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

Huazhong University of Science and Technology

Status: Not yet enrolling

Conditions: Nondepolarising Muscle Relaxants

Treatments: Procedure: TOF monitoring; 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 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.

Enrollment: 80 estimated 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 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 2 patient groups

Ulinastatin

Experimental group

Description:

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

Treatment:

Drug: Ulinastatin

Procedure: TOF monitoring

Conventional treatment group

Sham Comparator group

Description:

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

Treatment:

Drug: Ulinastatin

Procedure: TOF monitoring