Clinical trial NCT05227716: Clinical Response to Magnesium Sulfate as an Adjunct in the Anesthesia
Official title: Evaluation of the Clinical Response to Magnesium Sulfate as an Adjunct in the Anesthesia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anesthesia and Analgesia
Magnesium Sulfate
Keywords: Magnesium Sulfate
Anesthesia
Analgesia
Pain, Postoperative
Receptors, N-Methyl-D-Aspartate
Lead sponsor: Instituto Mexicano del Seguro Social
Sponsor class: OTHER_GOV
First posted: 2022-02-07
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Clinical trial: An intervention will be carried out in the population to be studied for the purpose of the research and there will be a control group.
* Triple blind: Participants and researchers will be unaware of the type of intervention used (administration of MgSO4 or Placebo).
* Randomized: A list of random numbers will be used to assign patients to study groups.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Magnesium sulfate (MgSO4) has multiple desirable effects in an anesthetic procedure, including modulation of the hemodynamic response to surgical stress, perioperative anesthetic and analgesic effect, potentiation of neuromuscular blockade, and central nervous system depression. MgSO4 is an antagonist of the N-methyl-d-aspartic acid (NMDA) receptor, therefore it produces an analgesic effect related to the prevention of central sensitization caused by peripheral tissue damage.

Objective. To evaluate the perioperative clinical response to MgSO4 as an adjunct to anesthesia.

Material and method. Randomized, triple-blind clinical trial that will include men and women over 18 years of age, scheduled for surgery under general or regional anesthesia. After accepting and signing the informed consent, all patients will be subjected to the same pre, trans and postoperative protocol and will be assigned to 2 groups according to the intravenous administration of MgSO4 (placebo and MgSO4). A brief preoperative medical history will be taken, a peripheral blood sample will be taken to determine preoperative serum Mg, the clinical effect of MgSO4 on trans and postoperative analgesia (EVAD), hemodynamic stability (blood pressure (BP) and heart rate ( HR)), motor and neuromuscular block time (Bromage and TOF), and recovery time. The presence of adverse reactions to anesthesia (nausea, vomiting, chills, pruritus, urinary retention, arrhythmias, laryngeal or bronchial spasm) and those secondary to the administration of Mg, SO4, as well as the total doses of all drugs used during the perioperative. The data will be analyzed in the SPSS software.

Detailed description: The participant selection process will be carried out through direct invitation to patients scheduled for surgery under regional or general anesthesia at the General Hospital of Zone No. 51 of the IMSS, Gómez Palacio, Durango. Explaining what their participation consists of for the subsequent signing of the informed consent letter in case of accepting. Afterwards, according to the type of surgery and scheduled anesthesia, 2 groups will be integrated randomly and blindly for the investigator: one that will receive MgSO4 pre and intraoperatively and another group that will be administered 0.9% NaCl intravenously (placebo). All participants will undergo the same pre, trans and postoperative surgical and anesthetic protocol.

Personal data, background and sociodemographic variables will be collected in a data collection sheet. Subsequently, anthropometric measurements will be made to determine weight, height, body mass index and blood pressure.

Peripheral venous blood samples will be taken in the operating room for the determination of pre and postoperative serum Mg and other analyzes.

Each participant will receive standard and continuous monitoring (electrocardiogram, oxygen saturation, blood pressure, capnography, temperature and TOF) and an intravenous access will be established. The MgSO4 group will receive 30 mg / kg of magnesium sulfate intravenously over a period of 15 minutes before induction of anesthesia and 10 mg / kg / h by continuous intravenous infusion during the operation. The control group (placebo) will receive 0.9% NaCl in the same volume as the study drug.

In procedures under general anesthesia, a standard protocol with propofol 2 mg / kg (IV), fentanyl 2 μg / kg (IV) and cisatracurium 0.2 mg / kg (IV) will be applied. Anesthesia will be maintained with 100% oxygen, and 0.5 to 4 vol% sevoflurane, to achieve a mean alveolar concentration (MAC) of 50%. Maintenance doses of fentanyl will be added to the anesthesia regimen as needed. The maintenance dose of cisatracurium will be administered according to the MNM with TOF. The total doses of the drugs used will be recorded. In cases with neuraxial regional anesthesia, a standard protocol with 10 mg heavy bupivacaine and subarachnoid buprenorphine 60 mcg will be applied.

Hemodynamic parameters will be recorded at baseline (before administration of magnesium sulfate or 0.9% isotonic saline solution and subsequently every 5 minutes during surgery, up to 180 minutes after drug administration.

Low blood pressure during surgery, defined as a mean blood pressure value \<50 mmHg, will be treated with a 5 mg bolus of ephedrine given intravenously or norepinephrine by IV infusion for persistent hypotension (this is the standard anesthetic management of variations in hemodynamic stability). Low heart rate during surgery, defined as \<50 beats per minute, will be treated with atropine at 10 mcg / kg intravenously.

The time until the MNM with TOF indicates the suitability of the neuromuscular block for intubation will be recorded, and the intubation conditions will be evaluated.

The postoperative analgesic protocol will include ketorolac 30mg IV, tramadol 100mg IV, or lysine clonixinate 100mg in case of allergy to ketorolac. Buprenorphine will be administered subcutaneously at a dose of 2 mcg / kg as rescue analgesia only when necessary.

As an adjunct to anesthesia, dexamethasone 8 mg IV, metoclopramide 10 mg IV, ondansetron 100 mcg / kg and omeprazole 40 mg IV will be administered.

Post-operative pain assessment will be performed by EVAD upon exiting anesthesia and at 2, 4, 6, and 24 hours.

The time elapsed until the first request for additional analgesic by the patient, and the total consumption of postoperative analgesics will be recorded, recording it as morphine equivalents.

All the information about all the drugs administered to the patient during their perioperative stay will be collected.

Episodes of nausea, vomiting, itching, chills, arrhythmias, laryngeal or bronchial spasm will be recorded during and after coming out of anesthesia and at the end of the hospital stay.

Satisfaction in recovery from anesthesia will be assessed at 24 hours by delivering a self-report questionnaire to patients.

Finally, the data will be captured in a database for subsequent statistical analysis.

Eligibility criteria: Inclusion Criteria:

* Patients scheduled for elective surgery under general or regional anesthesia at Hospital General de Zona No. 51.
* Physical state ASA 1 and 2
* BMI 18-30 kg / m2
* Acceptance and signing of the informed consent.

Exclusion Criteria:

* Treatment with calcium or magnesium channel blockers
* Drug use or alcoholism referred by the patient in the questioning
* Neurological diseases
* Myopathy
* Intracardiac block
* Renal insufficiency
* Liver failure
* Pregnancy
* Hematological disorders
* Contraindications to the use of magnesium sulfate (hypersensitivity to the active principle or to any of the excipients, concomitant use with quinidine derivatives, tachycardia, heart failure, myocardial injury, infarction).

Elimination criteria:

* Survey with incomplete data corresponding to the study variables.
* Revocation of informed consent or decision to withdraw by of the patient.
* Loss to follow-up

Primary outcomes:
measure: Changes in postoperative analgesia over 24 hours
timeFrame: 15 minutes after coming out of anesthesia, 2, 4, 6 and 24 hours after coming out of anesthesia
measure: Time to first request for pain reliever
timeFrame: 24 hours after departure from anesthesia
measure: Hemodynamic stability
timeFrame: 180 minutes intraoperatively
measure: Interaction with neuromuscular blockers (BNM): Onset time
timeFrame: 180 minutes intraoperatively
measure: Interaction with neuromuscular blockers (BNM):Clinical effect time
timeFrame: 180 minutes intraoperatively
measure: Interaction with neuromuscular blockers (BNM): Recovery index (RI)
timeFrame: 180 minutes intraoperatively
measure: Adverse reactions to magnesium sulfate
timeFrame: From the start of the magnesium sulfate infusion until 24 hours after leaving anesthesia
measure: Adverse reactions to anesthesia
timeFrame: 180 minutes intraoperatively up to 24 hours after discharge from anesthesia
measure: Number of participants carrying polymorphisms related to perioperative clinical response to magnesium sulfate
timeFrame: During the 3-year duration of the study
Secondary outcomes:
measure: Conditions for endotracheal intubation
timeFrame: 5 minutes after the administration of BNM
measure: Consumption of intraoperative analgesics
timeFrame: 180 minutes intraoperatively
measure: Postoperative analgesic consumption
timeFrame: From exit from anesthesia up to 24 hours
measure: Consumption of neuromuscular relaxant
timeFrame: 180 minutes intraoperatively
measure: Hypnotic use
timeFrame: 180 minutes intraoperatively
measure: Satisfaction in recovery from anesthesia
timeFrame: 24 hours after departure from anesthesia
Other outcomes:
measure: Serum magnesium
timeFrame: Before IV infusion of MgS04 or placebo (NaCl at 0.9%) and 24 hours after coming out of anesthesia
Locations:
city: Gómez Palacio
country: Mexico
facility: Lilia Edith Luque-Esparza
state: DGO
city: Gomez Palacio
country: Mexico
facility: Instituto Mexicano Del Seguro Social
state: Durango
Study officials:
References: