Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients: A meta-analysis.

BACKGROUND: Remimazolam is characterized by rapid action and inactive metabolites. It is used as the general anesthetic for many clinical surgeries. In this study, we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients. AIM: To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults. METHODS: The PubMed, Web of Science, the Cochrane Library databases were queried for the relevant key words "remimazolam," "and propofol," "and gastrointestinal endoscopy or gastroscopy." The search scope was "Title and Abstract," and the search was limited to human studies and publications in English. Seven studies wherein remimazolam and propofol were compared were included for the meta-analysis. RESULTS: We selected seven randomized controlled trials involving 1445 cases for the analysis. Remimazolam reduced the hypotension (relative risk, RR = 0.44, 95%CI: 0.29-0.66, P = 0.000), respiratory depression (RR = 0.46, 95%CI: 0.30-0.70, P = 0.000), injection pain (RR = 0.12, 95%CI: 0.05-0.25, P = 0.000), bradycardia (RR = 0.37, 95%CI: 0.24-0.58, P = 0.000), and time to discharge [weighted mean difference (WMD) = -0.58, 95%CI: -0.97 to -0.18, P = 0.005], compared to those after propofol administration. No obvious differences were observed for postoperative nausea and vomiting (RR = 1.09, 95%CI: 0.97-1.24, P = 0.151), dizziness (RR = 0.77, 95%CI: 0.43-1.36, P = 0.361), successful sedation rate (RR = 0.96, 95%CI: 0.93-1.00, P = 0.083), or the time to become fully alert (WMD = 0.00, 95%CI: -1.08-1.08, P = 0.998). CONCLUSION: Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults. However, further studies are required to confirm these findings.

Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy. / å³ç¾Žæ‰˜å’ªå®šå¯¹è€å¹´æ‚£è€ è‚å¶åˆ‡é™¤æœ¯åŽè°µå¦„å’Œæ—©æœŸæœ¯åŽè®¤çŸ¥åŠŸèƒ½éšœç¢çš„é¢„é˜²æ•ˆæžœ.

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 µg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 µg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1ß, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1ß decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1ß at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1ß and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

Propofol suppressed cell proliferation and enhanced apoptosis of bladder cancer cells by regulating the miR-340/CDK2 signal axis.

BACKGROUND: As widely reported, propofol can effectively inhibit tumors development. However, little is known about the molecular mechanisms. Here, we proved that propofol regulated miR-340/CDK2 axis to suppress bladder cancer progression in vitro. METHODS: MicroRNA (MiR)-340 expression in 5637 cells was examined using qRT-PCR. Cyclin-dependent kinase2 (CDK2) expression was detected using both qRT-PCR and western blot. The levels of apoptosis-related proteins and cell cycle-related proteins were evaluated using western blot. CCK-8 assay and BrdU assay were conducted to evaluate cell proliferation. Moreover, flow cytometry assay was employed to assess cell cycle and cell apoptosis. Finally, dual luciferase reporter assay was employed to verify the binding relationship between miR-340 and CDK2. RESULTS: Here we showed that propofol treatment inhibited cell proliferation of 5637 cells but enhanced cell apoptosis. Propofol upregulated miR-340 in a dose and time dependent manner. MiR-340 inhibitor could reverse the effect of propofol on the proliferation and apoptosis of 5637 cells. Next, dual luciferase reporter assay displayed that miR-340 directly bound to the 3'-UTR of CDK2. Finally, inhibition of CDK2 could partly reversed the effect of miR-340 inhibitor on cell proliferation and cell apoptosis of propofol-treated 5637 cells. CONCLUSION: In total, our results proved that targeting miR340/CDK2 axis was novel to enhance the anti-tumor effects of propofol in bladder cancer in vitro, and our study provided alternative therapeutic strategies for clinical treatment of bladder cancer.

Effect of Dexmedetomidine-Assisted Intravenous Inhalation Combined Anesthesia on Cerebral Oxygen Metabolism and Serum Th1/Th2 Level in Elderly Colorectal Cancer Patients.

OBJECTIVE: To observe the effect of dexmedetomidine-assisted intravenous inhalation combined anesthesia on cerebral oxygen metabolism and serum Th1/Th2 levels in elderly patients with colorectal cancer. METHOD: From April 2018 to May 2020,100 elderly patients undergoing elective laparoscopic radical resection of colorectal cancer were prospectively selected and randomly divided into observation group and control group. Before induction of anesthesia, the loading dose of dexmedetomidine was given at 0.5 µg/kg, and the infusion time was 15 min. After tracheal intubation, 0.4 µg/kg/h dexmedetomidine was continuously pumped, and the infusion was stopped 40 min before the end of the operation. In the control group, the same amount of 0.9% sodium chloride was injected intravenously in the same way. 30 min before induction of anesthesia (T0), immediately before induction of anesthesia (T1), immediately after tracheal intubation (T2), 40 min before operation (T3), and immediately after operation (T4), record the blood oxygen content of the artery and internal jugular vein Difference (D(a-jv)O2), brain oxygen uptake rate (COER%), brain oxygen saturation (rSO2) mean. VAS scale, Ramsay scale, MoCA scale were taken at 6, 12, 24, and 48 h postoperatively to evaluate analgesia, sedation, and cognitive function. And monitor the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), myelin basic protein (MBP), neuron-specific enolase (NSE) and S100ß. The occurrence of restlessness and adverse reactions during the recovery period of the two groups were compared. RESULT: The levels of D(a-jv)O2, COER%, and rSO2 in the control group and observation group were higher than the preoperative basic values at T2, T3, and T4 (P < 0.05); The levels of D(a-jv)O2, COER%, and rSO2 in the observation group were lower than those in the control group at T2, T3, and T4 (P < 0.05). The VAS score and Ramsay score of the observation group were lower than those of the control group at 6, 12, 24, and 48 h after surgery, while the MoCA score was higher than that of the control group (P < 0.05). In addition, the serum IFN-γ, MBP, NSE and S100ß levels of the observation group were lower than those of the control group (P < 0.05), and the ratio of IFN-γ/IL-4 was higher than that of the control group (P < 0.05). The overall incidence of adverse reactions in the observation group was lower than that in the control group [32.0% (16/50) vs. 12.0% (6/50), P < 0.05]. CONCLUSION: Dexmedetomidine-assisted combined intravenous and inhalation anesthesia is beneficial to reduce perioperative cerebral oxygen metabolism and improve postoperative immunosuppression in elderly patients with colorectal cancer. It has a certain protective effect on nerve injury after operation, thus improving the cognitive function of patients and reducing the occurrence of adverse reactions.

Clinicopathological findings and imaging features of intraductal papillary neoplasms in bile ducts.

BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is considered an uncommon tumor, and there is limited understanding of IPMN-B. This study aimed to investigate the prognosis and influential factors of the IPMN-B from 58 cases. METHODS: The clinical data of 58 patients with pathologically confirmed IPMN-B admitted to our hospital from January 1, 2012 to August 2017 were collected and analyzed. The patients were followed up by outpatient or telephone until January 1, 2019. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using Kaplan-Meier method and parallel Log-rank test. Prognostic factors were analyzed by univariate analysis and multiple Cox regression model. RESULTS: Among of all the patients, 26 cases were benign tumors and 32 cases were malignant tumors. The preoperative tumor markers CA242 and CEA of malignant IPNM-B patients were significantly higher than those in benign tumors (P < 0.05). Survival analysis showed that patients with malignant tumors had a worse prognosis. The median survival time of malignant IPMN-B patients was 40.6 ±  3.0 months, yet median survival time of benign IPMN-B patients was not reached (P = 0.19). The one-year survival rate and three-year survival rate of benign IPMN-B were 84% and 74% respectively. The one-year survival rate and three-year survival rate of malignant IPMN-B were 88% and 64% respectively. Univariate analysis showed that combined lymph node metastasis, surgical method, and differentiation degree could affect patients' prognosis (P < 0.05). Multivariate analysis showed differentiation degree was an independent risk factor affecting prognosis (OR = 0.06, 95% confidence interval: 0.007∼0.486, P < 0.05). CONCLUSION: The levels of CEA and CA242 were helpful to identify benign and malignant of IPNM-B. Moreover, radical surgical resection could prolong patients' survival. Finally, differentiation degree was an independent risk factor affecting malignant IPNM-B prognosis.

Clinical effect and safety evaluation of hydromorphone combined with sufentanil in patient-controlled intravenous analgesia for patients with hepatocellular cancer and its effect on serum immune factors.

The present study aimed to explore the clinical efficacy and safety of hydromorphone combined with sufentanil in patient-controlled intravenous analgesia (PCIA) for patients with hepatocellular carcinoma (HCC) and its effect on serum immune factors in serum. Data from 385 patients with HCC, admitted to the Hunan Provincial People's Hospital (Changsha, China) from February 2015 to September 2018, were retrospectively analyzed. Laparoscopic hepatectomy was performed in all patients. A total of 180 patients who received PCIA were treated with sufentanil (control group), and 205 patients who received PCIA were treated with hydromorphone and sufentanil (study group). PCIA was used after hepatocellular cancer operation. In the control group, the analgesic pump was filled with sufentanil (2 µg/kg) and tropisetron (5 mg), whereas in the study group, the analgesic pump was filled with sufentanil (2 µg/kg), tropisetron (5 mg) and hydromorphone (5 mg). Both groups of drugs were diluted into 100 ml with normal saline and the loading dose was 5 ml; the continuous dose was 2 ml/h and the single PCIA amount was 2 ml. The visual analogue scale (VAS) and numeric sedation scale (NSS) scores at 12 and 24 h after operation, as well as and satisfaction score at 24 h after operation, were recorded. The levels of CD3+, CD4+, CD8+ lymphocytes and NK cells in the peripheral blood of patients were detected by flow cytometry. The postoperative hospitalization time, first flatulence time, first defecation time and first ambulation time, as well as the adverse reactions, were recorded. The results revealed that the satisfaction score of the patients at 24 h after operation was significantly higher in the study group than that in the control group (P<0.05). Additionally, there were no serious adverse reactions in either group. In conclusion, PCIA with hydromorphone and sufentanil can provide safe and effective analgesia, may improve the levels of immune factors and enhance the recovery ability of the patients.

Effect of Tramadol Pretreatment on Sufentanil-Induced Cough.

PURPOSE: To investigate the effect of tramadol pretreatment on the incidence and severity of sufentanil-induced cough. DESIGN: Randomized controlled trial. METHODS: Adults of both genders (N = 304; 18 to 65 years old, American Society of Anesthesiologists physical status I to II), scheduled for elective surgery, were randomized into two groups (n = 152): intravenous administration of tramadol 1 mg/kg (group T) or normal saline (group C). Then sufentanil bolus 0.3 mcg/kg was administered intravenously in 5 seconds. The incidence and severity of cough were observed for 1 minute. Mean arterial pressure, heart rate, nausea, vomiting, and truncal rigidity during induction were also recorded. FINDINGS: Patient characteristics were similar between the two groups. The incidence of cough was significantly lower in group T when compared with group C (7.9% vs 18.4%, P < .05); there were nine patients coughing severely in group C, whereas no severe cough occurred in group T (P < .05). The mean arterial pressure, heart rate, and incidences of other side effects were comparable between the two groups. CONCLUSIONS: Pretreatment of intravenous tramadol 1 mg/kg could be a clinically effective intervention for attenuating sufentanil-induced cough.

Study of breakthrough cancer pain in an animal model induced by endothelin-1.

Cancer patients with bone metastases often suffer breakthrough pain. However, little progress has been made in the treatment of breakthrough pain and its associated mechanism(s) in the patient with cancer due to lacking of resembling and predictive animal models. We previously have demonstrated that endothelin-1 plays an important role in breakthrough cancer pain. In the present study, we have established an animal model of breakthrough cancer pain induced by endothelin-1. The animal model of breakthrough cancer pain is strictly followed the definition and meets the characteristics of breakthrough pain. The model is reliable, reproducible and easy to be produced. To our knowledge, this is the first report for establishing such an animal model. In addition, we also found that a selective ETA receptor antagonist BQ-123 could reverse endothelin-1 induced breakthrough pain. We further studied the characteristics of pain behaviors such as hind limb use score and voluntary wheel running as well as the electrophysiology of sciatic nerve fibers with the model. The murine model shows high resemblance compared to the breakthrough cancer pain in the patients with cancer clinically. It provides a platform for further study of the pathogenesis of breakthrough cancer pain and targeted intervention.