신경외과 수술 환자의 기관내 튜브 발관을 위한 Isoflurane의 호기말 최소 폐포 농도 측정

김시오 慶北大學校 醫科大學 1996 慶北醫大誌 Vol.37 No.1

목적 : 이 연구는 두부손상 신경외과 수술환자의 기관내 튜브발관에 의한 고혈압과 빈맥으로 뇌압상승을 초래하는 것을 방지할 목적으로, 마취가 깊게 유지된 상태에서의 기관내 튜브 발관시의 호기말 최소 폐포 농도 측정을 하기 위하여 시행하였다. 대상 및 방법 : 의식장애가 심하지 않고 계획수술로 진행된 뇌동맥류 환자 23명을 대상으로 수술이 끝난 후 미리 정해진 농도의 isoflurane을 최소한 15분간 투여후 기관내 튜브를 발관하였을때 환자가 기침, 숨 참기, 기도 폐색, 후두경련등이 있는 경우 불만족(unsatisfactory)하다고 하고 결과를 각각의 정해진 isoflurane농도에 만족과 불만족으로 표시한 후 50% 환자에서 만족하는 호기말 isoflurane의 농도를 구하였다. 결과 : 기관내 튜브 발관시 50%의 환자에서 만족하는 호기말 isoflurane의 농도는 0.90%이었고 이때의 standard error는 ±0.17이었다. 결론 : 호기말 isoflurane의 농도 0.90%에서 50%의 두부손상 신경외과 수술환자에서 기침등의 원치 않는 부작용 없이 기관내 튜브를 발관할 수 있다고 하겠다. Background : Tracheal extubation is also as important as tracheal intubation in anesthetic management. So deeply anesthetized extubation is recommended not to produce hypertension and tachycardia which is harmful in neurosurgical patients. This study was done to determine a minimum alveolar con centration of isoflurane for tracheal extubation in neurosurgical patients. Methods : Twenty-three patients with minimum neurologic deficit were undergone aneurysmal clip ping operation. At the end of surgery a predetermined end-tidal concentration was achieved, a steady state maintained for at least 15min, and the trachea was extubated. In patients who coughed or bucked on the endotracheal tube during suctioning of oropharynx, or who moved or coughed within 1 min of tracheal extubation, or who developed breath-holding or laryngospasm after tracheal extubation, extubation was considered unsatisfactory. Results were plotted as satisfactory or unsatisfactory extubation versus end-tidal isoflurane concentration. End-tidal concentration of isoflurane at which tracheal extubation was accomplished in 50% of pa tients satisfactorily was estimated by probit analysis. Results : The minimum alveolar concentrations of isoflurane at which 50% of patients has satisfactory tracheal extubation was found to be 0.90% (standard error ±0.17). Conclusions : In 50% of anesthetized neurosurgical patients tracheal extubation may be accomplished without coughing or moving at 0.90% end-tidal isoflurane concentration.

Isoflurane Induces Transient Anterograde Amnesia through Suppression of Brain-Derived Neurotrophic Factor in Hippocampus

Cho, Han-Jin,Sung, Yun-Hee,Lee, Seung-Hwan,Chung, Jun-Young,Kang, Jong-Man,Yi, Jae-Woo The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.53 No.3

Objective : Transient anterograde amnesia is occasionally observed in a number of conditions, including migraine, focal ischemia, venous flow abnormalities, and after general anesthesia. The inhalation anesthetic, isoflurane, is known to induce transient anterograde amnesia. We examined the involvement of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in the underlying mechanisms of the isoflurane-induced transient anterograde amnesia. Methods : Adult male Sprague-Dawley rats were divided into three groups : the control group, the 10 minutes after recovery from isoflurane anesthesia group, and the 2 hours after recovery from isoflurane anesthesia group (n=8 in each group). The rats in the isoflurane-exposed groups were anesthetized with 1.2% isoflurane in 75% nitrous oxide and 25% oxygen for 2 hours in a Plexiglas anesthetizing chamber. Short-term memory was determined using the step-down avoidance task. BDNF and TrkB expressions in the hippocampus were evaluated by immunofluorescence staining and western blot analysis. Results : Latency in the step-down avoidance task was decreased 10 minutes after recovery from isoflurane anesthesia, whereas it recovered to the control level 2 hours after isoflurane anesthesia. The expressions of BDNF and TrkB in the hippocampus were decreased immediately after isoflurane anesthesia but were increased 2 hours after isoflurane anesthesia. Conclusion : In this study, isoflurane anesthesia induced transient anterograde amnesia, and the expressions of BDNF and TrkB in the hippocampus might be involved in the underlying mechanisms of this transient anterograde amnesia.

Effects of Isoflurane/Remifentanil and Isoflurane/Fentanyl Anesthesia in Beagle Dogs

박지영,오승준,이해범,정성목 한국임상수의학회 2015 한국임상수의학회지 Vol.32 No.2

This study was performed to compare two opioid drugs with isoflurane and to determine the difference between isoflurane/remifentanil anesthesia and isoflurane/fentanyl anesthesia in terms of the anesthetic effects in beagle dogs. Isoflurane was maintained at 0.5 MAC, and the opioid drug was administered as a constant rate infusion. The anesthesia was maintained for 2 hours, and isoflurane and opioid drugs were discontinued 2 hours later. After discontinuing the anesthetics, the extremity movement time, eye global positioning time, gag reflex time, head up time, sternal recumbency time, standing time, walking time and complete recovery times were recorded for each dog. Both of the studied anesthetic protocols were suitable in beagle dogs because the anesthetic status was well maintained until the end of the procedure, and rapid recovery times were demonstrated in this experiment. And this study shows that the isoflurane/remifentanil group was more reliable than the isoflurane/fentanyl group because the recovery time CV was lower. Therefore, isoflurane/remifentanil combination anesthesia could be a better choice than isoflurane/ fentanyl anesthesia if the patient is severely ill and stable recovery time is needed.

Experimental Research Article : Preconditioning of isoflurane on spinal cord ischemia can increase the number of inducible nitric oxide synthaseexpressing motor neurons in rat

Yun Hee Sung,Sang Hak Lee,Joon Kyung Sung,Jin Hee Han,Hong Kim,Chang Ju Kim,Jong Man Kang 대한마취과학회 2010 Korean Journal of Anesthesiology Vol.58 No.1

Background: Spinal cord ischemia with resulting paraplegia remains one of the most common complications after repair of thoracoabdominal aortic aneurysms or dissection. Inducible nitric oxide synthase (iNOS) is known to have both neuroprotective and neurotoxic effects in the central nervous system. We investigated the possible relationship between the effect of pre-ischemic isoflurane exposure on mild spinal cord ischemia and the inducible nitric oxide synthase (iNOS) expression by using iNOS-specific antibody and pyrrolidinedithio carbamate (PDTC), NF-κB inhibitor, in the ventral horn of spinal cord in rats. Methods: The animals were divided into five groups (n = 6 in each group): sham group, control group, PDTC-treated group, isoflurane-treated group, and PDTC/isoflurane-treated group. In the PDTC-treated groups, 2% 100 mg/kg PDTC was administered intraperitoneally at 1 h before operation and at 24 h and 48 h after reperfusion. The rats in the isoflurane-treated groups received 30 min inhalation of 2.8% isoflurane at 24 h before spinal cord ischemia. Immunohistochemistry was performed to detect iNOS expression in the motor neuron of the ventral horn in spinal cord. Results: Preconditioning with isoflurane increased the iNOS expression when compared to the control group (P < 0.05), whereas pre-treatment with both PDTC and isoflurane significantly decreased the iNOS expression compared to isoflurane-treated group (P < 0.05). Conclusions: Pre-ischemic isoflurane exposure was related with increase of the iNOS expression via a pathway modulated by NF-κB. iNOS may act as an important mediator of delayed preconditioning with isoflurane for the protective effect against spinal cord ischemia. (Korean J Anesthesiol 2010; 58: 70~75)

Isoflurane은 인간 배아줄기세포에서 분화된 심장근육 전구세포의 산화스트레스에 의한 세포자멸사를 감소시킨다

구본욱,김진희,한성희,김미현,백지석 대한마취통증의학회 2013 Anesthesia and pain medicine Vol.8 No.3

Background: Despite the great potential of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) in the cardiac cell transplantation, the low graft survival still remains as one of the main obstacles in the way to its clinical application. We investigated whether pre-treatment with isoflurane can decrease apoptosis of hESC-derived CPCs under oxidative stress. Methods: Undifferentiated hESCs were differentiated in suspension media with 20% fetal bovine serum (FBS) and 20 ng/ml of bone morphogenetic protein (BMP)-4 through embryoid bodies and grown onto Matrigel-coated plates for 2 or 3 weeks. To identify the differentiated CPCs, immunostaining for nonspecific transcriptional marker (Nkx2.5) was performed. The CPCs were exposed to oxidative stress induced by Fenton reaction with H2O2 and FeSO4. For anesthetic preconditioning, CPCs were exposed to isoflurane (5 vol%) in an isolated chamber. Apoptosis of CPCs was determined by TUNEL staining and detection of activated caspase-3 cell. Results: hESC-derived CPCs stained with Nkx2.5 were 95 ± 3%of total cell number. Concentration of isoflurane in the media was 1.1 mM (2.2 MAC). Pretreatment of CPCs with isoflurane showed a significantly lower TUNEL (+) ratio as well as activated caspase-3cell number compared to control. Conclusions: Isoflurane decreased hESC-derived Nkx2.5+ CPCs apoptosis induced by oxidative stress. This result suggests that anti-apoptotic effect may play a role in the protective effect of isoflurane.

Isoflurane's Effect on Intraoperative Systolic Left Ventricular Performance in Cardiac Valve Surgery Patients

김주덕,손일순,권원경,성태윤,Hanafi Sidik,김가람,강현,방지연,여귀은,이동규,김태엽 대한의학회 2018 Journal of Korean medical science Vol.33 No.4

Background: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S′) in patients undergoing cardiac surgery. Methods: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S′ at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 μg/min/kg) by using transesophageal echocardiography. Results: Mean S′ values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8–12.2), 9.5 (8.3–10.8), and 8.4 (7.3–9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were −1.0 (−1.6, −0.3), −1.1 (−1.7, −0.6), and −2.1 (−3.1, −1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 μg/kg/min at T1, T2, and T3, respectively, P < 0.001). Conclusion: Isoflurane increments (1.0–2.0 MAC) dose-dependently reduced LV systolic long- axis performance during cardiac surgeries with a preserved preoperative systolic function.

Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury

Wang, Kun,Kong, Xiangang The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related $K^+$ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1.

Isoflurane의 최소폐포농도에 관한 척수강 칼슘통로 차단제의 효과

윤명하,최정일,정성욱 대한마취과학회 2002 Korean Journal of Anesthesiology Vol.43 No.5

Background: Much evidence suggests that the spinal cord may be an important anesthetic action site. Volatile anesthetics have been shown to inhibit neurotranmitter release by inhibition of intracellular calcium entry. Many types of calcium channels (L, N, P, Q, T) were demonstrated in the dorsal horn of the spinal cord. Therefore, the aim of this study was to determine whether intrathecal calcium channel antagonists may change the minimum alveolar concentration (MAC) of isoflurane in rats and examine the role of spinal calcium channels for anesthetic action of isoflurane. Methods: In Sprague-Dawley rats, the MAC of isoflurane was determined by the tail-clamp technique. First, control MAC was determined and then changes of control MAC were observed after intrathecal administration of calcium channel antagonists. Change of mean arterial pressure (MAP) and general behavior were also examined following intrathecal delivery of calcium antagonists. Results: Neither abnormal behavior nor change of MAP occured after intrathecal of all types of calcium channel antagonists. All drugs decreased the MAC of isoflurane. Conclusions: These results suggested that L, N, P, Q and T types of the calcium might play an important role in determining the MAC of isoflurane in the spinal cord. (Korean J Anesthesiol 2002; 43: 661~666)

Up-regulation of miR-106a targets LIMK1 and contributes to cognitive impairment induced by isoflurane anesthesia in mice

Ning Zhang,Weiguang Ye,Tianlong Wang,Hui Wen,Lan Yao 한국유전학회 2020 Genes & Genomics Vol.42 No.4

Background Postoperative cognitive dysfunction (POCD) had a great relationship with anesthesia during surgery, and miRNAs have been found involved in anesthesia-induced cognitive impairment. Objective To explore the role and potential mechanism of miR-106a in isoflurane anesthesia-induced cognitive impairment. Methods Adult male mice were treated with isoflurane anesthesia; Morris water maze tests and fear conditioning tests were performed; and expression levels of miR-106a and LIMK1 were determined by quantitative real-time PCR (qRT-PCR) and western blot. Dual luciferase reporter assay was used to determine the binding of miR-106a and 3’UTR of LIMK1. To verify the role of miR-106a, antagomir of miR-106a were intrahippocampally injected. Finally, expression of BCL2 apoptosis regulator (Bcl-2), LIM domain kinase 1 (LIMK1), BCL2-associated X, apoptosis regulator (Bax) and cleaved caspase3 was determined by western blot. Results In isoflurane anesthesia-treated group (IS), the percentage of target quadrant dwell time was significantly lower and the escape latency was significantly higher than in the control group (sham), and the freezing behavior of IS was significantly less in contextual fear conditioning tests. Expression levels of miR-106a were increased and those of LIMK1 were decreased in response to IS. Dual luciferase reporter assay showed that miR-106a could bind with the 3’UTR of LIMK1. Decreased expression levels of miR-106a improved the cognitive impairment of the mice treated with isoflurane. Intrahippocampally injected antagomir of miR-106a also increased LIMK1 and Bcl-2 levels, decreased the BAX and cleaved caspase3 expression levels in the mice treated with isoflurane. Conclusion Decrease of LIMK1 expression by miR-106a played an important role in isoflurane anesthesia-induced cognitive impairment.

임상연구 : 제왕절개술 초기 Isoflurane의 투여 방법이 Bispectral Index 수치에 미치는 영향: 과압을 이용한 호기말 또는 기화기 농도에 비교

이해진 ( Hae Jin Lee ),김종분 ( Jong Bun Kim ),최혜진 ( He Jin Choi ) 대한마취과학회 2007 Korean Journal of Anesthesiology Vol.52 No.2

Background: Patients undergoing a cesarean section under general anesthesia are at risk of intraoperative awareness due to the use of low concentration of volatile anesthetics used. This study investigated the effect of different methods for administering isoflurane on the anesthetic adequacy using bispectral index (BIS) in the early period of cesarean section. Methods: Eighty-two parturients undergoing a cesarean section were randomly assigned to receive 1 vol% isoflurane (Group EQ), 1.5 vol% isoflurane for the first 5 minutes and 1 vol% for the next 5 minutes (Group CO), 0.6 vol% end-tidal isoflurane immediately after intubation (Group ET). Thiopental 4 mg/kg was used to induce anesthesia. The bispectral index value, systolic and diastolic arterial pressure, heart rate and end-tidal concentration of isoflurane were recorded every minute for 10 minutes after intubation. Results: There were no significant differences in the systolic and diastolic pressure, and heart rate between the groups. The BIS values from 1 to 8 minutes after intubation were significantly lower in the ET group than in the EQ group. BIS values from 4 to 8 minutes after intubation were significantly lower in the CO group than in the EQ group. Conclusions: The administration of volatile anesthetics using the end-tidal concentration after thiopental induction shows the best anesthetic efficacy in the early period of cesarean section. This method may further reduce the level of intraoperative awareness. (Korean J Anesthesiol 2007; 52: 143~9)