1. Pharmacological characteristics of esketamine and its application progress in pediatric anesthesia
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):328-333
Esketamine is an antagonist of the N-methyl-D-aspartate (NMDA) receptor and exerts antianxiety, hypnotic, sedative, and analgesic effects by interacting with NMDA receptors, opioid receptors, M - choline receptors, monoamine receptors, adenosine receptors, and other purine receptors. As the more potents isomer of ketamine, it is about twice as potent as ketamine. Compared with ketamine, esketamine has the characteristics of rapid onset and metabolism, strong analgesia, slight respiratory depression, rapid recovery of cognitive function, and low incidence of psychiatric side effects. It has become a new choice of pediatric anesthesia drugs. This article reviews the pharmacological properties of esketamine and its recent application in pediatric anesthesia, and provides reference for the safe use of esketamine in pediatric perioperative period.
2. Effects of sodium pyruvate on the morphology, structure and function of erythrocytes stored in vitro in type 2 diabetes rats
Yu BAI ; Na YAO ; Xiaoyi XIE ; Mandi WU ; Yinghui CUI ; Jianrong GUO ; Yongbin CHI
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(2):139-145
AIM: To observe the effect of RBC preservation solution with sodium pyruvate on the morphology, structure and function of RBC stored in vitro in type 2 diabetes rats. METHODS: Thirty SPF male SD rats, were randomly divided into 3 groups (n=10): non-T2DM conventional RBC preservation solution (group A), T2DM conventional RBC preservation solution (group B) and T2DM sodium pyruvate RBC preservation solution (group C). The leukoreduced RBC from the tail vein and stored for 0 d (T0), 7 d (T1), 14 d (T2), 21 d (T3) and 28 d (T4) to detect the morphology, structure and the contents of 2, 3-DPG, reactive oxygen species (ROS), malondialdehyde (MDA) and lactic acid (LA) of RBC in group A, B and C. The RBC stored for 14 days in vitro were labeled with PKH26, and its survival rate were tested in vivo at 1, 4, 10 and 16 hours after intravenous infusion. RESULTS: At T0, the RBC morphology of group A was intact, which was better than that of group B and group C. With the extension of storage time, the morphology of RBC in each group gradually transformed into a spindle-spherical shape. Compared with group A, the incidence of acanthocytes in group B and group C was higher, and the incidence of acanthocytes in group C was lower than that in group B. Compared with group A, the content of 2, 3-DPG in group B and group C decreased, while ROS and MDA increased at different time points (P<0.05). The content of 2,3-DPG in group C was higher than that in group B (P<0.05), and the contents of ROS and MDA were lower than those in group B (P<0.05). LA content in group B was higher than that in group A and group C (P<0.05). At T2-T4, the LA content in group C was lower than that in group A (P<0.05). The survival rate of RBC in group A was higher than that in group B and C, and the survival rate of RBC in group B was lower than that in group C (P<0.05). CONCLUSION: Sodium pyruvate added RBC preservation solution has a certain protective effect on RBC stored in vitro in type 2 diabetic rats, and its mechanism may be related to its antioxidant effect.
3.Effect of novel erythrocyte preservation solution on quality of erythrocytes in stored blood of T2DM rats
Mandi WU ; Na YAO ; Yu BAI ; Yinghui CUI ; Xiaoyi XIE ; Yongbin CHI ; Jianrong GUO
Chinese Journal of Anesthesiology 2024;44(3):302-306
Objective:To evaluate the effect of novel erythrocyte preservation solution on the quality of erythrocytes in stored blood of type 2 diabetes mellitus (T2DM) rats.Methods:Forty SPF male Sprague-Dawley rats, aged 8 weeks, weighing 180-220 g, were used in this study. Ten rats randomly selected served as conventional erythrocyte preservation solution group (group A). T2DM model was prepared in the remaining 30 rats. Twenty T2DM rats were divided into 2 groups ( n=10 each) using a random number table method: T2DM conventional erythrocyte preservation solution control group (group C) and T2DM novel erythrocyte preservation solution observation group (group Y). Erythrocyte preservation solution was prepared to simulate the preoperative autologous blood donation process, and blood was collected from the tail vein to isolate the red blood cells, and then the corresponding preservation solution was added. Immediately after blood collection (T 0) and at 7, 14 and 21 days of preservation (T 1-3), the morphological structure of erythrocytes was observed with a light microscope, and the concentrations of 2, 3-diphosphoglycerate (2, 3-DPG) and reactive oxygen species (ROS) were also determined by enzyme-linked immunosorbent assay at T 0-T 3 and 28 days of preservation (T 4). PKH26 was used to label the erythrocytes stored in vitro for 28 days, and then the erythrocytes were transfused back into rats. The survival rate of erythrocytes was detected by flow cytometry at 1, 7, 13 and 18 h after retransfusion. Results:The erythrocyte damage was aggravated at different time points of preservation in group C when compared with group A. Compared with group C, the damage to erythrocytes was significantly alleviated at different time points of preservation in group Y. Compared with group A, the concentration of 2, 3-DPG in erythrocytes was significantly decreased at T 0 and T 2-T 4, the concentration of ROS was increased at T 0-T 4, and the survival rate of erythrocytes was decreased at 1, 7 and 18 h after retransfusion in group C ( P<0.05). Compared with group C, the concentration of 2, 3-DPG in erythrocytes was significantly increased at T 0-T 4, the content of ROS was decreased at T 1, T 3 and T 4, and the survival rate of erythrocytes was increased at 1, 7 and 18 h after retransfusion in group Y ( P<0.05). Conclusions:The novel erythrocyte preservation solution can improve the quality of stored erythrocytes and increase the survival rate of erythrocytes in vivo after retransfusion in T2DM rats.
4.Effects of acute normovolemic hemodilution on target-controlled infusion of etomidate blood concen-trations and adrenocortical function
Yinghui CUI ; Jiaming XU ; Tong LIU ; Haiyong TAO ; Xi-Aoyi XIE ; Shejun HU ; Xuefei WANG ; Jinghuo WANG ; Jianrong GUO
The Journal of Clinical Anesthesiology 2024;40(8):814-819
Objective To observe the effects of acute normovolemic hemodilution(ANH)on target-controlled infusion(TCI)of etomidate blood drug concentration and adrenal cortical function.Methods Sixty patients who undergo elective multisegmental spine surgery,35 males and 25 females,aged 30-60 years,BMI 20-25 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using random number table method:ANH group and control group,30 patients in each group.Both groups used a target-controlled infusion of etomidate for anesthesia induction and anesthesia maintenance.In the ANH group,ANH was performed after steady anesthesia induction,ideal Hct 28%to 30%,and transfused within 1 hour after surgery;the control group was routinely treated.The dosage of etomidate was recorded.Liquid chroma-tography-tandem mass spectrometry(LC-MS/MS)was used to detect etomidate blood concentrations at the immediate postoperative,10,20,and 30 minutes postoperative periods in the two groups,and the immedi-ate moment autologous blood collected into the storage bag,preserved in the storage bag for 1 hour,and the immediate moment transfused back in the ANH group.Plasma concentrations of cortisol(Cor),adrenocorti-cotropic hormone(ACTH),and aldosterone(ALD)were measured by chemiluminescence immunoassay(CLIA)before the induction of anesthesia,immediately after the operation,and at 1 day and 2 days postop-eratively.Results There was no significant difference in the total dosage of etomidate between the two groups.Compared with the immediate postoperative period,the plasma etomidate concentration was signifi-cantly decreased 10,20,and 30 minutes after surgery(P<0.05).Compared with the control group,the concentration increased significantly 10 minutes after surgery in the ANH group(P<0.05).The plasma concentrations of etomidate were(547.8±119.4)ng/ml at the immediate moment autologous blood collected into the storage bag,(536.7±107.8)ng/ml at the preserved in the storage bag for 1 hour,and(522.8±91.7)ng/ml at theimmediatemoment transfusedbackinthe ANHgroup.Comparedwithbeforein-duction of anesthesia,the concentration of Cor and ALD immediately after the operation decreased signifi-cantly(P<0.05)and the concentration of ACTH was significantly higher(P<0.05).There were no sta-tistically significant differences in the concentrations of Cor,ALD,and ACTH between the two groups before induction of anesthesia 1 day and 2 days postoperatively.Conclusion In the orthopedic surgery of TCI eto-midate,return transfusion of collected autologous blood transiently(about 10 minutes)increases etomidate blood concentrations,the function of adrenal cortical will recover to the preoperative level within 24 hours after the operation.
5.Research progress on the effects of propofol on tumor growth and metastasis mechanism
Baowei JIN ; Kai WANG ; Jianrong GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(9):1042-1048
Propofol,as a widely used intravenous anesthetic,has been found to have the potential of anti-tumor growth and metastasis in recent years.At present,the research on the mechanism of pro-pofol inhibiting tumor growth and metastasis is still relatively limited.In this paper,we summarize the recent studies on the role of propofol in inhibiting tumor growth and metastasis and its possible mo-lecular mechanisms,such as regulating specific sig-naling pathways or key molecules,and interacting with other molecules.At the same time,the appli-cation of propofol,including the optimization of ad-ministration route and dose,as well as the possibili-ty of being an adjunct therapy to radiotherapy and chemotherapy,was analyzed,and the recent stud-ies on the mechanism of propofol inhibiting tumor growth and metastasis were reviewed,providing a reference for further exploration of the application and research direction of propofol in clinical anti-tu-mor growth and metastasis therapy.
6. Changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute isovolumic hemodilution and its influence on anesthetic effect after reinfusion
Tong LIU ; Jinhuo WANG ; Yongquan CHEN ; Tong LIU ; Jiaming XU ; Jinhuo WANG ; Lei YIN ; Jianrong GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):413-418
To investigate the changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute normovolemic hemodiluti-on and its influence on the depth of anesthesia, muscle relaxant effect and blood drug concentration after reinfusion. METHODS: Forty patients of both sexes, aged 20-60 yr, American Society of Anesthesiologists physical status or Ⅱ, hemoglobin (Hb) >120 g / L, hematocrit (Hct) >35%, undergoing eletive multilevel spinal surgery were included, were divided into 2 groups (n=20 each) using a random number table. ANH group (group A): ANH was performed after stable induction of anesthesia, the target Hct value was 28%-30%, and autologous blood was reinfused after the main operation steps. Control group (group C): routine transfusion and infusion treatment. The bispectral index (BIS) and Train-of-Four stimulation (TOF) were observed and recorded at the stable induction of anesthesia (T1), 30 minutes of stable induction (T2), the end of operation (T3), 30 minutes after the end of the operation (T4), 1 hour after the end of the operation (T5) and 2 hours after the end of the operation (T6). The concentrations of propofol and cisatracurium besylate in plasma at T1-T6, stored blood at 1 h (TS1), 2 h (TS2), and before reinfusion (TS3) were detected by Liquid Chromatography-tandem Mass Spectrometry. The extubation time and recovery score at T4-6 hours were recorded. RESULTS: There was no significant difference in propofol between the two groups at each time point (P > 0.05). The plasma concentration of cisatracurium besylate in group A was higher than that in group C at T3 (P<0.05). The concentration of two kinds of anesthetic drugs in blood samples decreased slightly with time,but there was no significant difference between groups (P>0.05). The BIS value at T4 and TOF value at T3 in group A were significantly lower than those in group C. The recovery score of group A was lower than that of group C at T4 (P<0.05). There was no significant difference in extubation time (P>0.05). CONCLUSION: The plasma concentrations of propofol and cisatracurium besylate were basically unchanged during the in vitro isolation of ANH autologous blood. The plasma concentrations of cisatracurium besylate were only temporarily affected after the main operation steps, but the postoperative muscle relaxation recovery and recovery quality were not significantly affected.
7.Monitoring of residual cisatracurium besylate in elderly patients plasma at post operation by UPLC-MS/MS
Jiaming XU ; Xiaofang ZHOU ; Jianrong GUO
Journal of Pharmaceutical Practice 2023;41(3):192-196
Objective To establish a method for the determination of cisatracurium besylate in human plasma by UPLC-MS/MS which could be used in the monitoring of drug residual in plasma of elderly patients after operation. Methods The samples were precipitated with 0.1% formic acid-acetonitrile solution and separated by an SHISEIDO ADME column(3.0 mm×100 mm, 2.7 μm) for isocratic elution with the mobile phase of water containing 0.1% formic acid with 2 mmol/L ammonium acetate and acetonitrile (30:70, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent jet stream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were m/z 464.3→358.2 for cisatracurium besylate and m/z 557.4→356.3 for vecuronium bromide (the internal standard, IS). Plasma samples of elderly patients undergoing spinal surgery were collected after anesthesia induction, at the end of surgery, 0.5 h and 1 h after surgery, and from the blood bags while autologous blood transfusion, and stored in cryopreservation tubes with 2% formic acid solution. Then the contents of cisatracurium besylate were determined. The effects of autogenous blood transfusion on plasma concentration of cisatracurium besylate in elderly patients after surgery evaluated. Results The calibration curve was linear in the range of 20-5 000 ng/ml for cisatracurium besylate in human plasma, r=0.999 7. The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). The matrix effect of different concentrations was 71.88%~80.64%. The recovery of different concentrations was 83.62%~88.87%. The recovery of vecuronium bromide (IS) was 125.91%, which conformed with the requirement of methodological validation. There was a certain degree of residual cisatracurium besylate in the plasma of elderly patients, so the extubation time should be strictly controlled and the stay time of patients in the anesthesia recovery room should be appropriately extended. Conclusion The method is sensitive, accurate, and efficient, which could be used for the determination of cisatracurium besylate in human plasma of elderly patients after operation.
8.Effect of intraoperative cell salvage on the number and viability of cancer cells in salvaged autologous blood from patients undergoing liver cancer surgery
Jinhuo WANG ; Zhenzhou LI ; Yong CHENG ; Yuming SUN ; Lei CHEN ; Jianrong GUO
Chinese Journal of Anesthesiology 2023;43(5):580-584
Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.
9. Effect of COX-2 inhibitors on postoperative delirium in elderly patients undergoing orthopedic surgery and its possible mechanism
Jinhuo WANG ; Xinyue GAO ; Jianrong GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(8):863-869
AIM: To observe the effects of cyclooxygenase-2 (COX-2) inhibitors on the levels of inflammatory factors, nerve damage-related factors and antioxidant factors, as well as pain and delirium scores in the plasma of elderly patients with orthopaedic surgery, to clarify the role of COX-2 inhibitors in the prevention and treatment of POD and explore its possible mechanism. METHODS: Eighty patients undergoing elective hip arthroplasty were randomly divided into parecoxib sodium group (P group, n =40) and control group (C group, n = 40). Group C was injected with the same volume of normal saline at the same time point, and the preoperative cognitive function was screened 1 d (T
10.Application and risk assessment of intraoperative cell salvage in patient with malignancy
Zhenzhou LI ; Yaru CHEN ; Jianrong GUO
Chinese Journal of Blood Transfusion 2022;35(3):345-348
Patients with malignant tumour often require massive transfusion. Intraoperative cell salvage(IOCS) was initially limited in cancer surgery by concerns about the possibility of dissemination of tumor cells into circulation. However, as supportive literature concerning IOCS research and application in cancer surgery are increasing, it is necessary to reassess the perioperative application of IOCS in patients with malignancy. This review summarizes the application, risks and value of IOCS during cancer operations.

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