TheThe management management ofofseveresevere pprere--eclampsiaeclampsia

WhatWhat is new?is new?

Marianne JohansenMarianne JohansenObstetrisk Klinik, Obstetrisk Klinik, Rigshospitalet, CopenhagenRigshospitalet, Copenhagen

DiseaseDisease ofof hypothesishypothesisToxaemiaToxaemia•Phlebotomy

•Emetics/laxatives

•Diuretics

•Diets

•Termination of pregnancy/quick delivery

TheThe bulkybulky uterusuterus••TheThe pregnantpregnant womanwoman in in proneprone positionposition

••UretercatheterisationUretercatheterisation//uretertransplantationuretertransplantation

••DecapsulationDecapsulation ofof thethe kidneyskidneys

Guiseppe Arcimboldo, 1566

Historical perspective Historical perspective

- In pregnancy, drowsiness withheadache acompanied by heavinessand convulsion, is generally bad

AncientAncient GreeceGreece

-- Convulsions during pregnancy aremore dangerous than thosebeginning after delivery

MauriceauMauriceau, 1694, 1694

Maternal mortality rates (per million maternities) 2000-2002

Why mothers die, 2000-2002

Maternal death and hypertensive disorders of pregnancy

64 % CNS29 % Liver

7 % Lungs

43 % Eclampsia57 % HELLP

46 % Substandard care

Why mothers die, 2000-2002

MaternelMaternel complicationscomplications

• Placental abruption (1-4%)• DIC / HELLP (10-20%)• Pulmonary edema / aspiration (2-5%)• Acute renal failure (1-5%)• Liverdamage or rupture (<1%)• Stroke and death• Long-term cardiovascular morbidity

Fetal complicationsFetal complications• Iatrogenic preterm delivery (15-67%)• IUGR (10-25%)• Perinatal death (1-2%)• Hypoxic CNS damage (<1%)• Long-term cardiovascular morbidity

Management of severe pre-eclampsia

• Correct diagnosis• Timing of delivery• Prevention of maternal complications• Treatment of hypertension• Seizure prophylaxis• Fetal surveillance / monitoring• Treatment of severe complications

(HELLP, eclampsia, DIC, pulmonary edema, ATIN)

• Post partum counselling and check up

What is severe preeclampsia?Maternalsymptoms

Maternalsigns

Laboratoryfindings

Fetalassessment

Nausea/vomiting

Headache

Visual disturbances

Epigastic and/orRUQ pain

Chest painDyspnea

dBP > 110 mmHg

sBP > 160 mmHgOliguria (< 500 ml/d)

Pulmonary edema

Suspected abruption

Eclampsia

Thrombocytopenia

Liver enzymes ↑

Plasma albumin ↓

Heavy proteinuria(> 3-5g/d)

Hmolysis (HELLP)

IUGR

Oligohydramnios

Absent or reversediastolic flow in UAD

Imitators of severe preeclampsia

HELLPAFLPTTPHUSExaberation of SLEAcute abdomen

EclampsiaHypertensive diseaseCerebrovascular accidentSpace-occupying lesionsMetabolic disordersMeningitis, encephalitisEpilepsy

Frequency of signs and symptoms among imitators of severe preeclampsia

Signs and Symptoms

HELLP AFLP TTP HUS SLE

HypertensionProteinuriaFeverJaundiceNausea/vomitingAbdominal painCNS

8590-95Absent5-1040

60-8040-60

5030-5025-3240-9050-8035-5030-40

20-75w. haematuria

20-50Rare

CommonCommon

60-70

80-9080-90NRRare

CommonCommon

NR

80 w. APA, nephritis100 w. nephritisCommon w. flareAbsentOnly w. APAOnly w. APA50 w. APA

Sibai B, Obstet Gynecol, 2007

The ultimate treatmentis still

planning of delivery

On the best dayIn the best place

Through the best routeWith the best support team

Doctors dillemma!

• Severe preeclampsia remote from term• Expectant or active management?

Severe preeclampsia at GA < 34 wks.Admit to Intensive observation area; Maternal & fetal evaluation for 24 hrs., IV Magnesium sulphate; Antihypertensives when required; Corticosteroids for lung maturity (>GA > 23+5)

Eclampsia; Pulmonary edema; Acute renal failure;DIC; GA < 23 wks.; GA 33+0-34+0Non-reassuring fetal status

Delivery before completionof steroidsYes

HELLP; Severe FGR ± oligohydramnios; UAD with reverse diastolic flow; Persistent symptoms; Thrombocytopenia; GA 33+0 – 34+0; Labor or rupture of membranes

Yes

No

Steroids48 hrs delay if possible

GA < 23 wks.

Counselling

Termination of pregnancy

No

24+0 – 32+6 wks GA

Antihypertensives if needed; Daily evaluation of maternal-fetal conditions; Delivery at GA 33+6 wks.

Sibai; Am J Obstet Gynecol, 2006

Fetal surveillance

•CTG and steroids for lung maturation

•Ultrasound: Biometry, AFI and biophysicalprophile

•UAD-examination

Cerebral Cerebral autoregulationautoregulation of blood flow

Risk of intracerebralcatastrophy

Kaplan, Lancet, 1994

AcuteAcute management management ofof severesevere hypertensionhypertension(BP>160/110 (BP>160/110 mmHgmmHg))

• Considerable uncertainty on the choice of drug still exists!!!!- RCT are needed

• Choice of drug should depend on- Local experience- Ongoing treatment- Known side effects- Consideration of comorbidity

• Oral treatment should be preferred• Treatment goal is sBP < 160 mmHg and

dBP < 110 mmHg, slowly and carefully• Insufficient data to determine the optimal BP

Dadelszen Pv, Frontiers in Bioscience, 2007

AcuteAcute management management ofof severesevere hypertensionhypertensionOral treatment

Starting dose Time to effect

Contra-indications

Nifedipine Tbl. of 10 mg or (5 mg capsule)

45 min (30 min)

(CAVE Mg)Atheroscleroticcvd/risk of cvd

Labetalol Inj. bolus (20 mg) slowly- Either repeated every30 min or followed by infusion

5 min AsthmaMb. cordis

(Hydralazin) Inj. 6,25 mg . May berepeated after 30 min

5-15 min

Labetalol Tbl of 200 mg 30 min Severe asthma(Mb. Cordis)

IV-treatment

Dadelszen Pv, Frontiers in Bioscience, 2007

Acute antihypertensive treatment in PE

Bevare of me!!!dBP never below 90 mmHg

Too tight BP-control may cause placental perfusion ↓

Management Management ofof vaginal vaginal deliverydelivery

• Consider induction of labour• Consider instrumentel delivery• Management of BP as usual• Epidural analgesia advisable when no coagulopathy• Consider Magneseium sulphate for seizure

prophylaxis• CAVE Methergin (BP ↑)

Fluids:Fluids: 0-balance during and minus balance after delivery.

Anaesthesia

Vaginal delivery: Epidural

C/S:Epidural, Epi-spinal, Spinal

Coagulopathy with platelets < 80:General anaesthesia

NB Platelet count max 4 hrs old!

Visalyaputra, Anesthesia and Analgesia, 2005

MagpieMagpieA A randomisedrandomised studystudy ofof MMagnesiumagnesium sulphatesulphate for for seizureseizure

prophylaxisprophylaxis in in womenwomen withwith prepre--eclampsiaeclampsia

• 10441 women randomised• “Intention to treat” analysisResultsResults

More than 50 % reduction in the risk of eclampsiaRR 0,42 (40 / 5055 > < 96 / 5055) NNT 109 with mild-moderate preeclampsiaNNT 63 with severe preeclampsia

Reduced risk of placental abruptionNon-significant trend towards a reduction in maternal mortalityNo difference in neonatal morbidity / mortality

LLancetancet 2002;359:18772002;359:1877--18901890

Eclampsia

• Call for help!!!!(anesthetist)

•Free airways / patient on the side (Airway)• Oxygen (Breathing)• Seizure treatment / iv line (Circulation)• Chart / blood tests• Stabilize the patient• Fetal surveillance• Plan delivery

Management Management ofof eclampsiaeclampsia

Magnesium sulphate is the drug of choice for treatment of eclamptic fits and for prevention ofrecurrent seizures!

Treatment protocol:

• Bolus: 4-5 gr of Mg diluted in a total of 100 ml NaCl, IV-infusion over 10-30 min.

• Maintenance: 25 gr Mg diluted in NaCl to a total of 500 ml. Infusion-time: 40 ml/hr (~ 2 gr / hr) for at least 24 hrs since last fit.

The Eclampsia Trial, Lancet, 1995, Magpiestudiet 2001

MagnesiumIntensive monitoring of a patient treated with Magnesium

Every 2. hour:• Diuresis > 25 ml/time• Deep tendon reflexes• Respiratory frequency > 16 / min

Recurrent eclamptic seizure:If < 4 hrs since bolus: ½ new bolusIf > 4 hrs since bolus: New bolus Antidote :

Calcium chloride (0,5mmol/ml) 5-10 ml slowly i.v.

Infusion at least 24 hrs after last seizure!

HELLPHELLP--syndromsyndromHemolysisHemolysis, , ElevatedElevated Liver Liver EnzymesEnzymes, , LowLow PlateletsPlatelets

N = 442 women with HELLP

2/3 antepartum, 1/3 postpartum

Presenting-signs and symptoms %Epigastric/RUQ pain 65Nausea/Vomiting 36Headache 31Visual disturbances 10Bleeding 9Jaundice 5Diarrhea 5Shoulder or neck-pain 5

TomsenTomsen TR, Am J TR, Am J ObstetObstet GynecolGynecol. 1995. 1995

Severe preeclampsiaDIC / HELLP

Symptomatic treatment and intensive monitoring

Interdisciplinary team of coagulation-specialists, anaesthetists and obstetricians

Consider:• Blood transfusion• Antitrombin• Platelet concentrate transfusion• Fresh frozen plasma

HELLP:Consider Corticosteroid injections of 10 -12 mg x 2 IM or IV (Dexametason) even when lung maturation is not indicated. Especially helpful post partum. Again evidence is sparse.

Management Management ofof DICDIC

SymptomaticSymptomatic treatmenttreatment

•• LossLoss ofof bloodblood:: > 700 ml of blood loss should bereplaced by FFP, blood and / or plasma-expanders

•• PlateletPlatelet transfusion:transfusion: In cases of severethrombocytopenia (< 20 x 109/l )

•• AntithrombinAntithrombin (AT):(AT): When AT < 50 %

TreatmentTreatment ofof DIC DIC shouldshould alwaysalways bebe interdisciplinaryinterdisciplinary!!

PostPost--partumpartum counsellingcounselling

– Check up and counselling 2 months after delivery– Examination for trombophilia (including

antiphospholipid antibodies and lupus anticoagulans)

RecurrenceRecurrence riskrisk ofof 1010--40 %40 %• Worse for early and serious disease

RecurrentRecurrent prepre--eclampsiaeclampsia is is oftenoften mildermilder and and withwithlaterlater clinicalclinical presentationpresentation (4 (4 wkswks)!)!

Management of next pregnancy

– Antenatal check-up every 3-4 wks. from GA 24

– Regular ultrasound examinationsfor fetal growth and in GA 23 withflow-measurements in the uterinearteries to check for notches

– Low dose aspirin (75 mg daily) from week 12

Take Home Messages

• Severe preeclampsia / eclampsia multiorgan disease• Correct diagnosis and timely intervention• Optimal BP-control and strict fluid control• Stabilizing the patient before delivery• Regional anesthesia when possible• Avoid transfer of patients if at all possible• Seizure-prophylaxis and treatment with Magnesium • More trials are needed!!!• Ongoing updating of knowledge and skills training