Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder.

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.

Anesthetic Management Using Remimazolam in a Hemodialysis Patient.

Remimazolam, an ultra-short-acting benzodiazepine, is a new intravenous anesthetic used for sedation and general anesthesia. Because remimazolam is primarily metabolized by carboxylesterases in the liver and other tissues including the lung and has metabolites with little or no bioactivity, its anesthetic effect is not significantly influenced by renal dysfunction. Therefore, remimazolam may be considered an appropriate agent for hemodialysis patients and may have added benefits beyond midazolam and propofol. Remimazolam has also been suggested to cause less cardiac depression than propofol. This case report presents an 82-year-old female hemodialysis patient with chronic heart failure who underwent partial glossectomy for squamous cell carcinoma of the tongue under general anesthesia with remimazolam and remifentanil. Hemodynamic control was stable during the anesthetic, which was safely completed without any adverse events and resulted in a rapid, clear emergence without flumazenil. Remimazolam and remifentanil may be appropriate as first-line general anesthetic agents for hemodialysis patients with heart failure.

Evaluation of Sedation Levels Using SedLine During Intravenous Sedation for Dental Procedures: A Case-Series Study.

The Patient State Index (PSI) is the numerical value of anesthesia depth as measured using a SedLine Sedation Monitor (Masimo Corporation). In this pilot study, we evaluated PSI values captured during intravenous (IV) moderate sedation for dental treatment. During the dental treatment, a dental anesthesiologist maintained the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at 3 to 4 by adjusting the administration of midazolam and propofol while PSI values were recorded. The mean (SD) and median (25th percentile, 75th percentile) PSI values during dental treatment under IV moderate sedation were 72.7 (13.6) and 75 (65, 85), respectively.

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial.

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 µg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding.

Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial.

PURPOSE: In anesthetic management, it is widely accepted that obese patients are more likely to suffer airway obstructions and reductions in arterial oxygen saturation (SpO2). Therefore, it is important to take special measures to prevent oxygen desaturation during the deep sedation of obese patients. This clinical study examined whether the use of nasal high-flow systems (NHFS) keep higher SpO2 and reduced hypoxemia than conventional nasal cannula during the deep sedation of obese patients with intellectual disabilities for dental treatment. MATERIALS AND METHODS: Eighteen obese patients (body mass index: >25) with intellectual disabilities who underwent dental sedation were enrolled. In each case, sedation was induced using propofol and maintained at a bispectral index of 50 to 70. The subjects were randomly assigned to the control oxygen administration (5 L/min via a nasal cannula) or NHFS (40% O2, 40 L/min, 37 °C) arm in alternate shifts as a crossover trial. The primary endpoint was the minimum SpO2 value, and the incidence of hypoxemia during dental treatment was also evaluated. RESULTS: The mean minimum SpO2 value was significantly higher in the NHFS arm than in the control arm (95.8 ± 2.1 % vs 93.6 ± 4.1 %, P = 0.0052, 95% confidence interval: 0.608-3.947). Hypoxemic episodes (SpO2: ≤94%) occurred 3 cases (16.7%) in the NHFS arm and 11 cases (61.1%) in the control arm (P = 0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 - 0.630). CONCLUSION: NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatment.

Dexmedetomidine inhibits LPS-induced inflammatory responses through peroxisome proliferator-activated receptor gamma (PPARγ) activation following binding to α2 adrenoceptors.

Over the past decade, dexmedetomidine (DEX) has been found to possess an anti-inflammatory effect. However, the local anti-inflammatory mechanism of DEX has not been fully clarified. Some intracellular inflammatory pathways lead to negative feedback during the inflammatory process. The cyclooxygenase (COX) cascade synthesizes prostaglandins (PGs) and plays a key role in inflammation, but is known to also have anti-inflammatory properties through an alternative route of a PGD2 metabolite, 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), and its receptor, peroxisome proliferator-activated receptor gamma (PPARγ). Therefore, we hypothesized that DEX inhibits LPS-induced inflammatory responses through 15d-PGJ2 and/or PPARγ activation, and evaluated the effects of DEX on these responses. The RAW264.7 mouse macrophage-like cells were pre-incubated with DEX, followed by the addition of LPS to induce inflammatory responses. Concentrations of TNFα, IL-6, PGE2, and 15d-PGJ2 in the supernatants of the cells were measured, and gene expressions of PPARγ and COX-2 were evaluated in the cells. Furthermore, we evaluated whether a selective α2 adrenoceptor antagonist, yohimbine or a selective PPARγ antagonist, T0070907, reversed the effects of DEX on the LPS-induced inflammatory responses. DEX inhibited LPS-induced TNFα, IL-6, and PGE2 productions and COX-2 mRNA expression, and the effects of DEX were reversed by yohimbine. On the other hand, DEX significantly increased 15d-PGJ2 production and PPARγ mRNA expression, and yohimbine reversed these DEX's effects. Furthermore, T0070907 reversed the anti-inflammatory effects of DEX on TNFα and IL-6 productions in the cells. These results suggest that DEX inhibits LPS-induced inflammatory responses through PPARγ activation following binding to α2 adrenoceptors.

Assessing the Effectiveness of Combined Analgesics for Bilateral Ramus Osteotomies.

Pain management is important for alleviating patients' suffering and early recovery. Although analgesic combinations are known to be effective, a comparison of the effectiveness of different combinations has never been performed specifically for ramus osteotomy procedures. Therefore, the purpose of this observational retrospective cohort study was to identify an effective combination for pain management throughout the intraoperative and immediate postoperative period for patients undergoing bilateral ramus osteotomy procedures. Inclusion criteria consisted of patients who had undergone bilateral mandibular ramus osteotomies over a 2-year period. The analyzed predictor variables included patient gender, age, body weight, operation, anesthetic method, duration of operation, intraoperative use of fentanyl, nonsteroidal anti-inflammatory drugs (NSAIDs), and intravenous acetaminophen administered in the operating room at the end of the surgery. The outcome variable was the necessity for additional rescue analgesics (yes/no) in the recovery room. Bivariate statistics and multivariate analysis were computed with a p-value of <0.05. The study sample was comprised of 78 patients requiring bilateral mandibular ramus osteotomies. From the multivariate analysis, the combination of NSAIDs-acetaminophen-fentanyl was an independent factor for no additional rescue analgesics during the first 1 hour after bilateral ramus osteotomies, indicating that the combination is significantly effective for bilateral ramus osteotomies compared with the other combinations. Considering that this study consisted of a small sample size, the results of this study suggest that some of the combinations, particularly NSAIDs-acetaminophen-fentanyl, are more effective than NSAIDs alone for postoperative pain control immediately following bilateral ramus osteotomy procedures.

Locally injected ivabradine inhibits carrageenan-induced pain and inflammatory responses via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.

BACKGROUND: Recently, attention has been focused on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the mechanism of and as a treatment target for neuropathic and inflammatory pain. Ivabradine, a blocker of HCN channels, was demonstrated to have an effect on neuropathic pain in an animal model. Therefore, in the present study, we evaluated the effect of ivabradine on inflammatory pain, and under the hypothesis that ivabradine can directly influence inflammatory responses, we investigated its effect in in vivo and in vitro studies. METHODS: After approval from our institution, we studied male Sprague-Dawley rats aged 8 weeks. Peripheral inflammation was induced by the subcutaneous injection of carrageenan into the hindpaw of rats. The paw-withdrawal threshold (pain threshold) was evaluated by applying mechanical stimulation to the injected site with von Frey filaments. Ivabradine was subcutaneously injected, combined with carrageenan, and its effect on the pain threshold was evaluated. In addition, we evaluated the effects of ivabradine on the accumulation of leukocytes and TNF-alpha expression in the injected area of rats. Furthermore, we investigated the effects of ivabradine on LPS-stimulated production of TNF-alpha in incubated mouse macrophage-like cells. RESULTS: The addition of ivabradine to carrageenan increased the pain threshold lowered by carrageenan injection. Both lamotrigine and forskolin, activators of HCN channels, significantly reversed the inhibitory effect of ivabradine on the pain threshold. Ivabradine inhibited the carrageenan-induced accumulation of leukocytes and TNF-alpha expression in the injected area. Furthermore, ivabradine significantly inhibited LPS-stimulated production of TNF-alpha in the incubated cells. CONCLUSION: The results of the present study demonstrated that locally injected ivabradine is effective against carrageenan-induced inflammatory pain via HCN channels. Its effect was considered to involve not only an action on peripheral nerves but also an anti-inflammatory effect.

Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region.

Activating transcription factor (ATF) 5 is a transcription factor belonging to the ATF/cAMP-response element-binding protein gene family. We previously reported that ATF5 mRNA expression increased in response to amino acid limitation. The ATF5 gene allows transcription of mRNAs with at least two alternative 5'-untranslated regions (5'-UTRs), 5'-UTRalpha and 5'-UTRbeta, derived from exon1alpha and exon1beta. 5'-UTRalpha contains highly conserved sequences, in which the upstream open reading frames (uORFs) uORF1 and uORF2 are found in many species. This study was designed to investigate the potential role of 5'-UTRs in translational control. These 5'-UTRs differentially determined translation efficiency from mRNA. The presence of 5'-UTRalpha or 5'-UTRbeta represses translation from the downstream ATF5 ORF. Moreover, 5'-UTRalpha-regulated translational repression is released by amino acid limitation or NaAsO(2) exposure. This release was not seen for 5'-UTRbeta. Mutation of uAUG2 in the uORF2 of 5'-UTRalpha restored the basal expression and abolished the positive regulation by amino acid limitation or arsenite exposure. We demonstrated that phosphorylation of eukaryotic initiation factor 2alpha was required for amino acid limitation-induced translational regulation of ATF5. Furthermore, arsenite exposure activated the exogenously expressed heme-regulated inhibitor kinase and induced the phosphorylation of eukaryotic initiation factor 2alpha in nonerythroid cells. These results suggest that translation of ATF5 is regulated by the alternative 5'-UTR region of its mRNA, and ATF5 may play a role in protecting cells from amino acid limitation or arsenite-induced oxidative stress.