Effect of Ulinastatin on the Action of NDMRs (Rocuronium / Cisatracurium)

Huazhong University of Science and Technology

Status: Completed

Conditions: Nondepolarising Muscle Relaxants

Treatments: Drug: Placebo Comparator (0.9% NaCl); Drug: Ulinastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05716256

TJ-IRB20221241

Details and patient eligibility

About

The aim of this research was to determine the influence of ulinastatin on nondepolarising muscle relaxants Rocuronium and Cisatracurium.

Full 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.

Enrollment: 120 patients

Sex: All

Ages: 25 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 2 patient groups

Rocuronium

Experimental group

Description:

The Rocuronium groups received ulinastatin 5000U/kg or saline 0.1 mL/kg followed by rocuronium 0.6 mg/kg

Treatment:

Drug: Ulinastatin

Drug: Placebo Comparator (0.9% NaCl)

Cisatracurium

Experimental group

Description:

The Cisatracurium groups received ulinastatin 5000U/kg or normal saline 0.1 ml/kg followed by cisatracurium 0.1 mg/kg

Treatment:

Drug: Ulinastatin

Drug: Placebo Comparator (0.9% NaCl)