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.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

The Ethanol Extract of Syringa oblata Heartwood, a Mongolian Folk Medicine Containing Major Lignans, Exerts Analgesic and Sedative Effects on Mice.

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.

Management of Phenibut Use Disorder and Withdrawal in a Geriatric Patient.

Phenibut is a misused substance which has shown an increase in use over the past decade. Marketed as a "dietary supplement," it is not approved in the United States for use and is not regulated by the Food and Drug Administration. The substance, however, is readily available for purchase through online markets. It has a similar drug profile as alcohol, gabapentin and benzodiazepines. Clinical effects of this drug include physiologic dependence, euphoria, anxiolysis, antispasticity, sedation, and possible nootropic properties. While there are emerging new cases of managing phenibut withdrawal, no cases currently feature phenibut addiction and withdrawal management in the geriatric population. Here we discuss such a case of phenibut addiction and withdrawal in a 68-year-old male who initially began misusing phenibut to alleviate anxiety and insomnia precipitated by worsening affective disorder, sedative, hypnotic, or anxiolytic use disorder, and alcohol use disorder.

More than Drug Fever: Dexmedetomidine-Induced Hyperthermia in a Critically Ill Patient.

Dexmedetomidine is a selective alpha-2 adrenergic agonist utilized for sedation in critically ill patients.1 We present the case of a morbidly obese critically ill patient who experienced profound hyperthermia, with a maximum temperature of 41.4°C, hours after starting a dexmedetomidine infusion that was otherwise not explained by her clinical diagnoses. The hyperthermia resolved hours following cessation of the infusion. Dexmedetomidine was assessed as probable in terms of causing this adverse effect. Dexmedetomidine may be associated not only with low-grade fever, but as demonstrated in our case, it may be associated with significant temperature elevations requiring cessation of therapy to restore normothermia.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Sedative-hypnotic, anxiolytic and possible side effects of Salvia limbata C. A. Mey. Extracts and the effects of phenological stage and altitude on the rosmarinic acid content.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia limbata C. A. Mey. (Persian name: Maryam Goli-e-labeh dar) has been used for treating central nervous disorders such as insomnia, anxiety and depression in Persian traditional medicine. S. limbata is known for its pharmacological activities which could be at least in a part, upon the presence of rosmarinic acid (RA). However, the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extract has not yet been examined. AIM OF THE STUDY: In the current study the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extracts were evaluated. Besides, the effects of altitude and phenological stage on the RA content of S. limbata were investigated. MATERIALS AND METHODS: Sedative-hypnotic and anxiolytic effects were evaluated through the pentobarbital induced loss of righting reflex test and open field test, respectively. Flumazenil was used to reveal the mechanism of action. Possible side effects were investigated in the passive avoidance and grip strength tests. Besides, the effects of altitude and phenological stage (vegetative, flowering, and seed setting) on the RA content of S. limbata were evaluated using reversed-phase high-performance liquid chromatography (RP-HPLC). RESULTS: Following behavioral tests, sedative-hypnotic and anxiolytic effects were observed. Since the observed effects were reversed by flumazenil and no side effect on the memory and muscle strength was reported, modulation of the α1-containing GABA-A receptors could be proposed as one of the involved mechanisms. According to the RP-HPLC analysis, harvesting S. limbata in the vegetative stage at the altitude of 2500 m led to the highest content of RA (8.67 ± 0.13 mg/g dry matter). Among different extract of the plant samples collected in the vegetative stage at the altitude of 2500 m, the hydroalcoholic extract showed the highest rosmarinic acid content. CONCLUSION: The obtained results help to find the optimum situation to gain the highest content of RA as well as the pharmacological activity that could be economically important for the pharmaceutical industries.

Lipoic acid. Kinetics and pluripotent biological properties and derivatives.

Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.

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.

How to measure the effects and potential adverse events of palliative sedation? An integrative review.

BACKGROUND: Palliative sedation is the monitored use of medications intended to relieve refractory suffering. The assessment of palliative sedation has been focused on the assess of the level of consciousness but a more comprehensive approach to assessment is needed. AIM: To understand how the potential effects and possible adverse events of palliative sedation in Palliative Care patients are measured. DESIGN: Integrative review of most recent empirical research. DATA SOURCES: Cochrane Library, Embase, Medline, PubMed, and CINAHL were searched (2010-2020) using the terms sedation, palliative care, terminal care, assessment. Limits included studies in English and adults. Inclusion criteria were: scientific assessment papers, effects and complications of palliative sedation; patients with incurable illness. RESULTS: Out of 588 titles, 26 fulfilled inclusion criteria. The Discomfort Scale-Dementia of Alzheimer Type and Patient Comfort Score were used to assess comfort. The Richmond Agitation-Sedation Scale and The Ramsay Sedation Scale are the most used to measure its effect. Refractory symptoms were assessed through multi-symptom or specific scales; except for psychological or existential distress. Delirium was assessed using the Memorial Delirium Assessment Scale and pain through the Critical Care Pain Observation Tool. The use of technical approaches to monitor effects is upcoming. There is lack of measurement of possible adverse events and variability in timing measurement. CONCLUSIONS: There are palliative care validated instruments to assess the sedation effect but this review shows the need for a more standardized approach when assessing it. Instruments should be used within an experienced and trained expert, providing a holistic assessment.

Efficacy and safety of Zaoren Anshen capsules in the treatment of insomnia: A meta-analysis of randomized controlled trials.

BACKGROUND: Zaoren Anshen capsules (ZRAS) have been widely used to treat patients with insomnia. However, the efficacy and safety of ZRAS for insomnia treatment is not entirely clear. Therefore, it is necessary to clarify the effect of ZRAS for the treatment of insomnia by a systematic meta-analysis. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases and performed a manual search to retrieve relevant articles (available through January 2019) describing randomized controlled trials (RCTs) of ZRAS for the treatment of insomnia. The quality of the selected articles was assessed with the Cochrane risk-of-bias tool. A meta-analysis of the selected articles was performed with RevMan 5.3 software. RESULTS: A total of 13 articles including 1175 patients were included in the study. Overall, our results showed that ZRAS was slightly higher than that of the conventional Western medicine for insomnia in terms of clinical efficacy rate; but there was no statistical difference between the 2 groups (relative risk [RR] = 1.03, 95% confidence interval [CI] = [0.97, 1.09], P = .34). However, it should be noted that ZRAS treatment causes far fewer adverse reaction than treatment with conventional Western medicine (RR = 0.20, 95% CI = [0.14, 0.28], P < .00001). CONCLUSION: Our results suggested that ZRAS is an effective and safe treatment for insomnia, especially in adverse reaction. However, multi-regional and well-designed RCTs studies are needed in the future to validate the results.

Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study.

The purpose of the present double-blind randomized placebo-controlled clinical study was to investigate the effects of Passionflower on polysomnographic sleep parameters in subjects with insomnia disorder. A total number 110 adult participants (mean age = 40.47 ± 11.68, Female = 53.6%) met the inclusion criteria of insomnia disorder according to the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders). After randomization, patients received either the Passionflower extract or the placebo for 2 weeks. Patients underwent an overnight polysomnography and completed sleep diaries, Insomnia Severity Index, and Pittsburgh Sleep Quality Index. Within group comparisons were analyzed with paired t-tests or Wilcoxon's signed rank tests, and between-group comparisons were analyzed with independent t-tests or Mann-Whitney U Tests, as appropriate. Total sleep time (TST) was significantly increased in the Passionflower group compared with placebo (Passionflower vs placebo, 23.05 ± 54.26 vs -0.16 ± 53.12; P = 0.049). Sleep efficiency and wake after sleep onset (WASO) significantly improved after 2 weeks in the Passionflower group but there was no difference compared with the placebo group. The current study demonstrated the positive effects of Passionflower on objective sleep parameters including TST on polysomnography in adults with insomnia disorder. Further study is needed to investigate the clinical efficacy of Passionflower on insomnia.

Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is Not Associated With Alteration of Arrhythmia Inducibility.

BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation due to its unique pharmacodynamic profile, specifically affording predictable sedation without concurrent respiratory depression. However, Dex has previously been reported to prevent or terminate arrhythmias. The purpose of this study was to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and homeostatic stability during electrophysiology studies (EPSs) and ablation when a standardized Dex protocol was used as the primary sedation agent. METHODS: We performed a retrospective review of 163 consecutive procedures for PSVT ablation that received Dex as the primary sedative with adjunct fentanyl and midazolam boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control procedures wherein strictly fentanyl and midazolam were used for sedation. The primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed secondary outcomes included level of sedation and intraprocedure hemodynamics and oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control cohorts were very similar. The overall incidence of a "negative" EPSs in which arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the control group (P = .7). Unintended deep sedation was significantly less with DEX-FENT-MIDAZ (4.3% vs 27%; P ≤ .0001). However, DEX-FENT-MIDAZ use was associated with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension.

Efficacy and safety of traditional Chinese medicine yangxin anshen therapy for insomnia: A protocol of systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has gradually drawn the attention of clinicians as an alternative choice for insomniacs and TCM yangxin anshen therapy (TYAT), as a crucial therapy of treating insomniacs, is based on the theory of syndrome differentiation. However, owing to the lack of evidence-based medical evidence, the authors intend to carry out this study to evaluate TYAT's effectiveness and safety. METHODS: Seven electronic databases will be searched from inception to July 2019. Two authors will independently identify randomized controlled trials, fetch data and assess the risk of bias with tools provided by Cochrane. A comprehensive meta-analysis will be conducted with the Cochrane Collaboration software (Review Manager 5.3) for eligible and appropriate studies. Further, the evidence will be assessed with the grading of recommendations assessment, development, and evaluation approach. RESULTS: This article will be dedicated to assessing TYAT's efficacy and safety for insomniacs. CONCLUSION: This systematic review and meta-analysis may provide persuasive evidence for the clinical application of TYAT in treating insomnia. TRIAL REGISTRATION NUMBER: PROSPERO CRD 42019135115.

Effectiveness of Yi-Zhi-An-Shen granules on cognition and sleep quality in older adults with amnestic mild cognitive impairment: protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at greater risk of progressing to dementia. Current studies suggest that good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that the gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16S ribosomal DNA and metagenomics analyses, and serum markers. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60-85 years) will be recruited and allocated randomly to a treatment group and a placebo group in a 1:1 ratio and will then be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18 months follow-up. The primary outcome is the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Secondary outcome measures are the Mini-Mental State Examination, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, serum concentrations of immunological factors and inflammatory cytokines, and fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention. DISCUSSION: The results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbiota, and concentration of certain serum markers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03601000 . Registered on 26 July 2018.

Operator-Directed Procedural Sedation in the Congenital Cardiac Catheterization Laboratory.

OBJECTIVES: The purpose of this study was to evaluate the association between the method of procedural sedation and outcomes for congenital cardiac catheterization procedures. BACKGROUND: The safety of operator-directed sedation (ODS) in the pediatric/congenital cardiac catheterization laboratory has been questioned. To our knowledge, the relative safety of ODS versus general anesthesia (GA) in these cases has not to date been critically evaluated. METHODS: A single-center retrospective cohort study was performed to compare the relative safety, cost, and times of catheterization procedures performed with ODS and those performed with GA from a cardiac anesthesiologist. The risk of adverse outcomes was compared using propensity-score-adjusted models. Using the same propensity score, procedure times and relative charges were also compared. RESULTS: Over the study period, 4,424 procedures in 2,547 patients were studied. Of these, 27% of cases were performed with ODS. ODS procedures were 70% diagnostic procedures, 17% device closure of patent ductus arteriosus, 5% balloon pulmonary valvuloplasty, and 3% pulmonary artery angioplasty. The risk of adverse event in adjusted models for ODS cases was significantly lower than in GA cases (odds ratio: 0.66; 95% confidence interval: 0.45 to 0.95; p = 0.03). Total room time and case time were also significantly shorter (p < 0.001). Professional (charge ratio: 0.88; p < 0.001) and hospital (charge ratio: 0.84; p < 0.001) charges for ODS cases were also lower than those for GA cases. CONCLUSIONS: This study demonstrates that clinical judgment can identify subjects in whom ODS is not associated with increased risk of adverse events. The use of ODS was associated with reduced case times and charges. In combination, these findings suggest that the selective use of ODS can allow for greater efficiency and higher value care without sacrificing safety.