Evaluation of the Use of Ketamine in Prehospital Seizure Management: A Retrospective Review of the ESO Database.

Objectives: Benzodiazepines are the primary antiseizure medication used by Emergency Medical Services (EMS) for seizures. Available literature in the United States and internationally shows 30% to 40% of seizures do not terminate with benzodiazepines called benzodiazepine refractory status epilepticus (BRSE). Ketamine is a potential treatment for BRSE due to its unique pharmacology. However, its application in the prehospital setting is mostly documented in case reports. Little is known about its use by EMS professionals for seizure management, whether as initial treatment or for BRSE, creating an opportunity to describe its current use and inform future research.Methods: We performed a retrospective review of 9-1-1 EMS encounters with a primary or secondary impression of seizure using the ESO Data Collaborative from 2018-2021. We isolated encounters during which ketamine was administered. We excluded medication administrations prior to EMS arrival and encounters without medication administration. Subgroup analysis was performed to control for airway procedure as an indication for ketamine administration. We also evaluated for co-administration with other antiseizure medications, dose and route of administration, and response to treatment.Results: We identified 99,576 encounters that met inclusion. There were 2,531/99,576 (2.54%) encounters with ketamine administration and 50.7% (1,283/2,531) received ketamine without an airway procedure. There were 616 cases (48%, 616/1,283) where ketamine was given without another antiseizure medication (ASM) and without any airway procedure. The remaining 667 (52%) cases received ketamine with at least one other ASM, most commonly midazolam (89%, 593/667). Adjusted for the growth in the ESO dataset, ketamine use by EMS professionals during encounters for seizures without an airway procedure increased from 0.90% (139/15,375) to 1.45% (416/28,651) an increase of 62% over the study period.Conclusions: In this retrospective review of the ESO Data Collaborative, ketamine administration for seizure encounters without an airway procedure increased over the study period, both as a single agent and with another ASM. Most ketamine administrations were for adult patients in the south and in urban areas. The frequency of BRSE, the need for effective treatment, and the growth in ketamine use warrant prospective prehospital research to evaluate the value of ketamine in prehospital seizure management.

SURGICAL ISCHEMIC ASPECTS OF COVID-19: MANAGEMENT OF PATIENTS WITH COVID TOES AND FINGERS.

OBJECTIVE: The aim: Study of clinical manifestations and management of patients with COVID toes and fingers. PATIENTS AND METHODS: Materials and methods: 1,841 patients with laboratory-confirmed SARS-CoV-2 infection were hospitalized. All patients were divided into two groups: without surgical pathology - 1,693 (91.96%) and with surgical pathology (patients with COVID toes and fingers and abdominal syndrome) - 148 (8.04%). The diagnosis of COVID-19 was made on the basis of clinical data, laboratory test results (PCR test for SARS-CoV-2) and computed tomography of the chest. On admission, in addition to the general laboratory tests, mandatory special methods of examination included determination of D-dimer, procalcitonin (PCT), C-reactive protein, and interleukin-6 (IL-6). RESULTS: Results: Surgical ischemic manifestations were observed in 8.04% of all patients with COVID-19, of which 86.48% presented with ischemic abdominal syndrome and 13.52% with COVID toes and fingers. C-reactive protein and procalcitonin are the markers that may indicate the development of ischemic surgical problems. A direct statistically significant linear correlation was found between the severity of the underlying disease and the mean D-dimer (r = 0.815; p = 0.01). CONCLUSION: Conclusions: The confirmed phenomenon of COVID toes and fingers does not require active surgical tactics. It is necessary to conduct pathogenetic treatment of COVID-19 and dynamic monitoring of its clinical course.

Alterations in resting-state functional connectivity in pediatric patients with tuberous sclerosis complex.

OBJECTIVE: To investigate resting-state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery. METHODS: Resting-state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery. RESULTS: The majority of patients demonstrated a resting-state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo-opercular and visual resting-state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting-state network architecture just one day postoperatively. SIGNIFICANCE: Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting-state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high-risk population.

Brain mechanisms supporting violated expectations of pain.

The subjective experience of pain is influenced by interactions between experiences, future predictions, and incoming afferent information. Expectations of high pain can exacerbate pain, whereas expectations of low pain during a consistently noxious stimulus can produce significant reductions in pain. However, the brain mechanisms associated with processing mismatches between expected and experienced pain are poorly understood, but are important for imparting salience to a sensory event to override erroneous top-down expectancy-mediated information. This investigation examined pain-related brain activation when expectations of pain were abruptly violated. After conditioning participants to cues predicting low or high pain, 10 incorrectly cued stimuli were administered across 56 stimulus trials to determine whether expectations would be less influential on pain when there is a high discordance between prestimulus cues and corresponding thermal stimulation. Incorrectly cued stimuli produced pain ratings and pain-related brain activation consistent with placebo analgesia, nocebo hyperalgesia, and violated expectations. Violated expectations of pain were associated with activation in distinct regions of the inferior parietal lobe, including the supramarginal and angular gyrus, and intraparietal sulcus, the superior parietal lobe, cerebellum, and occipital lobe. Thus, violated expectations of pain engage mechanisms supporting salience-driven sensory discrimination, working memory, and associative learning processes. By overriding the influence of expectations on pain, these brain mechanisms are likely engaged in clinical situations in which patients' unrealistic expectations of pain relief diminish the efficacy of pain treatments. Accordingly, these findings underscore the importance of maintaining realistic expectations to augment the effectiveness of pain management.

From cue to meaning: brain mechanisms supporting the construction of expectations of pain.

The brain mechanisms by which sensory cues become transformed into expectations of impending events are a critical component of cognitive tuning of sensory processing. However, distinctions among the afferent processing of cue-related activity itself versus those mechanisms supporting the contextual meaning imparted to the cue remain limited. Do sensory cues with equal meaning engage similar patterns of brain activations even if they are delivered in separate modalities? To address this question, we used functional magnetic resonance imaging of an expectation paradigm in which cues were delivered with visual or innocuous thermal stimuli. Cues were designed to be highly meaningful because they predicted the delivery of high and low painful stimuli. As expected, the cues themselves activated unimodal sensory cortices. This cue modality-specific activation was transformed into a pattern of activity reflecting cue meaning. Cues signaling high pain produced greater activity in the left dorsolateral prefrontal cortex and anterior cingulate cortex. Such activity is consistent with the graded encoding of the magnitude of expected pain. In contrast, cues signaling low pain produced greater activity in the right intraparietal sulcus. This activation may reflect processes directing spatial attention to the stimulated body region in order to more accurately evaluate the relatively weak, low pain stimulus. Taken together, these findings indicate that cues arising from different sensory modalities ultimately engage common brain mechanisms that reflect the meaning of the cue. This meaning-related activity is presumably critical for preparing sensory systems to optimally process afferent information.

Pain sensitivity is inversely related to regional grey matter density in the brain.

Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure.

Frontoparietal mechanisms supporting attention to location and intensity of painful stimuli.

Attention can profoundly shape the experience of pain. However, little is known about the neural mechanisms that support directed attention to nociceptive information. In the present study, subjects were cued to attend to either the spatial location or the intensity of sequentially presented pairs of painful heat stimuli during a delayed match-to-sample discrimination task. We hypothesized that attention-related brain activation would be initiated after the presentation of the attentional cue and would be sustained through the discrimination task. Conjunction analysis confirmed that bilateral portions of the posterior parietal cortex (intraparietal sulcus [IPS] and superior parietal lobule) exhibited this sustained activity during attention to spatial but not intensity features of pain. Analyses contrasting activation during spatial and intensity attention tasks revealed that the right IPS region of the posterior parietal cortex was consistently more activated across multiple phases of the spatial task. However, attention to either feature of the noxious stimulus was associated with activation of frontoparietal areas (IPS and frontal eye fields) as well as priming of the primary somatosensory cortex. Taken together, these results delineate the neural substrates that support selective amplification of different features of noxious stimuli for utilization in discriminative processes.

Differential contribution of electrically evoked dorsal root reflexes to peripheral vasodilatation and plasma extravasation.

BACKGROUND: Dorsal root reflexes (DRRs) are antidromic activities traveling along the primary afferent fibers, which can be generated by peripheral stimulation or central stimulation. DRRs are thought to be involved in the generation of neurogenic inflammation, as indicated by plasma extravasation and vasodilatation. The hypothesis of this study was that electrical stimulation of the central stump of a cut dorsal root would lead to generation of DRRs, resulting in plasma extravasation and vasodilatation. METHODS: Sprague-Dawley rats were prepared to expose spinal cord and L4-L6 dorsal roots under pentobarbital general anesthesia. Electrical stimulation of either intact, proximal or distal, cut dorsal roots was applied while plasma extravasation or blood perfusion of the hindpaw was recorded. RESULTS: While stimulation of the peripheral stump of a dorsal root elicited plasma extravasation, electrical stimulation of the central stump of a cut dorsal root generated significant DRRs, but failed to induce plasma extravasation. However, stimulation of the central stump induced a significant increase in blood perfusion. CONCLUSIONS: It is suggested that DRRs are involved in vasodilatation but not plasma extravasation in neurogenic inflammation in normal animals.