Nondepolarising Muscle Relaxants
Conditions
Keywords
Ulinastatin, Rocuronium, Cisatracurium, Train of four (TOF)
Brief summary
The aim of this research was to determine the influence of ulinastatin on nondepolarising muscle relaxants Rocuronium and Cisatracurium.
Detailed description
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.
Interventions
DRUGUlinastatin
The ulinastatin groups received ulinastatin 5000U/kg two minutes before the administration of muscle relaxants
The saline control groups received normal saline 0.1ml/kg two minutes before the administration of muscle relaxants
Sponsors
Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patients undergo elective pancreaticoduodenectomy surgery 2. Age ranging from 25 to 60 years，body mass index (BMI)18-24kg/m2, American Society of Anesthesiologists (ASA) grades 1 or 2. 3. Receive general anesthesia and muscle relaxants intraoperatively.
Exclusion criteria
1. patients ASA class 3 and above 2. 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) 3. Pregnant women. 4. Patients with neurological dysfunction including myasthenia gravis, epilepsy or psychiatric disorders 5. Patients on any premedications including antisialagogues . 6. 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 7. Patients known allergy to propofol and sufentanil or remifentanil, 8. emergency operations. 9. Patients judged by the investigator to be unsuitable for participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration 25% | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Onset time | All measurements were performed before the creation of pneumoperitoneum | Onset time is defined as the period from the start of neuromuscular blocker injection to the time point at which T1 has decreased to 5% of its initial control value. |
| RT1 | All measurements were performed before the creation of pneumoperitoneum | RT1 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T1 |
| RT2 | All measurements were performed before the creation of pneumoperitoneum | RT2 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T2 |
| RT3 | All measurements were performed before the creation of pneumoperitoneum | RT3 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T3 |
| RT4 | All measurements were performed before the creation of pneumoperitoneum | RT4 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T4 |
| RT1-RT4 | All measurements were performed before the creation of pneumoperitoneum | RT1-RT4 defined as the duration of moderate neuromuscular block, was calculated as the interval between RT1 and RT4 |
| Dur-50% | All measurements were performed before the creation of pneumoperitoneum | Dur-50% is defined as the time interval from the end of injection of the neuromuscular blocking agent until the first twitch height returns to 50% of its baseline control value |
| Dur-TOF 0.7 | All measurements were performed before the creation of pneumoperitoneum | Duration TOF 0.7 (Dur-TOF 0.7) was defined as the time from the end of neuromuscular blocker injection to the recovery of TOF ratio to 0.7. |
| Rec-TOF 0.7 | All measurements were performed before the creation of pneumoperitoneum | The recovery period to TOF 0.7 (Rec-TOF 0.7) was defined as the time from the reappearance of T4 until the TOF ratio recovered to 0.7 |
Countries
China
Contacts
STUDY_CHAIRXu Hui
Department of Anaesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed