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.

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.

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.

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.

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.

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.

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.

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

Effect analysis of thoracic paravertebral nerve block combined with propofol intravenous anesthesia in radical treatment of lung cancer / 中国医师杂志

Objective:To investigate the effects of thoracic paravertebral nerve block combined with propofol intravenous anesthesia (PPA) on hemodynamic parameters, inflammatory stress indexes, postoperative analgesia and immune indexes in patients with lung cancer undergoing radical surgery.Methods:116 patients with lung cancer admitted to the Southern Theater General Hospital from January 2020 to December 2021 were randomly divided into observation group and control group, with 58 patients in each group. The observation group received PPA combined with general anesthesia, and the control group received sevoflurane inhalation combined with general anesthesia; the hemodynamic parameters, the amount of anesthetic and analgesic drugs used during and after the operation, the pain score of the patients after the operation, the serum interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol (Cor), norepinephrine (NE), vascular cell growth factor-C (VEGF-C), transforming growth factor-β 1(TGF-β1) and T lymphocytes before and after the operation, adverse reactions of the two groups were monitored and compared.Results:The intraoperative dosage of remifentanil and postoperative dosage of sufentanil in the observation group were lower than those in the control group (all P<0.05). There was no statistically significant difference in cardiac output (CO), systemic vascular resistance index (SVRI) and extravascular lung water index (EVLWI) between the observation group and the control group at T 0 to T 3 (all P>0.05); The mean arterial pressure (MAP) at T 1 to T 2 in the observation group was higher than that in the control group, and the MAP at T 3 was lower than that in the control group (all P<0.05). There was no significant difference between observation group and control group in Visual Analogue Scale (VAS) scores at resting state and coughing state 2 h after surgery(all P>0.05). The VAS scores in the observation group at resting state were lower than those in the control group at 4 h and 12 h after surgery (all P<0.05), and the VAS scores in the observation group at coughing state were lower than those in the control group at 4 h, 12 h and 24 h after surgery (all P<0.05). Before surgery, there was no significant difference in serum levels of IL-6, IL-10, Cor, NE, VEGF-C and TGF-β1 between observation group and control group (all P>0.05). The serum levels of IL-6, NE and VEGF-C in observation group were lower than those in control group 24 h after surgery (all P<0.05). Before surgery, there was no significant difference in CD3 +, CD4 + and CD8 + between observation group and control group (all P>0.05). 24 h after operation, the CD3 + in observation group was higher than that in control group ( P<0.05). The incidence of adverse reactions in observation group (10.34%) was lower than that in control group (24.14%, P<0.05). Conclusions:PPA anesthesia for patients undergoing radical resection of lung cancer is conducive to maintaining the stability of hemodynamic parameters, reducing the inflammatory stress response of patients, the impact of surgery on patients′ immune function, and the amount of anesthetic drugs and postoperative analgesics during surgery.

Regulation of AMPA receptor on propofol induced hippocampal mitochondrial injury in neonatal rats / 中华危重病急救医学

Objective:To investigate whether propofol can cause injury to hippocampal mitochondria in neonatal rats and the regulation of excitatory amino acid receptor AMPA receptor.Methods:Forty-eight Sprague-Dawley (SD) rats aged 7 days were randomly divided into control group, propofol group, propofol+AMPA receptor agonist AMPA group (propofol+AMPA group) and propofol+AMPA receptor inhibitor CNQX group (propofol+CNQX group), with 12 rats in each group. The rats in the propofol groups were intraperitoneally injected with 30 mg/kg propofol, while in control group with 3 mg/kg normal saline. Each group was given 1/2 of the first dose every 20 minutes after the first administration, three times a day, for three consecutive days. The rats in the propofol+AMPA group and the propofol+CNQX group were injected with 1 g/L AMPA or CNQX 5 μL through left ventricle after the first administration. Three days after administration, the rats were sacrificed to obtain brain tissue. Western blotting was used to determine the expression of AMPA receptor glutamate receptors (GluR1, GluR2) subunit totally (T) and on membrane (M) in hippocampus. The expression of dynamin-related protein-1 (DRP-1) and phosphorylated-DRP-1 (p-DRP-1) and mitofusin 2 (Mfn2) related to mitochondrial fission and fusion were determined. The adenosine triphosphate (ATP) content and ATPase activity were determined.Results:Compared with the control group, GluR1 expression and its M/T ratio were significantly increased after treatment of propofol, GluR2 expression and its M/T ratio were significantly decreased, the ATP content and ATP-related enzyme activity were decreased significantly, while the expression of DRP-1 and its phosphorylation was significantly increased, and the expression of Mfn2 was significantly decreased. The changes indicated that repeated intraperitoneal injection of 30 mg/kg propofol leading to the injury of mitochondria in neural cells. Compared with the propofol group, the GluR1 expression and its M/T ratio further increased after AMPA agonist administration [T-GluR1 protein (T-GluR1/β-actin): 2.41±0.29 vs. 1.72±0.11, M-GluR1 protein (M-GluR1/β-actin): 1.18±0.15 vs. 0.79±0.09, M/T ratio: 0.78±0.12 vs. 0.46±0.08, all P < 0.01], GluR2 expression was significantly increased [T-GluR2 protein (T-GluR2/β-actin): 0.65±0.13 vs. 0.30±0.14, P < 0.01; M-GluR2 protein (M-GluR2/β-actin): 0.17±0.05 vs. 0.13±0.07, P > 0.05], but its M/T ratio was further decreased (0.27±0.10 vs. 0.41±0.08, P < 0.05). The ATP-related enzyme activity was further decreased, and the ATP content was further decreased (μmol/g: 0.32±0.07 vs. 0.70±0.10, P < 0.01). Mitochondria DRP-1 expression and its phosphorylation were further increased [DRP-1 protein (DRP-1/GAPDH): 2.75±0.36 vs. 1.70±0.19, p-DRP-1 protein (p-DRP-1/GAPDH): 0.99±0.14 vs. 0.76±0.15, both P < 0.05], and Mfn2 expression was further decreased (Mfn2/GAPDH: 0.23±0.12 vs. 0.54±0.12, P < 0.05). This indicated that the AMPA agonist increased the expression of the AMPA receptor GluR1 subunit on the cell membrane and shifted the GluR2 into the cell, thus increasing the mitochondrial injury caused by propofol. Compared with the propofol group, the GluR1 expression and its M/T ratio decreased significantly after AMPA inhibitor administration [T-GluR1 protein (T-GluR1/β-actin): 0.99±0.14 vs. 1.72±0.11, M-GluR1 protein (M-GluR1/β-actin): 0.21±0.07 vs. 0.79±0.09, M/T ratio: 0.21±0.07 vs. 0.46±0.08, all P < 0.01], the change of GluR2 expression was not significant, but its M/T ratio was significantly increased (0.59±0.09 vs. 0.41±0.08, P < 0.05). The ATP-related enzyme activity was increased significantly, and the ATP content was increased significantly (μmol/g: 0.87±0.12 vs. 0.70±0.10, P < 0.05). Mitochondria DRP-1 expression and its phosphorylation were significantly decreased [DRP-1 protein (DRP-1/GAPDH): 1.18±0.17 vs. 1.70±0.19, p-DRP-1 protein (p-DRP-1/GAPDH): 0.37±0.10 vs. 0.76±0.10, both P < 0.05], and Mfn2 expression was significantly increased (Mfn2/GAPDH: 0.78±0.10 vs. 0.54±0.12, P < 0.05). This indicated that AMPA inhibitor promoted the movement to the cell membrane of GluR2 subunits meanwhile inhibited the expression of GluR1 subunits, thus alleviating the injury of mitochondrial caused by propofol in the brain. Conclusions:Repeated intraperitoneal injection of 30 mg/kg propofol for 3 days can increase the expression of GluR1 subunits of AMPA receptor in 7-day neonatal rats hippocampus mainly distributing in the cell membrane, decrease the expression of GluR2 subunits moving into the cell, thus causing injury of mitochondrial function and dynamics, which can be aggravated by AMPA receptor agonist and alleviated by AMPA receptor inhibitors.

Effects of dexmedetomidine combined with propofol on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy / 中国医师进修杂志

Objective:To investigate the effects of dexmedetomidine combined with propofol on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy.Methods:The clinical data of 82 patients who underwent painless gastroenteroscopy in Fuyang Minsheng Hospital from April 2021 to November 2022 were retrospectively collected, and they were divided into the control group and the observation group by anesthesia induction method, each group with 41 cases. The control group was anesthetized with propofol, and the observation group was anesthetized with dexmedetomidine and propofol. The recovery time, orientation recovery time and satisfaction of the two groups were compared; the cognitive function before anesthesia, 1, 12 h after anesthesia and 1, 7 d after anesthesia were compared; the changes of hemodynamics and diaphragm movement before anesthesia induction (T 0), 5 min after anesthesia induction (T 1) and at awakening (T 2) and adverse reactions were compared. Results:The recovery time, orientation recovery time in the observation group were shorter than those in the control group: (9.87 ± 1.52) min vs. (11.92 ± 1.74) min, (15.87 ± 2.31) min vs.(18.79 ± 2.54) min; the dosage of propofol was less than that in the control group: (200.21 ± 50.46) mg vs. (300.23 ± 60.29) mg; the satisfaction scores was higher than that in the control group: (9.54 ± 0.32) scores vs. (8.81 ± 0.47) scores, there were statistical differences ( P<0.05). The scores of Mini-Mental State Examination (MMSE) at 1 h after anesthesia and 12 h after anesthesia in the observation group were higher than those in the control group: (23.12 ± 1.86) scores vs. (20.31 ± 1.65) scores, (26.21 ± 1.43) scores vs. (24.12 ± 1.57) scores, there were statistical differences ( P<0.05). The scores of MMSE at 1, 7 d after anesthesia had no statistical differences between the two groups ( P>0.05). The levels of mean arterial pressure (MAP) and heart rate (HR) at T 1 and T 2 were decreased and the levels of MAP and HR at T 1 and T 2 in the observation group were higher than those in the control group: (76.48 ± 4.01) mmHg (1 mmHg = 0.133 kPa) vs. (72.31 ± 3.26) mmHg, (82.31 ± 3.27) mmHg vs. (77.97 ± 3.64) mmHg; (78.72 ± 2.17) bpm vs. (76.23 ± 2.35) bpm, (82.19 ± 3.08) bpm vs. (79.63 ± 2.56) bpm, there were statistical differences( P<0.05). The diaphragm thickness fraction (DTF) and diaphragmatic motion amplitude (DM) at T 1 and T 2 were decreased and the levels of DTF and DM at T 1 and T 2 in the observation group were higher than those in the control group: 0.21 ± 0.02 vs. 0.17 ± 0.03, 0.26 ± 0.03 vs. (0.22 ± 0.04); (15.67 ± 0.81) mm vs. (14.21 ± 0.77) mm, (16.72 ± 0.68) mm vs. (15.46 ± 0.82) mm, there were statistical differences ( P<0.05). The adverse reactions in the two groups had no significant difference ( P>0.05). Conclusions:The combination of dexmedetomidine and propofol has little effect on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy, which can accelerate the recovery of patients and improve patient satisfaction.

Effects of different carbon dioxide pneumoperitoneum pressures combined general anesthesia with sevoflurane-propofol on cerebral oxygenmetabolism balance and stress response in elderly patients undergoing colorectal cancer surgery / 中国医师进修杂志

Objective:To study the effects of different carbon dioxide (CO 2) pneumoperitoneum pressures combined general anesthesia with sevoflurane-propofol on cerebral oxygenmetabolism balance and stress response in elderly patients undergoing colorectal cancer surgery. Methods:A retrospective collection of 100 colon cancer cases from February 2020 to February 2021 in the Jiading Branch of Shanghai First People′s Hospital (Jiangqiao Hospital, Jiading District) and the Shanghai First People′s Hospital were divided into low pressure group and high pressure group according to different CO 2 pneumoperitoneum pressure values, each with 50 cases and 12 mmHg(1 mmHg = 0.133 kPa) and 18 mmHg CO 2 pneumoperitoneum pressure values were used to inflate, and the perioperative status, cerebral oxygen metabolism status, and stress response of the two groups were observed. Results:The take food time, first time out of bed in the low pressure group were lower than those in the high pressure group: (45.67 ± 7.34) h vs. (49.67 ± 8.16) h, (34.69 ± 8.26) h vs. (39.87 ± 7.16) h, there were statistical differences( P<0.05). The time of first anal exhaust and hospital stay in the two groups had no significant differences ( P>0.05). Repeated measures analysis of variance results showed that the levels of partial pressure of carbon dioxide in artery, oxyhemoglobin saturation, arterial blood lactate acid, benous blood lactic acid were different followed the time and treatment methods ( P<0.05). The levels of heart rate, mean arterial pressure, cortisol and thyroid stimulating hormone in the low pressure group were higher than those in the high pressure group: (73.68 ± 6.35) beats/min vs. (84.84 ± 6.86) beats/min, (81.67 ± 13.68) mmHg vs. (93.68 ± 14.37) mmHg, (100.24 ± 12.34) μg/L vs. (135.68 ± 13.69) μg/L, (3.12 ± 0.43) mU/L vs. (3.54 ± 0.34) mU/L, there were statistical differences ( P<0.05). Conclusions:Different CO 2 pneumoperitoneal pressures affect the brain oxygen metabolism of patients, and clinical attention should be paid to them.

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

Effects of midazolam combined with propofol on recovery of patients with laparoscopic cholecystectomy / 药学实践杂志

Objective To explore the effect midazolam combination with propofol on postoperative recovery in patients undergoing laparoscopic cholecystectomy. Methods A total of 162 patients who were admitted to the hospital for laparoscopic cholecystectomy from April 2019 to January 2021 were selected. According to different anesthesia methods, they were divided into control group (midazolam anesthesia) and observation group (midazolam combined with propofol anesthesia), with 81 cases in each group. The stress index levels before and after operation, MoCA scores before operation (T0), 24 h after operation (T1) and 48 h after operation (T2), sleep quality at T0, the first day after operation (T3) and the second day after operation (T4), the perioperative recovery were compared between the two groups. Results The levels of Cor and NE, the recovery time of eyes opening, extubation, orientation, and the incidence of adverse reactions in the observation group were lower than those in the control group (P<0.05). Observation group MMSE score when T1, T2, T3, T4 sleep quality score were higher than control group (P<0.05). Conclusion Midazolam combined with propofol was safe and had good postoperative recovery in patients undergoing laparoscopic cholecystectomy.

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.