|Year : 2015 | Volume
| Issue : 1 | Page : 50-55
Does magnesium sulfate affect the oxytocin bolus requirement in pre-eclamptic patients undergoing cesarean section?
Riham Hasanein, Sahar El-Shal
Anesthesia Department, Faculty of Medicine, Cairo University, Cairo, Egypt; Saad Specialist Hospital, Alkhobar, Saudi Arabia
|Date of Submission||29-Jul-2014|
|Date of Acceptance||06-Jan-2015|
|Date of Web Publication||25-Mar-2015|
King Faisal St, Alkhobar 31952, PO Box 30353
Source of Support: None, Conflict of Interest: None
The aim of this study was to determine whether the magnesium sulfate (MgSO 4 ) used for pre-eclamptic patients affects the oxytocin bolus dose requirement to maintain adequate uterine tone during cesarean section under spinal anesthesia.
Materials and methods
A total of 80 patients with mild pre-eclampsia were randomized to receive either intravenous MgSO 4 (group M, n = 40) or matched normal saline (group S, n = 40). After delivery of the baby, oxytocin was injected as an intravenous bolus of 3 IU. The uterine tone was assessed by the obstetrician to be either satisfactory or unsatisfactory at 2, 4, 6, 8, and 10 min. If the tone was assessed as unsatisfactory at any time less than 3 IU of oxytocin were injected as a 'rescue' bolus dose. A maximum of two 'rescue' doses of oxytocin were allowed at two separate recordings of inadequate uterine tone. If the uterine tone was still unsatisfactory after two rescue doses of oxytocin, then other uterotonic drugs were given. The primary endpoint was the number of patients who received rescue doses of oxytocin or other uterotonic medications. Secondary endpoints, including the change in the hematocrit value before surgery and within 30 min after cesarean section, the estimated amount of intraoperative blood loss, and any side effects associated with oxytocin, were recorded.
The number of patients who required one rescue dose of oxytocin during the study was significantly higher in group M in comparison with group S (P = 0.029). The total number of patients who received both additional oxytocin boluses and other uterotonic agents to achieve a satisfactory uterine tone was also statistically significant between both groups (P = 0.034).
The use of MgSO 4 in mild pre-eclamptic patients leads to increased oxytocin requirements in order to maintain a satisfactory uterine tone during cesarean section under spinal anesthesia.
Keywords: cesarean section, magnesium sulfate, oxytocin, pre-eclampsia
|How to cite this article:|
Hasanein R, El-Shal S. Does magnesium sulfate affect the oxytocin bolus requirement in pre-eclamptic patients undergoing cesarean section?. Ain-Shams J Anaesthesiol 2015;8:50-5
|How to cite this URL:|
Hasanein R, El-Shal S. Does magnesium sulfate affect the oxytocin bolus requirement in pre-eclamptic patients undergoing cesarean section?. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 May 6];8:50-5. Available from: http://www.asja.eg.net/text.asp?2015/8/1/50/153938
| Introduction|| |
Magnesium sulfate (MgSO 4 ) is used extensively for the prevention and the treatment of eclamptic seizure , and is considered as the ideal anticonvulsant drug in pre-eclampsia and eclampsia  . The effect of MgSO 4 in vitro and in vivo on relaxing human uterine contractility has been widely reported. Magnesium has a calcium antagonist effect that decreases the intracellular calcium concentration and inhibits the contraction process ,, .
Many studies conducted during normal labor failed to prove the effect of MgSO 4 on the uterine muscle, on prolonging labor, or on prompting cesarean section ,,, . However, one study on mild pre-eclampsia during labor induction reported that intravenous MgSO 4 resulted in a significantly higher maximum oxytocin dose requirement in labor when compared with placebo  .
Oxytocin is a uterotonic drug commonly used in obstetrics. It is routinely administered in both normal and cesarean delivery to initiate and maintain adequate uterine tone for minimizing blood loss and preventing postpartum hemorrhage  . Its vasodilator effect on vascular endothelial receptors causes a calcium-dependent response through the stimulation of the nitric oxide pathway  .
The aim of this study was to find out the impact of MgSO 4 on the requirement of a bolus dose of oxytocin to achieve adequate uterine tone in patients with mild pre-eclampsia during cesarean section.
| Materials and methods|| |
After obtaining approval from our Institutional Review Board and written informed consent from every participant, 80 parturients with mild pre-eclampsia and between 18 and 40 years of age were included in this randomized, double-blind study. The study was conducted at Saad Specialist Hospital, Alkhobar, Saudi Arabia, between March 2012 and December 2013. All parturients diagnosed as having mild pre-eclampsia and planned for elective cesarean delivery were considered as participants of the study. Mild pre-eclampsia was defined as the presence of hypertension (blood pressure ≥140/90 mmHg) on two different occasions, at least 6 h apart, without evidence of any end-organ damage, with new onset proteinuria (+1 or greater on dipstick on two different occasions).
Exclusion criteria were as follows: patient refusal, contraindication to spinal anesthesia, chronic hypertension, severe pre-eclampsia, coagulopathy, placenta previa, abruption placentae, cord prolapse, less than 28 weeks' gestation, morbid obesity, twin pregnancy, active labor, fetal distress, and any tocolytic medications. If spinal anesthesia failed, general anesthesia was given, and the patients were withdrawn from the study. If disease progression from mild to severe pre-eclampsia occurred, patients were excluded from the study.
Severe pre-eclampsia was defined as the presence of one of the following symptoms or signs in the presence of pre-eclampsia:
All patients were preloaded with Ringer's lactate 10 ml/kg after insertion of an 18-G venous cannula. Hydralazine 5 mg was given intravenously and can be repeated every 20 min (maximum 40 mg) to control the diastolic blood pressure to be ~90 mmHg. All patients were requested to fast for 8 h before operation and all of them received 30 ml of sodium citrate orally 20 min before shifting to the operating room.
- A systolic blood pressure of 160 mmHg or more or a diastolic blood pressure of 110 mmHg or more on two occasions at least 6 h apart.
- Proteinuria of greater than 5 g in a 24-h collection or more than 3+ on two random urine samples at least 4 h apart.
- Pulmonary edema or cyanosis.
- Oliguria (<400 ml in 24 h).
- Persistent headaches.
- Epigastric pain and/or impaired liver function.
- Thrombocytopenia (platelet count <100 000/mm 3 ).
- Oligohydramnios, decreased fetal growth, or placental abruption.
- HELLP syndrome.
Upon arrival to the operating room, noninvasive blood pressure monitoring, ECG, and pulse oximetry were applied, and the baseline hematocrit value was measured.
The baseline maternal heart rate (HR) and the mean arterial blood pressure (MAP) were recorded as the average of three consecutive readings. The patients were divided randomly into two groups of 40 patients each. Randomization was carried out using Microsoft Excel-generated allocations (Microsoft Excel version 15, SPSS Inc., Chicago, Illinois, USA). Opaque, concealed envelopes were used for group assignment to ensure blinding. Patients were divided into two groups: group M (MgSO 4 group) and group S (saline group). Group M (n = 40) patients received a loading dose of 4 g of MgSO 4 (20 ml of 20% solution in saline) injected slowly intravenously over 20 min, followed by a maintenance dose of 1 g/h of MgSO 4 (4 g MgSO 4 added to 100 ml saline and infused at a rate of 25 ml/h). Group S (n = 40) patients received a loading dose of 20 ml saline injected slowly intravenous over 20 min, followed by 100 ml saline infused at a rate of 25 ml/h. The study drugs were prepared by a pharmacist not included in the study. The bags were identical in appearance and were labeled by the study identification number from which the pharmacist can determine the study drug. The drugs were administered by a nurse according to the instructions written in a sealed envelope. All bags were labeled as the study drug. Both the anesthetist and the obstetrician were blinded to the study drugs except in emergency situations. The patient was sent to the operating room for a cesarean section 1 h after starting the maintenance dose of the study drug, which was continued for 24 h after the delivery of the baby.
Spinal anesthesia was performed in the sitting position in the L3/L4 or the L4/L5 space with a 25-G Quincke spinal needle with 2 ml of 0.5% hyperbaric bupivacaine with 20 μg of fentanyl. Patients were turned supine with a wedge under the right flank to achieve a lateral tilt of 15°. Surgery was started once the block height reached T4 to cold perception using ice. Oxytocin was injected as an intravenous bolus of 3 IU over a time period of 60 s using a stopwatch, after clamping of the umbilical cord and delivery of the baby. The uterine tone was assessed by the obstetrician after delivery of the placenta to be either satisfactory or unsatisfactory at 2, 4, 6, 8, and 10 min. If the tone was assessed as unsatisfactory at 2 min, 3 IU of oxytocin were injected as a 'rescue' bolus dose. A maximum of two 'rescue' doses of oxytocin were allowed at two separate recordings of inadequate uterine tone. If the uterine tone was still unsatisfactory after two rescue doses of oxytocin, then other uterotonic drugs were given in the following order: intramuscular carboprost tromethamine 0.25 mg and then rectal misoprostol 800-1000 mg. A maintenance infusion of oxytocin was then started immediately [20 IU of oxytocin in 500 ml 0.9% normal saline at 250 ml/h (0.16 IU/min)].
Our primary endpoint was the number of patients who received rescue doses of oxytocin and additional uterotonic medications. Secondary endpoints included the change in the hematocrit value before surgery and within 30 min after cesarean section, the estimated amount of intraoperative blood loss (by measuring the blood collected by suction and by calculating the weight of blood on surgical swabs), the need for blood transfusion, changes in the MAP and HR at 2, 4, 6, 8, and 10 min after oxytocin bolus, and any side effects associated with oxytocin such as tachycardia, hypotension, nausea, vomiting, and flushing were recorded. Hypotension was considered as a decrease in the MAP by 10% of the baseline value and each episode of hypotension was treated with 3 mg of ephedrine intravenous bolus. Tachycardia was considered as an increase in the HR by 10% of the baseline value.
Depending on a previous study  , the mean difference and the pooled SD were calculated, and the sample size was estimated (40 in each group), with the power of study being 80% and the confidence interval being 99%.
Data were statistically described in terms of mean ± SD, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups was performed using the Student t-test for independent samples. For comparing categorical data, the χ2 -test was performed. The exact test was used instead when the expected frequency was less than 5. P values less than 0.05 were considered statistically significant. All statistical calculations were performed using the computer program SPSS version 15 for Microsoft Windows (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Eighty patients were enrolled in the study; two cases in group S were excluded from the study due to failed spinal anesthesia. Patients' demographic data were comparable in both groups as shown in [Table 1].
The number of patients who required one rescue dose of oxytocin during the study was significantly higher in group M in comparison with group S as 12 (30%) out of 40 patients in group M required a rescue dose of oxytocin, whereas only three (7.8%) out of 38 patients in group S required a rescue dose of oxytocin after the initial oxytocin dose (P = 0.029) ([Table 2]).
|Table 2 The number and percentage of patients requiring supplemental oxytocin doses and other uterotonic agents|
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However, there was no statistically significant difference between both groups regarding the number of patients who needed second rescue doses of oxytocin: only three (7.5%) patients in group M compared with two (5.2%) patients in group S (P = 0.953) ([Table 2]).
Also, there was no significant difference between both groups with regard to the number of patients who needed other uterotonic agents: only one (2.5%) patient in group M and one (2.6%) patient in group S (P = 0.497) ([Table 2]).
The total number of patients who received both additional oxytocin boluses and other uterotonic agents to have a satisfactory uterine tone was statistically different between both groups: 16 (40%) patients in group M compared with six (2.3%) patients in group S (P = 0.034) ([Table 2]).
Preoperative and postoperative hematocrit, the estimated intraoperative blood loss, the need for blood transfusion, and intravenous crystalloid administered to the patients were comparable in both groups as shown in [Table 3].
There was a statistically significant difference between both groups in the hemodynamic values of both MAP and HR in the baseline values and all values after the initial oxytocin bolus ([Table 4] and [Table 5]).
|Table 4: Mean blood pressure changes (mmHg) at baseline and at 2, 4, 6, 8, and 10 min after the initial oxytocin bolus|
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|Table 5: Mean heart rate changes (beats/min) at baseline and at 2, 4, 6, 8, and 10 min after the initial oxytocin bolus|
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There was no significant difference in the incidence of nausea and vomiting, flushing, hypotension, and tachycardia ([Table 6]).
| Discussion|| |
In our study, we examined the impact of the prophylactic use of MgSO 4 in pre-eclamptic patients during cesarean sections on the requirement of oxytocin boluses and other uterotonic agents after injecting 3 IU oxytocin as an initial bolus dose to have an adequate uterine tone and prevent postpartum hemorrhage.
Although the use of oxytocin is widespread, there are no guidelines for its use in cesarean section. To our knowledge, no previous studies have been conducted to test the effect of MgSO 4 on oxytocin requirements during cesarean section in pre-eclamptic patients.
A study conducted by Butwick et al.  revealed that an adequate uterine tone can be achieved by a small bolus oxytocin dose of 0.5-3 IU. We chose 3 IU as the initial bolus dose; the uterine tone was assessed every 2 min after that as we expected our patients to have a high risk for uterine atony. Also, Sartain et al.  injected 2 and 5 IU bolus doses and reported that the use of 2 IU was more effective because the hemodynamic changes were more severe in the 5 IU group and the uterine tone was similar in the two groups.
We gave our bolus dose over 60 s to be standard in all our patients, keeping in mind that the side effects of oxytocin bolus are related to both the dose and the rate of injection , .
There was a significant increase in the requirement for the rescue dose of oxytocin in the patients who received MgSO 4 in comparison with the saline group; 30% of the patients who received MgSO 4 needed one rescue dose of oxytocin, whereas only 7.8% in the other group needed one rescue dose of oxytocin (P = 0.029). The total number of patients who needed rescue doses of oxytocin with or without additional uterotonic drugs was also significantly higher in the MgSO 4 group (40%) than in the saline group (15.7%) (P = 0.034). Magnesium competes with calcium intracellularly at the binding sites, decreasing the muscle contractility and stabilizing the membrane potential ,, . This effect of MgSO 4 might have resulted in reducing the uterine tone and increased the requirement of uterotonic agents (oxytocin and other uterotonics).
Our results are consistent with the study conducted by Witlin et al.  , who concluded that the use of MgSO 4 during labor in patients with mild pre-eclampsia at term necessitated higher oxytocin dose requirements. In contrast to this, Meier et al.  , who studied the effect of continuing oral magnesium therapy till the time of labor, concluded that it did not significantly increase the oxytocin requirement because the size of the oxytocin subgroup in their study was very small to reveal statistically significant results.
Although the use of MgSO 4 during pregnancy and at the time of delivery was associated with an increase in blood loss , , we found no intergroup difference in the estimated blood loss or the decrease in the hematocrit level. This can be explained by the rapid recognition and treatment of atony during cesarean section as the uterus is exposed and because it is easier to evaluate the uterine tone during cesarean section than during vaginal delivery.
There were a statistically significant difference in the measurement of baseline values of both MAP and HR between both groups and in all the values measured after the initial oxytocin bolus at 2, 4, 6, 8, and 10 min, which can be attributed to the suppression of catecholamine release induced by MgSO 4 and to its vasodilator effect , .
Although the incidence of hypotension was not statistically significant in both groups, the incidence was higher in the magnesium group (17.5%) than in the saline group (7.8%); this difference can be related to the effect of MgSO 4 or the effect of oxytocin boluses given to the magnesium group. In the study conducted by Sartain et al.  , they found hypotension to occur in 7% of the patients who received 2 IU of oxytocin, which is consistent with the incidence in our saline group. Our patients were from the high-risk group and the addition of MgSO 4 in the magnesium group could have resulted in this higher incidence of hypotension, either by its vasodilator effect or by the effect of the increased requirement of oxytocin bolus.
There was no significant difference in the incidence of other oxytocin-related side effects between both groups in our patients (nausea, vomiting, and flushing); these side effects were less than that previously recorded by Carvalho et al.  as they recorded a higher incidence of nausea, vomiting, and flushing (38, 13, and 63%, respectively), which can be explained by the slow rate of injection of the oxytocin bolus doses (over 60 s) in our study; the slow injection rate could have resulted in lesser side effects.
We chose spinal anesthesia for our patients because general anesthesia is a risk factor for uterine atony , .
Our study had the following limitations: first, the assessment of the uterine tone in our study was performed by obstetricians; however, there are no clinically validated or objective methods for assessing the uterine tone. Subjective assessments were used in previous studies for assessing uterine atony during cesarean section  . Second, we measured the blood loss by weighing the surgical swabs, by visual assessment of the suction chamber, and by changes in the preoperative and the postoperative hematocrit. The visual estimated blood loss may be inaccurate, and the difference in the hemoglobin and the hematocrit are difficult to interpret because of large fluid shifts that happen at the time of delivery  .
Further studies need to be conducted on patients with severe pre-eclampsia and using bolus doses less than 3 IU to minimize the hemodynamic changes.
| Conclusion|| |
Our results confirm our clinical impression that the use of MgSO 4 in mild pre-eclamptic patients leads to increased oxytocin requirements in order to maintain a satisfactory uterine tone during cesarean section under spinal anesthesia.
| Acknowledgements|| |
Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]