Potency of propofol for inducing loss of consciousness in end-stage kidney disease patients.

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 µg/ml and increased in increments of 0.5 µg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 µg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 µg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

Signature of consciousness in brain-wide synchronization patterns of monkey and human fMRI signals.

During the sleep-wake cycle, the brain undergoes profound dynamical changes, which manifest subjectively as transitions between conscious experience and unconsciousness. Yet, neurophysiological signatures that can objectively distinguish different consciousness states based are scarce. Here, we show that differences in the level of brain-wide signals can reliably distinguish different stages of sleep and anesthesia from the awake state in human and monkey fMRI resting state data. Moreover, a whole-brain computational model can faithfully reproduce changes in global synchronization and other metrics such as functional connectivity, structure-function relationship, integration and segregation across vigilance states. We demonstrate that the awake brain is close to a Hopf bifurcation, which naturally coincides with the emergence of globally correlated fMRI signals. Furthermore, simulating lesions of individual brain areas highlights the importance of connectivity hubs in the posterior brain and subcortical nuclei for maintaining the model in the awake state, as predicted by graph-theoretical analyses of structural data.

Spontaneous subarachnoidal hemorrhage in patients with Covid-19: case report.

In this article, subarachnoidal hemorrhage developing in a case with Covid-19-related pneumonia was evaluated. In the presence of respiratory system infection signs such as cough and weakness in patient who present with sudden loss of consciousness, performing lung imaging as well as performing brain computerized tomography scan can allow the detection of an underlying Covid-19 infection.

Altered Global Brain Signal during Physiologic, Pharmacologic, and Pathologic States of Unconsciousness in Humans and Rats.

BACKGROUND: Consciousness is supported by integrated brain activity across widespread functionally segregated networks. The functional magnetic resonance imaging-derived global brain signal is a candidate marker for a conscious state, and thus the authors hypothesized that unconsciousness would be accompanied by a loss of global temporal coordination, with specific patterns of decoupling between local regions and global activity differentiating among various unconscious states. METHODS: Functional magnetic resonance imaging global signals were studied in physiologic, pharmacologic, and pathologic states of unconsciousness in human natural sleep (n = 9), propofol anesthesia (humans, n = 14; male rats, n = 12), and neuropathological patients (n = 21). The global signal amplitude as well as the correlation between global signal and signals of local voxels were quantified. The former reflects the net strength of global temporal coordination, and the latter yields global signal topography. RESULTS: A profound reduction of global signal amplitude was seen consistently across the various unconscious states: wakefulness (median [1st, 3rd quartile], 0.46 [0.21, 0.50]) versus non-rapid eye movement stage 3 of sleep (0.30 [0.24, 0.32]; P = 0.035), wakefulness (0.36 [0.31, 0.42]) versus general anesthesia (0.25 [0.21, 0.28]; P = 0.001), healthy controls (0.30 [0.27, 0.37]) versus unresponsive wakefulness syndrome (0.22 [0.15, 0.24]; P < 0.001), and low dose (0.07 [0.06, 0.08]) versus high dose of propofol (0.04 [0.03, 0.05]; P = 0.028) in rats. Furthermore, non-rapid eye movement stage 3 of sleep was characterized by a decoupling of sensory and attention networks from the global network. General anesthesia and unresponsive wakefulness syndrome were characterized by a dissociation of the majority of functional networks from the global network. This decoupling, however, was dominated by distinct neuroanatomic foci (e.g., precuneus and anterior cingulate cortices). CONCLUSIONS: The global temporal coordination of various modules across the brain may distinguish the coarse-grained state of consciousness versus unconsciousness, while the relationship between the global and local signals may define the particular qualities of a particular unconscious state.

Pathological consequences of low atmospheric pressure stunning in broiler chickens.

Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.

Alpha-1-antitrypsin: a novel predictor for long-term recovery of chronic disorder of consciousness.

BACKGROUND: The aim of this manuscript was to explore the molecular basis and identify novel biomarkers for the diagnosis and prognosis of patients with chronic disorder of consciousness. METHODS: A coupled isobaric tag for relative and absolute quantitation-based approach was used to screen differentially expressed proteins (DEPs) between patients with chronic disorder of consciousness and healthy individuals. Candidate proteins were identified and measured. The Coma Recovery Scale-Revised (CRS-R) score was used to quantify the severity, and long-term recovery was assessed by Glasgow Outcome Scale (GOS). RESULTS: Between patients and controls, a total of 77 DEPs were identified. Based on the DEPs, a network containing 50 nodes and 207 edges was built, and alpha-1-antitrypsin was marked as the hub protein. The results indicated that alpha-1-antitrypsin correlated with the CRS-R score with a correlation coefficient of 0.631, and an outcome at 12 months (8.5 ± 2.1 ng/ml in patients with GOS 1-2 vs. 6.8 ± 1.6 ng/ml in those with GOS 3-5, p = 0.002). CONCLUSIONS: The data confirm the diagnostic and prognostic potential of alpha-1-antitrypsin in chronic disorder of consciousness, which may contribute to the development of novel therapeutic agents.

Breakdown in the temporal and spatial organization of spontaneous brain activity during general anesthesia.

Which temporal features that can characterize different brain states (i.e., consciousness or unconsciousness) is a fundamental question in the neuroscience of consciousness. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated the spatial patterns of two temporal features: the long-range temporal correlations (LRTCs), measured by power-law exponent (PLE), and temporal variability, measured by standard deviation (SD) during wakefulness and anesthetic-induced unconsciousness. We found that both PLE and SD showed global reductions across the whole brain during anesthetic state comparing to wakefulness. Importantly, the relationship between PLE and SD was altered in anesthetic state, in terms of a spatial "decoupling." This decoupling was mainly driven by a spatial pattern alteration of the PLE, rather than the SD, in the anesthetic state. Our results suggest differential physiological grounds of PLE and SD and highlight the functional importance of the topographical organization of LRTCs in maintaining an optimal spatiotemporal configuration of the neural dynamics during normal level of consciousness. The central role of the spatial distribution of LRTCs, reflecting temporo-spatial nestedness, may support the recently introduced temporo-spatial theory of consciousness (TTC).

Global reduction of information exchange during anesthetic-induced unconsciousness.

During anesthetic-induced unconsciousness (AIU), the brain undergoes a dramatic change in its capacity to exchange information between regions. However, the spatial distribution of information exchange loss/gain across the entire brain remains elusive. In the present study, we acquired and analyzed resting-state functional magnetic resonance imaging (rsfMRI) data in rats during wakefulness and graded levels of consciousness induced by incrementally increasing the concentration of isoflurane. We found that, regardless of spatial scale, the functional connectivity (FC) change (i.e., ∆FC) was proportionally dependent on the FC strength at the awake state across all connections. This dependency became stronger at higher doses of isoflurane. In addition, the relative FC change at each anesthetized condition (i.e., ∆FC normalized to the corresponding FC strength at the awake state) was exclusively negative across the whole brain, indicating a global loss of meaningful information exchange between brain regions during AIU. To further support this notion, we showed that during unconsciousness, the entropy of rsfMRI signal increased to a value comparable to random noise while the mutual information decreased appreciably. Importantly, consistent results were obtained when unconsciousness was induced by dexmedetomidine, an anesthetic agent with a distinct molecular action than isoflurane. This result indicates that the observed global reduction in information exchange may be agent invariant. Taken together, these findings provide compelling neuroimaging evidence suggesting that the brain undergoes a widespread disruption in the exchange of meaningful information during AIU and that this phenomenon may represent a common system-level neural mechanism of AIU.

Neurotological findings after electrical injury at the workplace.

OBJECTIVES/HYPOTHESIS: Neurotological findings secondary to electrical injuries have rarely been reported in the world literature. We attempt to characterize the neurotological findings following electrical injury and to determine the role head injury and loss of consciousness play in this population's clinical presentation. STUDY DESIGN: Retrospective cohort study. METHODS: A database containing 3,438 patients with work-related injuries was scanned for individuals who sustained and survived electrical injuries at work. Detailed analysis of the frequencies of presenting features and test results was performed. A comparative analysis was made between the subsets of patients with and without loss of consciousness and/or head injury. RESULTS: A cohort of 42 patients was identified. All patients had multiple symptoms. Dizziness was a significant complaint in all workers with electrical injuries. Other common complaints included tinnitus and imbalance. Characterization of these symptoms is provided in detail according to statistical frequency. In this cohort, 25 workers had a concomitant head injury and 17 workers had an associated loss of consciousness. There was no statistically significant difference when clinical presentation, examination, and balance testing results were compared between the subsets. CONCLUSIONS: Frequency and characterization of symptoms following electrical injury are provided. Dizziness is the most common presenting neurotological feature. Loss of consciousness and/or associated head injury do not affect the clinical presentation in this particular population. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:2126-2131, 2017.

Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy.

BACKGROUND: Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population. METHODS: This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5. RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83). CONCLUSION: NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations of serial NSE measurements may provide an increase in overall prognostic information, it is unclear whether actual clinical prognostication with low false-positive rates is improved by application of serial measurements in persistently unconscious patients. The findings of this study should be confirmed in another prospective cohort. TRIAL REGISTRATION: NCT01020916.

Dynamic Connectivity Patterns in Conscious and Unconscious Brain.

Brain functional connectivity undergoes dynamic changes from the awake to unconscious states. However, how the dynamics of functional connectivity patterns are linked to consciousness at the behavioral level remains elusive. In this study, we acquired resting-state functional magnetic resonance imaging data during wakefulness and graded levels of consciousness in rats. Data were analyzed using a dynamic approach combining the sliding window method and k-means clustering. Our results demonstrate that whole-brain networks contained several quasi-stable patterns that dynamically recurred from the awake state into anesthetized states. Remarkably, two brain connectivity states with distinct spatial similarity to the structure of anatomical connectivity were strongly biased toward high and low consciousness levels, respectively. These results provide compelling neuroimaging evidence linking the dynamics of whole-brain functional connectivity patterns and states of consciousness at the behavioral level.

Dynamics of Propofol-Induced Loss of Consciousness Across Primate Neocortex.

UNLABELLED: The precise neural mechanisms underlying transitions between consciousness and anesthetic-induced unconsciousness remain unclear. Here, we studied intracortical neuronal dynamics leading to propofol-induced unconsciousness by recording single-neuron activity and local field potentials directly in the functionally interconnecting somatosensory (S1) and frontal ventral premotor (PMv) network during a gradual behavioral transition from full alertness to loss of consciousness (LOC) and on through a deeper anesthetic level. Macaque monkeys were trained for a behavioral task designed to determine the trial-by-trial alertness and neuronal response to tactile and auditory stimulation. We show that disruption of coherent beta oscillations between S1 and PMv preceded, but did not coincide with, the LOC. LOC appeared to correspond to pronounced but brief gamma-/high-beta-band oscillations (lasting ∼3 min) in PMv, followed by a gamma peak in S1. We also demonstrate that the slow oscillations appeared after LOC in S1 and then in PMv after a delay, together suggesting that neuronal dynamics are very different across S1 versus PMv during LOC. Finally, neurons in both S1 and PMv transition from responding to bimodal (tactile and auditory) stimulation before LOC to only tactile modality during unconsciousness, consistent with an inhibition of multisensory integration in this network. Our results show that propofol-induced LOC is accompanied by spatiotemporally distinct oscillatory neuronal dynamics across the somatosensory and premotor network and suggest that a transitional state from wakefulness to unconsciousness is not a continuous process, but rather a series of discrete neural changes. SIGNIFICANCE STATEMENT: How information is processed by the brain during awake and anesthetized states and, crucially, during the transition is not clearly understood. We demonstrate that neuronal dynamics are very different within an interconnecting cortical network (primary somatosensory and frontal premotor area) during the loss of consciousness (LOC) induced by propofol in nonhuman primates. Coherent beta oscillations between these regions are disrupted before LOC. Pronounced but brief gamma-band oscillations appear to correspond to LOC. In addition, neurons in both of these cortices transition from responding to both tactile and auditory stimulation before LOC to only tactile modality during unconsciousness. We demonstrate that propofol-induced LOC is accompanied by spatiotemporally distinctive neuronal dynamics in this network with concurrent changes in multisensory processing.

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness.

Communication between brain areas and how they are influenced by changes in consciousness are not fully understood. One hypothesis is that brain areas communicate via oscillatory processes, utilizing network-specific frequency bands, that can be measured with metrics that reflect between-region interactions, such as coherence and phase amplitude coupling (PAC). To evaluate this hypothesis and understand how these interactions are modulated by state changes, we analyzed electrophysiological recordings in humans at different nodes of one well-studied brain network: the basal ganglia-thalamocortical loops of the motor system during loss of consciousness induced by anesthesia. We recorded simultaneous electrocorticography over primary motor cortex (M1) with local field potentials from subcortical motor regions (either basal ganglia or thalamus) in 15 movement disorder patients during anesthesia (propofol) induction as a part of their surgery for deep brain stimulation. We observed reduced coherence and PAC between M1 and the subcortical nuclei, which was specific to the beta band (∼18-24 Hz). The fact that this pattern occurs selectively in beta underscores the importance of this frequency band in the motor system and supports the idea that oscillatory interactions at specific frequencies are related to the capacity for normal brain function and behavior.

Decoupled temporal variability and signal synchronization of spontaneous brain activity in loss of consciousness: An fMRI study in anesthesia.

Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which "couple" the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC.

Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury.

We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our combat-exposed veterans.

The nature of white matter abnormalities in blast-related mild traumatic brain injury.

Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.

Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project.

BACKGROUND: The supply of unregulated "new psychoactive substances" (NPS) has shown a steady increase over the past six years. This report from the Swedish STRIDA project describes analytically confirmed non-fatal intoxications involving butyrfentanyl (butyrylfentanyl) or 4-fluorobutyrfentanyl (para-fluorobutyrfentanyl), two fentanyl analogues recently introduced as NPS opioids. STUDY DESIGN: Observational case series of consecutive patients with suspected acute NPS exposure and requiring hospital care from all over Sweden. PATIENTS AND METHODS: From May 2014 to January 2015, blood and urine samples were obtained from four intoxication cases involving butyrfentanyl and one case involving 4-fluorobutyrfentanyl (men, 19-30 years) presenting in emergency departments (ED) or intensive care units (ICU). Laboratory analysis of serum and/or urine samples was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during consultations with the Poisons Information Centre and retrieved from medical records. CASE DETAILS: Of the five patients, two were discharged home from the ED and three were admitted to the ICU, of whom two required intubation and mechanical ventilation. Clinical features included typical opioid symptoms such as unconsciousness, respiratory depression, and apnea. In one case, naloxone successfully countered the effects. All patients were discharged the same or the following day. Butyrfentanyl was detected in two serum (0.6 and 0.9 ng/mL) and three urine (2.0-65.6 ng/mL) samples from three of four cases; three cases also contained fentanyl. In the 4-fluorobutyrfentanyl case, the substance was detected in serum (∼15 ng/mL) and urine (∼10 ng/mL). In four cases, other NPS and/or classical drugs were also detected. Analysis of two "butyrfentanyl" NPS products (nasal spray and powder) brought to hospital by patients showed that the 10-fold more potent fentanyl was the main active ingredient (∼7.5-10-fold higher amount) in both. CONCLUSION: Typical and potentially life-threatening opioid toxicity was seen in acute intoxications involving butyrfentanyl, 4F-butyrfentanyl, and fentanyl. The incorrect labelling of butyrfentanyl NPS products which instead mainly contained fentanyl is alarming, given the narrow range between a safe and a lethal dose for opioids.

Gluteal compartment syndrome following drug-induced immobilization: a case report.

BACKGROUND: Gluteal compartment syndrome is a very rare condition characterized by non-specific symptoms that often lead to misdiagnosis. CASE PRESENTATION: We report a case of gluteal compartment syndrome in a 38 year-old Caucasian male (intravenous drug user) following prolonged immobilization due to loss of consciousness. The delay in the appropriate diagnosis and treatment led to a temporary acute kidney injury and to irreversible sciatic nerve palsy. CONCLUSION: Delay in the definitive diagnosis and treatment of gluteal compartment syndrome, may lead to higher morbidity of the affected extremity and in rare cases even patient mortality. Special emphasis is given to the aetiology, symptomatology, differential diagnosis as well as the treatment of this condition.

Reversible splenium diffusion weighted MRI changes associated with hypoglycemia.

Hypoglycemia can manifest as a stroke. MRI diffusion-weighted imaging is the most useful technique in diagnosing early ischemic injury. We report two cases of transient MRI lesions of the splenium of the corpus callosum related to hypoglycemia. Clinicians must be aware of such cases to avoid misdiagnosis.