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: Not yet recruiting
• Conditions: Nondepolarising Muscle Relaxants
• Intervention / Treatment: Drug: Ulinastatin; Procedure: TOF monitoring

Detailed Description

BACKGROUND: Ulinastatin is a protease inhibitor derived from human urine. The effects of ulinastatin on muscle relaxants have been attributed to its capacities to cause 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: 80 patients will be enrolled in this study and assigned randomly into 4 equal groups. The ROC-ULI group received ulinastatin 5000U/kg followed by rocuronium 0.6 mg/kg, the ROC-NS (control) group received normal saline 0.1ml/kg followed by rocuronium 0.6 mg/kg, the CIS-ULI group received ulinastatin 5000U/kg followed by cisatracurium 0.1 mg/kg and the CIS-NS (control) group received normal saline 0.1ml/kg followed by cisatracurium 0.1 mg/kg. The time lag between either ulinastatin or normal saline administration and muscle relaxant injection is 2 minutes. 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 time parameters assessed in each group are 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 25% (clinical duration), 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. Analgesia is achieved with an initial bolus of sufentanil followed by remifentanil infusion. Depth of anesthesia is monitored using the Narcotrend™ index. p < 0.05 is considered as statistically significant.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• 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
• Genders Eligible for Study: All

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 or kidney disease
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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ulinastatin; The experimental groups （Rocuronium-Ulinastatin group and Cisatracurium-Ulinastatin group）received ulinastatin 5000U/kg followed by rocuronium 0.6 mg/kg or cisatracurium 0.1 mg/kg	Drug: Ulinastatin; The CIS-ULI group received ulinastatin 5000U/kg followed by cisatracurium 0.1 mg/kg The CIS-NS (control) group received normal saline 0.1ml/kg followed by cisatracurium 0.1 mg/kg. The ROC-ULI group received ulinastatin 5000U/kg followed by rocuronium 0.6 mg/kg The ROC-NS (control) group received normal saline 0.1ml/kg followed by rocuronium 0.6 mg/kg; Procedure: TOF monitoring; The acceleromyograph TOF-Watch® SX (Organon, Ireland) is used for TOF monitoring. When the Narcotrend™ index is below 50 and level of anesthesia assessed as deep enough, TOF stimulation is started at 50 mA amplitudes and the setup is checked for any problem concerning the electrodes impedance and local hand temperature. After 1 minute, TOF stimulation is stopped and a tetanic stimulation (each electrical stimulus of 200μs duration and 50 mA amplitude) is delivered at a frequency of 50Hz for 5 seconds. After this procedure the alignment of sensors are checked to see if they are intact and readjust to their initial position if necessary. A no stimulation pause is observed during 3 minutes.
SHAM_COMPARATOR: Conventional treatment group; The control groups（Rocuronium-Saline group and Cisatracurium-Saline group） received normal saline 0.1ml/kg followed by rocuronium 0.6 mg/kg or cisatracurium 0.1 mg/kg	Drug: Ulinastatin; The CIS-ULI group received ulinastatin 5000U/kg followed by cisatracurium 0.1 mg/kg The CIS-NS (control) group received normal saline 0.1ml/kg followed by cisatracurium 0.1 mg/kg. The ROC-ULI group received ulinastatin 5000U/kg followed by rocuronium 0.6 mg/kg The ROC-NS (control) group received normal saline 0.1ml/kg followed by rocuronium 0.6 mg/kg; Procedure: TOF monitoring; The acceleromyograph TOF-Watch® SX (Organon, Ireland) is used for TOF monitoring. When the Narcotrend™ index is below 50 and level of anesthesia assessed as deep enough, TOF stimulation is started at 50 mA amplitudes and the setup is checked for any problem concerning the electrodes impedance and local hand temperature. After 1 minute, TOF stimulation is stopped and a tetanic stimulation (each electrical stimulus of 200μs duration and 50 mA amplitude) is delivered at a frequency of 50Hz for 5 seconds. After this procedure the alignment of sensors are checked to see if they are intact and readjust to their initial position if necessary. A no stimulation pause is observed during 3 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset time	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.	1 day
RT1	RT1 defined as the time from start of injection of neuromuscular blocker to T1 reappearance.	1 day
RT2	Duration of moderate neuromuscular block (RT1-RT4)	1 day
RT3	RT3 defined as the time from start of injection of neuromuscular blocker to T3 reappearance	1 day
RT4	RT4 defined as the time from start of injection of neuromuscular blocker to T4 reappearance	1 day
Duration of moderate neuromuscular block (RT1-RT4)	Duration of moderate neuromuscular block (RT1-RT4) defined as the time from reappearance of T1 to reappearance of T4.	1 day
Duration 25%	Duration 25% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 25%.	1 day
Duration 50%	Duration 50% defined as the time from start of injection of neuromuscular blocker to T1 recovery to 50%.	1 day
Duration TOF 0.7	Duration TOF 0.7 defined as the time from start of neuromuscular blocker injection to recovery of TOF ratio to 0.7.	1 day
Recovery TOF 0.7 period	Recovery TOF 0.7 period defined as the time from reappearance of T4 to recovery of TOF ratio to 0.7.	1 day

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 15, 2023
• Primary Completion (ANTICIPATED): June 15, 2023
• Study Completion (ANTICIPATED): 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): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 4, 2023
• 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