Comparing a 12 versus 24-h postpartum IV magnesium protocol for preeclampsia with severe features at an academic-affiliated community hospital

Abstract

Objective

To compare the safety and efficacy of 12 versus 24-h postpartum magnesium sulfate (MgSO₄) infusion protocol in women with severe preeclampsia.

Methods

This retrospective cohort study analyzed patient outcomes before and after a postpartum magnesium protocol change for cases of severe preeclampsia: 24-h MgSO₄ (Feb–Sep 2021) versus 12-h MgSO₄ (Sep 2021–Feb 2023). The primary outcome was eclampsia; secondary outcomes included magnesium toxicity, maternal complications, postpartum length of stay, ambulation time, and time to Foley catheter removal.

Results

Baseline characteristics were similar. No cases of eclampsia occurred in either protocol. Magnesium toxicity and maternal complications were comparable. Notably, 10 out of the 75 patients in the 12-h protocol required magnesium extension due to persistent preeclampsia symptoms. However, the 12-h protocol was associated with shorter postpartum stay, earlier ambulation, and earlier time to Foley catheter removal.

Conclusion

The 12-h MgSO₄ protocol is as safe and effective as the 24-h protocol. There were no differences in rates of convulsion or negative maternal outcomes between the two protocols.

Keywords

Preeclampsia pregnancy-induced hypertension eclampsia

Introduction

Preeclampsia is a systemic vascular disorder of pregnancy that affects between 5% and 10% of all pregnancies. While the exact pathophysiology remains unclear, preeclampsia is primarily thought to be caused by endothelial dysfunction due to an abnormal release of placental antiangiogenic factors.¹ Such dysfunction manifests as new-onset hypertension, proteinuria, and/or end-organ damage and is a leading cause of morbidity and mortality in mothers and perinates. One rare, life-threatening complication of preeclampsia is eclampsia—a seizure in the setting of preeclampsia and in the absence of known neurologic problems.²

Magnesium sulfate (MgSO₄) is a well-established drug used for seizure prophylaxis in cases of severe preeclampsia. Other anticonvulsants such as diazepam and phenytoin have been studied for the same purpose, but have proven inferior to MgSO₄ in eclampsia prevention.³ The American College of Obstetricians and Gynecologists (ACOG) currently recommends MgSO₄ infusion for 24 h after delivery in their clinical guidelines for eclampsia prophylaxis for patients with severe preeclampsia.⁴ These guidelines, however, do not provide guidance for particular patient populations or different manifestations of severe preeclampsia that could alter this recommendation. Given the limitations of magnesium infusion (e.g. toxicity, side effects, urine monitoring, bed rest), the ideal duration of magnesium infusion is an especially important consideration.⁵

Recent studies support an abbreviated postpartum magnesium infusion protocol to mitigate the undesirable effects of its prolonged use while maintaining the benefit of preventing eclampsia.^6–8 A 2024 meta-analysis reviewed 13 randomized controlled trials that compared the risks and benefits of a shortened course of MgSO₄ versus a traditional 24-h MgSO₄ course following delivery.⁹ The study found that a shortened postpartum MgSO₄ regimen was as effective as a longer 24-h MgSO₄ regimen in seizure prevention and total complications. More studies are needed to increase reliability to change current ACOG guidelines to support a reduced postpartum magnesium duration.

The purpose of the present study is to evaluate the effectiveness and outcomes of a 12 versus 24-h postpartum magnesium infusion protocol in cases of severe preeclampsia at Jefferson Abington Hospital, an academic-affiliated community hospital in Pennsylvania, USA. This hospital is a high-volume and high-acuity tertiary referral center that has over 5000 deliveries per year.

Material and methods

This retrospective cohort study of patients at Jefferson Abington Hospital from 2021 to 2023 compared the clinical efficacy and safety of two intravenous MgSO₄ protocols (12 vs 24-h) for treatment of severe preeclampsia. The 24-h protocol consisted of a default 24-h postpartum magnesium infusion for all patients diagnosed with severe preeclampsia. Following a change in protocol on 21 September 2021, patient outcomes between the original 24-h protocol (February–20 September 2021) and new 12-h protocol (21 September 2021–February 2023) were compared. The 12-h protocol used a default 12-h postpartum magnesium infusion for all patients diagnosed with severe preeclampsia. In the 12-h protocol, patients discontinued magnesium at 12 h if they remained without signs or symptoms of preeclampsia. If signs or symptoms persisted at 12 h, magnesium infusion was extended for a total of 24 h (Table 1). The diagnosis of preeclampsia with severe features was defined according to diagnostic criteria published by ACOG Practice Bulletin No. 222.⁴ Table 2 lists the diagnostic criteria met by each patient. Following a diagnosis, MgSO₄ was administered via infusion pump starting with a 4 g loading dose over 30 min followed by maintenance at 1–2 g per hour depending on kidney function.

Table 1.

Criteria to stop magnesium (12-h protocol)

Absence of persistent severe-range blood pressures

No eclampsia or HELLP syndrome

Patient is asymptomatic

UO ≥ 100 mL/h for previous 2 h

HELLP: hemolysis, elevated liver enzymes, low platelet levels; UO: urine output.

Table 2.

Preeclampsia with severe features diagnosis

Criteria	12-h Protocol	24-h Protocol	p-value
Criteria	N = 75	N = 75	p-value
Severe range blood pressure	66	69	0.68
Preeclampsia with new onset elevated liver enzymes	6	4	0.52
Preeclampsia with new onset headache	2	2	1
Preeclampsia with new onset renal impairment	1	0	1

Epic electronic medical records and ICD-10 codes (O11.9, O14.10, O14.13, O14.14, O14.15) were used to identify and conduct chart review on randomly selected patients with the diagnosis of preeclampsia with severe features prior to delivery (Figure 1). Patients who met criteria for HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, eclampsia, and/or patients who met criteria postpartum were excluded. Patients with HELLP syndrome and eclampsia were excluded because these patients receive 24 h of magnesium postpartum in the 12-h protocol as a standard of care at our institution. Additionally, patients who had incomplete documentation, patients incorrectly coded with severe preeclampsia in Epic and patients readmitted postpartum for severe preeclampsia were excluded. De-identified baseline characteristics and outcome measures were pulled directly from Epic into an Excel document for data collection.

Figure 1.

Patient enrollment flowchart

Convulsion or eclampsia served as the primary outcome. Secondary outcomes were magnesium toxicity and maternal complications. Statistical analysis was conducted using RStudio^® 2021.09.0 Build 351. Student's t-tests were used to compare means of continuous variables. Chi-squared and Fisher's exact tests were used to compare categorical variables. All p-values were two-tailed; p < 0.05 was considered statistically significant. This study was granted exemption from human research ethics review by the Thomas Jefferson University Institutional Review Board (iRISID-2023-1793).

Results

Baseline characteristics of age, race, parity, gestational age at delivery, delivery mode, and BMI were comparable between groups, gravidity differed between groups (Table 3A). Similarly, no significant differences were found in antihypertensive medication use, average blood pressures, hypertension, diabetes mellitus, or renal function (Table 3B). Laboratory indices of urine protein to creatinine and serum AST, ALT, hemoglobin, and platelets were comparable in both groups (Table 4). There were no significant differences in the diagnostic criteria for severe preeclampsia between groups. Most women were diagnosed based on severe-range blood pressures (Table 2).

Table 3A.

Baseline characteristics

Characteristic	12-h Protocol	24-h Protocol	p-value
Characteristic	N = 75	N = 75	p-value
Age (years), M ± SD	30.3 ± 6.1	31.3 ± 4.9	0.28
Body mass index (kg/m², mean+- SD), M ± SD	33.9 ± 8.0	36.5 ± 8.1	0.05
Gestational age at delivery (weeks; mean +-SD), M ± SD	36.3 ± 3.2	36.0 ± 3.0	0.56
Gravidity, N (%)	—	—	0 . 03
1	39 (52)	24 (32)
2–3	28 (37)	43 (57)
≥4	8 (11)	8 (11)
Parity, N (%)	—	—	0.32
0	47 (63)	47 (63)
1	21 (28)	17 (22)
2	3 (4)	7 (9)
3	4 (5)	2 (3)
4	0 (0)	2 (3)
Mode of delivery, N (%)	—	—	0.26
Vaginal	44 (59)	35 (47)
Primary caesarean	22 (29)	25 (33)
Repeat caesarean	9 (12)	15 (20)
Race, N (%)	—	—	0.17
Black	18 (24)	23 (31)
White	35 (47)	38 (51)
Hispanic	13 (17)	11 (15)
Asian	9 (12)	2 (2)
Unknown	0 (0)	1 (1)

Table 3B. Baseline characteristics
Characteristic	12-h Protocol	24-h Protocol	p-value
Characteristic	N = 75	N = 75	p-value
Antepartum admittance, N (%)	12 (16)	18 (24)	0.31
Average systolic BP on admission, mmHg, mean ± SD	148.8 ± 15.7	151.2 ± 20.9	0.42
Average diastolic BP on admission, mmHg, mean ± SD	89.7 ± 10.3	89.4 ± 11.5	0.88
Chronic hypertension, N (%)	7 (9.3)	13 (17.3)	0.23
Diabetes (pregestational and gestational), N (%)	18 (24)	17 (22.6)	1
Renal disease, N (%)	1 (0)	0 (0)	1
Anti-hypertensive drug use during pregnancy, N (%)	9 (12)	12 (16)	0.64
IV anti-hypertensives used prior to delivery, N (%)	57 (76)	58 (77.3)	1

SD: standard deviation Bold values indicate statistical significance (p < 0.05).

BP: blood pressure; IV: intravenous; SD: standard deviation

Table 4.

Laboratory Indices

Laboratory Index	12-h Protocol	24-h Protocol	p value
Laboratory Index	N=75	N=75	p value
Admission Urine P:C (mg/mmol), M ± SD	107.5 ± 237.6	146.9 ± 316.7	0.42
Peak ALT (U/L), M ± SD	43.07 ± 79.82	40.72 ± 93.5	0.87
Peak AST (U/L), M ± SD	44.2 ± 44.1	44.07 ± 79.8	0.99
Peak Cr (µmol/L), M ± SD	69 ± 23	65 ± 12	0.21
Nadir Hb (g/L), M ± SD	99 ± 16.3	96 ± 14.0	0.19
Nadir Platelet (10⁹/L), M ± SD	208.3 ± 55.0	222.8 ± 54.7	0.11

P:C= Protein to Creatine Ratio, ALT= Alanine Transaminase, AST= Aspartate Transaminase, Cr= Creatinine, Hb= Hemoglobin

Shortening MgSO₄ infusion from 24 to 12 h showed no difference in rates of postpartum eclampsia or negative maternal outcomes (magnesium toxicity, oliguria, pulmonary edema, readmission). In fact, shorter magnesium infusion led to several benefits: significantly reduced total postpartum inpatient time, time to ambulation, and time to Foley catheter removal (Table 5). Of note, however, 10 patients (out of 75) in the 12-h protocol needed to extend magnesium treatment for a total of 24 h due to persistent signs or symptoms of preeclampsia (Table 1).

Table 5.

Patient outcomes

Outcome	12-h Protocol	24-h Protocol	p-value
Outcome	N = 75	N = 75	p-value
Magnesium toxicity, N (%)	3 (4)	1 (1)	0.62
Need to extend magnesium treatment, N (%)	10 (13.3)	0 (0)	<0.01
Oliguria, N (%)	4 (5.3)	1 (1)	0.37
Postpartum eclampsia, N (%)	0 (0)	0 (0)	1
Pulmonary edema, N (%)	1 (1)	1 (1)	1
Readmission, N (%)	1 (1)	0 (0)	1
Time to ambulation (hours), M ± SD	14.4 ± 4.3	25.1 ± 0.6	<0.01
Time to foley catheter removal (hours), M ± SD	13.4 ± 4.3	24.1 ± 0.6	<0.01
Total postpartum inpatient time (hours), M ± SD	64.1 ± 19.9	80 ± 25.9	<0.01

M: mean; N: number; SD: standard deviation Bold values indicate statistical significance (p < 0.05).

Discussion

MgSO₄ therapy for the prophylaxis and treatment of eclampsia is cited as one of the 56 essential evidence-based interventions that could potentially eliminate the untimely deaths of 358,000 women and 7.6 million children in low- and middle-income countries.¹⁰ The drug currently appears on 50% of the essential medicine lists from 89 countries and has recently been included as one of 13 essential commodities in the UN Commission on Essential Drugs for Maternal and Child Health.^11,12 Despite global consensus about its effectiveness and safety, clinicians in many countries continue to demonstrate reluctance to use the drug in their management of patients with severe preeclampsia or eclampsia. Concerns have been raised about adverse side effects, toxicity, and the resources needed to monitor patients on magnesium.¹³ Many low- and middle-income countries may change their practice to include IV magnesium if large obstetric and gynecologic associations in developed countries such as ACOG support a shortened duration of treatment.

In the present study, MgSO₄ administration as a 12-h protocol after delivery was as effective as a 24-h protocol in preventing the primary outcome of eclampsia in 75 women with severe preeclampsia. Furthermore, benefits of a 12-h protocol apart from clinical efficacy compared to the 24-h protocol include: shorter duration of bedrest, faster time to ambulation, shorter duration of adverse side effects and potential for magnesium toxicity, shorter duration of needing hospital staff for close monitoring (e.g. magnesium checks) and interventions. This current study supports and increases the reliability of the meta-analysis conducted by RS Shaheen (2024) and recent randomized controlled trials by TK Beyuo (2022) and Farahani (2022), which demonstrated an equivalent safety of a shortened 12-h postpartum magnesium protocol compared to a 24-h protocol for treatment of severe preeclampsia.^6,9,14 These studies examined patient populations across Brazil, Egypt, Ghana, India, Iran, and Pakistan. Our study is the first to evaluate the efficacy of a shortened magnesium protocol for patients with severe preeclampsia in a North American population.

While the 12-h protocol examined in this study was found to be safe, this study did not have sufficient power to assess the frequency of eclampsia. Two systematic reviews by Witlin (1998) and Duley (2010) reported an approximately 0.9% incidence of eclampsia in patients with severe preeclampsia treated with 24 h of MgSO₄.^3,13 Therefore, to detect a 25% reduction in the incidence of eclampsia with 80% statistical power and a two-sided p-value of 0.05, a sample of approximately 24,000 patients per group would be required. Larger future studies are needed to provide the statistical power to compare the safety of both regimens. These investigations should not only assess the efficacy and safety of shorter regimens compared to the traditional 24-h protocol, but also comprehensively evaluate potential nonclinical benefits (e.g. cost reduction¹⁵ and improved hospital resource utilization). Future studies should also prioritize stratifying patients based on their individual needs: which patients need a 24 h duration of MgSO₄ and which patients may use a reduced duration.

Strengths/limitations

Strengths of this study include its diverse patient population, which enhances the generalizability of our findings. Approximately 49% of patients in our study were White, 27% Black, 17% Hispanic, and 7% Asian. Additionally, baseline characteristics were largely similar between groups. However, this study is limited by a lack of statistical power given its small sample size and limited by its retrospective single-center design. Readmission rates may also be underestimated due to potential readmissions to external hospitals.

Conclusion

This retrospective cohort study comparing a 12 versus 24-h postpartum MgSO₄ protocol in cases of severe preeclampsia showed no differences in rates of convulsion or negative maternal outcomes. The 12-h protocol led to several benefits including reduced postpartum inpatient time, faster time to ambulation, and faster time to Foley catheter removal. While these findings support recent studies favoring abbreviated magnesium protocols, larger, adequately powered studies are needed to confirm these results.

Footnotes

ORCID iDs

Jordan Beacham

Orchideh Alexander

Ethical approval

This study was approved by the Thomas Jefferson University Institutional Review Board (IRB) as IRB-exempt.

Contributorship

The primary authors of this article are Jordan Beacham and Orchideh Alexander under the supervision of the principal investigator, Stephen Smith.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

Orchideh Alexander.

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