A randomized controlled trial of loading dose alone versus pritchard regimen of magnesium sulphate, for seizure prophylaxis in severe preeclampsia.

Background: Preeclampsia poses a significant risk of maternal and neonatal morbidity and mortality. Magnesium sulfate superiority for seizure prophylaxis in severe preeclampsia has been proven globally. However, the search for the lowest effective dose is an area of continuing research. Aim: The aim of this study was to compare the effectiveness of loading dose with the Pritchard regimen of magnesium sulfate for seizure prophylaxis in severe preeclampsia. Materials and Methods: A total of 138 eligible women after 28-week gestation with severe preeclampsia were randomized to either receiving a single loading dose of MgSO4 (study arm: n = 69) or Pritchard regimen of MgSO4 (control: n = 69). The effectiveness was assessed by the development of seizure. The results obtained were analyzed using SPSS version 21. Categorical variables were analyzed using the Chi-square test and normally distributed continuous variables were analyzed with t-test and Fisher's exact test. P < 0.05 was considered statistical significance. Results: There were no significant differences between those who received only the loading dose when compared with those who had Pritchard regimen other than a single recorded convulsion among the control group (P = 0.316). Similarly, except for the duration of hospital stay which was significantly longer in the Pritchard group (P = 0.019), both the arms of the study shared similar maternal and fetal outcomes. Conclusion: This study suggests the effectiveness of just the loading dose of magnesium sulfate when compared with the standardized Pritchard regimen in the prevention of seizure among women with severe preeclampsia. The study also demonstrated safety and similarity in fetal-maternal outcome. The loading dose only had an added advantage of shorter duration of hospital stay.

Résumé Contexte: La prééclampsie pose un risque important de morbidité et de mortalité maternelle et néonatale. La supériorité du sulfate de magnésium pour 15 prophylaxies épileptiques dans la prééclampsie sévère a été prouvée à l'échelle mondiale. Cependant, la recherche de la dose efficace la plus faible est un domaine de recherche continue. Objectif: L'objectif de cette étude était de comparer l'efficacité de la dose de charge avec le schéma de Pritchard de sulfate de magnésium pour la prophylaxie de 17 épilepsies dans la prééclampsie sévère. Matériels et méthodes: Un total de 138 femmes éligibles après 28 semaines de gestation atteintes de 18 prééclampsie ont été randomisés pour recevoir soit une dose de charge unique de MgSO4 (groupe d'étude : n = 69) soit un régime de Pritchard de MgSO4 (contrôle : n = 69). L'efficacité a été évaluée par le développement de saisie. Les résultats obtenus ont été analysés à l'aide de SPSS version 21. Les 19 variables catégorielles ont été analysées à l'aide du test du chi carré et les variables continues normalement distribuées ont été analysées à l'aide du test t et du test exact de Fisher. 20 P < 0,05 était considéré comme une signification statistique. Résultats: Il n'y avait pas de différences significatives entre ceux qui n'avaient reçu que la dose de charge 21 par rapport à ceux qui avaient reçu le régime de Pritchard autre qu'une seule convulsion enregistrée parmi le groupe témoin (P = 0,316). 22 De même, à l'exception de la durée du séjour à l'hôpital qui était significativement plus longue dans le groupe Pritchard (P = 0,019), les deux bras de l'étude 23 partageaient des résultats maternels et fœtaux similaires. Conclusion: Cette étude suggère l'efficacité de la seule dose de charge de sulfate de magnésium par rapport au régime de Pritchard standardisé dans la prévention des convulsions chez les femmes atteintes de prééclampsie sévère. L'étude a également démontré 24 l'innocuité et la similarité des résultats fœto-maternels. La dose de charge n'avait qu'un avantage supplémentaire de durée d'hospitalisation plus courte. 25. Mots-clés: Éclampsie, dose de charge, sulfate de magnésium, régime de Pritchard, prophylaxie des crises, prééclampsie sévère.

Magnesium sulfate pharmacokinetics after intramuscular dosing in women with preeclampsia.

BACKGROUND: Current intramuscular magnesium dosing regimens in low and middle-income countries are based on indirect absorption parameters to inform pharmacokinetic and pharmacodynamic response. OBJECTIVE: To determine if therapeutic serum magnesium levels are obtained in women with severe preeclampsia receiving intramuscular administration of magnesium sulfate using the Pritchard regimen and to compare the key pharmacokinetic variables to those previously published. STUDY DESIGN: Serum magnesium levels were obtained at multiple time points at baseline and after magnesium sulfate administration from women with severe preeclampsia receiving the standard Pritchard regimen for seizure prophylaxis at Bayero University, Kano, Nigeria. The pharmacokinetic profiles were constructed for the study cohort and the updated pharmacokinetic model was compared with the one that was previously published. RESULTS: A total of 80 blood samples were collected from 20 women with severe preeclampsia (45 collected before childbirth and 35 collected after childbirth). After 11.5 hours of magnesium sulfate administration, 63% of women in the cohort had serum magnesium levels of ≥2.0 mmol/L. Data from women receiving the Pritchard regimen combined with data from women previously modeled after the receipt of intravenous magnesium sulfate were adequately described using a 2-compartment model with first-order absorption and linear elimination from the central compartment. All structural pharmacokinetic parameters including clearance, central volume of distribution, peripheral volume of distribution, and intercompartment clearance were adjusted for maternal weight, and the clearance was further adjusted for serum creatinine level and antepartum or postpartum status. The simulated pharmacokinetic profiles of the updated pharmacokinetic model and the previously published pharmacokinetic model are similar. In previously published pharmacokinetic modeling, absorption rate constant=0.32 and absolute bioavailability=0.86. In the updated pharmacokinetic model, absorption rate constant=0.45 and absolute bioavailability=0.91. CONCLUSION: These data support the use of the Pritchard regimen as acceptable to achieve therapeutic serum magnesium levels and support the reported simulation of serum magnesium levels and eclampsia response associated with different intramuscular regimens.