Safety of Magnesium Sulfate for Management of Severe Pre-Eclampsia and Eclampsia: A practical review of research findings

John E. Varallo, MD, MPH Senior Technical Advisor, FP/RH/MH Jhpiego Jhpiegos Mini-University - June 2013

Integrative Review of PE/E Recently Published in BMC Pregnancy & Childbirth

Why is this Important?

Globally, PE/E is second leading cause of maternal mortality
In developing countries, risk of dying from severe PE/

E is 300x higher than developed countries

Global focus on prevention, detection and management strategies

Magnesium sulfate (MgSO4)

A life-saving drug Anticonvulsant of choice for women with severe PE/E
Reduces risk of developing

eclampsia or suffering recurrent seizures by more than 50%

But MgSO4 is underutilized or used inappropriately in many settings

Barriers to increasing use: Lack of supportive policies Lack of clear, context relevant, based guidelines Lack of standardized MgSO4 Leads to: Provider lack of confidence and competence Safety concerns using MgSO4
5

evidenceformulation

Is MgSO4 a Dangerous Drug?

Side effects and risk of toxicity from magnesium sulfate for severe PE/E management

Fear that MgSO4 is highly toxic

We all know of cases of death due to MgSO4

overdose.
We mustnt let lower level workers use it due to

risk of toxicity
Magnesium sulfate is a dangerous drug! It is

safer to use Diazepam

30

Serum Magnesium Levels

Respiratory/Cardiac Arrest > 25 mEq/L

25

20

Respiratory Depression > 13 mEq/L

15

10

Marker of toxicity: Absent patellar reflex > 8-10 mEq/L

5

Suppression of eclamptic seizures 4 6 mEq/L Normal levels 1.7.- 2.2.

8

Routine Monitoring of MgSO4 Use

Neurologic status (level of alertness and patellar reflexes) Respiratory rate Urinary output (Oliguria is element of disease process) Typical management of more serious side effects: monitoring, delay next dose or suspend MgSO4 therapy, counteraction with calcium gluconate
9

Research Questions
Incidences of signs of toxicity: absent patellar reflex and respiratory depression Frequency of use of the antidote Ca++ gluconate Frequency of skipped or delayed doses of MgSO4 Number of maternal deaths of women with severe PE/E attributed to MgSO4 toxicity
10

Results Overview
Overall Outcome Rates for All Studies: 9556 subjects
Absent Patella Reflex Respi ratory Depressio n 1.3% Skipped Dose Calcium Gluconat e use Oliguria

Incidenc e

1.6%

3.6%

0.2%

2.5%

Only one maternal death reported as due to MgSO4 12 = 0.01%

Estimates of clinical impact

Absent Patellar Reflex
Incidence Number needed to treat 1.6% 61

Respiratory Skipped or Calcium depression delayed dose gluconate use

1.3% 77 3.6% 27 0.18% 555

Scenario: Hospital delivers 5000 women annually. Assuming 5% rate of PE/E, 250 women annually will require MgSO4 in treatment Frequency of 1 case 2.9 months 3.7 months 1.3 months 26.7 months

12

Conclusions: MgSO4 is a safe drug

Findings indicate: Low incidence of severe side effects (1-2%) When adverse effects occur, delaying the next scheduled dose is generally sufficient to mitigate the effect. Maternal mortality directly attributable to use of MgSO4 was extremely rare.

MgSO4 is NOT a dangerous drug

13

Conclusions: Policy and Practice

Severe PE/E should be diagnosed and treated using evidence-based regimens
MgSO4 is anticonvulsant of choice

Reasonable vigilance for side-effects/toxicity

Practical guidelines/protocols should be in place to

monitor for and manage side-effects and toxicity All clinical leaders in maternal health should guide adoption/use of MgSO4 as standard of care
Including ensuring adequate supply and standard

formulation of MgSO4
14

Thank you!
Questions/Comments