Search Results (533)

Volatile anesthetics have steadily become more popular in intensive care units for sedation for reasons related to their beneficial pharmacokinetic and pharmacodynamic properties. Common anesthetics such as isoflurane and sevoflurane rapidly reach sedative levels in the body, but they are also rapidly eliminated, allowing for quick recovery. These agents have minimal impact on the liver and kidneys, which makes them attractive options when compared to other agents including opioids, benzodiazepines, ketamine, and propofol. Use of delivery systems like AnaConDa^® (Anaesthetic Conserving Device; Sedana Medical AB, Danderyd, Sweden) has enabled providers to easily use these agents in the Intensive Care Unit (ICU). In this regard, they have recently provided additional beneficial consideration during intravenous drug shortages seen during the COVID-19 pandemic and at other times. These agents have shown organ-protective effects in the kidneys and lungs, which may even reduce the total time spent in the ICU. Pharmacodynamically, these anesthetics mediate their effects through central nervous system ion channels to exert analgesic and anxiolytic actions, thereby minimizing effects in the kidneys and lungs. These agents are primarily eliminated via exhalation, which makes them potential options for those with liver or kidney failure. This narrative review examines current efficacy and risks of using volatile anesthetics for sedation in the ICU setting and clinical roles for the future. Full article

The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders across six domains: perceived positive effects, adverse effects, reasons for use, route of administration, polydrug use, and dose amounts. Mood-related concerns were the primary reason for use (53%). Users reported positive effects, most often improvements in emotional well-being (65%). Adverse effects were predominantly psychological or mood-related (56%). A total of 70% of reported doses exceeded 149 mg, suggesting a trend toward higher dose use. Intravenous administration (40%) and sublingual troches (23%) were the most frequently reported routes. Concurrent use of prescribed psychotropics, cannabis, and psychedelics was also reported. This analysis identified substantial heterogeneity in individual-reported experiences. Frequent high-dose use, dose escalation, and polydrug exposure underscores the importance of clinical monitoring and attention to addiction potential and drug–drug interactions. The findings should be interpreted with caution, as follow-up and clinical verification were not possible; however, the data provide an unfiltered view of individual experiences in relation to ketamine use outside the clinical setting. Full article

Pharmacological antidepressant treatments alter the molecular and functional reactivity of stress-sensitive neural networks. However, how classical versus rapid-acting antidepressants differentially modulate acute stress-induced transcriptional responses across brain regions remains unclear. Here, we compared imipramine and ketamine in mice exposed to acute swim stress, assessing transcriptional adaptations across the frontal cortex, hippocampus, and striatum. Swim stress induced significant widespread activation of cFOS, which led to drug-specific modulations: imipramine primarily significantly dampened cortical and striatal cFOS expression, whereas ketamine preserved stress-evoked neuronal activation. In contrast, hippocampal activation was significantly robust but largely unaffected, indicating that acute antidepressant drug effects during stress coping preferentially target cortical and striatal plasticity mechanisms. In contrast, BDNF expression was altered only within the striatal region, where imipramine attenuated the stress-related increase in BDNF expression. Statistical analysis of behavioral outcomes during the swim stress confirmed a shared facilitation of active coping, yet these similar outcomes emerged from distinct molecular programs. Together, the data demonstrate that the treatment effects of the two substances diverge mechanistically, revealing cortical and striatal transcriptional signatures of classical versus rapid-acting antidepressant action. While these findings suggest potential translational relevance for understanding distinct mechanisms, further studies in humans are required to validate these signatures and their clinical implications. Full article

Major depressive disorder (MDD) is a highly prevalent psychiatric illness for which rapid-acting antidepressants such as ketamine provide only transient benefit. Because κ-opioid receptor (KOR) signaling contributes to stress-related dysphoria and impaired neuroplasticity, we examined whether KOR antagonism could prolong ketamine’s antidepressant-like effects in a mouse model of adolescent chronic unpredictable stress (CUS). Male C57BL/6J mice (n = 10 per group for behavioral analyses) were exposed to CUS during adolescence and developed persistent depression-like behavior in adulthood. Mice with depressive-like behavior received a single injection of ketamine, the selective KOR antagonist norbinaltorphimine (nBNI), or their combination. Behavioral testing showed that all treatments reduced immobility in the tail suspension test (TST) 24 h post-administration; however, only the combined ketamine/nBNI treatment maintained antidepressant-like effects one week post-treatment. Molecular analyses (n = 4–8 per group) were conducted at this single time point, one week post-treatment, to characterize region-specific signaling states in the prefrontal cortex, hippocampus, and striatum, focusing on ERK, AKT, JNK, mTOR, and BDNF pathways. These molecular findings represent correlates of sustained behavioral effects rather than evidence of causal mechanisms. Together, the data indicate that concurrent KOR antagonism is associated with prolonged antidepressant response to ketamine in stress-exposed male mice and with distinct region-dependent signaling profiles at one week post-treatment. Further studies are needed to establish mechanistic causality and confirm the possible applicability of these findings. Full article

Effective pain control after orthopedic surgery is essential in veterinary practice, particularly in small-breed dogs with low physiological reserves. This study aimed to compare the analgesic efficacy and tolerability of five postoperative pain protocols across nine surgical procedures. A retrospective analysis was conducted in 205 small-breed dogs (≤7 kg) undergoing orthopedic surgeries. Dogs were assigned to one of five analgesic protocols: (A) carprofen, (B) tramadol–lidocaine–ketamine continuous-rate infusion, (C) butorphanol continuous-rate infusion, (D) hydromorphone continuous-rate infusion, and (E) multimodal analgesia combining local anesthetics, hydromorphone, and meloxicam. Pain was assessed at 6, 12, 24, 48, and 72 h using the Glasgow Composite Measure Pain Scale—Short Form. Analgesic efficacy was evaluated using pain trajectories, area-under-the-curve analysis, and pain resolution rates, and adverse effects were recorded. Dogs receiving multimodal analgesia achieved the most rapid and sustained pain relief, with all patients reaching pain resolution by 48 h. Hydromorphone alone showed comparable efficacy but was associated with more adverse effects, while tramadol–lidocaine–ketamine showed delayed pain relief and the highest rate of severe side effects. Multimodal analgesia provides superior pain control with acceptable safety in small-breed dogs undergoing orthopedic surgery, supporting its use based on surgical invasiveness and individual patient response. Full article

Introduction: Severe traumatic brain injury (sTBI) frequently coexists with polytrauma and often necessitates damage control neurosurgery (DCNS), where rapid decompression and temporary stabilization take precedence over definitive reconstruction. Within this context, anesthetic management must balance cerebral protection with ongoing resuscitation, yet high-quality DCNS-specific evidence remains limited. Materials and Methods: A comprehensive search of PubMed, Scopus, and Google Scholar (2015–2025) was conducted using MeSH terms and keywords related to neurotrauma, anesthesia, intracranial pressure, and perioperative management. Studies were included if they examined anesthetic or hemodynamic strategies in severe TBI or DCNS and reported relevant clinical or physiologic outcomes. Results: Nineteen articles addressing perioperative strategies for optimizing DCNS outcomes were analyzed. Discussion: Preoperative care emphasizes hemodynamic stabilization and permissive hypertension, damage control resuscitation including massive transfusion protocols, optimization of cerebral perfusion pressure (CPP) and neuromonitoring, and the use of hyperosmolar therapy. Transexamic acid can be used in sTBI safely but with unclear improvement in outcomes. Intraoperatively, propofol-based total intravenous anesthesia is generally preferred over volatile agents due to favorable effects on intracranial pressure (ICP), cerebral blood flow (CBF), autoregulation, and emergence. While historically contraindicated, ketamine and etomidate are now increasingly used as hemodynamically protective induction agents. Analgesic and sedative strategies prioritize dexmedetomidine and carefully titrated opioids to minimize respiratory depression and reduce postoperative complications. CPP and ICP-directed management relies on individualized blood pressure targets, vasopressor selection, lung-protective ventilation, and strict temperature control. Conclusions: Emerging evidence has suggested the benefit of DCNS for patient survival. Overall, perioperative care is guided largely by physiology and extrapolation, highlighting the need for standardized protocols. Full article

Background/Objectives: Insulin and glucagon are key hormones in metabolic regulation. There are limited comparative data on how common rodent anesthetic regimens influence hormone secretion, leading to misinterpretation of results. We aimed to compare the effects of several anesthetic regimens on insulin and glucagon secretion using the physiologically relevant isolated perfused rat pancreas model. Methods: Six commonly used rodent anesthetic regimens were assessed for their ability to induce surgical depth of anesthesia. Once achieved, the pancreas was vascularly isolated and perfused. After euthanasia, the pancreas was stimulated with glucose and glucagon-like peptide-1 (GLP-1). Insulin and glucagon were measured in the effluent using radioimmunoassay. Results: Anesthesia with Hypnorm^® (fentanyl/fluanisone)/midazolam produced the most physiological responses, meaning that insulin was secreted in response to hyperglycemia and GLP-1, and glucagon was secreted under hypoglycemia. Ketamine/dexmedetomidine anesthesia abolished insulin dynamic secretion and blunted glucagon secretion. Isoflurane/buprenorphine anesthesia partially suppressed insulin secretion, but it still followed a physiological pattern in response to glucose fluctuations. However, it abolished the dynamic glucagon responses to glucose. Three additional anesthetic regimens failed to produce surgical depth anesthesia and were therefore not further analyzed. Conclusions: Different anesthetic regimens altered pancreatic hormone secretion. Fentanyl/fluanisone/midazolam was associated with dynamic insulin and glucagon secretion, whereas ketamine/dexmedetomidine and isoflurane/buprenorphine altered the pattern and/or magnitude of hormone secretion. Overall, the choice of anesthesia is a critical variable in animal experimentation for metabolic studies and may confound the interpretation of results. Full article

Background: Dental fear and anxiety are highly prevalent in children, resulting in avoidance or incomplete dental treatment; sedation emerges as a possible behavioral management strategy. This umbrella review aimed to provide a structured and critical synthesis of the available knowledge on sedative single-agent efficacy and routes of administration employed for achieving sedation (excluding deep sedation/general anesthesia) during dental procedures in children for behavior management, as well as to evaluate acceptability and satisfaction for child, caregiver, and provider, and to assess the influence of clinical setting and provider. Methods: In line with the PRISMA statement, the protocol was registered on PROSPERO (CRD420251043738), and 18 systematic reviews were included and synthesized qualitatively. Results: Single-agent sedation was safe and effective for managing behavior in children during dental procedures, with midazolam and nitrous oxide being the most studied agents. Different routes of administration showed distinct characteristics in onset, recovery time, adverse effects and cooperation, while agent selection appeared influenced by clinical setting and provider type. However, data on acceptability and satisfaction from children, caregivers, and providers remains limited. Conclusions: Evidence suggests potential effectiveness of selected agents and routes in appropriately monitored settings, but data heterogeneity precludes strong comparative recommendations. Further studies are therefore needed to address the existing gaps in pediatric dental sedation. Full article

Recently, complementary and alternative medicine (CAM) has been actively employed for patients experiencing symptoms unresponsive to Western medical treatments like drug therapy. The natural compounds carotenoids and astaxanthin (AST) have demonstrated various beneficial biological actions for human health in several studies. Given their broad pharmacological activities and reduced toxicity, ASTs possess significant potential as resources for the development of natural analgesic drugs. Given recent studies showing that AST can modulate neuronal excitability, including nociceptive sensory transmission through voltage-gated Ca²⁺ channels and the n-methyl-D-aspartate (NMDA) glutamate receptor, and inhibit the cyclooxygenase-2 cascade, AST holds promise as a CAM, particularly as a therapeutic agent for nociceptive and pathological pain. Based on the in vivo research findings from our laboratory presented in this review, we have confirmed that carotenoid ASTs possess: (i) an intravenous anesthetic effect on both nociceptive and inflammatory pain comparable to existing analgesics such as ketamine; and (ii) an anti-inflammatory effect on chronic pain with an efficacy almost equivalent to that of the commonly used non-steroidal anti-inflammatory drug (NSAID) celecoxib. Therefore, these findings suggest that, as natural compounds, ASTs contribute to the relief of nociceptive and inflammatory pain, implying their potential for clinical application. Full article

This narrative literature review explores the clinical use of Ketamine as part of an untested hypothetical model framework for bridge therapy for acute suicidality. Long-term suicide rates continue to increase in the United States and in many other countries, creating a pressing public health challenge with a variety of treatment considerations. Existing standard-of-care SSRI therapeutics have a delay between administration and symptom relief at 2–6 weeks, leaving a so-called danger zone of about 1–3 months of risk for suicidal follow-through behaviors. Ketamine, a potent NMDA (N-methyl-D-aspartate) receptor antagonist, has recently seen widespread interest in both regulatory and clinical settings for increasing neuroplasticity and alleviating depressive symptoms. Ketamine’s mechanism-of-action through mTORC1 is much faster than SSRI’s downstream transcriptional regulation, leading to quicker relief of suicidal symptoms and the removal of the danger zone lag period. The current literature suggests that a controlled, supervised subanesthetic dose of Ketamine in a clinical setting has low risks of addiction or abuse, distinguishing therapeutic uses of Ketamine from recreational uses. While the biological efficacy of Ketamine is established, this conceptual review focuses on a possible initial hypothetical framework of a “Bridge Protocol.” We searched PubMed, Google Scholar, The Cochrane Library, and PsycINFO (January 2000–December 2025) to synthesize evidence regarding SSRI latency, acute Ketamine protocols, and post-discharge safety. We conclude that while promising, the proposed Ketamine Bridge Therapy requires rigorous longitudinal validation and sustained clinical studies before it can be safely used and experience widespread adoption. Full article

Suicidal behavior in children and adolescents is a major global public health issue, and suicide is one of the leading causes of death in this age group. While psychosocial determinants of suicidality are well established, understanding its biological risk factors is crucial for targeted prevention and treatment. This review presents a narrative synthesis of recent literature examining current evidence on the biological mechanisms that contribute to youth suicidality. Genetic liability plays a substantial role, often interacting with environmental stressors. Key neurobiological factors include dysfunction of the serotonin system and impaired neuroplasticity, characterized by a glutamate–gamma-aminobutyric acid imbalance and reduced brain-derived neurotrophic factor. Psychosocial stress appears linked to these changes through several pathways, including dysregulation of the hypothalamic–pituitary–adrenal axis, chronic low-grade inflammation, oxidative stress, and activation of the kynurenine pathway. Neurodevelopmental conditions like autism spectrum disorders and attention deficit hyperactivity disorder, as well as sleep disturbances, may further increase risk. While therapeutic agents such as ketamine and lithium target these neurobiological systems, evidence for their anti-suicidal efficacy in youth remains limited, with only a small number of randomized controlled trials conducted in pediatric populations. Biological research offers valuable insights, but the use of varied study methods and a lack of longitudinal data complicate its translation into clinical practice. Future studies should employ integrative, developmentally informed models to elucidate causal mechanisms and inform more effective interventions. Full article

Introduction: Postoperative delirium, including emergence agitation, is recognized in the post-anesthesia care unit as a fluctuating disturbance of attention and cognition. The current evidence examined suggests that both anesthetic agents and postoperative pain intensity may influence the risk of delirium. The aim of this review is to discuss the significance of pharmacological agents used during anesthesia and the relationship between the intensity of postoperative pain and the occurrence of postoperative delirium in patients undergoing surgical procedures, regardless of age. Methods: A scoping review was conducted from December 2024 to December 2025. The articles identified in each search were limited to those published between 2015 and 2025. Results: Agents such as dexmedetomidine, remimazolam, and magnesium sulfate were examined in the included trials and were reported to be associated with reducing the incidence and severity of postoperative delirium, particularly in pediatric and elderly patients. Analysis of clinical trial outcomes conducted in pediatric populations undergoing various surgical procedures suggests that dexmedetomidine (administered intranasally and intravenously) and alfentanil were associated with lower incidence and severity of emergence delirium compared to standard care or other agents (e.g., midazolam). Higher doses of dexmedetomidine (2 µg/kg) were reported to be associated with improved postoperative analgesia and reduced agitation, without prolonging recovery time or causing serious adverse effects. Propofol, due to its rapid metabolism, was suggested to contribute to shorter emergence times; however, its impact on cognitive function requires further investigation. Additionally, there remains a lack of agreed-upon and/or validated tools and strategies for pain assessment in patients experiencing delirium. Conclusions: The current evidence examined suggests that the use of intranasal dexmedetomidine at appropriate doses may be associated with reduced postoperative pain and agitation without prolonging recovery time or increasing the risk of serious adverse events. Hydromorphone was reported in the included trials to be associated with better postoperative pain control than sufentanil, whereas remimazolam, although associated with reduced delirium incidence in some trials, did not influence the length of stay in the post-anesthesia care unit. Magnesium sulfate, although not significantly affecting the incidence of delirium, was associated with alleviation of postoperative symptoms such as pain and insomnia in adult patients. Ketamine, while commonly used for analgesic therapy, did not demonstrate a consistent association with delirium prevention and, in some studies, was associated with increased neuropsychiatric events. Further research is required to more precisely define optimal perioperative delirium prevention protocols. Full article

Accumulating evidence indicates that epigenetic and post-transcriptional mechanisms interact to shape stress vulnerability and the adaptive capacity of the central nervous system (CNS). This review aimed to identify molecular markers with potential prognostic value for stress-induced CNS disorders. We analyzed 93 publications (2008–2025) identified in PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library, including 80 original experimental and clinical studies, as well as 13 reviews and meta-analyses addressing epigenetic regulation, hypothalamic–pituitary–adrenal (HPA) axis function, CNS remodeling, and therapeutic or environmental modulation in stress-exposed models and clinical cohorts with stress-related disorders. Across studies, altered methylation of NR3C1, FKBP5, and BDNF, reduced hippocampal histone acetylation, and shifts in microRNA profiles (miR-16, miR-124, miR-132, miR-135a, miR-34c) were repeatedly associated with HPA axis dysregulation, limbic system remodeling, and phenotypes relevant to PTSD and depression. Evidence further suggests that at least some of these signatures show partial reversibility, with modulation reported after pharmacological interventions (e.g., SSRIs, histone deacetylase inhibitors, FKBP51 inhibitors, ketamine) and non-pharmacological approaches (e.g., physical activity, social support) in animal models and, to a lesser extent, in clinical and observational studies. We conclude that targeted modulation of specific epigenetic and post-transcriptional pathways supports the development of candidate biomarkers and may inform stratified prevention and treatment strategies for stress-induced CNS disorders, while acknowledging that further validation in large, well-characterized cohorts is required. Full article

Glaucoma is increasingly recognized as an ischemic neurodegenerative disorder that extends beyond elevated intraocular pressure (IOP) to involve complex vascular, metabolic, and inflammatory mechanisms. Retinal ganglion cells are particularly vulnerable to ischemia–reperfusion injury, oxidative stress, and chronic neuroinflammation, leading to progressive disconnection from central visual pathways. Current therapies primarily target IOP reduction but fail to address ischemia-driven neurodegeneration or to restore lost neuronal connectivity. Ischemia triggers excitotoxicity, oxidative stress, and a maladaptive inflammatory response involving activated microglia and astrocytes, perpetuating neuronal injury and suppressing intrinsic regenerative capacity. Thus, restoring neural plasticity and mitigating neuroinflammation represent key unmet therapeutic needs. Psychoplastogens are a class of compounds capable of rapidly enhancing structural and functional neuroplasticity and have recently emerged as promising multitarget agents. Compounds such as ketamine, psilocybin, N,N-dimethyltryptamine (DMT), and some newly synthesized non-hallucinogenic analogs act through convergent signaling pathways involving BDNF–TrkB–mTOR, promoting dendritic growth, synaptogenesis, and glial modulation. Beyond their neurotrophic effects, psychoplastogens seem to exert potent immunomodulatory actions. In this review we will explore the interplay between ischemia, neurodegeneration, neuroinflammation, and impaired plasticity in glaucoma, integrating mechanistic insights from cerebral ischemia. We discuss emerging preclinical evidence supporting psychoplastogens as neurorestorative and anti-inflammatory agents, propose their potential application in ocular ischemic neurodegeneration, and outline translational challenges for future studies. Full article