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

Effect of Ulinastatin on the Action of Nondepolarising Muscle Relaxants Rocuronium / Cisatracurium

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

Study Overview

• Status: Completed
• Conditions: Nondepolarising Muscle Relaxants
• Intervention / Treatment: Drug: Ulinastatin; Drug: Placebo Comparator (0.9% NaCl)

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Department of Anaesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rocuronium; The Rocuronium groups received ulinastatin 5000U/kg or saline 0.1 mL/kg followed by rocuronium 0.6 mg/kg	Drug: Ulinastatin; The ulinastatin groups received ulinastatin 5000U/kg two minutes before the administration of muscle relaxants; Drug: Placebo Comparator (0.9% NaCl); The saline control groups received normal saline 0.1ml/kg two minutes before the administration of muscle relaxants
Experimental: Cisatracurium; The Cisatracurium groups received ulinastatin 5000U/kg or normal saline 0.1 ml/kg followed by cisatracurium 0.1 mg/kg	Drug: Ulinastatin; The ulinastatin groups received ulinastatin 5000U/kg two minutes before the administration of muscle relaxants; Drug: Placebo Comparator (0.9% NaCl); The saline control groups received normal saline 0.1ml/kg two minutes before the administration of muscle relaxants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration 25%	Duration 25% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 25%.	All measurements were performed before the creation of pneumoperitoneum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset time	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.	All measurements were performed before the creation of pneumoperitoneum
RT1	RT1 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T1	All measurements were performed before the creation of pneumoperitoneum
RT2	RT2 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T2	All measurements were performed before the creation of pneumoperitoneum
RT3	RT3 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T3	All measurements were performed before the creation of pneumoperitoneum
RT4	RT4 is defined as the time from the start of injection of the neuromuscular blocker to the reappearance of T4	All measurements were performed before the creation of pneumoperitoneum
RT1-RT4	RT1-RT4 defined as the duration of moderate neuromuscular block, was calculated as the interval between RT1 and RT4	All measurements were performed before the creation of pneumoperitoneum
Dur-50%	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	All measurements were performed before the creation of pneumoperitoneum
Dur-TOF 0.7	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.	All measurements were performed before the creation of pneumoperitoneum
Rec-TOF 0.7	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	All measurements were performed before the creation of pneumoperitoneum

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Investigators: Study Chair: Xu Hui, Department of Anaesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): June 15, 2023
• Study Completion (Actual): June 25, 2023

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: February 4, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cisatracurium; Rocuronium; Train of four (TOF); Ulinastatin
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Muscle Hypotonia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; urinastatin
• Other Study ID Numbers: TJ-IRB20221241

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No