Search Results (81)

Humane euthanasia is an endpoint for production animals succumbing to disease or trauma. Euthanasia performed with barbiturates or other anesthetic/sedative drugs observes zero withdrawal time, and drug residues may remain in tissues. Carcasses may be submitted for rendering, and rendered products can be used to manufacture pet foods. The purpose of this study was to determine the concentration of two drugs, xylazine and ketamine, that may be used during the euthanasia process of food animals and to determine the fate of these drugs following a simulated rendering process using a commercial autoclave. Twelve cattle were administered xylazine or xylazine and ketamine prior to euthanasia via penetrating captive bolt, and samples of muscle, fat, liver, and kidney were collected. The tissue samples were analyzed by LC-MS/MS, both raw and following rendering. The parent compounds xylazine and ketamine were detected in all tissues, both before and after rendering. The highest concentrations were found in rendered kidney for both drugs, and the lowest in rendered and raw fat for xylazine and ketamine, respectively. Full article

Sedation and anesthesia are essential for ensuring animal welfare during surgical procedures such as hernia repair in swine. However, the number of sedative and anesthetic agents officially approved for livestock use remained limited. This study evaluated the sedative efficacy and serotonergic effects of a romifidine/ketamine/diazepam protocol, with and without the addition of tramadol, in swine undergoing umbilical hernia repair. Sixty-six crossbred Large White swine were randomly allocated to three groups: LL (lidocaine 4 mg/kg by infiltration), LT (lidocaine 2 mg/kg by infiltration + tramadol 2 mg/kg intraperitoneally), and TT (lidocaine2 mg/kg by infiltration + tramadol 4 mg/kg intraperitoneally). The physiological parameters heart rate, arterial pressure, oxygen saturation, rectal body temperature, and respiratory rate were assessed. The depth of intraoperative anesthesia and postoperative sedation was assessed using an ordinal scoring system (0–3). Plasma serotonin (5-HT) concentration was measured at baseline and 24 h post-surgery. Physiological parameters remained within species-specific reference ranges throughout the procedure. Anesthesia depth scores significantly decreased over time in all groups (p ≤ 0.001), with the tramadol-treated groups (LT and TT) showing more prolonged deeper anesthesia. Postoperative sedation was significantly higher in the TT group (p ≤ 0.001). Serotonin concentration decreased in LL, increased in LT, and remained stable in TT. These findings suggest that tramadol may enhance sedation and recovery, potentially through serotonergic modulation. Moreover, serotonin could serve as a physiological marker warranting further investigation in future studies of anesthetic protocols in veterinary medicine. Full article

Ketamine, originally developed as an anesthetic, is gaining increasing attention due to its multifaceted pharmacological properties. In addition to its use in anesthesia, ketamine exerts potent analgesic effects via N-methyl-D-aspartate (NMDA) receptor antagonism, modulating pain perception and reducing central sensitization, particularly in chronic and neuropathic pain conditions. Emerging evidence also supports ketamine’s potential in the treatment of substance use disorder, where it may disrupt maladaptive reward-related memories and promote neuroplasticity which facilitates behavioral change. Moreover, in recent years, S-ketamine has shown rapid and potent antidepressant effects, especially in treatment-resistant depression (TRD), probably due to increased glutamatergic signaling, synaptic plasticity and the release of neurotrophic factors. This heterogeneous therapeutic profile positions ketamine as a unique agent at the interface of anesthesia, pain management, addiction medicine and psychiatry, warranting further exploration into its mechanism and long-term effectiveness. Full article

Ketamine and esketamine are two closely related compounds with fast-acting antidepressant properties that have reshaped the treatment landscape for individuals with treatment-resistant depression (TRD). Originally developed as anesthetic agents, both have since demonstrated rapid and robust antidepressant effects in patients who have not responded to conventional treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy. This narrative review synthesizes evidence on their pharmacology, mechanisms of action, clinical efficacy, safety profiles, and regulatory considerations, with a particular focus on their neuroplastic effects. While ketamine is a racemic mixture composed of equal parts R- and S-enantiomers, esketamine consists solely of the S-enantiomer and has been approved for intranasal use by the FDA and EMA for TRD. These agents have been shown to produce symptom relief within hours of administration—an unprecedented effect in psychiatric pharmacology. This rapid onset is particularly valuable in managing suicidal ideation, offering potential lifesaving benefits in acute settings. Furthermore, ketamine and esketamine’s influence on synaptic plasticity, brain-derived neurotrophic factor (BDNF), and glutamate transmission provides insights into novel therapeutic targets beyond monoaminergic systems. This review incorporates recent real-world findings and peer-reviewed literature to contextualize the clinical use of these agents in modern psychiatry, bridging experimental research with practical application. Full article

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit. Full article

Dried blood spot (DBS) sampling has emerged as a promising microsampling technique in biomedical and clinical research, offering advantages such as reduced invasiveness, minimal blood volume requirements, and enhanced analyte stability. Although well established in human medicine for neonatal screening and diagnostic applications, its potential in veterinary pharmacology remains underexplored. This study investigated the feasibility of using DBS samples to quantify anesthetic agents—ketamine and medetomidine in cats and lidocaine in horses—during routine surgical procedures at a veterinary teaching hospital. A standardized DBS collection protocol was developed, and LC-MS/MS methods were validated for the quantification of target analytes in both DBS and plasma samples. These methods were subsequently applied to real samples collected during anesthesia to conduct pharmacokinetic analyses. Comparative evaluations, including Bland–Altman analysis, assessed the suitability of DBS samples for pharmacokinetic studies in veterinary medicine. Preliminary results indicated satisfactory agreement for medetomidine, meeting EMA guidelines, with 75.6% of mean values falling within ±20% of paired measurements. Results for ketamine (46.9%) were promising but require further optimization, while those for lidocaine (21.4%) highlighted the need for additional investigation. These findings underscore the potential of DBS sampling as a minimally invasive alternative for pharmacokinetic studies in veterinary medicine, particularly for medetomidine, while identifying areas for further methodological refinement. Future research should optimize DBS techniques and expand their application to other drugs and species, broadening their impact on veterinary pharmacology. Full article

Background: Every year, over 40 million people sustain mild traumatic brain injury (mTBI) which affects the glucocorticoid stress pathway and synaptic plasticity. Ketamine, a multimodal dissociative anesthetic, modulates the stress pathway and synaptic plasticity. However, the effects of post-mTBI ketamine administration on plasma stress hormones and brain synaptic plasticity are largely unknown. Methods: Adult male Sprague-Dawley rats with indwelling jugular venous catheters sustained mTBI with the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) in a single session (3 impacts × 1.5 J). One hour later, rats received intravenous (IV) ketamine (0, 10, or 20 mg/kg, 2 h). Catheter blood samples were collected for plasma corticosterone and progesterone assays. Brain tissue sections were double-labeled for presynaptic synapsin-1 and postsynaptic density protein 95 (PSD-95). Utilizing the Synaptic Evaluation and Quantification by Imaging Nanostructure (SEQUIN) workflow, super-resolution confocal images were generated, and synapsin-1, PSD-95, and synaptic density were quantified in the CA1 of the hippocampus and medial prefrontal cortex (mPFC). Results: IV ketamine infusion produced biphasic effects on corticosterone levels: a robust elevation during the infusion followed by a reduction after the infusion. CHIMERA injury elevated progesterone levels at post-injury day (PID)-1 and reduced synaptic density in the CA1 at PID-4, regardless of ketamine infusion. Ketamine infusion increased synaptic density in the mPFC at PID-4. Conclusions: Mild TBI and IV ketamine modulate the stress pathway and synaptic plasticity in the brain. Further research is warranted to investigate the functional outcomes of subanesthetic doses of ketamine on stress pathways and neuroplasticity following mTBI. Full article

Jaguars play a crucial role in population control across multiple biomes. They are endangered and protected by in situ and ex situ conservation mechanisms to ensure their conservation. Cardiovascular diseases in wild mammals, including jaguars, often have unclear etiopathogenies, underscoring the need for research into novel hemodynamic parameters. This study evaluates the cardiovascular health of fifteen clinically healthy jaguars using conventional and Holter electrocardiography, non-invasive systemic blood pressure measurement, and echocardiography. Chemical restraint was achieved with medetomidine (0.08–0.1 mg/kg) and ketamine (5 mg/kg), with anesthesia reversed using atipamezole (0.25 mg/kg). The average heart rate was 72 ± 18 bpm, with sinus rhythm in ten animals and sinus arrhythmia in five. Six animals exhibited first and second-degree atrioventricular blocks, one had supraventricular complexes, and another had premature ventricular complexes. Non-invasive systolic blood pressure remained stable at 163 ± 29 mmHg during anesthesia. Echocardiographic examination revealed mitral, tricuspid, pulmonary, and aortic valve insufficiencies via color Doppler. The transmitral flow showed a normal E/A ratio and E` < A`, suggesting a pseudonormal ventricular filling pattern. No significant anesthetic complications were observed, affirming the protocol’s safety. This study provides valuable data, validating the anesthetic protocol and establishing reference cardiovascular values for jaguars, thus paving the way for future research in other veterinary species. Full article

The membrane fluidity increases induced by popular anesthetic agents (propofol, isoflurane, sevoflurane, and ketamine/xylazine) were measured at the clinical and supra-clinical concentrations in red blood cell (RBC) membrane as well as four model membranes. Membrane fluidity changes were monitored using the excimer/monomer (E/M) ratio of dipyrene-PC and fluorescence anisotropies of DPH-PC and TMA-DPH. Propofol, sevoflurane and isoflurane increased membrane fluidity instantaneously. The largest increase occurs in membranes made of saturated lipids. RBCs were labeled with TMA-DPH, and the increase in membrane fluidity at clinical concentrations of isoflurane and sevoflurane was more than that induced by ten times the legal limit of alcohol in human blood. However, membrane fluidity was essentially unchanged by ketamine/xylazine up to 210 µM. These results strongly correlate with our recent in vivo experiments and reveal a clear connection between increasing membrane fluidity in model membranes, increasing the blood–brain barrier (BBB) permeability in mice, and inducing effective anesthesia in animals. Interestingly, at the most commonly used clinical concentrations, the membrane fluidity increases induced by propofol, sevoflurane, and isoflurane were very similar, despite the fact that different categories of anesthetics were used and their chemical concentrations were different by 100 times. This indicates that at clinical concentrations of these anesthetics, a similar level of membrane disruption at the BBB is achieved. Thus, our results strongly support the lipid hypothesis of the mechanism of general anesthetics. Full article

Background: Rigid bronchoscopy (RB) is the gold standard for managing central airway obstruction (CAO), a life-threatening condition caused by both malignant and benign etiologies. Anesthetic management is challenging as it requires balancing deep sedation with maintaining spontaneous breathing to avoid airway collapse. There is no consensus on the optimal anesthetic approach, with options including general anesthesia with neuromuscular blockers or spontaneous assisted ventilation (SAV). Methods: This case series presents our anesthetic protocol using remifentanil–propofol–ketamine total intravenous anesthesia (TIVA) with SAV in four patients with airway obstructions. Muscle relaxants were avoided in all cases. Results: Ketamine’s ability to preserve respiratory drive and airway reflexes, along with its bronchodilating properties, made it ideal for managing CAO. All procedures successfully restored airway patency without complications or drug-related side effects. Conclusions: Our findings suggest that remifentanil–propofol–ketamine TIVA combined with SAV is a viable anesthetic approach for therapeutic RB, offering effective sedation, maintaining airway patency, and minimizing perioperative complications. Full article

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. Full article

Cancer recurrence and metastasis remain critical challenges following surgical resection, influenced by complex perioperative mechanisms. This review explores how surgical stress triggers systemic changes, such as neuroendocrine responses, immune suppression, and inflammation, which promote the dissemination of residual cancer cells and circulating tumor cells. Key mechanisms, such as epithelial–mesenchymal transition and angiogenesis, further enhance metastasis, while hypoxia-inducible factors and inflammatory responses create a microenvironment conducive to tumor progression. Anesthetic agents and techniques modulate these mechanisms in distinct ways. Inhaled anesthetics, such as sevoflurane, may suppress immune function by increasing catecholamines and cytokines, thereby promoting cancer progression. In contrast, propofol-based total intravenous anesthesia mitigates stress responses and preserves natural killer cell activity, supporting immune function. Opioids suppress immune surveillance and promote angiogenesis through the activation of the mu-opioid receptor. Opioid-sparing strategies using NSAIDs show potential in preserving immune function and reducing recurrence risk. Regional anesthesia offers benefits by reducing systemic stress and immune suppression, though the clinical outcomes remain inconsistent. Additionally, dexmedetomidine and ketamine exhibit dual effects, both enhancing and inhibiting tumor progression depending on the dosage and context. This review emphasizes the importance of individualized anesthetic strategies to optimize long-term cancer outcomes. While retrospective studies suggest potential benefits of propofol-based total intravenous anesthesia and regional anesthesia, further large-scale trials are essential to establish the definitive role of anesthetic management in cancer recurrence and survival. Full article

Respiratory disease is common in rabbits, but subclinical conditions can be challenging to diagnose and may cause respiratory problems during anesthesia. CT is the preferred method for diagnosing lung diseases, but anesthesia can alter lung volume and cause lung lobe collapse. In this study, seventeen healthy 5-month-old male New Zealand white rabbits underwent thoracic CT scans under different conditions. Rabbits were sedated with midazolam and butorphanol and scanned in a sphinx position; they were then anesthetized with dexmedetomidine and ketamine and scanned again in sternal recumbency during spontaneous breathing. Lastly, apnea was induced using intermittent positive pressure ventilation (IPPV) for a final scan. Lung volume and density were measured using the 3D Slicer version 5.6.2 software, with thresholds set between −1050 and −100 Hounsfield Units (HU). Sedated animals had significantly higher total lung volume (69.39 ± 10.04 cm³) than anesthetized (47.10 ± 9.28 cm³) and anesthetized apnea rabbits (48.60 ± 7.40 cm³). Mean lung attenuation during sedation was −611.26 HU (right) and −636.00 HU (left). After anesthesia induction, values increased to −552.75 HU (right) and −561.90 HU (left). Following apnea induction, attenuation slightly decreased to −569.40 HU (right) and −579.94 HU (left). The results indicate that sedation may be preferable for rabbit lung CT to minimize anesthesia-related changes. Full article

Background/Objectives: Abdominoplasties are prevalent surgical procedures for improving lower abdominal contours, necessitating effective pain management. Insufficient management can increase opioid usage, dependency risks, and adverse effects. This review investigates various strategies in abdominoplasty pain management, aiming to reduce opioid dependence and improve patient care. Methods: A comprehensive systematic literature search (MEDLINE, Cochrane, PubMed, Web of Science, EMBASE) was conducted, spanning from their inception to January 2024, using keywords such as ‘abdominoplasty’ and ‘postoperative pain management’. Included studies focused on nonopioid interventions in adults, encompassing various study designs. Non-English publications and those not meeting outcome criteria were excluded. Bias in studies was assessed using specific tools for randomized and non-randomized trials. Results: Thirty-five studies, published between 2005 and 2024, were included, involving 3636 patients with an average age of 41.8. Key findings highlighted the effectiveness of transversus abdominis plane blocks in reducing opioid use and pain. Pain pump catheters also showed promise in improving pain management and reducing opioid dependency. Local anesthetics demonstrated varying degrees of efficacy, while other alternatives like ketamine and NSAIDs successfully reduced postoperative pain and opioid requirements. The bias assessment of the RCTs revealed “low” and “some concerns” ratings, indicating a need for more detailed methodology reporting and management of missing data. The cohort studies generally attained “moderate” risks of bias, primarily due to confounding variables and outcome data reporting. Conclusions: Nonopioid analgesics show potential in postoperative pain management for abdominoplasties, but further research is needed to confirm their effectiveness and optimize patient care. Full article

Background and Objective: The alteration of mitochondrial functions, especially the opening of the mitochondrial permeability transition pore (mPTP), has been proposed as a key mechanism in the development of lesions in cerebral ischemia, wherefore it is considered as an important target for drugs against ischemic injury. In this study, we aimed to investigate the effects of mitochondrial complex I inhibitors as possible regulators of mPTP using an in vitro brain ischemia model of the pentobarbital/ketamine (PBK)-anesthetized rats. Results: We found that PBK anesthesia itself delayed Ca²⁺-induced mPTP opening and partially recovered the respiratory functions of mitochondria, isolated from rat brain cortex and cerebellum. In addition, PBK reduced cell death in rat brain slices of cerebral cortex and cerebellum. PBK inhibited the adenosine diphosphate (ADP)-stimulated respiration of isolated cortical and cerebellar mitochondria respiring with complex I-dependent substrates pyruvate and malate. Moreover, pentobarbital alone directly increased the resistance of isolated cortex mitochondria to Ca²⁺-induced activation of mPTP and inhibited complex I-dependent respiration and mitochondrial complex I activity. In contrast, ketamine had no direct effect on functions of isolated normal cortex and cerebellum mitochondria. Conclusions: Altogether, this suggests that modulation of mitochondrial complex I activity by pentobarbital during PBK anesthesia may increase the resistance of mitochondria to mPTP opening, which is considered the key event in brain cell necrosis during ischemia. Full article