Comparison of sedation with dexmedetomidine/atipamezole administered subcutaneously at GV20 acupuncture point with usual routes of administration in dogs presented for orthopaedic radiographs.

OBJECTIVES: To evaluate the efficacy of subcutaneous administration of dexmedetomidine/atipamezole at the Governing Vessel 20 (GV20) acupuncture point compared with other administration routes (intramuscular and intravenous) in dogs presented for orthopaedic radiographs. MATERIALS AND METHODS: Prospective, randomised, blinded, controlled clinical study. Sixty-four client-owned dogs were randomly injected with 200 µg/m2 of dexmedetomidine intramuscular (lumbar muscles) (n=20), intravenous (n=23) or subcutaneous at the GV20 point (n=21). Following radiographs, dogs received 2000 µg/m2 of atipamezole intramuscular (n=31), or subcutaneous at the GV20 point (n=27). Degree and time to sedation and recovery were assessed using a sedation scale and a Dynamic and Interactive Visual Analog Scale (DIVAS). Clinical physiological variables and adverse events were used. Statistical linear mixed-effect models (analysis of variance) and Cox models were performed. Significance was set at P-value <0.05. RESULTS: Sedation was insufficient to perform orthopaedic radiographs in six dogs in the intramuscular group. The time to sedation was significantly longer, and sedation scale and DIVAS scores were significantly lower in the intramuscular group. The intravenous group had significantly higher sedation scale and DIVAS scores than the GV20 group. No significant differences were observed between the intramuscular and GV20 recovery groups, although the time effect was significantly more pronounced in the GV20 recovery group. CLINICAL SIGNIFICANCE: Subcutaneous administration of dexmedetomidine and atipamezole at GV20 provided effective sedation and recovery in dogs undergoing orthopaedic radiographic studies. GV20 administration provided a clinically similar level of sedation to the intravenous route, and greater and faster sedation and similar recovery to intramuscular.

In Vivo Photoadduction of Anesthetic Ligands in Mouse Brain Markedly Extends Sedation and Hypnosis.

Photoaffinity ligands are best known as tools used to identify the specific binding sites of drugs to their molecular targets. However, photoaffinity ligands have the potential to further define critical neuroanatomic targets of drug action. In the brains of WT male mice, we demonstrate the feasibility of using photoaffinity ligands in vivo to prolong anesthesia via targeted yet spatially restricted photoadduction of azi-m-propofol (aziPm), a photoreactive analog of the general anesthetic propofol. Systemic administration of aziPm with bilateral near-ultraviolet photoadduction in the rostral pons, at the border of the parabrachial nucleus and locus coeruleus, produced a 20-fold increase in the duration of sedative and hypnotic effects compared with control mice without UV illumination. Photoadduction that missed the parabrachial-coerulean complex also failed to extend the sedative or hypnotic actions of aziPm and was indistinguishable from nonadducted controls. Paralleling the prolonged behavioral and EEG consequences of on target in vivo photoadduction, we conducted electrophysiologic recordings in rostral pontine brain slices. Using neurons within the locus coeruleus to further highlight the cellular consequences of irreversible aziPm binding, we demonstrate transient slowing of spontaneous action potentials with a brief bath application of aziPm that becomes irreversible on photoadduction. Together, these findings suggest that photochemistry-based strategies are a viable new approach for probing CNS physiology and pathophysiology.SIGNIFICANCE STATEMENT Photoaffinity ligands are drugs capable of light-induced irreversible binding, which have unexploited potential to identify the neuroanatomic sites of drug action. We systemically administer a centrally acting anesthetic photoaffinity ligand in mice, conduct localized photoillumination within the brain to covalently adduct the drug at its in vivo sites of action, and successfully enrich irreversible drug binding within a restricted 250 µm radius. When photoadduction encompassed the pontine parabrachial-coerulean complex, anesthetic sedation and hypnosis was prolonged 20-fold, thus illustrating the power of in vivo photochemistry to help unravel neuronal mechanisms of drug action.

Effect of intracutaneous pyonex on analgesia and sedation in critically ill patients with mechanical ventilation.

The purpose of this study was to evaluate the effect of intracutaneous pyonex on analgesia and sedation in critically ill patients who underwent mechanical ventilation. A total of 88 critically ill patients were divided into a control group and an intervention group. Critical Care Pain Observation Tool (CPOT) and Richmond Agitation and Sedation Scale (RASS) were used to evaluate pain and agitation. The dosage and treatment period of sedative and analgesic drugs in the intervention group were notably lower than the control group (p < 0.05). Analgesia compliance time in the intervention group was superior to control group (p < 0.05). The shallow sedation compliance rate in the intervention group was significantly higher than the control group (p < 0.01). There was significant difference in blood gas analysis before and after treatment between the two groups (p < 0.05). After 2 h of sedation and analgesia, heart rate in the intervention group was lower than control group, but respiratory rate was higher than the control group (p < 0.05). The traditional analgesia and sedation combined with intracutaneous pyonex reduced the total amount and treatment period of sedative and analgesic drugs in critically ill patients throughout the treatment process, and it also decreased the adverse reactions such as blood pressure drops and respiratory depression.

Music Therapy in Dialysis Access Procedures With Moderate Sedation.

BACKGROUND: The aim was to evaluate the effects of music on patients' anxiety and satisfaction after undergoing dialysis access procedures under moderate sedation. METHODS: Patients (n = 30) undergoing moderate sedation for dialysis access procedures were evaluated at a single institution. Each patient filled out a survey preoperatively and postoperatively using the short form State-Trait Anxiety Inventory (STAI-6). Patient-selected music was provided by using a MP3 player with noise canceling headphones. RESULTS: Postoperatively, 77% of patients perceived music intervention as very or extremely helpful in decreasing anxiety during the procedure. Further, 93% of patients were somewhat or very satisfied with their procedure. The average pain rating was 3.1 on a scale of 0-10, in which 70% of patients had no to mild pain and 30% of patients rated moderate to severe pain. In comparison to prior procedures without music, 63% of patients rated better experience with the music intervention, 37% rated a similar experience, and 3.7% rated having a worse experience. Approximately, 93% of patients were willing to repeat procedure with music and would recommend it to other patients. Preoperative anxiety average score was 35.6 ± 13 and was reduced postoperatively to 28.9 ± 12.9 (P = .006). Preoperatively, 23% of patients rated high anxiety and postoperatively only 6.7% of patients rated high anxiety (P = .016). CONCLUSION: Music is an easy, feasible, inexpensive intervention that may reduce patients' anxiety and improve satisfaction during moderate sedation procedures and in the postoperative period.

An aqueous extract of Canarium schweinfurthii attenuates seizures and potentiates sleep in mice: Evidence for involvement of GABA Pathway.

About 30% of epileptic patients continue to have seizures. The present study investigates the anticonvulsant and sedative effects of an aqueous extract of C. schweinfurthii in mice. Anticonvulsant effects of C. schweinfurthii aqueous extract (0.01-300 mg/kg, p.o.) were tested against 4-aminopyridine (4-AP, 15 mg/kg, i.p.) -, pilocarpine (PILO, 380 mg/kg, i.p.) - and pentylenetetrazole (PTZ, 75 mg/kg, i.p.) -induced seizures, while sedative effects were tested on diazepam (35 mg/kg, i.p.)-induced sleep. Afterward, the most effective dose of the extract (11.9 mg/kg) was antagonized with N-methyl-ß-carboline-3-carboxamide or flumazenil. In another set of experiments, mice were sacrificed for the estimation of GABA content and GABA-T activity in the cerebral cortex. The dose of the extract that protected 50% of mice (ED50) against 4-AP, PILO, and PTZ was respectively 4.43 mg/kg (versus 12.01 for phenobarbital), 9.59 mg/kg (vs 8.67 for diazepam), and 2.12 mg/kg (vs 0.20 for clonazepam). Further, the ED50 of the extract that increased the duration of sleep was 0.24 mg/kg (vs 0.84 for phenobarbital). N-methyl-ß-carboline-3-carboxamide or flumazenil antagonized (p < 0.001) the anticonvulsant effect of C. schweinfurthii in PTZ-induced seizures and diazepam-induced sleep when compared to the negative control group. The extract at all doses increased (p < 0.001) the GABA content and decreased (p < 0.001) GABA-T activity. These findings suggest that C. schweinfurthii possesses anticonvulsant and sedative effects. These effects seem to be mediated via the modulation of the GABA neurotransmission. These data explain the use of this plant to treat epilepsy in Cameroon traditional medicine.

Kamishoyosan potentiates pentobarbital-induced sleep in socially isolated, ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep disorders are among the most common symptoms in both peri- and post-menopausal women. Kamishoyosan (KSS) is a Kampo medicine prescribed for the treatment of sleep disorders in menopausal women in Japan. However, its precise mechanism of action remains unclear. AIM OF THE STUDY: In the present study, we developed a new animal model of menopausal sleep disorders by inducing social isolation stress in ovariectomized mice. Using pentobarbital-induced sleeping time as an index, we aimed to investigate the effects of KSS and involvement of the benzodiazepine receptors. MATERIALS AND METHODS: Eight-week-old, female ddY mice were ovariectomized or subjected to a sham operation (control) and housed in social isolation or groups for 9 weeks. The animals were divided into four groups, group-housed sham-operated, isolated sham-operated, group-housed ovariectomized, and socially isolated ovariectomized. Pentobarbital (50 mg/kg) was administered intraperitoneally (i.p.). Sleeping time was considered the period between the loss of righting reflex and its return (up to 180 min). KSS was administered orally (p.o.) 60 min before the test. Diazepam and flumazenil were administered i.p. 30 and 45 min before the test, respectively. On the day after administration, the mice were euthanized, and their uteri were weighed. RESULTS: Socially isolated, ovariectomized mice had shorter sleeping times than mice in all other groups. In mice with intact ovaries, diazepam (1 mg/kg, i.p.) considerably prolonged the pentobarbital-induced sleeping time, but KSS (30-1000 mg/kg, p.o.) did not. However, KSS (100 mg/kg, p.o.) significantly prolonged the pentobarbital-induced sleeping time in socially isolated ovariectomized mice. The prolongation of sleeping time mediated by KSS was reversed by flumazenil (3 mg/kg, i.p.). CONCLUSIONS: KSS potentiated pentobarbital-induced sleep in socially isolated, ovariectomized mice, and the benzodiazepine receptors are possibly involved in its pharmacological mechanism. These findings suggest that KSS is beneficial for the treatment of menopausal sleep disorders.

Patient Satisfaction Through an Immersive Experience Using a Mobile Phone-Based Head-Mounted Display During Arthroscopic Knee Surgery Under Spinal Anesthesia: A Randomized Clinical Trial.

BACKGROUND: Patient satisfaction is an important element of high-quality health care. Virtual reality has been studied for its sedative and analgesic effects, as it immerses the patient into an artificial interactive environment. Deriving from this concept, we hypothesized that an immersive experience that engulfs the senses with noninteractive visual and auditory stimuli would have a positive effect on satisfaction and anxiety in patients undergoing spinal anesthesia. METHODS: We enrolled and randomized 90 patients undergoing spinal anesthesia for arthroscopic knee surgery into an immersive experience arm and an intravenous midazolam sedation arm. The immersive experience was provided through a mobile phone-based head-mounted display showing binocular monoscopic video and noise-canceling headphones playing audio. The primary outcome measure was postoperative satisfaction, measured using a visual analog scale and compared using the Mann-Whitney U test; secondary outcomes included anxiety score (measured using the 6-item State-Trait Anxiety Inventory), hemodynamic stability, and additional sedative requirement. RESULTS: The visual analog scale satisfaction score with immersive experience was significantly higher than with midazolam (median [interquartile range {IQR}] of 93 [82-98] and 80 [73-93], respectively, P = .004), with Hodges-Lehmann median difference estimate of 7 (95% confidence interval, 3-14). The change in anxiety scores from the preoperative to postoperative period between the groups was not significantly different (P = .08), with a Hodges-Lehmann median difference estimate of 3.3 (95% confidence interval, 0-6.7). All patients were hemodynamically stable, were without significant adverse events, and did not require additional sedatives. CONCLUSIONS: We have found that an immersive experience is an effective and acceptable intraoperative alternative to pharmacological sedation in patients undergoing arthroscopic knee surgery under spinal anesthesia, with higher satisfaction levels and no detected difference in preoperative to postoperative anxiolytic effect.

Factors Associated with Benzodiazepines Prolonged-Term Use in Post-Stroke Subjective Sleep Disturbance: A Single-Centre Retrospective Study from China.

PURPOSE: To investigate the prevalence of short- and long-term benzodiazepine and z-drugs (BZD) for the treatment of post-stroke subjective sleep disturbance (SSD) and to evaluate the risk factors associated with prolonged BZD treatment in this patient body. PATIENTS AND METHODS: Between 1st January 2018 and 1st December 2018, we identified 542 inpatients suffering from acute stroke in Heyuan People's Hospital. Of these, 290 inpatients were included in our final analysis. These patients were divided into three groups according to the treatment they received: non/occasional BZD (non-BZD), short-term BZD (short-term) and prolonged-term BZD (prolonged-term) treatment. We investigated the prevalence of each BZD treatment term and identified differences between the groups. Univariate logistic regression analysis was used to identify potential predictors for the prolonged use of BZD. Multinomial logistic regression analysis was used to assess the correlation between the prolonged use of BZD and potential predictors. RESULTS: The prevalence of cases receiving short and prolonged BZD treatments were 40.35% and 31.72%, respectively; none of the patients received polysomnography (PSG) screening from obstructive sleep apnoea (OSP). Treatment strategies were limited to BZD and traditional Chinese medicine; none of the patients received cognitive-behavioral treatment (CBT) or other forms of treatment. Logistic regression analysis showed that the short-term use was associated with z-drugs (odds ratio [OR]: 2.189, 95% confidence interval [CI]: 1.419-3.378), non-communication barriers (OR =0.535, 95% CI: 0.325-0.880) and posterior circulation infarct (POCI) (OR =2.199, 95% CI: 1.112-4.349). The prolonged-term use was associated with z-drugs (OR =3.012, 95% CI: 1.637-5.542), non-communication barriers (OR =0.530, 95% CI: 0.307-0.916), partial anterior circulation infarct (PACI) (OR =0.455, 95% CI: 0.250-0.827), and non pain after stroke (OR =0.315, 95% CI: 0.207-0.480). CONCLUSION: The status of BZD abuse for post-stroke SSD is worrying. Additional research attention and treatment options are needed for the treatment of post-stroke SSD. In particular, the potential combination of stroke and OSP appears to be underestimated and neglected. Post-stroke SSD patients should receive more comprehensive assessment and rigid follow-up to avoid the prolonged use of BZD. Additional and effective therapeutic strategies (such as positive pressure ventilation treatment or CBT) are urgently needed for cause-specific intervention.

Effects of Thai Local Ingredient Odorants, Litsea cubeba and Garlic Essential Oils, on Brainwaves and Moods.

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.

Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia Mill. Essential oil (Lavender EO) has a long history of medicinal use and is particularly claimed to possess anxiolytic and sedative properties. Lavender EO aromatherapy has been used to reduce distress and improve insomnia naturally. Increasing evidence appeared to show similarities between the effects of lavender EO and the anxiolytic drugs, benzodiazepines. However, its effects on sleep-wake and electrical brain patterns in comparison to that of the standard anxiolytic, diazepam, remained to be explored. AIM OF THE STUDY: The aim of this work was to investigate electroencephalography (EEG) profiles and sleep-pattern elicited by lavender EO inhalation compared to that of diazepam, a standard anxiolytic drug in in vivo rat model. MATERIALS AND METHODS: Adult male Wistar rats were anesthetized for electrode implantation on the frontal and parietal skulls. EEG signals were recorded for 180 min following intraperitoneal injection of diazepam (10 mg/kg) or during continuous inhalation of lavender EO (200 µL) or distilled water (control). Fast Fourier transform was used for the analyses of EEG power spectra and sleep-wake parameters. RESULTS: During a 30-60 min period, diazepam and lavender EO significantly increased frontal powers of 0.78-45.31 and 7.03-18.36 Hz, respectively. Both treatments also increased parietal powers with lower magnitudes of significant change. Significant increases in some frequency ranges remained until a 60-90 min period. Sleep-wake analyses also revealed that diazepam significantly reduced time spent in wake, increased time spent in non-rapid eye movement (NREM), increased episode duration of NREM, decreased numbers of wake episode and decreased rapid eye movement (REM) sleep latency. On the other hand, lavender EO only significantly decreased wake episodes and latency to REM sleep. Lavender EO inhalation reduced numbers of wake episode but maintain normal time spent in wake, NREM and REM sleeps. CONCLUSIONS: These findings might suggest beneficial and distinct anxiolytic-like effects of lavender EO for sleep enhancing purposes.

Individual and Combined Inhalational Sedative Effects in Mice of Low Molecular Weight Aromatic Compounds Found in Agarwood Aroma.

Agarwood is known to have a sedative effect and the less studied volatile aromatic constituents it contains may have contribution to the activity. In this study, two Kyara grade (highest-grade agarwood in Japan) samples were extracted using headspace-solid phase microextraction (HS-SPME) and analyzed through gas chromatography-mass spectrometry (GC-MS). Six low molecular weight aromatic compounds (LACs) and one structurally simple compound (diethylene glycol monoethyl ether) present in the aromas were individually evaluated for inhalational sedative activity in mice through open field test. Doses of 0.0001 g/L to 1 g/L were prepared for each compound and administered to mice (n = 6/dose/compound). Results revealed all compounds decreased spontaneous motor activity at almost all doses. Strongest sedative activity of each compound reduced total spontaneous motor activity by more than half against control, demonstrating their contribution to agarwood aroma and potential as independent sedating agents. Mixtures of compounds using their most effective dose were made and evaluated again for inhalational sedative effect. Interestingly, the combination of all compounds showed no significant effect and even caused stimulation in mice movements. This result suggests antagonistic-like interaction between the compounds, which is probably due to structural similarities. Consequently, it implies the other constituents present in agarwood, along with LACs, are also important to the overall sedative activity.

High quantities: Evaluating the association between cannabis use and propofol anesthesia during endoscopy.

BACKGROUND: Endoscopy under propofol sedation has become a routine procedure. Given the number of Canadians undergoing an endoscopy annually, as well as the pervasive use of cannabis by many patients, understanding the effect of cannabis use on the propofol dose at endoscopy is highly relevant. We aimed to evaluate the association between cannabis exposure and the propofol dose needed to achieve adequate sedation at endoscopy. METHODS: A case-control study of individuals undergoing endoscopy was conducted at a single outpatient endoscopy clinic in London, Ontario between 2014 and 2017. Cases included all individuals with any self-reported cannabis exposure, while controls included all individuals without any self-reported history of cannabis use. Dose of propofol administered by a single anesthetist was collected on each subject as well as additional demographic and procedure-related covariates. RESULTS: Three hundred and eighteen participants were included (cases, n = 151; controls, n = 167). Cannabis exposure was associated with an increase in propofol dose (cases 0.33 mg/kg/minute ±0.24; controls, 0.18 mg/kg/minute ±0.11; p<0.0001). Cannabis exposure remained an independent predictor of propofol dose on multivariate linear regression accounting for other important covariates (p<0.0001). Daily cannabis users required a higher propofol dose than weekly or monthly users. Three procedural sedation-related complications occurred in the cannabis-exposed group, while none occurred in the unexposed group. CONCLUSION: Our data suggest that cannabis use is significantly associated with the quantity of propofol needed for sedation at endoscopy. Further study is needed to better understand the molecular basis for this possible drug-drug interaction.

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

A Systematic Review of the Efficacy and Safety of Over-the-Counter Medications Used in Older People for the Treatment of Primary insomnia.

OBJECTIVE: The purpose of this systematic review is to evaluate the available evidence for safety and efficacy of over-the-counter (OTC) sleep aids used for the treatment of insomnia in older people.
DATA SOURCES: PubMed, EBSCO, and International Pharmaceutical Abstracts.
STUDY SELECTION: Five studies were included that involved humans 65 years of age and older being evaluated on OTC sleep aids in the outpatient setting.
DATA EXTRACTION: Data extraction from each study included primary and secondary efficacy endpoints, such as differences in the mean total sleep time, sleep latency, sleep efficiency, and number of awakenings, along with safety endpoints, such as psychomotor ability, cognitive ability, and adverse effect profiles. Both subjective and objective measures of changes in sleep and adverse effects were included.
DATA SYNTHESIS: Diphenhydramine had a statistically significant increase in sedation and decrease in number of awakenings but was not shown to be any less or more safe than compared products. Despite lacking safety issues, valerian was found to have no effect on subjective or objective sleep outcomes. Overall, melatonin had the most evidence and was found to have a statistically significant positive impact on sleep measures without safety issues.
CONCLUSION: Diphenhydramine and melatonin appear to be efficacious in improving some sleep measures while causing minimal adverse effects. However, there are very few studies that examine the use of over-the-counter sleep aids in those 65 years of age and older with primary insomnia. Additional studies are needed in this population.

Hypnotic Activity of Capparis spinosa Hydro-alcoholic Extract in Mice.

BACKGROUND: Sleep disorders are among the most common psychiatric and medical conditions. Herbal medicine appears to be effective in the treatment of sleep disorders which have been valued by many of publications and patents. OBJECTIVE: The present study aimed at investigating the hypnotic activity of the hydro-alcoholic extract of Capparis spinosa (HAE) in mice. METHODS: Three doses of HAE (30, 60 and 120 mg/kg) and three fractions of it, namely n-hexane fraction (NHF), water fraction (WF), and ethyl acetate fraction (EAF), were given in comparison with diazepam (3 mg/kg body weight i.p.) as a positive control and saline as a negative control. After 30 min, pentobarbital (30 mg/kg body weight i.p.) was administered. In addition, LD50 of HAE was examined and the cytotoxicity of HAE was assessed in l929 cells using the MTT assay. Moreover, for motorcoordination ability, 30 mins after administration of HAE, the rotarod test was performed. RESULTS: The results exhibited that the HAE and all the fractions significantly augmented pentobarbital induced sleeping time, which was comparable to that of induced by diazepam. The LD50 value was 2.4 g/kg. The extract did not induce any cytotoxic effects in L929 fibroblast cells. HAE did not affect the animals' performance on the rotarod test. CONCLUSION: Our finding suggests that the hydro-alcoholic extract of C. spinosa possesses a hypnotic potential that may require further scientific investigations.

Cochlear Implantation Under Local Anesthesia With Conscious Sedation in the Elderly: First 100 Cases.

OBJECTIVE: To report the outcomes on a large series of elderly patients who underwent cochlear implantation (CI) surgery under local anesthesia with conscious sedation (LA-CS). METHODS: Retrospective chart review on 100 consecutive elderly patients (> 65 years) who underwent CI with LA-CS at a tertiary care center between August 2013 and January 2020. An age-matched control group of 50 patients who underwent CI with general anesthesia (GA) are used for comparison. Outcomes measured included time in the operating room, time in the postanesthesia care unit (PACU), and rate of adverse events. RESULTS: Cochlear implant surgery under LA-CS was successfully performed in 99 (99%) patients. One patient requiring conversion to GA intraoperatively. No patients in the LA-CS group experienced cardiopulmonary adverse events; however, three patients (6%) in the GA group experienced minor events including atrial fibrillation and/or demand ischemia. Overnight observation in the hospital due to postoperative medical concerns or prolonged wake-up from anesthesia was required in one patient (1%) from the LA-CS cohort and 12 patients (24%) from the GA cohort. Perioperative adverse events exclusive to the LA-CS group included severe intraoperative vertigo (8%), temporary facial nerve paresis (3%), and wound infection (1%). The average amount of time spent in the operating room was 37 minutes less for procedures performed under LA-CS compared to GA (P < .05). The average amount of time in recovery was similar for both groups (P > .05). CONCLUSION: Cochlear implant surgery under LA-CS offers many benefits and is a safe, feasible, and cost-effective alternative to GA when performed by experienced CI surgeons. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E946-E951, 2021.

Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial / Efeito da pré‐ administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Abstract Background and objectives Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results The EC50 of propofol was lower in Group C (2.32 µg.mL−1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL−1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL−1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL−1, 95% CI 2.33-2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). Conclusion High-dose FA (0.75 mg.kg−1 or 1 mg.kg−1) reduces the EC50 of propofol, and 1 mg.kg−1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Resumo Justificativa e objetivos A administração pré‐operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol. Métodos Noventa e seis pacientes (ASA I ou II, com idades de 18-65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up‐and‐down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo‐controlada 0,5 µg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados A CE50 do propofol foi menor no Grupo C (2,32 µg.mL‐1, Intervalo de Confiança de 95% [95% IC] 1,85-2,75) e D (2,39 µg.mL‐1, 95% IC 1,91-2,67) do que no Grupo A (2,96 µg.mL‐1; 95% IC 2,55-3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 µg.mL‐1, 95% IC 2,33-2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05). Conclusão FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré‐administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

Standing Sedation and Iocoregional Analgesia in Equine Dental Surgery.

Procedural sedation has become popular for describing a semiconscious state that allows patients to be comfortable during certain surgical or diagnostic procedures. Sedation may be enhanced by locoregional anesthetic techniques to produce sufficient analgesia and muscle relaxation for surgery to occur. Sedation and local anesthesia for standing diagnostic and surgical procedures on the horse's head circumvents the potential complications of general anesthesia (particularly, complications related to recovery). However, the implementation of a locoregional anesthetic technique requires a thorough understanding of the anatomy to maximize success and minimize possible complications.

[Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial]. / Efeito da pré­administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. METHODS: Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg-1, 0.75 mg.kg-1 and 1 mg.kg-1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL-1-lower (or-higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation, and 15 minutes after intubation. RESULTS: The EC50 of propofol was lower in Group C (2.32 µg.mL-1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL-1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL-1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL-1, 95% CI 2.33-2.71) and Group A (p ˃ 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). CONCLUSION: High-dose FA (0.75 mg.kg-1 or 1 mg.kg-1) reduces the EC50 of propofol, and 1 mg.kg-1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Chemical Composition of Essential Oil from Flower of 'Shanzhizi' (Gardenia jasminoides Ellis) and Involvement of Serotonergic System in Its Anxiolytic Effect.

Gardenia jasminoides Ellis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of 'Shanzhizi', which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation of G. jasminoides essential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation of G. jasminoides essential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.