Increasing Uptake and Correct Administration of Magnesium Sulfate for Management of Severe Preeclampsia and Eclampsia Susheela M. Engelbrecht Mini University.

Increasing Uptake and Correct Administration of Magnesium Sulfate for Management of Severe Preeclampsia and Eclampsia

Susheela M. Engelbrecht

Mini University

Washington, DC

March 2, 2015

This presentation was adapted from a presentation created and presented at the ICM in Prague under MCHIP

Objectives

At the end of the workshop, participants will be able to: Describe new WHO guidelines for management of severe pre-

eclampsia and eclampsia, including the recommended regimen for MgSO4

Describe new findings on prevalence of magnesium toxicity Describe job aids to assist providers to correctly administer MgSO4 Describe a simple monitoring tool for women being treated with

MgSO4 Describe measures to implement to increase access to MgSO4

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Price of preeclampsia and eclampsia

A woman in a developing country: Is 7 times more likely to develop PE (2.8% of live births)

than in developed countries (0.4% of live births). Is 3 times more likely to progress to eclampsia If she

develops PE (2.3% of pre-eclamptic women in the developing world compared with 0.8%).

Is up to 14 times more likely to die of eclampsia should she develop it—even in hospital settings.

Has an approximately 300 times higher risk of dying of PE and eclampsia than a woman in a developed country.

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Time of eclampsia occurrence

Approximately 38 to 55% of all cases of eclampsia occur antepartum

13-36% occur intrapartum 5-39% occur within the first 48 hours following

childbirth 5-17% occur greater than 48 hours postpartum

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MgSO4 – An important pillar of management

Comprehensive management of women with severe PE and eclampsia should include: Anticonvulsant drugs Antihypertensive drugs, and Timed childbirth

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We are only focusing on MgSO4 today.

Aspirational goals

All women with severe preeclampsia receive MgSO4 for prevention of eclamptic seizures.

MgSO4 is administered as soon as possible after the first eclamptic seizure, wherever that occurs, to prevent recurrent fits.

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Photo credit: Susheela Engelbrecht

Two randomized control trials provided the scientific evidence needed to promote MgSO4 as the anticonvulsant of choice for the treatment of severe preeclampsia and eclampsia:

o The Collaborative Eclampsia Trial for women with eclampsia (1995).

o The Magnesium Sulfate for Prevention of Eclampsia (MAGPIE) Trial for women with preeclampsia (2002).

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Evidence for using MgSO4

Current situation

Despite its endorsement by WHO and its presence on most essential medicines lists, MgSO4 is still:

Underutilized; Incorrectly administered; or Unavailable in many low-resource settings

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Barriers to uptake of MgSO4

Low coverage of MgSO4 for management of severe preeclampsia and eclampsia is due to a combination of factors: Restrictive policies Supply/Logistics issues Provider factors

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Photo: PATH/Evelyn Hockstein

Barriers to uptake of MgSO4 : Policy

Administration may be limited to:

- MDs - Comprehensive emergency obstetric and

newborn care facilities Clinical protocols may not include MgSO4 as

the anticonvulsant of choice for treatment of severe PE/E

Clinical protocols may only recommend MgSO4 for “imminent” eclampsia or eclampsia

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Barriers to uptake of MgSO4 : Multiple product presentations of MgSO4

Available presentations:• 1% (10 mg/mL)• 2% (20 mg/mL)• 10% (100 mg/mL)• 15% (150 mg/mL)• 20% (200 mg/mL)• 50% (500 mg/mL)

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Photo: PATH/Evelyn Hockstein

Barriers to uptake of MgSO4 : Complex dosing

The current regimen is complex and requires: Different dilutions for initial intravenous (IV) loading

dose (20%), IV additional dose for recurrent seizures after loading dose (50%), and intramuscular (IM) doses (50%):

o Requires calculating the amount of diluent to add to the solution to get the correct dilution.

Different doses for:

o IV and IM doses.o Loading and maintenance doses.

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Barriers to uptake of MgSO4 : Confusing data on MgSO4 dosing

Published dosage regimens for MgSO4 vary widely

There does not appear to be a clear threshold concentration for ensuring the prevention of convulsions

Timing of drug discontinuation has been arbitrary; there are no high quality data to guide therapy

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Barriers to uptake of MgSO4 : Perception of risk of magnesium toxicity

Providers may be reluctant to administer maintenance dosing because of fear of toxicity.

Administering maintenance dosing requires careful monitoring which may be difficult when there are shortages of qualified health care providers.

Providers may have difficulty remembering signs of toxicity and how to assess for them.

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Provider Reluctanc

e

• Review of literature shows very few cases of toxicity.

• Toxicity mostly related to medication errors or in cases of renal insufficiency.

Evidence

Barriers to uptake of MgSO4 : Preference for IM injections

Most high resource settings administer MgSO4 by continuous IV perfusion

In many low resource settings, however, IM dosing is favored because: Pump devices that facilitate continuous IV infusion of

MgSO4 may not be available or may not be reliable IM injections are relatively safer than continuous IV

infusions in settings that do not have pumps to control the IV infusion

All providers administering MgSO4 may not be competent/comfortable to do so by continuous IV infusion

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Barriers to uptake of MgSO4 : Pain of IM injections

Complaints of pain and side effects during IM injections may negatively influence: A health care provider’s decision to initiate or continue

treatment A patient’s acceptance of ongoing treatment

The repeated IM maintenance injections could potentially lead to development of abscess

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Any other barriers to uptake of MgSO4 that you have

experienced??

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There are four key opportunities for increasing uptake of MgSO4

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4- Increase provider

confidence and comfort

1- Develop enabling policies

3- Develop simplified regimen

to reduce complexity

2 – Improve product

presentation

Photo: Susheela Engelbrecht

1 – Develop enabling policies: MgSO4

MgSO4 included in clinical protocols: Anticonvulsant recommended for all women with

severe PE and eclampsia MgSO4 listed as the first-line anticonvulsant for

management of severe PE/E Use of MgSO4 not limited to CEmONC facilities

All skilled maternal care providers authorized to diagnose severe PE/E and administer MgSO4

Consider task shifting at least the initial dose to cadres working in the community

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1 – Develop enabling policies: Task shift

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Task shifting administration of initial dose of MgSO4 to community- or peripheral facility-based providers will lead to:

• Increased uptake of MgSO4. Increased

Uptake

Reduced Mortality

Timely administration • Earlier administration of MgSO4.

• Prevention of eclampsia and recurrent fits.• Reduced mortality (perinatal / maternal).

1 – Develop enabling policies: Include MgSO4 for treatment of severe PE/E in NLEM

• Include MgSO4 for treatment of severe PE/E on national list of essential medicines

• Only register WHO-recommended presentations of MgSO4 :- 500 mg/mL in 2‐mL ampoule

(50%)- 500 mg/mL in 10‐mL

ampoule (50%)

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1 – Develop enabling policies: Include MgSO4 in HMIS

Monitor: Availability of MgSO4 at the MOH medical store /

health care facilities Cases of severe PE/E Uptake of MgSO4 Deaths attributed to severe PE/E

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1 – Develop enabling policies: Quality improvement initiatives

Maternal death reviews: Number of women who died from severe PE/E who

did not receive MgSO4

Chart audits Review management of women with severe PE/E

Performance standards for management of severe PE/E

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Any other recommendations to improve policy environment?

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2 - Improve product presentation

Develop package(s) with the correct strengths of MgSO4 for loading and maintenance doses with an appropriate identification (e.g., color coding).

There is ongoing work under the UN Commission on Life-Saving Commodities for Women and Children (UNCoLSC) recommendation 10 to revise product presentation.

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3 - Develop simplified regimen to reduce complexity

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Simplified regimen will lead to:

• Increased uptake of a safe, effective dosing regimen of MgSO4.

• Reduced mortality (perinatal/maternal).

Increased Uptake

Reduced Mortality

Simplified MgSO4 regimen

Study in India used 50% solution for loading and continuous maintenance IV infusion.

Loading dose only regimen for treatment of eclampsia Approximately 10 percent of eclamptic women will have

repeated seizures if managed expectantly. Some researchers observed that many patients with eclampsia

who did not receive maintenance therapy due to suspicion/fear of toxicity or stockouts of MgSO4 did not convulse any further

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Any other recommendations to improve product presentation / dosing?

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4 – Increase provider confidence and comfort: Computer animation tool

Includes a tool where the learner can enter any concentration of MgS04 and determine the appropriate preparation and administration

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4 – Increase provider confidence and comfort: Use of apps to assist with dosing

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• Interactive mobile phone application guides providers through the steps for safe preparation and administration using the current WHO protocol.

• Based on demand, it can be revised for country-specific dosing regimens and translated into other languages.Photo: PATH

4 – Increase provider confidence and comfort: Use checklists to guide administration of MGSO4

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Checklists:

• Break down complex tasks into steps.

• Facilitate standardization of procedures.

• Provide prompts / reminders for students and veteran providers.

• Can be used for training and quality improvement initiatives.

4 – Increase provider confidence and comfort: Use simple tools to monitor women receiving MGSO4

• Contains all parameters to be monitored

• Provides space for administration of medications

• Provides a “snapshot” of the woman and baby’s conditions

• Currently being evaluated in both basic and comprehensive emergency obstetric care facilities in sub-Saharan African countries

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4 - Increase provider confidence and comfort: Develop simplified delivery mechanisms

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Mundle et al, 2012

Any other recommendations to improve provider competence / comfort with

administering MgSO4 ?

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Unite!!

Together we can make a difference and ensure that every woman who needs

MgSO4 receives it in a safe, timely manner.

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Comments?

Questions?

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Materials

Computer animation tool Checklists LIVKAN Chart Suggested indicators for M&E of programs

to detect and treat severe PE/E

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Thank you!

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Photo credit: Susheela Engelbrecht

For more information, please contact Susheela Engelbrecht

([email protected])

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References

Anonymous. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. 1995, 345(8963):1455–1463.

Altman D, Carroli G, Duley L, Farrell B, Moodley J, Neilson J, Smith D; Magpie Trial Collaboration Group. Do women with preeclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002, 359(9321):1877–1890.

Ameh CAM, Ekechi CI, Tukur J. Monitoring Severe Pre-Eclampsia and Eclampsia Treatment in Resource Poor Countries: Skilled Birth Attendant Perception of a New Treatment and Monitoring Chart (LIVKAN Chart). Matern Child Health J (2012) 16:941–946. DOI 10.1007/s10995-011-0832-7.

Begum MR, Begum A, Quadir E. Loading dose versus standard regime of magnesium sulfate in the management of eclampsia: a randomized trial. Journal of Obstetrics and Gynaecology Research. 2002;28:154–9.

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References

Ekele, BA, Muhammed D, Bello LN, and Namadina IM. Magnesium sulphate therapy in eclampsia: the Sokoto (ultra short) regimen. BMC Research Notes 2009, 2:165 doi:10.1186/1756-0500-2-165.

• Engender Health. Balancing the Scales: Expanding Treatment for Pregnant Women with Life-Threatening Hypertensive Conditions in Developing Countries, a Report on Barriers and Solutions to Treat Preeclampsia & Eclampsia. New York: EngenderHealth; 2007. Available at: http://www.engenderhealth.org/files/pubs/maternal-health/EngenderHealth-Eclampsia-Report.pdf.

Mundle S, Regi A, Easterling T, Biswas B, Bracken H, Khedekar V, Shekhavat DR, Durocher J, Winikoff B. Treatment approaches for preeclampsia in low-resource settings: A randomized trial of the Springfusor pump for delivery of magnesium sulfate. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health. 2012;2:32–38.

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References

Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Memorial Hospital protocol for treatment of eclampsia: evaluation of 245 cases. Am J Obstet Gynecol. 1984;148(7):951.

Regmi MC, Aggrawal A, Pradhan T, Rijal P, Subedi Aand UpretyD. Loading dose versus standard regimen of magnesium sulphate in eclampsia – a randomized trial. Nepal Med Coll J. 2010; 12(4): 244-247.

Seth S, Nagrath A, Singh DK. Comparison of low dose, single loading dose, and standard Pritchard regimen of magnesium sulfate in antepartum eclampsia. Anatol J Obstet Gynecol. 2010; 1:1.

Shoaib T, Khan S, Javed I, Bhutta SZ. Loading dose of magnesium sulphate versus standard regime for prophylaxis of pre-eclampsia. J Coll Physicians Surg Pak. 2009 Jan;19(1):30-3.

• Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402.

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References

Smith JM, Lowe RF, Fullerton J, Currie S, Harris L, Felker-Kantor E. An integrative review of the side effects related to the use of magnesium sulfate for preeclampsia and eclampsia management. BMC Pregnancy and Childbirth. 2013, 13:34.

Tuffnell DJ, Jankowicz D, Lindow SW, Lyons G, Mason GC, Russell IF, Walker JJ, Yorkshire Obstetric Critical Care Group. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG. 2005;112(7):875.

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