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This trial showed no significant difference in the percentage of patients who died or had severe disability or coma when higher or lower blood-pressure targets were used after an out-of-hospital cardiac arrest.

Patients diagnosed as vegetative have periods of wakefulness, but seem to be unaware of themselves or their environment. Although functional MRI (fMRI) studies have shown that some of these patients are consciously aware, issues of expense and accessibility preclude the use of fMRI assessment in most of these individuals. We aimed to assess bedside detection of awareness with an electroencephalography (EEG) technique in patients in the vegetative state. This study was undertaken at two European centres. We recruited patients with traumatic brain injury and non-traumatic brain injury who met the Coma Recovery Scale-Revised definition of vegetative state. We developed a novel EEG task involving motor imagery to detect command-following—a universally accepted clinical indicator of awareness—in the absence of overt behaviour. Patients completed the task in which they were required to imagine movements of their right-hand and toes to command. We analysed the command-specific EEG responses of each patient for robust evidence of appropriate, consistent, and statistically reliable markers of motor imagery, similar to those noted in healthy, conscious controls. We assessed 16 patients diagnosed in the vegetative state, and 12 healthy controls. Three (19%) of 16 patients could repeatedly and reliably generate appropriate EEG responses to two distinct commands, despite being behaviourally entirely unresponsive (classification accuracy 61–78%). We noted no significant relation between patients' clinical histories (age, time since injury, cause, and behavioural score) and their ability to follow commands. When separated according to cause, two (20%) of the five traumatic and one (9%) of the 11 non-traumatic patients were able to successfully complete this task. Despite rigorous clinical assessment, many patients in the vegetative state are misdiagnosed. The EEG method that we developed is cheap, portable, widely available, and objective. It could allow the widespread use of this bedside technique for the rediagnosis of patients who behaviourally seem to be entirely vegetative, but who might have residual cognitive function and conscious awareness. Medical Research Council, James S McDonnell Foundation, Canada Excellence Research Chairs Program, European Commission, Fonds de la Recherche Scientifique, Mind Science Foundation, Belgian French-Speaking Community Concerted Research Action, University Hospital of Liège, University of Liège.

BackgroundDelayed cerebral ischaemia (DCI) is frequent after poor grade aneurysmal subarachnoid haemorrhage (SAH). Owing to the limited accuracy of clinical examination, DCI diagnosis is often based on multimodal monitoring. We examined the value of cerebral microdialysis (CMD) in this setting.Methods20 comatose SAH participants underwent CMD monitoring—for hourly sampling of cerebral extracellular lactate/pyruvate ratio (LPR) and glucose—and brain perfusion CT (PCT). Patients were categorised as DCI when PCT (8±3 days after SAH) showed cerebral hypoperfusion, defined as cerebral blood flow <32.5 mL/100 g/min with a mean transit time >5.7 s. Clinicians were blinded to CMD data; for the purpose of the study, only patients who developed cerebral hypoperfusion in anterior and/or middle cerebral arteries were analysed.ResultsDCI (n=9/20 patients) was associated with higher CMD LPR (51±36 vs 31±10 in patients without DCI, p=0.0007) and lower CMD glucose (0.64±0.34 vs 1.22±1.05, p=0.0005). In patients with DCI, CMD changes over the 18 hours preceding PCT diagnosis revealed a pattern of CMD LPR increase (coefficient +2.96 (95% CI 0.13 to 5.79), p=0.04) with simultaneous CMD glucose decrease (coefficient −0.06 (95% CI −0.08 to −0.01), p=0.03, mixed-effects multilevel regression model). No significant CMD changes were noted in patients without DCI.ConclusionsIn comatose patients with SAH, delayed cerebral hypoperfusion correlates with a CMD pattern of lactate increase and simultaneous glucose decrease. CMD abnormalities became apparent in the hours preceding PCT, thereby suggesting that CMD monitoring may anticipate targeted therapeutic interventions.

Background Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP). Methods We prospectively studied over a 1-year period (June 2012–June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1–2) versus poor (CPC 3–5). Predictive performance was analyzed using area under the ROC curves (AUC). Results Patients with good outcome [ n  = 23 (46 %)] had higher quantitative PLR than those with poor outcome [ n  = 27; 16 (range 9–23) vs. 10 (1–30) % at day 1, and 20 (13–39) vs. 11 (1–55) % at day 2, both p  < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p  = 0.005; day 2, 0.81 vs. 0.64, p  = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p  > 0.20). Conclusions Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP.

Background Although median nerve somatosensory evoked potentials are routinely used for prognostication in comatose cardiac arrest survivors, myogenic artifact can reduce inter-rater reliability, leading to unreliable or inaccurate results. To minimize this risk, we determined the benefit of neuromuscular blockade agents in improving the inter-rater reliability and signal-to-noise ratio of SSEPs in the context of prognostication. Methods Thirty comatose survivors of cardiac arrest were enrolled in the study, following the request from an intensivist to complete an SSEP for prognostication. Right and left median nerve SSEPs were obtained from each patient, before and after administration of an NMB agent. Clinical histories and outcomes were retrospectively reviewed. The SSEP recordings before and after NMB were randomized and reviewed by five blinded raters, who assessed the latency and amplitude of cortical and noncortical potentials (vs. absence of response) as well as the diagnostic quality of cortical recordings. The inter-rater reliability of SSEP interpretation before and after NMB was compared via Fleiss’ κ score. Results Following NMB administration, Fleiss’ κ score for cortical SSEP interpretation significantly improved from 0.37 to 0.60, corresponding to greater agreement among raters. The raters were also less likely to report the cortical recordings as nondiagnostic following NMB (40.7% nondiagnostic SSEPs pre-NMB; 17% post-NMB). The SNR significantly improved following NMB, especially when the pre-NMB SNR was low (< 10 dB). Across the raters, there were three patients whose SSEP interpretation changed from bilaterally absent to bilaterally present after NMB was administered (potential false positives without NMB). Conclusions NMB significantly improves the inter-rater reliability and SNR of median SSEPs for prognostication among comatose cardiac arrest survivors. To ensure the most reliable prognostic information in comatose post-cardiac arrest survivors, pharmacologic paralysis should be consistently used before recording SSEPs.

The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS). The EEG of 31 patients was recorded and analyzed. Power spectra were obtained using modern multitaper methods. Three connectivity measures (coherence, the imaginary part of coherency and the phase lag index) were computed. Of the 31 patients, 21 were diagnosed as MCS and 10 as VS/UWS using the Coma Recovery Scale-Revised (CRS-R). EEG power spectra revealed differences between the two conditions. The VS/UWS patients showed increased delta power but decreased alpha power compared with the MCS patients. Connectivity measures were correlated with the CRS-R diagnosis; patients in the VS/UWS had significantly lower connectivity than MCS patients in the theta and alpha bands. Standard EEG recorded in clinical conditions could be used as a tool to help the clinician in the diagnosis of disorders of consciousness.

Background Intensive care unit-acquired atrophy and weakness are associated with high mortality, a reduction in physical function, and quality of life. Passive mobilization (PM) and neuromuscular electrical stimulation were applied in comatose patients; however, evidence is inconclusive regarding atrophy and weakness prevention. Blood flow restriction (BFR) associated with PM (BFRp) or with electrical stimulation (BFRpE) was able to reduce atrophy and increase muscle mass in spinal cord-injured patients, respectively. Bulky venous return occurs after releasing BFR, which can cause unknown repercussions on the cardiovascular system. Hence, the aim of this study was to investigate the effect of BFRp and BFRpE on cardiovascular safety and applicability, neuromuscular adaptations, physical function, and quality of life in comatose patients in intensive care units (ICUs). Methods Thirty-nine patients will be assessed at baseline (T0–18 h of coma) and randomly assigned to the PM (control group), BFRp, or BFRpE groups. The training protocol will be applied in both legs alternately, twice a day with a 4-h interval until coma awake, death, or ICU discharge. Cardiovascular safety and applicability will be evaluated at the first training session (T1). At T0 and 12 h after the last session (T2), muscle thickness and quality will be assessed. Global muscle strength and physical function will be assessed 12 h after T2 and ICU and hospital discharge for those who wake up from coma. Six and 12 months after hospital discharge, physical function and quality of life will be re-assessed. Discussion In view of applicability, the data will be used to inform the design and sample size of a prospective trial to clarify the effect of BFRpE on preventing muscle atrophy and weakness and to exert the greatest beneficial effects on physical function and quality of life compared to BFRp in comatose patients in the ICU. Trial registration Universal Trial Number (UTN) Registry UTN U1111-1241-4344. Retrospectively registered on 2 October 2019. Brazilian Clinical Trials Registry (ReBec) RBR-2qpyxf . Retrospectively registered on 21 January 2020, http://ensaiosclinicos.gov.br/rg/RBR-2qpyxf/

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. •Evidence of trace conditioning can be found in comatose patients•Learning an association can manifest as a reactivation of the EEG activity•This association is temporally specific•Healthy controls can also show the same reactivation effect•Trace conditioning may not require consciousness

Background Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. In the Target Temperature Management (TTM) trial, a large international trial on temperature management after cardiac arrest, EEG-examinations were part of the prospective study design. The main objective of this study is to evaluate EEG-data from the TTM-trial and to identify malignant EEG-patterns reliably predicting a poor neurological outcome. Methods/Design In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. After the end of the trial, the EEGs were retrieved to form a central EEG-database. The EEG-data will be analysed using the ACNS EEG terminology. We designed an electronic case record form (eCRF). Four EEG-specialists from different countries, blinded to patient outcome, will independently classify the EEGs and report through the eCRF. We will describe the prognostic values of pre-specified EEG patterns to predict poor as well as good outcome. We hypothesise three patterns to always be associated with a poor outcome (suppressed background without discharges, suppressed background with continuous periodic discharges and burst-suppression). Inter- and intra-rater variability and whether sedation or level of temperature affects the prognostic values will also be analyzed. Discussion A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. The results of this study may help to validate the ACNS terminology for assessing post cardiac arrest EEGs and identify patterns that could reliably predict outcome. Trial registration The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence.