Eclampsia and Role of Magnesium Sulfate

SUMMARY:  

Eclampsia is a severe, life-threatening manifestation of preeclampsia.  While long-term neurologic damage is rare, there is risk of maternal hypoxia and death. Most women will experience signs such as headaches or visual changes prior to a seizure.

Eclampsia

• Defined as convulsions during pregnancy and/or postpartum
  • Tonic-clonic, focal, or multifocal
  • New onset
  • Unexplained by other neurologic pathology
• Consider other underlying cerebral conditions when
  • Seizures occur 2 to 3 days postpartum
  • Patient on magnesium sulfate

Note: Not all women will demonstrate classic features of preeclampsia (hypertension, proteinuria)

Magnesium Sulfate – How to Use  

• Magnesium sulfate is the treatment of choice for seizure prophylaxis (ACOG recommended dosing) 
  • Loading dose of 4–6 g of magnesium sulfate administered per infusion pump over 20–30 minutes (i.e., slowly) followed by a maintenance dose of 1-2 g per hour as a continuous intravenous infusion  
  • Continue 24 hours postpartum
• Recurrent seizures
  • Additional dose of 2-4 g can be infused over 5 minutes
• Refractory seizures
  • Sodium amobarbital: 250 mg IV in 3 minutes
  • Thiopental or phenytoin: 1,250 mg IV at a rate of 50 mg/minute
  • Patient should be managed in ICU
  • Consider neuroimaging
• IM option
  • 10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
  • Use if IV access limited
  • Mix with 1 mL xylocaine 2% to alleviate pain

Note: Magnesium sulfate should not be considered an antihypertensive agent

Magnesium Sulfate – When to Use

• Severe features of preeclampsia 
  • Administer to all women 
• No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg 
  • There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
  • ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy” 

Delivery and Postpartum 

• Vaginal delivery
  • Continue infusion 24 hours postpartum
• Cesarean
  • Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
  • Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended

 Prevention of Magnesium Sulfate toxicity 

• Place Foley to monitor renal function (hourly output)  
• Confirm normal serum creatinine  
• Serial evaluation of patellar deep tendon reflexes 
• Monitor respiratory rate  
• Serum magnesium levels not routinely required
  • Monitor serum magnesium levels in setting of renal dysfunction and/or absence of patellar reflexes 
  • Maintain serum concentrations 5 to 9 mg/dL (4–7 mEq/L) range  
• Predictive symptoms of magnesium sulfate toxicity  
  • Loss of deep tendon reflexes >9 mg/dL (greater than 7 mEq/L)  
  • Respiratory depression >12 mg/dL (greater than 10 mEq/L) 
  • Cardiac arrest >30 mg/dL (greater than 25 mEq/L) 

Pending toxicity 

• Notify appropriate health care provider  
• Discontinue magnesium infusion  
• Administer supplemental oxygen  
• Obtain a serum magnesium level  
• Reverse magnesium 
  • 10 mL of 10% calcium gluconate IV (1 g total) and over 3 min (i.e., slowly) to avoid hypotension and/or bradycardia 
  • Calcium effect (competitively inhibits magnesium at neuromuscular junction) can wear off if magnesium level stays high 
  • Furosemide may help increase urinary excretion
• Respiratory arrest: Intubation and assisted ventilation as indicated

Other Prophylactic Agents

• Magnesium sulfate is superior to diazepam, phenytoin and lytic cocktail (chlorpromazine, promethazine, pethidine) in reducing significantly the risk of seizure recurrence  
  • Cochrane Review 2010: Magnesium sulfate reduced eclampsia compared to phenytoin (relative risk 0.08, 95% CI 0.01 to 0.60)   
• Morbidity related to pneumonia, mechanical ventilation and admission to an intensive care unit are significantly reduced with the use of magnesium sulfate compared with phenytoin  
• Magnesium sulfate does not cause maternal or newborn CNS depression 
  • Diazepam or lorazepam does stop or shorten seizures, but risk of maternal apnea and/or cardiac arrest
• Diazepam and phenytoin may be considered if
  • Patient on these medications to treat epilepsy
  • Magnesium sulfate is contraindicated
    • Myasthenia gravis | Hypocalcemia | Moderate-to-severe renal failure | Cardiac ischemia | Heart block | Myocarditis

Learn More – Primary Sources:

National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period 

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

Management of pre-eclampsia: issues for anaesthetists 

Acute pulmonary oedema in pregnant women 

Cochrane Review: Magnesium sulphate and other anticonvulsants for women with pre-eclampsia 

Emergency Treatment for Severe Hypertension in Pregnancy

Summary:

Severe hypertension can be a life-threatening event during pregnancy and requires special vigilance in the postpartum period, particularly following hospital discharge. The goal of treatment is to control hypertension and prevent seizures.  Uncontrolled hypertension can lead to heart failure, myocardial ischemia, renal injury and stroke.

When to Treat:

Urgently treat acute onset severe hypertension in pregnancy or postpartum period

• SBP ≥160 and and/or DBP ≥110 mm Hg persisting for 15 minutes
  • systolic BP a predictor of maternal morbidity/mortality

First Line Therapy:

Nifedipine

Hydralazine

Labetalol

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Immediate Release Oral Nifedipine

Onset

• 5 to 10 minutes

Administration

• 10 to 20 mg orally
• Repeat in 20 minutes if needed
• Then 10 to 20 mg every 2 to 6 hours
• Maximum dose: 180 mg

Medication Risks

• Maternal tachycardia and headaches

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IV Hydralazine

Onset

• 10 to 20 minutes

Administration

• IV
  • 5  to 10 mg IV (or IM)
  • Then 5 to 10 mg IV every 20 to 40 minutes
• Infusion
  • 0.5 to 10 mg/hr
• Maximum dose: 20 mg

Medication Risks 

• Maternal hypotension and headaches
• Abnormal FH tracings

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IV Labetalol

Onset

• 1 to 2 minutes

Administration 

• IV
  • 10 to 20 mg IV
  • Then 20 to 80 mg every 10 to 30 minutes
• Infusion
  • 1 to 2 mg/min
• Maximum dose: 300 mg

Medication Risks 

• Avoid in the following clinical settings
  • Asthma
  • Preexisting myocardial disease | Decompensated cardiac function | Heart block | Bradycardia

Note: ACOG states that “any of these agents can be used to treat acute severe hypertension in pregnancy” | An approach detailed in ACOG guidance uses “an initial regimen of labetalol at 200 mg orally every 12 hours and increase the dose up to 800 mg orally every 8–12 hours as needed (maximum total 2,400 mg/d). If the maximum dose is inadequate to achieve the desired blood pressure goal, or the dosage is limited by adverse effect, then short-acting oral nifedipine can be added gradually”

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Seizure Prophylaxis: Magnesium Sulfate

• Remains drug of choice for seizure prophylaxis
• Magnesium sulfate should not be used to reduce blood pressure
• See more on magnesium sulfate in ‘Related ObG Topics’

When to Use

• Severe features of preeclampsia
  • Administer to all women
• No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg
  • There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
  • ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy”

Delivery and Postpartum

• Vaginal delivery
  • Continue infusion 24 hours postpartum
• Cesarean
  • Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
  • Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended

Administration

• Loading dose of 4 to 6 g administered per infusion pump over 20 to 30 minutes (i.e., slowly) followed by a maintenance dose of 1 to 2 g per hour as a continuous intravenous infusion
• IM option if IV access limited
  • 10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
  • Mix with 1 mL xylocaine 2% to alleviate pain

Learn More – Primary Sources:

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

ACOG II Severe Hypertension in Pregnancy Bundle

FIGO: A literature review and best practice advice for second and third trimester risk stratification, monitoring, and management of pre-eclampsia

Aspirin Treatment for Women at Risk for Preeclampsia – ACOG, SMFM and USPSTF Recommendations

FINDINGS:

ACOG/SMFM have released guidance aligned with USPSTF regarding the use of low-dose aspirin during pregnancy to prevent preeclampsia.  When indicated, low-dose aspirin should be started between 12 to 28 weeks and continued until delivery.  Optimally, aspirin usage should begin <16 weeks.

Recommended (high risk)

• Offer low-dose aspirin (81 mg/day) to women with ≥1 high risk factors
  • History of preeclampsia, especially if accompanied by an adverse outcome
  • Multifetal gestation
  • Chronic hypertension
  • Diabetes (Type 1 or Type 2)
  • Renal disease
  • Autoimmune disease (for example, systematic lupus erythematosus, antiphospholipid syndrome)

Moderate Risk Factors

• Offer low-dose aspirin (81 mg/day) to women with ≥2 moderate risk factors
  • Nulliparity
  • Obesity (BMI >30)
  • Personal history
    • Low birthweight or SGA
    • Previous adverse pregnancy outcome
    • >10-year pregnancy interval
  • Family history of preeclampsia
    • Sister or mother
  • Social and demographic characteristics
    • Black race (as a proxy for underlying racism)
    • Lower income
    • Maternal age ≥35 years
  • IVF

Note: USPSTF does allow for consideration of aspirin prophylaxis if ≥1 moderate risk factor is present and states “Clinicians should use clinical judgment in assessing the risk for preeclampsia and discuss the benefits and harms of low-dose aspirin use with their patients”

Universal Implementation

• Evidence supports a risk-based approach
• ACOG/SMFM acknowledges that in some settings, a majority of patients will fall in to either high or moderate risk categories, and therefore

In these instances, universal implementation (eg, offering low-dose aspirin to all patients within such practices or institutions) may be medically reasonable

Not Recommended Without Preeclampsia Risk Factors

• Low risk: Previous uncomplicated full-term delivery
• Insufficient Evidence
  • Prior unexplained stillbirth (insufficient evidence)
  • Prevention of fetal growth restriction
  • Prevention of spontaneous PTB
• No Benefit
  • Prevention of early pregnancy loss

USPSTF Guidance

• The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia as per categories above (B recommendation – offer or provide this service)

Benefits

• The most recent systematic evidence review (see ‘Learn More – Primary Sources) provided more precise estimate of the association between aspirin and the prevention of perinatal mortality (4% to 44% reduction in fetal and neonatal deaths)
• Otherwise, benefits of low-dose aspirin for women at risk for preeclampsia were similar to previous reviews with lower risks for the following (moderate certainty)
  • Preeclampsia: Pooled relative risk (RR) 0.85 (95% CI, 0.75-0.95)
  • Perinatal mortality: Pooled RR 0.79 (95% CI, 0.66-0.96)
  • Preterm birth: Pooled RR 0.80 (95% CI, 0.67-0.95)
  • Intrauterine growth restriction: Pooled RR 0.82 (95% CI, 0.68-0.99)

Harms

• No significant association was found for
  • PPH or other bleeding-related harms
  • Rare perinatal or longer-term harms
• Long-term child developmental outcomes in offspring from in utero exposure to low-dose aspirin
  • Follow-up data from the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), found no differences in physical or developmental outcomes at 12 to 18 months

KEY POINTS:

• Risk factors used for ACOG/SMFM recommendations only include factors obtained from the medical record
  • Uterine artery Doppler ultrasonography and biochemical markers are not included
  • ACOG/SMFM acknowledge that other studies, in particular the ASPRE trial (see ‘Related ObG Topics’ below), have incorporated ultrasound and maternal serum markers as well as doses >81 mg, but state

Further, the screening algorithm used includes first-trimester serum markers, including placental growth factor and pregnancy-associated plasma protein-A, as well as uterine artery dopplers, which limits the generalizability to a U.S. population. Therefore, a higher dose or doubling of the available 81-mg dose cannot be recommended at this time.

Screening for Preeclampsia

• USPSTF
  • Recommends that blood pressure measurements should be obtained during each prenatal care visit throughout pregnancy
  • Does not find evidence to support routine use of point-of-care urine protein tests for preeclampsia screening
• Various studies have incorporated not only clinical risk factors but also biochemical markers and ultrasound to determine which women are at risk for early onset preeclampsia and may benefit from aspirin prevention (see ‘Related ObG Topics’)
• ACOG/SMFM considers the supporting data for the use of such combined risk assessment algorithms to be limited and without more prospective clinical utility trials, states that

…biomarkers and ultrasonography cannot accurately predict preeclampsia and should remain investigational.

Learn More – Primary Sources:

ACOG Practice Advisory: Low-Dose Aspirin Use for the Prevention of Preeclampsia and Related Morbidity and Mortality

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia 

USPSTF: Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality

USPSTF: Screening for Hypertensive Disorders of Pregnancy

USPSTF: Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

ACOG/SMFM Committee Opinion 743: Low-Dose Aspirin Use During Pregnancy

SMFM: Prophylactic low-dose aspirin for preeclampsia prevention—quality metric and opportunities for quality improvement