECG asystole rhythm, early coma, hepatic insufficiency, non-shockable heart rhythm, and PEA are dominant predictors for CPR failure in cancer patients.

Editorial introductions

Current Opinion in Critical Care was launched in 1995. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of critical care is divided into 13 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Mauro OddoMauro OddoMauro Oddo is Professor of Critical Care Medicine at the University of Lausanne, Head Physician at the Department of Intensive Care Medicine, at the CHUV-Lausanne University Hospital, Switzerland. He is a general intensivist with a specific interest and expertise in neurocritical care and neuromonitoring. He is also a Swiss National Science Foundation (SNF) supported researcher, Director of the Critical Care Clinical Research Unit, leading the Neuroscience Critical Care Research Group inside the same Department. His clinical research focuses on the mechanisms of energy dysfunction after acute brain injury in humans, and the use of advanced neuromonitoring techniques in metabolomics studies, Phase II translational trials, and to assess early coma prognostication. He is actively involved and regularly invited at main international postgraduate congresses of intensive care, neurocritical care and resuscitation medicine. He has published more than 180 articles in the field. Constantine J. KarvellasConstantine J. KarvellasDr Constantine J. Karvellas is an Associate Professor of Medicine (Critical Care Medicine and Gastroenterology/Hepatology) at the University of Alberta, Canada, and an Adjunct Professor in the School of Public Health Sciences. He has been an attending intensivist in the E. Garner King General Systems Intensive Care Unit since 2009 and is involved with the Liver Transplant program as a Hepatologist. Dr Karvellas is a co-investigator in the NIH-funded United States Acute Liver Failure study group (US ALFSG). He is also a Vice-chair of the Society of Critical Care Medicine (SCCM) Liver management task force. Dr Karvellas’ publications reflect his interests in acute liver failure (ALF), acute on chronic liver failure (ACLF), liver transplantation and extracorporeal liver support.

Role of automated pupillometry in critically ill patients.

Pupillary examination has fundamental diagnostic and prognostic values in clinical practice. However, pupillary assessment was relied until present on manual, qualitative, examination, using manual flash penlights or lamps. Quantitative examination with the use of automated infrared video-pupillometers allows an objective assessment of several pupillary parameters and may be superior to manual subjective examination. The potential for quantitative pupillometry is multiple in the setting of critical care, for the monitoring and detection of secondary cerebral insults and to assess brainstem dysfunction and early coma outcome prognostication, and in the intra-operative anesthesiology setting, to assess analgesia and opioid requirement. Here, we describe the pupillometry technique and review recent critical care and anesthesiology studies that demonstrate the value and potential clinical utility of quantitative pupillometry as neuromonitoring bedside modality.

Automated auditory mismatch negativity paradigm improves coma prognostic accuracy after cardiac arrest and therapeutic hypothermia.

EEG and somatosensory evoked potential are highly predictive of poor outcome after cardiac arrest; their accuracy for good recovery is however low. We evaluated whether addition of an automated mismatch negativity-based auditory discrimination paradigm (ADP) to EEG and somatosensory evoked potential improves prediction of awakening. EEG and ADP were prospectively recorded in 30 adults during therapeutic hypothermia and in normothermia. We studied the progression of auditory discrimination on single-trial multivariate analyses from therapeutic hypothermia to normothermia, and its correlation to outcome at 3 months, assessed with cerebral performance categories. At 3 months, 18 of 30 patients (60%) survived; 5 had severe neurologic impairment (cerebral performance categories = 3) and 13 had good recovery (cerebral performance categories = 1-2). All 10 subjects showing improvements of auditory discrimination from therapeutic hypothermia to normothermia regained consciousness: ADP was 100% predictive for awakening. The addition of ADP significantly improved mortality prediction (area under the curve, 0.77 for standard model including clinical examination, EEG, somatosensory evoked potential, versus 0.86 after adding ADP, P = 0.02). This automated ADP significantly improves early coma prognostic accuracy after cardiac arrest and therapeutic hypothermia. The progression of auditory discrimination is strongly predictive of favorable recovery and appears complementary to existing prognosticators of poor outcome. Before routine implementation, validation on larger cohorts is warranted.

Robust discrimination between EEG responses to categories of environmental sounds in early coma

Humans can recognize categories of environmental sounds, including vocalizations produced by humans and animals and the sounds of man-made objects. Most neuroimaging investigations of environmental sound discrimination have studied subjects while consciously perceiving and often explicitly recognizing the stimuli. Consequently, it remains unclear to what extent auditory object processing occurs independently of task demands and consciousness. Studies in animal models have shown that environmental sound discrimination at a neural level persists even in anesthetized preparations, whereas data from anesthetized humans has thus far provided null results. Here, we studied comatose patients as a model of environmental sound discrimination capacities during unconsciousness. We included 19 comatose patients treated with therapeutic hypothermia (TH) during the first 2 days of coma, while recording nineteen-channel electroencephalography (EEG). At the level of each individual patient, we applied a decoding algorithm to quantify the differential EEG responses to human vs. animal vocalizations as well as to sounds of living vocalizations vs. man-made objects. Discrimination between vocalization types was accurate in 11 patients and discrimination between sounds from living and man-made sources in 10 patients. At the group level, the results were significant only for the comparison between vocalization types. These results lay the groundwork for disentangling truly preferential activations in response to auditory categories, and the contribution of awareness to auditory category discrimination.

Improvements in Hepatic Serological Biomarkers Are Associated with Clinical Benefit of Intravenous N-Acetylcysteine in Early Stage Non-Acetaminophen Acute Liver Failure

N-acetylcysteine (NAC) improves transplant-free survival in early coma grade (I-II) patients with non-acetaminophen induced acute liver failure (ALF). We determined whether the clinical benefit was associated with improvements in hepatic function. In a prospective, double blind trial, 173 ALF patients without evidence of acetaminophen overdose were stratified by coma grade (I-II vs. III-IV) and randomly assigned to receive either intravenous NAC or dextrose (placebo) for 72 h, resulting in four patient groups. INR, ALT, bilirubin, creatinine, and AST obtained on admission (day 1) and subsequent days (days 2-4) were used for secondary analysis performed by fitting longitudinal logistic regression models to predict death or transplantation or transplantation alone. Treatment group and day of study in models including bilirubin or ALT were predictors of transplantation or death (maximum p < 0.03). Those patients with early coma grade who were treated with NAC showed significant improvement in bilirubin and ALT levels when compared to the other three groups (maximum p < 0.02 for NAC 1-2 vs. the 3 other treatments) when predicting death or transplantation. Treatment group, day of study, and bilirubin were predictors of transplantation (maximum p < 0.03) in ALF patients. The decreased risk of transplantation or death or of transplantation alone with intravenous NAC in early coma grade patients with non-acetaminophen induced ALF was reflected in improvement in parameters related to hepatocyte necrosis and bile excretion including ALT and bilirubin, but not in INR, creatinine, or AST. Hepatic recovery appears hastened by NAC as measured by several important lab values.

The significance of the anticipation and evaluation of S-100 protein for the patients with brain damage after cardiopulmonary-cerebral resuscitation

Objective To approach the anticipation and evaluation of S-100 protein for the patients with brain damage after cardiopulmonary-cerebral resuscitation(CPCR). Methods S-100 protein in blood serum of 40 patients with brain damage after CPCR were deteced by ELISA after 2h, 12h, 24h, 48h, 72h and 32 healthy controls. Results The level of serum S-100 protein in 40 patients after CPCR increased early and obviously, and be peaked from 2h (P<0.05). It was significance higher in each period than that in control group(P<0.01). Serum S-100 value at 2, 12, 24, 48 hour after resuscitation negatively correlated with GCS (P<0.01 or P<0.05). Conclusion S-100 protein can be a marker of the patients with brain damage after CPCR, it's high level cue to unfavurable prognosis. Also it was conducted to evaluate the pathogenetic condition of early coma patients after cardiac arrest. Key words: S-100 protein; Cardiopulmonary-cerebral resuscitation: Brain damage

Somatosensory evoked potentials in children with severe head trauma

We evaluated the predictive value of somatosensory evoked potentials (SEP) in a series of children with severe traumatic brain injury (TBI). The prospective clinical investigation was performed in a Level I paediatric trauma centre. We included 26 consecutive comatose paediatric patients aged from 1 month to 17 years (median age 11 years) following severe TBI (initial Glasgow Coma Score (GCS) 8 or below). Besides SEP recordings, the intracranial pressure and the results of an initial cranial CT scan were filed. The Glasgow Outcome Scale (GOS) was used to assess outcome at discharge. Thirteen children had normal SEP measurements, three patients had abnormal SEP recordings and a cortical response was bilaterally absent in ten children. Out of 26 children, 10 died whereas two remained in a persistent vegetative state. Only one child suffered from significant neurological deficits (GOS 3) at discharge. Seven patients survived with a GOS of 4 and six children survived without neurological impairment (GOS 5). Normal SEP indicated a favourable outcome in most children but did not rule out the occurrence of death, while absence of SEP was related to unfavourable outcome in all cases. Measurement of somatosensory evoked potentials provides valuable data for determining the prognosis at early coma stages. Our data show that an unfavourable outcome can be predicted with higher precision than a favourable outcome.

Development of Glasgow Coma and Outcome Scales

These scales were developed primarily to facilitate the assessment and recording of initial severity of brain dysfunction and of ultimate outcome in a multicenter study of outcome after severe brain damage. The aim was to use simple terms that could be readily understood by a wide range of observers, including doctors, nurses and others. Repeated observations of the coma scale displayed on a bedside chart give it a second use - the monitoring of improvement or deterioration in conscious level as an indication of recovery or of complications. Early sedation and ventilation can make assessment difficult but the motor score alone is still a good guide to severity. Giving numbers to the level of response in the three components of the coma scale (eye opening, motor and verbal responses) facilitates communication between different staff, including those consulted by telephone. Adding up these scores to give an overall coma score (from 3 to 15) results in some loss of information but is useful for triage and for epidemiological studies. Even among mild injuries (coma score 13-15) the score discriminates between those more or less likely to develop complications. The outcome scale describes overall social function rather than neurological deficits, and is useful in monitoring recovery. The outcomes so described at six months after injury correlate well with the early coma scale scores, which are therefore useful predictors of likely outcome. Nepal Journal of Neuroscience, Volume 2, Number 1, 2005, Page: 24-28

Early Metabolic Acidosis and Coma After Acetaminophen Ingestion

Metabolic acidosis and coma may develop in patients who experience severe hepatic injury after acetaminophen poisoning. The onset of acidosis and coma soon after acetaminophen overdose, but preceding manifest hepatic injury, contrasts with the typical course of poisoning. This pattern has been reported in a limited number of cases. Coingestions and the rare occurrence of these findings after an overdose have engendered controversy as to whether acetaminophen alone is the cause of early coma and acidosis. We describe 4 separate overdoses among 3 patients who arrived at the emergency department comatose with a metabolic acidosis soon after ingesting large amounts of acetaminophen without evidence of toxic liver injury. Our cases support the view that early metabolic acidosis with coma does indeed occur after acetaminophen poisoning, independent of hepatic failure or its complications.[Roth B, Woo O, Blanc P: Early metabolic acidosis and coma after acetaminophen ingestion. Ann Emerg Med April 1999;33:452-456.]

Fulminant hepatic failure in poisoning due to ingestion of T 61, a veterinary euthanasia drug

A patient developed fulminant hepatic failure 48 h after the ingestion of T 61, a veterinary euthanasia drug which contains both general and local anesthetics, a neuromuscular blocking agent, and dimethylformamide (DMF) as a solvent. This is the first report of such severe hepatic manifestation in T 61 poisoning, the most common symptoms of which are early coma and respiratory failure due to the anesthetic and the neuromuscular blocking agent. In a very few cases mild and transitory symptoms of hepatic insufficiency have been observed. In this case the fulminant hepatic failure was due to the high dose (0.6 ml/kg) ingestion of DMF.

Encephalite herpetique: Elements de pronostic chez l'adulte et l'enfant (49 cas)

In 49 cases (26 children, 23 adults) of proven Herpes simplex encephalitis, the authors studied the influence of age, disturbances of consciousness, time of diagnosis and therapy on patients' outcome, as well as the prognostic value of EEG data. Mortality was low in late childhood and young adulthood in spite of the constancy and depth of coma; it was very high in newborns and adults over 40 years of age and it was always correlated with the severeness of initial consciousness disturbances. The onset of periodic complexes (in 65% of the children and 78% of adults on the first EEG) does not systematically imply a poor outcome. Correlations between these EEG patterns and bioptic or surgical data tend to prove that these periodic complexes are already present in a prenecrotic state. Reversibility may be complete. On the other hand, the association between a contralateral focus or diffusion of initial abnormalities and an early coma imply a poor prognosis (12 deaths and 2 major sequellae in 14 cases). The importance of early presumptive diagnosis and therapeutical onset is stressed. The only cases of complete recovery are found among young adults treated early (surgery for older cases) thanks to an initial typical EEG. In young children, first clinical symptoms are often not evocative. Great importance should be attached to the onset of partial seizures and interictal loss of consciousness in a feverish child (24 out of 26 cases). Antiviral therapy should be started as soon as a Herpes simplex encephalitis is suspected, since the new antiviral drugs have a relatively low toxicity and do not interfere with the immunological diagnosis.

Effect of acute ammonia intoxication on energy stores in the cerebral reticular activating system.

Ammonia intoxication causes loss of consciousness. One postulated mechanism for this stipulates impaired energy metabolism in critical brain sites. The ascending reticular activating system in the brainstem may modulate consciousness. Accordingly, the present study, using micromethods, assessed energy stores in cells from the reticular activating system of mice acutely intoxicated with ammonia. In the early coma period (3.5 min after ammonia) phosphocreatine, adenosine triphosphate and glucose fell significantly while glycogen decreased later. Subsequently during coma, the high energy phosphates returned to normal and supranormal. The maximal fall in these metabolites was not accompanied by a rise in lactate, implying lack of local hypoxia or acidosis. The cells of the posterior coliculus in the same animals failed to show a significant fall in energy stores. These data suggest a selective effect of ammonia on energy metabolism in the cells of the reticular activating system of the brainstem.