Canterbury DHB

Womens & Childrens Health

MANAGEMENT OF SEVERE HYPERTENSION / PRE-ECLAMPSIA / ECLAMPSIA

DEFINITION Pre-eclampsia is pregnancy-induced hypertension in association with proteinuria (>300mg in 24 hours or protein / creatinine ratio 30mg/mmol). Virtually any organ system may be affected. Severe pre-eclampsia is variously defined but involves Severe hypertension is confirmed with a systolic blood pressure 170 mmHg or diastolic blood pressure 110 mmHg on two occasions + Significant proteinuria (>300mg in 24 hours or protein / creatinine ratio 30mg/mmol) HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count). Many criteria are subjective; women should be managed according to a careful clinical assessment. Severe pre-eclampsia - clinical features include Symptoms of severe headache Visual disturbance Epigastric pain and/or vomiting Severe hypertension ( 170 / 110mmHg) Signs of clonus (> 2 beats) Papilloedema Liver tenderness Falling platelet count, raised liver function, abnormal renal function. INITIAL ASSESSMENT AND DIAGNOSIS How should women be assessed at initial presentation? Assessment symptoms headache, blurred vision, abdominal pain, general malaise, decreased fetal movements BP and proteinuria measurement MSU to exclude UTI General examination, epigastric tenderness, clonus (> 2 beats) NB: Reflexes are not diagnostic (but useful for assessing MgSO4 toxicity) Uterine size, fetal heart rate and CTG Oxygen saturation if concerned about pulmonary oedema. How should the blood pressure be taken? Rested and sitting 45 degree angle (chair or bed) Appropriate sized cuff at level of heart Phase 5 Korotkoff appropriate measure for diastolic BP Beware, automated devices may markedly underestimate systolic BP in pre-eclampsia, and need regular maintenance At CWH, use mercury sphygmomanometer until convinced BP is stable.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 1 of 10

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Womens & Childrens Health

How should proteinuria be measured? Dipstick 1+ or greater (Use automated dipstick reader if possible) Must be confirmed by one of the following: Protein / creatinine spot urine sample (> 30mg/mmol) or 24 hr urine (> 300mg per 24 hours). Other investigations (NB: insert IV access at time of taking bloods) FBC Coagulation profile (only if platelets are low or PET severe) Liver function tests Renal function Group and Hold if unstable CTG (continuous if unstable or in labour) Ultrasound scan to assess fetal size, amniotic fluid, UA Doppler once stable. IUGR occurs in 30% pre-eclamptic pregnancies. Ongoing regular assessments advised twice weekly if conservative management planned.

ONGOING MONITORING Acute Observation monitoring chart should be used for all measures and results. This should be reviewed at every handover and especially the 0800hrs handover when fluid volumes are totalled. Blood Pressure BP measured every 15 minutes initially Reduce to 30 minutes once stable Checked 4 hourly if conservative management is planned and woman is stable with no symptoms.

If stable, admit to ward (See Appendix A).

Fluid Balance Fluid balance measuring input and output Urinary catheter is seldom indicated purely for monitoring but may be used in severely ill patients to allow hourly urine volume measurements Daily weigh. Knee Reflexes Every 60 minutes while on MgSO4 infusion. Respiratory Rate Every 60 minutes while on MgSO4 infusion. Temperature Every 4 hours.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 2 of 10

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Womens & Childrens Health

MANAGEMENT Control of Blood Pressure Antihypertensive treatment should be commenced if Systolic BP 160mmHg or a diastolic BP 105 mmHg. Combined with other markers of severe disease (i.e. risk of cerebral haemorrhage), treatment can be considered at lower levels. Acute treatment: Labetalol oral or IV (avoid if history of asthma) Nifedipine oral Hydralazine IV Whenever acute treatment is required background antihypertensive treatment should also be initiated.

See Appendix B for recommended dosage regime.

Nonacute (background) treatment for moderate hypertension Methyldopa Labetalol Nifedipine (3rd line as get a reflex tachycardia if started on its own). Avoid Atenolol, ACE inhibitors or Angiotensin Receptor blocking drugs and diuretics.

See Appendix C for recommended dosage regime.

Fluid Balance Fluid restriction advised to reduce overload in the intrapartum and postpartum periods Oliguria is common in pre-eclampsia, and no evidence that fluid expansion or maintenance of a specific urine output prevents renal failure (which is rare) or improves preeclampsia outcome Most patients who are already oedematous from fluid retention do not need IV fluids and once able to drink are best left to take fluids according to thirst If IV fluids are required, use very cautiously and limit to a maximum of 80 ml/hour. Beware of pulmonary oedema. Postpartum haemorrhage may complicate fluid balance and require volume for resuscitation Close fluid balance is advised. CVP lines are rarely recommended NOTE: Syntocinon is the only drug that should be used after delivery in pre-eclampsia for PPH prevention. Avoid syntometrine / ergometrine. Syntocinon infusion should run at increased concentration to avoid fluid overload (40 units in 100ml saline run at 25 ml /hour over 4 hours).

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 3 of 10

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Womens & Childrens Health

Prevention of Seizures (Eclampsia) Magnesium Sulphate is advised when severe preeclampsia is diagnosed and a plan for delivery is made or postpartum. MgSO4 IV loading dose (4g by infusion pump over 20 minutes), followed by an infusion 1g/hour maintained for 24 hours after delivery. See Appendix D for recommended dosage regime. Should be continued for 24 hours following delivery or 24 hours after the last seizure, whichever is the later, unless there is a clinical reason to continue. Need to monitor infusion effects by regular assessment (1) respiratory rate (2) oxygen saturation (3) urine output (4) knee reflexes.

Management of Seizures Airway, Breathing, Circulation - basic principles + pulse oximetry Obtain help and inform anaesthetist and senior obstetrician Left lateral position, administer oxygen. Aim to prevent maternal injury Most eclamptic seizures self terminate within 2 to 3 minutes. Diazepam is not indicated unless a seizure is prolonged (status epilepticus) Magnesium sulphate is the treatment of choice to prevent further seizures. MgSO4 IV loading dose 4g by infusion pump over 20 minutes, followed by an infusion 1g/hour maintained for 24 hours after the last seizure Cardiac monitoring during and following MgSO4 loading dose Fetal CTG Aim for delivery, but stabilise mother first, even if there is fetal distress If urine output is <20ml/hr magnesium infusion should be stopped. Magnesium toxicity unlikely with above regime so levels are not routinely required. Mg toxicity identified clinically by loss of tendon reflexes followed by respiratory depression (< 12 breaths / min). If concern, stop MgSO4. If major concern over respiratory depression, consider Calcium Gluconate (1g (10ml) over 10 minutes). When and how should the baby be delivered? Decision regarding delivery should be made once the woman is stable and appropriate senior personnel are present. A carefully planned delivery with all professionals available is appropriate. Vaginal delivery is generally preferable, but less than 32 weeks caesarean section is most likely. After 34 weeks, vaginal delivery should be considered If fetus less than 34 weeks gestation, and delivery can be safely deferred, corticosteroids should be given, and plan for delivery reviewed after 24 hours Conservative management at very early gestations may improve perinatal outcome but must be carefully balanced against risk of maternal morbidity Mode of delivery should be determined after considering fetal presentation and fetal condition, together with success of induction of labour after cervical assessment Regional analgesia / anaesthesia preferred, unless platelets are low (less than 50-100 x 109 /l need to discuss with the anaesthetist on call). General Anaesthesia then should be considered 3rd stage management should be ACTIVE, using Syntocinon.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 4 of 10

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Womens & Childrens Health

Syntometrine or ergometrine should be avoided as will cause increase in blood pressure. Syntocinon infusion (40u) should be given as a concentrated solution (40u in 100ml saline, run over 4 hours at 25 ml/hr). Management Post Delivery Intensive observation should continue on Birthing Suite (AOU) for at least 24 hours with severe pre-eclampsia. Fluid restriction should continue until spontaneous diuresis occurs Monitor bloods (FBC, renal and liver function) the day after delivery, and twice weekly until stabilised ( may need more frequent monitoring if very unstable) Late seizures do occur and clinicians should review carefully before discharge Anti-hypertensive treatment should be continued after delivery as dictated by blood pressure. Most women can have treatment stopped prior to 4-6 weeks postpartum 44% of eclampsia occurs postpartum so any symptoms or signs should be carefully assessed, although the majority occur within 48 hours Early-onset pre-eclampsia (< 32 weeks gestation), particularly if associated with IUGR, requires further investigation at 6-8 weeks (inherited and acquired thrombophilia, antiphospholipid syndrome), and renal ultrasound if proteinuria persists. Occasionally need to consider testing for phaeochromocytoma if there are extreme and fluctuating levels of hypertension.

REFERENCES RCOG Evidence-based Guideline. The management of severe pre-eclampsia / eclampsia. March 2006 Magee L, Ornstein M, von Dadelszen P. Management of hypertension in pregnancy. BMJ 1999;318:1322-36 Tan L, de Swiet M. The management of postpartum hypertension. BJOG 2002;109:733-36 Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994;309:1395-400 Duley L et al. The Collaborative Eclampsia Trial. Lancet 1995; 345:1455-63

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 5 of 10

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Womens & Childrens Health

APPENDIX A In-patient ward observation of stable pre-eclampsia Indication for patient admission Raised BP and significant proteinuria Maternal symptoms Concern regarding fetal wellbeing. Monitoring when on ward Maternal BP - 6 hourly (qid) 4 hourly if significantly elevated Blood tests FBC, LFTs, U&Es and creatinine, uric acid, coagulation screen day of admission (only if platelets are low or PET severe), day after admission, then twice weekly (Mon / Thurs) Dipstick urinalysis day of admission, day after admission, then 2 x weekly (Mon / Thurs) Protein / creatinine ratio - day of admission, day after admission then 2 x weekly (Mon / Thurs) according to present protocol Pulse oximetry Daily weigh. Fetal CTG daily or twice daily if concerned Ultrasound scan growth every 2 weeks amniotic fluid index (AFI) and UA Doppler weekly. Management Steroids if less than 34 weeks gestation Anti-hypertensive treatment if meets criteria and planning to continue conservative management. Delivery if any of the following Gestation greater than 36-38 weeks if proteinuric PET BP uncontrolled despite treatment Deterioration in LFT, renal function, or fall in platelet count Maternal symptoms Concern regarding fetal wellbeing Severe thrombocytopenia.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 6 of 10

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Womens & Childrens Health

APPENDIX B Acute Management of Severe Hypertension Systolic blood pressure 160 mmHg and /or diastolic blood pressure 110 mmHg On at least 2 separate measurements 10 minutes apart. Remember: Aim to reduce BP to systolic 140-160 mmHg and diastolic 90-100 mmHg Maternal BP/pulse every 10 minutes until stable, then half hourly plus urine output hourly Review for severe pre-eclampsia Continuous CTG if antenatal. First-line therapy NB: Commence background therapy at the same time. Labetalol (exclude asthma) Oral 200mg stat dose. BP should fall within 30 minutes. Repeat oral 200mg dose if BP not controlled at 30 minutes. IV therapy Bolus Preparation: Use undiluted labetalol from vial (100mg/20ml). Administration: Give 50mg (10ml) bolus over at least 1 minute. There should be a fall in BP within 5 minutes. Repeat at 5 minute intervals to a maximum dose 200mg (40ml). Infusion Preparation: 1) Discard 40ml from a 100ml bag of Normal Saline 0.9%. 2) Add 40ml labetalol (200mg) to bag. This makes a 2mg/ml solution for infusion. Administration: Commence labetalol infusion at rate 10ml/hr (20mg/hr) via IV infusion pump. Increase infusion rate by 10ml/hr every 30 minutes until BP controlled, up to maximum 50ml/hr (100mg/hr). If BP not controlled on 100mg/hr seek medical review. Second-line therapy Nifedipine Oral 10mg stat dose (not slow release) Repeat every 30 minutes until BP controlled. At the same time commence slow release preparation twice daily and postnatally.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 7 of 10

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Womens & Childrens Health

Third-line therapy Hydralazine (exclude cardiac / renal disease) IV therapy Bolus Preparation: Hydralazine comes in a vial containing 20mg of powdered medication. 1) Add 1ml of normal saline to reconstitute. 2) Add 1 reconstituted vial of Hydralazine to 19 ml of normal saline. This makes a 1mg/ml solution for boluses. Administration: Give 5mg (5ml) bolus over 5 minutes. Repeat every 20 minutes until BP controlled, i.e. systolic 140-160 mmHg and diastolic 90-100 mmHg. Then run maintenance infusion as follows. Infusion Preparation: Hydralazine comes in a vial containing 20mg of powdered medication. 1) Add 1ml of normal saline to reconstitute each vial. 2) Remove 22ml from a 100ml bag of normal saline. 3) Add 2 vials of reconstituted Hydralazine to normal saline. This makes 40mg in 80ml = 1mg/2ml solution for infusion. Administration: Run maintenance infusion at 5mg (10ml) per hour.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 8 of 10

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Womens & Childrens Health

APPENDIX C Non-acute (Background) management of Hypertension First-line therapy Methyldopa Oral 500mg stat dose, then regular dose of 250mg tds. Can increase up to 500mg qds. Warn woman that she may feel dopey. After delivery consider using an alternative antihypertensive if required. Monitor LFTs monthly. Second-line therapy Labetalol (exclude asthma) Oral 100mg stat dose, then regular dose of 100mg tds. Can increase up to 200mg qds. Third-line therapy Nifedipine Oral 10mg slow release twice daily, and can increase up to 30mg b.d. Postnatal BP Management: Labetalol, Nifedipine or Enalapril are all appropriate antihypertensives to use in the postpartum period. Can breast feed with all these medications: Labetalol - avoid if asthmatic Usually first-line choice, starting at 100mg tds and can increase to 200 mg tds Nifedipine - Useful additional therapy after Labetalol, as get less side-effects from the vasodilatory aspect of the drug. Start at 10mg SR bd, and can increase to 20mg SR bd Enalapril Start at 5-10 mg daily. Usually used in those with likely chronic hypertension Ensure normal renal function before commencing and measure serum creatinine 3-5 days after commencing therapy.

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 9 of 10

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Womens & Childrens Health

APPENDIX D Magnesium Sulphate Indications Prophylaxis of convulsions in the presence of severe pre-eclampsia Treatment of eclamptic convulsions. Contraindications Cardiac disease or acute renal failure. Loading Dose 4g Magnesium Sulphate over 20 minutes PREMIXED (or reconstituted) 40mmol MgSO4 in 128ml (equals 10g MgSO4). Run at 153ml per hour for 20 minutes. Volume to be infused (VTBI) must be set at 51ml. Maintenance Dose 1g Magnesium Sulphate per hr PREMIXED (or reconstituted) 40mmol MgSO4 in 128ml (equals 10g MgSO4). Run at 13 ml per hour. If PREMIXED Magnesium Sulphate is not available Add four 5ml vials of 2.47g MgSO4 (total 10g) to 108 ml bag normal saline. This will give the same strength solution as the premixed bag. All 100ml bags saline actually contain 8ml overage so total solution is now 128ml, the same volume as premixed bags.

Remember: Cardiac monitoring during and for 1 hour post loading dose Hourly check that knee reflexes are present Continue baseline recordings BP, pulse Hourly Respiratory rate (should be > 12 rpm) Continuous pulse oximetry Magnesium levels not required. Magnesium Toxicity Disappearance of knee reflexes is an early sign of Magnesium toxicity and occurs before respiratory muscle weakness occurs. If concern about toxicity, stop MGSO4. If major concern over respiratory depression, consider Calcium Gluconate (1gm (10ml) over 10 minutes).

Created: May 2008 W&CH/GL/M/0003 Protocol Development: Prof Pippa Kyle, Dr Peter Moore, Dr Ruth Hughes, MW Barbra Pullar Page 10 of 10