Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHP-score and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. CONCLUSIONS: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness.

OBJECTIVE: This study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. METHODS: We enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale-Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. RESULTS: Power spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. CONCLUSIONS: Auditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SIGNIFICANCE: Our findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

A Brain-Computer Interface Based on Three-Dimensional Stereo Stimuli for Assisting Clinical Object Recognition Assessment in Patients With Disorders of Consciousness.

The coma recovery scale-revised (CRS-R) behavioral scale is commonly used for the clinical evaluation of patients with disorders of consciousness (DOC). However, since DOC patients generally cannot supply stable and efficient behavioral responses to external stimulation, evaluation results based on behavioral scales are not sufficiently accurate. In this paper, we proposed a novel brain-computer interface (BCI) based on 3D stereo audiovisual stimuli to supplement object recognition evaluation in the CRS-R. During the experiment, subjects needed to follow the instructions and to focus on the target object on the screen, whereas EEG data were recorded and analyzed in real time to determine the object of focus, and the detection result was output as feedback. Thirteen DOC patients participated in the object recognition assessments using the 3D audiovisual BCI and CRS-R. None of the patients showed object recognition function in the CRS-R assessment before the BCI experiment. However, six of these DOC patients achieved accuracies that were significantly higher than the chance level in the BCI-based assessment, indicating the successful detection of object recognition function in these six patients using our 3D audiovisual BCI system. These results suggest that the BCI method may provide a more sensitive object recognition evaluation compared with CRS-R and may be used to assist clinical CRS-R for DOC patients.

[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

An interesting case of opium tea toxicity.

We present an unusual cause of respiratory arrest resulting from sole ingestion of home-brewed opium tea. A 64-year-old woman was found unresponsive and in respiratory arrest by a first responder. There were no obvious signs of regular recreational drug use. On presentation to the local district general hospital, the patient was in extremis, with severe physiological and biochemical derangements. A naloxone infusion was commenced and she later made a good recovery. It was subsequently discovered that she had brewed opium tea from opium buds she had picked from a nearby commercial poppy farm, a practice she had learnt while in Afghanistan.

Stimulus induced bursts in severe postanoxic encephalopathy.

OBJECTIVE: To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. METHODS: In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. RESULTS: In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (<1s) did not induce bursts. In both patients bursts were not accompanied by myoclonia. Both patients deceased. CONCLUSIONS: Bursts in patients with a severe postanoxic encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. SIGNIFICANCE: Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity.

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds.

Trace conditioning refers to a learning process occurring after repeated presentation of a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies have reported that trace conditioning can occur in humans in reduced levels of consciousness by showing a transfer of the unconditioned autonomic response to the CS+ in healthy sleeping individuals and in vegetative state patients. However, no previous studies have investigated the neural underpinning of trace conditioning in the absence of consciousness in humans. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the EEG activity during the period where the UCS is omitted after CS+ presentation. Specifically we assessed the 'reactivation' of the neural response to UCS omission by applying a decoding algorithm derived from the statistical model of the EEG activity in response to the UCS presentation. The same procedure was used in a group of 12 awake healthy controls. We found a reactivation of the UCS response in absence of stimulation in eight patients (five under therapeutic hypothermia) and four healthy controls. Additionally, the reactivation effect was temporally specific within trials since it manifested primarily at the specific latency of UCS presentation and significantly less before or after this period. Our results show for the first time that trace conditioning may manifest as a reactivation of the EEG activity related to the UCS and even in the absence of consciousness.

Music therapy for coma patients: preliminary results.

OBJECTIVE: The application of quantitative EEG (δ+θ/α+ß value) and GCS value to evaluate the role of music therapy for traumatic brain injury coma patients. PATIENTS AND METHODS: Forty patients of traumatic brain injury coma were selected to meet the inclusion criteria. Twenty cases were selected for the rehabilitation, neurology and neurosurgery ward, whose families could actively cooperate with, and the patients could receive a long-term fixed nursing staff with formal music therapy (music group). Twenty cases were in the intensive care unit of the rehabilitation, neurology and neurosurgery ward. Their families members cooperated poorly, had often changing nursing staff, and without a formal music therapy (control group). After a one monthe follow up, the GCS value and quantitative EEG (δ+θ/α+ß value) were compared between the two groups. Between the two groups, except for the presence or absence of formal music therapy, the rest of treatment had no significant difference and was matched by age, gender, and injury types. RESULTS: In 40 cases of traumatic brain injury patients, the GCS value increased in the music group after treatment when compared to the control group. The difference between the two groups was significant (p < 0.05). The quantitative EEG value (δ+θ/α+ß value) of music group values were decreased after treatment, and the difference was significant compared with the control group (p < 0.05). CONCLUSIONS: Through the quantitative EEG (δ+θ/α+ß value) and the GCS observation score, music therapy in patients with craniocerebral trauma coma has obviously an effect on promoting to regain consciousness. The quantitative EEG (δ+θ/α+ß value) can be used as an objective index to evaluate the state of brain function.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

MMN and novelty P3 in coma and other altered states of consciousness: a review.

In recent decades, there has been a growing interest in the assessment of patients in altered states of consciousness. There is a need for accurate and early prediction of awakening and recovery from coma. Neurophysiological assessment of coma was once restricted to brainstem auditory and primary cortex somatosensory evoked potentials elicited in the 30 ms range, which have both shown good predictive value for poor coma outcome only. In this paper, we review how passive auditory oddball paradigms including deviant and novel sounds have proved their efficiency in assessing brain function at a higher level, without requiring the patient's active involvement, thus providing an enhanced tool for the prediction of coma outcome. The presence of an MMN in response to deviant stimuli highlights preserved automatic sensory memory processes. Recorded during coma, MMN has shown high specificity as a predictor of recovery of consciousness. The presence of a novelty P3 in response to the subject's own first name presented as a novel (rare) stimulus has shown a good correlation with coma awakening. There is now a growing interest in the search for markers of consciousness, if there are any, in unresponsive patients (chronic vegetative or minimally conscious states). We discuss the different ERP patterns observed in these patients. The presence of novelty P3, including parietal components and possibly followed by a late parietal positivity, raises the possibility that some awareness processes are at work in these unresponsive patients.