Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-centre, non-inferiority, randomized, controlled phase 3 clinical trial.

Ciprofol is a propofol analogue with improved pharmacokinetic properties. A multi-centre, non-inferiority trial was conducted to compare the deep sedation properties of ciprofol and propofol with a non-inferiority margin of 8% in patients undergoing gastroscopy and colonoscopy. In total, 289 patients were randomly allocated for surgery (259 colonoscopy and 30 gastroscopy) at a 1:1 ratio to be given intravenous injections of ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). The primary outcome was the success rate of colonoscopy defined as colonoscopy completion with no need for an alternative sedative or >5 ciprofol or propofol top up doses within any 15-min time period. The success rate of colonoscopy was 100% in the ciprofol group vs. 99.2% in the propofol group (mean difference 0.8%, 95% CI: -2.2% to 4.2%). Except for the gastrointestinal lesions found during the gastroscopy and colonoscopy procedures, the occurrence rates of adverse drug reactions in the ciprofol and propofol groups were 31.3% and 62.8%, respectively (P < 0.001). Pain on injection was less common in the ciprofol group (4.9% vs. 52.4%, P < 0.001). The outcomes demonstrated that ciprofol was non-inferior to propofol with regard to successful sedation for gastroscopy or colonoscopy procedures and no obvious important adverse events occurred.

Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

OBJECTIVE: Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial. METHODS: A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests. RESULTS: In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750). CONCLUSIONS: Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.

[Electroacupuncture Treatment Conduced Before and After Surgery Is Better in Promoting Reco-very of Gastrointestinal Function in Colorectal Cancer Patients Undergoing Radical Resection].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at different time-points on postoperative gastrointestinal function in patients undergoing colorectal cancer surgery. METHODS: Eighty patients with colorectal cancer undergoing laparotomy were randomly assigned to intravenous anesthesia, EA A, EA B, and EA C groups (n＝20 cases in each group). All the patients in the four groups received intravenous anesthesia with midazolam, sufentanil, cisatracurium besylate and Propofol, postoperative gastrointestinal decompression and drug analgesia. EA (2－3 mA, 2 Hz) was applied to Zhongwan (CV 12) and Tianshu (ST 25), Neiguan (PC 6), Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39) on the right side for 30 min, once (one day before surgery) in the EA A group, twice (one day and 30 min before surgery) in the EA B group, and 3 times (one day, 30 min before and one day after surgery) in the EA C group. The acupoints used after surgery were PC 6, ST 36, ST 37 and ST 39. The time of postoperative ventilation, defecation, food-intake and water drinking, stomach tube removal and abdominal drainage tube removal, the volumes of stomach tube drainage and abdominal drainage, and postoperative adverse reactions were recorded. RESULTS: The first ventilation time, after surgery in the EA C group was significantly earlier than those in the intravenous anesthesia, EA A and EA B groups (P<0.05); and the water intake and abdomicnal drainage tube removal time after surgery in the EA C group were significantly earlier than those in the intravenous anesthesia group (P<0.05). No significant differences were found among the 4 groups in the time of defecation, food intake, stomach tube removal, stomach tube drainage and abdominal drainage volumes, and numbers of patients with nausea, vomiting, fever and other adverse reactions (P>0.05)．. CONCLUSION: EA treatment combined with intravenous anesthesia conducted before and after surgery is effective in promoting the recovery of gastrointestinal function in patients undergoing colorectal cancer laparotomy, and is obviously better than simple pre-operative EA.

[Influence of electroacupuncture pretreatment on intestinal function in the patients of colorectal cancer surgery].

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment on the intestinal function, inflammatory reaction and blood lactic acid in the patients of colorectal cancer surgery. METHODS: Sixty patients of colorectal cancer laparotomy at selective period, aged from 18 to 59 years old were selected. According toⅠ-Ⅲ grade of American Society of Anesthesiologists (ASA), the patients were randomized into group A (total intravenous anesthesia), group B[total intravenous anesthesia combined with EA pretreatment at Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) on the right side] and group C[total intravenous anesthesia combined with EA pretreatment at Zhongwan (CV 12), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) on the right side], 20 cases in each one. The total intravenous anesthesia was applied to all of the three groups. EA pretreatment was used one day before surgery and 30 min before surgery at corresponding acupoints in the group B and group C separately, 30 min each time. After surgery, the recovery time of bowel sound, the recovery time of flatus, the recovery time of defecation, the duration of diet fasting, the time of peritoneal drainage tube withdrawal and the total peritoneal drainage volume were observed in the three groups. The venous blood was collected to determine white blood cell count (WBC) and neutrophil count (NEUT) before surgery (T0), 24 h after surgery (T1) and on the 5th day after surgery (T2) separately. The arterial blood was collected to determine the level of lactic acid before surgery (TⅠ), after peritoneal douching (TⅡ) and 24 h after surgery (TⅢ)separately. RESULTS: The recovery time of bowel sound, the recovery time of flatus, the duration of diet fasting and the time of peritoneal drainage tube withdrawal in the group C were apparently earlier than those in the group A (all P<0.05). WBC and NEUT at T1 in the group C were apparently less than those in the group A (both P<0.05). The differences in lactic acid at TⅠ, TⅡ and TⅢ were not significant statistically in comparison of the three groups (all P>0.05). CONCLUSIONS: The total intravenous anesthesia combined with EA pretreatment at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25) and Zhongwan (CV 12) reduce the recovery time of bowel sound, the recovery time of flatus, the duration of diet fasting and the time of peritoneal drainage tube withdrawal so as to improve the recovery of intestinal function, reduce WBC in 24 h after surgery and alleviate inflammatory reaction. This therapy has no influence on blood lactic acid.

High-dose propofol reduces S-100ß protein and neuron-specific enolase levels in patients undergoing cardiac surgery.

OBJECTIVES: In a variety of experimental models, propofol has been shown to protect the brain. It was hypothesized that a clinically achievable high dose of propofol would induce cerebral protective effects in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The authors investigated the effects of different target plasma concentrations of propofol on cerebral injury by measuring serum S-100ß protein and neuron-specific enolase (NSE) levels in patients undergoing single-valve replacement with CPB. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-two patients undergoing single-valve replacement with CPB. INTERVENTIONS: Patients were randomly divided into 3 groups (n = 14 each). Each group received a target-controlled infusion of propofol with plasma concentrations of 1.8 µg/mL (low dose, Group-L), 2.4 µg/mL (medium dose, Group-M), or 3.2 µg/mL (high dose, Group-H). The propofol target concentrations were unchanged throughout the surgery. MEASUREMENTS AND MAIN RESULTS: In all 3 groups of patients, at all time points after CPB, the plasma S-100ß protein and NSE levels, which served as biochemical markers of brain damage, were significantly higher than the preoperative levels (p<0.05). Group-H showed significant decreases in S-100ß protein and NSE compared with Group-L (p< 0.05). CONCLUSION: In the range of commonly used clinical concentrations, administration of a high dose of propofol during CPB attenuated the biochemical markers of brain damage as compared with low-dose propofol anesthesia.

ED50 and recovery times after propofol in rats with graded cirrhosis.

BACKGROUND: Patients with end-stage liver disease have increased sensitivity to general anesthetics. In this study, we sought to quantify sensitivity to propofol as a function of the degree of liver disease, in a rat model of cirrhosis. METHODS: Liver disease was induced by carbon tetrachloride (CCl(4)) injections for 6, 9, or 12 weeks in 3 study groups. Control rats received saline injections on the same schedule as CCl(4)-injected rats. A second control (comparison) group was treated with phenobarbital for a week followed by 9 weeks of phenobarbital and 10% ethanol in drinking water. Liver function was assessed by liver function tests and pathologic scoring of liver histology. RESULTS: Progressively worse cirrhosis was associated with longer CCl(4) treatment by histologic criteria, by hypersplenism, liver to body weight ratios, and liver function tests. The major findings were that mild liver disease (either steatosis or fibrosis) was not associated with increased propofol sensitivity, but recovery times after propofol bolus and propofol infusion were significantly increased in rats with more severe liver fibrosis. CONCLUSION: Propofol sensitivity is not significantly affected in the setting of mild liver disease, similar to clinical observations, but end-stage liver disease (fibrosis) is associated with significantly prolonged time to recovery after propofol infusion. The progressive liver disease model used in these studies is useful for rigorously studying anesthetic sensitivity as a function of degree of hepatocellular-fibrotic liver disease.