Propofol과 Remifentanil을 이용한 목표농도조절 주입 전정맥마취에서 이중관 기관내관 삽관 시 혈역학적 반응을 억제하는 Remifentanil의 효과처 농도

허봉하 ( Bong Ha Heo ),윤명하 ( Myung Ha Yoon ),이형곤 ( Hyung Gon Lee ),김웅모 ( Woong Mo Kim ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.57 No.1

Background: This study was undertaken to determine the effect-site concentration of remifentanil for blunting hemodynamic responses to double lumen endobronchial intubation during target controlled infusion (TCI)-total intravenous anesthesia (TIVA) using 4.0 μg/ml of propofol with remifentanil. Methods: Sixty patients (American society of anesthesiologists physical status classification 1 or 2) were randomly allocated according to the target effect-site concentration of remifentanil (R3.0: remifentanil 3.0 ng/ml; R3.5: remifentanil 3.5 ng/ml; R4.0: remifentanil 4.0 ng/ml). The effect-site concentration of propofol at loss of consciousness was recorded. Mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS) were recorded at just before remifentanil administration (baseline), at the time of target effect site concentration of remifentanil and propofol, at just before intubation and 1, 2, 3 min after intubation. Results: MAP was significantly increased compared with baseline at 1, 2 min after intubation in R3.0, but was significantly decreased in R4.0. MAP of R3.5 was not different from the baseline after intubation. HR was significantly decreased compared with baseline at the time of target effect site concentration of propofol and immediate before intubation in R3.5 and R4.0. After intubation, HR was significantly increased compared with baseline at only 1 min after intubation and returned to the baseline in R3.0. However, HR was continuously decreased in R4.0. Conclusions: These findings suggest that effective target effect-site concentration of remifentanil for blunting hemodynamic responses to double lumen endotracheal intubation was 3.5 ng/ml during TCI-TIVA using 4.0 μg/ml of propofol with remifentanil. (Korean J Anesthesiol 2009; 57: 8~12)

중환자에서 Dexmedetomidine의 Opioid-Sparing Effect를 고려한 Remifentanil 용량 조절

한수정,김형숙,이정화,이은숙,이연주,조영재 한국병원약사회 2014 병원약사회지 Vol.31 No.4

Background : Since the ‘analgosedation’was emerged as an important concept forcritically ill patients, the recommendation for a combinational usage of remifentanil anddexmedetomidine as well as its usage has increased. Taking the opioid-sparing effect ofdexmedetomidine into account, the dosage of remifentanil can be reduced if the combination oftwo drugs is used for the purpose of analgosedation which may consequently lead to the reductionof total drug costs. However, no tapering protocol of remifentanil in case of dexmedetomidinecombined as sedative drug has been studied yet and there are no cost-effectiveness data for the opioid-sparing effect of dexmedetomidine. Methods : A retrospective cohort analysis was done on patients treated with remifentanil anddexmedetomidine at the medical intensive care unit (MICU) of a tertiary teaching hospital fromAugust 2013 to September 2013. The success rates of remifentanil reduction and cost reduction ofanalgesics were analyzed via the data of dosage and costs of remifentanil, dexmedetomidine andother rescue analgesics. Results : Of 63 patients admitted to the MICU, 29 patients were treated with remifentanil anddexmedetomidine for analgosedation under mechanical ventilator care and 10 patients weretreated with a half reduced dose of remifentanil. Eight (80%) patients succeeded in reducing theirdose of remifentanil since the used Richmond Agitation-Sedation Scale showed scores between-2and 0 and the numeric rating score for pain was maintained below 5. The rate of cost reductionwas 32.8% (from ￦159,059 to ￦105,283) in comparing the remifentanil-reduction succeeded groupto the failed group (p=0.044). The overall rate of cost reduction was 26.9% in the whole remifentanil-reduction trial group. Conclusions : The dose reduction of remifentanil was successfully achieved in critically illpatients under administration of remifentanil and dexmedetomidine, and it might be cost-effective. This study presents the possibility of an analgosedation adjustment that can be applied toMICU patients treated with both of dexmedetomidine and remifentanil.

임상연구 : Remifentanil과 Ketamine 전투여가 Propofol 정주 시 발생되는 혈관통에 미치는 영향

홍성욱 ( Seong Wook Hong ),곽경화 ( Kyung Hwa Kwak ) 대한마취과학회 2006 Korean Journal of Anesthesiology Vol.51 No.3

Background: There is a high incidence of pain associated with an intravenous injection of propofol, and different methods have been used in an attempt to minimize the incidence and severity of this pain. This study compared the effect of a ketamine pretreatment with that of a remifentanil pretreatment on the pain associated with a propofol injection. Methods: 225 ASA physical status 1-2 adult patients scheduled for elective surgery were enrolled into this randomized double blind study. The patients received 2 ml of saline (n = 45), 2 ml of ketamine 20 mg (n = 45), 2 ml of remifentanil 0.01 mg (n = 45), or 2 ml of remifentanil 0.02 mg (n = 45) or 2 ml of remifentanil 0.03 mg (n = 45) 30 seconds prior to administering 2 mg/kg of 1% propofol. An anesthesiologist who was blinded to the study asked the patients to evaluate the pain using a four-point scale (none, mild, moderate, severe). Results: The remifentanil 0.02 mg, remifentanil 0.03 mg and ketamine groups showed significantly less frequent and intense pain than the saline group (P < 0.05). The remifentanil 0.02 mg and 0.03 mg provided as much pain relief as ketamine (P > 0.05), but the remifentanil 0.01 mg did not (P < 0.05). There was a similar incidence of injection pain in the remifentanil 0.02 mg and remifentanil 0.03 mg groups. Conclusions: An intravenous remifentanil 0.02 mg or remifentanil 0.03 mg pretreatment is as effective in alleviating the pain associated with a propofol injection as a intravenous ketamine pretreatment. The remifentanil 0.03 mg pretreatment had a similar analgesic effect relative to the remifentanil 0.02 mg pretreatment. (Korean J Anesthesiol 2006; 51: 302~7)

Optimal dose of remifentanil for the prevention of hemodynamic responses during induction of anesthesia with desflurane

강효석,박혜진,백승민,김선오 대한마취통증의학회 2015 Anesthesia and pain medicine Vol.10 No.2

Background: This study was designed to determine the optimal dose of remifentanil single bolus for the prevention of cardiovascular disturbance due to both a rapid increase in desflurane concentration and stimulation by intubation. Methods: One hundred three adult patients were enrolled in this prospective, double-blind, randomized study. Before anesthesia induction, all patients received normal saline (control) or one of the following 3 doses of remifentanil: 1.0 μg/kg of remifentanil (remifentanil 1.0), 1.5 μg/kg of remifentanil (remifentanil 1.5), and 2.0 μg/kg of remifentanil (remifentanil 2.0). After induction with propofol and rocuronium, 1.3 minimal alveolar concentration of desflurane with oxygen was administered via a face mask. Heart rate (HR) and mean blood pressure (MBP) were recorded before remifentanil administration, and 1, 2, and 3 min after inhalation of desflurane, as well as 0, 1, 2, and 3 min after intubation. The proportions of patients with hemodynamics that maintained within ± 25% of preinduction values (MBP and HR proportion) were calculated. Results: MBP and HR were lower in the 3 remifentanil groups than in the control group throughout the study period. The MBP proportion was higher in remifentanil 1.0 group than in control group. The HR proportion was higher in the 3 remifentanil groups than in control group. Conclusions: A single bolus injection of remifentanil (1.0–2.0 μg/kg) may be effective in alleviating adverse hemodynamic changes induced by both desflurane inhalation and tracheal intubation. Especially, administration of remifentanil 1.0 μg/kg maintained more stable blood pressure compared to the control group throughout the study period.

Clinical Research Article : The target concentration of remifentanil to suppress the hemodynamic response to endotracheal intubation during inhalational induction with desflurane

( Ji Won Lee ),( Chul Woo Jung ) 대한마취과학회 2011 Korean Journal of Anesthesiology Vol.60 No.1

Background: Anesthesia induction with desflurane is troublesome because of the frequent sympathetic hyperactivity during desflurane administration. We thought that a low concentration of desflurane combined with a targetcontrolled infusion (TCI) of remifentanil would eliminate the desflurane-related complications and provide hemodynamic stability during desflurane induction. An up-and-down study was planned to find the target effect-site concentration of remifentanil to block the hemodynamic response to endotracheal intubation, the highest level of stimulus, during anesthesia induction with administering desflurane at 1 MAC. Methods: Remifentanil TCI was initiated before desflurane administration. When the preset target was achieved,spontaneous inhalation of desflurane 1 MAC was performed until the patients became unconscious. Laryngoscopic tracheal intubation was facilitated with rocuronium injection. The starting concentration of remifentanil and thetest space were 5 and 1 ng/ml, respectively. The criteria for up-and-down was a 20% increase of the mean arterial pressure or heart rate after intubation. The median effective concentration (EC50) of remifentanil was calculated from 6 independent pairs. The complications related with remifentanil and desflurane were assessed during the study. Results: We studied 20 patients using 2-5 ng/ml of the effect-site concentrations of remifentanil. The EC50 of remifentanil was 3.7 ng/ml. Loss of consciousness was achieved at 125 ± 22 s after desflurane inhalation and this wasirrespective of the combined remifentanil concentrations. Any remifentanil-related complication was not observed. Transient cough was seen in one patient who received 2 ng/ml of remifentanil. Conclusions: We demonstrated that uncomplicated induction with desflurane was possible by the use of targetcontrolled remifentanil. The EC50 of remifentanil to block the hemodynamic response to tracheal intubation was 3.7 ng/ml during inhalational induction with 1 MAC desflurane. (Korean J Anesthesiol 2011; 60: 12-18)

The median effective effect-site concentration of remifentanil for minimizing the cardiovascular changes to endotracheal intubation during desflurane anesthesia in pediatric patients

김은정,신상욱,김태균,윤지욱,변경조,김혜진 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.4

Background: Desflurane has the most rapid onset and offset of action among the volatile anesthetic agents used for general anesthesia, but it can cause airway reactivity, tachycardia, and hypertension during induction, especially in pediatric patients. This study was designed to determine a median effective effect-site concentration (EC50) of remifentanil to prevent the cardiovascular changes due to tracheal intubation during the 1 minimum alveolar concentration (MAC) desflurane inhalation, which was required to prevent movement in response to a noxious stimulus in 50% of subjects, in pediatric patients. Methods: Twenty-four pediatric patients between the ages 5-15 years were enrolled in this study. We injected thiopental intravenously, at the same time remifentanil was infused by Target Controlled Infusion (TCI) device. When the target effect-site concentration (Ce) of remifentanil reached a preset level, desflurane was administrated through the facial mask. Then, we assessed the signs of desflurane related airway reactivity and cardiovascular changes for 2 min. The up-and-down criteria was a 20% change in systolic blood pressure (SBP) and a heart rate (HR) between just prior to intubation and 1 min after intubation. The EC50 of remifentanil was calculated from 8 independent pairs using Dixon’s up-and-down method. Results: We studied 24 pediatric patients in range of 1-5 ng/ml of the Ce of remifentanil. No patient showed airway reactivity during the study. The EC50 of remifentanil to suppress the hemodynamic changes after tracheal intubation during desflurane anesthesia was calculated as 3.4 ± 0.9 ng/ml. Conclusions: In pediatric anesthesia, the EC50 of remifentanil to minimize the cardiovascular changes due to tracheal intubation during 1 MAC desflurane anesthesia was 3.4 ± 0.9 ng/ml. Background: Desflurane has the most rapid onset and offset of action among the volatile anesthetic agents used for general anesthesia, but it can cause airway reactivity, tachycardia, and hypertension during induction, especially in pediatric patients. This study was designed to determine a median effective effect-site concentration (EC50) of remifentanil to prevent the cardiovascular changes due to tracheal intubation during the 1 minimum alveolar concentration (MAC) desflurane inhalation, which was required to prevent movement in response to a noxious stimulus in 50% of subjects, in pediatric patients. Methods: Twenty-four pediatric patients between the ages 5-15 years were enrolled in this study. We injected thiopental intravenously, at the same time remifentanil was infused by Target Controlled Infusion (TCI) device. When the target effect-site concentration (Ce) of remifentanil reached a preset level, desflurane was administrated through the facial mask. Then, we assessed the signs of desflurane related airway reactivity and cardiovascular changes for 2 min. The up-and-down criteria was a 20% change in systolic blood pressure (SBP) and a heart rate (HR) between just prior to intubation and 1 min after intubation. The EC50 of remifentanil was calculated from 8 independent pairs using Dixon’s up-and-down method. Results: We studied 24 pediatric patients in range of 1-5 ng/ml of the Ce of remifentanil. No patient showed airway reactivity during the study. The EC50 of remifentanil to suppress the hemodynamic changes after tracheal intubation during desflurane anesthesia was calculated as 3.4 ± 0.9 ng/ml. Conclusions: In pediatric anesthesia, the EC50 of remifentanil to minimize the cardiovascular changes due to tracheal intubation during 1 MAC desflurane anesthesia was 3.4 ± 0.9 ng/ml.

The EC50 of remifentanil to minimize the cardiovascular changes during head holder pinning in neurosurgery

도왕석,김태균,김해규,김철홍 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.4

Background: During neuroanesthesia, head holder pinning commonly results in sympathetic stimulation manifested by hemodynamic changes, such as increased heart rate and arterial blood pressure. Remifentanil has been used successfully to control acute autonomic responses during neurosurgical procedures. The objective of this study was to determine effect-site concentration of remifentanil for suppressing the hemodynamic response to head holder pinning with the probability of 50% (EC50). Methods: Forty-one ASA physical status I or II patients, between the ages of 20-70, who were scheduled for neurosurgery were recruited into this study. After arrival in the operating room, standard monitoring was applied throughout the study, which included a bispectral index monitor. Both propofol and remifentanil were administered by Target-control infusion device. The Dixon "up-and-down" sequential allocation method was used to determine the EC50 of remifentanil. Results: The EC50 of remifentanil was 2.19 ± 0.76 ng/ml by the turning point estimate (TPE). In probit analysis, EC50 was 2.42 ng/ml (95% CI : -0.62-4.66) and EC95 was 5.70 ng/ml (95% CI : 4.02-67.53). The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65). The EC95 estimator comes from isotonic regression is 4.28 ng/ml (95% CI : 3.85-4.41). Conclusions: This study showed that EC50 of remifentanil was 2.19 ± 0.76 ng/ml by TPE. EC50 was 2.42 ng/ml (95% CI -0.62-4.66) in probit analysis, as back up analysis. The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65). Background: During neuroanesthesia, head holder pinning commonly results in sympathetic stimulation manifested by hemodynamic changes, such as increased heart rate and arterial blood pressure. Remifentanil has been used successfully to control acute autonomic responses during neurosurgical procedures. The objective of this study was to determine effect-site concentration of remifentanil for suppressing the hemodynamic response to head holder pinning with the probability of 50% (EC50). Methods: Forty-one ASA physical status I or II patients, between the ages of 20-70, who were scheduled for neurosurgery were recruited into this study. After arrival in the operating room, standard monitoring was applied throughout the study, which included a bispectral index monitor. Both propofol and remifentanil were administered by Target-control infusion device. The Dixon "up-and-down" sequential allocation method was used to determine the EC50 of remifentanil. Results: The EC50 of remifentanil was 2.19 ± 0.76 ng/ml by the turning point estimate (TPE). In probit analysis, EC50 was 2.42 ng/ml (95% CI : -0.62-4.66) and EC95 was 5.70 ng/ml (95% CI : 4.02-67.53). The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65). The EC95 estimator comes from isotonic regression is 4.28 ng/ml (95% CI : 3.85-4.41). Conclusions: This study showed that EC50 of remifentanil was 2.19 ± 0.76 ng/ml by TPE. EC50 was 2.42 ng/ml (95% CI -0.62-4.66) in probit analysis, as back up analysis. The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65).

Clinical Research Article : Remifentanil-induced pronociceptive effect and its prevention with pregabalin

( Hyong Rae Jo ),( Young Keun Chae ),( Yong Ho Kim ),( Hong Seok Chai ),( Woo Kyung Lee ),( Sun Soon Choi ),( Jin Hye Min ),( In Gyu Choi ),( Young Soon Choi ) 대한마취과학회 2011 Korean Journal of Anesthesiology Vol.60 No.3

Background: Experimental and clinical studies have suggested that remifentanil probably causes acute tolerance or postinfusion hyperalgesia. This study was designed to confirm whether remifentanil given during propofol anesthesia induced postoperative pain sensitization, and we wanted to investigate whether pregabalin could prevent this pronociceptive effect. Methods: Sixty patients who were scheduled for total abdominal hysterectomy were randomly allocated to receive (1) a placebo as premedication and an intraoperative saline infusion (control group), (2) a placebo as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (remifentanil group), or (3) pregabalin 150 mg as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (pregabalin-remifentanil group). Postoperative pain was controlled by titration of fentanyl in the postanesthetic care unit (PACU), followed by patient-controlled analgesia (PCA) with fentanyl. The patients were evaluated using the visual analogue scale (VAS) for pain scores at rest and after cough, consumption of fentanyl, sedation score and any side effects that were noted over the 48 h postoperative period. Results: The fentanyl titration dose given in the PACU was significantly larger in the remifentanil group as compared with those of the other two groups. At rest, the VAS pain score in the remifentanil group at 2 h after arrival in the PACU was significantly higher than those in the other two groups. Conclusions: The results of this study show that remifentanil added to propofol anesthesia causes pain sensitization in the immediate postoperative period. Pretreatment with pregabalin prevents this pronociceptive effect and so this may be useful for the management of acute postoperative pain when remifentanil and propofol are used as anesthetics. (Korean J Anesthesiol 2011; 60: 198-204)

Remifentanil Negatively Regulates RANKL-Induced Osteoclast Differentiation and Bone Resorption by Inhibiting c-Fos/NFATc1 Expression

윤지영,백철우,김형준,김은정,변경조,윤지욱 한국조직공학과 재생의학회 2018 조직공학과 재생의학 Vol.15 No.3

Remifentanil is commonly used in operating rooms and intensive care units for the purpose of anesthesia and sedation or analgesia. Although remifentanil may significantly affect the bone regeneration process in patients, there have been few studies to date on the effects of remifentanil on bone physiology. The purpose of this study was to investigate the effects of remifentanil on osteoclast differentiation and bone resorption. Bone marrow-derived macrophages (BMMs) were cultured for 4 days in remifentanil concentrations ranging from 0 to 100 ng/ml, macrophage colony-stimulating factor (MCSF) alone, or in osteoclastogenic medium to induce the production of mature osteoclasts. To determine the degree of osteoclast maturity, tartrate-resistant acid phosphatase (TRAP) staining was performed. RT-PCR and western blotting analyses were used to determine the effect of remifentanil on the signaling pathways involved in osteoclast differentiation and maturation. Bone resorption and migration of BMMs were analyzed to determine the osteoclastic activity. Remifentanil reduced the number and size of osteoclasts and the formation of TRAP-positive multinuclear osteoclasts in a dose-dependent manner. Expression of c-Fos and NFATC1 was most strongly decreased in the presence of RANKL and remifentanil, and the activity of ERK was also inhibited by remifentanil. In the bone resorption assay, remifentanil reduced bone resorption and did not significantly affect cell migration. This study shows that remifentanil inhibits the differentiation and maturation of osteoclasts and reduces bone resorption.

임상연구 : 한국인에서 Propofol-Remifentanil 전정맥 마취시 기관내 삽관에 따르는 혈압과 맥박수의 증가를 예방하기 위한 Remifentanil의 효과처 농도

신혜란 ( Helen Ki Shinn ),이홍식 ( Hong Sik Lee ),이춘수 ( Choon Soo Lee ),정종권 ( Chong Kweon Chung ),차두천 ( Doo Cheon Cha ),김혜하 ( Hye Ha Kim ),송장호 ( Jang Ho Song ) 대한마취과학회 2006 Korean Journal of Anesthesiology Vol.51 No.3

Background: Combination of propofol and remifentanil is an ideal regimen for total intravenous anesthesia. The purpose of this study is to determine the effect-site concentration of remifentanil for prevention of hemodynamic responses to tracheal intubation during fixed propofol infusion (4μg/ml) and to find any sexual differences. Methods: Thirty ASA physical status I-II patients undergoing general anesthesia were assigned to male (n = 15), and female (n = 15) group. All patients received a target controlled infusion (TCI) of propofol with a fixed effect-site concentration of 4μg/ml. After target effect-site concentration of propofol and remifentanil was reached, tracheal intubation was performed. The hemodynamic changes (systolic/diastolic blood pressure, mean arterial pressure, and heart rate) were measured at 1 and 2 min before tracheal intubation (baseline), immediately after, 1, 2, 3, 4 and 5 min following tracheal intubation. In both groups, effect-site concentration of remifentanil was initiated with 3 ng/ml. Subsequent concentration of remifentanil was determined by hemodynamic responses of the previous patient to tracheal intubation based on up and down sequential allocation. Results: The mean EC50 of remifentanil for prevention of hemodynamic responses to tracheal intubation were 1.37 ng/ml (95% CI, 0.95-1.81 ng/ml) in male group and 1.05 ng/ml (95% CI, 0.68-1.40 ng/ml) in female group, respectively. In addition, there were no statistical significant differences between two groups. Conclusions: Relatively small dosages of remifentanil (0.68-1.81 ng/ml) for attenuation of hemodynamic responses to tracheal intubation was needed in Korean population in propofol TCI and there were no sexual differences. (Korean J Anesthesiol 2006; 51: 312~7)