The Role of Intravenous Magnesium in Preventing Chronic Postoperative Pain – a Systematic Review

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• Published: 10 January 2022

Magnesium sulphate inside multimodal analgesia, pre-emptive, or preventive analgesia

Ain-Shams Journal of Anesthesiology book 14, Article number:7 (2022) Cite this article

Abstract

Groundwork

Magnesium (Mg) is a non-competitive N-methyl d-aspartate receptor antagonist with antinociceptive effects. Multimodal therapy is the optimal strategy for perioperative pain control to minimize the demand for opioids. Inflammation caused by tissue trauma or straight nerve injury is responsible for the perioperative pain. The concept of "pre-emptive" analgesia, analgesic strategies administered prior to the stimulus, can modify the peripheral and cardinal nervous organization processing of noxious stimuli, thereby reducing central sensitization, hyperalgesia, and allodynia remains controversial. A more encompassing arroyo to the reduction of postoperative pain is the concept of "preventive" analgesia. The purpose of the study is to discover the proper use of MgSO4 as an analgesic existence a not-competitive N-methyl d-aspartate (NMDA).

Results

There is no statistically significant difference in the haemodynamic parameters, intraoperative (33% vs 20%) and postoperative requirement for analgesics six.vi% vs ten% amongst groups I and II, respectively. In that location is no significant difference in the numerical counterpart calibration, where xvi vs 17 patients with no hurting, 12 vs x with mild pain, and two vs 3 with moderate pain in groups I and II, respectively.

Conclusion

The use of MgSO4 in a bolus with or without infusion is comparable in the command of intraoperative and postoperative pain.

Backgrounds

Perioperative pain management is indicated to relieve the patients' suffering, allow early mobilization after surgery, reduce the length of hospital stay, and have better satisfaction. Pain control regimens must consider medical, psychological, and physical conditions; historic period; level of fearfulness or feet; surgical procedure; personal preference; and the patients' response.

Traditionally, acute perioperative hurting management is targeting the central mechanisms involved in the perception of pain by opioid medications (Mudumbai et al., 2016; Sun et al., 2016). Thus, opioid utilize has reached a critical level worldwide; accordingly, multimodal therapy is the optimal choice for perioperative hurting control to minimize the demand for opioids (Alam & Juurlink, 2016).

The perioperative hurting is initiated either by an inflammatory process induced by tissue trauma or by direct nerve injury from nervus transection, stretching, or compression. Tissue trauma is not only initiating hurting at the site of the trauma but also to the surrounding expanse through local inflammatory mediators that augment the sensitivity to stimuli (hyperalgesia) or even misperception of hurting to not-noxious stimuli (allodynia). Other mechanisms contributing to hyperalgesia and allodynia include sensitization of the peripheral pain receptors (primary hyperalgesia) and increased excitability of central nervous arrangement neurons (secondary hyperalgesia) (Kelly et al., 2001; Woolf & Chong, 1993a; Suzuki, 1995).

Multimodal analgesia is the analgesia achieved by using several agents instead of using a single agent, each acting at dissimilar sites of the pain pathway. This arroyo reduces the dependence on a unmarried medication and reduces or eliminates the demand for opioids. The Synergism betwixt opioid and non-opioid medications reduces the required opioid dose and the side effects related to them.

Pain receptor activity can be blocked directly by (e.1000. lidocaine) or indirectly by anti-inflammatory agents to diminish the local hormonal response to injury, thus decreasing the pain receptor activation.

Other analgesic agents (e.g. ketamine, gabapentin, pregabalin) modulate the activity of neurotransmitters (substance P, calcitonin factor-related peptide, aspartate, glutamate, and gamma-aminobutyric acid (GABA)), by inhibiting or augmenting their activity.

The concept of "pre-emptive" analgesia, significant that analgesic strategies administered prior to surgical incision or stimulus can modify the peripheral and central nervous system processing of baneful stimuli, thereby reducing central sensitization, hyperalgesia, and allodynia (Kelly et al., 2001; Woolf & Chong, 1993a; Suzuki, 1995), remains controversial. Several studies have concluded that preoperative timing is not necessary to achieve a reduction in postoperative pain and opioid utilize (Møiniche et al., 2002a).

An approach with a wider spectrum to the reduction of acute as well as chronic postoperative hurting is the concept of "preventive" analgesia. The aim of preventive analgesia is to reduce the sensitization to the perioperative noxious stimuli, by treatments administered at whatever time in the perioperative menstruum (Rosero & Joshi, 2014; Katz et al., 2011).

Magnesium (Mg) is a non-competitive Due north-methyl d-aspartate (NMDA) receptor antagonist with analgesic effects (Mayer et al., 1984; McCarthy et al., 1998). It has been accepted as an adjuvant for intra- and postoperative analgesia. Perioperative magnesium sulphate reduces the need for anaesthetics and improves postoperative analgesia (Choi et al., 2002; Wilder-Smith et al., 1997). However, some claim that magnesium sulphate has limited if any effect does exist (Choi et al., 2002; Ko et al., 2001; Paech et al., 2006). The role of magnesium sulphate infusion on the consumption of anaesthetics and opioids has been reported to be variable depending on the procedures done (Schulz-Stubner et al., 2001; Telci et al., 2002).

However, since the magnesium ion poorly crosses the blood-brain bulwark in humans, information technology is non clear whether the therapeutic event is related to NMDA antagonism in the central nervous organization, dorsal horn NMDA receptors, or peripheral (Buvanendran, 2011).

Owing to this "protective" consequence on the nociceptive pathways, pre-emptive analgesia has the potential to be more than effective than a similar analgesic treatment initiated later on surgery(Dahl & Møiniche, 2004). Consequently, firsthand postoperative hurting may be reduced, and the development of chronic pain may exist prevented (Woolf & Chong, 1993b).

Aim of work

The aim of the work is to discover the proper use of MgSO4 as an analgesic being a NMDA receptor blocker

Methods

The written report is a blinded observational study that was conducted in Ain shams University Hospitals on 60 patients scheduled for a variety of surgical procedures. The study was canonical past the Inquiry Ethics Committee of the Faculty of Medicine, Ain Shams University and conducted in accordance with the principles of the Declaration of Helsinki. A written informed consent before enrolment was taken. The patients were randomly divided into two equal groups, group I and group II. Randomization was done by calculator-generated number lists and used opaque sealed envelopes.

Sample size and statistics

The sample size was calculated using ClinCalc.com, setting the type ane error (α) at 0.05, ability (1 − β) at 0,.8 and confidence width level at 0.1. Calculation according to the values of similar studies produced a minimal sample size of 25 cases.

The Mann-Whitney test is used to compare non-parametric between the ii report groups. The chi-square and Fisher'south verbal tests were used to examine the relationship betwixt chiselled variables. P value < 0.05 was considered statistically significant. All statistical procedures were carried out using Microsoft Excel 365. The median and interquartile range were used for skewed numerical data, and per centum and proportions for categoric values.

The primary result is to report the proper timing for initiating the MgSo4 every bit an analgesic, and the secondary outcome is to report the complications of using MgSo4 equally an analgesic.

Inclusion criteria

The following are the inclusion criteria:

• Age eighteen–seventy years

• Both sex

• ASA I, II, III, and IV

• The patients scheduled for general amazement

• Procedure > 60 min with expected moderate to severe pain postoperative

Exclusion criteria

The following are the exclusion criteria:

• Patients refusing to participate in the written report

• Patients with renal insufficiency

• Patients with liver disease

A standard monitor was fastened to the patients including 5 leads ECG, pulse oximeter, and NIBP, and the Four line was secured.

The anaesthesia was induced by propofol 1.5 mg/kg and atracurium 0.five mg/kg, and the patients will exist intubated by endotracheal tube size 7 for females and 8 for males; after then, the patients will be ventilated using volume-controlled mode at a rate of iv–6 ml/kg, RR 12 bpm

The patients in group I were given a MgSO4 50-mg/kg bolus dose with the induction of anaesthesia; the induction of anaesthesia was conducted with 100 μg of fentanyl, paracetamol ane m and NSAID (Ketorolac) 30 mg/ml given during the procedure and 10 mg of nalbuphine past the end of the procedure. In group II, MgSO4 50 mg/kg bolus with the induction of anaesthesia and 100 μg of fentanyl were given in the induction phase. In addition to paracetamol 1 g and NSAID (Ketorolac) 30 mg/ml, MgSO4 at a dose of xv mg/kg/hour were given during the procedure and 10 mg of nalbuphine past the finish of the procedure.

When at that place was a change in the blood pressure and the heart rate by more than than twenty% of the preoperative value, 50 μg of fentanyl were given after excluding other possible causes.

Another incremental dose of fentanyl was given up to a total dose of 200 μg in improver to paracetamol on need every half dozen hr and NSAID (Ketorolac) 30 mg prn every half-dozen h upward to a full of 120 mg per day during the procedure.

After extubating the patients, the pain scores were assessed subsequently an hour using a numerical rating scale, where 0 = no pain and 10 = the worst pain that has ever been experienced. I classify the hurting as from 0 to ≤ iii as mild, 4 to less than 7 as moderate hurting, and greater than or equal to seven as severe pain. If it was recorded > 4, an additional five mg nalbuphine is given and the narcotics used were recorded.

In instance of failure of command of the pain past these strategies, the patient was excluded and replaced by another.

The haemodynamic parameters recorded every 15 min including systolic BP, diastolic BP, and HR were nerveless. An average reading for the haemodynamic for each patient was recorded by the end of the procedure. The number of the patients who received intraoperative as well every bit postoperative adjuvant analgesics were recorded. The complications from using MgSo₄ including hypotension, delayed recovery, visual changes, and respiratory paralysis were likewise monitored. The amazement nurse who records the data and who was applying the NAS were blinded.

Results

The demographic data were comparable in both groups; almost of the patients were ASA I and ASA 2 (Table 1).

Table 1 Demographic data amongst the two groups

Total size tabular array

There was no intraoperative statistically meaning difference in the haemodynamic parameters among the two groups where the median for the systolic blood force per unit area was 120 mmHg in the two groups, 75 mmHg for the diastolic blood pressure level amid group I vs 70 mmHg among group Ii while the median for heart charge per unit was 80 bpm vs 76 bpm in group 2 (Table two).

Table 2 Haemodynamic changes among the two groups

Total size table

There was no statistically significant increase in the requirement of intraoperative adjuvant and the postoperative requirement for analgesics half-dozen.6% vs 10% with a P value < 0.05 amidst groups I and II, respectively (Table 3).

Table 3 Requirement of intraoperative and postoperative analgesics

Full size table

The numerical rating scale for pain was almost the aforementioned among the two groups with no pregnant statistical divergence among them, where xvi patients in grouping I vs 17 in grouping II with no pain, 12 vs x with mild hurting, ii vs 3 with moderate pain, and no patients in any of the ii groups complaining of astringent pain [Table iv, Fig. 1]. The cliff's delta statistics arroyo almost to 0.0 (− 0.07) indicating that the compared groups tend to overlap, making the effect size correlate to non-statistical difference.

Tabular array 4 The numerical rating calibration for pain among the two group

Full size table

Fig. 1

The median and interquartile range of the numerical rating scale

Total size prototype

The types of surgery were similar in the two groups with the almost frequent were intestinal surgery, spine, and orthopaedic surgeries [Figs. 2 and 3]. No reported complications were recorded in the 2 groups including hypotension, respiratory paralysis, delayed recovery, and abnormality in vision.

Fig. 2

The type of surgery amidst group I

Full size image

Fig. 3

The type of surgery amidst group Two

Total size image

Discussion

Magnesium is a NMDA receptor adversary. Intravenous magnesium has been accustomed to be an effective adjuvant for the reduction of the opioid requirement, especially useful in opioid-tolerant patients or when there are medical concerns related to opioid dose.

In ii meta-analyses trials, intraoperative Four magnesium sulphate has been proven to be superior compared with placebo in over 1200 patients in regard to reduced perioperative opioid consumption and pain scores in the first 24 h postoperatively, with no serious result (Mariano, 2020; Albrecht et al., 2013).

In i of the analyses, opioid consumption was dramatically decreased for morphine in 24 h, 24.four%, and the pain scores at 24 h subsequently surgery were reduced to be four.2 at rest and 9.2 on movement (De Oliveira Jr et al., 2013). Both bolus and continuous infusion regimens were effective.

Assistants of magnesium at a dose of 40 mg/kg earlier induction, followed by a 10 mg/kg/h infusion, resulted in a decrease of the total opioid without any major haemodynamic consequences. Higher infusion doses have no added value (Buvanendran, 2011); yet, Ryu et al. successfully uses a dose of fifty mg/kg magnesium sulphate intravenous as a bolus and then 15 mg/kg/hr by continuous intravenous infusion (Ryu et al., 2008).

The results of the current study match this analysis in the regard that there is neither divergence in the requirement of analgesics nor the postoperative pain score betwixt the bolus dose and the infusion; withal, our study was carried out on a limited number of patients in early postoperative catamenia.

Multimodal analgesia using magnesium may provide benefit peculiarly when used with ketamine. In a trial of 50 patients scheduled for scoliosis surgery, the addition of magnesium to ketamine decreased postoperative morphine consumption by thirty%, with improved sleep and satisfaction scores, but no alter in pain scores (Jabbour et al., 2014).

The results from a lot of studies largely declare that the pre-emptive assistants of analgesics in surgical patients had not proved to add major benefits in regard to immediate postoperative pain relief or reduced need for supplemental analgesics (Dahl & Møiniche, 2004; Møiniche et al., 2002b).

It was concluded every bit well that no overall improvement in postoperative pain control was observed after pre-emptive administration of systemic NSAID, opioids, and ketamine (Møiniche et al., 2002b). However, the addition of acetaminophen to nonsteroidal anti-inflammatory drugs (NSAIDs) within a multimodal regimen can improve hurting control and reduce postoperative morphine consumption (Martinez et al., 2017). A systematic review comparison the use of NSAIDs alone or in combination with acetaminophen for postoperative pain showed that the combination was more effective than NSAIDs lone in 64% of the studies (Ong et al., 2010). The benefits of combining acetaminophen and NSAIDs, vs NSAID solitary, may differ according to the procedures (Thybo et al., 2019).

Conclusions

This study come to a conclusion that the continuous infusion of MgSo_iv has no added value in the control of intraoperative and the postoperative pain, likewise as information technology has no value in the regard to decreasing the requirement for adjuvant analgesics.

Limitation of the written report

The current conclusion needs to be investigated over a wider scale of patients, with an extended monitoring for the postoperative pain over a longer time frame.

Availability of data and materials

The datasets used and/or analysed during the electric current study are available from the corresponding writer on reasonable request besides as on the following link MgSO4 Pre-emtive or Preventive.xlsx.

Abbreviations

GABA:

Gamma-aminobutyric acid

NMDA:

Not-competitive Due north-methyl d-aspartate

MgSO4:

Magnesium sulphate

NSAIDs:

Nonsteroidal anti-inflammatory drugs

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Acknowledgements

We would like to acknowledge Professor Dr. Rafaat Abd Al Azzim for the wise revision and supervising of this piece of work.

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Affiliations

1. Department of anesthesia, ICU and Hurting Management, Faculty of Medicine, Own Shams University, Cairo, Egypt

   Walid Y. Kamel & Aktham Adel Shoukry

Contributions

West.Y.M contributed to the data collections, thought pick, source collections, and writing. A.A.Southward contributed to the inclusion of source collections and revision. The authors accept read and canonical the last manuscript.

Corresponding writer

Correspondence to Walid Y. Kamel.

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The study was canonical by the Research Ethics Committee of the Kinesthesia of Medicine (R72/2021), Ain Shams University, and conducted in accordance with the principles of the Declaration of Helsinki. A written informed consent before enrolment was taken.

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Not applicative

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Kamel, Due west.Y., Shoukry, A.A. Magnesium sulphate inside multimodal analgesia, pre-emptive, or preventive analgesia. Ain-Shams J Anesthesiol 14, 7 (2022). https://doi.org/10.1186/s42077-021-00210-1

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• Received: 18 June 2021

• Accepted: 25 December 2021

• Published: 10 Jan 2022

• DOI : https://doi.org/10.1186/s42077-021-00210-1

Keywords

• MgSO4
• Analgesia
• Preventive
• Pre-emptive

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