Effect of Ulinastatin on the Action of Nondepolarising Muscle Relaxants Rocuronium / Cisatracurium
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- RT2
研究概览
简要总结
The aim of this research was to determine the influence of ulinastatin on nondepolarising muscle relaxants Rocuronium and Cisatracurium.
详细描述
BACKGROUND: Ulinastatin is a protease inhibitor derived from human urine. The effects of ulinastatin on muscle relaxants have been attributed to its capacity to cause an increase in liver circulation, diuresis and possibly increased acetylcholine release. Rocuronium is mainly eliminated via the liver and kidneys, whereas cisatracurium is mainly cleared via Hofmann elimination, which is organ-independent. The effects of ulinastatin on cisatracurium have not been assessed before. Moreover, the effects of ulinastatin on the recovery period of rocuronium have not been adequately studied before. In this study, the effects of ulinastatin on cisatracurium are compared with the effects of ulinastatin on rocuronium. This is done by contrasting the ulinastatin-induced changes in onset time, clinical duration, and recovery duration for rocuronium with those for cisatracurium.
METHODS: 120 patients will be enrolled in this study and assigned randomly into 4 equal groups using a computer-generated randomization sequence:
ROC-ULI Group: Ulinastatin (5000 U/kg) administered 2 minutes prior to rocuronium (0.6 mg/kg) ROC-NS Group (Control): Normal saline (0.1 mL/kg) administered 2 minutes prior to rocuronium (0.6 mg/kg) CIS-ULI Group: Ulinastatin (5000 U/kg) administered 2 minutes prior to cisatracurium (0.1 mg/kg) CIS-NS Group (Control): Normal saline (0.1 mL/kg) administered 2 minutes prior to cisatracurium (0.1 mg/kg) Acceleromyography using response to TOF (train of four) stimulation is used to assess neuromuscular function. The site of stimulation and response assessment are the ulnar nerve and the adductor pollicis muscle respectively. The primary outcome measure is clinical duration (Dur-25%), defined as the time interval from the end of injection of the neuromuscular blocking agent until recovery of T1 to 25% of baseline.
Secondary outcomes include: the onset time, the times to return of the first, second, third, and fourth response to TOF stimulation (RT1, RT2, RT3, and RT4 respectively), the duration of moderate neuromuscular block (RT1-RT4), the duration 50%, the recovery TOF 0.7 period, and the duration TOF 0.7. Anesthesia is induced and maintained with propofol using target-controlled infusion. p < 0.05 is considered statistically significant. Analgesia is achieved with an initial bolus of sufentanil followed by remifentanil infusion. Depth of anesthesia is monitored using the Narcotrend™ index.
Statistical Analysis
Sample size calculation was based on the primary outcome, the clinical duration of neuromuscular blockade (Dur-25%). Because no previous study had investigated the effect of ulinastatin on cisatracurium, the estimation was derived from the study by Kim et al. evaluating rocuronium-induced neuromuscular blockade. A mean difference of 5 minutes with a standard deviation of 4.5 minutes was assumed. A minimum of 16 patients per group was required to achieve 90% power with a two-sided α of 0.05. To enhance the robustness of the analysis, 30 patients will be enrolled in each group (120 patients in total).Continuous data will be assessed for normality via Shapiro-Wilk test and expressed as mean ± SD or median (IQR) . Inter-group comparisons will be performed using one-way ANOVA , Kruskal-Wallis , or chi-square tests as appropriate. Longitudinal outcomes will be evaluated using a linear mixed-effects model , incorporating a participant-specific random intercept and fixed effects for group, categorical time, and their interaction . Continuous data will be standardized to facilitate model convergence . All tests are two-sided with P < 0.05 considered significant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergo elective pancreaticoduodenectomy surgery
- •Age ranging from 25 to 60 years，body mass index (BMI)18-24kg/m2, American Society of Anesthesiologists (ASA) grades 1 or
- •Receive general anesthesia and muscle relaxants intraoperatively.
排除标准
- •patients ASA class 3 and above
- •Severe cardiac or respiratory diseases, liver( Child-Pugh class B or C ) or kidney disease( estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m²)
- •Pregnant women.
- •Patients with neurological dysfunction including myasthenia gravis, epilepsy or psychiatric disorders
- •Patients on any premedications including antisialagogues .
- •Patients on drugs known to interfere with neuromuscular transmission including but not exclusive to anticonvulsants, calcium channel blockers, β-blockers, corticosteroids, diuretics and antibiotics of the aminoglycoside group
- •Patients known allergy to propofol and sufentanil or remifentanil,
- •emergency operations.
- •Patients judged by the investigator to be unsuitable for participation in this study
结局指标
主要结局
RT2
时间窗: 1 day
Duration of moderate neuromuscular block (RT1-RT4)
Duration 25%
时间窗: 1 day
Duration 25% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 25%.
RT3
时间窗: 1 day
RT3 defined as the time from start of injection of neuromuscular blocker to T3 reappearance
Recovery TOF 0.7 period
时间窗: 1 day
Recovery TOF 0.7 period defined as the time from reappearance of T4 to recovery of TOF ratio to 0.7.
RT1
时间窗: 1 day
RT1 defined as the time from start of injection of neuromuscular blocker to T1 reappearance.
Duration of moderate neuromuscular block (RT1-RT4)
时间窗: 1 day
Duration of moderate neuromuscular block (RT1-RT4) defined as the time from reappearance of T1 to reappearance of T4.
Duration 50%
时间窗: 1 day
Duration 50% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 50%.
Duration TOF 0.7
时间窗: 1 day
Duration TOF 0.7 defined as the time from start of neuromuscular blocker injection to recovery of TOF ratio to 0.7.
Onset time
时间窗: 1 day
Onset time defined as the period from start of injection of neuromuscular blocker to the time point when T1 has depressed to 5% of its initial control value.
RT4
时间窗: 1 day
RT4 defined as the time from start of injection of neuromuscular blocker to T4 reappearance
Duration 25%
时间窗: All measurements were performed before the creation of pneumoperitoneum
Duration 25% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 25%.
次要结局
- Onset time(All measurements were performed before the creation of pneumoperitoneum)
- RT1(All measurements were performed before the creation of pneumoperitoneum)
- RT2(All measurements were performed before the creation of pneumoperitoneum)
- RT3(All measurements were performed before the creation of pneumoperitoneum)
- RT4(All measurements were performed before the creation of pneumoperitoneum)
- RT1-RT4(All measurements were performed before the creation of pneumoperitoneum)
- Dur-50%(All measurements were performed before the creation of pneumoperitoneum)
- Dur-TOF 0.7(All measurements were performed before the creation of pneumoperitoneum)
- Rec-TOF 0.7(All measurements were performed before the creation of pneumoperitoneum)
研究者
Ai Ling
Ai Ling, Doctor
Huazhong University of Science and Technology