• Journal of the korean academy of Pediatric Dentistry
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• v.47 no.2
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• pp.228-234
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• 2020

Chloral hydrate (CH) has been used in sedation for over 100 years. CH was first synthesized in 1832, the sedative properties were observed in 1861. Because of its easy synthesis, its use was widespread since 1869. There is a record of the use of CH in children as early as 1894. Recently there have been many controversies about safety of CH. Because of the low cost and relatively safe experience CH has still been used for dental sedation in children. After the US FDA recommendation in 2006, US pharmaceutical companies no longer produce commercial CH. However, CH has been used in the form of suspensions prepared from raw materials in many areas of the United States, and reports of adverse events related to death have continued. CH is the most commonly used drug for sedation in Korea, and there have been some reports of side effects. Dexmedetomidine, propofol and midazolam were introduced as an alternative for CH. There are various limitations in using them in the pediatric dentistry area and there are many things to consider. The purpose of this review is to analyze the complications of CH and status of use in Korea, and to introduce alternatives to CH.

• Journal of Veterinary Clinics
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• v.33 no.4
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• pp.234-236
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• 2016

A 14 kg, 9-year-old, spayed female, Cocker Spaniel was presented to the Veterinary Medical Teaching Hospital of Seoul National University with a history of head tilt and circling. Otitis externa and media were diagnosed by computerized tomography, and total ear canal ablation was performed. In preanesthetic evaluation, systemic hypertension and second-degree atrioventricular block were observed, but there was no regurgitation through the heart valves. Systemic hypertension was managed with amlodipine (0.1 mg/kg, PO, BID) for the anesthesia. The dog was premedicated with cefazolin (22 mg/kg, IV) and midazolam (0.2 mg/kg, IV). Anesthesia was induced with alfaxalone (2 mg/kg, IV) and maintained with isoflurane and 100% oxygen following intubation. During surgery, vital signs (heart rate, respiratory rate, blood pressure, end tidal carbon dioxide partial pressure and body temperature) were maintained within normal ranges, but bradycardia was observed and corrected with glycopyrrolate (5 ug/kg IV, twice). During subcuticular suture, electrohemostasis was applied at the incision line, which was close to the trigeminal nerve. In no time at all, heart rate dramatically decreased from 110 to 60 beats per minute. No additional treatment was done because mean blood pressure was maintained above 70 mmHg. The heart rate recovered according to the decrease of end tidal isoflurane concentration and there were no complications associated with the anesthesia and surgery. Sudden bradycardia after electrical stimulation around the trigeminal nerve was considered as trigeminocardiac reflex (TCR). It is recommended to be careful of bradycardia from TCR when electrocautery is used in the craniofacial area during surgery.

• Tuberculosis and Respiratory Diseases
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• v.73 no.3
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• pp.151-161
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• 2012

Background: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. Methods: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. Results: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, $1.3{\pm}0.5{\mu}g/kg/min$; day 2, $0.9{\pm}0.4{\mu}g/kg/min$; p<0.01), and was significantly lower than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; $r_s$=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; $r_s$=0.77), and RASS and BIS ($r_s$=-0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. Conclusion: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability.

• Journal of Korean Academy of Nursing
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• v.31 no.2
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• pp.304-314
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• 2001

Major purposes of this study were to investigate the administration patterns of analgesics and sedatives in SICU and to identify the factors influencing the use of prn analgesics and sedatives by ICU nurses. The sample of this descriptive study was 50 adult patients in SICU and 53 ICU nurses. Patient's medical records were reviewed to investigate names, doses, the routes of administration, the interval of administration, and the type of prescription of sedatives and analgesics administered. Study medications were narcotics, hypnotics, and antipsychotics. To identify the factors influencing the use of prn analgesics and sedatives, 53 ICU nurses checked 9 items, and rank them from first to fifth. The selection of items was based on the previous studies and the experience of the investigator. The results of the study are as follows: 1. The mean age of the subjects was 53 years, 24 patients out of 50 subjects had received mechanical ventilation therapy. Most of the patients received neurosurgeries and abdominal surgeries. 2. For 4 days, 13 total study medications and combination of these were administered to the patients. Commonly prescribed drugs were Ketoprofen and Midazolam. Twenty six to fourty two percent of the patients did not receive any drugs for at least one day during the four days. 3. On the average, the study drugs were administerd 1.4 to 2.6 times per day during 4 days. 4. More than 50 percent of the prescription was as-needed (prn) except those of the POD 3. Fourteen percent of the patients did not have any prescription for sedation and pain control after surgery. 5. Examination of the frequency of sedatives and analgesics bolus administration revealed that a greater number of doses were given during daytime (from 7 am. to 7 pm.) than nighttime (from 7 pm. to 7 am.). The difference was significant at Alpha, .05. 6. First factor that most influenced nurses to administer sedatives and analgesics for intubated patients was the evaluation of patient's vital signs (51%). For non- intubated patients, the factors that nurses considered important were the patients' complaints of pain (64%) and evaluations of patients' vital signs (23%). In conclusion, the results of this study indicate that patients in SICU might not receive enough analgesics and sedatives to feel completely free from pain during the post operational period. Future study should be focused on the evaluation of the adequacy of current practice for pain and anxiety control in terms of the SICU patient's response.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.36-42
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• 1999

Background: The current maximal recommended doses of lidocaine are 7 mg/kg with $5\;{\mu}g/ml$ of epinephrine. But in clinical practice, sometimes more doses of lidocaine are required to produce adequate regional anesthesia. Method: Twenty-two healthy women patients were divided into two groups and pretreated with valium 5 mg p.o., morphine 5 mg i.m., and midazolam 2 mg i.v. before operation. Of these, 7 mg/kg of 2% lidocaine with $5\;{\mu}g/ml$ of epinephrine were given to 11 patients epidurally. Initial 3 ml of epinephrine mixed lidocaine was given as a test dose and remaining doses were given 5 ml/30 sec with 3 min intervals. Radial arterial blood were drawn at 5, 10, 15, 20, 30, 45, 60, 90, 120 min to measure plasma lidocaine concentrations. After confirming all of the peak plasma concentrations of 7 mg/kg lidocaine were absolutely under $5\;{\mu}g/ml$, the other 11 patients were given 10 mg/kg of 2% lidocaine with $5\;{\mu}g/ml$ of epinephrine epidurally and blood samplings were taken according to the same method of 7 mg/kg group. The peak plasma concentration ($C_{max}$), time to reach to $C_{max}$ ($T_{max}$), time to reach to $T_4$, maximal sensory block level, systemic toxicity, and vital sign changes were investigated. Result: $C_{max}$ was significantly higher in 10 mg/kg group ($5.1{\pm}1.3\;{\mu}g/ml$) than 7 mg/kg group($3.3{\pm}0.5\;{\mu}g/ml$), but $T_{max}$ ($10.5{\pm}2.7$ min vs $10.9{\pm}3.1$ min) was not different. Time to reach $T_4$ was significantly shorter in 10 mg/kg group ($9.5{\pm}2.7$ min) than 7 mg/kg group ($12.7{\pm}3.2$ min) but maximal sensory block level ($T_{3.7{\pm}0.7}$ vs $T_{2.7{\pm}1.0}$) was not different. In four patients of 10 mg/kg group, peak plasma concentrations exceeded $5\;{\mu}g/ml$, but no systemic toxicities appeared. No significant vital sign changes were observed. Conclusion: The current maximal recommended doses of lidocaine, merely based on body weight are not always appropriate. Further studies are needed to determine more precise guideline of maximal doses that include various pharmacokinetic components.

• Molecules and Cells
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• v.38 no.12
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• pp.1064-1070
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• 2015

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO ($0.1-0.5{\mu}m$), a specific mitochondrial antioxidants, and cyclosporin A ($1-5{\mu}m$), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam ($1-50{\mu}m$), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1659-1664
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• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.334-339
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• 2007

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

• Journal of Dental Anesthesia and Pain Medicine
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• v.23 no.2
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• pp.101-110
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• 2023

Background: Dentists make various efforts to reduce patients' anxiety and fear associated with dental treatment. Dental sedation is an advanced method that dentists can perform to reduce patients' anxiety and fear and provide effective dental treatment. However, dental sedation is different from general dental treatment and requires separate learning, and if done incorrectly, can lead to serious complications. Therefore, sedation is performed by a limited number of dentists who have received specific training. This study aimed to investigate the proportion of dentists who practice sedation and the main sedatives they use in the context of the Republic of Korea. Methods: We used the customized health information data provided by the Korean National Health Insurance. We investigated the number of dental hospitals or clinics that claimed insurance for eight main sedatives commonly used in dental sedation from January, 2007 to September, 2019 at the Health Insurance Review and Assessment Service. We also identified the changes in the number of dental medical institutions by region and year and analyzed the number and proportion of dental medical institutions prescribing each sedative. Results: In 2007, 302 dental hospitals prescribed sedatives, and the number increased to 613 in 2019. In 2007, approximately 2.18% of the total 13,796 dental institutions prescribed sedatives, increasing to 3.31% in 2019. In 2007, 168 institutions (55.6%) prescribed N₂O alone, and in 2019, 510 institutions (83.1%) made claims for it. In 2007, 76 (25.1%) hospitals made claims for chloral hydrate, but the number gradually decreased, with only 29 hospitals (4.7%) prescribing it in 2019. Hospitals that prescribed a combination of N₂O, chloral hydrate, and hydroxyzine increased from 27 (8.9%) in 2007 to 51 (9%) in 2017 but decreased to 38 (6.1%) in 2019. The use of a combination of N₂O and midazolam increased from 20 hospitals (6.6%) in 2007 to 51 hospitals (8.3%) in 2019. Conclusion: While there is a critical limitation to the investigation of dental hospitals performing sedation using insurance claims data, namely exclusion of dental clinics providing non-insured treatments, we found that in 2019, approximately 3.31% of the dental clinics were practicing sedation and that N₂O was the most commonly prescribed sedative.

• Journal of Dental Anesthesia and Pain Medicine
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• v.24 no.3
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• pp.187-193
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• 2024

Background: Patients with autism spectrum disorder (ASD) present challenges in dental treatment cooperation owing to deficits in communication skills and social interaction. Behavioral guidance, sedation, and general anesthesia may be employed to ensure the quality of dental care for individuals with ASD. This study aimed to examine the trends in dental treatment for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital, an oral health center for the disabled in the Gyeonggi region, over the past 10 years. Methods: This study utilized the order communication system to gather data on sex, age, cooperation level, number of quadrants treated, and administration of sedation or general anesthesia for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital between January 2013 and December 2022. Results: The total number of patients with ASD increased annually, possibly due to an increase in ASD prevalence and the hospital's designation as a center for disabled oral health. General anesthesia was predominant before 2017, with a shift towards N₂O-O₂ sedation. The most common age group for sedation or general anesthesia was 6-9 years, with a higher prevalence in males than in females. Notably, N₂O-O₂ and midazolam sedation resulted in better cooperation and fewer treated teeth than general anesthesia. Conclusion: This study highlights the evolving trends in dental treatment for individuals with ASD, indicating a shift towards outpatient methods, particularly N₂O-O₂ sedation. The sex distribution aligns with national statistics, emphasizing a higher prevalence of ASD in males than in females. These findings underscore the need for further research to establish evidence-based guidelines for optimal dental care strategies tailored to the unique needs of individuals with ASD.