Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: a randomized, double-blind, controlled study of 120 patients.

PURPOSE: To evaluate the impact of alanyl-glutamine (Ala-Gln)-supplemented parenteral nutrition (PN) on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients. METHODS: One hundred twenty patients undergoing major abdominal surgery were enrolled. Protocol was approved and informed consent obtained. A double-blind protocol was designed as used in Europe. The clinical safety and outcome were observed for 60 patients in 2 centers (30 each). Sixty patients from 2 additional centers (30 each) were observed for clinical safety, nitrogen balance, intestinal permeability, and clinical outcome. All patients received isonitrogenous (0.20 g/kg body wt per day) and isocaloric (30 kcal/kg body wt per day) parenteral nutrition. The study group received Ala-Gln (Dipeptiven, Fresenius Kabi, Bad Homberg, Germany) 0.50 g/kg per day. Clinical chemistry variables, plasma amino acids profile, nitrogen balance, intestinal permeability (lactulose/mannitol ratio [L/M ratio]) were measured; hospital stay and infection rate were monitored. Statview was used for analysis of variance (ANOVA) or chi2 tests. Data were expressed as means +/- SD, and the significance level was p < .05. RESULTS: The patients in both groups were comparable prior to the operation. Vital signs and clinical chemical parameters were similar between groups. L/M ratio was 0.047+/-0.029 in control and 0.058+/-0.049 in study group before the operation (AOD-3). The L/M ratio was 0.132+/-0.081 in the control group, and 0.097+/-0.063 in study group on the seventh postoperative day. The difference of L/M ratio between groups was significant (p = .02). The cumulative nitrogen balance values were -5+/-162 mg/kg for 6 days in control and 144+/-145 mg/kg for 6 days in study group (p = .0004). All the patients recovered without incision infection. However, there were 3 cases that had infection-related complications in the control group; the difference was not significant between groups. The hospital stay in the study group was 12.5 days, which was 4 days less than that of the control group (p = .02). CONCLUSIONS: Ala-Gln-supplemented PN was clinically safe, had better nitrogen balance, and maintained intestinal permeability in postoperative patients. The clinical outcome of the patients in study group was better; it was significantly different from the control group.

Ion-exchange chromatography in simultaneous determination of serum copper and zinc levels in patients with cancer of digestive tract.

Serum copper and zinc were simultaneously determined by ion-exchange chromatography (IC) in 35 normal volunteers and 45 patients with benign diseases or different stage cancers of digestive tract. No significant differences of serum Cu, Zn (both expressed in mumol/L) and Cu/Zn ratio were found among normal volunteers, patients with benign diseases and those with stage I or II cancer. While in the group of stage III and IV cancer patients, the mean of serum Cu (26.5 +/- 1.4 mumol/L) and Cu/Zn ratio (2.25 +/- 0.16) increased significantly (P < 0.01) and that of serum Zn (11.8 +/- 0.5 mumol/L) decreased markedly (P < 0.05). Our results showed that serum Cu, Zn and Cu/Zn ratio was of no help in detecting early stage cancers and in differentiating them from benign diseases but was useful in predicting stages of cancers before operation for a better choice of therapy.

[Changes of protein turnover in perioperative patients and effect of recombinant human growth hormone].

15N-Glycine constant infusion method was applied to study the changes of protein metabolism after major abdominal operation and the influence of recombinant human growth hormone (GH). Our results showed: (1) under the support of total parenteral nutrition (30 cal/kg/d and 1.25 g protein/kg/d), the protein turnover rate (Q), synthetic rate (S) and catabolic rate (C) all increased significantly (P < 0.05) with an outstriping increase of C over S on postoperative day 3 in comparison with that on preoperative day 3; (2) with the support of hypocaloric parenteral nutrition (20 cal/kg/d and 1.00 g protein/kg/d), Q, C values also increased significantly (P < 0.05) comparing with that of the control group on post operative day 7 in patients treated with one week GH (0.15 iu/kg/d), but S value increased more significantly (P < 0.01), which indicated that the postoperative use of TPN plus GH is much better than giving TPN alone.

Determination of protein turnover changes in perioperative patients by the 15N-glycine constant infusion method.

The N-glycine constant infusion method was used to study protein turnover in normal adults and perioperative patients. The protein turnover rate (Q), synthetic rate (S) and catabolic rate (C) were derived according to Picou's two-pool system model, and the "end-product averaging technique" showed the 15N-glycine constant infusion method to be reliable, with a reproducibility of +/-5.1%. This measurement can be repeated after a short period, so it should be useful for surgical nutrition study. Our results show the following: Q was significantly increased after operation (3.4 +/- 0.6 to 5.0 +/- 0.5 g protein/kg/d, P less than 0.01), and S (2.6 +/- 0.5 to 3.7 +/- 0.6 g protein/kg/d, P less than 0.05) and C (2.3 +/- 0.5 to 3.9 +/- 0.5 g protein/kg/d, P less than 0.01) were increased as well. This suggests that the protein degradation rate outstripped the synthesis rate on post-operative day three (POD+3) when traditional (glutamine-free) total parenteral nutrition support was used.

Alteration in chromatin conformation of proliferating and differentiating enzyme genes in normal mouse liver and ascites hepatoma cells and its relation to the gene expression of enzymes.

Nuclei from the normal mouse liver were partially digested with micrococcal nuclease, followed by DNA extraction, agarose gel electrophoresis and dot blot hybridization with 32P-labeled cDNA probes of CPS1 and ACT complex. It was clearly shown that the CPS1 genes were distributed on the monomer, dimer. and trimer of nucleosomes, while the genes coding for ACT complex were distributed on the condensed oligonucleosomes. An opposite manner of distribution of CPS1 and ACT complex genes was, however, noted in the case of ascites hepatoma cells, in which the specific activity of ACT was 13 times higher than that in the normal liver, while that of CPS1 was remarkably reduced. Similar patterns of change in mRNA level of CPS1 and ACT complex were observed in the normal mouse liver and ascites hepatoma cells, indicating a close relationship between chromatin structure and gene expression of these enzymes.