An Integrative Review of the Side Effects Related to the Use of Magnesium Sulfate for Pre-eclampsia and Eclampsia Management

Jeffrey Michael Smith; Richard F Lowe; Judith Fullerton; Sheena M Currie; Laura Harris; Erica Felker-Kantor

Disclosures

BMC Pregnancy Childbirth. 2013;13(34) 

In This Article

Background

Pre-eclampsia/eclampsia (PE/E) is a life-threatening multisystem disorder affecting 2 - 8% of all pregnancies worldwide[1,2] that has substantial effect on maternal and newborn health. PE/E is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries.[3] Globally, approximately 63,000 women die each year of PE/E which accounts for an estimated 9% of maternal deaths in Asia and Africa and about one-quarter of maternal deaths in Latin America and the Caribbean.[1,3–6]

Manifestations of severe pre-eclampsia should be treated in accord with World Health Organization recommendations.[7] Comprehensive management of the disease includes vigilant monitoring of the woman and fetus, management of acute hypertension and prevention of seizures in women with pre-eclampsia, and prevention of recurrent seizures in women with eclampsia. The definitive treatment of PE/E is delivery of the fetus.

Magnesium sulfate is the drug of choice for prevention of seizures in the pre-eclamptic woman, or prevention of recurrence of seizures in the eclamptic woman, as demonstrated in two large clinical studies. In 1995, the Eclampsia Trial Collaborative Group reported that when magnesium sulfate was used for treatment the risk of recurrent convulsions in women with eclampsia was reduced by 52% when compared with diazepam, and by 67% when compared with phenytoin.[8] In 2002, the Magpie trial reported that women with severe pre-eclampsia given magnesium sulfate had a 58% lower risk of developing eclampsia compared to the placebo group.[9] Findings from a recent Cochrane review[10] also support the use of magnesium sulfate as the drug of choice. Although the precise mechanism of action is unclear, magnesium sulfate appears to have a peripheral site of action at the neuromuscular junction and does not cross the intact blood brain barrier.[11] Pritchard showed that magnesium serum concentration required for eclampsia prevention or treatment should be higher than normal serum levels, and suggested that therapeutic concentration should be between 4 and 7 mEq/L.[12]

Magnesium sulfate is associated with several minor side effects such as a feeling of warmth, flushing, nausea and vomiting, muscle weakness, somnolence, dizziness, and irritation at the injection site. More serious side effects are rare but include the loss of the patellar reflex (typically occurring at a serum concentration of 8 -10 mEq/L) and respiratory depression (>13 mEq/L).[11,13]

Routine monitoring of a woman undergoing magnesium sulfate therapy includes simple assessment of neurologic status (level of alertness and patellar reflexes), respiratory rate and urinary output.[14] Typical management of the more serious side effects includes heightened monitoring, delay in administration of next dose or suspension of magnesium sulfate therapy. Oliguria is an element of the disease process [reduced clearance by the kidneys], and not an adverse effect of magnesium sulfate use. Because magnesium is cleared by the kidneys, oliguria of less than 30 cc per hour is used as a determinant for withholding a scheduled dose, in order to prevent toxic levels. If serious toxicity is suspected, and immediate counteraction of magnesium is desired, calcium gluconate can be administered to counteract the effect of magnesium levels that are well above the therapeutic range.[13]

Despite the compelling evidence for the effectiveness of magnesium sulfate concern has been expressed about the safety of its administration and use, particularly in clinical environments where the capacity for patient monitoring is limited. These concerns can constrain initiation of treatment for all women with indicated need, or may impede sustaining therapy over the recommended timeline established for the particular regimen, once treatment has been initiated.[15,16]

The purpose of this review was to determine whether the published literature from low- and middle-income countries supports the concerns about the safety of use of magnesium sulfate. The review identifies the frequency of severe adverse reactions when the drug is used according to a recommended protocol, and the frequency of the need for intervention as a result of those reactions.

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