Clinical trial NCT06681662: Ephedrine for Reducing Onset Time of Rocurinium in Elderly Patients
Official title: A Blinded Randomized Study of Ephedrine 0.15 Mg/kg for Reducing Onset Time of Rocuronium 0.6 Mg/kg in Elderly Patients (≥ 80 Years)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neuromuscular Blockade
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2024-11-08
Enrollment: 80
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized study. Patients will be allocated randomly at a ratio of 1:1 to receive either 0.15 mg/kg ephedrine or saline (placebo). Randomization will be done at the day of operation after written informed consent is obtained. An independent investigator will allocate patients by using a computerized random number generator in REDCap. In REDCap patients also receive a number, which pseudo anonymizes data.

The study drug is prepared in the medicine room before the operation. This is done under double control by the investigator who also performed the randomization. The study drug, either ephedrine or saline, will be prepared in a 1 mL syringe. The dose will be mixed with saline to a total of 1 mL to secure blinding.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to determine the onset time of rocuronium after administration of ephedrine 0.15 mg/kg in patients with age ≥ 80 years. The hypothesis of this study is that ephedrine 0.15 mg/kg provides a shorter onset time compared to placebo (saline).

Detailed description: Numbers of elderly patients requiring anesthesia and surgery are increasing, and as a group, elderly patients are at high risk of postoperative complications. Aging leads to a progressive impairment of organ function and a decline in physiologic reserve and in the elderly patient population, pharmacodynamics and pharmacokinetics of medications administered during anesthesia may be influenced by the age-related reduction in cardiac output, liver function and renal function. Also, the body composition changes with age and elderly have lower total body water and an increase in body fat.

Neuromuscular blocking agents (NMBAs) are administered during anesthesia to facilitate tracheal intubation. However, in elderly patients onset time of standard doses of NMBAs are prolonged, and for 0.6 mg/kg of rocuronium it is prolonged by 50% when comparing elderly with younger adults (median 135 seconds vs 90 seconds). A prolonged onset time of rocuronium may result in prolonged time to tracheal intubation which aims to secure the patients airway and breathing during anesthesia and thereby prevents pulmonary aspiration and hypoxia. It is therefore relevant to investigate measures to reduce onset time of rocuronium in the elderly.

Ephedrine administered in younger adults undergoing general anesthesia has reduced the onset time of rocuronium 0.6 mg/kg. The mechanism behind this is speculated to be an increase in cardiac output.

It is possible to detect onset time of NMBAs with objective neuromuscular monitoring perioperatively by train-of-four (TOF) stimulation at the ulnar nerve. The effect of ephedrine on onset time of rocuronium has not been assessed in elderly patients above 80 years of age.

The possible benefit of this trial is to investigate whether ephedrine 0.15 mg/kg reduces onset time of rocuronium 0.6 mg/kg in the elderly. This may result in a shorter time to tracheal intubation and also establish better intubating conditions. The results may help to detect the optimal method for administering rocuronium to facilitate tracheal intubation in elderly patients.

The investigators hypothesize that ephedrine 0.15 mg/kg will provide a shorter onset time of rocuronium compared to placebo (saline).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 80
* Scheduled for elective operations under general anesthesia with intubation
* American Society of Anesthesiologists physical status classification (ASA) I to III
* Informed consent
* Read and understand Danish

Exclusion Criteria:

* Known allergy to rocuronium or ephedrine
* Neuromuscular disease that may interfere with neuromuscular data
* Indication for rapid sequence induction
* Daily use of beta-blocking agents
* Known cardiac arrythmia (atrial fibrillation, supraventricular or ventricular)

Primary outcomes:
measure: Onset time of rocuronium 0.6 mg/kg defined as the time from administration of rocuronium until TOF count of 0.
timeFrame: Within 1 hour
Secondary outcomes:
measure: Intubating conditions assessed by The Intubation Difficulty Scale (IDS)
timeFrame: Within 1 hour
measure: Intubating conditions assessed by Fuchs-Buder scale
timeFrame: Within 1 hour
measure: Occurrence of new cardiac arrythmia during induction of anaesthesia (<15 minutes after administration of ephedrine or saline)
timeFrame: Within 15 minutes
measure: Change in mean arterial blood pressure from before induction to immediately after intubation
timeFrame: Within 1 hour
measure: Time to TOF 0.9
timeFrame: Within 4 hours
Other outcomes:
measure: Occurrence of hoarseness and sore throat 24 and 72 hours postoperatively
timeFrame: Within 72 hours
Locations:
city: Copenhagen
country: Denmark
facility: Department of Anaesthesiology, Pain and Respiratory Support, Rigshospitalet Glostrup
city: Copenhagen
country: Denmark
facility: Department of Anesthesia, Centre of Head and Orthopedics, 6013 Rigshospitalet
Study officials:
affiliation: Rigshospitalet, University of Copenhagen
name: Matias Vested
role: STUDY_CHAIR
References: