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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
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