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Developing a guideline for severe pre-eclampsia


Sherry Wright
BPharm(Hons) MSc
Lead Directorate
Reproductive Health
Royal Infirmary of Edinburgh,
E:[email protected]

Our strategy has been to deliver consistent evidence-based care by utilising locally produced and ratified guidelines,(1) especially in situations that involve high-risk patients and unlicensed medicines. A standard template for guideline production has evolved, enabling a standardised approach to pharmaceutical care issues. Guidelines are intended to be user-friendly, accessible, amenable to audit and pragmatic (cross-referenced to other relevant guidelines within the directorate).

Guidelines are ratified by a multidisciplinary group, and independent evaluation is performed before development. It is encouraging to find regular use of the guideline within clinical practice and improvements in care as a result.(2) Access is made easier by an intranet system and the incorporation of guidelines into integrated care pathways. This article highlights our guideline development strategy by sharing some of the key issues involved in a recent update of the “Magnesium sulphate in severe pre-eclampsia” guideline.

Choice and content of guidelines
Selection of an area for guideline development is determined according to the severity of a condition and the risks associated with its management. The request for a guideline is made to the clinical improvement programme (CLIP) group, a multidisciplinary forum where all clinical governance issues within the directorate are addressed. Audit is usually incorporated as appropriate. The template guideline incorporates an introduction/background, indication, clinical presentation and symptoms (if relevant), pretreatment monitoring, contraindications, dosage and administration, documentation, side-effects, interactions, references, audit, who ratified the guideline, and date of production/review. Information is provided in a concise form with standalone appendices to provide greater detail where appropriate.

Background for the guideline
Severe pre-eclampsia continues to be a cause of maternal and fetal mortality. Several treatment strategies have been tried to prevent and manage it with varying degrees of success.(3,4) Increasing evidence on the benefits of magnesium sulphate in the management of preeclampsia led to its introduction into clinical practice.(3) The recent MAGPIE trial confirmed that magnesium sulphate can reduce the risk of placental abruption and eclampsia in women with pre-eclampsia.(5) Its place in clinical practice has the support of WHO, UNFPA, UNICEF and the World Bank.(6) Although serious sideeffects are rare, the risk of respiratory and cardiovascular arrest posed grave concerns.(3,4) A guideline was produced to direct practice and optimise this unlicensed yet well-established use of magnesium sulphate.

Following discussion of the treatment indications used in the MAGPIE trial, it was decided that the following definitions of severe pre-eclampsia determine the need for treatment within 24 hours, after discussion with a consultant:

  • Diastolic >100mmHg and systolic >150mmHg (on two occasions) and proteinuria >3+, or
  • Diastolic >90mmHg and systolic >140mmHg (on two occasions) and proteinuria >1+ plus the presence of two or more of the following: severe frontal headaches, visual disturbances, hyperreflexia with clonus, blurred vision, epigastric pain.

Early diagnosis and prompt management of severe pre-eclampsia are essential, and other nonpregnancyrelated causes of hypertension need to be excluded.

If eclampsia occurs, the user is directed to another guideline for the acute management of eclampsia. This is an emergency situation, so all the management details are in the form of a flowchart to improve clarity; the medicines and equipment required are kept in an easily identifiable box to enable a prompt response.

Clinical presentation and symptoms
Onset usually takes place after 20 weeks’ gestation in previously normotensive and nonproteinuric women. Features include hypertension, hyperreflexia, frontal headaches, blurred vision and epigastric tenderness. Liver enzymes may be raised. In severe pre-eclampsia, cerebral oedema, vasospasm, microinfarcts and haemorrhage can lead to eclamptic fits.

HELLP syndrome – haemolysis with raised liver enzymes (AST>50IU/l) and low platelets (<100 × 10(9)/l) and urate (>0.45mmol/l) – can occur in severe pre-eclampsia. Renal effects vary from mildly raised serum creatinine to oliguria and anuria, which can result in fluid retention and pulmonary oedema. Disseminated intravascular coagulation can develop acutely or over several days. The user is referred to the acute and follow-on (period immediately after eclampsia) management guidelines.

Contraindications to magnesium sulphate
The manufacturer’s recommendations need to be included, together with findings from well-controlled trials. As it is unlicensed, contraindications have been based on published studies.(3–5) These include known hypersensitivity to magnesium sulphate, myasthenia gravis, hepatic coma and severe renal failure.

Pretreatment monitoring
Baselines and key symptoms are defined and monitored (on the high-dependency chart) to detectchanges in condition or  toxicity as follows:

  • Knee or other tendon reflexes absent or forearm reflex if patient is on epidural infusion or postspinal.
  • Respiratory rate (<12 breaths/min).
  • Urine output (<100ml over four hours).
  • Blood pressure confirmed by two readings at least half an hour or preferably one hour apart.

(The user is referred to the pregnancy-induced hypertension guideline for further details on management of hypertension.)

Dosage and administration
In a previous protocol, different concentrations of magnesium sulphate were used for loading and maintenance doses. Apart from the extra preparation steps, inadvertent flushing of remaining drug in the administration
tubing at the end of the infusion loading dose may occur at the start of the maintenance infusion. Based on stability data and maximum rate of infusion, a standard concentration of 200mg/ml in dextrose 5% was chosen. The dosage given was a loading dose of 4g (20ml) over 15 minutes followed by a maintenance dose of 1g (5ml)/hour for 24 hours. The volume of diluted solution prepared should be sufficient for the desired duration. Pump failure was a matter of concern in view of the narrow therapeutic index of magnesium (therapeutic range 2–4mmol/l). In line with trust policy, a system of documentation to record regular checks of the pump and infusion was introduced.

Magnesium toxicity can cause loss of deep tendon reflexes, progressing to respiratory depression and arrest. Cerebral haemorrhage and cardiac arrest have rarely been reported. Side-effects include nausea, vomiting, diarrhoea, dizziness, drowsiness, confusion, muscle weakness, thirst, headache, itching/tingling, hypotension, palpitation, tachycardia and site problems such as phlebitis, abscess, pain and burning. A separate appendix provides details on the management of toxicities and monitoring of serum of magnesium concentration. In collaboration with the hospital’s clinical biochemistry department, all medical staff know how to access the urgent request and results service.

Clinically significant drug interactions are included, such as risk of renal failure and possibly bleeds with NSAIDs. Magnesium can enhance neuromuscular blockade when used with other neuromuscular blocking agents, nifedipine(7) and gentamicin. Although enhanced neuromuscular blockade with nifedipine is of debatable significance we decided to include it. Additive hypotensive effects are expected with nifedipine and other calcium channel blockers likely to be used to manage accompanying hypertension.

All references used are available to users through the clinical pharmacists. The multidisciplinary team then ratifies the document. Guidelines are controlled documents that can be amended only through a process of consultation. Uncontrolled amendments can lead to errors and reduce the usefulness of guidelines. A system to enable comments and feedback is available. Audit is essential to assess adherence or use of the guideline and these are directed to the CLIP team.

Awareness of new and modified guidelines is raised via the CLIP group, clinical teams, availability on the intranet and at induction tutorials for new doctors. Reinforcement of awareness is done on request by means of short tutorials. This aspect can be essential during periods of rapid change of staff mix or ward mergers.


Guidelines are now available for a wide range of conditions and diseases (see Resources). In fact, the Scottish Intercollegiate Guidelines Network has produced a guide on guideline production. Despite national efforts, adoption of guidelines into clinical practice is not widespread. Our experience has shown that it is essential to have a strategy involving a multidisciplinary forum to enable us to customise and adopt national guidelines into clinical practice with some success, especially for high-risk patient groups.


  1. 1. Wright S. Hosp Pharm Eur 2002;4:23-5.
  2. Wright SA, et al. Pharm World Sci 2000;22:B16.
  3. Jones P, et al. Lancet 1998;352:1988-9.
  4. Duley L, et al. (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software; 2002.
  5. The Magpie Trial Collaborative Group. Lancet 2002;359:1877-90.
  6. Sheth SS, Chalmers I. Lancet 2002;359:1872-3.
  7. Ben-Ami M, Giladi Y, Shalev E. Br J Obstet Gynaecol 1994;101:262-3.

Cochrane Library
Guidelines and Guidelines in practice.
Online publications summarising UK and European clinical guidelines for primary and shared care
NHS Centre for Reviews and Dissemination
Royal College of Obstetricians and Gynaecologists (UK)

Further reading
Jackson R, Feder G, editors. BMJ
SIGN. A guideline developers’ handbook. Updated August 2002.

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