Clinical trial NCT05261516: Interaction of Volatile Anesthetics With Magnesium
Official title: Interaction Between Intravenous Magnesium Sulfate and Volatile Anesthetics Compared to Propofol. A Three-center Prospective Randomized Single-blinded Electrophysiological Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neuromuscular Blockade
Keywords: Magnesium
Volatiles anesthetics
Neuromuscular transmission
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier du Centre du Valais
name: Ospedale Regionale di Lugano
First posted: 2022-03-02
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a three centers prospective randomized, electrophysiological, single blinded study that will include 96 patients allocated to one of four arms: one arm with propofol anesthesia and three arms with volatile anesthetics (one arm with isoflurane, one with sevoflurane and one with desflurane). Each arm will have 24 patients.
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in TOF ratio after perfusion of magnesium
timeFrame: 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 outcomes:
measure: Lowest T1 twitch height and TOF ratio
timeFrame: After the perfusion of magnesium and until the T1 twitch height and the TOF ratio reach the initial values again.
Other outcomes:
Locations:
city: Sion
country: Switzerland
facility: Department of Anesthesiology and Intensive Care, Valais Hospital
Study officials:
References: