Multiple algorithms highlight key brain genes driven by multiple anesthetics.

Anesthesia serves as a pivotal tool in modern medicine, creating a transient state of sensory deprivation to ensure a pain-free surgical or medical intervention. While proficient in alleviating pain, anesthesia significantly modulates brain dynamics, metabolic processes, and neural signaling, thereby impairing typical cognitive functions. Furthermore, anesthesia can induce notable impacts such as memory impairment, decreased cognitive function, and diminished intelligence, emphasizing the imperative need to explore the concealed repercussions of anesthesia on individuals. In this investigation, we aggregated gene expression profiles (GSE64617, GSE141242, GSE161322, GSE175894, and GSE178995) from public repositories following second-generation sequencing analysis of various anesthetics. Through scrutinizing post-anesthesia brain tissue gene expression utilizing Gene Set Enrichment Analysis (GSEA), Robust Rank Aggregation (RRA), and Weighted Gene Co-expression Network Analysis (WGCNA), this research aims to pinpoint pivotal genes, pathways, and regulatory networks linked to anesthesia. This undertaking not only enhances comprehension of the physiological changes brought about by anesthesia but also lays the groundwork for future investigations, cultivating new insights and innovative perspectives in medical practice.

Adding Dexmedetomidine to Intra-articular Local Anesthetics Results in Prolonged Analgesia after Knee Arthroscopy: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aims to assess the efficacy and safety of dexmedetomidine as an adjuvant to intra-articular (IA) injections of local anesthetics (LA) in adult patients undergoing knee arthroscopy. METHODS: We searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing IA dexmedetomidine plus LA versus LA alone for knee arthroscopy in adults. We used the DerSimonian and Laird random-effects model for all outcomes, and conducted a sensitivity analysis with the leave-one-out method, as well as a subgroup analysis for the type of LA. We used R version 4.1.2 for all statistical analyses. RESULTS: We included 16 RCT encompassing 799 patients, of whom 49.8% received IA dexmedetomidine. In the pooled analysis, time to first analgesia rescue was prolonged in almost 4 hours with the use of dexmedetomidine (MD 229 min; p<0.001). We found statistically significant differences favoring dexmedetomidine in pain scores at rest and movement throughout the first 2, 6, 12 and 24 hours postoperatively (p<0.001). Although the mean difference (MD) ranged from -0.3 to -0.9 cm, corresponding to a 3 to 9% reduction in pain scores, this change is not clinically significant when compared to the minimal clinically important difference (MCID). Additionally, the intervention group showed a statistically significant reduction in cumulative opioid consumption over 24 hours (MD -4.5 mg; p<0.001). However, this reduction did not meet the threshold for the MCID. There was no difference between groups on the incidence of hypotension (p=0.190), bradycardia (p=0.430) and postoperative nausea and vomiting (p=0.550). CONCLUSIONS: Adding dexmedetomidine to LA in IA injections for knee arthroscopy significantly extended analgesia duration. Additionally, it lowered pain scores and opioid use, although these effects did not reach the MCID. Furthermore, this addition did not increase the risk of adverse events.

Evaluation of safety and operative time in tumescent-free robotic nipple-sparing mastectomy: a retrospective single-center cohort study.

Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.

Development of ropivacaine hydrochloride-loaded dissolving microneedles as a local anesthetic agent: A proof-of-concept.

Ropivacaine hydrochloride (RPL) is a local anesthetic agent that has been widely used for the treatment of pain during or after surgery. However, this drug is only available in parenteral dosage form and may contribute to the infiltration of RPL into the plasma, causing some undesirable side effects. Intradermal delivery of RPL using dissolving microneedles may become a promising strategy to deliver such drugs into the skin. This research aimed to develop RPL-loaded dissolving microneedles (DMN-RPLs) as a proof of the concept of intradermal delivery of a local anesthetic. The DMN-RPLs were fabricated using either centrifugation or air-pressurized chamber methods. Several polymers, such as poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), and sodium hyaluronate (SH), were utilized for manufacturing the DMN-RPLs. The prepared DMN-RPLs were assessed for their thermal properties, chemical bonds, mechanical strength, insertion ability, skin-dissolution study, and drug content. Furthermore, in-skin deposition and dermatokinetic studies were also performed. The results showed that F9 (30 % w/w PVP-4 % w/w SH) and F10 (30 % w/w PVP-5 % w/w PVA) containing 5 % w/w of RPL were the most promising formulations, as shown by their needle height reduction (<10 %) and insertion depth (∼400 µm). Both formulations were also able to deliver more than 60 % of the RPL contained in the DMNs into the epidermis, dermis, and receiver compartment. This study, for the first time, has provided a proof concept to deliver RPL as a local anesthetic using DMNs and the intradermal route, aiming to minimize pain and discomfort during administration and improve the patient's experience.

Topical Ophthalmic Anesthetics for CornealAbrasions: Findings from a Cochrane SystematicReview and Meta-Analysis.

Background: Despite potential benefit, outpatient use of topical ophthalmic anesthetics can result in poor healing, infection, scar, and blindness. An unbiased analysis of randomized controlled trials (RCTs) is needed to examine their effectiveness and safety compared with placebo or other treatments for corneal abrasions. Methods: Cochrane Central Register of Controlled Trials, MEDLINE, Embase.com, Latin American and Caribbean Health Sciences, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched on February 10, 2023, without restriction on language or publication date. Results: Systematic review and meta-analysis of nine RCTs describing 314 participants with post-traumatic abrasions and 242 participants with post-surgical abrasions, with a median study length of 7 days (interquartile range, 7-14), show no evidence of a difference in pain control between anesthetics and placebo at 24 hours in post-trauma cases. Self-reported pain at 24 hours is reduced with anesthetics plus topical nonsteroid anti-inflammatory drug in post-surgical participants (mean difference [MD], -5.72 on a 10-point scale; 95% CI, -7.35 to -4.09; 1 RCT; 30 participants) and at 48 hours with anesthetics alone in post-trauma participants (MD, -5.68; 95% CI, -6.38 to -4.98; 1 RCT; 111 participants). Anesthetics are associated with 37% increased risk of non-healing defects (risk ratio, 1.37; 95% CI, 0.78 to 2.42; 3 RCTs; 221 post-trauma participants). All evidence is of very low certainty. Over 50% of trials have an overall high risk of bias. Conclusions: Available evidence is insufficient to support outpatient use of topical anesthetics for corneal abrasions with respect to pain, re-epithelialization, and complication risk.

Current anesthesia practice for preterm infants undergoing surgery for necrotizing enterocolitis: A European survey.

STUDY OBJECTIVE: Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients. Therefore, this study aimed to describe current anesthesia practices across Europe for infants undergoing surgery for NEC. DESIGN: Cross-sectional survey study. PARTICIPANTS: Anesthesiologists working in centers where surgery for NEC is performed across Europe. MEASUREMENTS: A 46-item questionnaire assessing protocols for anesthesia practice, preoperative care, intraoperative care, postoperative care, and the respondent's opinion on the adequacy of anesthetic care for patients with NEC in their center. MAIN RESULTS: Out of the 173 responding anesthesiologists from 31 countries, approximately a third had a written standard protocol for anesthetic care in infants. Three quarters of the respondents screened all patients with NEC preoperatively, and a third structurally performed preoperative multidisciplinary consultation. For induction of general anesthesia, most respondents opted for intravenous anesthesia (n = 73, 43%) or a combination of intravenous and inhalation anesthesia (n = 57, 33%). For intravenous induction, they mostly used propofol (n = 58, 44%), followed by midazolam (n = 43, 33%) and esketamine (n = 42, 32%). For maintenance of anesthesia, inhalation anesthetic agents were more commonly used (solely: n = 71, 41%; in combination: n = 37, 22%), almost exclusively with sevoflurane. Postoperative analgesics mainly included paracetamol and/or morphine. Sixty percent of the respondents (n = 104) considered their anesthetic care for patients with NEC adequate. Suggestions for further improvement mainly revolved around monitoring, protocols, and collaboration. CONCLUSIONS: Anesthesia practice for infants undergoing surgery for NEC was highly variable. Most respondents considered the provided anesthetic care for patients with NEC adequate, but also recognized opportunities for further improvement, especially with regards to monitoring, protocols, and interdisciplinary collaboration.

Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.

Inhalation of hydrogen (H2) gas is therapeutically effective for cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders including pathologies induced by anesthetic gases. To understand the mechanisms underlying the protective effects of H2 on the brain, we investigated the molecular signals affected by H2 in sevoflurane-induced neuronal cell death. We confirmed that neural progenitor cells are susceptible to sevoflurane and undergo apoptosis in the retrosplenial cortex of neonatal mice. Co-administration of 1-8% H2 gas for 3 h to sevoflurane-exposed pups suppressed elevated caspase-3-mediated apoptotic cell death and concomitantly decreased c-Jun phosphorylation and activation of the c-Jun pathway, all of which are induced by oxidative stress. Anesthesia-induced increases in lipid peroxidation and oxidative DNA damage were alleviated by H2 inhalation. Phosphoproteome analysis revealed enriched clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain that included proteins involved in neuronal development and synaptic signaling. H2 inhalation modified cellular transport pathways that depend on hyperphosphorylated proteins including microtubule-associated protein family. These modifications may be involved in the protective mechanisms of H2 against sevoflurane-induced neuronal cell death.

Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM). Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes. Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05). Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.

Local Anesthetics, Local Anesthetic Systemic Toxicity (LAST), and Liposomal Bupivacaine.

Local anesthetics have played a vital role in the multimodal analgesia approach to patient care by decreasing the use of perioperative opioids, enhancing patient satisfaction, decreasing the incidence of postoperative nausea and vomiting, decreasing the length of hospital stay, and reducing the risk of chronic postsurgical pain. The opioid-reduced anesthetic management for perioperative analgesia has been largely successful with the use of local anesthetics during procedures such as peripheral nerve blocks and neuraxial analgesia. It is important that practitioners who use local anesthetics are aware of the risk factors, presentation, and management of local anesthetic systemic toxicity (LAST).

A Comparative Study to Evaluate the Efficacy of Topical and Infiltrative Anesthesia for Dermatosurgery Through a Subject-Oriented Approach.

Introduction The skin, along with its subcutaneous tissue, constitutes one of the major organ systems of the human body. Dermatosurgery is the branch dealing with skin conditions that operate at the level of skin, without disturbing the milieu intérieur of the human organ system. Materials and methods A cross-sectional study was undertaken, which included 100 patients comprised of 50 patients in each group. For group A, the topical anesthetic agent used was a eutectic mixture of topical 2.5% lignocaine and 2.5% prilocaine cream (EMLA); for group B, infiltration anesthesia with 2% lignocaine injection. Patients satisfying the inclusion and exclusion criteria were recruited for the study. All the participants were requested to rate the pain at the time of drug administration, during the dermatosurgical procedure, and post-procedurally with a visual analogue scale (VAS) separately. Results In this study, 50% of the participants were of the age group of 21-40 years. Males constituted 57.8% whereas females constituted 42.2%. The common procedures performed in the study were electrocautery at 37%, intralesional platelet-rich plasma (PRP) at 16%, and intralesional steroid at 7%. In group A, the VAS score during drug administration was 0. In the group B, 70% had a VAS score of 4-6, and 30% had a VAS score of 1-3 pre-procedurally. The mean VAS score during procedure was 3.06 for group A and 1.03 for group B. Conclusion The study inferred that topical anesthesia is a better choice in superficial dermatosurgical procedures for providing adequate anesthesia and improved compliance when compared to infiltrative anesthesia.

Anesthesia and cancer recurrence: a narrative review.

Cancer is a leading cause of death worldwide. With the increasingly aging population, the number of emerging cancer cases is expected to increase markedly in the foreseeable future. Surgical resection with adjuvant therapy is the best available option for the potential cure of many solid tumors; thus, approximately 80% of patients with cancer undergo at least one surgical procedure during their disease. Agents used in general anesthesia can modulate cytokine release, transcription factors, and/or oncogenes. This can affect host immunity and the capability of cancer cells to survive and migrate, not only during surgery but for up to several weeks after surgery. However, it remains unknown whether exposure to anesthetic agents affects cancer recurrence or metastasis. This review explores the current literature to explain whether and how the choice of anesthetic and perioperative medication affect cancer surgery outcomes.

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

BACKGROUND: This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. METHODS: The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. RESULTS: Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). CONCLUSIONS: The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

How to Personalize General Anesthesia-A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning.

Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.

The impact of volatile anesthetics and propofol on phosphatidylinositol 4,5-bisphosphate signaling.

Phosphatidylinositol 4,5-bisphosphate (PIP2), as well as other anionic phospholipids, play a pivotal role in various cellular processes, including ion channel regulation, receptor trafficking, and intracellular signaling pathways. The binding of volatile anesthetics and propofol to PIP2 leads to alterations in PIP2-mediated signaling causing modulation of ion channels such as ɣ-aminobutyric acid type A (GABAA) receptors, voltage-gated calcium channels, and potassium channels through various mechanisms. Additionally, the interaction between anionic phospholipids and G protein-coupled receptors plays a critical role in various anesthetic pathways, with these anesthetic-induced changes impacting PIP2 levels which cause cascading effects on receptor trafficking, including GABAA receptor internalization. This comprehensive review of various mechanisms of interaction provides insights into the intricate interplay between PIP2 signaling and anesthetic-induced changes, shedding light on the molecular mechanisms underlying anesthesia.

Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.

OBJECTIVE: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 female dogs with mammary tumors. METHODS: Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 µg kg-1 loading dose (LD) and 1 µg kg-1 hour-1; lidocaine 2 mg kg-1 LD and 3 mg kg-1 hour-1; ketamine 1 mg kg-1 LD and 0.6 mg kg-1 hour-1; n = 14] or FLK (fentanyl 5 µg kg-1 LD and 9 µg kg-1 hour-1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe'Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann-Whitney test. RESULTS: More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe'Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.

The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review.

BACKGROUND: Ketamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus. METHODS: We conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis. RESULTS: Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low. CONCLUSION: This systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.