Magnesium Sulphate Versus Fentanyl Sedation During Burr-hole Surgery

Magnesium Sulphate Versus Fentanyl as Adjuvants to Propofol for Monitored Anesthesia Care During Burr-hole Surgery for Chronic Subdural Hematoma: Randomized Clinical Trial

MgSO4 was found to reduce the perioperative anesthetic and analgesic requirements when used as an adjuvant to general anesthesia. Fentanyl is a potent opioid and used as adjuvant to other sedatives in awake craniotomy procedure. No study, to the best of our knowledge had evaluated fentanyl continuous infusion, nor MgSo4 infusion as adjuvant sedative agents to propofol during Burr-hole surgery. The aim of this study is to evaluate and compare MgSO4 versus fentanyl continuous infusions for conscious sedation in patients undergoing burr hole surgery for evacuation of subdural hematoma with local infiltration.

Study Overview

• Status: Completed
• Conditions: Monitored Anesthesia Care
• Intervention / Treatment: Drug: Magnesium Sulphate; Drug: Propofol; Drug: Fentanyl

Detailed Description

All participants or their proxy will be informed about the anesthetic techniques and the operative procedure and will provide written informed consent before enrollment in the study.

The eligible patients will be randomly divided by computer designed lists and then will be concealed in closed envelopes into the two study groups. A research assistant who will not be involved in patient management will be responsible for opening the envelope, group assignment and drugs preparation.

Anesthetic management Pre-induction No premedication will be administered. Upon arrival to the operating theater, an intravenous (IV) cannula will be placed, and standard monitors, including 5-lead electrocardiogram, noninvasive arterial blood pressure monitor, and pulse oximetry, will be applied. Oxygen supplementation at fraction of inspired oxygen (FiO2) of 0.35 will be achieved through a suitable air entrainment mask. Bispectral index (BIS: apparatus info) will be applied before starting the drug infusions and will be used for maintenance of sedation during operation.

Induction of anesthesia Group M (n=17): will receive a loading of 50 mg/kg in 15 minutes of Magnesium sulphate, and will be followed by continuous infusion at 1 ml/kg/h of 15 mg/ml solution Group F (n=17): will receive a loading of 1 mcg/kg in over 15 minutes of fentanyl then will receive continuous infusion starting at 1 ml /kg/h. of 0.5 mcg/ml solution Both groups will be given 0.5-1.5 mg/kg bolus of propofol over 10 minutes to achieve target Ramsay sedation scale (RSS) of 3 (respond to command), if RSS afterwards does not reach 3 a supplementary bolus dose of 0.2 mg/kg propofol will be given to the patients, and will be followed by 1-2.5 mg/kg/hr infusion to maintain Intraoperative BIS readings between 60 - 80.

Intraoperative management After achieving the target sedation level (RSS of 3), surgeons will infiltrate the surgical site with 20 mL of a local anesthetic solution containing 10 mL of 0.5% bupivacaine and 10 mL of 2% lidocaine with adrenaline at least 5 minutes before surgical incision. After performing burr-hole craniotomy soaked pledgets with lidocaine will be applied to anaesthetize the dura, the dura will be then opened, and the hematoma will be evacuated. The Infusion of sedatives will be ceased after skin closure.

Intraoperative patient's movements (defined as those which may interfere with the surgical conduct such as twisting of hand and/or leg and head mobility) will be managed by reassurance and support for 30 seconds. However, when movements continue, a bolus dose of propofol of 0.5 mg/kg will be given then infusion dose will be increased till the maximum dose (2.5mg/kg/hr) to regain BIS sedation score between 60-80. If the patient starts to move again the same sequence will be repeated. Minute movements of other body parts as well as movements of fingers or toes that unlikely to hinder the operative intervention, will be deemed insignificant to be documented.

Induction of general anesthesia will be only indicated if satisfactory surgical conditions will not be attained by the rescue propofol.

Intraoperative bradycardia and tachycardia (defined as heart rate (HR) < 45 bpm or > 120 bpm respectively) will be treated with intravenous atropine 0.2 mg, or propranolol 0.5-1 mg respectively. Hypertension and hypotension (defined as a more than 25% increase or decrease from baseline respectively) will be treated with nitroglycerine (0.1-10 mcg/min) or ephedrine (5 mg) respectively.

Postoperative management All patients will be transferred to the post-anesthesia care unit (PACU) after surgery where they will be closely monitored with the aid of five-lead electrocardiography and non-invasive arterial blood pressure, peripheral oxygen saturation (SpO2), and respiratory rate readings using an automated system for 24 h after surgery. Postoperative pain intensity will be assessed using VAS score at 1, 2, 3 and 6 hours after PACU admission. If VAS score exceeds 3, 30 mg of ketorolac will be administered.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11562
    • Kasr Alaini Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with unilateral, chronic subdural hematoma,
• aged above 50 years,
• american society of anesthesiologist-physical status (ASA-PS) grade I-II,
• Glasgow coma scale of 14-15.

Exclusion Criteria:

• Patients with hypertension (Systolic blood pressure > 160 mmHg),
• bradycardia (<50 bpm),
• ischemic heart disease,
• second- or third-degree heart block,
• long-term abuse of or addiction to opioids, and sedative-hypnotic drugs (>6 months),
• allergy to study drugs
• neuropsychiatric diseases
• patients with predicted difficult airway
• patients with history of obstructive sleep apnea
• patients with deviation in the surgical technique
• inadequacy of local anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group M; magnesium sulphate as adjuvant to propofol	Drug: Magnesium Sulphate; a loading of 50 mg/kg in 15 minutes of Magnesium sulphate, and will be followed by continuous infusion at 1 ml/kg/h of 15 mg/ml solution; Other Names: magnesium sulfate; Drug: Propofol; 0.5-1.5 mg/kg bolus of propofol over 10 minutes to achieve target Ramsay sedation scale (RSS) of 3 (respond to command), if RSS afterwards does not reach 3 a supplementary bolus dose of 0.2 mg/kg propofol will be given to the patients, and will be followed by 1-2.5 mg/kg/hr infusion to maintain Intraoperative BIS readings between 60 - 80
ACTIVE_COMPARATOR: Group F; fentanyl as adjuvant to propofol	Drug: Propofol; 0.5-1.5 mg/kg bolus of propofol over 10 minutes to achieve target Ramsay sedation scale (RSS) of 3 (respond to command), if RSS afterwards does not reach 3 a supplementary bolus dose of 0.2 mg/kg propofol will be given to the patients, and will be followed by 1-2.5 mg/kg/hr infusion to maintain Intraoperative BIS readings between 60 - 80; Drug: Fentanyl; loading of 1 mcg/kg in over 15 minutes of fentanyl then will receive continuous infusion starting at 1 ml /kg/h. of 0.5 mcg/ml solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
average systolic blood pressure	mmgh	after induction of conscious sedation till end of procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ephedrine use	mg	after induction of conscious sedation till end of procedure
Total amount of Propofol consumption	mg	after induction of conscious sedation till end of procedure
Total number of intraoperative patient's movements	defined as those likely to interfere with surgical procedure such as bending of hand and/or leg and movement of head	after induction of conscious sedation till end of procedure
Systolic blood pressure	mmgh	upon arrival at the operating room, after induction of conscious sedation, at skin incision, at 1,2,5,10,15 min and 10 min after skin incision, every 15 minutes intraoperative, on arrival at PACU, 5,10,15,30 min and 1 hour at the PACU
Diastolic blood pressure	mmgh	upon arrival at the operating room, after induction of conscious sedation, at skin incision, at 1,2,5,10,15 min and 10 min after skin incision, every 15 minutes intraoperative, on arrival at PACU, 5,10,15,30 min and 1 hour at the PACU
Heart rate	bpm	upon arrival at the operating room, after induction of conscious sedation, at skin incision, at 1,2,5,10,15 min and 10 min after skin incision, every 15 minutes intraoperative, on arrival at PACU, 5,10,15,30 min and 1 hour at the PACU
Surgeon satisfaction score	1, extremely dissatisfied; 2, not satisfied but able to manage; 3, satisfied; 4, extremely satisfied.	30 minutes after the end of the surgery
Ramsay sedation scale	Ramsey 1 Anxious, agitated, restless Ramsey 2 Cooperative, oriented, tranquil Ramsey 3 Responsive to commands only If Asleep Ramsey 4 Brisk response to light glabellar tap or loud auditory stimulus Ramsey 5 Sluggish response to light glabellar tap or loud auditory stimulus Ramsey 6 No response to light glabellar tap or loud auditory stimulus	15 and 30 minutes postoperative
Visual Analogue Scale (VAS) for pain	10 cm horizontal line on which the patient's pain intensity is represented by a point between the extremes of 0=no pain at all and 10 cm = worst pain imaginable."	at 15 minutes, 30 minutes, 1hr, 2 hrs. 3hrs and 6 hrs after PACU admission
atropine use	mg	after induction of conscious sedation till end of procedure
first rescue analgesic during 1 hour post operative	incidence of patients requiring analgesics	1 hour postoperative
postoperative nausea and vomiting	incidence	first 24 hours in the postoperative period

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: Maha mostafa, MD, Kasr El Aini

Publications and helpful links

General Publications

• Rodriguez-Rubio L, Nava E, Del Pozo JSG, Jordan J. Influence of the perioperative administration of magnesium sulfate on the total dose of anesthetics during general anesthesia. A systematic review and meta-analysis. J Clin Anesth. 2017 Jun;39:129-138. doi: 10.1016/j.jclinane.2017.03.038. Epub 2017 Apr 7.
• Sinha PK, Koshy T, Gayatri P, Smitha V, Abraham M, Rathod RC. Anesthesia for awake craniotomy: a retrospective study. Neurol India. 2007 Oct-Dec;55(4):376-81. doi: 10.4103/0028-3886.33308.
• Gignac E, Manninen PH, Gelb AW. Comparison of fentanyl, sufentanil and alfentanil during awake craniotomy for epilepsy. Can J Anaesth. 1993 May;40(5 Pt 1):421-4. doi: 10.1007/BF03009510.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ACTUAL): October 12, 2019
• Study Completion (ACTUAL): October 12, 2019

Study Registration Dates

• First Submitted: February 24, 2019
• First Submitted That Met QC Criteria: February 24, 2019
• First Posted (ACTUAL): February 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 11, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: fentanyl; propofol; magnesium sulphate; monitored anesthesia care; chronic subdural hematoma; burr-hole evacuation
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma; Hematoma, Subdural; Hematoma, Subdural, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Fentanyl; Propofol; Magnesium Sulfate
• Other Study ID Numbers: N28-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No