Interaction of Volatile Anesthetics With Magnesium (Volmag)

Christoph Czarnetzki

Status and phase

Enrolling

Phase 4

Conditions

Neuromuscular Blockade

Treatments

Drug: Magnesium Sulfate

Study type

Interventional

Funder types

Other

Identifiers

NCT05261516

2019-02104/CE3541

Details and patient eligibility

About

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.

Full 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.

Enrollment

96 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

96 participants in 4 patient groups

Propofol

Active Comparator group

Description:

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.

Treatment:

Drug: Magnesium Sulfate

Isoflurane

Experimental group

Description:

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.

Treatment:

Drug: Magnesium Sulfate

Desflurane

Experimental group

Description:

Treatment:

Drug: Magnesium Sulfate

Sevoflurane

Experimental group

Description:

Treatment:

Drug: Magnesium Sulfate