The Effect of Epidural Magnesium Sulfate as An Adjuvant to Fentanyl for Postoperative Analgesia after Lower Limb Orthopedic Surgery

INTRODUCTION

Regional anesthesia is a competent, cheap procedure, with the advantage of postoperative pain relief. Adequate treatment of post-operative pain blunts autonomic, somatic, and endocrine responses. ¹

 It has become a common tradition to use a poly-pharmacological strategy for the treatment of postoperative pain because no drug has yet been classified that specifically hinders nociception without associated side effects. ²

 Epidural analgesia is usually implemented using a mixture of local anesthetic and an opioid (typically a lipophilic opioid). Compared with opioids or local anesthetic alone, a local anesthetic-opioid mixture affords superior postoperative analgesia with less local anesthetic doses. ³

Epidural opioids award several advantages when compared with epidural local anesthetics, related principally to the vacancy of sensory and motor block as well as the lack of sympathetic block. ⁴  

Unluckily, an epidural and intra-spinal opioid can be affiliated with dose-dependent side effects including nausea, vomiting, urinary retention, respiratory depression, pruritis and development of tolerance and physical dependence). ⁵

Other classes of drugs have been investigated more recently to try to promote the quality of neuraxial blockade, both in the subarachnoid space and in the epidural space. ⁶ 

Magnesium is the 4th most liberal cation in the body. It has antinociceptive outcomes in human and animal patterns of pain, it has also been stated that it can exhibit the analgesic characteristics of opioids ⁷, these results are essentially based on the control of calcium influx into the cell that is typical physiological calcium opposition and opposition of NMDA receptors. ⁸

So this study was designed to emit more light on this topic and to study the effect of two dosed of epidural magnesium sulfate infusions on postoperative analgesia as well as to study its effect as an adjuvant to fentanyl for postoperative analgesia.

The aim of this work is to investigate the effects of two concentrations of epidural magnesium sulfate infusions on postoperative analgesia in patients undergoing lower extremities orthopedic surgery. The primary outcome will be the level of pain relief and secondary outcomes will be the level of patient satisfaction and the occurrence of adverse effects.

Sample size calculation:

The minimal sample size was 60 divided into three groups. To attain a power of test 90% at an alpha error of 0.05, we included 20 patients in each group. Statistical analysis was performed with IBM SPSS version 21.0 software. Mean and the standard deviation was calculated for age, weight, and postoperative analgesia requirements; independent student t-test was used. Frequency and percentages were used for descriptive parameters. A chi-square test was used to compare parameters.

PATIENTS AND METHODS

This prospective randomized controlled double-blinded study was carried on 60 patients of both sexes, after permission from the ethics committee of Al-Azhar university hospitals and getting informed written consent. The study was carried in Al-Azhar University hospitals from April 2015 to November 2016. Inclusion criteria were: age between 21 and 60 years, American Society of Anesthesiologists (ASA) I and II physical status, and listed for orthopedic lower limb procedures. Patients with evidence of any major systemic disease or a history of allergy to any of the medicines in the study were omitted from the study.

 Standard monitoring escorted, baseline hemodynamic readings were recorded. Once intravenous access had been achieved an infusion of ringer lactate started (10ml/Kg over 20- 30 minutes), Spinal anesthesia was given to all patients and epidural catheters inserted at L4/ L5 or L3/ L4 inter-space, prior to surgery for postoperative pain management. Preoperatively,  all patients will be familiarized with the visual analog pain scales (VAS) that consisted of an unmarked 10cm line, with 0cm; no pain, 10cm; worst pain ever).

Spinal anesthesia was conducted at L3-4 or L4-5 interspace with 12.5 mg 0.5% heavy bupivacaine, using a 25 G Quincke needle. During the course of surgery, epidural bupivacaine 0.5% will be supplied, if required. The sensory block will be evaluated bilaterally by using pinprick with a short needle; Motor block will be assessed using a modified Bromage scale (Bromage, 1965). ⁽⁹⁾  No analgesic or sedative drugs were used intraoperatively to avoid interruption with the outcomes of the study.

At the end of the procedure, patients will be randomized by a sealed envelope method, into one of three groups. All patients will be provided with an epidural syringe pump device and both magnesium sulfate and fentanyl infusions started. The primary setting of background infusion of fentanyl 3 mic/ml at a rate of 10 ml/h).

Group I (Control group (S) group; n=20 patients) Patients will receive epidural normal saline at a rate of 1ml/h for 24 hours plus epidural fentanyl via another infusion pump. Group II (MI); n=20 patients) Patients will receive epidural 50 mg magnesium sulfate (phenol-free) (Otsuka pharm, Egypt) in 5ml volume of normal saline as a bolus dose followed by continuous epidural infusion of 100 mg at a total 24ml volume for 24 hours at a rate of 4mg/h. Group III (MII); contain 20 patients) Patients will receive epidural 50mg magnesium sulfate in 5ml volume of normal saline as a bolus dose followed by continuous epidural infusion of 500 mg at a total 24ml volume for 24 hours at a rate of 20 mg/h.

All patients were observed at time intervals 30 minutes, 1, 2, 3, 4, 6, 12, 18 and 24 hourly in the postoperative period for 24 h for the following parameters: mean arterial blood pressure (MABP), heart rate (HR), Sp02, respiratory rate, time of first request for rescue analgesia (usually associated with VAS >3), motor block using a modified Bromage scale,⁹ and need for supplemental analgesia. Supplemental analgesia was administered with (pethidine) 50 mg intramuscular injection if VAS greater than 3 and the total consumption of pethidine was recorded over 24 h. Adverse events like nausea, vomiting, pruritus, and respiratory depression were recorded. The study medications were arranged by one anesthetist and injected by another anesthetist who was blinded to the study medicines. The nurse who was inspecting the patient and recording the postoperative study parameters was also blinded to the study medicines.

Statistical presentation and analysis of the present study were conducted, using the mean, standard error, student t-test, paired t-test, Chi-square, Linear Correlation Coefficient and ROC curve by SPSS v 17.

RESULTS

As regards demographic data, ASA, and type of surgery, there were no significant differences among all groups as shown in Table (1) and (2) (P>0.05).  

Table 1: Patient characteristics and type of surgery

Table (2): Patient characteristics of the studied groups

When analyzing the VAS of the three groups, the patients in the control group showed the highest VAS all through the postoperative phase. It was found that there is a significant statistical difference at the 1st hour and the 2nd hour of the postoperative course when comparing the control group with the M I group and M II group. But there was no significant statistical difference when comparing the three groups at the other time points of the postoperative course as shown in Figure1, and Table 3.

    Fig.1: VAS of the study groups

Table 3: VAS readings of the three groups

As regards time for first analgesic demand, there was no statistically significant difference between the control group (40.380 ± 10.258 min) and M I group  (41.912  ± 10.166

min) and M II (40.358 ± 9.445 min)  with P-value 0.852 as shown in Table 4.

  Table 4: Time for the first analgesic request (hours)  *Time is expressed in hours.

As regards the total consumptn of fentanyl per 24 hours, epidural fentanyl infusion was fixed for all groups with another epidural syringe pump device and the primary setting of background infusion of fentanyl 3 mic/ml at a rate of 10 ml/h. Regarding total analgesic (pethidine)

requirement it was significantly lower in both M I and M II groups than in the control group with p-value < 0.001 as in the control group, the total consumption was (144.215±18.18) mg while there was no significant difference between the two magnesium groups as in the M I group, the total consumption was (103.25±13.20) mg, while in the M II group, the total consumption was (97.24±10.28) mg,  with p-value (0.480)  (Table 5)

   Table 5: Total analgesic requirements ** Statistically significant difference (p<0.001)

     *Dose expressed in mg.

As regards motor block assessment using a modified Bromage scale, there was no difference between all groups either intraoperatively or postoperatively.

    As regards the HR, MAP, SpO2, and respiratory rate showed no statistically significant difference among all groups in the postoperative periods (P>0.05) as shown in table 6.

 Table 6: Patient MAP in relation to surgery*readings are expressed in mmHg.  

  This study did not record any significant epidural drug-related or any significant neurological adverse effects postoperatively.