• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.2
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• pp.91-99
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• 2019

Background: The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods: The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results: ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions: We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.117-128
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• 2022

Background: Moderate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times. Methods: In this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups. Results: Eighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO₂ was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO₂ levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05). Conclusion: The combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.

• Journal of The Korean Dental Society of Anesthesiology
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• v.10 no.2
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• pp.166-171
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• 2010

Background: Controlled hypotension is used to reduce bleeding and improve surgical conditions during surgery. Nicardipine and remifentanil have been used to induce controlled hypotension in healthy patients. This study compared controllability of nicardipine and remifentanil on hemodynamic stability during controlled hypotension. Methods: Forty healthy patients scheduled for orthognathic two jaw surgery were randomly allocated to nicardipine (group N) and remifentanil (group R) group. After induction of anesthesia, group N (n = 20) was infused with nicardipine to induce hypotension and group R (n = 20) was infused with remifentanil. Mean arterial pressure (MAP) and heart rate (HR) were measured over 5 minute interval. Surgical field rating and blood loss were measured after surgery. Results: HR was lower in group R than group N. MAP was maintained at 50-60 mmHg during controlled hypotension but the fluctuation of blood pressure and HR were more frequent in group N than group R. There were no significant differences in the surgical field rating and blood loss between the groups. Conclusions: Nicardipine and remifentanil enabled controlled hypotension and provided good surgical conditions, but the fluctuation of hemodynamic parameters was more frequent in nicardipine group.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.1
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• pp.65-69
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• 2017

Patients with severe gag reflex (SGR) have difficulty getting the treatment they require in local clinics, and many tend to postpone the start of their treatment. To address this problem, dentists have used behavioral techniques and/or pharmacological techniques for treatment. Among the pharmacological methods available, propofol IV sedation is preferred over general anesthesia because it is a simpler procedure. Propofol in combination with remifentanil is characterized by stable sedative effects and quick recovery, leading to a deep sedation. Remifentanil acts to reduce the pain caused by lipid-soluble propofol on injection. The synergistic effects of propofol-remifentanil include reduction in the total amount of drug required to achieve a desired sedation level and anti-emetic effects. In this case report, we outline how the use of propofol-remifentanil IV sedation enabled us to successfully complete a wide range of dental treatments in a patient with SGR.

• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.3
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• pp.89-94
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• 2013

Background: Various strategies have been studied to reduce the propofol injection pain. This study was designed to find out effect-site target concentration (Ce) of remifentanil at which there was a 50% probability of preventing the propofol injection pain (EC50). Methods: Anesthesia was induced with a remifentanil TCI (Minto model). The Ce of remifentanil for the first patient started from 2.0 ng/ml. The Ce of remifentanil for each subsequent patient was determined by the response of the previous patient by Dixon up-and-down method with the interval of 0.5 ng/ml. After the remifentanil reached target concentrations, propofol was administered via a target-controlled infusion system based on a Marsh pharmacokinetic model using a TCI device (Orchestra$^{(R)}$; Fresenius-Vial, Brezins, France). The dose of propofol was effect site target-controlled infusion (TCI) of $3{\mu}g/ml$. Results: The EC50 of remifentanil to prevent the propofol injection pain was $1.80{\pm}0.35ng/ml$ by Dixon's up and down method. Conclusions: The EC50 of remifentanil to blunt the pain responses to propofol injection was $1.80{\pm}0.35ng/ml$ for propofol TCI anesthesia.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.5
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• pp.253-260
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• 2019

Background: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B ($NF-{\kappa}B$) and p38 and the expression of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$, cyclooxygenase (COX)2, and prostaglandin E $(PGE)_2$ were quantified using western blotting and RT-PCR, respectively. Results: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of $NF-{\kappa}B$, and expression of COX2 and $PGE_2$ in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of $IL-1{\beta}$ and $TNF-{\alpha}$ expression was also observed with RT-PCR. Conclusion: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.

• International Journal of Contents
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• v.11 no.2
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• pp.69-73
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• 2015

This study was performed to determine the optimal doses of alfentanil or remifentanil (effect-site concentrations) required to prevent pain and other suffering after abdominal general surgery in ICU patients. A total of 52 general abdominal surgical patients (ASA IIIII) requiring artificial ventilatory care in the ICU were provided with either alfentanil (24 patients) or remifentanil (28 patients) through target controlled infusion (TCI). Alfentanil and remifentanil concentrations were titrated up and down until the pain score became less than 3 (VAS; Visual Analogue Score < 3). The effect-site concentrations (ng/ml) of alfentanil or remifentanil required to adequately control postoperative pain in the ICU were 64 +/- 12 and 1.9 +/- 0.5 for intubation with artificial ventilation, 57 +/- 9 and 1.7 +/- 0.7 for intubation with spontaneous ventilation, and 41 +/- 10 and 1.2 +/- 0.5 after extubation, respectively. Pain scores and the corresponding opioid concentrations were independent from respiratory condition. The three effect-site concentrations of alfentanil and remifentanil obtained from this clinical trial using the TCI technique can be a guideline in the administration of the same opioids to relieve the discomfort of ICU patients who have undergone abdominal general surgery.

• Journal of Dental Anesthesia and Pain Medicine
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• v.16 no.4
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• pp.263-271
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• 2016

Background: Bone injury is common in many clinical situations, such as surgery or trauma. During surgery, excessive reactive oxygen species (ROS) production decreases the quality and quantity of osteoblasts. Remifentanil decreases ROS production, reducing oxidative stress and the inflammatory response. We investigated remifentanil's protective effects against $H_2O_2$-induced oxidative stress in osteoblasts. Methods: To investigate the effect of remifentanil on human fetal osteoblast (hFOB) cells, the cells were incubated with 1 ng/ml of remifentanil for 2 h before exposure to $H_2O_2$. For induction of oxidative stress, hFOB cells were then treated with $200{\mu}M$ $H_2O_2$ for 2 h. To evaluate the effect on autophagy, a separate group of cells were incubated with 1 mM 3-methyladenine (3-MA) before treatment with remifentanil and $H_2O_2$. Cell viability and apoptotic cell death were determined via MTT assay and Hoechst staining, respectively. Mineralized matrix formation was visualized using alizarin red S staining. Western blot analysis was used to determine the expression levels of bone-related genes. Results: Cell viability and mineralized matrix formation increased on remifentanil pretreatment before exposure to $H_2O_2$-induced oxidative stress. As determined via western blot analysis, remifentanil pretreatment increased the expression of bone-related genes (Col I, BMP-2, osterix, and $TGF-{\beta}$). However, pretreatment with 3-MA before exposure to remifentanil and $H_2O_2$ inhibited remifentanil's protective effects on hFOB cells during oxidative stress. Conclusions: We showed that remifentanil prevents oxidative damage in hFOB cells via a mechanism that may be highly related to autophagy. Further clinical studies are required to investigate its potential as a therapeutic agent.

• Journal of Dental Anesthesia and Pain Medicine
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• v.15 no.4
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• pp.221-227
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• 2015

Background: Endotracheal intubation induces clinically adverse cardiovascular changes. Various pharmacological strategies for controlling these responses have been suggested with opioids being widely administered. In this study, the optimal effect-site concentration (Ce) of remifentanil for minimizing hemodynamic responses to fiberoptic nasotracheal intubation was evaluated. Methods: Thirty patients, aged 18-63 years, scheduled for elective surgery were included. Anesthesia was induced with a propofol and remifentanil infusion via target-controlled infusion (TCI). Remifentanil infusion was initiated at 3.0 ng/mL, and the response of each patient determined the Ce of remifentanil for the next patient by the Dixon up-and-down method at an interval of 0.5 ng/mL. Rocuronium was administered after propofol and remifentanil reached their preset Ce; 90 seconds later fiberoptic nasotracheal intubation was initiated. Non-invasive blood pressure and heart rate (HR) were measured at pre-induction, the time Ce was reached, immediately before and after intubation, and at 1 and 3 minutes after intubation. The up-and-down criteria comprised a 20% change in mean blood pressure and HR between just prior to intubation and 1 minute after intubation. Results: The median effective effect-site concentration ($EC_{50}$) of remifentanil was $3.11{\pm}0.38ng/mL$ by the Dixon's up-and-down method. From the probit analysis, the $EC_{50}$ of remifentanil was 3.43 ng/mL (95% confidence interval, 2.90-4.06 ng/mL). In PAVA, the EC50 and EC95 of remifentanil were 3.57 ng/mL (95% CI, 2.95-3.89) and 4.35 ng/mL (95% CI, 3.93-4.45). No remifentanil-related complications were observed. Conclusions: The $EC_{50}$ of remifentanil for minimizing the cardiovascular changes and side effects associated with fiberoptic nasotracheal intubation was 3.11-3.43 ng/mL during propofol TCI anesthesia with a Ce of 4 ug/mL.

• Journal of The Korean Dental Society of Anesthesiology
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• v.14 no.2
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• pp.101-106
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• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.