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 – Seizure Prophylaxis  

• 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 

Diagnosing Preeclampsia – Key Definitions and ACOG Guidelines

WHAT IS IT?

Preeclampsia is a pregnancy specific hypertensive disease with multi-system involvement. It usually occurs after 20 weeks of gestation and can be superimposed on another hypertensive disorder. While preeclampsia was historically defined by the new onset of hypertension in combination with proteinuria, some women will present with hypertension and multisystemic signs in the absence of proteinuria. The presence of multisystemic signs is an indication of disease severity.

SUMMARY:

Diagnostic Criteria

Blood Pressure Criteria

• Hypertension – systolic BP > 140 mm hg or diastolic BP > 90 mm hg or both
  • On two occasions at least 4 hours apart after 20 weeks gestations with previously normal BP
  • Considered ‘mild’ until diastolic BP > 110mm hg or systolic BP ≥160 mm Hg
• Severe Hypertension – systolic BP > 160 mm hg or diastolic BP > 110 mm hg or both
  • Can confirm using a short time interval (e.g., minutes) to facilitate timely antihypertensive therapy

Note: Gestational Hypertension

• ACOG defines gestational hypertension as “hypertension without proteinuria or severe features develops after 20 weeks of gestation and blood pressure levels return to normal in the postpartum period”
• Caution and close follow-up is warranted as up to a half of women with gestational hypertension will go on to manifest signs an symptoms consistent with preeclampsia
• Women with severe gestational hypertension, even in the absence of proteinuria should be managed similar to women with severe preeclampsia
• ACOG states

Women with gestational hypertension with severe range blood pressures (a systolic blood pressure of 160 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher) should be diagnosed with preeclampsia with severe features.

Proteinuria Criteria

• 24 hour urine collection >300 mg protein or
• Single voided urine protein/creatinine ratio ≥0.3
• Dipstick reading of 2+ (use only if other quantitative methods not available)

Preeclampsia Definitions

Preeclampsia

• Hypertension and proteinuria or
• In absence of proteinuria, new-onset hypertension with the new onset of any of the following
  • Thrombocytopenia: Platelets <100 x 10⁹/L
  • Renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
  • Impaired liver function: Elevated blood concentrations of liver transaminases to twice normal concentration
  • Pulmonary edema
  • Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms

Preeclampsia with severe features

• Preeclampsia diagnosis, above, with any of the following
  • Severe hypertension
    • On two occasions at least 4 hours apart while on bed rest (unless already on antihypertensive therapy)
  • Thrombocytopenia: Platelets <100 x 10⁹/L
  • Impaired liver function (without an alternative diagnosis): Elevated liver transaminases greater than twice upper limit of normal or severe persistent right upper quadrant or epigastric pain not responsive to medications
  • Progressive renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
  • Pulmonary edema
  • Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms

Note: The following are not diagnostic criteria for the diagnosis of preeclampsia or preeclampsia with severe features

• Clinically evident edema
• Rapid weight gain
• Massive proteinuria
  • Does not qualify as a ‘severe feature’
• Fetal growth restriction
  • ACOG states that while it is important to monitor fetal status, FGR in the setting of all other fetal assessment being within normal limits (e.g., AFV, Doppler), expectant management ‘may be reasonable’ if mother and fetus appear stable and no other clinical indication is present that would indicate the need for early delivery
• Uric acid
  • Hyperuricemia in hypertensive pregnancy is not a diagnostic marker, but is an important finding as a risk factor for adverse maternal and fetal outcomes
    • Small for gestational age (SGA) infant
    • Prematurity
    • Risk for adverse maternal outcomes if include patients with preeclampsia and risks increase with increasing concentration of uric acid
  • May be warranted in the setting of ‘diagnostic dilemmas’ such as diagnosing superimposed preeclampsia in the setting of chronic hypertension

Learn More – Primary Sources

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

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

Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study

Pre-eclampsia: pathophysiology and clinical implications