Hemodynamic impact of increasing time between fentanyl and propofol administration during anesthesia induction: a randomised, clinical trial

Abstract Background and objective: Anesthesia induction can produce severe propofol dose-dependent hypotension. Fentanyl coadministration reduces the catecholaminergic response to orotracheal intubation allowing propofol dose reduction. The aim of this study is to determine whether the hemodynamic response is improved by increasing the time between fentanyl and propofol administration and reducing the dose of the latter without increasing the time to achieve optimal hypnosis. Methods: After approval by the Research Ethics Committee, patients undergoing non-cardiac surgery with endotracheal intubation were randomized by a computer-generated table into six time-dose groups (1 or 2 minutes/1, 1.5, or 2mg.kg-1 of propofol). Patients with high bronchoaspiration risk, a difficult airway, hemodynamic instability, or anesthetic allergies were excluded. After giving intravenous fentanyl (2 μg.kg-1 ), each group received different doses of propofol after 1 or 2 minutes. Non-invasive blood pressure (BP) and heart rate (HR) were measured at pre-induction, pre-intubation, and post-intubation. Time to hypnosis (bispectral index < 60) was also recorded. Results: Of the 192 recruited patients, 186 completed the study (1 min group n = 94; 2 min group n = 92). It was observed that HR and BP decreased after propofol administration and increased after intubation in all groups (p<0.0001). In patients over 55 years, the 2 min - 2 mg.kg-1 group showed the greatest systolic BP reduction (36 ± 12%) at pre-intubation, while the 1 min - 1.5 mg.kg-1 group showed the least hemodynamic alteration between pre- and post-intubation (-4 ± 13%). No significant differences were found in younger patients or in the time to reach hypnosis between the six groups. While no cases of severe bradycardia were recorded, 5,4% of the sample required vasopressors. Conclusion: Increasing the time between the administration of fentanyl and propofol by up to two minutes results in greater hypotension in patients over 55 years.

Accuracy of closed-loop and open-loop propofol delivery systems by bispectral index monitoring in breast surgery patients: a prospective randomized trial

Abstract Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number:ChiCTR-INR-17010399.

Comparison Between the Protective Effect of Isoflurane and Propofol on Myocardium During Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ABSTRACT Objective: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). Methods: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. Results: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). Conclusion: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.

Establishment of a method for detecting propofol concentration in plasma and its application in patients with lymphedema / 中国药房

OBJECTIVE To establish a method for the determination of propofol concentration in human plasma and apply it in patients with lymphedema. METHODS The concentration of propofol was determined by UPLC-MS/MS after protein precipitation of plasma samples using thymol as internal standard. The sample was eluted on a Kinetex C18 column with a mobile phase consisting of acetonitrile （A）-water （B） for gradient elution at the flow rate of 200 μL/min. The sample size was 5 μL， and the column temperature was set at 40 ℃. The sample chamber temperature was 15 ℃. Using multi-reaction monitoring mode， the ion pairs for quantitative analysis were m/z 177.0→161.2 （propofol） and m/z 149.0→133.1 （internal standard）， respectively. The above method was used to determine the plasma concentration of propofol in 6 patients with lymphedema. RESULTS The linear range of propofol was 50-5 000 ng/mL （r＝0.995 0）. RSDs of within- and between-batch precision were not more than 8.08%； no endogenous interference， carryover effect， or dilution effect was observed in blank plasma. The extraction recovery ranged from 89.80% to 93.73%， and matrix effects were within the range of 97.93%-101.73%. RSDs of the stability test were all lower than 3.27%. During intraoperative TCI 2-30 min， the plasma concentration of propofol in 6 patients was maintained in the range of 1 865.3-6 056.2 ng/mL， and the propofol was almost excreted within 4-8 h after operation. CONCLUSIONS The established UPLC-MS/MS method in this study can achieve the determination of propofol and a simple and fast sample pretreatment process without derivatization； it is proved to be suitable for the concentration monitoring of propofol in plasma samples of patients with lymphedema.

Meta-analysis of efficacy and safety of sedative therapy with midazolam and dexmedetomidine/propofol in critically ill patients undergoing mechanical ventilation / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of midazolam and dexmedetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Clinical trials. gov， China Journal Full Text Database， Chinese Science and Technology Journal Database， Wanfang database and China Biomedical Literature Database， the data on the efficacy and safety of midazolam and dexmetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation were collected from the establishment of the database to March 31， 2023. After extracting data from clinical studies that met the inclusion criteria， the meta-analysis was conducted by using the RevMan 5.3 statistical software. RESULTS A total of 31 literature were included， with a total of 2 765 patients. Results of meta-analysis showed that the mechanical ventilation time [MD＝14.13， 95%CI （13.75， 14.52）， P＜0.000 01] and the length of hospitalization in the intensive care unit [MD＝0.92， 95%CI （0.54， 1.30）， P＜0.000 01] of patients in the midazolam group was longer than dexmedetomidine/ propofol group. The incidence of bradycardia in midazolam group was lower dexmedetomidine/propofol group [OR＝0.60， 95%CI （0.41， 0.90）， P＝0.01]， but there was no statistically significant difference in the incidence of hypotension between the two groups [OR＝0.69， 95%CI （0.47， 1.01）， P＝0.06]. The incidence of delirium [OR＝3.88， 95%CI （2.74， 5.49）， P＜0.000 01]， ventilator- associated pneumonia [OR＝2.32， 95%CI （1.19， 4.51）， P＝0.01]， and respiratory depression [OR＝5.70， 95%CI （3.09， 10.52）， P＜0.000 01] in midazolam group were higher than dexmedetomidine/propofol group. CONCLUSIONS Compared with dexmedetomidine/propofol， midazolam increases patients’ mechanical ventilation time and the length of hospitalization in the intensive care unit in terms of efficacy， and increases the risk of delirium and pulmonary complications in terms of safety， but has a smaller cardiovascular impact.

Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial

Abstract Background: Our objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. Methods: We conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.mr-2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 μg.mL-1 plus 0.5 μg.mL-1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg-1 plus 0.5 mg.kg-1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. Results: The median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0-0) vs. 0 (0-0) (p = 0.239) and 1 (0-1) vs. 3 (1-4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group - 2 (0-2) vs. 1 (0-1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 μg.kg-1.min-1 vs. 195 ± 44 μg.kg-1.min-1 (p = 0.040)). Conclusions: During colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Presentación de un caso y revisión de literatura: anestesia total intravenosa en cirugía de estesioneuroblastoma / Presentation of a case and literature review: total intravenous anesthesia in estesioneuroblastoma surgery

Resumen: El estesioneuroblastoma es una neoplasia de las células del neuroepitelio olfatorio. Tiene una baja incidencia de 0.4 por cada millón de habitantes. Se caracteriza por síntomas como sinusitis, epistaxis, cefalea, discapacidad visual, obstrucción nasal, hiposmia y rinorrea. En este reporte se presenta el caso de un paciente masculino de 29 años con estesioneuroblastoma estadio Kadish C, quien fue programado para resección quirúrgica bajo anestesia total intravenosa con resultados satisfactorios durante el procedimiento quirúrgico.

Abstract: Esthesioneuroblastoma is a neoplasm of the olfactory neuroepithelium cells, it has a low incidence of 0.4 per million inhabitants. It is characterized by symptoms such as sinusitis, epistaxis, headache, visual impairment, nasal obstruction, hyposmia, and rhinorrhea. We present the case of a 29-year-old male patient with Kadish C stage esthesioneuroblastoma, who was scheduled for surgical resection under total intravenous anesthesia with satisfactory results during the surgical procedure.

Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

A comparison between propofol and sevoflurane for easy insertion of laryngeal mask airway among adults in minor elective surgeries: An observational study

Background: The laryngeal mask airway (LMA) has reached ample popularity for the management of airway during surgery. Propofol, used as induction agent, causes change in blood pressure and heart rate (HR) while insertion of LMA. Sevoflurane, whereas, has the potential to be a good induction agent as propofol. We have compared propofol and sevoflurane for easy insertion of LMA among adults in minor surgeries. Aim and Objectives: The primary objective of the study was to compare the ease of insertion of LMA and its characteristics related to insertion among adults in minor elective surgeries using intravenous propofol or inhalational sevoflurane. While time taken to set induction and actual event of LMA insertion along with number of attempts, jaw relaxation time, LMA insertion time, apnea time, monitoring hemodynamic changes, and occurrence of complications were taken as secondary objectives. Materials and Methods: It was a prospective and observational study done in Department of Anesthesiology and Operation Theaters of Fortis Hospital, Kolkata, after getting ethical approval. Total 100 patients were recruited by consecutive sampling and divided into two groups - P (propofol) and S (sevoflurane) group. Anesthesia induction time, jaw relaxation time, LMA insertion time, etc. were noted. LMA insertion conditions were assessed by a 3-point scale using six variables, total score was calculated for each group. Hemodynamic parameters and induction complications were also recorded. Results: There was no significant difference in demographic parameters, American Society of Anesthesiologists class, Modified Mallampati Grading, and LMA size, between the groups. LMA insertion time was comparable between the two groups. Regarding complications, there was no incidence of coughing while minor gagging (4%) and laryngospasm (6%) were noted only with sevoflurane. Final summation of scores showed excellent insertion characteristics with propofol (94%) and sevoflurane (84%), respectively, with no significant difference. Conclusion: Inhalational sevoflurane may be regarded as a viable alternative to inj. propofol for insertion of laryngeal mask among adults in minor elective surgeries.

Comparative-study-of-etomidate-and-propofol-for-induction-of-general-anesthesia-in-elderly-patients

Introduction: An ideal induction agent for general anesthesia should have hemodynamic stability, minimal respiratory side effect and rapid recovery. Presently etomidate and propofol are popular rapid acting inducing agents. Material and methods: After obtaining informed written consent from patients this prospective, randomized, double blind study was conducted in 100 patients of ASA grade 3 and 4 posted for elective surgeries under general anaesthesia. They were divided into two groups of 50 in each group based on random number as group A and group B. The patients in Group A given Inj. Propofol and the patients in Group B received Inj. Etomidate. Parameters such as heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and spo2 were monitored continuously and recorded. Incidence and degree of pain of myoclonic movements were recorded. Demographic variables such as age,Result: gender, weight and ASA grade were comparable no significant difference existed between both the groups.Baseline mean heart rate, mean systolic blood pressure and mean diastolic blood pressure were comparable in both the Groups. (P>0.05)Significant (P<0.05) fall in mean systolic blood pressure, mean diastolic pressure and mean arterial pressure was observed immediately after induction, at 2, 5, 10 minutes up to 30 minutes in group A (propofol) compare to group B (etomidate). After then no significant difference seen in mean systolic pressure, mean diastolic pressure and mean arterial pressure. Etomidate was found ideal for its hemodynamic stability when compared to PropofolConclusion: along with less incidence of pain on injection, the only drawback being high incidence of myoclonus elderly patient.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study

Abstract Background Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. Methods Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n = 32 each). Melatonin group received two tablets (3 mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120 min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15 minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. Results Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1 min, respectively) (p< 0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p< 0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01 mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. Conclusion Premedication with 6 mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Anestesia intravenosa total para cirugía videolaparoscópica electiva en pacientes geriátricos / Total intravenous anesthesia for elective videolaparoscopic surgery in geriatric patients

Introducción: El surgimiento de fármacos anestésicos de corta duración estimularon a los anestesiólogos a plantearse un nuevo enfoque para la cirugía videolaparoscópica en el adulto mayor. Analgesia intensa, menor consumo de opioides, rápida recuperación de la conciencia y ventilación espontánea; extubación precoz, disminución de complicaciones y reducción de la estancia hospitalaria. Objetivo: Evaluar en los pacientes geriátricos programados para colecistectomía videolaparoscópica electiva, el efecto de la anestesia intravenosa total con la asociación ketamina/propofol en comparación con fentanil/propofol. Métodos: Se realizó un estudio cuasiexperimental en 40 pacientes con 60 años y más, estado físico II-III según la clasificación de ASA, en el Hospital Universitario "Faustino Pérez Hernández" de Matanzas, programados para cirugía videolaparoscópica electiva. Resultados: La edad promedio osciló entre 63 y 78 años, con una superioridad del sexo femenino y la raza blanca, la clasificación ASA II fue la más representativa en ambos grupos. Imperaron los antecedentes cardiovasculares, hubo ligera disminución de valores espirados de CO2 respecto a los basales, sin diferencias significativas. Hubo variación de la TAM indistintamente en ambos grupos. En el grupo 1 la frecuencia cardiaca posterior a la inducción disminuyó (70 ± 5 lat/min) y se mantuvieron valores inferiores a los basales durante los primeros 20 min, el tiempo medio de recuperación fue significativamente menor en el grupo 2. Conclusiones: La asociación ketamina/propofol proporciona resultados positivos finales.

Introduction: The emergence of short-acting anesthetic drugs stimulated the anesthesiologist to consider a new approach for videolaparoscopic surgery in the elderly. Intense analgesia, decreased opioid consumption, rapid recovery of consciousness, and spontaneous ventilation; early extubation, reduction of complications and reduction of hospital stay. Objective: To evaluate in geriatric patients scheduled for elective videolaparoscopic cholecystectomy the effects of total intravenous anesthesia with the combination of ketamine / propofol, comparing it with fentanyl / propofol. Materials and methods: a descriptive, prospective, longitudinal study was carried out in 40 patients aged 60 years and over, ASA II-III at the "Faustino Pérez Hernández" University Hospital in Matanzas in 2018, scheduled for elective videolaparoscopic surgery. Results: The average age ranged between 63 and 78 years, with a superiority of the female sex and the white race. The ASA II classification was the most representative in both groups. Cardiovascular antecedents prevailed, there was a slight decrease in expired CO2 values compared to baseline, without significant differences. There was variation of the TAM indistately in both groups. In group 1, the heart rate after induction decreased (70 ± 5 beats/min) and values lower than baseline were maintained during the first 20 min. The mean recovery time was significantly shorter in group 2. Conclusions: The association ketamine / propofol provides final positive results.

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxiareoxygenated endothelial cells via lncCCT4-2/CCT4 signaling

BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

Effect of combined sedation using multiple drugs on inflammatory cytokines in patients with acute respiratory distress syndrome

Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS

Propofol relieves the subcutaneous chloroquine-induced pruritus in rats via TRPV1 and CB1 receptors of spinal cord / 中国临床药理学与治疗学

AIM: To explore the possible mechanism of propofol in alleviating pruritus induced by subcutaneous injection of chloroquine in rats. METHODS: The pruritus model of chloroquine in SD rats was established and the administration time was determined. 18 rats with successful pruritus model induced by subcutaneous injection of chloroquine were randomly divided into NS group, I group and P group. Normal saline 80 μL/kg, fat emulsion 80 μL/kg and propofol 0.8 mg/kg were injected through internal jugular vein catheter 5 minutes after subcutaneous injection of chloroquine. Another 6 rats were randomly selected as group C, and the same volume of normal saline as the other 3 groups was injected subcutaneously in the back of the neck and through the internal jugular vein catheter. The rats were killed 16 minutes after the corresponding drugs were injected into the internal jugular vein. The expressions of TRPV1 and CB1 receptors in the spinal cord were detected by Western blot. RESULTS: Compared with NS group and I group, the expression level of TRPV1 receptor in the spinal cord of P group rats was significantly increased (P<0.01), while there was no statistically significant difference between C group, NS group, and I group; The expression level of CB1 receptor was significantly higher than that of group C, NS, and I (P<0.05), while there was no statistically significant difference between group C, NS, and I. CONCLUSION: Propofol can significantly alleviate pruritus caused by subcutaneous injection of chloroquine in rats, which may exert an antipruritic effect by increasing the expression of TRPV1 and CB1 receptors in the spinal cord of rats.

Application of remimazolam combined with propofol in painless endoscopic retrograde cholangiopancreatography / 中国临床药理学与治疗学

AIM: To observe and compare the clinical efficacy and safety of remimazolam and propofol alone and in combination in endoscopic retrograde cholangiopancreatography (ERCP) anesthesia. METHODS: A total of 120 patients undergoing elective ERCP were divided into the propofol group (P group), the remimazolam group (R group), and the remimazolam combined with propofol group (RP group) according to a random number table, with 40 patients in each group, and the three groups completed anesthesia according to the designated drug regimen (propofol in group P; remimazolam in group R; and remimazolam combined with propofol in group RP). General information, operation time and awakening time of the patients in the three groups were compared, as well as oxygen saturation (SpO

Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice / 南方医科大学学报

OBJECTIVE@#To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.@*METHODS@#Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.@*RESULTS@#In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.@*CONCLUSION@#Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.

Quality of psychomotility recovery after propofol sedation for painless gastroscopy and colonoscopy / 北京大学学报(医学版)

OBJECTIVE@#To study the effect of propofol used for painless gastroscopy and colonoscopy on psychomotility recovery.@*METHODS@#One hundred adult patients undergoing painless gastroscopy and colonoscopy were recruited, aged 18-72 years, with American Society of Anesthesiologist (ASA) physical status Ⅰ-Ⅱ. According to age, the patients were divided into youth group (20-39 years old, 27 cases), middle age group (40-54 years old, 37 cases), and elder group (55-64 years old, 36 cases). Propofol was continuously infused according to the patients' condition to mantain the bispectal index (BIS) score 55-64. All the patients received psychomotility assesment 30 min before the operations when the discharge criteria were met including number cancellation test, number connection test and board test. The heart rate, blood pressure, saturation of pulse oximetry, electrocardiograph and BIS were monitored during the operation. The operating time, recovery time, total volume of propofol and discharge time were recorded. If the results obtained were inferior to those before operation, a third assessment was taken 30 minutes later until the results recovered or being superior to the baseline levels.@*RESULTS@#All the patients completed the first and second assessments, and 25 patients had taken the third assessment. There was no statistically significant difference in the results of psychomotility assessment when the patients met the discharge standard. Furthermore, the results were analyzed by grouping with age, and there was no statistical difference in the test results of the youth and middle age groups compared with the preoperative group, among which, the efficiency of the number cancellation test was significantly better than that before operation in the youth group (P < 0.05). However, in the elderly patients the number cancellation efficiency, number connection test and board test were significantly inferior to that before operation (P < 0.05). There was no significant difference in the accuracy of number cancellation compared with that before operation. The patients who needed the third test in the elder group were significantly more than in the other groups (P < 0.05). Compared with the preoperative results, there was no statistical difference in the test results of those who completed the third test.@*CONCLUSION@#The psychomotility function of the patients who underwent painless gastroscopy and colonoscopy was recovered when they met discharge criteria. The elderly patients had a prolonged recovery period.

Effects of propofol on glutamatergic neuronal activity in paraventricular thalamus / 药学学报

This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as FB, FD and FW; and the membrane potentials were recorded as MPB and MPD. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABAA) receptors during the application of propofol at 10 μmol·L-1. Then, GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in FB, FD and FW during intralipid and 2 μmol·L-1 propofol application. With propofol at 5, 10 and 20 μmol·L-1, FD decreased significantly when compared with FB, and FW increased significantly as compared with FD (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L-1, MPD hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABAA receptors.