Springer Science and Business Media LLCActa Medica Okayama2050-65112612025PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally166ENYukikoNishiokaDepartment of Dental Anesthesiology, Okayama University HospitalYanyinLuDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiHiguchiDepartment of Dental Anesthesiology, Okayama University HospitalSakiMiyakeDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakiFujimotoDepartment of Dental Anesthesiology, Okayama University HospitalMidoriHamaoka-InoueDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTanimuraDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitomiUjitaDepartment of Dental Anesthesiology, Okayama University HospitalShigeruMaedaDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground 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.<br>
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.<br>
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.<br>
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.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1360-23223742024Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disordere13265ENHitoshiHiguchiDepartment of Dental Anesthesiology, Okayama University HospitalKotaMiyakeDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSakiMiyakeDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakiFujimotoDepartment of Dental Anesthesiology, Okayama University HospitalYukikoNishiokaDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShigeruMaedaDepartment of Dental Anesthesiology, Okayama University HospitalTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: 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.<br>
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.<br>
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.<br>
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.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0278-23917992021Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial18421850ENHitoshiHiguchiDepartment of Dental Anesthesiology, Okayama University HospitaKumikoTakaya-IshidaDepartment of Dental Anesthesiology, Okayama University HospitalSakiMiyakeDepartment of Dental Anesthesiology, Okayama University HospitalMakiFujimotoDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukikoNishiokaDepartment of Dental Anesthesiology, Okayama University HospitalShigeruMaedaDepartment of Dental Anesthesiology, Okayama University HospitalTakuyaMiyawakiDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPurpose:<br>
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.<br>
Materials and Methods:<br>
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 50–70. 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
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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 case (61.1%) in the control arm (P=0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 to 0.630).
Conclusion:
NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatmentNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6852014Chronic Orofacial Pain in Dental Patients: Retrospective Investigation over 12 years269275ENYumikoTomoyasuHitoshiHiguchiMegumiMoriKumikoTakayaYukaHondaAyakaYamaneAkikoYabukiTomokoHayashiMinakoIshii-MaruhamaAyakoJinzenjiShigeruMaedaAtsushiKohjitaniMasahikoShimadaTakuyaMiyawakiOriginal Article10.18926/AMO/52895Orofacial pain is often difficult to diagnose and treat. However, there have been few reports on the clinical observation of dental patients with orofacial pain. We retrospectively investigated the characteristics of 221 dental patients who had suffered from persistent orofacial pain. Data were collected from the outpatient medical records in our clinic over the past 12 years. More than half of the patients (53.8%) had suffered with pain for more than 6 months from pain onset until the first visit to our clinic. The main diagnoses were neuropathic pain (30.3%), myofascial pain (23.5%), psychogenic pain (20.4%), odontogenic toothache (17.2%), and others (7.7%) such as temporomandibular disorders and glossitis. The treatments included pharmacotherapy, splint therapy, and others such as nerve block, dental treatment, physiotherapy, and/or psychotherapy. Excluding the patients (52 of 221 initially enrolled patients) with unknown responses to treatment, 65.7% showed remission or a significant improvement in pain in response to treatment. Although only a small group of patients had odontogenic toothache, the rate of improvement was highest for this disorder. In conclusion, early consultation with a dentist is useful to prevent chronicity of odontogenic pain and to make a differential diagnosis in patients with orofacial pain.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1999末梢型ベンゾジアゼピン受容体とミダゾラムの臨床効果との関係についてENNo potential conflict of interest relevant to this article was reported.