AnalgesiaPhase 4NCT04161729
Effects of Intraoperative Magnesium Sulfate on Perioperative Pain Relief After Spine Surgery
A Phase 4 study testing Magnesium Sulfate and Isotonic saline 0.9% in people with Analgesia and Pain, Postoperative, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
The treatment of postoperative pain is increasingly based on a multimodal approach and although opioids remain the drug of choice, they are often used in combination with other analgesics (paracetamol, cyclooxygenase inhibitors or non-steroidal anti-inflammatory drugs) and co-analgesic agents (clonidine and anti- NMDA… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Analgesia, Pain, Postoperative, Spine Disease
- What is being tested?
- Magnesium Sulfate and Isotonic saline 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteGreece
- Study dates
- 28 Jan 2020to 5 May 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged between 18 and 80 years
- ASA Physical status 1 to 3
- Elective or semi-elective lumbar laminectomy surgery
- Signed informed consent
Who cannot join
- Under medication with calcium channel blockers or magnesium
- Drugs or alcohol abuse
- Neurological disorders
- Myopathy
- Intracardiac block
- Hepatic failure
- Renal failure
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Intraoperative Magnesium Sulfate on Pain Relief, Hemodynamics and Quality of Recovery After Spine Surgery
The treatment of postoperative pain is increasingly based on a multimodal approach and although opioids remain the drug of choice, they are often used in combination with other analgesics (paracetamol, cyclooxygenase inhibitors or non-steroidal anti-inflammatory drugs) and co-analgesic agents (clonidine and anti- NMDA such as ketamine or MgSO4). The rationale for combined analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitisation. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period.
Although magnesium is not a primary analgesic in itself, it enhances the analgesic actions of more established analgesics as an adjuvant agent. Magnesium produces a voltage-dependent block of NMDA receptors and has been reported to have analgesic properties that might be related to this inhibiting property. Magnesium sulfate has been reported to be effective in perioperative pain treatment and in blunting somatic, autonomic and endocrine reflexes provoked by noxious stimuli.
Read more
When magnesium was used intraoperatively, many researchers reported that it reduced the requirement for anesthetics and/or muscle relaxants.
Intraoperative use of magnesium sulfate can also be associated with decreased incidences of nausea and vomiting after surgery, which could have been due to the lower consumption of anesthetics (i.e. volatile agents), rather than any antiemetic effect of magnesium sulfate. In addition, perioperative i.v. administration of magnesium sulfate has another advantageous effect, as it decreases the incidence of shivering by up to 70-90%. Previous studies investigating the analgesic efficacy of MgSO4 in general, gynaecological, ophthalmic and orthopaedic surgery have shown conflicting results, while reports regarding spine surgery are extremely limited.
Our study was designed to investigate the effects of MgSO4 on perioperative pain relief and postoperative quality of recovery after lumbar laminectomy surgery.
Read the detailed description
Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature, accelerography) and an intravenous access will be established. The level of anaesthesia will be monitored with the bispectral index (BIS), targeting to a BIS level 40-50.
Group M patients will receive intravenous magnesium sulfate 20 mg/kg over a 15-min period before induction of anaesthesia and 20 mg/kg/h by continuous i.v. infusion during the operation. Group C will be given isotonic solution of 0.9% in the same volume as the study drug.
A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and fendanyl 2 μg/kg (iv). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anaesthesia will be maintained with air 50% and oxygen 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil will be added to the anesthesia regimen as needed.
Hemodynamic parameters will be recorded upon
- Baseline: Before the administration of the tested drug
- T5: 5 minutes after the administration of the tested drug
- T10: 10 minutes after the administration of the tested drug
- T15: 15 minutes after the administration of the tested drug
- Ts: surgical incision
- T30: 30 minutes after the administration of the tested drug
- T45: 45 minutes after the administration of the tested drug
- T60: 60 minutes after the administration of the tested drug
- T90: 90 minutes after the administration of the tested drug
- T120: 120 minutes after the administration of the tested drug
- T180: 180 minutes after the administration of the tested drug
Low arterial blood pressure during surgery defined as a mean blood pressure value < 50 mmHg will be treated by a bolus of 5 mg ephedrine administered intravenously or phenylephirne civ for persistent hypotension.
Also, time to accelerography recording indicating the appropriateness of neuromuscular block for intubation, mean expired desflurane concentration (from 30 min after skin incision to the end of surgery), boluses of ephedrine and total intraoperative remifentanil consumption will be recorded.
Postoperative analgesic protocol will involve paracetamol 1 mg (iv), lornoxicam 8mg (iv) and morphine 3 mg (upon request).
Postoperatively pain assessment will be performed by Visual Analogue Scale (VAS), Verbal Rating Scale (VRS) and Numerical Rating Scale (NRS) at emergence from anesthesia and 2, 4, 6, and 24 h in the study period. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded. Episodes of shivering, as well as episodes of nausea and vomiting (PONV), will be recorded at emergence and thereafter, throughout the study period. Finally, patients' global satisfaction will be assessed the first day after surgery using a 5-grade scale (1= worst discomfort ever experienced in their life and 5= totally satisfied during the immediate postoperative period).
- Conditions
- Analgesia, Pain, Postoperative, Spine Disease
- Being tested
- Magnesium Sulfate, Isotonic saline 0.9%
- Keywords
- magnesium, analgesia, pain score, opioid consumption, spine surgery
- Medical subject headings
- Agnosia, Pain, Postoperative, Spinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium SulfateDrug
Intravenous magnesium sulfate 20 mg/kg in 100ml isotonic saline 0.9% over a 15-min period before induction of anesthesia and 20 mg/kg/h by continuous i.v. infusion until surgery completion.
Isotonic saline 0.9%Drug
Isotonic saline 0.9% 100ml over a 15-min period before induction of anesthesia and thereafter continuous i.v. infusion until surgery completion in dosage identical to magnesium sulfate group.
| Study group | Role | What they receive |
|---|---|---|
| Magnesium sulfate | Active comparator | Magnesium sulfate 20 mg/kg intravenous over a 15-min period before induction of anesthesia and 20 mg/kg/h by continuous i.v. infusion until surgery completion. Receives: Drug: Magnesium Sulfate; Drug: Isotonic saline 0.9% |
| Isotonic solution 0.9% | Placebo comparator | Isotonic solution 0.9% in the same volume as the study drug using identical pattern of administration. Receives: Drug: Magnesium Sulfate; Drug: Isotonic saline 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analgesics consumption postoperatively in morphine equivalents
The difference in analgesic consumption (assessed as mg of morphine equivalents) postoperatively after intravenous infusion of magnesium sulfate or isotonic saline 0.9%
Measured: 24 hours after the emergence from anesthesia
Secondary outcomes (3)
Analgesics consumption intraoperatively
The difference in analgesics consumption (μg of remifentanil) intraoperatively after /during intravenous infusion of magnesium sulfate or isotonic saline 0.9%
Measured: 180 minutes intraoperatively
Pain intensity
The difference in pain intensity postoperatively assessed by Visual Analogue Scale, Numerical Pain Scale or Verbal Pain Scale after intravenous infusion of magnesium sulfate or isotonic saline 0.9%
Measured: 10 minutes after emergence from anesthesia, 2, 4 and 6 hours after the emergence from anesthesia
Time to first analgesic request in minutes
The difference in the time frame (minutes) for analgesia request after emergence from anesthesia after intravenous infusion of magnesium sulfate or isotonic saline 0.9%
Measured: 24 hours after the emergence from anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start28 Jan 2020
- Primary completion3 May 2020
- Study completion5 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnalgesiaStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Georgia Tsaousi, Aristotle University Of Thessaloniki
- Investigators
- Georgia Tsaousi, Principal investigator, Aristotle University Of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04161729
- Sponsor's protocol ID
- SpiMag
- Status last verified
- May 2020
- First submitted
- 3 Nov 2019
- Last updated
- 14 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Intraoperative Magnesium Sulfate on Pain Relief, Hemodynamics and Quality of Recovery After Spine Surgery
- ClinicalTrials.gov ID
- NCT04161729
- Acronym / sponsor ID
- SpiMag
- Conditions
- Analgesia, Pain, Postoperative, Spine Disease
- Keywords
- magnesium, analgesia, pain score, opioid consumption, spine surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 28 Jan 2020 (actual)
- Primary completion
- 3 May 2020 (actual)
- Study completion
- 5 May 2020 (actual)
- First posted
- 13 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatment of postoperative pain is increasingly based on a multimodal approach and although opioids remain the drug of choice, they are often used in combination with other analgesics (paracetamol, cyclooxygenase inhibitors or non-steroidal anti-inflammatory drugs) and co-analgesic agents (clonidine and anti- NMDA such as ketamine or MgSO4). The rationale for combined analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitisation. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period.
Although magnesium is not a primary analgesic in itself, it enhances the analgesic actions of more established analgesics as an adjuvant agent. Magnesium produces a voltage-dependent block of NMDA receptors and has been reported to have analgesic properties that might be related to this inhibiting property. Magnesium sulfate has been reported to be effective in perioperative pain treatment and in blunting somatic, autonomic and endocrine reflexes provoked by noxious stimuli.
When magnesium was used intraoperatively, many researchers reported that it reduced the requirement for anesthetics and/or muscle relaxants.
Intraoperative use of magnesium sulfate can also be associated with decreased incidences of nausea and vomiting after surgery, which could have been due to the lower consumption of anesthetics (i.e. volatile agents), rather than any antiemetic effect of magnesium sulfate. In addition, perioperative i.v. administration of magnesium sulfate has another advantageous effect, as it decreases the incidence of shivering by up to 70-90%. Previous studies investigating the analgesic efficacy of MgSO4 in general, gynaecological, ophthalmic and orthopaedic surgery have shown conflicting results, while reports regarding spine surgery are extremely limited.
Our study was designed to investigate the effects of MgSO4 on perioperative pain relief and postoperative quality of recovery after lumbar laminectomy surgery.
Detailed description
Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature, accelerography) and an intravenous access will be established. The level of anaesthesia will be monitored with the bispectral index (BIS), targeting to a BIS level 40-50.
Group M patients will receive intravenous magnesium sulfate 20 mg/kg over a 15-min period before induction of anaesthesia and 20 mg/kg/h by continuous i.v. infusion during the operation. Group C will be given isotonic solution of 0.9% in the same volume as the study drug.
A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and fendanyl 2 μg/kg (iv). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anaesthesia will be maintained with air 50% and oxygen 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil will be added to the anesthesia regimen as needed.
Hemodynamic parameters will be recorded upon
- Baseline: Before the administration of the tested drug
- T5: 5 minutes after the administration of the tested drug
- T10: 10 minutes after the administration of the tested drug
- T15: 15 minutes after the administration of the tested drug
- Ts: surgical incision
- T30: 30 minutes after the administration of the tested drug
- T45: 45 minutes after the administration of the tested drug
- T60: 60 minutes after the administration of the tested drug
- T90: 90 minutes after the administration of the tested drug
- T120: 120 minutes after the administration of the tested drug
- T180: 180 minutes after the administration of the tested drug
Low arterial blood pressure during surgery defined as a mean blood pressure value < 50 mmHg will be treated by a bolus of 5 mg ephedrine administered intravenously or phenylephirne civ for persistent hypotension.
Also, time to accelerography recording indicating the appropriateness of neuromuscular block for intubation, mean expired desflurane concentration (from 30 min after skin incision to the end of surgery), boluses of ephedrine and total intraoperative remifentanil consumption will be recorded.
Postoperative analgesic protocol will involve paracetamol 1 mg (iv), lornoxicam 8mg (iv) and morphine 3 mg (upon request).
Postoperatively pain assessment will be performed by Visual Analogue Scale (VAS), Verbal Rating Scale (VRS) and Numerical Rating Scale (NRS) at emergence from anesthesia and 2, 4, 6, and 24 h in the study period. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded. Episodes of shivering, as well as episodes of nausea and vomiting (PONV), will be recorded at emergence and thereafter, throughout the study period. Finally, patients' global satisfaction will be assessed the first day after surgery using a 5-grade scale (1= worst discomfort ever experienced in their life and 5= totally satisfied during the immediate postoperative period).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Magnesium sulfate | Active comparator | Drug: Magnesium Sulfate, Drug: Isotonic saline 0.9%Magnesium sulfate 20 mg/kg intravenous over a 15-min period before induction of anesthesia and 20 mg/kg/h by continuous i.v. infusion until surgery completion. |
| Isotonic solution 0.9% | Placebo comparator | Drug: Magnesium Sulfate, Drug: Isotonic saline 0.9%Isotonic solution 0.9% in the same volume as the study drug using identical pattern of administration. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients aged between 18 and 80 years
- ASA Physical status 1 to 3
- Elective or semi-elective lumbar laminectomy surgery
- Signed informed consent
Key exclusion criteria (8 listed)
- Under medication with calcium channel blockers or magnesium
- Drugs or alcohol abuse
- Neurological disorders
- Myopathy
- Intracardiac block
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium SulfateIntravenous magnesium sulfate 20 mg/kg in 100ml isotonic saline 0.9% over a 15-min period before induction of anesthesia and 20 mg/kg/h by continuous i.v. infusion until surgery completion. | Drug | Isotonic solution 0.9%, Magnesium sulfate |
| Isotonic saline 0.9%Isotonic saline 0.9% 100ml over a 15-min period before induction of anesthesia and thereafter continuous i.v. infusion until surgery completion in dosage identical to magnesium sulfate group. | Drug | Isotonic solution 0.9%, Magnesium sulfate |
Primary outcome
Analgesics consumption postoperatively in morphine equivalents
Time frame: 24 hours after the emergence from anesthesia
The difference in analgesic consumption (assessed as mg of morphine equivalents) postoperatively after intravenous infusion of magnesium sulfate or isotonic saline 0.9%
3 secondary outcomes
Analgesics consumption intraoperatively
Time frame: 180 minutes intraoperatively
Pain intensity
Time frame: 10 minutes after emergence from anesthesia, 2, 4 and 6 hours after the emergence from anesthesia
Time to first analgesic request in minutes
Time frame: 24 hours after the emergence from anesthesia
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Georgia Tsaousi principal investigator
Aristotle University Of Thessaloniki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Magnesium Sulfate and Isotonic saline 0.9% in people with Analgesia and Pain, Postoperative, run by Aristotle University Of Thessaloniki at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analgesics consumption postoperatively in morphine equivalents (time frame: 24 hours after the emergence from anesthesia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2020.