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Randomized Controlled Trial
. 2018 Jul 6;18(1):290.
doi: 10.1186/s12884-018-1919-6.

A randomized trial comparing the pharmacology of magnesium sulfate when used to treat severe preeclampsia with serial intravenous boluses versus a continuous intravenous infusion

Thomas Easterling  1 , Mary Hebert  2 , Hillary Bracken  3 , Emad Darwish  4 , Mohamed Cherine Ramadan  5 , Salwa Shaarawy  4 , Dyanna Charles  3 , Tamer Abdel-Aziz  4 , Ahmed Shokry Nasr  5 , Sherif Mohamed Safwal  5 , Beverly Winikoff  3
Affiliations
Randomized Controlled Trial

A randomized trial comparing the pharmacology of magnesium sulfate when used to treat severe preeclampsia with serial intravenous boluses versus a continuous intravenous infusion

Thomas Easterling et al. BMC Pregnancy Childbirth. .

Abstract

Background: Magnesium sulfate is the preferred pharmacological intervention for the prevention and treatment of eclamptic seizures in pregnancy. Pain associated with intramuscular injections and the need for an electronic infusion pump for use intravenously represent significant barriers to broader utilization. We hypothesize that an alternative regimen based on serial intravenous (IV) boluses can produce serum concentrations comparable to those produced by a continuous infusion.

Methods: An open-label randomized trial was performed at two hospitals in Egypt. Women with severe preeclampsia were eligible and enrolled between January 2015 and February 2016. Two hundred subjects were randomized by random numbers generated centrally in distinct blocks and stratified by study site. They were assigned to a continuous infusion arm, (4 g loading dose with 1 g/hr. continuous infusion) or a serial IV bolus arm, (6 g loading dose with 2 g bolus every 2 h using a Springfusor® pump). Sparsely sampled magnesium serum concentrations were collected, nonlinear mixed effect modeling was conducted and Monte Carlo simulations were used to generate 200 simulated subjects in each treatment arm. The simulated populations were used to determine area under the concentration-time curve (AUC) as a measure of total drug exposure and compared.

Results: Simulated area under the magnesium serum concentration-time curve was significantly higher in the serial IV bolus arm than in the continuous infusion arm (1107 ± 461 mmol•min /L vs. 1010 ± 398 mmol•min /L, (P = 0.02)). Four percent of women in the serial bolus arm considered the treatment unacceptable or very unacceptable compared to 2% in the continuous infusion arm, (P = 0.68).

Conclusions: Serial IV boluses achieve serum magnesium concentrations statistically significantly higher but clinically comparable to those achieved with a continuous infusion and offer a third option for the administration of MgSO4 to women with preeclampsia that may reduce barriers to utilization.

Trial registration: Trial no. NCT02091401, March 17, 2014.

Keywords: Magnesium sulfate; Pharmacokinetics; Preeclampsia.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by Ethics Committee of the Faculty of Medicine—Alexandria University and the El Galaa Maternity Teaching Hospital Ethical Committee. Written consent was obtained from each subject.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Consort Diagram
Fig. 2
Fig. 2
Observed vs. predicted magnesium concentrations in final model. The RED line represents the regression results. The BLACK line is the line of unity where X = Y
Fig. 3
Fig. 3
Individual magnesium concentrations over time. A-Continuous Infusion. B-Serial IV Bolus
Fig. 4
Fig. 4
Median simulated magnesium concentrations over time with observed magnesium concentrations. A-Continuous Infusion. B-Serial IV Bolus
Fig. 5
Fig. 5
Median simulated magnesium concentrations over time. Red-Continuous Infusion. Blue-Serial IV Bolus
See this image and copyright information in PMC

References

    1. The Eclampsia Trial Collaborative Group Which anticonvulsant for women with eclampsia? Evidence from the collaborative Eclampsia trial. Lancet. 1995;345:1455–1463. doi: 10.1016/S0140-6736(95)91034-4. - DOI - PubMed
    1. The Magpie Trial Collaboration Group Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359:1877–1890. doi: 10.1016/S0140-6736(02)08778-0. - DOI - PubMed
    1. Belfort M, Anthony J, Saade G, Allen J. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003;348:304–311. doi: 10.1056/NEJMoa021180. - DOI - PubMed
    1. Mundle S, Regi A, Easterling T, Biswas B, Bracken H, Khedekar V, et al. Treatment approaches for preeclampsia in low-resource settings: a randomized trial of the Springfusor pump for delivery of magnesium sulfate. Pregnancy Hypertension. 2012;2:32–38. doi: 10.1016/j.preghy.2011.09.002. - DOI - PubMed
    1. Abbade J, Costa R, Martins A, Borges V, Rudge M, Peraçoli J. Zuspan’s scheme versus an alternative magnesium sulfate scheme: randomized clinical trial of magnesium serum concentrations. Hypertension in Pregnancy. 2010;29:82–92. doi: 10.3109/10641950902928704. - DOI - PubMed

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