|Year : 2011 | Volume
| Issue : 1 | Page : 21-25
Comparison of the analgesic effects of intravenous magnesium sulfate infusion versus intrathecal fentanyl in patients with severe pre-eclampsia undergoing caesarean section
Ahmed Said Elgebaly1, Ahmed Ali Eldabaa1, Ahmed Ali Abd ELhafez1, Manal Mostafa Abdalla2
1 Anaesthesia and SICU, Faculty of Medicine, Tanta University, Egypt
2 Department of Obstetrics and Gynecology , Faculty of Medicine, Tanta University, Egypt
|Date of Web Publication||25-Aug-2011|
Ahmed Said Elgebaly
Anaesthesia and SICU, Faculty of Medicine, Tanta University, Eygpt.43 IBN ELFARD Str., Elgharbia, Tanta
Source of Support: None, Conflict of Interest: None
Background : A double-blinded, prospective, randomized, controlled study was designed to determine the analgesic efficacy and tolerability of intravenous magnesium sulfate versus intrathecal fentanyl, in patients with severe pre-eclampsia, scheduled for caesarean section, under spinal anaesthesia.
Materials and Methods : One hundred and five patients were randomly allocated to one of the three groups; the control group B received spinal anaesthesia with 10 mg of 0.5% heavy bupivacaine, the test group FB received spinal anaesthesia with 10 mg of 0.5% heavy bupivacaine plus 25 ΅g of preservative-free fentanyl and the test group MB received spinal anaesthesia with 10 mg of 0.5% heavy bupivacaine along with intravenous magnesium sulfate (6 gm iv as a loading dose over 20-30 minutes, followed by infusion of magnesium sulfate 2 gm per hour for 24 hours).
Results : The time required for the first postoperative analgesic requirement was significantly more in groups FB and MB, as compared to the control group. (Group FB: 6.85 + 1.7 hours, group MB: 7.05 + 1.95 hours and Group B: 3.75 + 0.75 hours). This difference, however, was not significant between group FB and group MB. The frequency of postoperative analgesic requirement was significantly less in the FB and MB groups, as compared to the control group. (Control group: 3.9 + 0.5, group FB 2.3 + 0.25 and group MB: 2.5 + 0.4). Perioperative sedation was significantly higher in group FB as compared to group B and group MB. Nine patients in group FB had postoperative nausea and vomiting, whereas, none of the patients in the control group or group MB experienced this. This difference too was statistically significant.
Conclusion : Intravenous magnesium sulfate and intrathecal fentanyl in the doses mentioned, increased the duration of postoperative analgesia in severely pre-eclamptic patients undergoing caesarean section under spinal anaesthesia; however, patients who received intravenous magnesium sulfate experienced lesser side effects than those who received intrathecal fentanyl.
Keywords: Caesarean section, intrathecal fentanyl, magnesium sulfate, postoperative analgesia, severe pre-eclampsia
|How to cite this article:|
Elgebaly AS, Eldabaa AA, Abd ELhafez AA, Abdalla MM. Comparison of the analgesic effects of intravenous magnesium sulfate infusion versus intrathecal fentanyl in patients with severe pre-eclampsia undergoing caesarean section. J Obstet Anaesth Crit Care 2011;1:21-5
|How to cite this URL:|
Elgebaly AS, Eldabaa AA, Abd ELhafez AA, Abdalla MM. Comparison of the analgesic effects of intravenous magnesium sulfate infusion versus intrathecal fentanyl in patients with severe pre-eclampsia undergoing caesarean section. J Obstet Anaesth Crit Care [serial online] 2011 [cited 2020 Nov 25];1:21-5. Available from: https://www.joacc.com/text.asp?2011/1/1/21/84251
| Introduction|| |
Intravenous magnesium sulfate during spinal anaesthesia has been shown to improve postoperative analgesia in non-obstetric surgery.  However, there are only few reports regarding the effects of intravenous magnesium sulfate after spinal anaesthesia in patients with severe pre-eclampsia undergoing caesarean sections. 
Magnesium sulfate has been used in obstetrics since 1925, for prevention of seizures in eclampsia, with the advantage of decreasing peripheral vascular resistance, without changing the uterine blood flow.  The advantages of magnesium sulfate in anaesthesia have been increasing over the years to include situations out of the obstetric field. It has analgesic and sedative properties with potential neuro- and cardioprotective effects, although the mechanisms of these actions are still unknown. ,
Previously, spinal anaesthesia was relatively contraindicated in patients with severe pre-eclampsia, due to the potential risk of sudden hypotension, with a rapid onset of sympathetic blockade.  However, low-dose spinal anaesthesia offered many advantages, which included simplicity, rapidity, reliability, predictability, safety for the mother and newborn, cost-effectiveness and effective perioperative analgesia. ,
Intrathecal opioids are a popular additive to enhance the potency and duration of the neuraxial blockade and they lengthen the postoperative analgesic period.  Nevertheless, they are fraught with side effects like pruritus, postoperative nausea and vomiting (PONV), urine retention and respiratory depression.  Therefore, anaesthesiologists are increasingly turning to non-opioid adjuvants for managing pain during the perioperative period, to minimize the adverse effects of analgesic medications. , Intravenous magnesium sulfate infusion is reported to have antinociceptive and effective analgesic and sedative properties.  Magnesium has postsynaptic N-methyl D-aspartate (NMDA) receptor antagonist and calcium channel blocker properties. It has been used successfully to potentiate opioid analgesia and to treat neuropathic pain in animals. , Tramer et al., conducted the first clinical trial showing that perioperative administration of magnesium sulfate is associated with lower analgesic requirements in the postoperative period. The present study is initiated to study the postoperative analgesic effect of intravenous magnesium sulfate infusion and compare it with that of intrathecal fentanyl, in patients with severe pre-eclampsia undergoing caesarean sections under spinal anaesthesia.
| Materials and Methods|| |
A double blinded, randomized, controlled study was carried out with the approval of the Ethics and Research Committee of the Institution. A written informed consent was obtained from 105 severely pre-eclamptic patients (gestation 31 - 40 weeks) scheduled for elective or urgent caesarean delivery under spinal anaesthesia, during a two-year period. Severe pre-eclampsia was defined as a systolic arterial blood pressure (SAP) of 160 mm Hg or more or a diastolic arterial blood pressure (DAP) of 110 mm Hg or more and proteinuria of 100 mg/dL or more.  Patients with eclampsia, coagulopathy, placental abruption, severe fetal distress, contraindications to regional anaesthesia or a history of allergy to local anaesthetics were excluded from the study. On arrival at the Operating Room, two peripheral venous cannulae and a urinary catheter were inserted and all the patients were preloaded with 10 ml / kg Lactated Ringer's solution. Monitoring consisted of echocardiogram (ECG), pulse oximeter and non-invasive blood pressure recording. Ramsay's score  was used to monitor the sedation levels. Intravenous hydralazine 5 mg was given to all patients at 20-minute intervals, to decrease the DAP to about 90 mm Hg, prior to the start of anaesthesia.
Spinal anaesthesia was administered in the sitting position with a 25 G needle, under strict aseptic conditions in the L3-4 space. The patients were randomly divided into the following three groups by the sealed envelopes method.  Group B patients (control) received 10 mg (2 ml) heavy bupivacaine 0.5% + 1 ml saline intrathecally, group FB patients received 10 mg (2 ml) heavy bupivacaine plus 25 μg (diluted in 1 ml) preservative-free fentanyl intrathecally and group MB patients received 10 mg (2 ml) heavy bupivacaine 0.5% + 1 ml saline intrathecally, plus an intravenous bolus of magnesium sulfate, 6 gm (60 ml), diluted with 100 ml of normal saline, over 30 minutes before administration of spinal anaesthesia. This was followed by an infusion of magnesium sulfate 2 gm per hour diluted in 40 ml normal saline (total 60 ml) at the rate of 1 ml per minute, for 24 hours.
In addition, both group B and group FB patients received a bolus of 160 ml infusion of normal saline over 30 minutes before the start of the spinal block, followed by an infusion of 60 ml normal saline at the rate of 1 ml per minute, for 24 hours.
All the medications were prepared by an anaesthesiologist who was not involved in any other aspect of the study. All syringes were identical and had similar volumes of the test and placebo solutions. The investigator who administered the drug, the anaesthesiologist who performed the intrathecal injections and the patients, were unaware of the group allocated and the drug that was received by the patient.
All the patients were closely observed and monitored for any seizures and in case the same occurred the patients were managed as per standard protocol and excluded from the study.
At the end of the procedure, the patients were observed for six hours in the recovery room, where a postoperative analgesic protocol was followed, in the form of paracetamol 500 mg, given intravenously, to be administered to the patient at the start of pain sensation at the site of the surgery. Subsequent doses of paracetamol were given on the patient's request, with a maximum of 3 gm in a 24-hour period.
During the first 24 hours in the postoperative period an anaesthetist, who was not part of the anaesthesia team, visited the patients and assessed them hourly. Hemodynamic parameters, pain score on VAS (0 = no pain and 100 = worst imaginable pain), neurological signs for hyper-magnesemia (positive patellar reflex), oliguria (urine output less than 25 mL / hour), respiratory depression (rate less than 8 / minute), the time to the first analgesic requirement and the number of analgesic doses required were noted. The other side effects noted were - incidence and severity of PONV (by four-point verbal rating score where 0 = none, 1 = nausea, 2 = vomited once and 3 = repeated vomiting), pruritus, sensory / motor disturbances and bowel and bladder dysfunction.
Statistical analysis was performed using one-way analysis of variance (ANOVA) for normally distributed parametric data. Time for the first analgesia, pain scores at the first pain medication and the number of analgesics requested in 24 hours were analyzed by the Kruskal-Wallis test followed by the post hoc multiple comparison tests using the Dunnett method. A P value < 0.05 was considered statistically significant.
| Results|| |
One hundred and five patients were randomized into the study, of which fifteen patients were excluded. Of these, six had inadequate anaesthesia and were given general anaesthesia. Three patients went into active labor, two patients developed seizures and four patients had surgical complications leading to prolonged surgical time. Statistical analysis was performed in the remaining 90 patients, 30 in each group.
There was no statistically significant difference between the groups with regard to patient demography and the duration of the caesarean section [Table 1]. The time to the first analgesic intake in group FB was 6.85 ± 1.7 hours and in group MB was 7.05 ± 1.95 hours. These timings were comparable. The time to the first analgesic intake in group B was 3.7 + 0.75 hours, which was significantly less when compared to that of group FB and group MB ( p < 0.01) [Table 2]. VAS at the time of the first analgesic requirement was comparable in the three groups [Table 2]. The frequency of analgesic intake was significantly less in the group FB and group MB as compared to group B ( P < 0.01) [Table 2]. None of the patients in group B and group MB had PONV, whereas, nine patients (30%) in the FB group had PONV. Perioperative sedation was noted to be significantly higher in the FB group (14 patients (47%)) as compared to the control and MB groups. Pruritus was significantly higher in the FB group compared to the other groups [Table 3]. Urine retention occurred in all the three groups, but the incidence was comparable. None of the patients experienced apneic spells, bradypnea or desaturation in the postoperative period [Table 3].
| Discussion|| |
Magnesium is a calcium channel blocker and N-Methyl-D-aspartate (NMDA) receptor antagonist. It has been explored for a role in postoperative pain, sensitization processes and hyperalgesia, throughout the early postoperative period. , The adjuvant analgesic effect of magnesium has been probably attributed to the activation of the NMDA receptors of the dorsal horn and the process of central sensitization., The dosage used in this study resulted in an analgesic effect, without any adverse reactions. We hypothesize that at this dosage the levels of magnesium in the cerebrospinal fluid rose sufficiently to depress the electrophysiological effect of the NMDA receptors. The results of the present study demonstrate that the infusion of magnesium significantly delays the need for the first analgesic requirement in the subgroup of patients studied, when compared to the need for the first analgesic requirement in patients who received a placebo infusion (7.05 ± 1.95 hours versus 3.7 ± 0.75 hours). A similar delay in the need for the first analgesic requirement was seen in patients who received intrathecal fentanyl (6.85 ± 1.7 hours versus 3.7 ± 0.75 hours). The time taken for this was less in patients who received intrathecal fentanyl than those who received a magnesium infusion, however, this difference was not statistically significant. Many studies have confirmed the efficacy of the opioid-sparing effect of intravenous magnesium sulfate. In their study on patients undergoing vitrectomy, Schulz-stubner et al., recommended the use of magnesium sulfate as a safe analgesic adjuvant. They attributed its analgesic effect to its calcium blocking properties and inhibition of neurotransmitter and catecholamine release. Ryu et al., showed that the infusion of magnesium sulfate during total intravenous anaesthesia (TIVA) with propofol infusion did not reduce propofol and remifentanil requirements, although the quality of postoperative analgesia was better in patients who received magnesium. In another recent report, Seyhan et al. compared the effects of magnesium sulfate on propofol requirements, hemodynamic variables and postoperative pain relief and observed significant reductions in intraoperative propofol, atracurium and postoperative morphine consumption. Studies  have observed results similar to our findings in context to the prolongation of analgesia produced by spinal bupivacaine, when administered either with intrathecal fentanyl or intravenous magnesium infusion.
Intrathecal fentanyl usage is very popular, but is associated with distressing side effects like postoperative nausea, vomiting, pruritus and sedation. In the present study the patients who received intravenous magnesium instead of intrathecal fentanyl did not have any of these common side effects. Magnesium could be very useful for multimodal postoperative pain relief in patients with a history of PONV or cardiac or respiratory diseases, commonly seen in severe pre-eclamptic patients undergoing caesarean section.
There are two main limitations to the present study. First is the inability to measure serum magnesium concentrations. However, it is known that the plasma magnesium concentration does not represent the magnesium content of the tissues. The lack of correlation between plasma magnesium and total body magnesium content in healthy subjects is also well-recognized.  Arnold and colleagues  have shown that the measurements of intra- and extracellular magnesium concentrations do not predict the magnesium levels in other body tissues accurately. Doses of magnesium, similar to the ones used in this study, have been shown to produce reductions in analgesic requirements, both during and after surgical interventions.  Second, limitation of the present study is the absence of data regarding the evaluation of the outcomes of the newborns in the three groups.
In conclusion, this study demonstrates that the analgesic efficacy of intravenous magnesium in severely pre-eclamptic patients is similar to that seen with intrathecal fentanyl in patients undergoing caesarean sections under a subarachnoid block. Magnesium infusion in such patients also avoids distressing side effects of intrathecal fentanyl like PONV, pruritus, respiratory depression and sedation.
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[Table 1], [Table 2], [Table 3]