Developing a Physiology-Pharmacodynamic Model of Rocuronium Dose and Cardiac Output to Investigate the Onset Time of Neuromuscular Relaxation

NCT ID: NCT07168252

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2026-12-31

Brief Summary

After a patient is put to sleep, a breathing tube is often placed through the larynx (voice box) into the trachea (windpipe). To place a breathing tube requires the muscles of the jaw, voice box, and diaphragm to be relaxed. This relaxation is usually done with muscle relaxant drugs and called paralysis. Which paralysis drug and what dose should be used has been the subject of many studies.

In certain situations it is important for the patient to be fully paralysed before being intubated. Trying to intubate a partially paralysed person may result in coughing that could spread aerosols (e.g. COVID-19), patient desaturation (dropping oxygen levels), greater physiological response to intubation (heart rate, blood pressure and intra-cranial pressure rises) as well as expose the patient to risk of harm through repeated intubation attempts.

Current standard practice for patients needing critical care is to use the drug rocuronium at 1-1.2 mg/kg and wait 60 seconds for paralysis to occur. Unfortunately, 1.2mg/kg rocuronium often fails to provide good intubating conditions at 60s in some patients. The early studies revealed that 1 mg/kg rocuronium paralysis at 60s to be 'adequate' rather than 'excellent', as judged by those doing the intubation. One suggestion from 2000, was that a dose of 1.8 - 2.3 mg/kg rocuronium may be required to achieve 'excellent' intubating conditions at 60s in the vast majority of patients as is necessary clinically. The question of whether larger doses might be better has not been further investigated.

One of the reasons that the paralysis does not seem to work as fast in some patients may be related to the speed with which the drug travels round the body, pumped around the circulation, to the muscles, by the heart. This speed of circulation called cardiac output can be measured in patients at the time of injection. It may be possible to create a mathematical model for onset of paralysis by combining the information cardiac output, patient size, rocuronium dose administered, and time to paralysis. Such a model has been started by earlier researchers. The model needs further data for completion.

Once available, the model may be able to explain how fast the onset of paralysis might be in certain cardiac outputs. It might also deduce whether giving larger doses might help speed up the onset of paralysis in those patients.

Conditions

Induction of Anaesthesia; Muscle Relaxants; Rocuronium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

0.6 mg/kg rocuronium IV bolus

Group Type: ACTIVE_COMPARATOR

Rocuronium dosing

Intervention Type: DRUG

Rocuronium doses of 0.6ng/kg, 1.2mg/kg, 1.6mg/kg and 2.0 mg/kg will be compared for onset speed of muscle relaxation and information on speed, cardiac output and patient body size entered into a computer model

1.2 mg/kg rocuronium

Group Type: ACTIVE_COMPARATOR

Rocuronium dosing

Intervention Type: DRUG

Rocuronium doses of 0.6ng/kg, 1.2mg/kg, 1.6mg/kg and 2.0 mg/kg will be compared for onset speed of muscle relaxation and information on speed, cardiac output and patient body size entered into a computer model

1.6mg/kg rocuronium

Group Type: EXPERIMENTAL

Rocuronium dosing

Intervention Type: DRUG

Rocuronium doses of 0.6ng/kg, 1.2mg/kg, 1.6mg/kg and 2.0 mg/kg will be compared for onset speed of muscle relaxation and information on speed, cardiac output and patient body size entered into a computer model

2.0 mg/kg

Group Type: EXPERIMENTAL

Rocuronium dosing

Intervention Type: DRUG

Rocuronium doses of 0.6ng/kg, 1.2mg/kg, 1.6mg/kg and 2.0 mg/kg will be compared for onset speed of muscle relaxation and information on speed, cardiac output and patient body size entered into a computer model

Interventions

Rocuronium dosing

Rocuronium doses of 0.6ng/kg, 1.2mg/kg, 1.6mg/kg and 2.0 mg/kg will be compared for onset speed of muscle relaxation and information on speed, cardiac output and patient body size entered into a computer model

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• General anaesthesia utilising an arterial line and rocuronium at an approved study site hospital (WSLHD - Blacktown & Mount Druitt hospitals)
• Expected procedure duration >1.5 hours
• no contraindications to rocuronium neuromuscular blockade
• no contraindications to propofol TCI anaesthesia

Exclusion Criteria

• Unable to consent for themselves for procedure
• Need for hospital interpreter (not currently funded for research use)
• pregnancy or lactation
• BMI > 50
• neuromuscular condition (e.g. affecting muscle or neuromuscular junction)
• renal failure (eGFR <30)
• chronic liver failure diagnosis
• epilepsy or antiepileptics
• lithium
• Atrial Fibrillation/Aflutter (regular rhythm needed for cardiac output monitor)
• gentamicin administered before induction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clare Hayes-Bradley

OTHER

Sponsor Role: lead

Responsible Party

Clare Hayes-Bradley

Staff Specialist Anaesthetics

Responsibility Role: SPONSOR_INVESTIGATOR

Central Contacts

Clare Hayes-Bradley

Role: CONTACT

clare.hayes-bradley@monash.edu

+61 2 8670 8019

Other Identifiers

2025/PID00382 - 2025/ETH00325

Identifier Type: -

Identifier Source: org_study_id