Clinical trial NCT04938765: Effect of Magnesium Sulfate Bolus on Intraoperative Neuromonitoring
Official title: Randomized and Placebo Controlled Study to Evaluate the Effect of Magnesium Sulfate on Intraoperative Neuromonitoring.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Intraoperative Neurophysiological Monitoring
Magnesium Sulfate
Keywords: multimodal analgesia
Lead sponsor: Loma Linda University
Sponsor class: OTHER
First posted: 2021-06-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective double blind randomized clinical trial
Primary purpose: DIAGNOSTIC

Brief summary: Magnesium Sulfate(MgSo4) is increasingly being used as part of the multimodal pain regimen in the perioperative period. The intraoperative neurophysiological monitoring (IONM) is utilized in complex spine and cranial surgeries to assess the functional integrity of the neural pathways. The effect of Magnesium sulfate on IONM has not been studied.

This is a prospective, double blind, randomized placebo controlled trial to study the effect of Magnesium sulfate bolus on the amplitude and latency of somatosensory(SSEPs) and motor evoked potentials(MEPs) in patients undergoing surgery requiring IONM.

Detailed description: The primary objective of this study is to investigate the effect of magnesium sulfate on the amplitude of the SSEP with tibial nerve stimulation. Secondary objectives are to study the effect of magnesium sulfate on the latency of SSEPs and the amplitude of MEPs in patients undergoing spine and/or cranial surgery requiring intraoperative neuromonitoring.

Background: Magnesium Sulfate is increasingly being used as part of the multimodal pain regimen in the perioperative period. The efficacy of intravenous (IV) magnesium sulfate in reducing the postoperative pain scores and/or postoperative opioid use has been established in several randomized controlled trials, systematic reviews, and meta-analyses. The multimodal intraoperative neurophysiological monitoring (IONM) is increasingly being utilized in complex spine surgeries to assess the functional integrity of the neural pathways. The goal of IONM is to avert permanent damage by proving real-time feedback from sensory tracts, motor tracts, and individual nerve roots thus alerting any impending injury which allows for modification of management in time.

Several factors like, hypoxia, hypercarbia, changes in blood pressure and temperature can affect the IONM in addition to direct surgical injury to neural structures. In addition, several drugs including anesthetic agents can have a significant effect on IONM. Hence anesthetic regimen is usually tailored to facilitate IONM during these surgeries. The infusion of propofol and remifentanil are commonly used for maintenance of anesthesia during these procedures. Opioid analgesics play a central role in the anesthetic cocktail as the pain associated with complex spinal surgery can be debilitating. However, opioids can also complicate the postoperative pain management by inducing opioid induced hyperalgesia and /or tolerance. The current trend is to implement a multimodal analgesic approach to achieve an additive or synergistic analgesic effect by targeting different receptors in the peripheral and central pain signaling pathways while minimizing opioid-related adverse effects. Magnesium sulfate has shown promising results when used as part of the multimodal pain management in previous studies in addition it can also has shown to attenuate the remifentanil-induced hyperalgesia which is commonly used as part of the anesthetic regimen. However, the effect of Magnesium Sulfate on intraoperative neuromonitoring is not been studied.

Methods Procedures involved (Research Interventions):

After obtaining the written informed consent and premedication, patients will be taken to the operating room. The standard ASA monitors will be applied. They will be monitored with electrocardiography, noninvasive and/or invasive blood pressure (BP), pulse oximetry, and temperature monitor along with brain function monitor to monitor the depth of anesthesia (Sedline monitor) during surgery.

After preoxygenation, the patient will be induced with general anesthesia using fentanyl 1-3 mg/kg or Remifentanil 1-3 mcg/kg, lidocaine 1-2 mg/kg, Propofol 1-3 mg/kg, and succinylcholine 1-2 mg/kg or Rocuronium 0.3-0.5 mg/kg. Inhalation anesthetic agents will not be used for induction or maintenance of anesthesia but may be used after the end of data collection for this study and/or during closing. Anesthetic infusion consisting of propofol 50-150 mg/kg, remifentanil 0.05-0.2 mg/kg will be started immediately after the induction for maintenance of general anesthesia and doses may be adjusted to higher amounts if needed. The BP will be maintained within 20% of patient's baseline using phenylephrine infusion or other appropriate vasoactive agents after the induction of anesthesia. End-tidal carbon dioxide will be maintained within normal limits. Patients will be actively warmed using a Bair Hugger™ or similar device(s) ("warmer(s)") to prevent any hypothermia.

In patients given rocuronium, neuromuscular blockage will be reversed before obtaining the baseline IONM recordings. The baseline set of SSEPs and MEPs will be recorded before the study drug administration and consisting of 2 to 4 measurements; T0 represents the average of these measurements. For study group, MgSo4 diluted to \< 20% concentration in 20 ml normal saline will be administered as 40 mg/kg bolus dosed to ideal body weight over 10 min. For control group, 20 ml of normal saline bolus will be administered over 10 mins. Magnesium group will also be given continuous infusion of MgSO4 at 10mg/kg/hr. till the end of the surgery. Repeat SSEPs and MEPs will be recorded at the end of the bolus ("0" minutes) (T1) as well as 10 (T2) and 30 (T3) minutes following the completion of the bolus dose.

Patient's hemodynamic data also will be collected at baseline and every 5 mins up to 30 mins following the administration of the drug.

The T1,T2,T3 data will be compared with the To(baseline) data to evaluate the effect of MgSO4 on intraoperative neuromonitoring.

Eligibility criteria: Inclusion Criteria.

* Patients aged 18 to 80 years
* Belonging to American Society of Anesthesiologists physical status (ASA) I, II
* Undergoing elective spine or cranial surgery where intraoperative neuromonitoring including short latency somatosensory evoked potentials (SSEP or SEP) and transcranial electrical muscle motor evoked potentials recording from muscles (TceMEP or TcMEP or mMEP or MEP) is planned.

Exclusion Criteria:

* Magnesium use within the last 2 days, either intravenous or oral supplements.
* Patients with known electrolyte imbalances (Sodium \<135 or \>145 mmol/L OR Potassium \< 3.5 or \> 5.0 mmol/L, Magnesium \>1.2 mmol/L.
* Severe cardiac or cardiac conduction disorders.
* Severe pulmonary disease.
* Patients with significant neuromuscular disorders or preexisting motor or sensory deficits other than focal upper limb neuropathy or focal cervical radiculopathy or mild cervical myelopathy.
* Severe Renal disease - serum creatinine of \> 2 mg/dl.
* Pregnant or breastfeeding patients.
* Unable to obtain adequate baseline SSEPs and MEPs.

Primary outcomes:
measure: Change in the amplitude of SSEPs.
timeFrame: Up to 30 minutes after the end of bolus dose of MgSO4 or Normal saline.
Secondary outcomes:
measure: Change in the latency of SSEP compared to baseline.
timeFrame: Up to 30 minutes after the end of bolus dose of MgSO4 or Normal saline.
measure: Change in the amplitude of MEPs.
timeFrame: Up to 30 minutes after the end of bolus dose of MgSO4 or Normal saline.
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma linda University Medical Center
state: California
Study officials:
affiliation: Loma Linda University
name: Rashmi Vandse, MD
role: PRINCIPAL_INVESTIGATOR
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