The Efficacy of Intravenous Magnesium Sulfate versus Intravenous Paracetamol on Children Posttonsillectomy Pain and Analgesic Requirement: A Randomized Controlled Study

Abstract

Background:

One of the most common complications of tonsillectomy is pain, which leading to delayed recovery and later hospital discharge.

Aims:

We intended to compare the efficacy of magnesium sulfate versus paracetamol on the posttonsillectomy pain and analgesic requirement.

Settings and Design:

This study design was a prospective randomized controlled double-blinded clinical study.

Patients and Methods:

A total of 60 children with the American Society of Anesthesiologists physical status classes I and II, aged 3–12 years, scheduled for tonsillectomy were randomly divided into two groups each group contains 30 patients: (Group M): received an initial loading dose of magnesium sulfate 30 mg/kg over 15 min started with induction followed by continuous infusion of 10 mg/kg/h for 1 h regardless of the operation time and (Group P): received paracetamol infusion 10 mg/kg started with induction and continued for 1 h. Postoperatively, a blinded postanesthesia care unit (PACU) nurse observed the quality of analgesia using the face, legs, activity, cry, and consolability pain scores, bleeding, and sedation.

Statistical Analysis Used:

Student's t-test and Chi-square test were used for analysis.

Results:

Regarding postoperative pain, there was a statistically significant difference between the two groups at the time of admission in PACU (P = 0.025) as children who experienced pain already had taken rescue analgesic to alleviate pain. There was a statistically significant difference between the two groups regarding the need for analgesics (P = 0.038). There was no statistically significant difference regarding bleeding and sedation scores between the two study groups.

Conclusions:

Magnesium sulfate provided better postoperative analgesia and reduced need for analgesics after tonsillectomy compared to paracetamol, and regarding the incidence of bleeding and the degree of sedation the outcome in both groups was readily comparable.

INTRODUCTION

Tonsillectomy is commonly associated with morbidity as postoperative pain nausea, vomiting, bleeding, and dehydration.[1] Postoperative pain control after the tonsillectomy has a very important role in recovery time, hospitalization duration, hemodynamic effects, bleeding, nausea, vomiting, and financial costs.[2] On the other hand, most patients undergoing this surgery are children that have lower pain thresholds and experience restlessness early, having negative psychological effects on them and their family.[1] At the beginning of the last century, the role of magnesium sulfate in postoperative pain and opioid consumption has been studied. However, results of those studies are variable. Whereas most reports describe the reduction of postoperative analgesic requirements after magnesium sulfate, a few studies show insignificant beneficial effects.[3] Magnesium sulfate has an important role in central nervous system suppression that can increase the depth of anesthesia. It also has calcium antagonist properties that increase flaccidity.[4] Paracetamol is a nonopioid analgesic belongs to a group of drugs named the nonacidic antipyretic analgesics, the mechanism for analgesia is not completely clear, but it is believed to act through the inhibition of cyclooxygenase (COX) enzymes with a preference for COX-2 over COX-1,[5] Its analgesic and antipyretic actions are similar to those of aspirin. However, unlike aspirin, it has no anti-inflammatory effects and does not show adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as gastrointestinal disorders, anticoagulant effects, and renal function affection.[6]

Paracetamol is considered the nonopioid analgesic of choice to treat postoperative mild and moderate pain; furthermore, in the treatment of severe pain, it can reduce the need for opioid analgesics.[7] Paracetamol has minimal effect on platelet function and does not increase the bleeding time as NSAIDs, which is an important safety issue in tonsillectomy complicated with a risk of postoperative bleeding.[8] In many kinds of research, different drugs as opioids, NSAIDs, steroids, and paracetamol have been studied to decrease that pain.[1] NSAIDs are commonly used for analgesia after tonsillectomy; although, their usage is controversial because of the increased risk of platelet adhesion disorder leading to postoperative bleeding.[9]

PATIENTS AND METHODS

The ethical committee of our institute approved this randomized prospective double-blinded controlled study to be done in Fayoum university hospital for 1 year (from April 2017 to April 2018) on 60 children scheduled for tonsillectomy after obtaining a written informed consent for anesthesia from each parent and assent from children after explaining to them the nature of the study and complications.

Inclusion criteria included children aged 3–12 years of either sex and with the American Society of Anesthesiologists physical status classes I and II scheduled for tonsillectomy.

Exclusion criteria children with emergency surgeries, operations are done due to posttonsillectomy bleeding, history of difficult intubation, and history of cardiac, respiratory and renal diseases, infections of the upper respiratory system, history of myasthenia gravis, hypotension, and the record of passive smoking.

The patients were randomly divided into two groups as simple randomization by computer-generated random numbers. Each group contains 30 patients (Group M): which received magnesium sulfate and (Group P): which received paracetamol. Routine preoperative investigations including complete blood picture and coagulation profile were done.

All patients were fasting 6 h regarding solid food, 4 h regarding semi-solid food, and 2 h regarding clear fluids.

Patients were monitored using electrocardiography, pulse oximetry, and noninvasive blood pressure monitoring upon arrival to operating theater and throughout surgery.

All patients received inhalation induction of anesthesia by sevoflurane until sedation which allowed IV access insertion. Fentanyl 1 ug/kg and atropine 0.01 mg/kg was given in both groups.

• Group M – Patients received an initial loading dose of magnesium sulfate 30 mg/kg over 15 min started with induction followed by continuous infusion of 10 mg/kg/h for 1 h regardless of the operation time[10]

• Group P – Patients received paracetamol infusion 15 mg/kg started with induction and continued for 1 h.[11]

After reaching an adequate depth of anesthesia, intubation was done, and tube position was confirmed by auscultation then operation proceeded.

Anesthesia was maintained by 100% oxygen and isoflurane. All patients were allowed to breathe spontaneously throughout the operation.

At the end of the operation, all patients had their tracheas extubated when awake and with intact gag reflex and were transferred to postanesthesia care unit (PACU) and were observed by nursing staff who were unaware of the drugs given. Pain assessment was done at the time of PACU admission, at 30 min, and only before PACU discharge using the face, legs, activity, cry, and consolability (FLACC) pain scores [Table 1].[12] If there was continuous complaint of pain (score >4) rectal diclofenac sodium 12.5 mg would be given.

Table 1.

FLACC pain scores

Sedation and bleeding were recorded at the time of PACU admission, at 30 min and just before discharge.

The primary outcomes of this prospective, randomized and observer-blinded study were to compare the effect of magnesium sulfate versus paracetamol on posttonsillectomy pain and analgesic requirement. The secondary outcomes of this study were to compare bleeding and sedation between groups.

Statistical analysis

The sample size was calculated using the G power program 3.1.7 (Universitat Kiel, Germany). Data were collected, coded, and double entered into Microsoft access and data analysis was performed using SPSS software version 21.0 (IBM Corporation, Armonk, NY, USA) statistics. The simple descriptive analysis in the form of numbers and percentages for qualitative data and arithmetic means as central tendency measurement, standard deviations as a measure of dispersion for quantitative parametric data and inferential statistic test. In-depended Student “t”-test used to compare measures of two independent groups of quantitative data. Chi-square test to compare two or more than two qualitative groups. P < 0.05 was considered as statistically significant.

RESULTS

The present study included 60 children in Fayoum university hospital, randomly divided into two study groups. Each group contains 30 patients: Group M (n = 30): patients received an initial loading dose of magnesium sulfate 30 mg/kg over 15 min started with induction followed by continuous infusion of 10 mg/kg/h for 1 h.[10] Group P (n = 30): patients received paracetamol infusion 15 mg/kg started with induction and continued for 1 h.[11]

There was a statistically significant difference between the two groups as regards the pain scoring performed in PACU using the FLACC score when patient firstly admitted to the PACU (P = 0.025), but it should be taken into consideration that children who experienced pain already had taken rescue analgesic to alleviate pain. However, there was no statistically significant difference between the two groups after 30 and 60 min after admission to PACU [Table 2].

Table 2.

The face, legs, activity, cry, and consolability pain score for the two groups while in the postanesthesia care unit

There was a statistically significant difference between the two groups as regards the need for analgesics while in PACU [Table 3].

Table 3.

Number of patients taking analgesics among the two groups

There was no statistically significant difference as regards bleeding, and sedation scores while in PACU between the two study groups as shown in [Tables 4 and 5].

Table 4.

Incidence of bleeding in the studied groups at different times while in postanesthetic care unit

Table 5.

Sedation score in the two study groups at different times while in Postanesthetic care unit

DISCUSSION

In the current study, we compared the efficacy of magnesium sulfate and paracetamol as regard posttonsillectomy pain in children, in addition to their effect on bleeding and sedation.

Several kinds of the research report the role of magnesium when administered intravenously or intrathecally[13] through inhibition of calcium influx (calcium channel blockers augment opioids-induced analgesia and reduce total opioids consumption),[14] Antagonism of N-Methyl-D-aspartate (NMDA) receptors and the prevention of enhanced ligand-induced NMDA signaling when magnesium reduced.[14] In addition, magnesium attenuates or even prevent central sensitization after peripheral tissue injury or inflammation because of inhibition of dorsal horn NMDA receptors.[15]

Paracetamol belongs to a group of drugs called the nonacidic antipyretic analgesics. The mechanism for analgesia is not completely clear, but it is believed to work through the inhibition of COX enzymes as NSAIDs with a preference for COX-2 over COX-1.[16] Paracetamol has minimal effect on platelet function and does not increase the bleeding time as NSAIDs, which is an important safety issue in tonsillectomy complicated with a risk of postoperative bleeding.[8]

Regarding the pain scoring done in PACU using the FLACC score results showed statistical significance between the two groups at PACU admission. On the other hand, there was no statistical significance between the two groups after 30 and 60 min from PACU admission. It also should be taken into consideration that children who experienced pain already had taken rescue analgesic to reduce pain.

There was a statistically significant difference between the two groups as regards the need for analgesics while in PACU.

Regarding the incidence of bleeding and degree of sedation, the outcome in both groups was readily comparable.

In the current study, magnesium sulfate had more analgesic effect than paracetamol on the postoperative pain following tonsillectomy and reduced postoperative analgesics required.

Benzon et al.,[17] who studied the effect of systemic magnesium on postsurgical pain in children undergoing tonsillectomies, founded that continuous intraoperative infusion of IV magnesium did not cause a clinically important decrease in postoperative pain scores or opioid consumption in children undergoing tonsillectomies which different from our study results despite having the same administration protocol and the same pain scoring system. This may be contributed to the fact that in our study, we continued magnesium maintenance infusion for 1 h regardless of the procedure time.

Christopher et al.,[18] who conducted a systematic review of randomized trials to show the effect of magnesium as an adjuvant to postoperative analgesia, found that the beneficial effects of magnesium were not unequivocal.

Lysakowski et al.,[19] who studied the effect of intra-operative magnesium sulfate on pain relief and patient comfort after major lumbar orthopedic surgery, demonstrated that 50 mg/kg magnesium sulfate given as a bolus at induction of anesthesia significantly decrease opioid consumption and provided patient comfort after major lumbar surgery.

In the current study, MgSO₄ was administered intravenously at induction of anesthesia as a bolus dose of 50 mg/kg administered over 30 min without any subsequent continuous infusion.

Such a dose has been reported in several studies to be devoid of adverse effects. Lower bolus doses have not been shown to improve postoperative analgesia.[20] Hence, a continuous infusion of MgSO₄ seems to have no benefit compared with a single bolus dose of 50 mg/kg. It has been suggested that NMDA blocking agents should be administered before the beginning of nociceptive stimulation to inhibit the process of central sensitization.[21]

Kalani et al.,[11] who compared the analgesic effect of paracetamol and magnesium sulfate during surgeries, reported that intravenous paracetamol had a postoperative analgesic effect and could reduce the number of injections and the total dose of injected narcotics. Therefore, intravenous paracetamol can be used as a suitable adjuvant anesthetic for narcotics. Moreover, intravenous magnesium sulfate had postoperative analgesic effect and reduced the number of injections and the total dose of injected narcotics too. Furthermore, magnesium sulfate had longer analgesic effects compared with paracetamol and caused a greater decrease in the required narcotic doses compared to paracetamol.

In a study conducted by Ozcan et al.[22] on the effect of magnesium sulfate injection for postoperative pain in patients undergoing thoracotomy, it was reported that the scores given to pain intensity declined in the magnesium sulfate group and the narcotics needed in this group was less than the control group that confirming our study.

Hamers et al.,[23] who studied the effect of paracetamol, fentanyl, and systematic assessments on children's pain after tonsillectomy, showed that a high loading dose of paracetamol combined with fentanyl given intraoperatively to relieve early postoperative pain following tonsillectomy did not lead to improved analgesia when compared to a high loading dose of paracetamol combined with a placebo.

Roberts et al.,[24] who studied effect of single dose intraoperative IV acetaminophen in pediatric tonsillectomy expected patients receiving intraoperative IV acetaminophen to require less narcotic analgesic for breakthrough pain in the recovery room,[25] but they did not find that.

Santhi et al.,[26] who studied the efficacy of intraoperative intravenous magnesium sulfate versus intravenous paracetamol on the postoperative analgesic requirement in major surgeries under general anesthesia founded that paracetamol provided more postoperative analgesia than magnesium sulfate.

Our limitation was a small sample size. The second was the short time of monitoring patients postoperatively.

We recommend further studies with a large number of patients; different dose regimens, especially magnesium sulfate and with more postoperative follow-up.

CONCLUSIONS

Magnesium sulfate provided better postoperative analgesia and reduced need for analgesics after tonsillectomy compared to paracetamol, and regarding the incidence of bleeding and the degree of sedation, the outcome in both groups was readily comparable.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.