Inhibiting α5 Subunit-Containing γ-Aminobutyric Acid Type A Receptors Attenuates Cognitive Deficits After Traumatic Brain Injury.

OBJECTIVES: Cognitive deficits after traumatic brain injury are a leading cause of disability worldwide, yet no effective pharmacologic treatments exist to improve cognition. Traumatic brain injury increases proinflammatory cytokines, which trigger excess function of α5 subunit-containing γ-aminobutyric acid type A receptors. In several models of brain injury, drugs that inhibit α5 subunit-containing γ-aminobutyric acid type A receptor function improve cognitive performance. Thus, we postulated that inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors would improve cognitive performance after traumatic brain injury. In addition, because traumatic brain injury reduces long-term potentiation in the hippocampus, a cellular correlate of memory, we studied whether inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated deficits in long-term potentiation after traumatic brain injury. DESIGN: Experimental animal study. SETTING: Research laboratory. SUBJECTS: Adult male mice and hippocampal brain slices. INTERVENTIONS: Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ-aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM). MEASUREMENTS AND MAIN RESULTS: Traumatic brain injury increased the time required to solve difficult but not simple tasks in the puzzle box assay and impaired memory in the novel object recognition and object place recognition assays. L-655,708 improved both problem solving and memory in the traumatic brain injury mice. Traumatic brain injury reduced long-term potentiation in the hippocampal slices, and L-655,708 attenuated this reduction. CONCLUSIONS: Pharmacologic inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ-aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.

Dexmedetomidine Prevents Excessive γ-Aminobutyric Acid Type A Receptor Function after Anesthesia.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors. METHODS: Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied. RESULTS: The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia. CONCLUSIONS: Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.

Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group.

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

Tranexamic acid-associated seizures: Causes and treatment.

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients.

Inflammation Increases Neuronal Sensitivity to General Anesthetics.

BACKGROUND: Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of γ-aminobutyric acid type A (GABAA) receptors expressed on the surface of neurons, which supports the hypothesis that inflammation increases up-regulation of GABAA receptor activity by anesthetics, thereby enhancing the behavioral sensitivity to these drugs. METHODS: To mimic inflammation in vitro, cultured hippocampal and cortical neurons were pretreated with interleukin (IL)-1ß. Whole cell patch clamp methods were used to record currents evoked by γ-aminobutyric acid (GABA) (0.5 µM) in the absence and presence of etomidate or isoflurane. To mimic inflammation in vivo, mice were treated with lipopolysaccharide, and several anesthetic-related behavioral endpoints were examined. RESULTS: IL-1ß increased the amplitude of current evoked by GABA in combination with clinically relevant concentrations of either etomidate (3 µM) or isoflurane (250 µM) (n = 5 to 17, P < 0.05). Concentration-response plots for etomidate and isoflurane showed that IL-1ß increased the maximal current 3.3-fold (n = 5 to 9) and 1.5-fold (n = 8 to 11), respectively (P < 0.05 for both), whereas the half-maximal effective concentrations were unchanged. Lipopolysaccharide enhanced the hypnotic properties of both etomidate and isoflurane. The immobilizing properties of etomidate, but not isoflurane, were also increased by lipopolysaccharide. Both lipopolysaccharide and etomidate impaired contextual fear memory. CONCLUSIONS: These results provide proof-of-concept evidence that inflammation increases the sensitivity of neurons to general anesthetics. This increase in anesthetic up-regulation of GABAA receptor activity in vitro correlates with enhanced sensitivity for GABAA receptor-dependent behavioral endpoints in vivo.

δGABAA Receptors Are Necessary for Synaptic Plasticity in the Hippocampus: Implications for Memory Behavior.

BACKGROUND: Extrasynaptic γ-aminobutyric acid type A (GABAA) receptors that contain the δ subunit (δGABAA receptors) contribute to memory performance. Dysregulation of δGABAA receptor expression, which occurs in some neurological disorders, is associated with memory impairment. Mice lacking δGABAA receptors (Gabrd) exhibit deficits in their ability to distinguish between similar memories, a process which is referred to as pattern separation. The CA3 and dentate gyrus subfields of the hippocampus regulate pattern separation, raising the possibility that synaptic plasticity is impaired in these regions in Gabrd mice. Although long-term potentiation (LTP), the most widely studied form of synaptic plasticity, is normal in the dentate gyrus of Gabrd mice, LTP in the CA3 subfield has not been studied. Here, we tested the hypothesis that LTP is reduced in the CA3 subfield of Gabrd mice. METHODS: LTP of extracellular field postsynaptic potentials was studied in the mossy fiber (MF)-CA3 pathway using hippocampal slices from Gabrd and wild-type (WT) mice. We also examined paired pulse responses and input-output relationships at MF-CA3 synapses. RESULTS: MF-CA3 LTP was reduced in Gabrd mice, as evidenced by decreased potentiation of field postsynaptic potentials (WT: 178.3% ± 16.1% versus Gabrd: 126.3% ± 6.9%; P = 0.0091). Thus, the deletion of δGABAA receptors is associated with impaired plasticity. Bicuculline (BIC), a GABAA receptor antagonist, reduced plasticity in WT but not in Gabrd mice (WT + BIC: 123.9% ± 7.6% versus Gabrd + BIC: 136.5% ± 7.0%). Paired pulse responses and input-output relationships did not differ between the genotypes (all Ps > 0.05). CONCLUSIONS: Both genetic deletion and pharmacological blockade of δGABAA receptors impair MF-CA3 LTP, suggesting that δGABAA receptors are necessary for synaptic plasticity in the CA3 subfield. Drugs that enhance δGABAA receptor function may reverse deficits in synaptic plasticity in the CA3 subfield and improve pattern separation in neurological disorders.

Hospital policy of tranexamic acid to reduce transfusion in major non-cardiac surgery (TRACTION): protocol for a phase IV randomised controlled trial.

INTRODUCTION: Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk. METHODS AND ANALYSIS: A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention. ETHICS AND DISSEMINATION: Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT04803747.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Identification of cervicothoracic intervertebral spaces by surface landmarks and ultrasound.

PURPOSE: Precise localization of the cervicothoracic vertebral levels is essential for accurate placement of epidural catheters. Previous studies have demonstrated that anesthesiologists are inaccurate when using surface anatomy to locate lumbar vertebral levels. Our study was designed to determine the agreement between anatomical landmarks and the ultrasound technique in identifying the T7-8 and C7-T1 intervertebral spaces. METHODS: Adult healthy volunteers were assessed for the identification of cervicothoracic intervertebral spaces, initially in the anatomic position (AP)-upright, back straight, arms at the sides, and palms forward and then in the epidural position (EP) routinely used for epidural placement-seated, back arched, neck flexed, and arms across the chest. The T7 and C7 spinous processes were identified by one investigator using the inferior tip of the scapula and the vertebra prominens, respectively, as landmarks. Ultrasound was then used by a second investigator to identify the intervertebral spaces corresponding to the previously marked levels. RESULTS: Fifty-five volunteers (23 males, 32 females) were recruited. The T7-8 intervertebral space determined by ultrasound coincided with the landmark findings in the AP and in the EP in 18% and 36% of the cases, respectively. The C7-T1 interspace identified by ultrasound corresponded with the surface landmarks in the AP and in the EP in 53% and 58% of the cases, respectively. In most cases, when the surface landmark and ultrasound findings of T7-8 did not agree, the surface landmark identified a lower interspace than ultrasound. CONCLUSION: Identification of cervicothoracic intervertebral spaces by surface landmarks corresponded poorly with their identification using ultrasound. However, compared with the upright position, agreement in identifying the T7-8 interspace improved in the epidural position.

The Role of Virtual Reality in Screening, Diagnosing, and Rehabilitating Spatial Memory Deficits.

Impairment of spatial memory, including an inability to recall previous locations and navigate the world, is often one of the first signs of functional disability on the road to cognitive impairment. While there are many screening and diagnostic tools which attempt to measure spatial memory ability, they are often not representative of real-life situations and can therefore lack applicability. One potential solution to this problem involves the use of virtual reality (VR), which immerses individuals in a virtually-simulated environment, allowing for scenarios more representative of real-life without any of the associated risks. Here, we review the evidence surrounding the use of VR for the screening and diagnosis of spatial memory impairments, including potential limitations and how it compares to standard neuropsychological tests. We will also discuss the evidence regarding the potential use of VR in the rehabilitation of spatial memory deficits, which has not been well studied, but which could be game-changing if proven successful.

Cognitive decline among older adults: A hidden preexisting condition and its role in 'brain-at-risk' surgical patients.

Preexisting cognitive impairment is an important, but underrecognized, predictor of postoperative neurocognitive dysfunction, a common and important sequela of surgery. We have applied computerized neuropsychological testing as an efficient and reliable means of detecting preexisting cognitive impairment in two studies of cardiac and noncardiac surgical populations and propose that this tool has great potential in routine clinical diagnosis.

Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol.

INTRODUCTION: Older patients undergoing cardiac surgery carry the highest risk for developing major postoperative neurocognitive disorder (postoperative NCD or P-NCD) with up to 25% incidence 3 months after surgery. P-NCD is associated with significant morbidity, mortality, loss of independence, premature retirement and increased healthcare costs. This multicentre randomised trial is investigating the efficacy of postoperative dexmedetomidine sedation in reducing the incidence of major P-NCD after cardiac surgery compared with standard protocols. CODEX will be the largest interventional trial with major P-NCD as the primary outcome. METHODS AND ANALYSIS: CODEX is recruiting patients ≥60 years old, undergoing elective cardiac surgery and without pre-existing major cognitive dysfunction or dementia. Eligible participants are randomised to receive postoperative dexmedetomidine or standard institutional sedation protocols in the intensive care unit. Baseline preoperative cognitive function is assessed with the computer-based Cogstate Brief Battery. The primary outcome, major P-NCD, 3 months after surgery is defined as a decrease in cognitive function ≥1.96 SD below age-matched, non-operative controls. Secondary outcomes include delirium, major P-NCD at 6/12 months, depressive symptoms, mild P-NCD and quality of surgical recovery at 3/6/12 months. The specific diagnostic criteria used in this protocol are consistent with the recommendations for clinical assessment and management of NCD from the Nomenclature Consensus Working Group on perioperative cognitive changes. Intention-to-treat analysis will compare major P-NCD at 3 months between study groups. ETHICS AND DISSEMINATION: CODEX was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB) (Project ID 1743). This will be the first multicentre, randomised controlled trial to assess the efficacy of a pharmacological intervention to reduce the incidence of major P-NCD after cardiac surgery in patients ≥60 years old. Dissemination of the study results will include briefings of key findings and interpretation, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04289142.

Synaptic strength modulation after cortical trauma: a role in epileptogenesis.

Traumatic brain injuries are often followed by abnormal hyperexcitability, leading to acute seizures and epilepsy. Previous studies documented the rewiring capacity of neocortical neurons in response to various cortical and subcortical lesions. However, little information is available on the functional consequences of these anatomical changes after cortical trauma and the adaptation of synaptic connectivity to a decreased input produced by chronic deafferentation. In this study, we recorded intracellular (IC) activities of cortical neurons simultaneously with extracellular (EC) unit activities and field potentials of neighboring cells in cat cortex, after a large transection of the white matter underneath the suprasylvian gyrus, in acute and chronic conditions (at 2, 4, and 6 weeks) in ketamine-xylazine-anesthetized cats. Using EC spikes to compute the spike-triggered averages of IC membrane potential, we found an increased connection probability and efficacy between cortical neurons weeks after cortical trauma. Inhibitory interactions showed no significant changes in the traumatized cortex compared with control. The increased synaptic efficacy was accompanied by enhanced input resistance and intrinsic excitability of cortical neurons, as well as by increased duration of silent network periods. Our electrophysiological data revealed functional consequences of previously reported anatomical changes in the injured cortex. We suggest that homeostatic synaptic plasticity compensating the decreased activity in the undercut cortex leads to an uncontrollable cortical hyperexcitability and seizure generation.

Future Directions for Geriatric Anesthesiology.

"With a rapidly aging world population, it is critical for physicians of every specialty to adapt the ways they provide medical and perioperative care to patients. Older adults represent the largest population of health care users, and they have very different needs and preferences compared with their younger counterparts. In this article, the authors discuss some of the current gaps in geriatric anesthesia and perioperative care, as they elaborate on what can be expected in the near future at different levels of the health care system: the patient, the environment, and the anesthesia specialty."

Protocol for a prospective cohort study of assessing postoperative cognitive changes after total hip and knee arthroplasty in the Greater Toronto area.

INTRODUCTION: Cognitive changes after anaesthesia and surgery, such as delirium and postoperative cognitive dysfunction (POCD), are common and lead to poor outcomes and increased healthcare costs. While several interventions for delirium exist, there are no effective treatment strategies for POCD. Understanding the risks and contributing factors may offer clinicians unique opportunities to better identify and develop preventative interventions for those at higher risk. Elderly patients undergoing orthopaedic surgery are at high risk of developing postoperative delirium (PD) and POCD. The incidence of POCD has not been rigorously studied in the total hip and knee arthroplasty (THA/TKA) population. Therefore, we have designed a prospective, observational cohort study to assess POCD in patients undergoing THA/TKA, both increasingly common procedures. The incidence of PD and POCD in a high volume, tertiary care arthroplasty centre will be determined and associated risk factors will be identified. METHODS AND ANALYSIS: Cognitive function will be tested with a computer-based cognitive assessment tool [CogState Brief Battery], preoperatively at baseline and postoperatively while in hospital at (<3 days), 6 weeks and 4.5 months. The primary outcome is the incidence of postoperative cognitive decline at 4.5 months. Logistic regression analysis is planned to test the association of POCD with several potential risk factors. In addition, delirium will be assessed preoperatively and postoperatively in the hospital using the Confusion Assessment Method (3D-CAM). ETHICS AND DISSEMINATION: The protocol for this prospective observational study was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (REB#: 040-2017). Recruitment commenced in May 2017 and will continue until 2019. The results will be disseminated in a peer-reviewed journal and in scientific meetings. TRIAL REGISTRATION NUMBER: NCT03147937.

Burst-suppression is reactive to photic stimulation in comatose children with acquired brain injury.

OBJECTIVE: Burst-suppression is an electroencephalographic pattern observed during coma. In individuals without known brain pathologies undergoing deep general anesthesia, somatosensory stimulation transiently increases the occurrence of bursts. We investigated the reactivity of burst-suppression in children with acquired brain injury. METHODS: Intensive care unit electroencephalographic monitoring recordings containing burst-suppression were obtained from 5 comatose children with acquired brain injury of various etiologies. Intermittent photic stimulation was performed at 1Hz for 1min to assess reactivity. We quantified reactivity by measuring the change in the burst ratio (fraction of time in burst) following photic stimulation. RESULTS: Photic stimulation evoked bursts in all patients, resulting in a transient increase in the burst ratio, while the mean heart rate remained unchanged. The regression slope of the change in burst ratio, referred to as the standardized burst ratio reactivity, correlated with subjects' Glasgow Coma Scale scores. CONCLUSIONS: Reactivity of the burst-suppression pattern to photic stimulation occurs across diverse coma etiologies. Standardized burst ratio reactivity appears to reflect coma severity. SIGNIFICANCE: Measurement of burst ratio reactivity could represent a simple method to monitor coma severity in critically ill children.

Sonoanatomy of the thoracic spine in adult volunteers.

BACKGROUND AND OBJECTIVES: Ultrasonography of the lumbar spine provides information to facilitate the placement of neuraxial anesthesia. Likewise, thoracic spine ultrasound (US) might conceivably improve the quality and safety of thoracic epidural anesthesia. The objective of this study was to advance our understanding in this area by providing a detailed description of the sonoanatomy of the thoracic spine. METHODS: This was a prospective, observational, cohort study in 61 adult volunteers. We performed US scanning of all thoracic interspaces in the right paramedian sagittal oblique (PSO) and transverse median (TM) planes. The images were classified as conclusive and inconclusive, depending on the visibility of ligamentum flavum-dura mater complex (Lf-Dm). The primary outcome was the presence of conclusive images. The secondary outcomes were measurements of various distances between sonoanatomic elements. Data are presented as mean (SD), unless otherwise specified. RESULTS: Overall, the incidence of conclusive images was higher in the PSO than in the TM plane (74.5% [15.4%] versus 37.5% [39.7%], P < 0.001). In the lower thoracic levels, 98% of images were conclusive in both planes, but the number of conclusive images decreased progressively in the upper thoracic levels, more so in the TM than in the PSO plane. The mean depth to Lf-Dm was similar when measured in both PSO (4.0 [0.7] cm) and TM planes (4.1 [0.7] cm). CONCLUSIONS: Ultrasound imaging of the thoracic spine in the PSO plane provides better views of the Lf-Dm compared with the TM plane. A upper incidence of inconclusive sonograms should be expected in the upper thoracic segments, which can be attributed to the narrower acoustic windows at these levels.