• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.3
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• pp.169-172
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• 2003

Purpose : We examined the relationship between BIS, sedation score and plasma midazolam concentration to verify the usefulness of BIS to assess the patient's consciousness during sedation. Patients and Methods : Twenty-five young, healthy adult volunteers participated in this clinical study. Midazolam was administered intravenously up to 0.08 mg/kg to induce unconsciousness and we monitored the patient's physiological and conscious status until complete recovery from sedation. BIS and sedation score were measured before sedation, 10, 20, 30 minutes after midazolam administration. Plasma midazolam concentration was measured 10 minutes after midazolam administration. BIS was measured using A-2000 BISTM monitor (Aspect Medical Systems, USA) and the degree of sedation was evaluated with the sedation score. Results : The BIS score correlated with the sedation score (r = 0.676; P < 0.05). With the decreased plasma midazolam concentration, the correlation was better with sedation score (r = -0.656). Although BIS values did not correlate with calculated plasma concentration of midazolam (r = 0.467) at 10 minutes after midazolam administration, values after sedation were well distinguished from those before sedation. Conclusions : BIS is known for an effective predictor of patient's hypnotic state, and it is correlated with the sedation score. But, it doesn't always coincide with the clinical parameters of depth of sedation. So more attention is needed using BIS only during sedation, and it is advisable that the patient's consciousness is monitored with variable sedation score systems every several minutes.

• Bulletin of the Korean Chemical Society
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• v.19 no.5
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• pp.524-526
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• 1998

A sensitive and specific method is described for the determination of midazolam in human plasma. The drug was extracted from 1 mL of carbonate buffered plasma (pH 9.6) with 8 mL of diethyl ether. Famprofazone was used as internal standard. The organic phase was evaporated to dryness. The residue was dissolved in methanol for the direct analysis by gas chromatograph-nitrogen phosphorus detector system. In the concentration range of 1-5000 ng/mL, the calibration curve was linear. The coefficients of variation from the precision test were <6% at the range of the concentration of 0.10-2.00 μg/mL and the detection limit for midazolam in 1 mL of plasma was o.5 ng. This assay is more sensitive, selective, simple and rapid than earlier methods. Plasma midazolam concentrations were determined by this method after administration of midazolam.

• Journal of the korean academy of Pediatric Dentistry
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• v.32 no.3
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• pp.499-508
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• 2005

The purpose of this study were to evaluate the effect on the reversion of sedation induced by midazolam with flumazenil and to determine the plasma concentration of flumazenil according to the method of administration. Intranasal and intravenous flumazenil were administered to sedated health volunteers aged from 23 to 25 years, in doses typical of those used clinically to induce sedation with midazolam and for reversal with flumazenil. Objective assessment for degree of sedation and vital signs, plasma concentration were made for 2 hours period. 1. Systolic and diastolic blood pressure, $SpO_2$ were not changed by adminstration of flumazenil in sedated subject with midazolam, but pulse rate was increased temporarily. 2. Flumazenil showed the reversal of the sedative effect induced by midazolam regardless of administration methods. But intravenous administration showed more effect on the degree and the duration of reversion than intranasal administration with the exception of on set time. 3. Peak plasma concentration of flumazenil administered by intranasal route reached after 2 min and that of flumazenil administered by intravenous route was 4 min. Thus uptake of flumazenil did not showed any difference in accordance with the adminstration route. 4. Administration of flumazenil resulted in the temporary increase of midazolam plasma concentration.

• Journal of The Korean Dental Society of Anesthesiology
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• v.1 no.1 s.1
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• pp.21-25
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• 2001

연구배경: 임상적으로 진정법을 시행할 경우 뇌의 상태에 대한 접근은 매우 중요하다. 환자의 뇌에 대한 마취제의 영향을 측정하기 위해 개발된 Bispectral Index (BIS)는 환자의 진정을 방해하지 않고 객관적인 진정정도를 평가할 수 있다. 그러나 이는 항상 진정 깊이의 임상적인 척도와는 일치하지 않는다. 이번 연구에서는 진정법 시행시 환자의 진정 정도를 측정하기 위한 BIS의 유용성을 검증하기 위하여 BIS, 진정점수, 그리고 midazolam의 혈중 농도와의 관계를 연구하였다. 방법: 25명의 건강한 성인 지원자들을 대상으로 무의식을 유도하기 위하여 midazolam 0.08 mg/kg을 정맥으로 주입하였으며 환자의 의식 상태를 진정 회복 시까지 관하였다. BIS와 진정점수는 진정 전과, midazolam 투여 후 10, 20, 30분 간격으로 측정하였다. Midazolam의 혈중 농도는 주입 후 10분 경과 후에 정맥혈 채취 후 HPLC를 이용하여 측정하였다. BIS는 BISTM monitor (Aspect Medical Systems, USA)으로 측정하였으며 또한 진정 정도는 진정 점수로도 평가하였다. 결과: BIS 수치는 진정점수와 유의한 상관관계를 보였다(r = 0.676, p < 0.05). 혈중 midazolam 농도가 감소함에 따라 혈중 농도는 진정점수와 유의한 상관관계를 보였다(r = -0.656). Midazolam 투여 후 10분에서 BIS 수치와 midazolam의 혈중 농도는 유의한 상관관계를 보이지 않았지만(r =0.467) 진정 후 수치는 진정 전 수치와 명확히 구분되었다. 결론: BIS는 환자의 수면상태의 효과적인 척도로 알려져 있으며 진정점수와도 높은 상관관계를 보였다. 그러나 항상 진정 깊이를 나타내는 임상적인 척도와는 일치하지 않았다. 그러므로 진정법 시행동안 BIS 만을 사용하는 것은 더욱 많은 주의가 필요하며 매 주어진 시간마다 다양한 진정 점수 측정방법으로 환자의 의식을 감시하는 것이 추천된다.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.2
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• pp.159-167
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• 2002

The purpose of this study was to evaluate the efficacy and safety depending on the route of flumazenil, as an antagonist against midazolam. The subjects of this study were 15 volunteers of $22{\sim}24$ years old. They were sedated with midazolam 0.2mg/Kg intranasal spray, and then 40 minutes after midazolam administration, they were given flumazenil 0.2mg intranasal spray for their reversal. For evaluation of the efficacy and safety of intranasal spray for flumazenil, they were monitored with pulse-oxymeter(Nellcor symphony N-3000, Nellcor Puritan CO. USA) and electric sphygmomanometer (Heartcare 200, National CO. Japan), and were assessed themselves using visual analogue scale(VAS) for tranquilization, sleep, fatigue and attitude. All of these subjects were reduced completely without any undesired situations. The results from this study can be summarized as follows ; 1. Nasaly administered flumazenil using spray device produced much more rapid reduction than intravenously administered flumazenil, but soon after fell in more deep sedated state than intravenously administered flumazenil. 2. There were no considerable side effects or bad influence on vital signs of both nasaly administered flumazenil and intravenously administered flumazenil. These results suggested that the flumazenil administered nasaly using spray device for reversal, we could treat patients safely and effectively under conscious sedation using midazolam administration. But, We will have to research about its optimal dosages for flumazenil, used as intranasal spray for reversal agents against the midazolam by evaluating the blood plasma concentration of midazolam and flumazenil.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.16.1-16.9
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• 2016

Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

• 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.