Hitoshi Higuchi

Introduction: Patients with intellectual disabilities, autism spectrum disorder, and related conditions often require sedation or general anesthesia to receive dental treatment. Many of these patients routinely take multiple medications, including antiepileptic and antipsychotic drugs, which may influence anesthetic management through drug interactions. However, medication use among patients receiving dental anesthesia in special needs dentistry has not been well investigated. This study aimed to clarify patterns of oral medication use in this population. Methods: This retrospective descriptive study included patients who underwent dental treatment under general anesthesia or intravenous sedation at Okayama University Hospital, Japan, between April 2022 and March 2025. Demographic characteristics, anesthesia-related variables, and regularly prescribed oral medications were collected from electronic medical records. Medications were categorized by pharmacological class, and descriptive statistical analyses were performed. Results: A total of 424 patients were analyzed. The mean age was 27.6 ± 15.3 years, and 67.4% were male. General anesthesia was used in 70.5% of patients. Overall, 71.0% regularly used oral medications, and polypharmacy, defined as the use of five or more medications, was observed in 23.5%. Antiepileptic drugs (36.8%) and antipsychotics (35.4%) were the most frequently prescribed medication classes. Risperidone and sodium valproate were the most commonly prescribed medications. Conclusion: Despite the relatively young age of the study population, medication use and polypharmacy were highly prevalent. The frequent use of antiepileptic and antipsychotic medications highlights the importance of understanding potential drug interactions during anesthetic management in special needs dentistry.

Remimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points ( p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam.

Noda K, et al. J Dent Anesth Pain Med. 2026 Apr;26(2):175-180. https://doi.org/10.17245/jdapm.2026.26.2.175

Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC_0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiple-comparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC_0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol.

Background: In order to understand the psychological aspects of chronic pain, it is important to consider the relationships between pain and psychosocial factors in patients with chronic pain. While psychosocial factors are known to affect pain intensity in temporomandibular disorders, few studies have evaluated them in patients with other types of chronic orofacial pain. Objective: The purpose of the present study was to evaluate the relationships between pain intensity and patient characteristics, diagnostic categories and psychosocial factors in chronic non‐nociceptive orofacial pain patients. Methods: In a retrospective, cross‐sectional study, we collected information from the medical records of 123 patients with chronic non‐nociceptive orofacial pain. Pain intensity was measured using the Brief Pain Inventory (BPI) total score. Analysis of the correlations among the variables revealed several strong correlations. Principal component analysis identified two components: the psychological distress and self‐efficacy/quality of life (QOL) components. Multiple linear regression analyses of the overall study population and each ICOP pain category were also performed. Results: In the overall sample, higher BPI scores were significantly associated with a greater psychological distress component and lower self‐efficacy/QOL component. The pain category was not a significant predictor of the BPI score. In the subgroup analyses, both components were significant predictors of the BPI score in myofascial orofacial pain; whereas, only the self‐efficacy/QOL component was in idiopathic orofacial pain. Conclusion: The results indicated that pain intensity in chronic non‐nociceptive orofacial pain is related to the self‐efficacy/QOL psychosocial factor component. These findings suggest that assessing psychosocial factors may be clinically important for the diagnosis and treatment of chronic orofacial pain.

Background: Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver. Methods: Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated. Results: The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions. Conclusions: These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam.

The oral health of people with intellectual disabilities remains poor due to a complex combination of physical and social problems, and often requires invasive dental treatment. However, it can be difficult to obtain their cooperation for dental treatment because they may not fully understand the need for treatment or may experience high levels of anxiety due to lack of understanding and/or sensory aversions to stimuli present in the dental environment, and behavioral management is often necessary during such treatment. Sedation is a very useful patient management method for dental treatment for people with intellectual disabilities; however, the dental treatment-related sedation of people with intellectual disabilities has different characteristics to the dental treatment-related sedation of others or other procedure-related sedation. For example, deep sedation is required for behavioral management; drug interactions between the patient’s regular medications, such as antiepileptic and antipsychotic drugs, and anesthetics may make the depth of sedation deeper; and the prevalence rate of obesity is higher among people with intellectual disabilities. The fact that the patient is in the supine position with their mouth open also makes airway management during sedation for dental treatment more difficult. It is therefore imperative that airway management during dental treatment for people with intellectual disabilities be conducted with the utmost precision and vigilance. Various attempts have been made to improve airway management during such sedation, and new technologies, such as capnography, nasal high-flow systems, and acoustic respiration monitors, may help. The objective of this review is to enhance comprehension of the attributes of airway management in dental sedation for people with intellectual disabilities and to properly understand the usefulness of the techniques that have been attempted thus far to ensure safer and more secure airway management for this population. The ultimate goal is to provide them with safe and secure medical care and improve their health outcomes.

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.

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.

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.