Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial.

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

Influence of different anesthesia on liver and renal function in elderly patients undergoing laparoscopic colon or rectal resection.

BACKGROUND/AIMS: To investigate the influence of different anesthesia methods on liver and renal function in elderly patients undergoing laparoscopic colon or rectal resection. METHODOLOGY: Forty ASA I-II elderly patients undergoing elective laparoscopic colon or rectal resection were randomly divided into 2 groups (n=20 each): Group A: routine general anesthesia and Group B: general combined epidural anesthesia. All patients received general anesthesia, tracheal catheterized and mechanical ventilation. Data of liver and renal function were noted at these time points: before operation (T1), during operation (T2), 1-day after operation (T3), 2-day after operation during bowel anastomoses (T4), 3-day after operation (T5). Duration of surgery, blood loss, urine output and intravenous fluid volume was registered. RESULTS: Compared with group A, the total fluid volume and urine volume were increased in group B (p<0.05), while the amount of fentanyl was decreased (p<0.05). TP, TBIL and DBIL between the two groups were not significantly different (p>0.05). Compared with group A, group B ALT/BUN decreased at T2 and T3, AST decreased at T2, Cr at T3 decreased, ALB decreased at T2 (p<0.05). CONCLUSIONS: Continuous epidural block compound general anesthesia in elderly laparoscopic colorectal resection surgery is more conducive to the protection of perioperative liver and kidney function.

Effect of stroke volume variability- guided intraoperative fluid restriction on gastrointestinal functional recovery.

To investigate the effect of stroke volume variability(SVV)-guided intraoperative fluid restriction on gastrointestinal functional recovery and postoperative outcome after gastrointestinal surgery. Forty ASA I-II patients undergoing elective gastrointestinal surgery were randomly divided into 2 groups (n=20 each):group A routine fluid administration and group B restricted fluid administration. SW value was maintained at 5-7 in group A and 11-13 in group B. All patients received general anesthesia, tracheal catheterized and mechanical ventilation. Hemodynamic monitoring parameters (MBP, HR, CVP, CO) were noted at 5 time points. The hemodynamic parameters were maintained within normal limits during operation in both groups. The intraoperative intravenous fluid volume in group B was significant less than in group A (p<0.01).Urine output in group A was significant less than in group B (p<0.05). Stroke volume variation measured from Edwards Flotrac sensor and Edwards Vigileo monitor could be a security and sensitive parameter as an index of volume administration. In elective gastrointestinal surgery, volume resuscitation with a goal SVV of11-13 not only reduced intravenous fluid volume but also maintained the stable hemodynamic and tissue perfusion, enhanced gastrointestinal functional recovery and reduced the length of hospital stay

[Risk factors for excessive bleeding in patients undergoing open heart surgery with cardiopulmonary bypass].

OBJECTIVE: To evaluate the pre- and intraoperative risk factors associated with excessive bleeding during the perioperative period in adult patients undergoing open heart surgery with cardiopulmonary bypass (CPB). METHODS: A total of 1079 consecutive patients undergoing open heart surgery with CPB from January 2001 to May 2010 were included (except for emergency operation). The possible risk factors associated with excessive bleeding were retrospectively analyzed. Patients who received ≥ 7 units of RBC or had a re-operation during which no active bleeding point was found within one day of operation were classified as excessive bleeding. According to the occurrence of excessive bleeding, they were divided into 2 groups: excessive and non-excessive bleeding groups. The possible risk factors associated with excessive bleeding were retrospectively analyzed. Univariate analysis and multivariate Logistic regression analysis were used to examine the relationship between these factors and excessive bleeding. RESULTS: Among them, 120 (11.1%) developed excessive bleeding. Multivariate Logistic analysis indicated that the risk factors for excessive bleeding were age (OR = 4.533, 95%CI 2.624 - 7.831), previous sternotomy (OR = 2.781, 95%CI 1.410 - 5.486), preoperative hematocrit concentration (OR = 0.896, 95%CI 0.861 - 0.932), CPB duration (OR = 2.782, 95%CI 1.791 - 4.322) and type of procedure (OR = 2.292, 95%CI 1.376 - 3.817). CONCLUSION: Age ≥ 65 years, previous sternotomy, preoperative low hematocrit concentration, CPB duration ≥ 120 min and complex operation were the significant predictors for excessive bleeding in patient undergoing open heart surgery with CPB.

[Oral controlled-release oxycodone for uterine cramping pain after cesarean section].

OBJECTIVE: To evaluate whether combined oral oxycodone hydrochloride controlled-release tablets plus paracetamol and tramadol hydrochloride tablets is better than epidural analgesia with respect to uterine cramping pain control and side effects after cesarean section. METHODS: Sixty consecutive patients scheduled for cesarean section from April to May, 2010 were randomized to either patient-controlled epidural analgesia with 0.1% ropivacaine, 0.1 µg/ml sufentanil (for postoperative 48 h) plus injected pethidine on demand (EDA group) or controlled-release oxycodone (2 × 15 mg for 1st postoperative 24 h; 2 × 10 mg for 2nd postoperative 24 h), paracetamol & tramadol hydrochloride tablets (8 × 1 tablet for postoperative 48 h) orally plus pethidine injection on demand (OXY group). Two groups were compared with respects to uterine cramping pain control when the oxytocin infusion (20 U plus 500 ml 5% glucose solution, iv. gtt within 2 h) once per day for postoperative 3 days as determined by the means of a visual analogue scale (VAS), pethidine consumption, side effects and costs. RESULTS: The EDA group experienced significant more pain than the OXY group when the oxytocin infusion was administered (mm) [50.0 (15.0, 72.5) vs 25.0 (0, 40.0), 60.0 (47.5, 72.5) vs 20.0 (0, 30.0), 35.0 (20.0, 50.0) vs 0 (0, 20.0)]. all P < 0.05). Pethidine was used for pain control in 2 patients (150 mg total) of EDA group during the oxytocin infusion whereas none of the OXY group received an injection of pethidine. There was a higher level of maternal satisfaction with a lower analgesic dose in the EDA group (80.9 ± 9.3 vs 90.0 ± 9.8, P < 0.01). The median duration of hospital stay was around 5 days in both groups. CONCLUSION: Postoperative pain control after cesarean section with the above combined regimen is superior to EDA in terms of a lower cost and a higher level of maternal satisfaction.

[Comparison and superiority of streamlined liner of the pharynx airway to laryngeal mask airway or tracheal tubes for gynecological laparoscopy].

OBJECTIVE: To compare the variations of hemodynamics or respiratory parameters and postoperative complications incidence in gynecological laparoscopy to perform Laryngeal Mask Airway (LMA), Streamlined Liner of the Pharynx Airway (SLIPA) or Tracheal Tube (TT) and to appraise the safety or superiority SLIPA in gynecological laparoscopy. METHODS: 90 patients as ASA I-II grade for gynecological laparoscopy to divide randomly into three groups (n = 30): SLIPA group(S), LMA group(L), TT group(T). Patients were intubated with SLIPA, LMA or TT respectively after general anesthesia induction. Record and count baseline or variable values on heart rate, mean arterial pressure, peak inspiratory pressure, flat inspiratory pressure, airway compliance, airway resistance as pre- and post-intubation. To observe intra- and post-complications on backflow or aspiration, airway shifting, oral mucosa damage, cough or expectoration, pharyngodynia, trachyphonia and to appraise patient's comfort as extubation. RESULTS: S or L group is more stable than T on hemodynamic (P < 0.05) during intubation, S group is more stable than L or T group on respiratory parameters (P < 0.05). Intraoperative incidences are significantly lower in S group than L group on backflow or aspiration, airway shifting or oral mucosa damage (P < 0.05), postoperative incidences are significantly lower in S group than L or T group on pharyngodynia, trachyphonia or cough or expectoration (P < 0.05). In addition, extubation comfort degree is better to patient as resuscitation (P < 0.05). CONCLUSIONS: SLIPA are safely or conveniently applicable in gynecological laparoscopy. It impacts little on variations of hemodynamics or respiratory parameters after general anesthesia and reduces intra- or post-operative complications significantly compared to L or T group, increases patient's comfort as extubation. SLIPA is superior to other two on clinical applications.

[The effect of flurbiprofen axetil on laparoscopic cholecystectomy].

OBJECTIVE: To evaluate whether administration of flurbiprofen axetil before elective laparoscopic cholecystectomy can affect the BIS index and hemodynamics. METHOD: Sixty patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups. Flurbiprofen axetil 1 mg/kg was used intravenous 15 minutes before induction of general anesthesia in group B, while group A without premedication. Total intravenous anesthesia was maintained with propofol TCI. BIS index, blood pressure and heart rate were recorded at the time just before induction, after endotracheal intubation, 5 minutes before incision, incision, 5, 10, 15, 20 and 25 mins after incision. RESULT: There were no significant difference between two groups in BIS index during period of anesthesia and awareness (all P > 0.05). Compared with group A, both systolic and diastolic blood pressure in group B at time of incision (T(1)) are apparently lower (P < 0.05). While, blood pressures were no significant different at other time (all P > 0.05). CONCLUSION: In this study, administration of flurbiprofen before surgery of laparoscopic cholecystectomy did not alter BIS and the degree of sedation during total intravenous anesthesia. But it can reduce the harmful stimulation to cardiovascular reaction from surgery and make hemodynamic status more stable. Flurbiprofen can be safely and effectively used on elective laparoscopic cholecystectomy.

[Effect of intravenous esmolol on BIS index and anesthesia emergence during sedation anesthesia for ambulatory surgery].

OBJECTIVE: The aim of this research is to observe whether esmolol infusion as an adjunct to propofol can affect BIS index, reduce anesthetic dose and decrease emergence time. METHOD: Sixty ASA I-II patients, age 18-35, undergoing uterine dilatation and curettage surgery were studied. They were randomized into two groups. Before induction, patients in esmolol group (Group E) were received 1 mg/kg esmolol intravenously and followed by esmolol 150 microg x kg(-1) x min(-1) intravenous infusion; patients in group C received normal saline instead of esmolol. Fentanyl (1 microg/kg) and propofol (2 mg/kg) were used as induction drugs. The change of BIS index, heart rate and MAP during operation; total amount of propofol; time when patients opened eyes and time when patients reached the standard for discharge from hospital were recorded. RESULTS: BIS and heart rate of Group C at 1,2,3 minute after surgery started, increased significantly compared with the time after induction and those in Group E (P < 0.05). The time patients reached the score of discharging from hospital in Group C is longer than that in Group E (P < 0.05). CONCLUSION: Esmolol combined with propofol administering in minor ambulatory operations can control the increase of BIS index caused by surgical nociceptive stimulus. Meanwhile the combination could reduce the dose of sedatives and decrease anesthesia emergence time.

Targeted Epidural Blood Patch Treatment for Refractory Spontaneous Intracranial Hypotension in China.

Objective An epidural blood patch (EBP) is the mainstay of treatment for refractory spontaneous intracranial hypotension (SIH). We evaluated the treatment efficacy of targeted EBP in refractory SIH. Methods All patients underwent brain magnetic resonance imaging (MRI) with contrast and heavily T2-weighted spine MRI. Whole spine computed tomography (CT) myelography with non-ionic contrast was performed in 46 patients, and whole spine MR myelography with intrathecal gadolinium was performed in 119 patients. Targeted EBPs were placed in the prone position one or two vertebral levels below the cerebrospinal fluid (CSF) leaks. Repeat EBPs were offered at 1-week intervals to patients with persistent symptoms, continued CSF leakage, or with multiple leakage sites. Results Brain MRIs showed pachymeningeal enhancement in 127 patients and subdural hematomas in 32 patients. One hundred fifty-two patients had CSF leakages on heavily T2-weighted spine MRIs. CSF leaks were also detected on CT and MR myelography in 43 and 111 patients, respectively. Good recovery was achieved in all patients after targeted EBP. No serious complications occurred in patients treated with targeted EBP during the 1 to 7 years of follow-up. Conclusions Targeted and repeat EBPs are rational choices for treatment of refractory SIH caused by CSF leakage.

Amide-linked local anesthetics induce apoptosis in human non-small cell lung cancer.

BACKGROUND: A retrospective analysis of patients undergoing cancer surgery suggested that using local anesthetics could reduce cancer recurrence and improve survival rate. Previous studies have indicated that local anesthetics may induce apoptosis in several kinds of cells in vitro, but the mechanism is unclear. METHODS: Cell viability was analyzed by MTS; reactive oxygen species (ROS), mitochondrial membrane potential (MMP, ∆Ψm), cell cycle distribution, and cell apoptosis assay were detected by flow cytometry; DNA damage was measured by comet assay; cell invasion and migration were observed by microscopy; The expression level of related proteins was detected by western blot assay. RESULTS: The results indicated that lidocaine and ropivacaine could decrease viability, induce G0/G1 phase arrest and apoptosis in human non-small cell lung cancer (NSCLC) cells A549 and H520. Invasion and migration were suppressed. Western blot indicated the related apoptotic pathways proteins changed accordingly. Additionally, lidocaine and ropivacaine downregulated ∆Ψm, provoked DNA damage, upregulated ROS production and activated mitogen-activated protein kinase (MAPK) pathways in A549 and H520 cells. CONCLUSIONS: The cytotoxic effect of amide-linked local anesthetics on NSCLC cells were mainly due to apoptosis. The antitumor mechanism of lidocaine and ropivacaine may involve apoptotic pathways and MAPK pathways.

Saikosaponin-d attenuates ventilator-induced lung injury in rats.

Saikosaponin-d is one of the main bioactive components in the traditional Chinese medicine Bupleurum falcatum L and possesses anti-inflammatory and immune-modulatory properties. The current study aimed to investigate the protective effects of saikosaponin-d on ventilator-induced lung injury (VILI) in rats. We found that saikosaponin-d treatment significantly attenuated the pathological changes of lungs induced by mechanical ventilation. Administration of saikosaponin-d reduced the pulmonary neutrophil infiltration as well as the MPO concentrations. Saikosaponin-d also decreased the expression of pro-inflammatory cytokines including MIP-2, IL-6 and TNF-α. Meanwhile, the expression of anti-inflammatory mediators, such as TGF-ß1 and IL-10, was obviously elevated after saikosaponin-d administration. Saikosaponin-d remarkably reduced the oxidative stress and apoptosis rate in lung tissues. On the molecular level, saikosaponin-d treatment obviously downregulated the expression of caspases-3 and the pro-apoptotic protein bax, and promoted the expression level of anti-apoptotic protein bcl-2. Collectively, our study demonstrated that saikosaponin-d may attenuate ventilator induced lung injury through inhibition of inflammatory responses, oxidative stress and apoptosis.