Interaction of Volatile Anesthetics With Magnesium (Volmag)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: Magnesium Sulfate

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sina Grape, MD, MBA; Phone Number: 0041276038759; Email: sina.grape@hopitalvs.ch
• Study Contact Backup: Name: Christoph Czarnetzki, MD, MBA; Phone Number: +41 091 8116664; Email: christoph.czarnetzki@hcuge.ch

Study Locations

• Switzerland
  • Sion, Switzerland, 1951
    • Recruiting
    • Department of Anesthesiology and Intensive Care, Valais Hospital
    • Contact: Sina Grape, MD, MBA; Email: sina.grape@hopitalvs.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol; In all patients 3 minutes before induction sufentanil 0.2 mcg/kg or fentanyl 2 mcg/kg will be given. In patients in the propofol group, anesthesia will be induced and maintained with a total intravenous anesthesia pump following the model of Schnider et al, at a targeted effect-site concentration of 4 +/- 1 mcg/ml. In patients in all groups, after induction of anesthesia and loss of consciousness, a laryngeal mask airway will be inserted. The TetraGraph device will be calibrated. Once general anesthesia is established, a blood sample will be taken to measure serum magnesium and calcium levels. This blood sample will be analysed in the certified laboratory of each participating hospital.	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.
Experimental: Isoflurane; In all patients 3 minutes before induction sufentanil 0.2 mcg/kg or fentanyl 2 mcg/kg will be given. After induction of anesthesia and loss of consciousness, a laryngeal mask airway will be inserted. The TetraGraph device will be calibrated. Once general anesthesia is established, a blood sample will be taken to measure serum magnesium and calcium levels. This blood sample will be analysed in the certified laboratory of each participating hospital. The anesthesia will be maintained with the agent specified by randomization: isoflurane in this group.	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.
Experimental: Desflurane; In all patients 3 minutes before induction sufentanil 0.2 mcg/kg or fentanyl 2 mcg/kg will be given. After induction of anesthesia and loss of consciousness, a laryngeal mask airway will be inserted. The TetraGraph device will be calibrated. Once general anesthesia is established, a blood sample will be taken to measure serum magnesium and calcium levels. This blood sample will be analysed in the certified laboratory of each participating hospital. The anesthesia will be maintained with the agent specified by randomization: desflurane in this group.	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.
Experimental: Sevoflurane; In all patients 3 minutes before induction sufentanil 0.2 mcg/kg or fentanyl 2 mcg/kg will be given. After induction of anesthesia and loss of consciousness, a laryngeal mask airway will be inserted. The TetraGraph device will be calibrated. Once general anesthesia is established, a blood sample will be taken to measure serum magnesium and calcium levels. This blood sample will be analysed in the certified laboratory of each participating hospital. The anesthesia will be maintained with the agent specified by randomization: sevoflurane in this group.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Christoph Czarnetzki
• Collaborators: Ospedale Regionale di Lugano; Centre Hospitalier du Centre du Valais

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Magnesium; Neuromuscular transmission; Volatiles anesthetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: 2019-02104/CE3541

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No