Magnesium Sulfate for Pre-eclampsia and Eclampsia Management
Magnesium Sulfate for Pre-eclampsia and Eclampsia Management
Of the 54 clinical studies conducted in low- and middle-income countries identified, 24 were included in the final analysis (Figure 1). Of the 30 studies that were excluded, 15 did not record the incidence of side effects, five were available as conference abstracts only, and ten studies were unable to be located despite searching several libraries and contacting authors where possible.
(Enlarge Image)
Figure 1.
Selection of studies included in the review.
The final studies that were reviewed included randomized and non-randomized trials, either open or blinded (Table 1). Most studies were randomized controlled trials in which a magnesium sulfate regimen was compared against other drug regimens, or another magnesium sulfate regimen. Prospective cohort trials typically involved just one magnesium sulfate regimen. A single case control study was identified.
In the 24 studies, we identified 34 distinct subject groups that were administered magnesium sulfate, comprising a total of 9556 women. The women in these groups received one of three common magnesium sulfate regimens (Table 2) or a modification of one of these standard regimens. In total 16 different magnesium sulfate regimens were used in the 24 studies. Eleven subject groups received the standard Pritchard regimen and six groups received one of six different modified Pritchard regimens. Three groups received the standard Zuspan regimen and five groups received one of six Zuspan modified regimens. In three groups, some women received either the Zuspan or one of the six modified Zuspan regimens. Two groups received the Dhaka regimen and one a modified Dhaka regimen, and in three subject groups women received either the Pritchard or Zuspan regimen.
Table 3, Table 4 and Table 5 show the numbers of women enrolled in magnesium sulfate treatment groups, and the seven outcomes of interest. These included affected (either sluggish or absent) patellar tendon reflex, respiratory depression of less than 16 respirations per minute, oliguria of less than 30cc per hour, a decision to skip or delay the administration of the next scheduled dose, administration of calcium gluconate for perceived toxicity, all maternal deaths and maternal deaths considered to be due to magnesium sulfate toxicity. The calculated overall incidence rates for the outcomes of interest in all 9556 women are presented in Table 6.
Absent patellar reflex was specifically reported for 20 subject groups. The overall incidence among all 9556 aggregated women was 1.6%, with the incidence rate ranging from 0–57%. Three studies containing less than 60 women in each subject group recorded incidences ranging from 35%-57%, while the incidence was only 1.2% for the 5055 subjects in the Magpie trial.
Respiratory depression was specifically reported for 25 subject groups. The overall incidence among all 9556 women was 1.3%, with the incidence ranging from 0–8.2%. The highest incidences (7.7% and 8.2%) were reported for the two magnesium sulfate groups in the Eclampsia Collaborative Trial which included a total of 841 subjects. In the three studies that reported very high incidences of absent patellar reflex, the incidence of respiratory depression was less than 1%.
The skipping or delaying of a dose of magnesium sulfate was usually done in the presence of an adverse side effect (noted above), but in some studies, was also done following provider or patient preference. This outcome was reported for 22 subject groups. Repeat administration of magnesium sulfate was skipped or delayed in 348 women out of the total of 9556 in all trials, for a rate of 3.6%, with the rate ranging from 0–65%. The highest rates ranging from 20–65% were reported in studies in which subject groups were smaller than 70, while the largest study in 5055 women reported a rate of 3.7%.
The use of calcium gluconate was only reported for 12 of the 34 subject groups. The drug was administered only 17 times, resulting in an overall rate among 9556 women of less than 0.2%. In one study, calcium gluconate was administered to a woman following a dosing error which resulted in administration of 4 g of magnesium sulfate in one hour instead of four hours. The majority of the events (n = 14) occurred in the Magpie trial.
There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate in the 24 studies. The authors reported that the death was caused by severe respiratory depression and the woman's serum magnesium level was reported at 24 mEq/L, well above the therapeutic limits for prevention of eclamptic seizures.
Results
Of the 54 clinical studies conducted in low- and middle-income countries identified, 24 were included in the final analysis (Figure 1). Of the 30 studies that were excluded, 15 did not record the incidence of side effects, five were available as conference abstracts only, and ten studies were unable to be located despite searching several libraries and contacting authors where possible.
(Enlarge Image)
Figure 1.
Selection of studies included in the review.
The final studies that were reviewed included randomized and non-randomized trials, either open or blinded (Table 1). Most studies were randomized controlled trials in which a magnesium sulfate regimen was compared against other drug regimens, or another magnesium sulfate regimen. Prospective cohort trials typically involved just one magnesium sulfate regimen. A single case control study was identified.
In the 24 studies, we identified 34 distinct subject groups that were administered magnesium sulfate, comprising a total of 9556 women. The women in these groups received one of three common magnesium sulfate regimens (Table 2) or a modification of one of these standard regimens. In total 16 different magnesium sulfate regimens were used in the 24 studies. Eleven subject groups received the standard Pritchard regimen and six groups received one of six different modified Pritchard regimens. Three groups received the standard Zuspan regimen and five groups received one of six Zuspan modified regimens. In three groups, some women received either the Zuspan or one of the six modified Zuspan regimens. Two groups received the Dhaka regimen and one a modified Dhaka regimen, and in three subject groups women received either the Pritchard or Zuspan regimen.
Table 3, Table 4 and Table 5 show the numbers of women enrolled in magnesium sulfate treatment groups, and the seven outcomes of interest. These included affected (either sluggish or absent) patellar tendon reflex, respiratory depression of less than 16 respirations per minute, oliguria of less than 30cc per hour, a decision to skip or delay the administration of the next scheduled dose, administration of calcium gluconate for perceived toxicity, all maternal deaths and maternal deaths considered to be due to magnesium sulfate toxicity. The calculated overall incidence rates for the outcomes of interest in all 9556 women are presented in Table 6.
Incidence of Affected Patellar Reflex
Absent patellar reflex was specifically reported for 20 subject groups. The overall incidence among all 9556 aggregated women was 1.6%, with the incidence rate ranging from 0–57%. Three studies containing less than 60 women in each subject group recorded incidences ranging from 35%-57%, while the incidence was only 1.2% for the 5055 subjects in the Magpie trial.
Incidence of Respiratory Depression
Respiratory depression was specifically reported for 25 subject groups. The overall incidence among all 9556 women was 1.3%, with the incidence ranging from 0–8.2%. The highest incidences (7.7% and 8.2%) were reported for the two magnesium sulfate groups in the Eclampsia Collaborative Trial which included a total of 841 subjects. In the three studies that reported very high incidences of absent patellar reflex, the incidence of respiratory depression was less than 1%.
Frequency With Which Doses of Magnesium Sulfate were Skipped or Delayed
The skipping or delaying of a dose of magnesium sulfate was usually done in the presence of an adverse side effect (noted above), but in some studies, was also done following provider or patient preference. This outcome was reported for 22 subject groups. Repeat administration of magnesium sulfate was skipped or delayed in 348 women out of the total of 9556 in all trials, for a rate of 3.6%, with the rate ranging from 0–65%. The highest rates ranging from 20–65% were reported in studies in which subject groups were smaller than 70, while the largest study in 5055 women reported a rate of 3.7%.
Frequency of Use of Calcium Gluconate
The use of calcium gluconate was only reported for 12 of the 34 subject groups. The drug was administered only 17 times, resulting in an overall rate among 9556 women of less than 0.2%. In one study, calcium gluconate was administered to a woman following a dosing error which resulted in administration of 4 g of magnesium sulfate in one hour instead of four hours. The majority of the events (n = 14) occurred in the Magpie trial.
Maternal Deaths Attributable to Magnesium Sulfate
There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate in the 24 studies. The authors reported that the death was caused by severe respiratory depression and the woman's serum magnesium level was reported at 24 mEq/L, well above the therapeutic limits for prevention of eclamptic seizures.
Source...