Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAcCRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAcCRH neurons during wakefulness and rewarding stimulation. Activation of NAcCRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAcCRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAcCRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAcCRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.

Differential Utilization of Parental Presence and Premedication for Induction of Anesthesia in Pediatric Patients.

PURPOSE: Known disparities exist in pain treatment between African American, Latino, and White children. A recent study described 'adultification' of Black children, with Black children being less likely to have a parent present at induction of anesthesia and less likely to receive an anxiolytic premedication before proceeding to the operating room. The aim of this study is to identify differences based on race and socioeconomic status when treating children and their families for anesthetic induction. We hypothesize that differences exist such that certain populations are less likely to receive sedative premedication and less likely to have parents present at induction of anesthesia. DESIGN: This was a retrospective cohort study. METHODS: Demographic data were obtained along with type of surgical procedure, type of anesthesia induction, use of premedication, and involvement of child life services (including the plan for parental presence at induction) for all pediatric patients presenting for anesthetics from February 2019 to March 2020. Statistical analysis consisted of fitting logistic mixed effects models for caregiver presence or for midazolam use during induction, with fixed effects for sex, race, ethnicity, language, public/private insurance, and anesthetic risk, and with the provider as a random effect. FINDINGS: A total of 7,753 patients were included in our statistical analyses, and parental presence focused on 4,102 patients with documentation from child life specialists. Females were less likely than males to have parents present at induction (odds ratio [OR] 0.77, confidence interval [CI] [0.67, 0.89]). When looking at race, American Indian/Alaskan Native patients (OR 0.23 [CI 0.093, 0.47]) and Black/African American patients OR 0.64 [CI 0.47, 0.89]) were less likely to have a parent present induction than White patients. Patients with private insurance were more likely to have parents present than patients with public insurance (OR 0.63 CI [0.5, 0.78]). These findings held true in age-separated sensitivity analysis. Asian patients were less likely to receive midazolam premedication (OR 0.65 CI [0.49, 0.86]). CONCLUSIONS: This study supports previous work showing differential use of parental presence at induction based on race. Additionally, it also shows different treatment based on sex and public insurance status, a surrogate for socioeconomic status.

Out of touch? How trauma shapes the experience of social touch - Neural and endocrine pathways.

Trauma can shape the way an individual experiences the world and interacts with other people. Touch is a key component of social interactions, but surprisingly little is known about how trauma exposure influences the processing of social touch. In this review, we examine possible neurobiological pathways through which trauma can influence touch processing and lead to touch aversion and avoidance in trauma-exposed individuals. Emerging evidence indicates that trauma may affect sensory touch thresholds by modulating activity in the primary sensory cortex and posterior insula. Disturbances in multisensory integration and oxytocin reactivity combined with diminished reward-related and anxiolytic responses may induce a bias towards negative appraisal of touch contexts. Furthermore, hippocampus deactivation during social touch may reflect a dissociative state. These changes depend not only on the type and severity of the trauma but also on the features of the touch. We hypothesise that disrupted touch processing may impair social interactions and confer elevated risk for future stress-related disorders.

Nitrous oxide use in Canadian pediatric emergency departments: a survey of physician's knowledge, attitudes, and practices.

OBJECTIVES: Nitrous oxide (N2O) is an inhaled analgesic/ anxiolytic gas with evidence supporting its safety and efficacy for distressing procedures in children. Despite this, its use is not consistent across Canadian pediatric emergency departments (EDs). We aimed to characterize a) physicians' knowledge and practices with N2O and b) site-specific N2O protocols in Canadian pediatric EDs to help optimize its use nationally. METHODS: This cross-sectional survey was distributed to physician members of Pediatric Emergency Research Canada (PERC) in early 2021. Survey items addressed practice patterns, clinician comfort, and perceived barriers/ facilitators to use. Further, a representative from each ED completed a site-specific inventory of N2O policies and procedures. RESULTS: N2O was available in 40.0% of 15 pediatric EDs, with 83.3% of these sites having written policies in place. Of 230 distributed surveys, 67.8% were completed with mean (SD) attending experience of 14.7 (8.6) years and 70.1% having pediatric emergency subspecialty training. Of the 156 respondents, 48.7% used N2O in their clinical practice. The most common indications for use were digit fracture/ dislocation reduction (69.7%), wound closure (60.5%), and incision & drainage (59.2%). Commonly perceived facilitators were N2O equipment availability (73.0% of 156) and previous clinical experience (71.7% of 156). Of the 51.3% of physicians who reported not using N2O, 93.7% did not have availability at their site; importantly, the majority indicated a desire to acquire access. They identified concerns about ventilation/ scavenging systems (71.2% of 80) and unfamiliarity with equipment (52.5% of 80) as the most common barriers to use. CONCLUSIONS: Despite evidence to support its use, only half of Canadian pediatric ED physicians surveyed use N2O in their clinical practice for treating procedure-related pain and distress. Increased availability of N2O equipment, protocols, and training may improve clinicians' abilities to better manage pediatric acute pain and distress in the ED.

RéSUMé: OBJECTIFS: Le protoxyde d'azote (N2O) est un gaz analgésique/anxiolytique inhalé dont l'innocuité et l'efficacité ont été démontrées lors d'interventions pénibles chez l'enfant. Malgré cela, son utilisation n'est pas uniforme dans les services d'urgences pédiatriques (SU) du Canada. Nous avons cherché à caractériser a) les connaissances et les pratiques des médecins en matière de N2O et b) les protocoles de N2O spécifiques à un site dans les urgences pédiatriques canadiennes afin d'aider à optimiser son utilisation à l'échelle nationale. MéTHODES: Cette enquête transversale a été distribuée aux médecins membres de Recherche d'urgence pédiatrique Canada (PERC) au début de 2021. Les questions de l'enquête portaient sur les modes de pratique, l'aisance du clinicien et les obstacles/facilitateurs perçus pour l'utilisation. En outre, un représentant de chaque SU a dressé un inventaire des politiques et procédures N2O propres à chaque site. RéSULTATS: La N2O était disponible dans 40,0% des 15 services d'urgence pédiatriques, et 83,3% de ces sites avaient mis en place des politiques écrites. Sur 230 enquêtes distribuées, 67,8% ont été réalisées avec une expérience moyenne (SD) de 14,7 (8,6) ans et 70,1% ont suivi une formation en surspécialité pédiatrique d'urgence. Sur les 156 répondants, 48,7% utilisaient le N2O dans leur pratique clinique. Les indications les plus courantes étaient la réduction des fractures digitales et des luxations (69,7%), la fermeture des plaies (60,5%) et l'incision et le drainage (59,2%). Les facilitateurs généralement perçus étaient la disponibilité de l'équipement N2O (73,0% sur 156) et l'expérience clinique antérieure (71,7% sur 156). Parmi les 51,3% de médecins qui ont déclaré ne pas utiliser de N2O, 93,7% n'avaient pas de disponibilité sur leur site; il est important de noter que la majorité d'entre eux ont indiqué qu'ils souhaitaient y avoir accès. Ils ont identifié les préoccupations concernant les systèmes de ventilation/de récupération (71,2% sur 80) et la méconnaissance de l'équipement (52,5% sur 80) comme étant les obstacles les plus courants à l'utilisation de l'appareil. CONCLUSIONS: Malgré les données probantes à l'appui de son utilisation, seulement la moitié des médecins canadiens des urgences pédiatriques interrogés utilisent le N2O dans leur pratique clinique pour traiter la douleur et la détresse liées à l'intervention. Une plus grande disponibilité de l'équipement N2O, des protocoles et de la formation peut améliorer les capacités des cliniciens à mieux gérer la douleur aiguë et la détresse pédiatrique aux urgences.

Midazolam for Anesthetic Premedication in Children: Considerations and Alternatives.

Premedication in anesthesia has long been used to reduce patient anxiety, increase patient compliance, and supplement the overall anesthetic. In pediatric populations, premedication also has the indirect benefits of reducing parental anxiety as well as both the incidence and severity of emergence delirium. Oral midazolam, selected for its ease of administration, short duration of action, and reliable anxiolytic and amnestic effects, has been a favorite choice in this role for decades. The side effect profile of midazolam is also relatively benign, heavily dose-dependent, and easily managed in the perioperative setting. While midazolam appears to be an ideal adjunct in the anesthetic care of pediatric patients, there is a growing body of evidence suggesting prolonged benzodiazepine exposure causes neurodevelopmental changes in infants. This evidence, along with the 2017 Food and Drug Administration (FDA) warning labels for the use of select anesthetic medications, including midazolam in children under the age of three, has led to some debate in the anesthetic community over the continued use of this anesthetic for premedication in pediatric populations. This article aims to educate the reader on the history of midazolam as a premedication agent in pediatric populations and examine the evidence supporting and against its continued use in this role.

Advances in Anesthesia for Shoulder Surgery: A Comprehensive Review of Dexmedetomidine-Enhanced Interscalene Brachial Plexus Block.

Surgical procedures on the shoulder pose distinctive challenges in managing pain during the perioperative period, underscoring the importance of exploring innovative anesthesia techniques. This comprehensive review article delves into integrating dexmedetomidine, an alpha-2 adrenergic agonist, within interscalene brachial plexus blocks for shoulder surgery. The review initiates by underscoring the pivotal role of effective anesthesia in shoulder surgery and elucidates the rationale behind investigating dexmedetomidine as an adjunct. It meticulously examines the anatomy and physiology of the brachial plexus, emphasizing its critical significance in shoulder surgery. Furthermore, the article expounds on dexmedetomidine's mechanisms of action and pharmacokinetics, encompassing its safety profile and potential side effects. The conventional interscalene brachial plexus block techniques, along with their limitations and challenges, are discussed, laying the foundation for the integration of dexmedetomidine. The review subsequently delves into exploring the role of dexmedetomidine in regional anesthesia, covering previous studies, mechanisms of action, and the potential advantages of incorporating it into nerve blocks. The review's core concentrates on the practical application of dexmedetomidine-enhanced interscalene brachial plexus blocks. This includes discussions on administration techniques, dosage guidelines, and compelling evidence supporting its utilization. Clinical scenarios where this approach proves most advantageous are thoroughly explored, comparing its effectiveness with traditional techniques in terms of pain control and patient outcomes. A comprehensive examination of relevant clinical trials and case studies highlights the evidence supporting its efficacy. The review also underscores safety considerations associated with dexmedetomidine. It proposes strategies for mitigating risks to ensure patient safety. Insights into future directions and research are provided, encompassing ongoing studies, areas necessitating further investigation, and potential refinements in technique. Finally, the article summarizes key findings, emphasizing the practicality of dexmedetomidine-enhanced interscalene brachial plexus blocks in shoulder surgery and its far-reaching implications for clinical practice and patient care.

Does Acupuncture Hurt? A Retrospective Study on Pain and Satisfaction during Pediatric Acupuncture.

Previous studies have shown the benefit and safety of pediatric acupuncture, but it is often rejected by patients and their caregivers due to the perception of needling pain associated with acupuncture. A retrospective cohort study of 230 unique patients (1380 sessions) aged 8 to 21 underwent Kiiko Matsumoto Style acupuncture in an outpatient pain clinic. Patients completed a post-acupuncture survey, including the Faces Pain Scale-Revised and Likert-like scales about overall satisfaction, relaxation, and anxiolysis. Univariate analyses were conducted on all outcomes of interest. The mean needling pain score was 1.3 out of 10 with 57.7% of patients reporting no needling pain during their first acupuncture session. The mean score for overall satisfaction was 8.4 out of 10, relaxation was 8.2 out of 10, and anxiety reduction was 7.7 out of 10. The overall satisfaction, relaxation, and anxiolytic effect of acupuncture was increased in patients with more sessions (p = 0.003, 0.022, 0.004, respectively). There was no change in needling pain scores in patients with an increased number of acupuncture sessions (p = 0.776). Patients experience minimal needling pain during acupuncture needling and are highly satisfied with acupuncture. Those with more treatment sessions report feeling increased satisfaction and relaxation.

Exposure to an enriched environment exerts anxiolytic effects in Sardinian alcohol-preferring rats.

Exposure to an enriched environment (EE) has been reported to generate multiple beneficial effects in rodents, including - among the many - amelioration of anxiety-related behaviors. The present study investigated whether living in an EE produced anxiolytic effects also in selectively bred Sardinian alcohol-preferring (sP) rats. The relevance of this research question relied on two factors: sP rats displayed an inherent, high anxiety-like state under different experimental conditions; exposure to EE reduced operant, oral alcohol self-administration in sP rats. Starting from weaning, male sP rats were kept under 3 different housing conditions: impoverished environment (IE; single housing with no environmental enrichment); standard environment (SE; 3 rats/cage with no environmental enrichment); EE (6 rats/cage with various elements of environmental enrichment). At the age of approximately 80 days, rats were exposed to an elevated plus maze test for assessment of anxiety-related behaviors. Compared to IE and SE rats, EE rats displayed higher basal levels of exploratory activity (i.e., increased number of entries into closed arms). Compared to IE and SE rats, EE rats also displayed a less "anxious" profile, as suggested by the increase in percent number of entries into open arms (OAs), percent time spent in OAs, number of head dips, and number of end-arm explorations in OAs. These data extend the protective (anxiolytic) effects of EE to a proposed animal model of comorbid alcohol use disorder and anxiety disorders.

Real-world data of non-invasive stimulation of the human insula-prefrontal cortices using deep TMS to treat anxiety for occupational stress and generalized anxiety disorder.

Activation of the insula is found in all anxiety-related disorders and increased insular-prefrontal cortex (PFC) functional connectivity is associated with reduced anxiety. In this study, the combined stimulation of the insula and PFC using the dTMS H4 (insula+LPFC) and H2 (PFC) coils were used to reduce anxiety in 13 subjects experiencing occupational stress, and 55 participants suffering from generalized anxiety disorder (GAD). The combined HF stimulation of the insula and PFC significantly decreased anxiety scores according to the HARS, CAS, and STAI anxiety scales, leading to a reduction in anxiety according to HARS of 88.7% and 70.7% in participants with occupational stress and the clinical sample of participants diagnosed with GAD, respectively. The findings suggest that the prefrontal-insular axis is critical for the regulation of anxiety and its stimulation can be used for the treatment of anxiety in people suffering from occupational stress and GAD.

The Anxiolytic-like Properties of a Tryptic Hydrolysate of Bovine αs1 Casein Containing α-Casozepine Rely on GABAA Receptor Benzodiazepine Binding Sites but Not the Vagus Nerve.

(1) Background: A tryptic hydrolysate of bovine αs1-casein (CH) exerts anxiolytic-like properties in many species, including humans. This is mainly related to the presence of α-casozepine (α-CZP), which yields these properties in rodents. This study evaluates, in a rat model, the roles of the vagus nerve and the benzodiazepine binding site of GABAA receptors in the mode of action of CH. (2) Methods: The conditioned defensive burying test was used to evaluate anxiety. (3) Results: Participation of the vagus nerve in the mode of action of CH was excluded, as the global anxiety score in vagotomised rats was not significantly different from that of non-vagotomised animals. The blocking of the binding sites of benzodiazepines with flumazenil antagonised CH anxiolytic-like properties. (4) Conclusions: The vagus nerve does not play a role in the anxiolytic-like properties of CH. On the other hand, this anxiolytic-like activity relies on the benzodiazepine binding site of the GABAA receptors. This result is consistent with previous in vitro studies and, more specifically with the discovery of α-CZP, the peptide responsible for the anxiolytic-like properties of CH.

Randomised clinical trial evaluating the effect of a single preappointment dose of gabapentin on signs of stress in hyperthyroid cats.

OBJECTIVES: The aim of this study was to evaluate the efficacy of gabapentin as an anxiolytic in hyperthyroid cats. METHODS: Cats (n = 47) with confirmed hyperthyroidism were successfully enrolled. The cat owner allocated a temperament score and a transport stress score at their first visit. For the second visit the cat owner (blinded to treatment) administered either liquid gabapentin 20 mg/kg (n = 22) or an indistinguishable placebo solution (n = 25) 1 h prior to leaving home. A second transport score was allocated by the cat owner at this visit. Upon admission a compliance score was independently assigned by two veterinary nurses blinded to treatment. Excess blood from routine blood draw was analysed for gabapentin plasma concentration from cats in the gabapentin group. RESULTS: There were no significant differences in baseline transport score between groups (P = 0.13), but significant differences were noted in the second visit transport score between cats medicated with gabapentin compared with placebo (P = 0.018). Mean compliance scores were significantly different between cats in the treatment group compared with placebo (P = 0.019). Further sedation was required to complete the procedures in 24% of cats in the placebo group compared to 9% in the gabapentin group (P = 0.25). Mean plasma gabapentin concentrations were 10.1 mg/l (range 1.7-22.7) in the gabapentin group within a 1-3 h time frame post-administration. CONCLUSIONS AND RELEVANCE: Hyperthyroid cats medicated with 20 mg/kg gabapentin 1 h prior to leaving home were more relaxed during transport and more compliant with veterinary procedures than cats administered a placebo solution.

Frequency of Prescribing and Administering Premedication in Paediatric Surgical Patients at a Tertiary Care Hospital: An Observational Study.

INTRODUCTION:  Preoperative period is a stressful event, especially for paediatric patients undergoing surgery. Stress may lead to the development of perioperative maladaptive behaviour, activation of stress responses, and susceptibility to postoperative infections. To alleviate preoperative stress, the use of a multimodal approach including preoperative pharmacological premedication in the ward is recommended. We conducted an observational study to determine the frequency of prescribing and administering premedication in paediatric surgical patients. METHODS: This three-month retrospective observational study was conducted in the main operating room of the Aga Khan University Hospital, Karachi, from October to December 2014. It included all paediatric patients (aged 1-16 years) coming for elective surgery. Patients' preoperative forms and medical records were reviewed, and data recorded for written orders of premedication and the timing of administration of the premedication drug in the inpatient ward/surgical day care ward. A p-value <0.05 was considered statistically significant. RESULTS: This study included 125 paediatric patients. Premedication was not prescribed to 40% (50/125) patients. In these patients, drug and dose were properly mentioned in 98.7% (74/75) of cases while the route and time of administration were not mentioned in 26.6% and 12% prescription orders, respectively. The premedication drug was administered in 67 out of 75 patients (89.3%) by ward nurses as per prescription. The administration of premedication was documented in 95.5% patients, but the time was missing in 46.3% of cases. CONCLUSION: A significant number of patients were not prescribed preoperative premedication by the anaesthetist. Moreover, the route and timing of administration of drug were not mentioned especially in cases when premedication was prescribed in the wards.

Effectiveness and Safety of Elevated Dosages of Nitrous Oxide on Behavior Management in Pediatric Dentistry.

OBJECTIVE: To determine if administering a higher dosage of nitrous oxide (>50%), with a nasal hood in pediatric dental restorative procedures, can allow for a safe and more cooperative experience for the pediatric patient as measured by observable adverse reactions and the Frankl Behavior Rating Scale. STUDY DESIGN: A retrospective chart review was completed of 200 patients total, 100 for each nitrous oxide (N2O) dosage group (≤50% vs >50%). Adverse reactions and The Frankl Behavior Rating Scale during pediatric restorative procedures with N2O were compared between the two dosage groups. RESULTS: There were few adverse reactions for both nitrous oxide groups (≤50% vs >50%) and there was no statistical difference in the Frankl Behavior Rating Scale for each group. CONCLUSIONS: Patients given more than 50% of nitrous oxide were not found to have an increase in adverse events. Higher concentrations of nitrous oxide (>50%) were not found to be associated with a better behavior score when completing pediatric restorative procedures.

Optimizing anxiolysis and analgesia for percutaneous intervention by the abdominal radiologist.

Abdominal radiologists perform a wide variety of image-guided interventions. Procedures performed by abdominal radiologists can be broadly categorized into paracentesis, thoracentesis, superficial and deep soft tissue biopsy, drain placement, and ablation. As these procedures continue to develop as an alternative to more invasive and potentially morbid interventions, and with continued improvements in minimally invasive technologies, it becomes increasingly important for abdominal radiologists to be familiar with options for peri-procedural analgesia and anxiolysis, as well as when to consult anesthesiology. In this review, we discuss analgesic, anxiolytic, and nonpharmacologic options available to the abdominal radiologist. We focus on practical agents that are relatively safe for general use, special populations, and considerations for post-procedural monitoring.

Update on Medications for Oral Sedation in the Oral and Maxillofacial Surgery Office.

Dental anxiety is a leading cause of postponing treatment and/or complete avoidance of professional oral care. Therefore, effective sedation and pain control are integral components of dental care for the fearful and anxious patient. The application of oral sedation aids the trained practitioner to provide care to the anxious dental patient and remains the safest, most established, and most commonly used route of drug administration. Proper training and understanding of pharmacologic properties allows for safe and effective application of analgesics and sedatives for oral sedation.

A Review of Sedation Agents.

The oral and maxillofacial surgery model of anesthesia delivery is the subject of some controversy. However, a long track record of patient safety provides compelling support for the dual role of the oral and maxillofacial surgeon as proceduralist and anesthetist. Among the elements critical to continued success is a clear understanding of the pharmacology of the agents used to produce sedation and general anesthesia. This review highlights 6 sedation agents used as part of a balanced anesthesia technique in oral and maxillofacial surgery.

Anxiolysis for laceration repair in children: a survey of pediatric emergency providers in Canada.

OBJECTIVES: Intranasal dexmedetomidine is a potentially effective anxiolytic but its role in pediatric laceration repair is only emerging. Future trials and clinical adoption of intranasal dexmedetomidine depend on understanding pediatric emergency providers' practice patterns surrounding anxiolysis and perceived barriers to intranasal dexmedetomidine for anxiolysis during suture repair in children. Our objectives were to characterize these parameters to inform future research and facilitate clinical adoption. METHODS: We conducted an online survey of pediatric emergency physician members of Pediatric Emergency Research Canada from September to December 2020. Questions pertained to perceptions of anxiolysis for suture repair, with a focus on intranasal dexmedetomidine. The primary outcome was anxiolysis for suture repair. Data were reported using descriptive statistics. RESULTS: The response rate was 155/225 (68.9%). During suture repair, 127/148 (86%) believed that > 25% of young children experience distress requiring physical restraint. 116/148 (78%) would provide anxiolysis, mainly intranasal benzodiazepines (100/148, 68%). Only 6/148 (4%) would provide intranasal dexmedetomidine but 95/148 (64%) would consider it if there was evidence of benefit. The most common perceived barriers to intranasal dexmedetomidine included inadequate personal experience (114/145, 79%) and lack of access (60/145, 41%). CONCLUSIONS: Most Canadian pediatric emergency providers believe that laceration repair in a young child is distressing. Despite questionable efficacy, most would provide intranasal benzodiazepines, but would consider intranasal dexmedetomidine if there was evidence of benefit.

RéSUMé: OBJECTIFS: La dexmédétomidine intranasale est un anxiolytique potentiellement efficace mais son rôle dans la réparation des lacérations en pédiatrie n'est qu'émergent. Les futurs essais et l'adoption clinique de la dexmédétomidine intranasale dépendent de la compréhension des habitudes de pratique des urgentistes pédiatriques en matière d'anxiolyse et des obstacles perçus à la dexmédétomidine intranasale pour l'anxiolyse pendant la réparation des sutures chez les enfants. Nos objectifs étaient de caractériser ces paramètres pour éclairer les recherches futures et faciliter l'adoption clinique. MéTHODES: Nous avons mené un sondage en ligne auprès des médecins urgentistes pédiatriques membres de Recherche en urgence pédiatrique Canada (Pediatric Emergency Research Canada) de septembre à décembre 2020. Les questions portaient sur les perceptions de l'anxiolyse pour la réparation des sutures, en mettant l'accent sur la dexmédétomidine intranasale. Le résultat principal était l'anxiolyse pour la réparation des sutures. Les données ont été rapportées à l'aide de statistiques descriptives. RéSULTATS: Le taux de réponse était de 155/225 (68,9 %). Pendant la suture, 127/148 (86 %) ont estimé que > 25 % des jeunes enfants éprouvent une détresse nécessitant une contention physique. 116/148 (78 %) fourniraient une anxiolyse, principalement des benzodiazépines intranasales (100/148, 68 %). Seulement 6/148 (4 %) fourniraient de la dexmédétomidine intranasale, mais 95/148 (64 %) l'envisageraient s'il y avait une preuve de bénéfice. Les obstacles les plus fréquemment perçus à la dexmédétomidine intranasale étaient une expérience personnelle insuffisante (114/145, 79 %) et un manque d'accès (60/145, 41 %). CONCLUSIONS: La plupart des fournisseurs canadiens de services d'urgence pédiatriques croient que la réparation des lacérations chez un jeune enfant est pénible. En dépit d'une efficacité douteuse, la plupart d'entre eux fourniraient des benzodiazépines intranasales, mais envisageraient la dexmédétomidine intranasale s'il était prouvé qu'elle était bénéfique.

Modulation of GABAA receptors and of GABAergic synapses by the natural alkaloid gelsemine.

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABAA receptors (GABAARs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABAARs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABAARs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABAARs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABAARs but support a role of GABAARs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system.

Intranasal Fentanyl and Midazolam Use in Children 3 Years of Age and Younger in the Emergency Department.

BACKGROUND: Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger children. OBJECTIVES: To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger. METHODS: This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED. RESULTS: Of 6198 patients included, 1762 received intranasal fentanyl alone, 1115 received intranasal midazolam alone, and 3321 received combination therapy. The median (interquartile range [IQR]) patient age was 2.2 (1.5-3) years. Initial median (IQR) fentanyl dose was 2.7 (2-3) µg/kg, with 13.3% receiving a repeat dose. Initial median (IQR) midazolam dose was 0.3 (0.2-0.3) mg/kg, with 3.3% receiving a second dose. Children receiving both fentanyl and midazolam had median (IQR) initial doses of 2.8 (2.1-3) µg/kg and 0.3 (0.2-0.3) mg/kg, respectively. Of these, 3.2% received repeat doses of both medications. Laceration repairs (33.8%) and incision and drainage (22.2%) accounted for the majority of indications. Only 2.9% (n = 178) received additional opioids. No serious adverse events requiring a reversal agent or respiratory support were reported. CONCLUSIONS: Intranasal fentanyl and midazolam, alone and in combination, can provide analgesia and anxiolysis to children aged 3 years and younger in the ED setting. Further prospective studies are needed to better evaluate their safety and efficacy in this younger population.