Isoelectric EEG Research Articles

Perioperative EEG background and discharge abnormalities in children undergoing cardiac surgery: a prospective single-centre observational study

BackgroundWe analysed the characteristics of abnormal electroencephalogram (EEG) patterns before, during, and 48 h after cardiac surgery in patients with heterogeneous congenital heart disease to assess their relationship to demographic and perioperative variables and to early patient outcomes. MethodsIn 437 patients enrolled in a single centre, EEG was evaluated for background (including sleep-wake cycle) and discharge (seizures, spikes/sharp waves, pathological delta brushes) abnormalities. Clinical data (arterial blood pressure, doses of inotropic drugs, and serum lactate concentrations) were recorded every 3 h. Postoperative brain MRI was performed before discharge. ResultsPreoperative, intraoperative, and postoperative EEG was monitored in 139, 215, and 437 patients, respectively. Patients with a degree of preoperative background abnormalities (n=40) had more severe intraoperative and postoperative EEG abnormalities (P<0.0001). Intraoperatively, 106/215 (49.3%) patients progressed into an isoelectric EEG. Longer durations of isoelectric EEG were associated with more severe postoperative EEG abnormalities and brain injury on MRI (Ps≤0.003). Postoperative background abnormalities occurred in 218/437 (49.9%) patients, and 119 (54.6%) of them had not recovered after surgery. Seizures occurred in 36/437 (8.2%) patients, spikes/sharp waves in 359/437 (82.2%), and pathological delta brushes in 9/437 (2.0%). Postoperative EEG abnormalities correlated with degree of brain injury on MRI (Ps≤0.02). Demographic and perioperative variables were significantly correlated with postoperative EEG abnormalities, which in turn correlated with adverse clinical outcomes. ConclusionsPerioperative EEG abnormalities occurred frequently and correlated with numerous demographic and perioperative variables and adversely correlated with postoperative EEG abnormalities and early outcomes. The relation of EEG background and discharge abnormalities with long-term neurodevelopmental outcomes remains to be explored.

A novel genetically modified mouse seizure model for evaluating anticonvulsive and neuroprotective efficacy of an A1 adenosine receptor agonist following soman intoxication

Recently a novel humanized mouse strain has been successfully generated, in which serum carboxylesterase (CES) knock out (KO) mice (Es1−/−) were further genetically modified by knocking in (KI), or adding, the gene that encodes the human form of acetylcholinesterase (AChE). The resulting human AChE KI and serum CES KO (or KIKO) mouse strain should not only exhibit organophosphorus nerve agent (NA) intoxication in a manner more similar to humans, but also display AChE-specific treatment responses more closely mimicking those of humans to facilitate data translation to pre-clinic trials. In this study, we utilized the KIKO mouse to develop a seizure model for NA medical countermeasure investigation, and then applied it to evaluate the anticonvulsant and neuroprotectant (A/N) efficacy of a specific A1 adenosine receptor (A1AR) agonist, N-bicyclo-(2.2.1)hept-2-yl-5′-chloro-5′-deoxyadenosine (ENBA), which has been shown in a rat seizure model to be a potent A/N compound. Male mice surgically implanted with cortical electroencephalographic (EEG) electrodes a week earlier were pretreated with HI-6 and challenged with various doses (26 to 47 μg/kg, SC) of soman (GD) to determine a minimum effective dose (MED) that induced sustained status epilepticus (SSE) activity in 100% of animals while causing minimum lethality at 24 h. The GD dose selected was then used to investigate the MED doses of ENBA when given either immediately following SSE initiation (similar to wartime military first aid application) or at 15 min after ongoing SSE seizure activity (applicable to civilian chemical attack emergency triage). The selected GD dose of 33 μg/kg (1.4 x LD50) generated SSE in 100% of KIKO mice and produced only 30% mortality. ENBA at a dose as little as 10 mg/kg, IP, caused isoelectric EEG activity within minutes after administration in naïve un-exposed KIKO mice. The MED doses of ENBA to terminate GD-induced SSE activity were determined to be 10 and 15 mg/kg when treatment was given at the time of SSE onset and when seizure activity was ongoing for 15 min, respectively. These doses were much lower than in the non-genetically modified rat model, which required an ENBA dose of 60 mg/kg to terminate SSE in 100% GD-exposed rats. At MED doses, all mice survived for 24 h, and no neuropathology was observed when the SSE was stopped. The findings confirmed that ENBA is a potent A/N for both immediate and delayed (i.e., dual purposed) therapy to victims of NA exposure and serves as a promising neuroprotective antidotal and adjunctive medical countermeasure candidate for pre-clinical research and development for human application.

Application of Electroencephalography in Preslaughter Management: A Review.

Simple SummaryPreslaughter stress has a negative impact on animal welfare, consumer acceptance, carcass, and meat quality. These preslaughter stressors include mishandling, the novelty of place and environment, social isolation, mixing with unfamiliar animals, knife sharpness, and slaughtering of animals in front of other animals (psychological/emotional stress). This is assumed to occur due to the ignorance and lack of awareness of the personnel involved in the industry, especially in developing countries. Previously, research has proven the impact of these factors by measuring neurohormonal and biochemical parameters. At the time of slaughter, these factors may have a greater influence on animals’ welfare in terms of pain during slaughter, as these hormonal-based methods often have a lag time following the stress or pain-induced change. A timely, rapid, and accurate pain assessment is crucial for proper animal welfare during slaughter. Electroencephalography measures the electric activity of the brain and pain instantaneously, accurately, and objectively. Various physiological and biochemical parameters are well correlated with the changes in EEG variables. The application of EEG in animal welfare studies has significantly enhanced our current scientific knowledge about pain perceptions, such as the effect of various non-noxious and noxious stimuli during slaughter.Electroencephalography (EEG) can be reliable for assessing the brain’s electrical activity of preslaughter stress and pain. The duration between the ventral neck cut and induction of a state of unconsciousness/insensibility is crucial in the slaughtering of animals, reducing pain, fear, and distress. Various EEG variables, such as median frequency (F50), the total power of EEG spectrum (Ptot), waves patterns (amplitude and frequencies), epileptiform EEG, index of consciousness, and isoelectric EEG, are used to identify a valid indicator of the state of unconsciousness. Association among various behavioral, physiological, and hematological parameters with EEG variables could provide an overall assessment and deep insights into the animal stress levels or welfare status during various managemental and preslaughter operations, such as transport, stunning, and slaughtering operations. The application of EEG could help in further refining the stunning technologies and slaughter protocols in livestock, poultry, and fish. The present review analyzed the application of EEG as a neurophysiological tool for assessing animal welfare during the critical state of preslaughter handling and slaughter, thus ensuring proper compliance with animal welfare principles.

This Month in Anesthesiology

This Month in Anesthesiology

Association of EEG and Blood-Based Brain Injury Biomarker Accuracy to Prognosticate Mortality After Pediatric Cardiac Arrest: An Exploratory Study

BackgroundEvaluate the accuracy of brain-based blood biomarkers neuron-specific enolase (NSE) and S100b and electroencephalography (EEG) features alone and in combination with prognosticate 6-month mortality after pediatric cardiac arrest. We hypothesized that the combination of blood brain-based biomarkers and EEG features would have superior classification accuracy of outcome versus either alone. MethodsChildren (n = 58) aged between 1 week and 17 years admitted to the ICU following cardiac arrest at a tertiary care children's hopital were eligible for this secondary study. Blood NSE and S100b were measured closest to 24 hours after return of spontaneous circulation (ROSC). EEGs closest to 24 hours (median 11, interquartile range [IQR] 6 to 16 h) post-ROSC were evaluated by two epileptologists. EEG grade was informed by background frequency, amplitude, and continuity. Sleep spindles were present or absent. Mortality was assessed at six months post-ROSC. Area under the receiver operator curve (AUC) was performed for individual and combined brain-based biomarkers and EEG features. ResultsChildren were aged 2.6 (IQR 0.6 to 10.4) years, and 25 (43%) died. Children who died had increased blood NSE (49.7 [28.0 to 63.1] vs 18.2 [9.8 to 31.8] ng/mL) and S100b (0.118 [0.036 to 0.296] vs 0.012 [0.003 to 0.021] ng/mL) and poor (discontinuous or isoelectric) EEG grade (76% vs 33%) more frequently than survivors (P < 0.05). AUC for NSE to predict mortality was 0.789, and was 0.841 when combined with EEG grade and spindles. S100b AUC for mortality was 0.856 and was optimal alone. ConclusionsIn this exploratory study, the combination of brain-based biomarkers and EEG features may provide more accurate prognostication than either test alone after pediatric cardiac arrest.

Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study.

Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95% CI, 2.57 to 7.4; P < 0.001), endotracheal tube use (odds ratio, 1.78; 95% CI, 1.16 to 2.73; P = 0.008), and propofol bolus for airway placement after sevoflurane induction (odds ratio, 2.92; 95% CI, 1.78 to 4.8; P < 0.001), and less likely with use of muscle relaxant for intubation (odds ratio, 0.67; 95% CI, 0.46 to 0.99; P = 0.046]. Expired sevoflurane was higher in patients with isoelectric events during preincision (mean difference, 0.2%; 95% CI, 0.1 to 0.4; P = 0.005) and surgical maintenance (mean difference, 0.2%; 95% CI, 0.1 to 0.3; P = 0.002). Isoelectric events were associated with moderate (8 of 12, 67%) and severe hypotension (11 of 18, 61%) during preincision (odds ratio, 4.6; 95% CI, 1.30 to 16.1; P = 0.018) (odds ratio, 3.54; 95% CI, 1.27 to 9.9; P = 0.015) and surgical maintenance (odds ratio, 3.64; 95% CI, 1.71 to 7.8; P = 0.001) (odds ratio, 7.1; 95% CI, 1.78 to 28.1; P = 0.005), and lower Pediatric Quality of Life scores at baseline in patients 0 to 12 months (median of differences, -3.5; 95% CI, -6.2 to -0.7; P = 0.008) and 25 to 36 months (median of differences, -6.3; 95% CI, -10.4 to -2.1; P = 0.003) and 30-day follow-up in 0 to 12 months (median of differences, -2.8; 95% CI, -4.9 to 0; P = 0.036). Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs. propofol). Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.

Electroencephalography and somatosensory evoked potentials in Covid-19 patients. Experience in recording and using telemedicine technologies to analyze results

A new coronavirus COVID-19 has led to the development of a global pandemic. It is characterized by a high risk of developing pneumonia and multiple organ failure along with its capability to influence the central nervous system. The main methods of instrumental assessment of the functional state of the brain are electroencephalography (EEG) and somatosensory evoked potentials (SEPs), which have been routinely used with patients in critical care units.We recorded the EEGs and short-latency SEPs of 31 COVID-19 patients, all were treated at the N. V. Sklifosovsky Research Institute of Emergency Care in 2020. The combined data was used to analyse the following outcome.We detected abnormal EEGs in 23 COVID-19 patients (74 %). Seven (30.4 %) patients showed EEGs consisting of diffuse non-specific slowing, 4 patients had lateralized hemispheric slowing (17.4 %) and one patient (4,3 %) had frontal intermittent delta activity (FIRDA). Three (13 %) patients in comas had “burst-suppression» pattern, three (13 %) had isoelectric EEGs and two (8,7 %) had areactive alpha rhythm, regarded as an electrographic manifestation of alpha coma. Two patients had evidence of epileptiform discharges (9 %), triphasic waves were presented in one patient (4.3 %).EEG and SEPs with the median nerve stimulation in COVID-19 patients do not reveal specific changes, nevertheless they are informative instrumental methods for assessing the functional state of the brain to identify biomarkers of epileptic seizures and to prognosticate survival and recovery in comatose patients.

Are neurophysiologic tests reliable, ultra-early prognostic indices after cardiac arrest?

ObjectivesDetermining early and reliable prognosis in comatose subjects after cardiac arrest is a central component of post–cardiac arrest care both for developing realistic prognostic expectations for families, and for better determining which resources are mobilized or withheld for individual patients. The aim of the study was to evaluate the prognostic accuracy of EEG and SEP patterns during the very early period (within the first 6 h) after cardiac arrest. MethodsWe retrospectively analysed comatose patients after CA, either inside or outside the hospital, in which prognostic evaluation was made during the first 6 h from CA. Prognostic evaluation comprised clinical evaluation (GCS and pupillary light reflex) and neurophysiological (electroencephalography (EEG) and somatosensory evoked potentials (SEP)) studies. Prognosis was evaluated with regards to likelihood of recovery of consciousness and also likelihood of failure to regain consciousness. ResultsForty-one comatose patients after cardiac arrest were included. All patients with continuous and nearly continuous EEG recovered consciousness. Isoelectric EEG was always associated with poor outcome. Burst-suppression, suppression and discontinuous patterns were usually associated with poor outcome although some consciousness recovery was observed. Bilaterally absent SEP responses were always associated with poor outcome. Continuous and nearly continuous EEG patterns were never associated with bilaterally absent SEP. ConclusionsDuring the very early period following cardiac arrest (first 6 h), EEG and SEP maintain their high predictive value to predict respectively recovery and failure of recovery of consciousness. A very early EEG exam allows identification of patients with very high probability of a good outcome, allowing rapid use of the most appropriate therapeutic procedures.

Pharmacological and toxicological effects of Ruta chalepensis L. on experimentally induced seizures and electroencephalographic spectral power in mice

Ethnopharmacological relevanceRuta chalepensis L. (Rutaceae) is used in traditional medicine to treat a wide variety of disorders such as rheumatism, fever, mental disorders, dropsy, neuralgia, menstrual problems, anxiety, and epilepsy. Aim of the studyTo evaluate and compare the anticonvulsant properties of an aqueous extract and ethyl acetate (AcOEt) fraction of R. chalepensis on pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) test in mice, by analyzing behavior and electroencephalogram (EEG), as well as GABAA receptors involvement. MethodsThe effect of an acute administration of different dosage of the aqueous extract (300 or 500 mg/kg) or AcOEt fraction (100, 300, 500 or 1000 mg/kg) of R. chalepensis was explored on two different models of acute seizure induction in mice, the PTZ and maximal electroshock (MES) tests. Behavioral and electrographic effects were quantified. Additionally, the possible involvement of the GABAA receptors was explored in the presence of picrotoxin (a non-competitive antagonist of the GABAA receptor). ResultsAcOEt fraction of R. chalepensis was more efficient than aqueous extract to reduce the incidence of tonic-clonic seizures and mortality in a significant and dose-dependent manner in both the PTZ and MES tests. This anticonvulsant effect was not abolished in the presence of picrotoxin. The EEG spectral power analysis revealed that aqueous extract decreased alpha and beta power, while AcOEt fraction decreased alpha and gamma power confirming previous findings of its depressant effect in the central nervous system. It is important to mention that the highest dosage of the AcOEt (1000 mg/kg) produced a severe suppression or isoelectric EEG activity (EEG flattening), recognized as a comatose state, suggesting a neurotoxic effect at this dosage. ConclusionOur data reinforce that depressant and anticonvulsant effects of R. chalepensis depend in part on the presence of constituents from medium polarity. We also found that anticonvulsant effect is not mediated by GABAA receptors. In addition, cautious is emphasized when high doses of this natural product are used in traditional medicine since it might produce neurotoxic effects.

Electrocution as an alternative euthanasia method to blunt force trauma to the head followed by exsanguination for non-viable piglets

BackgroundOn farms, the currently approved and most widely practised method of euthanising non-viable piglets is blunt force trauma to the head followed by exsanguination. However, the use of this method is criticised due to public perceptions and aversion to the methodology by caretakers. Therefore, electrocution after electrical stunning was examined as an alternative approach in 80 hybrid piglets. Initially, electrocution was simulated with finite element analysis using a computer piglet-model, where current density in the heart was visualised and size and position of the electrodes were defined. The following step investigated electrical parameters for electrocution in anaesthetised piglets; first, with a constant voltage power source and then with a constant current power source. The electrical stunning was examined using the constant current supply. Finally, the results of electrical stunning and electrocution were verified in 25 healthy piglets with a body weight between 1 and 2 kg. Unconsciousness was proven by testing palpebral, corneal and nociceptive reflexes. Time of death was confirmed by electroencephalography (EEG) and electrocardiography (ECG) records.ResultsStunning succeeded with the preset of 1.3 A and 50 Hz, placing the electrodes on both sides of the head between the eyes and ears using different timespans between 8 and 20 s. Prolonged electrical flow resulted in reduced paddling movements after the epileptic seizure, and allowed undisturbed reflex tests and installation of electrodes for EEG and ECG recording during electrocution. Using 0.75 A and 400 Hz, pin-shaped electrodes were first positioned on both sides of the chest for 5 s, followed by a break of 20–30 s and a second current flow, whereby the electrodes were placed above the withers and the sternum for 5 s. Cardiac arrest and an isoelectric EEG were induced within 3 min after the onset of the electrical flow through the chest. The most obvious indicator of effective stunning and electrocution was termination of rhythmic breathing. Piglets with cardiac arrest showed only single gasps lasting up to 3 min after electrocution.ConclusionsThe evaluated stunning and electrocution protocol might ease concerns about timely piglet euthanasia. However, this should be verified in non-viable piglets to exclude influencing factors like dehydration and diseases.

Wireless ‘under the skull’ epidural EEG and behavior in piglets during nitrous oxide or carbon dioxide gas euthanasia

Consciousness is central to animal welfare concerns. Its assessment is most often conducted based on behavior, with a poor understanding of the correspondence between behavior and the neurobiological processes that underlie the subjective experience of consciousness. Recording of brain electrical activity using electrodes placed under the skull improves EEG recording by minimizing artifacts from muscular or cardiac activities, and it can now be combined with wireless recording in free-moving animals. This experiment investigated the correspondence between wireless ‘under the skull’ epidural EEG and the behavior of 18 five-week-old female piglets undergoing nitrous oxide (N2O) or carbon dioxide (CO2) gradual fill gas euthanasia at 25% replacement rate per minute of the chamber volume. Piglets exposed to CO2 had a peak in EEG total power (‘Ptot’) during the flailing stage, whereas piglets exposed to N2O had a higher EEG 95% spectral edge frequency (‘F95’) during their initial explorative behavior phase and a drop in EEG median frequency (‘F50’) after loss of posture. Loss of posture without righting attempt, as the last behavioral state observed during euthanasia, preceded the onset of transitional EEG on average by 0.9 and 3.1 min (for CO2 and N2O treatments, respectively), and the onset of isoelectric EEG by 4.5 and 6.2 min (for CO2 and N2O treatments, respectively). Paddling movements occurred shortly before and during transitional EEG but never during isoelectric EEG, whereas gasps persisted after the EEG had become isoelectric. The dynamics of EEG spectral changes were complex to interpret in relation to the degree of consciousness, but isoelectric EEG as an unequivocal indicator of unconsciousness appeared several minutes after loss of posture with no righting attempt. This leaves a window of uncertainty in regards to the potential for consciousness after loss of posture during gradual fill gas euthanasia in piglets.

Dietary Caffeine Synergizes Adverse Peripheral and Central Responses to Anesthesia in Malignant Hyperthermia Susceptible Mice.

Ryanodine receptor (RYR) mutations confer stress-triggered malignant hyperthermia (MH) susceptibility. Dietary caffeine (CAF) is the most commonly consumed psychoactive compound by humans. CAF-triggered Ca2+ release and its influences on skeletal muscle contractility are widely used as experimental tools to study RYR function/dysfunction and diagnose MH susceptibility. We hypothesize that dietary CAF achieving blood levels measured in human plasma exacerbates the penetrance of RYR1 MH susceptibility mutations triggered by gaseous anesthetic, affecting both central and peripheral adverse responses. Heterozygous R163C-RYR1 (HET) MH susceptible mice are used to investigate the influences of dietary CAF on both peripheral and central responses before and after induction of halothane (HAL) maintenance anesthesia under experimental conditions that maintain normal core body temperature. HET mice receiving CAF (plasma CAF 893 ng/ml) have significantly shorter times to respiratory arrest compared with wild type, without altering blood chemistry or displaying hyperthermia or muscle rigor. Intraperitoneal bolus dantrolene before HAL prolongs time to respiratory arrest. A pilot electrographic study using subcutaneous electrodes reveals that dietary CAF does not alter baseline electroencephalogram (EEG) total power, but significantly shortens delay to isoelectric EEG, which precedes respiratory and cardiac arrest. CAF ± HAL are studied on RYR1 single-channel currents and HET myotubes to define molecular mechanisms of gene-by-environment synergism. Strong pharmacological synergism between CAF and HAL is demonstrated in both single-channel and myotube preparations. Central and peripheral nervous systems mediate adverse responses to HAL in a HET model of MH susceptibility exposed to dietary CAF, a modifiable lifestyle factor that may mitigate risks of acute and chronic diseases associated with RYR1 mutations. SIGNIFICANCE STATEMENT: Dietary caffeine at a human-relevant dose synergizes adverse peripheral and central responses to anesthesia in malignant hyperthermia susceptible mice. Synergism of these drugs can be attributed to their actions at ryanodine receptors.

Evaluation of physical euthanasia for neonatal piglets on-farm.

Twenty-seven neonate piglets (range from 0.35 to 1.17 kg) were evaluated for the effectiveness of blunt force trauma as a method of on-farm cull. Brainstem function, brain injury, and hemorrhage scores (increasing from 0 to 3) were assessed after striking the head against a concrete floor. Electroencephalograms (EEG) from a subset of 15 piglets were recorded before and after blunt force trauma for electrophysiological assessments. Blunt force trauma was performed by a single experienced farmer in a commercial farm by holding the piglet by its both hind legs and striking the head against the concrete floor. All piglets remained recumbent and did not show brainstem reflexes. Only one piglet did not presented tonic/clonic physical activity. The mean time to the onset of persistent isoelectric EEG was 64.3 ± 7.3 s (range 18 to 115). Total power, theta, alpha, and beta power decreased to approximately 45%, 30%, 20%, and 15% from pretreatment power, respectively, by 15-s post-impact. There were no periods of normal-like EEG after the culling. Bruises in the neck and shoulder were found in 67% and 70% of piglets, respectively. All piglets presented skull fractures with 20% having the nasal bone(s) fractured. Brain damage was found in all piglets, mainly in the frontal lobe(s). The occipital lobe(s) presented the greatest frequency of severe damage. The analysis of the radiographs also found a high frequency of fractures in this region. Hemorrhage was most frequent in the frontal, parietal, occipital lobes, and midbrain. When performed correctly with the appropriate weight class, blunt force trauma can be used as an effective method for the on-farm killing of nursing piglets resulting in death. However, this method should not be promoted over more reliable and repeatable cull methods such as captive bolt gun. As with blunt force trauma, there is a significant potential for animal welfare harm associated with inappropriate practice, lack of accuracy, issues with repeatability, and operator fatigue.

Prevalence of Isoelectric Electroencephalography Events in Infants and Young Children Undergoing General Anesthesia.

In infants and young children, anesthetic dosing is based on population pharmacokinetics and patient hemodynamics not on patient-specific brain activity. Electroencephalography (EEG) provides insight into brain activity during anesthesia. The primary goal of this prospective observational pilot study was to assess the prevalence of isoelectric EEG events-a sign of deep anesthesia-in infants and young children undergoing general anesthesia using sevoflurane or propofol infusion for maintenance. Children 0-37 months of age requiring general anesthesia for surgery excluding cardiac, intracranial, and emergency cases were enrolled by age: 0-3, 4-6, 7-12, 13-18, and 19-37 months. Anesthesia was maintained with sevoflurane or propofol infusion. EEG was recorded from induction to extubation. Isoelectric EEG events (amplitude <20 µV, lasting ≥2 seconds) were characterized by occurrence, number, duration, and percent of isoelectric EEG time over anesthetic time. Associations with patient demographics, anesthetic, and surgical factors were determined. Isoelectric events were observed in 63% (32/51) (95% confidence interval [CI], 49-76) of patients. The median (interquartile range [IQR]) number of isoelectric events per patient was 3 (0-31), cumulative isoelectric time per patient was 12 seconds (0-142 seconds), isoelectric time per event was 3 seconds (0-4 seconds), and percent of total isoelectric over anesthetic time was 0.1% (0%-2.2%). The greatest proportion of isoelectric events occurred between induction and incision. Isoelectric events were associated with higher American Society of Anesthesiologists (ASA) physical status, propofol bolus, endotracheal tube use, and lower arterial pressure during surgical phase. Isoelectric EEG events were common in infants and young children undergoing sevoflurane or propofol anesthesia. Although the clinical significance of these events remains uncertain, they suggest that dosing based on population pharmacokinetics and patient hemodynamics is often associated with unnecessary deep anesthesia during surgical procedures.

Comparison of penetrating and non-penetrating captive bolt in an alternative occipital approach in calves

AbstractThe objective of this study was to describe the effect of penetrating or non-penetrating captive bolt using an occipital approach in 4-5 month old, Holstein steers weighing between 100-200 kg. Twelve calves were divided into two treatment groups; penetrating captive bolt (PCB; n = 6) and non-penetrating captive bolt (NPCB; n = 6). This sample size was chosen out of convenience and in conjunction with a separate study. Each calf was sedated with xylazine hydrochloride, then a captive-bolt device, outfitted with a standard penetrating bolt or a non-penetrating bolt, was placed flush on the dorsal midline of the cranium at the external occipital protuberance and aimed downward as though to intersect the intermandibular area. Following impact, indicators for loss of consciousness, such as respiration, righting response, corneal reflex, movement and vocalisation were recorded and characterised along with electrocardiogram and electroencephalogram recordings. After a 5-min observation period, all calves were administered potassium chloride. All calves experienced immediate and sustained loss of consciousness. The mean (± SEM) time to cessation of respiration was 60 (± 53.67) and 0 (± 0.0) s for PCB and NPCB, respectively. The mean time to cessation of convulsions was 310.4 (± 79.74) and 180.0 (± 60.24) s, respectively, and the mean number of convulsions was 2.75 (± 1.03) and 2.0 (± 0.837) for PCB and NPCB, respectively. Isoelectric EEG patterns were observed in 3/5 PCB and 3/4 NPCB with mean time to onset of isoelectric pattern in 69.0 (±52.24) and 113.5 (± 56.87) s. Both treatments induced a successful stun, which suggests these techniques are appropriate for humane euthanasia in calves of this age.

Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposal.

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post‐mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.

Neurophysiology for predicting good and poor neurological outcome at 12 and 72 h after cardiac arrest: The ProNeCA multicentre prospective study

AimsTo assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. MethodsProspective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1–3) vs. poor (CPC 4–5). None of the patients underwent withdrawal of life-sustaining treatment. ResultsA total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61–80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8–21]% and 59[50–68]% sensitivity, respectively. Specificity was 100[97–100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97–100]% specificity. Their sensitivities were 63[55–70]% and 66[58–74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. ConclusionsIn comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.

Abstract 10: Early Neuroprognostication After Refractory VF/VT Cardiac Arrest Requiring ECPR

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) can improve survival for refractory ventricular fibrillation (VF) cardiac arrest. Early prognostication will be critical to focus this resource-intensive care to patients likely to benefit. Objectives: The aim of this study is to examine the efficacy of current neuroprognostication tools early in the setting of ECPR for refractory VF. Methods: Consecutive patients transported for the University of Minnesota ECPR program and surviving to hospital admission between December 2015 and May 2019 were assessed. All patients received neurologic assessment with head CT, continuous EEG, cerebral near-infrared spectroscopy (NIRS), biomarkers including S100B and neuron specific enolase (NSE), and neurologic exam. All patients were considered viable unless they developed refractory shock, devastating brain injury, or family requested cessation of efforts. For this analysis, patients were divided into two groups: 1) neurologically favorable survival (CPC 1-2) and 2) those who died or had CPC 3-4. Data from the first 24 hours of hospital admission were used. Results: Of 168 patients, 130 patients survived to hospital admission. Of these, 42% (54/130) survived neurologically favorable. Abnormalities on admission head CT were predictive of poor outcomes; cerebral edema was 100% specific and 30% sensitive for poor outcomes while anoxic injury provided 98% specificity and 39% sensitivity. Admission NSE levels greater than three times the upper limit of normal were predictive with 98% specificity and 26% sensitivity for poor outcome. Admission S100B was highly variable failing to discriminate patient outcome. Absence of brainstem reflexes at 24 hours had 100% specificity and 32% sensitivity. An isoelectric EEG at 24 hours had 100% specificity and 20% sensitivity. NIRS did not predict poor outcomes. When combined, ≥ 1 of the following: anoxic injury on CT, edema on CT, NSE, absence of brainstem reflexes, isoelectric EEG have a specificity of 96% and sensitivity of 67% for poor outcome. Conclusions: Neuroprognostication after 24 hours of hospital admission may be possible in the refractory VF population requiring ECPR. High specificity is possible but sensitivity is limited. Further study is needed.

Evaluation of euthanasia of sheep with intravenous saturated salt solutions to enable the collection of whole, intact brains

Abstract Captive bolts or firearms are unsuitable for euthanasia of livestock when an intact brain is required for diagnostics. Injectable barbiturates can be used, but this method carries risk of poisoning animals eating the carcase. Intravenous saturated salt solutions have been used to euthanase heavily sedated ruminants and are cheap, readily available and not a risk to scavenging animals. However, there is concern that they may be painful or cause distress to animals that are not unconscious. This study aimed to determine the suitability of saturated salt solutions, in combination with xylazine, as a method of euthanasia of ruminants using a sheep model. Thirty-two sheep were sedated with xylazine (0.4 mg kg-1 IM) and euthanased with an intravenous overdose of pentobarbitone (PENT; n = 10), saturated potassium chloride (KCL; n = 11) or saturated magnesium sulphate (MGS; n = 10). Time until end of rhythmic breathing and cardiac arrest, and movement events were recorded. Conscious perception of pain was evaluated by measuring cortical brain activity by electroencephalography (EEG). There was no evidence of perceived pain or unpleasant sensory experience for any treatment as indicated by P50, P95 and Ptot and so all methods were deemed humane. Time until transient EEG was comparable for all treatments. Time until onset of isoelectric EEG was prolonged for KCL. Animals euthanased with KCL consistently exhibited severe reflex movements during infusion (eg kicking, convulsion). No severe movement events were observed in animals euthanased with MGS, hence, physiological and movement data support the preferential use of MGS over KCL.

Evaluation of Brain Death in Laying Hens During On-Farm Killing by Cervical Dislocation Methods or Pentobarbital Sodium Injection.

This study investigated changes in the electroencephalograph (EEG) power spectrum as well as physiological and behavioral responses to on-farm killing via mechanical cervical dislocation (MCD), manual cervical dislocation (CD) or intravenous pentobarbital sodium administration in lightly anesthetized laying hens, to evaluate the welfare impact of each method. A mixed group of 44 white Leghorn and Smoky Joe laying hens (60 weeks-old) were anesthetized with isoflurane in oxygen and maintained at 1.5–2% isoflurane/O2 until the killing method was applied. Birds were randomly assigned to one of three experimental groups on each trial day. The EEG was recorded bilaterally in a four-electrode montage. After recording a 5-min baseline, the killing method was applied and EEGs and other behavioral and physiological responses, including convulsions, gasping, cessation of body movements and feather erection were recorded for 5 min. Changes in EEG frequency bands (alpha, beta, delta, theta), median frequency (F50), 95% spectral edge frequency (F95), and total power (Ptot) were used to assess the quality of the on-farm killing event. Within 15 s after administration of pentobarbital sodium, there were significant decreases in mean frequency bands, increases in mean F50 and F95, and decreases in Ptot, suggesting brain death. In addition, birds presented a shorter latency to cessation of movement after pentobarbital sodium injection compared to MCD and CD (22 vs. 115 s and 136 s, respectively). There were significant increases in F95 and decreases in Ptot at 120 s after application of CD; and a concomitant decrease in the frequency bands at 135 s and isoelectric EEG at 171 ± 15 s. Changes consistent with brain death after MCD included isoelectric EEG at 207 ± 23 s and a significant decreases in some frequency bands at 300 s post-application. No other significant spectrum frequency changes were observed in the MCD group, suggesting brain death likely occurred near the 5-min endpoint. There was no clear association between behavioral, physiological, and EEG responses within CD and MCD treatments. The data demonstrate that pentobarbital sodium induced a rapid death with minimal behavioral and physiological responses regardless of strain of hens. In comparison, use of CD and MCD resulted in a slow onset of brain death in hens.