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.

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.

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.

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.

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.

Female Patients Require a Higher Propofol Infusion Rate for Sedation.

Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study.

Some patients have transient hypertension before dental treatment as a result of anxiety and stress. Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension. We have evaluated in a randomised, controlled trial whether a low dose of midazolam can lower blood pressure in dental patients to an acceptable level without excessive sedation. Suitable patients were randomised to be given midazolam (trial group) or physiological saline (control group) intravenously. Blood pressure, heart rate, degree of anxiety, and amount of sedation were measured before and after injection. After injection, blood pressure in the trial group significantly decreased to clinically acceptable levels compared with controls. The degree of anxiety in the trial group was also significantly less than that in the control group, but there were no significant differences in sedation. These results suggest that injection of a low dose of midazolam stabilises the blood pressure of dental patients with transient hypertension.

Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study.

PURPOSE: Recently, attention has been paid to dexmedetomidine, a selective α-2 adrenoceptor agonist, as a possible additive for local anesthesia. However, the effect of locally injected dexmedetomidine on the anesthetic action in humans has not fully been clarified. Thus, the purpose of the present study was to evaluate the effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans. MATERIALS AND METHODS: Twenty healthy volunteers were included in the present crossover double-blinded study. Lidocaine solution or lidocaine plus dexmedetomidine solution was submucosally injected into the alveolar mucosa in a crossover and double-blinded manner. The local anesthetic effect of the solutions was evaluated by measuring the current perception threshold (CPT) in the oral mucosa for 120 minutes after injection. Furthermore, the sedation level, blood pressure, and heart rate of the volunteers were evaluated. For statistical analysis, the Wilcoxon signed rank test and 2-way repeated measures analysis of variation were used. RESULTS: The CPT was increased with the 2 solutions and peaked 10 minutes after injection. CPT values 10 and 20 minutes after injection of lidocaine plus dexmedetomidine solution were considerably higher than those with lidocaine solution. The duration of an important increase in the CPT after injection with lidocaine plus dexmedetomidine solution was longer than that with lidocaine. Furthermore, the area under the time curve of CPT was considerably higher with lidocaine plus dexmedetomidine solution than with lidocaine solution. No volunteer showed a change in sedation level, blood pressure, or heart rate after injection with either test solution throughout the experiment. CONCLUSION: The present study showed that a combination of dexmedetomidine plus lidocaine considerably enhances the local anesthetic potency of lidocaine without any major influences on the cardiovascular system when locally injected into the oral mucosa.

Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory responses in the injected region.

BACKGROUND: Dexmedetomidine, a highly selective agonist of α2-adrenoceptors, is a commonly used sedative; however, a potent anti-inflammatory effect has also been found. In the present study we evaluated the inhibitory effect of locally injected dexmedetomidine on inflammatory responses in the injected region. METHODS: Local inflammation was induced in the hindpaws of male mice (aged 6-8 weeks) by intraplantar injection of lambda-carrageenin. To offset the central effect of tested agents, different agents were blindly injected into the left and right paws in the pairs of comparison. The effect of dexmedetomidine on edema (increase in paw volume), the accumulation of leukocytes, and production of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) were evaluated after carrageenin injection, using water displacement plethysmometry, histological imaging, immunohistochemistry, and Western blotting analysis. Furthermore, we also evaluated the effect of yohimbine, a full antagonist of α2-adrenoceptors, and phenylephrine, an agonist of the α1-adrenoceptor, on dexmedetomidine's action on inflammatory responses. RESULTS: Paw volume and amount of leukocytes in the injected region significantly increased after the injection of carrageenin. Similarly, TNF-α and COX-2 production was found in the subcutaneous region injected with carrageenin, 4 hours after injection. Dexmedetomidine significantly inhibited all increases in paw volume, leukocytes, and production of TNF-α and COX-2. Furthermore, yohimbine significantly antagonized the anti-inflammatory effects of dexmedetomidine, whereas phenylephrine did not significantly alter them. CONCLUSIONS: The findings suggest that locally injected dexmedetomidine exhibits an anti-inflammatory effect against local acute inflammatory responses, mediated by α2-adrenoceptors.

Midazolam is associated with delay in recovery and agitation after ambulatory general anesthesia for dental treatment in patients with disabilities: a retrospective cohort study.

PURPOSE: Some patients with intellectual disabilities (IDs) who undergo total intravenous anesthesia (TIVA) have complications associated with the anesthesia such as prolonged recovery. The purposes of this study were to estimate the frequency of TIVA complications among patients with IDs and to identify factors associated with TIVA complications. MATERIALS AND METHODS: This study was designed as a retrospective cohort study. Study samples were selected from the clinical records of patients with IDs who underwent ambulatory general anesthesia in a special dental clinic at the Okayama University Hospital, Okayama, Japan. Predictor variables were patient background, anesthesia-related variables, and dental treatment. Outcome variables were delayed recovery and the complication of agitation. Factors affecting delayed recovery and complications were examined with multivariable analysis. RESULTS: We enrolled 106 cases (81 male and 25 female patients) in this study. The mean age was 23.9 years. Serious complications were not observed in any cases. The amount of intravenous midazolam was an independent determinant of delayed recovery. Oral midazolam contributed to delayed recovery, although it is very useful for induction in patients with a high level of fear. Oral midazolam and a younger age were independent predictors of agitation. CONCLUSIONS: Intravenous midazolam may not have an advantage in ambulatory general anesthesia. Oral midazolam contributes to delayed recovery and is an independent predictor of agitation.

Combination of midazolam and a cyclooxygenase-2 inhibitor inhibits lipopolysaccharide-induced interleukin-6 production in human peripheral blood mononuclear cells.

CONTEXT: Interleukin-6 (IL-6) plays an important role in immune and inflammatory responses. Midazolam has been reported to modulate IL-6 response. Cyclooxygenase (COX) inhibitors, which are used together with midazolam in some patients undergoing surgery, also modulate it. We hypothesized that their combination results in eliciting the synergistical effect on the IL-6 response. OBJECTIVE: The aim of the present study was to evaluate the effect of the combination of midazolam and a COX inhibitor on IL-6 production. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and incubated with lipopolysaccharide (LPS), midazolam, and/or COX inhibitors, including indomethacin, SC-560, a COX-1 selective inhibitor, and NS-398, a COX-2 selective inhibitor. The supernatant concentrations of IL-6 and prostaglandins (PGs), including PGE2, PGF2α, PGD2, and 15-deoxy-Δ¹²,¹4-prostaglandin J2 (15dPGJ2) were measured. RESULTS: Midazolam had no effect on IL-6 production in the cells incubated for 12 h, and any COX inhibitors also had no effect. However, the combination of midazolam and NS-398 significantly inhibited it. Midazolam raised the concentration of 15dPGJ2 in the supernatant of the cells, but not the concentration of other PGs. DISSCUSSION AND CONCLUSION: The results in the present study demonstrated that the combination of midazolam and a COX-2 inhibitor inhibited LPS-induced IL-6 production in human PBMCs even if each drug separately did not have any effect on it. The finding suggests that their combination is effective against excessive IL-6 production such as severe inflammatory response and that the effect of midazolam on IL-6 production is possibly elicited via 15dPGJ2.

Extreme tooth abnormalities and treatment under general anesthesia in a child with chronic GVHD surviving relapse of acute lymphoblastic leukemia.

Treatment for acute lymphoblastic leukemia (ALL) mainly consists of chemotherapy, irradiation and bone marrow transplantation. In terms of long-term treatment effects, dental abnormalities and chronic graft-versus host disease (GVHD) are problems. We present a patient surviving relapse of ALL at one year of age. He had extreme dental abnormalities and multiple caries. Most of his permanent teeth were abnormal, and multiple caries were observed. Since he had a strong vomiting reaction to dental treatment, general anesthesia was given. During the general anesthesia, much sputum was aspirated because of chronic GVHD. His dental condition was worse than other cases reported previously. Since the survival rate has increased recently, the dental effects of ALL treatment have become significant. Especially, in patients undergoing total body irradiation at under 2 years of age, it is highly likely that dental problems will occur in the future.

Oxidative changes in the rat brain by intraperitoneal injection of ferric nitrilotriacetate.

Iron is known to be involved in neuronal diseases such as neurodegenerative diseases, brain ischemia and epilepsy. However, it is unclear if a high level of peripheral iron induces these pathological conditions. Since ferric nitrilotriacetate (Fe-NTA), a low molecule iron chelate, causes kidney carcinoma and diabetes in animals due to its strong and unique oxidative stress, it is also considered to cause pathological conditions in the brain. Therefore, we studied brain changes after intraperitoneal (i.p.) injection of Fe-NTA. We investigated iron distribution in the brain and evaluated heme oxygenase (HO)-1 mRNA, IL-6 mRNA and 4-hydroxy-2-nonenal (4-HNE) quantitatively. In addition, changes in muscarinic acetylcholine receptor mRNAs were measured. It was found that iron was localized in the cortex and the hypothalamus, but not in other areas of the brain. HO-1 was induced in both the cortex and hypothalamus, and the levels of IL-6 and 4-HNE were raised in the hypothalamus, but not in the cortex. In the cortex, expression in M1 and M2 mAChRs were suppressed. In conclusion, iron reached the brain parenchyma after i.p. injection of Fe-NTA, and Fe-NTA caused oxidative reactions and suppression of mAChRs in the brain.

Oral midazolam for sedation in minor oral operations in children: a retrospective study.

Our aim was to find out the optimal dose of oral midazolam to sedate children according to age. Thirty-five patients aged 10 or under who had minor oral operations under sedation with midazolam were enrolled. Correlations between age (X) and dose of midazolam (mg/kg; Y) were analysed by Pearson's correlation coefficient, and relations were fitted by simple regression. Doses of midazolam were significantly reduced as age increased (Y=0.969-0.04X; R=0.48) in the satisfactory group (n=25), whereas those in the overdose group (n=10) (patients who vomited, became agitated, or took some time to come round) were significantly higher, decreased with age, and showed a better correlation coefficient (Y=1.375-0.65X; R=0.78). These findings suggest that both the requirement and threshold of midazolam decreases with age.

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.