Interaction of Volatile Anesthetics With Magnesium

Neuromuscular Blockade Clinical Trial

— Volmag  

Official title:

Interaction Between Intravenous Magnesium Sulfate and Volatile Anesthetics Compared to Propofol. A Three-center Prospective Randomized Single-blinded Electrophysiological Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05261516
• Other study ID #: 2019-02104/CE3541
• Status: Recruiting
• Phase: Phase 4
• Start date: November 18, 2022
• Est. completion date: August 31, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Geneva
• Contact: Christoph Czarnetzki, MD, MBA
• Phone: +41 091 8116664
• Email: christoph.czarnetzki[@]hcuge.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Magnesium and volatiles anesthetics both have an effect on the neuromuscular transmission. The primary objective of the study is to quantify the effect of a perfusion of intravenous magnesium on neuromuscular transmission measured by electromyography device TetraGraph device in patients undergoing general anesthesia with volatile anesthetics (desflurane, sevoflurane and isoflurane) as compared to intravenous anesthesia with propofol.

Description:

Magnesium sulfate is regularly used during anesthesia, for instance for the reduction of postoperative pain. It reduces the liberation of acetylcholine at the neuromuscular junction. At high plasma concentrations it can induce muscle weakness, flaccid paralysis and in cases of intoxication lead to respiratory arrest. It enhances the effect of muscle relaxants.

Volatiles anesthetics influence neuromuscular transmission. They inhibit postsynaptic nicotinic acetylcholine receptors by causing open channel block, receptor desensitization and reducing exocytosis from pre-synaptic vesicles at the neuromuscular junction. The ranking order of these effects of volatile anesthetics on neuromuscular transmission is: desflurane > sevoflurane > isoflurane, depending on their blood-gas and tissue-gas solubility index.

Magnesium given intravenously during volatile anesthesia induces effects on neuromuscular transmission similar to that of neuromuscular blocking agents. This effect has never been investigated and quantified systematically and prospectively.

Propofol, an intravenous anesthetic, has very little effects on neuromuscular transmission. Therefore magnesium given intravenously during total intravenous anesthesia with propofol has no or only very little effect on neuromuscular transmission.

The primary objective of the study is to quantify the effect of a perfusion of intravenous magnesium on neuromuscular transmission measured by accelerometry with theTetraGraph device in patients undergoing general anesthesia with volatile anesthetics (desflurane, sevoflurane and isoflurane) as compared to intravenous anesthesia with propofol. The investigators expect a following rank order of the effect: desflurane > sevoflurane > isoflurane > propofol.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients, age 18 to 65 years inclusive

• American Society of Anesthesiology [ASA] status I or II

• Body mass index 19 - 30 kg/m2

• Patient scheduled for elective surgery lasting = 60 minutes

• Patient is able to read and understand the information sheet and to sign and date the consent form.

• Negative urinary or serum pregnancy test (not applicable if status post hysterectomy or tubal ligation or menopausal woman)

Exclusion Criteria:

• Surgery with need for neuromuscular block

• Contraindication for general anesthesia with laryngeal mask airway, such as gastro-oesophageal reflux.

• Hypersensitivity or allergy to magnesium sulfate or propofol

• Contraindication to volatile anesthetics such as malignant hyperthermia

• Patients with neuromuscular disease

• Patients receiving medications known to influence neuromuscular function (for instance, aminoglycosides or phenytoine)

• Known electrolyte abnormalities (for instance, hypermagnesemia)

• Atrioventricular heart block

• Patients with magnesium treatment within 48 hours before start of study

• Liver insufficiency (bilirubine <1.5x, ALAT/ASAT<2.5x the upper limit of normal value)

• Renal insuffisancy (créatinine <1.5x upper limit of normal value, clearance<30ml/minute)

• Patient having participated in any clinical trial within 30 days, inclusive, of signing the informed consent form of the current trial.

• Pregnant or breast-feeding women.

Related Conditions & MeSH terms

• Neuromuscular Blockade

Intervention

Drug:
• Magnesium Sulfate
The experimental intervention is the injection of magnesium sulfate. This will be done as soon as TetraGraph calibration is done and neuromuscular measurements are stable. Each patient will receive 60 mg/kg of magnesium sulfate as an intravenous perfusion over 5 minutes. Vital signs before, during and after the perfusion will be taken and documented.

Locations

Country	Name	City	State
Switzerland	Department of Anesthesiology and Intensive Care, Valais Hospital	Sion

Sponsors (3)

Lead Sponsor	Collaborator
Christoph Czarnetzki	Centre Hospitalier du Centre du Valais, Ospedale Regionale di Lugano

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in TOF ratio after perfusion of magnesium	This primary outcome will be assessed with neuromuscular monitoring, carried out according to international guidelines. The ulnar nerve will be stimulated by train-of-four (TOF) using a TofScan monitor.	After starting TOF AUTO mode. patients will receive an intravenous perfusion of magnesium 60mg/kg mg kg-1 over 5 minutes. Neuromuscular monitoring will be continued until the end of surgery, but at least until a TOF ratio of 0.9 is reached.
Secondary	Lowest T1 twitch height and TOF ratio	The secondary outcomes are the lowest T1 twitch height and TOF ratio measured after starting the magnesium perfusion and the time required for the return of single twitch height (T1) and TOF ratio to its control value according to the TofScan measurements.	After the perfusion of magnesium and until the T1 twitch height and the TOF ratio reach the initial values again.