Magnesium Sulfate in Children Undergoing Laparoscopic Appendectomy

Phase 4

Recruiting

• Conditions: Complication of Treatment; Opioid Consumption; Multimodal Analgesia; Acute Appendicitis
• Interventions: Drug: Normal saline infusion; Drug: Intravenous magnesium sulfate

• Registration Number: NCT06563349
• Lead Sponsor: Medical University of Warsaw

Brief Summary

Magnesium sulfate is one of the most commonly used co-analgetics. Its antinociceptive effect is related to antagonizing NMDA (N-methyl-D-aspartate) receptors of the nervous system, has an anti-inflammatory effect by reducing the concentration of IL-6 (interleukin 6) and tumor necrosis factor alpha. In adult patients, the need for morphine in the perioperative period is reduced when magnesium infusion is used. In current guidelines for treatment of acute pain in children, magnesium sulfate may be considered as a co-analgetic. However, the strength of such a recommendation is low due to the lack of reliable scientific research confirming the effectiveness of magnesium infusion in the pediatric population. The aim of this study is to evaluate the efficacy of intravenous magnesium sulfate infusion on the opioid consumption, the circulatory, metabolic and hormonal response to intubation and surgical trauma during anesthesia for laparoscopic appendectomy in children.

Detailed Description

Pain in the perioperative period is associated with surgical stimuli but also with laryngoscopy and intubation. According to the currently applicable ERAS (Enhanced Recovery After Surgery) doctrine, the recommended method of anesthesia is multimodal, low-opioid anesthesia. The essence of multimodal anesthesia is to combine different methods (e.g. general and regional anesthesia) and various anesthetic drugs in order to reduce the intraoperative use of opioids. The one of commonly used co-analgetic is magnesium. The use of magnesium infusion before induction of anesthesia may enhance the analgesic effect of the opioid administered before intubation. In current guidelines for the relief of acute pain in children, magnesium sulfate may be considered as a coanalgesic. It is based only on expert consensus opinion and/or data from small studies, retrospective studies, registries.

According to available data magnesium sulfate is superior to placebo in decreasing analgesic consumption and pain scores during the first 48 h after operation without any adverse effects in children with cerebral pals. In other groups of pediatric patients, the effectiveness of magnesium as a co-analgetic has not been proven. High quality randomized controlled trials are still missing.

The primary outcome of this study is to assess opioid consumption during the laparoscopic appendectomy. Number of patients requiring rescue dose of opioids will be measured.

The secondary aim is to examine total intraoperative fentanyl consumption, fluctuations of heart rate and blood pressure, metabolic, hormonal and inflammatory response (glucose, cortisol and IL-6 concentrations) and occurrence of side effects that may result from magnesium intake (decrease in blood pressure, bradycardia or allergic reaction).

In the pediatric population, the optimal perioperative magnesium dosage is 50 mg/kg as a bolus followed by an infusion of 15 mg/kg/hour until the end of the operation.

The general aim of the study is to evaluate the analgesic efficacy of intravenous magnesium sulfate as an adjunct to standard general anesthesia (involving intravenous induction and opioid with sevoflurane maintenance) for intubation and surgical trauma during anesthesia for laparoscopic appendectomy in children.

Study Timeline

• Study First Submitted: 2024-08-05
• Study First Submitted QC: 2024-08-17
• Study First Posted: 2024-08-20
• Study Start: 2024-09-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-09
• Last Update Posted: 2024-11-12
• Primary Completion: 2027-09-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

• ASA (American Society of Anesthesiologists) physical status class 1E, 2E, 3E (E - emergency)
• Patients undergoing laparoscopic appendectomy

Exclusion Criteria

• Allergy to the magnesium sulfate or the excipient
• Hypermagnesemia
• Renal failure (GFR <30 ml/min)
• Myasthenia gravis
• Preoperative atrioventricular block
• Hypotension
• The use of digitalis glycosides
• The use of oral anticoagulants
• ASA physical status class 4E or higher
• Chronic treatment with analgesics
• Legal guardians or patient refusal

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Normal saline infusion	0.9% NaCl (sodium chloride) intravenous bolus of 0.5 ml/kg (maximum 20 ml) over 5 min before induction of anesthesia followed by 0.9% NaCl infusion at 0.15 ml/kg/h (maximum 5ml/h) intraoperatively will be administered. The infusion will be discontinued before the patients' transfer to the postanesthesia care unit.
Magnesium Sulfate	Intravenous magnesium sulfate	10% magnesium sulfate intravenous bolus of 0.5 ml/kg (maximum 20 ml) over 5 min before induction of anesthesia followed by magnesium sulfate infusion at 0.15 ml/kg/h (maximum 6 ml/h) intraoperatively will be administered. The infusion will be discontinued before the patients' transfer to the postanesthesia care unit.

Primary Outcome Measures

Name	Time	Method
Number of patients requiring rescue dose of opioids.	From tracheal intubation through to postanesthesia care unit admission (10 minutes after extubation).	Patients who experience a 20% increase in BP (Blood Pressure) or HR (Heart Rate) from baseline during surgery and the early post-extubation period will receive a bolus of fentanyl (1 mcg/kg) as rescue analgesia. The number of these patients will be compared between the groups.; Baseline parameters will be recorded after premedication with an IV bolus of 0.05 mg/kg midazolam, just before intubation.

Secondary Outcome Measures

Name	Time	Method
Hemodynamic reaction to tracheal intubation	Pre-intubation - immediately after intubation.	A change in arterial blood pressure of more than 20% from baseline will be noted, and the fractions of these patients in each group will be compared. Baseline parameters will be recorded after premedication with an IV bolus of 0.05 mg/kg midazolam, just before intubation.
The requirement for opioids during anesthesia	From operating theatre admission through to postanesthesia care unit admission (10 minutes after extubation).	Total amount of fentanyl in micrograms per kilogram of body weight used during anesthesia (dose for induction of anesthesia + doses added during surgery and in the early post-extubation period).
Hormonal response to laparoscopic procedure	From 5 minutes after tracheal intubation until the end of surgery, defined as the completion of dressing application.	Cortisol levels \[mcg/dl\] will be measured and compared before and after laparoscopic procedure.; The first blood sample will be taken 5 minutes after tracheal intubation, before the skin incision. The second blood sample will be taken immediately after the end of surgery, at the time of dressing application.
Inflammatory response to laparoscopic procedure	From 5 minutes after tracheal intubation until the end of surgery, defined as the completion of dressing application.	IL-6 levels \[pg/ml\] will be measured and compared before and after laparoscopic procedure.; The first blood sample will be taken 5 minutes after tracheal intubation, before the skin incision. The second blood sample will be taken immediately after the end of surgery, at the time of dressing application.
Side effects of magnesium sulfate	From the beginning of magnesium sulfate application until transfer to the postanesthesia care unit (10 minutes after extubation).	Side effects of magnesium sulfate will be assessed by recording the rates of the following complications: hypotension \& bradycardia (both defined as 2 SD (standard deviation) below the 50th percentile for age), allergic reaction. Need to discontinue the magnesium sulfate/placebo infusion due to side effects.; Need to administer calcium gluconate.
Metabolic response to laparoscopic procedure	From 5 minutes after tracheal intubation until the end of surgery, defined as the completion of dressing application.	Glucose \[mg/dl\] levels will be measured and compared before and after laparoscopic procedure.; The first blood sample will be taken 5 minutes after tracheal intubation, before the skin incision. The second blood sample will be taken immediately after the end of surgery, at the time of dressing application.
Magnesium blood level	From 5 minutes after tracheal intubation until the end of surgery, defined as the completion of dressing application.	Magnesium level \[mg/dl\] will be measured after initial bolus and just before the end of its infusion.; The first blood sample will be taken 5 minutes after tracheal intubation, before the skin incision. The second blood sample will be taken immediately after the end of surgery, at the time of dressing application. Magnesium infusion will be discontinued after the second blood sample is collected.

Trial Locations

Locations (1)

Uniwersity Clinic Centre of Medical Uniwersity of Warsaw; 🇵🇱 Warsaw, Poland