Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil

Abstract Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, "slug-flow" regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.

Remifentanil Down-regulates GIRK2 Expression in Rat Dorsal Root Ganglion and Spinal Dorsal Horn / 中山大学学报(医学科学版)

ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.

Effects of propofol and remifentanil in different TCI sequences on hypotension during induction of general anesthesia in hypertensive patients / 中华麻醉学杂志

Objective:To evaluate the effect of propofol and remifentanil in different target-controlled infusion(TCI) sequences on hypotension during induction of general anesthesia in hypertensive patients.Methods:A total of 132 patients with hypertension of both sexes, aged 50-75 yr, of American Society of Anesthesiologists Physical Status classificationⅡ or Ⅲ, with body mass index of 18-30 kg/m 2, scheduled for elective tracheal intubation under general anesthesia, were divided into 3 groups( n=44 each) using a random number table method: group C, PR group and RP group. In group C, propofol(target effect-site concentration 5 μg/ml) and remifentanil(target effect-site concentration 5 ng/ml) were simultaneously given by TCI. Propofol was given by TCI followed by TCI of remifentanil in PR group. Remifentanil was given by TCI followed by TCI of propofol in RP group. The development of hypotension was observed within 10 min after induction of general anesthesia, and the consumption of propofol, remifentanil and ephedrine, time of loss of consciousness, time of tracheal intubation and adverse reactions during the perioperative period were recorded. Results:Compared with group C, the incidence of hypotension during induction was significantly decreased, the consumption of propofol and ephedrine was decreased, and the BIS value was increased when consciousness disappeared, the time of loss of consciousness and time of tracheal intubation were prolonged, the BIS value was increased at loss of consciousness in PR group, and the consumption of ephedrine was significantly decreased, and the time of loss of consciousness and time of tracheal intubation were prolonged in RP group( P<0.05). Compared with PR group, the consumption of ephedrine was significantly decreased, and the time of loss of consciousness was prolonged in RP group( P<0.05). There was no significant difference in the incidence of responses to tracheal intubation, injection pain, bucking, inhibition ratio, postoperative delirium, postoperative nausea and vomiting, and intraoperative awareness during induction among the three groups( P>0.05). Conclusions:TCI of remifentanil followed by TCI of propofol can decrease the development of hypotension during induction of general anesthesia in hypertensive patients.

Effect of low-dose esketamine on remifentanil-induced postoperative hyperalgesia / 中华麻醉学杂志

Objective:To evaluate the effects of low-dose esketamine on remifentanil-induced postoperative hyperalgesia in the patients.Methods:Ninety-six American Society of Anesthesiologist Physical Status classificationⅠ or Ⅱ patients, aged 18-60 yr, with body mass index of 18-30 kg/m 2, scheduled for elective thyroidectomy under general anesthesia, were divided into 3 groups ( n=32 each) using a random number table method: control group (group C), esketamine administered before anesthesia induction group (group K1), and esketamine administered immediately after the end of surgery group (group K2). Esketamine 0.4 mg/kg was intravenously injected in group K1, and the equal volume of normal saline was given instead in C and K2 groups at 5 min before anesthesia induction. Anesthesia was induced by intravenous injection of propofol, remifentanil and rocuronium. Remifentanil was intravenously infused at a rate of 0.3 μg · kg -1·min -1 and 1.5%-2.5% sevoflurane was inhaled for anesthesia maintenance. Esketamine 0.4 mg/kg was intravenously injected in group K2 and the equal volume of normal saline was given instead in C and K1 groups immediately after the end of surgery. The mechanical pain thresholds of surgical incision and forearm of non-dominant hand were measured at 1 day before surgery and 30 min, 6 h, 24 h and 48 h after surgery, and flurbiprofen axetil was intravenously injected for rescue analgesia when the NRS score≥4 or the patient needed sedation. The intensity of pain was estimated using numeric rating scale at 30 min, 6 h, 24 h and 48 h after surgery. The intraoperative consumption of remifentanil, use of vasoactive drugs, recovery time, tracheal extubation time, duration of PACU stay, postoperative rescue analgesia and adverse reactions were recorded. Results:Compared with C group, the mechanical pain threshold around surgical incision and of the forearm of non-dominant hand was significantly increased at 30 min and 6 h after surgery in K1 and K2 groups ( P<0.05). Compared with C and K1 groups, the emergence time, tracheal extubation time, and duration of PACU stay were significantly prolonged, and the incidence of hallucinations and increased glandular secretion was increased in group K2 ( P<0.05). There were no significant differences in the consumption of remifentanil, intraoperative utilization rate of atropine and ephedrine, numeric rating scale scores at each time point after surgery, incidence of postoperative nausea and vomiting, and rate of rescue analgesia among the three groups ( P>0.05). Conclusions:Intravenous injection of small dose of esketamine (0.4 mg/kg) before anesthesia induction and immediately after the end of surgery can reduce postoperative hyperalgesia induced by remifentanil, and administration before anesthesia induction provides better efficacy in the patients.

The effect of sevoflurane combined with remifentanil on anesthetic effect and stress indexes in patients undergoing laparoscopic hysterectomy / 中国医师进修杂志

Objective:To investigate the effect of conducting general anesthesia with sevoflurane combined with remifentanil on the anesthetic effect and stress indexes in patients undergoing laparoscopic hysterectomy.Methods:A total of 80 patients undergoing laparoscopic hysterectomy in the Affiliated Hospital of Jining Medical College from April 2020 to August 2020 were selected and divided into the observation group and the control group according of the number table method, with 40 cases in each group. In the control group, sufentanil, propofol and rocuronium were used to induce anesthesia, and propofol and remifentanil were intravenously administered during anesthesia maintenance.The observation group received the same induction anesthesia, followed by 2% sevoflurane inhalation combined with remifentanil to maintain anesthesia. The anesthetic effect, stress indexes at different postoperative time points and adverse reaction between the two groups were compared.Results:The scores of mini mental state evaluation (MMSE) at 0.5, 1 and 2 h after the surgery and the scores of observer′sassessment of alertness/sedation scale (OAA/S) atimmediately after extubation, 1 and 2 h after surgery in the observation group were higher than those in the control group, there were statistical differences ( P<0.05). The wake up time and extubation time in the observation group were shorter than those in the control group: (9.22 ± 1.67) min vs. (15.94 ± 1.44) min, (10.34 ± 1.46) min vs. (17.11 ± 1.33) min, there were statistical differences ( P<0.01). The systolic blood pressure, diastolic blood pressure, epinephrine and cortisol at 10 min after intubation and at the end of surgery in the observation group were lower than those in the control group, there were statistical differences ( P<0.05). Conclusions:Sevoflurane combined with remifentanil conducting anesthesia can better improve the cognitive function of patients, shorten the recovery time of postoperative consciousness, and reduce the intraoperative stress response.

The efficacy of esmolol, remifentanil and nitroglycerin in controlled hypotension for functional endoscopic sinus surgery / Eficácia do esmolol, remifentanil e nitroglicerina na hipotensão controlada para cirurgia sinusal endoscópica funcional

Abstract Introduction Controlled hypotension is a reversible procedure in which the patient's baseline mean arterial blood pressure is reduced by 30% and sustained at 60-70 mmHg during the procedure. It decreases blood loss and provides clear surgical field during the procedures. Objectives The purpose of this study was to compare the efficacy of controlled hypotension agents esmolol, remifentanil, and nitroglycerin in functional endoscopic sinus surgery, in terms of hemodynamic changes and impact on the surgical efficiency. Methods The research was carried out as a cohort study. Patients who underwent functional endoscopic sinus surgery were randomized into 3 groups. Controlled hypotension was achieved with remifentanil (Group R), esmolol (Group E) and nitroglycerin (Group N). The efficacy of the drugs was tested by comparing the length of time with the targeted mean arterial pressure, the amount of anesthetics used, surgical field bleeding score and surgeon's satisfaction. Results Between May to December 2015, 60 patients were included and randomized equally into 3 different study groups. The median of the length of time with the targeted mean arterial pressure was shorter in the Group R when compared with Group E (p = 0.01) and Group N (p = 0.14). The amount of volatile anesthetics used was 25.0 mL (15-51), 43.0 mL (21-105) and 40.0 mL (26-97) in Groups R, E and N, respectively (p < 0.001). While there was more bleeding with nitroglycerin, surgical field bleeding scores were lower in Group R when compared with esmolol (p = 0.001) and nitroglycerin (p < 0.001). The analysis of surgeon's satisfaction scores concluded that surgeons were more satisfied with the group R (100%), when compared with group E (60%) and group N (30%) (p < 0.001). Conclusion Less volatile agent, short time to achieve controlled hypotension, stable blood pressure, lower surgical field bleeding scores and larger length of time with the targeted mean arterial pressure were found as the advantages of Remifentanil. Less costly, efficiency of achieving the targeted median arterial pressure and less postoperative complications were the advantages of nitroglycerin. In functional endoscopic sinus surgery procedures, appropriate controlled hypotensive agents should be selected according to the patients' characteristics and advantages/disadvantages of the drugs.

Resumo Introdução Hipotensão controlada é um procedimento reversível no qual a pressão arterial média basal do paciente é reduzida em 30% e mantida em 60-70 mmHg durante o procedimento. Isso diminui a perda de sangue e propicia um campo cirúrgico limpo durante os procedimentos. Objetivo Comparar agentes usados para hipotensão controlada: esmolol, remifentanil e nitroglicerina em cirurgia sinusal endoscópica funcional, em termos de alterações hemodinâmicas e impactos na eficácia cirúrgica. Método O estudo foi feito como de coorte. Pacientes submetidos à cirurgia sinusal endoscópica funcional foram randomizados em 3 grupos. A hipotensão controlada foi feita com remifentanil (Grupo R), esmolol (Grupo E) e nitroglicerina (Grupo R). A eficácia dos medicamentos foi testada com a comparação do período de tempo com a pressão arterial média desejada, a quantidade de anestésicos usados, o escore de sangramento no campo cirúrgico e a satisfação do cirurgião. Resultados Entre maio e dezembro de 2015, 60 pacientes foram incluídos e randomizados igualmente nos três grupos de estudo. A mediana do período com a pressão arterial desejada foi menor no Grupo R quando comparado ao Grupo E (p = 0,01) e Grupo N (p = 0,14). A quantidade de anestésicos voláteis usados foi de 25,0 mL (15 ± 51), 43,0 mL (21 ± 105) e 40,0 mL (26 ± 97) nos Grupos R, E e N, respectivamente (p < 0,001). Houve mais sangramento com nitroglicerina e escores de sangramento no campo cirúrgico foram menores no Grupo R quando comparados com esmolol (p = 0,001) e nitroglicerina (p < 0,001). A análise dos escores da satisfação do cirurgião concluiu que os cirurgiões estavam mais satisfeitos com o grupo R (100%) quando comparados ao grupo E (60%) e o grupo N (30%) (p < 0,001). Conclusão Agente menos volátil, pouco tempo para obter a hipotensão controlada, pressão arterial estável, menor escore de sangramento no campo cirúrgico e período de pressão arterial desejada curto foram considerados como vantagens do remifentanil. Menor custo, eficácia de obtenção da pressão arterial média desejada e menos complicações pós-operatórias foram as vantagens da nitroglicerina. Nos procedimentos de cirurgia sinusal endoscópica funcional, os agentes apropriados para obtenção de hipotensão controlada devem ser selecionados de acordo com as características dos pacientes e as vantagens/desvantagens dos fármacos.

Efficacy of remimazolam combined with remifentanil used for painless gastroscopy / 中华麻醉学杂志

Objective:To evaluate the effect of remimazolam combined with remifentanil used for painless gastroscopy.Methods:A total of 150 patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective painless gastroscopy, were divided into 3 groups ( n=50 each) using a random number table method: propofol combined with remifentanil group (group P), remimazolam 0.3 mg/kg combined with remifentanil group (group R1) and remimazolam 12 mg combined with remifentanil group (group R2). Drugs were administrated according to body weight, and calculation was carried out according to ideal body weight.Remifentanil 0.25 μg/kg was injected intravenously, propofol 1.5 mg/kg was then injected intravenously in group P, remimazolam 0.3 mg/kg was injected intravenously in group R1, and remimazolam 12 mg was injected intravenously in group R2.When Modified Observer′s Assessment/Alertness and Sedation (MOAA/S) score was≤3, gastroscopy was performed.It was defined as sedation failure when MOAA/S score was still ≥4 at 3 min after administration of propofol or remimazolam.When intraoperative body movement occurred, 1/4 of the initial dose of propofol was injected intravenously in group P, 1/4 of the initial dose of remimazolam was injected intravenously in group R1, and remimazolam 2.5 mg was injected intravenously in group R2 to maintain MOAA/S score ≤3.It was defined as sedation failure when sufficient sedation was not maintained after the additional drugs were given more than 3 times within 15 min.The success of sedation, time for gastroscopy, emergence time and discharge time were recorded.The occurrence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, hiccup, coughing and injection pain was recorded. Results:Compared with group P, no significant change was found in the success rate of sedation ( P>0.05), and the incidence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, hiccup, coughing and injection pain was decreased in group R1, and the success rate of sedation was significantly decreased, the incidence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, coughing and injection pain was decreased, and the incidence of hiccup was increased in group R2 ( P<0.05). Compared with group R2, the success rate of sedation was significantly increased, and the incidence of intraoperative body movement, coughing and hiccup was decreased in group R1 ( P<0.05). Conclusion:Remimazolam 0.3 mg/kg combined with remifentanil can be safely and effectively used for painless gastroscopy.

Anestesia total intravenosa con remifentanilo vs fentanilo como base analgésica en cirugía torácica electiva / Intravenous total anesthesia with remifentanil and fentanyl as analgesic base in elective thoracic surgery

Introducción: Mantener una oxigenación adecuada durante la ventilación a un solo pulmón es el problema fundamental al que se enfrenta el anestesiólogo durante la cirugía torácica, es por ello que se mantiene una constante búsqueda del método anestésico ideal que ayude a lograr dicho objetivo. Objetivos: Evaluar los resultados de dos técnicas de anestesia total intravenosa con remifentanilo y fentanilo como base analgésica e identificar la aparición de complicaciones durante la intervención quirúrgica. Métodos: Se realizó un estudio causiexperimental prospectivo, en el Hospital Docente Clínico Quirúrgico Dr. Salvador Allende, entre enero 2013 a diciembre 2015 en 40 pacientes ASA II o III que requirieron procedimientos intratorácicos. Estos se dividieron en dos grupos. A (remifentanilo-propofol) y B (fentanilo-propofol). Se estudiaron variables hemodinámicas, de oxigenación durante la ventilación unipulmonar, el tiempo de recuperación anestésica (ventilación espontánea, apertura ocular, extubación) y la analgesia posoperatoria. Resultados: No existieron variaciones significativas en la hemodinamia, ni en la oxigenación de los enfermos con el empleo de ambas técnicas anestésicas; sin embargo, el despertar y recuperación posoperatoria a corto plazo fue mejor en el grupo A. La intensidad del dolor posoperatorio según la escala visual análoga fue menor en el grupo B. Conclusiones: Ambas técnicas son efectivas para procedimientos quirúrgicos torácicos. Con mínima interferencia en la hemodinámia y parámetros de oxigenación(AU)

Introduction: Maintaining adequate oxygenation during single-lung ventilation is a fundamental concern faced by the anesthesiologist during thoracic surgery; therefore, a constant search is maintained for the ideal anesthetic method that helps achieve this goal is maintained. Objectives: To evaluate the outcomes of two total intravenous anesthesia techniques with remifentanil and fentanyl as analgesic base and to identify the onset of complications during surgery. Methods: A prospective and quasi-experimental study was carried out at Dr. Salvador Allende Clinical-Surgical Hospital, between January 2013 and December, with 40 ASA II or III patients who required intrathoracic procedures. These were divided into two groups: A (remifentanil-propofol) and B (fentanyl-propofol). Hemodynamic variables and others of oxygenation during one-lung ventilation were studied, together with anesthetic recovery time (spontaneous ventilation, ocular opening, extubation) and postoperative analgesia. Results: There were no significant variations in the hemodynamics or oxygenation of patients with the use of both anesthetic techniques; however, awakening and short-term postoperative recovery was better in group A. Postoperative pain intensity, based on the analogue-visual scale, was lower in group B. Conclusion: Both techniques are effective for thoracic surgical procedures, with minimal effect in hemodynamics and oxygenation parameters(AU)

Effects of remifentanil on awakening of propofol sedated patients submitted to upper gastrointestinal endoscopy: a randomized clinical trial / Efeitos do remifentanil sobre despertar de pacientes sedados com propofol para endoscopia digestiva alta: estudo clínico randomizado

Abstract Background and objectives: Sedation for endoscopic procedures aims to provide high quality sedation, lower risks, short recovery time, superior recovery quality and absence of side effects, seeking high patient level of satisfaction. The goal of the study was to assess administration of remifentanil combined with propofol regarding the effects of the drug association during sedation and recovery for patients submitted to upper gastrointestinal diagnostic endoscopy. Method: One hundred and five patients were assessed, randomly divided into three groups of 35 patients. The Control Group was sedated with propofol alone. Study Group 1 was sedated with a fixed dose of 0.2 µg.kg−1 remifentanil combined with propofol. Study Group 2 was sedated with 0.3 µg.kg−1 remifentanil combined with propofol. We assessed the quality of sedation, hemodynamic parameters, incidence of significant hypoxemia, time for spontaneous eye opening, post-anesthetic recovery time, quality of post-anesthetic recovery, presence of side effects and patient satisfaction. Results: Study Group 1 showed better quality of sedation. The groups in which remifentanil was administered combined with propofol showed shorter eye-opening time and shorter post-anesthetic recovery time compared to the control group. The three groups presented hemodynamic changes at some of the moments assessed. The incidence of significant hypoxemia, the quality of post-anesthetic recovery, the incidence of side effects and patient satisfaction were similar in the three groups. Conclusions: The combination of propofol with remifentanil at a dose of 0.2 µg.kg−1 was effective in improving the quality of sedation, and at doses of 0.2 µg.kg−1 and 0.3 µg.kg−1 reduced the time to spontaneous eye opening and post-anesthetic recovery in comparison to sedation with propofol administered alone.

Resumo Justificativa e objetivos: A sedação para procedimentos endoscópicos pretende fornecer boa qualidade de sono, menores riscos, tempo de recuperação mais curto, qualidade de recuperação superior e ausência de efeitos colaterais, buscando um elevado nível de satisfação dos pacientes. O objetivo deste estudo foi avaliar a influência da associação do remifentanil ao propofol e seus efeitos durante a sedação e a recuperação em exames de endoscopia digestiva alta diagnóstica. Método: Foram avaliados 105, divididos aleatoriamente em três grupos de 35 pacientes. O Grupo Controle foi sedado apenas com o uso de propofol, o Grupo de Estudo 1 foi sedado com uso de remifentanil em dose fixa de 0,2 µg.Kg-1 associado ao propofol. E o Grupo de Estudo 2 foi sedado com o uso de remifentanil em dose fixa de 0,3 µg.Kg-1 associado ao propofol. Foram avaliadas a qualidade da sedação, comportamento hemodinâmico, incidência de hipoxemia significativa, tempo para abertura ocular espontânea, tempo de recuperação pós-anestésica, qualidade da recuperação pós-anestésica, presença de efeitos colaterais e satisfação do paciente. Resultado: O Grupo de Estudo 1 apresentou melhor qualidade de sedação. Os grupos em que se associou o remifentanil apresentaram tempo para abertura ocular e tempo de recuperação anestésica mais curtos em relação ao grupo controle. Os três grupos apresentaram alterações hemodinâmicas em algum dos momentos avaliados. A incidência de hipoxemia significativa, a qualidade da recuperação pós-anestésica, a incidência de efeitos colaterais e a satisfação dos pacientes foram similares nos três grupos. Conclusão: Conclui-se que a associação do remifentanil na dose de 0,2 µg.kg-1 mostrou-se efetivo na melhora da qualidade da sedação, e nas doses 0,2 µg.kg-1 e de 0,3 µg.kg-1 reduziu o tempo de abertura ocular espontânea e o tempo de recuperação pós-anestésica dos pacientes em relação a sedação apenas com propofol.

Anestesia intravenosa total: Propofol/remifentanil vs. midazolam/remifentanil en cirugía torácica / Total intravenous anesthesia: propofol/remifentanil vs midazolam/remifentanil in thoracic surgery

Introducción: Las técnicas de administración de anestesia en cirugía torácica han experimentado gran evolución y mayor fundamento científico. La anestesia intravenosa total basada en la analgesia favorece a que el período perioperatorio transcurra sin dolor y la recuperación sin complicaciones. Objetivo: Comparar la efectividad y seguridad de dos técnicas de anestesia intravenosa total en cirugía torácica electiva con remifentanilo como base analgésica. Métodos: Estudio causiexperimental, prospectivo realizado en el Hospital Docente Clínico Quirúrgico Dr. Salvador Allende, en el período comprendido entre enero de 2013 a enero de 2015, en 45 pacientes, programados para cirugía torácica electiva, divididos en dos grupos según hipnótico utilizado. Grupo A: Propofol/Remifentanil y Grupo B: Midazolam/Remifentanil. Se evaluaron variables hemodinámicas en diferentes momentos del período intraoperatorio. Variables de oxigenación (PaO2 y SaO2) durante la ventilación unipulmonar y los tiempos de recuperación anestésica. Resultados: Predominaron los pacientes mayores de 60 años en los dos grupos, con estado físico ASA III. No hubo diferencias en la oxigenación arterial entre los grupos. Hubo disminución de la tensión arterial sistólica en el grupo A sin diferencias significativas. La recuperación de la anestesia fue significativamente más demorada en el grupo B. Conclusiones: La técnica de anestesia intravenosa total con remifentanil como base analgésica asociado a propofol resultó segura y efectiva en pacientes operados de cirugía torácica(AU)

Introduction: Anesthesia administration techniques in thoracic surgery have undergone great evolution and greater scientific foundation. Total intravenous anesthesia based on analgesia favors the perioperative period without pain and recovery without complications. Objective: To compare the effectiveness and safety of two techniques of total intravenous anesthesia in elective thoracic surgery with remifentanil as an analgesic base. Methods: Prospective and causiexperimental study carried out at Dr. Salvador Allende Clinical-Surgical Teaching Hospital, in the period from January 2013 to January 2015, with 45 patients scheduled for elective thoracic surgery, who were divided into two groups according to the hypnotic drug used. Group A: propofol/remifentanil, and group B: midazolam/remifentanil. Hemodynamic variables were evaluated at different times during the intraoperative period. Oxygenation variables (PaO2 and SaO2) during unipulmonary ventilation and anesthetic recovery times. Results: Patients older than 60 years predominated in the two groups, with a physical status of ASA III. There were no differences in arterial oxygenation between the groups. There was a decrease in systolic blood pressure in group A without significant differences. The recovery of anesthesia was significantly more delayed in group B. Conclusions: The total intravenous anesthesia technique with remifentanil as an analgesic base associated with propofol was safe and effective in patients undergoing thoracic surgery(AU)

Comparison of remifentanil and sufentanil on hemodynamics, recovery and cognitive function in patients undergoing laparoscopic cholecystectomy / 中国医师进修杂志

Objective To compare the effects of remifentanil and sufentanil on hemodynamics,recovery and cognitive function in patients undergoing laparoscopic cholecystectomy.Methods A total of 136 patients undergoing laparoscopic cholecystectomy in Second People's Hospital of Fuyang District of Hangzhou from March 2013 to March 2018 were collected and divided into two groups,with 68 patients in each group.The remifentanil group was given conventional anesthesia induction and remifentanil anesthesia maintenance,while the sufentanil group was given conventional anesthesia induction and sufentanil anesthesia maintenance.The levels of hemodynamics,awakening,cognitive function and complications of the two groups were compared.Results The levels of hemodynamics (heart rate,systolic blood pressure,diastolic blood pressure) in sufentanil group was stable than those in remifentanil group.Compared with the remifentanil group,the respiratory recovery time,eye opening time and extubation time of sufentanil group were all increased [(10.01 ± 1.25) min vs.(8.17 ± 0.82) min,(10.27 ± 1.39) min vs.(8.05 ± 0.72) min,(14.65 ± 1.51) min vs.(11.08 ± 1.03) min] (P＜0.05).In addition,the scores of mini mental state examination (MMSE) on the 1st day after operation in both groups were lower than those on the 3rd day before and after operation,and the scores in remifentanil group were significantly lower than those in sufentanil group,and the scores of sufentanil group were significantly higher on the 1st day after operation [(21.04 ± 2.02) scores vs.(25.08 ± 2.31) scores] (P ＜0.05).The incidence of abdominal distension,nausea and vomiting in sufentanil group was significantly lower than those in remifentanil group [2.94％(2/68) vs.13.24％(9/68),5.88％(4/68) vs.26.47％(18/68)](P＜ 0.05).Conclusions Compared with remifentanil group,sufentanil group has less influence on hemodynamics,faster recovery of cognitive function and less incidence of adverse reactions in patients undergoing laparoscopic cholecystectomy.

Role of aquaporin-4 in mediating protective effect of remifentanil postconditioning against adult myocardial hypoxia/reoxygenation injury / 中国药理学与毒理学杂志

OBJECTIVE: To investigate the effect of remifentanil postconditioning on myocardial hypoxia/reoxygenation (H/R) injury in adults, and to further explore the role of aquaporin-4 (AQP-4) in mediating this effect. METHODS: Trabecular muscles from the right atrial appendage of adults were treated with hypoxia for 90 min, followed by reoxygenation for 120 min. Then, remifentanil 0.01, 0.1 and 1.0 nmol·L-1was infused 10 min before the end of hypoxia until 10 min after the start of reoxygenation. The contractile tension of the trabecular muscles was monitored during the experiment. Western blotting was performed to evaluate AQP-4 expression at the end of the experiment. RESULTS: Compared with normal control group, muscle tension decreased significantly after 30 min of induction in H/R group (P<0.05), and it was reduced to the minimum at 90 min. The muscle tension at 150 min and 180 min in remifentanil 0.1 nmol·L-1group was higher than that in H/R group (P<0.05). The muscle tension in remifentanil 1.0 nmol·L-1group was higher than that in H/R group during reoxygenation (P<0.05). Compared with normal control group, the expression of AQP-4 protein in H/R group was significantly higher (P< 0.05), whereas the expression of AQP-4 in remifentanil 0.1 and 1.0 nmol·L-1groups was down-regulated compared with H/R group (P<0.05). CONCLUSION: Remifentanil can alleviate myocardial H/R injury in adults, and its effect may be related to the decreased expression of AQP-4.

Clinical application of remifentanil in children with critical diseases / 中国小儿急救医学

Analgesia and sedation are important for children with acute critical diseases.With the new development of the concept of analgesia and sedation, new analgesics and sedatives are constantly introduced.Remifentanil has the characteristics of short half-life, no accumulation, less impact on important organs of patients, better controllability, better analgesic effect and quick onset, and has been widely used in children with critical diseases.This paper discussed the application advantages of remifentanil in children with critical diseases.

Comparison of remifentanil and sufentanil on hemodynamics, recovery and cognitive function in patients undergoing laparoscopic cholecystectomy / 中国医师进修杂志

Objective@#To compare the effects of remifentanil and sufentanil on hemodynamics, recovery and cognitive function in patients undergoing laparoscopic cholecystectomy.@*Methods@#A total of 136 patients undergoing laparoscopic cholecystectomy in Second People′s Hospital of Fuyang District of Hangzhou from March 2013 to March 2018 were collected and divided into two groups, with 68 patients in each group. The remifentanil group was given conventional anesthesia induction and remifentanil anesthesia maintenance, while the sufentanil group was given conventional anesthesia induction and sufentanil anesthesia maintenance. The levels of hemodynamics, awakening, cognitive function and complications of the two groups were compared.@*Results@#The levels of hemodynamics (heart rate, systolic blood pressure, diastolic blood pressure) in sufentanil group was stable than those in remifentanil group. Compared with the remifentanil group, the respiratory recovery time, eye opening time and extubation time of sufentanil group were all increased [(10.01 ± 1.25) min vs. (8.17 ± 0.82) min, (10.27 ± 1.39) min vs. (8.05 ± 0.72) min, (14.65 ± 1.51) min vs. (11.08 ± 1.03) min] (P<0.05). In addition, the scores of mini mental state examination (MMSE) on the 1st day after operation in both groups were lower than those on the 3rd day before and after operation, and the scores in remifentanil group were significantly lower than those in sufentanil group, and the scores of sufentanil group were significantly higher on the 1st day after operation [(21.04 ± 2.02) scores vs. (25.08 ± 2.31) scores] (P< 0.05). The incidence of abdominal distension, nausea and vomiting in sufentanil group was significantly lower than those in remifentanil group [2.94%(2/68) vs. 13.24%(9/68), 5.88%(4/68) vs. 26.47%(18/68)] (P<0.05).@*Conclusions@#Compared with remifentanil group, sufentanil group has less influence on hemodynamics, faster recovery of cognitive function and less incidence of adverse reactions in patients undergoing laparoscopic cholecystectomy.

Comparison of anesthesia effects between closed / 中南大学学报(医学版)

OBJECTIVES@#Bispectral index (BIS) can reflect the depth of propofol sedation. This study aims to compare the anesthetic satisfaction, anesthetic dose, and hemodynamic changes between closed-loop target controlled infusion (CLTCI) and open-loop target controlled infusion (OLTCI) during abdominal surgery.@*METHODS@#From December 2016 to December 2018, 70 patients undergoing abdominal surgery under general anesthesia were selected in Beijing Hospital, including 51 males and 19 females, at the age from 49 to 65 years old. They were classified as grade I-II by the American Society of anesthesiologists (ASA) and were randomly divided into the CLTCI group and the OLTCI group (@*RESULTS@#In the induction stage, the percentage of adequate anesthesia time in the CLTCI group was higher than that in the OLTCI group, and the percentage of deep anesthesia time in the CLTCI group was significantly lower than that in the OLTCI group (both @*CONCLUSIONS@#Compared with propofol OLTCI, anesthesia with propofol CLTCI under BIS guidance can maintain a more appropriate depth of anesthesia sedation and more stable hemodynamics.

Response surface model to optimize the concentration range of propofol and remifentanil / 中国临床药理学与治疗学

AIM: To investigate the pharmacodynamic interactions between propofol and remifentanil by response surface methodology. The response surface for inhibition of somatic, hemodynamic responses to laryngoscopy and response surface of cardiovascular side effects were combined to identify the optimal combination of propofol and remifentanil. METHODS: Seventy ASA I-II patients were grouped randomly and parallelly. The patients received target-controlled infusion (TCI) of propofol (0-9 μg/mL) at a fixed concentration, then remifentanil was administrated with TCI device from 0 to 10 ng/mL in a stepwise ascending fashion. After reaching pseudo-steady-state drug levels, the somatic and hemodynamic responses to laryngoscopy and cardiovascular side effects were observed. The pharmacodynamic interactions were investigated by response surface methodology. RESULTS:Response surface models revealed significant synergy between propofol and remifentanil. Imax were 2.89, 5.02 and 2.55 for the somatic and hemodynamic responses to laryngoscopy and cardiovascular side effects. Based on the results of response surface method, the optimal dose range of propofol and remifentanil was constructed.CONCLUSION: Response surface method can analyze the pharmacodynamic interactions qualitatively and quantitatively and provide the optimal dose range.

The effects of remifentanil used during cesarean section on oxidative stress markers in correlation with maternal hemodynamics and neonatal outcome: a randomized controlled trial / Os efeitos do remifentanil sobre os marcadores do estresse oxidativo durante a cesariana, em correlação com a hemodinâmica materna e o desfecho neonatal: um estudo randômico controlado

Abstract Background and objective: Remifentanil is used to attenuate maternal hemodynamic response to intubation and surgical stress during Induction-Delivery period of cesarean section. The goal was to compare the effects of two remifentanil dosing regimens on oxidative stress level, in correlation with its hemodynamic and neonatal effects. Methods: Fifty-one patients, 17 per group, enrolled for elective cesarean section were randomly divided by computer-generated codes into three parallel groups: (A) patients received a 1 µg.kg-1 remifentanil bolus immediately before induction, followed by 0.15 µg.kg-1.min-1 infusion, that was stopped after skin incision; (B) patients received a 1 µg.kg-1 remifentanil bolus immediately before induction; (C) (control), patients did not receive remifentanil until delivery. Maternal venous blood samples were taken at basal time, at extraction and 30 minutes after the end of operation for spectrophotometrical determination of malondialdehyde and advanced oxidation protein products concentration. The same was conducted for umbilical venous sample. Results: Systolic blood pressure and heart rate remained significantly lower in group A compared to B and C during entire Induction-Delivery period (p < 0.001, p = 0.02 after intubation; p = 0.006, p = 0.03 after skin incision; p = 0.029, p = 0.04 after extraction; respectively). Malondialdehyde concentration was lower at time of extraction in maternal blood in group A compared to B and C (p = 0.026). All neonatal Apgar scores were ≥ 8 and umbilical acid-base values within normal range. Conclusions: The remifentanil dosing regimen applied in group A significantly attenuated lipid peroxidation and maternal hemodynamic response during entire I-D period, without compromising neonatal outcome.

Resumo Justificativa e objetivo: O remifentanil é usado para atenuar a resposta hemodinâmica materna à intubação e ao estresse cirúrgico durante o intervalo indução-parto cesariana. O objetivo foi comparar os efeitos de dois regimes posológicos de remifentanil sobre o nível de estresse oxidativo, em correlação com seus efeitos na hemodinâmica materna e no neonato. Métodos: Mediante códigos gerados por computador, 51 pacientes (17 por grupo) programadas para cesariana eletiva foram randomicamente divididas em três grupos paralelos (A, B e C). No Grupo A, as pacientes receberam remifentanil em bolus de 1 µg.kg-1 imediatamente antes da indução, seguido por infusão de 0,15 µg.kg-1.min-1 que foi interrompida após a incisão da pele; no Grupo B, as pacientes receberam remifentanil em bolus de 1 µg.kg-1 imediatamente antes da indução; no Grupo C (controle), as pacientes não receberam remifentanil até o parto. Amostras de sangue venoso materno foram colhidas no momento basal, na extração do feto e 30 minutos após o término da operação para determinar espectrofotometricamente as concentrações do malondialdeído e dos produtos proteicos de oxidação avançada. O mesmo foi feito para a coleta das amostras de sangue venoso umbilical. Resultados: A pressão arterial sistólica e a frequência cardíaca permaneceram significativamente menores no Grupo A, comparado aos grupos B e C, durante todo o intervalo indução-parto (p < 0,001, p = 0,02 após a intubação; p = 0,006, p = 0,03 após a incisão da pele; p = 0,029, p = 0,04 após a extração do feto, respectivamente). No momento da extração do feto, a concentração do malondialdeído foi menor no sangue materno do Grupo A, comparado aos grupos B e C (p = 0,026). Todos os escores de Apgar neonatais foram ≥ 8 e os valores da avaliação ácido-base do cordão umbilical estavam dentro da faixa normal. Conclusões: O regime posológico de remifentanil aplicado ao Grupo A atenuou de modo significativo a peroxidação lipídica e a resposta hemodinâmica materna durante todo o intervalo indução-parto, sem comprometer o desfecho neonatal.

Remifentanil y propofol con infusión controlada por objetivo para legrado uterino / Remifentanil and propofol infusion controlled by target for uterine curettage

OBJETIVO: analizar el comportamiento hemodinámico frente al manejo anestésico con remifentanilo y propofol con infusión controlada por objetivo en pacientes sometidas a legrado uterino por aborto incompleto. MÉTODOS: se realizó un ensayo clínico no controlado utilizando un protocolo de atención aprobado por el servicio de anestesiología obstétrica del Hospital Obrero Nº2, entre enero a mayo de 2019, ingresando 39 pacientes sometidas a legrado uterino instrumental; usando el modelo Minto para remifentanil y el modelo Schnider para Propofol para la infusión controlada. La valoración de las diferencias estadísticas en los parámetros hemodinámicos se realizó mediante comparación de medias por T de student. RESULTADOS: la edad media de las participantes del fue 34,77±7,9 años, tiempo quirúrgico de 12 ± 2,9 minutos. El tiempo anestésico de 15 ± 3 minutos; el tiempo del alta de la recuperación anestésica a salas de 14 ±3,3 minutos. La dosis de inducción del remifentanilo utilizada fue de 4,8 ± 0,3 ng/ml (p >0,001) y la dosis de inducción del propofol fue de 3,77± 0,4 mcg/ml (p >0,001). Las dosis de mantenimiento del remifentanilo de 4,56 ± 0,5 ng/ml y la dosis del propofol es de 3,8 ± 0,6 mcg/ml (p >0,001). No se encontró complicaciones ni hallazgos secundarios por el uso de los medicamentos. CONCLUSIONES: el uso del sistema de infusión controlado por objetivo (TCI) para remifentanilo en el modelo de Minto y modelo de Schinder para el propofol proporciona a las pacientes buena estabilidad hemodinámica.

OBJECTIVE: to analyze hemodynamic behavior in anesthetic management with an objective-controlled infusion of remifentanil and propofol in uterine curettage by incomplete abortion. METHODS: an uncontrolled clinical trial was conducted using a service protocol approved by the obstetric anesthesiology department of Obrero Hospital Nº2, between January and May of 2019, including 39 patients treated by instrumental curettage; the Minto model for remifentanil and the Schnider model for propofol were used to controlled infusion. The assessment of the statistical differences in the hemodynamic parameters was made by Student's T test. RESULTS: the age average of participants was 34.77±7.9 years, surgical time of 12±2.9 minutes. Duration of anesthetic time of 15±3 minutes; the time of discharge from the anesthetic recovery to rooms of 14±3.3 minutes. The induction dose of remifentanil used was 4.8±0.3 ng/ml (p>0.001) and the induction dose of propofol was 3.77±0.4 mcg/ml (p>0.001). The maintenance doses of remifentanil of 4.56±0.5 ng/ml and the dose of propofol was 3.8±0.6 mcg/ml (p>0.001). There were no complications or secondary findings due to the use of the medications. CONCLUSIONS: the use of the objective-controlled infusion system (TCI) for remifentanil in the Minto model and the Schinder model for propofol provides patients with good hemodynamic stability.

Effects of preanesthetic single administration of dexmedetomidine on the remifentanil and propofol requirement during laparoscopic cholecystectomy

BACKGROUND: Dexmedetomidine, an α2-adrenergic agonist, can be used for sedation and as an adjuvant to anesthetics. This study aimed to evaluate the effects of preanesthetic administration of dexmedetomidine on the propofol and remifentanil requirement during general anesthesia and postoperative pain in patients undergoing laparoscopic cholecystectomy. METHODS: Sixty patients were randomly assigned to group D or S (n = 30 each). Dexmedetomidine (0.5 µg/kg) and a comparable volume of saline were administered in groups D and S, respectively, over a 10 minutes period before induction. General anesthesia was induced and maintained with propofol and remifentanil; the bispectral index was maintained at 40–60. The intraoperative remifentanil and propofol dosages were recorded, and postoperative pain was assessed using a visual analog scale (VAS). RESULTS: In groups S and D, propofol dosage was 8.52 ± 1.64 and 6.83 ± 1.55 mg/kg/h, respectively (P < 0.001), while remifentanil dosage was 7.18 ± 2.42 and 4.84 ± 1.44 µg/ kg/h, respectively (P < 0.001). VAS scores for postoperative pain were 6.50 (6–7) and 6.0 (6–7), respectively, at 30 minutes (P = 0.569), 5 (4–5) and 4 (3–5), respectively, at 12 hours (P = 0.039), and 2 (2–3) and 2 (1.25–2), respectively, at 24 hours (P = 0.044). The Friedman test revealed that VAS scores changed over time in both groups (P < 0.001). CONCLUSIONS: Preanesthetic single administration of a low dose of dexmedetomidine (0.5 µg/kg) can significantly decrease the remifentanil and propofol requirement during short surgeries and alleviate postoperative pain.

Remifentanil promotes osteoblastogenesis by upregulating Runx2/osterix expression in preosteoblastic C2C12 cells

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.