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

Sponsor

Huazhong University of Science and Technology (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05716256

Collaborator

(none)

Enrollment

Location

Arms

4.3

Anticipated Duration (Months)

18.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Nondepolarising Muscle Relaxants	Drug: Ulinastatin Procedure: TOF monitoring	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Feb 15, 2023

Anticipated Primary Completion Date :

Jun 15, 2023

Anticipated Study Completion Date :

Jun 25, 2023

Arms and Interventions

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.

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

Procedure: TOF monitoring

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 2.
Receive general anesthesia and muscle relaxants intraoperatively.

Exclusion Criteria:

patients ASA class 3 and above
Severe cardiac or respiratory diseases, liver or kidney disease
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