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.

Dental findings and intravenous sedation in a patient with Potocki-Lupski syndrome: A case report.

AIMS: Potocki-Lupski syndrome (PTLS), which is caused by the partial duplication of the short arm of autosome 17, is characterized by feeding difficulties associated with muscle hypotonia and dysphagia in infancy, followed by growth retardation and low body weight in later stages. Speech and motor developmental disorders are observed in childhood, accompanied by autism spectrum disorders in several cases. Other disorders include dental and skeletal abnormalities, and associated sleep apnea. Herein, we describe the first case of dental evaluation and treatment under intravenous sedation in a patient with PTLS. METHODS: A 13-year-old boy with PTLS and intellectual disability was referred for the treatment of dental caries. Routine intraoral examination and dental treatment were not feasible. As the patient had no muscle hypotonia, dysphagia, or severe growth delay, intraoral examination and dental treatment were successfully performed under intravenous sedation. No incidence of intraoral airway obstruction or aspiration was reported. The patient was followed-up post-operatively. CONCLUSION: PTLS, a newly identified syndrome, is associated with cardiovascular abnormalities, dysphagia, failure to thrive, and sleep apnea, which are potential risk factors for sedation. This case report highlights the importance of facial and oral findings in determining the risks of difficulties in airway management.

Factors associated with transient bradycardia during local anesthesia administration to the oral cavity under intravenous sedation: A retrospective cohort study.

Background/purpose: The possibility of triggering the trigeminocardiac reflex (TCR) during oral surgery is considerably lower than that during other surgeries. A reduced heart rate (HR) of ≥20% from baseline is usually considered a diagnostical criterion for the TCR. Our automated anesthesia charting system often revealed cases of slight transient HR decrease during sedation. We aimed to explore its incidence and associated factors during local anesthesia administration under intravenous sedation. Materials and methods: This study analyzed the data of 2636 cases that received infiltration anesthesia under intravenous sedation from 2008 to 2010 and had vital signs recorded using an automated anesthesia charting system. Especially, data concerning the average HR before anesthesia and the minimum HR between the initiation and end of anesthesia from anesthetic records were extracted. Moreover, data regarding patients' medical history and unusual reactions during dental treatment were collected. Multivariate logistic regression analysis was performed to identify factors associated with transient bradycardia (TB). Results: TB occurred in 472 patients (17.9%); no patient developed hypotension or any associated symptoms, suggesting that intravenous sedation was effective in stabilizing vital signs. The factors associated with TB were younger age, gag reflex, and allergy to local anesthetics. There were no differences in sex, patient history, or dose of sedatives between patients with TB and those without TB. Conclusion: The incidence of TB during infiltration anesthesia under sedation was found to be higher than that previously reported. Additionally, young age and gag reflex were identified as factors associated with bradycardia development.

Considerations for Satisfactory Sedation during Dental Implant Surgery.

Implant surgery is a lengthy dental procedure, and sedation is often used to reduce discomfort. The effectiveness of sedation has traditionally been evaluated in terms of patient and surgeon satisfaction, but the most important goal is not to induce a deep sleep in the patient, but rather to ensure that the surgery is performed safely and as planned. Additionally, adequate pain control is a necessary requirement for patient and surgeon satisfaction. Most patients undergoing implant surgery are middle-aged or older, and a relatively large number of them have cardiovascular disease. Infiltration anesthesia using articaine or lidocaine in combination with adrenaline is widely used, but its use in patients with cardiovascular disease is limited because of adrenaline's effects on the cardiovascular system. The use of long-acting local anesthetics and the potential efficacy of ultrasound-guided jaw nerve block have been investigated to enhance analgesia without resorting to adrenaline. Midazolam and propofol are usually used for sedation, but dexmedetomidine, which causes less respiratory depression, and the ultrashort-acting benzodiazepine remimazolam are emerging as potential alternatives. Monitoring of anesthetic depth using electroencephalography is effective in maintaining a constant level of sedation. In addition, sedation promotes the stabilization of heart rate and blood pressure, reducing the risks associated with adrenaline and allowing for safer management.

Perioperative Management of a Patient With Tongue Cancer Who Developed Pneumomediastinum Following Tracheostomy Performed to Secure the Airway.

Prior to a scheduled operation for a 45-year-old male patient with tongue cancer, a tracheotomy performed under intravenous sedation to prevent asphyxia due to extensive bleeding resulted in pneumomediastinum and subcutaneous emphysema. The planned operations were postponed until reduction of the pneumomediastinum was confirmed. During operation, airway pressure was kept low to prevent tension pneumomediastinum along with a sufficient depth of anesthesia, controlled analgesia, and continuous administration of muscle relaxants. Postoperatively, sedation was used to avoid stress and complications with the vascular anastomosis site. In this case, air leakage into the soft tissues was one of the possible causes of the event associated with increased airway pressure. Although the incidence of such complications is relatively low, caution should be exercised after tracheostomy.

Coronary Spasm During Postoperative Sedation With Dexmedetomidine.

This is a case report of an 81-year-old woman who underwent tracheostomy, bilateral cervical dissection, partial tongue resection, radial forearm free flap reconstruction, and split-thickness skin grafting under general anesthesia. After successful surgery, she was moderately sedated postoperatively with intravenous dexmedetomidine (DEX) and fentanyl. The fentanyl was discontinued 5 hours postoperatively. Eight hours after the operation, an atrioventricular junctional rhythm, a 2-mm elevation of the ST segment, and biphasic T waves were detected in lead II that lasted approximately 3 minutes. Hypotension and bradycardia were observed simultaneously with the abnormal electrocardiogram. The next day, a cardiologist examined the patient and suggested that coronary spasm had occurred based on those findings. The transient coronary spasm was likely caused by a combination of various factors including surgical stress and altered autonomic function. However, it is possible that stimulation of α-2 adrenergic receptors induced by DEX may also be linked to the coronary vasospasm that occurred.

Factors Associated with Variability in Pulse Wave Transit Time Using Pulse Oximetry: A Retrospective Study.

Pulse wave transit time (PWTT) is the time difference between the occurrence of an R-wave on an electrocardiogram and the detection of pulsatile signals on a pulse oximeter, which reflects changes in blood pressure (BP) corresponding to the vessel wall compliance. However, the factors affecting PWTT variability have not been determined. Thus, we investigated the BP changes associated with variations in PWTT and identified the clinical characteristics associated with these variations. Data related to 605 cases of dental procedures performed under intravenous conscious sedation from April 2020 to November 2021 were collected, and 485 cases were enrolled. Heart rate, systolic blood pressure before and after local anesthesia (LA) administration, and crest and trough PWTT waves during LA administration were recorded. Thereafter, PWTT variability was calculated; cases were divided into two groups: large PWTT variability (LPV, n = 357) and small PWTT variability (SPV, n = 128). The index of large PWTT variability could not detect changes in BP. Logistic regression analysis revealed that factors, such as LA use, age, hypertension, and dental treatment phobia were associated with PWTT variability. The use of epinephrine more than 36.25 µg in each LA resulted in PWTT variability of more than 15 ms.

The clinical advantage of nasal high-flow in respiratory management during procedural sedation: A scoping review on the application of nasal high-flow during dental procedures with sedation.

Structured summary: Rationale: Nasal high-flow (NHF), a new method for respiratory management during procedural sedation, has greater advantages than conventional nasal therapy with oxygen. However, its clinical relevance for patients undergoing oral maxillofacial surgery and/or dental treatment remains uncertain and controversial, due to a paucity of studies. This scoping review compared and evaluated NHF and conventional nasal therapy with oxygen in patients undergoing oral maxillofacial surgery and/or dental treatment. Materials and methods: A literature search of two public electronic databases was conducted, and English writing randomized controlled trials (RCTs) of nasal high flow during dental procedure with sedation reviewed. The primary and secondary outcomes of interest were the incidence of hypoxemia and hypercapnia during sedation and the need for intervention to relieve upper airway obstruction, respectively. Results: The search strategy yielded 7 studies, of which three RCTs met our eligibility criteria, with a total of 78 patients. Compared with conventional nasal therapy with oxygen, NHF significantly reduced the incidence of hypoxemia and hypercapnia during procedural sedation. Conclusion: NHF can maintain oxygenation and possibly prevent hypercapnia in patients undergoing dental treatment. Additional RCTs are needed to clarify and confirm these findings.

Effect of Different Maxillary Oral Appliance Designs on Respiratory Variables during Sleep.

This study aimed to analyze the efficacy of maxillary oral appliance (MOA) designs on respiratory variables during sleep. At baseline, 23 participants underwent a sleep test with a portable device for two nights and were categorized as participants with mild obstructive sleep apnea (mild-OSA) (n = 13) and without OSA (w/o-OSA) (n = 10). Three types of MOAs, standard-OA (S-OA), palatal covering-OA (PC-OA), and vertically increasing-OA (VI-OA), were each worn for three nights, and sleep tests with each MOA were performed with a portable device for two nights. Based on the average of the respiratory event index (REI) values for the two nights for each MOA, w/o-OSA participants with an REI ≥ 5.0 were defined as the exacerbation group and those with an REI < 5.0 as the non-exacerbation group. In mild-OSA participants, an REI ≥ 15.0 or REI ≥ baseline REI × 1.5 were defined as the exacerbation group and those with an REI < 15.0 and REI < baseline REI × 1.5 were defined as the non-exacerbation group. The percentage of the exacerbation and non-exacerbation groups with MOA was evaluated in the w/o-OSA and mild-OSA participants. The maxillary and mandibular dental-arch dimension was compared by dentition model analysis. The exacerbation group in w/o-OSA participants (n = 10) comprised 10.0% participants (n = 1) with S-OA, 40.0% (n = 4) with PC-OA, and 30.0% (n = 3) with VI-OA. The exacerbation group in the mild-OSA participants (n = 13) comprised 15.4% subjects (n = 2) with S-OA, 23.1% (n = 3) with PC-OA, and 23.1% (n = 3) in VI-OA. In the model analysis for w/o-OSA, the posterior dental arch width was significantly greater in the exacerbation group than in the non-exacerbation group wearing S-OA (p < 0.05). In addition, the ratio of the maxillary to mandibular dental arch width (anterior dental arch width) was significantly greater in the exacerbation group than in the non-exacerbation group for both PC-OA and VI-OA (p < 0.05). In mild-OSA, the maxillary and mandibular dental arch lengths and the ratio of maxillary to mandibular dental arch width (posterior dental arch width) were significantly smaller in the exacerbation group than in the non-exacerbation group for S-OA (p < 0.05). This study confirmed that wearing an MOA by w/o-OSA and mild-OSA participants may increase the REI during sleep and that PC-OA and VI-OA may increase the REI more than S-OA. The maxillary and mandibular dental-arch dimensions may affect the REI when using an MOA.

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.

Transient ventricular bigeminy during emergence from general anesthesia in a pediatric patient with catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare genetic disease that is characterized by ventricular arrhythmias and sudden death, induced by exogenous and endogenous catecholamine. We performed general anesthesia for dental treatment of multiple teeth in a 7-year-old boy with CPVT. To avoid sympathetic tone, anesthesia was maintained by total intravenous anesthesia, but ventricular bigeminy was induced by stimulation on emergence form general anesthesia. Although bigeminy in the present case might have been less likely to induce a fatal arrhythmia, we should keep in mind that a small amount of sympathetic tone may induce arrhythmias in a patient with CPVT.

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.

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol's pharmacokinetics: a prospective cohort study.

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.

Pulmonary Aspiration During Induction of General Anesthesia.

Perioperative pulmonary aspiration of gastric contents can induce complications of varying severity, including aspiration pneumonitis or pneumonia, which may be lethal. A 34-year-old man with no significant medical history presented to Okayama University Hospital for extraction of the third molars and incisive canal cystectomy under general anesthesia. He experienced pulmonary aspiration of clear stomach fluid during mask ventilation after induction. After aspiration occurred, the patient was immediately intubated, and suctioning was performed through the endotracheal tube (ETT). An anteroposterior (AP) chest radiograph was obtained that demonstrated atelectasis in the left lower lobe, in addition to increased peak airway pressures being noted, although SpO2 remained at 96% to 99% at an FiO2 of 1.0. The decision was made to proceed, and the scheduled procedures were completed in approximately 2 hours. A repeat AP chest radiograph obtained at the end of the operation revealed improvement of the atelectasis, and no residual atelectasis was observed on the next day. Although the patient reported following standard preoperative fasting instructions (no fluids for 2 hours preoperatively), more than 50 mL of clear fluid remained in his stomach. Because vomiting can occur despite following NPO guidelines, the need for continued vigilance by anesthesia providers and proper timely management is reinforced.

Age and female gender associated with periodontal disease in Japanese patients with rheumatoid arthritis: Results from self-reported questionnaires from the IORRA cohort study.

Objectives: This study aimed to evaluate the prevalence of, and the factors associated with, periodontal disease in Japanese patients with rheumatoid arthritis (RA).Methods: Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed three self-administered questionnaires including questions about recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and any history of periodontitis. Logistic regression analyses were used to evaluate associations with clinical variables for each questionnaire.Results: Among 5600 Japanese patients with RA, 31.0%, 18.3%, and 20.4% of patients self-reported recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and a history of periodontitis, respectively. In multivariate models, younger age, fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), and prednisolone dosage were significantly (p < .05) associated with recent gingival bleeding during toothbrushing. Older age, female gender, and ever-smoker status were significantly correlated with a recent diagnosis of periodontitis.Conclusion: Many Japanese patients with RA experience gingival bleeding during toothbrushing and are diagnosed with periodontitis. Age, female gender, ever-smoker status, fracture history, JHAQ-DI, and prednisolone dosage appeared to be associated with periodontal disease in Japanese patients with RA.

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.

Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis.

PURPOSE: Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study. METHODS: Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated. RESULTS: Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS. CONCLUSION: Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.