Pre eclampsia and eclampsia
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Pre-Eclampsia and Eclampsia. Dr Suzy Matts MRCOG Dept Obstetric and Gynaecology George Eliot Hospital. Introduction. Definitions Prevalence Risk Factors Pathogenesis Interventions Prevention treatment. Definition. Hypertension and proteinuria with onset ≥20 weeks

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Pre eclampsia and eclampsia

Pre-Eclampsia and Eclampsia

Dr Suzy Matts MRCOG

Dept Obstetric and Gynaecology

George Eliot Hospital

George Eliot Hospital, Nuneaton


Introduction

Introduction

  • Definitions

  • Prevalence

  • Risk Factors

  • Pathogenesis

  • Interventions

    • Prevention

    • treatment

George Eliot Hospital, Nuneaton


Definition

Definition

  • Hypertension and proteinuria with onset ≥20 weeks

    • Oedema from classical definition dropped as not discriminating clinically

  • Diastolic ≥90mmHg on 2 occasions 4-6 hours apart OR ≥110mmHg on one occasion

  • Proteinuria >300mg/24 hours

  • Symptoms

  • Differentiation from PIH/renal disease

George Eliot Hospital, Nuneaton


Hypertensive disorders

Hypertensive disorders

George Eliot Hospital, Nuneaton


Incidence

Incidence

  • 2-3% pregnancies

  • 5-7% primips

  • 1.8% PET will develop eclampsia (from Collaborative Eclampsia Trial = 49/ 100000)

  • Rates eclampsia 26.8/100 000 maternities (UKOSS reporting system 2003-5)

  • Worldwide 1.5-8 million develop PET with 150 000 deaths

George Eliot Hospital, Nuneaton


Importance

Importance

  • Important cause of maternal and fetal death

  • 2nd most common cause maternal death over a number of years

    • 15 deaths 1997-9

    • 14 deaths 2000-2

    • 18 deaths 2003-5 (=8.5/million maternities)

    • High rates of substandard care (72% 2003-5)

George Eliot Hospital, Nuneaton


Importance1

Importance

  • Maternal morbidity

    • Blindness

    • Neurological

    • renal

  • Fetal death

    • Abruption, hypoxia, IUGR

  • Fetal morbidity

    • Prematurity (PET is cause of >40% iatrogenic preterm dels) with risks respiratory and neurodevelopmental complications (inc.learning difficulty/IQ in up to 60%)

George Eliot Hospital, Nuneaton


Causes of death

Causes of death

George Eliot Hospital, Nuneaton


Pre eclampsia and eclampsia deaths 2003 5

Pre-Eclampsia and EclampsiaDeaths 2003-5

  • 18 women

  • 10 died of cerebral haemorrhage

  • 2 died of cerebral infarction (one with 2ry haemorrhage)

  • 2 from multiorgan failure (inc ARDS)

  • 1 from massive liver infarction

  • 3 from other causes

  • Rate of death overall unchanged from previous report

George Eliot Hospital, Nuneaton


Risk factors pre eclampsia

Primiparous

First pregnancy with new partner

Family history (1 in 3 risk if mother had PET)

Twins/multiples

Pregestational Diabetes

Essential hypertension

Renal disease

SLE

Antiphospholipid syndrome

Thrombophilias

Age >40

Obesity

Risk Factors:-Pre-Eclampsia

George Eliot Hospital, Nuneaton


Pathophysiology

Pathophysiology

  • “The disease of theories”

  • Pregnancy specific syndrome

  • Placenta has a central role to play

    • Reduced placental perfusion

    • Inadequate vascular remodelling at ~16 wks

  • Genetic component in some women tho’ not in others

    • No candidate genes or consistent results

George Eliot Hospital, Nuneaton


Pathophysiology of pet

Pathophysiology of PET

George Eliot Hospital, Nuneaton


2 stage process

2 stage process

  • Inadequate implantation

  • Poor remodelling

  • Cytokines produced +

    growth factors

  • placental apoptosis/necrosis

  • Shedding of microparticles into circulation

  • Markers seen

    preceding PET

  • Inflammation and

    endotheial activation

STAGE 1:Reduced placental perfusion

STAGE 2: Maternal syndrome (multisystem disorder)

George Eliot Hospital, Nuneaton


Oxidative stress

Oxidative stress

  • Evidence includes superoxide dysmutase in placenta and maternal blood in PET

Maternal constitutional factors eg obesity, genetic, diabetes, environment, diet

Stage 1: placental perfusion

OXIDATIVE STRESS

Stage 2: Maternal syndrome (activation of maternal endothelium)

George Eliot Hospital, Nuneaton


Angiogenic factors

Angiogenic Factors

  • e.g. sFlt-1 or soluble endglin coreceptor-inhibit growth factors in placenta and vasculature

Maternal constitutional factors eg obesity, genetic, diabetes, environment, diet

Stage 1: placental perfusion

ANGIOGENIC FACTORS

Stage 2: Maternal syndrome (activation of maternal endothelium)

George Eliot Hospital, Nuneaton


Prevention of pet aspirin

Prevention of PET: Aspirin

  • Several small trials suggested reduction in rates PET with low dose aspirin therapy

  • Large multicentre trial (CLASP) in 9364 women did not demonstrate benefit for wholescale prophylaxis for low risk women

    • Trend towards reduction in likelihood to preterm delivery

    • No significant increased risk of haemorrhages

    • No statistically significant effect on stillbirths/ neonatal deaths

    • Non significant (12%) reduction in incidence PET

      Lancet 1994; 343: 619-629

George Eliot Hospital, Nuneaton


Clasp

CLASP

  • Trial suggested only benefits in women at high risk of severe early onset IUGR ? How to identify

  • Benefits thus suggested in women with previous severe early onset PET and IUGR

  • ?relationships to APLS (not investigated in original trial)

George Eliot Hospital, Nuneaton


Prevention aspirin

Prevention: Aspirin

  • More recent study showed aspirin treatment produced at RR of 0.9 (95% CI 0.84-0.97) for PET

  • Moderate but consistent reductions in PET, preterm delivery and serious outcomes

    Lancet 2007

George Eliot Hospital, Nuneaton


Prevention calcium

Prevention: Calcium

  • Calcium levels lower in women with PET compared to ‘normal’ pregnancy

  • Australian Randomised Study in 456 singleton nullips from <24/40 showed reduction in risk PET with 1.8g calcium/day compared to placebo

  • RR 0.44 95% CI 0.21-0.90

    Aus NZ J Obstet Gynaecol 1999; 39: 12-18.

George Eliot Hospital, Nuneaton


Prevention calcium1

Prevention: Calcium

  • Calcium for Eclampsia Prevention Study (CPEP) Am J Obstet Gynecol 1997; 177: 1003-10

  • 4589 US women in multicentre trial

  • All nullips

  • Analysis of risk factors for development of subsequent PET did not show any benefit from Ca++ supplementation

George Eliot Hospital, Nuneaton


Prevention calcium2

Prevention: Calcium

  • Cochrane Review Cochrane Database 2000 (3), OUS.

  • 9 studies, all good quality

  • Ca++ dose > 1g/day

  • Modest reduction in risk PET for all women (RR 0.72, 95% CI 0.6-0.86)

  • Greatest effect where highest risk- RR 0.22, 0.11-0.43 and low dietary intake (0.32, 0.21-0.49)

  • No effect on preterm delivery

  • Smaller effects seen for hypertension

    • Ca++ appears of benefit for women at high risk of developing PET

    • Also women from communities with low dietary intake

    • Optimum dosage requires further evaluation

George Eliot Hospital, Nuneaton


Prevention antioxidants

Prevention: Antioxidants

  • Vitamin C 1000mg and Vit E 400 IU/day

  • 58% reduction in PET in treated group

    Chappell et al, Lancet 1999 354: 810-5

  • A number of trials ongoing globally

  • All using above dosages

  • 3 reported so far-NO difference in rates treatment vs placebo.

George Eliot Hospital, Nuneaton


Diagnosis pre eclampsia

Diagnosis: Pre-Eclampsia

  • Classic triad

    • Hypertension 140/90

    • Proteinuria >300mg in 24 hours (RCOG)

    • Oedema (least reliable)

  • BP rise should be from booking >30/15

  • Proteinuria and raised BP x 2 occasions 6 hrs apart (or once if DBP ≥110 and heavy proteinuria >2+ (=1g/24h))

George Eliot Hospital, Nuneaton


Mild pet

Mild PET

  • Classically asymptomatic

  • BP 140/90 (ish)

  • Maybe trace-+ proteinuria

  • Often incidental finding at CMW clinic attendance

George Eliot Hospital, Nuneaton


Pet investigations

PET-Investigations

  • FBC-platelet count

  • U+Esigns renal dysfunction (late)

  • Uratehyperuricaemia ( early )

  • LFTselevated transaminases

  • ClottingXXXX (not routinely if plts>100)

  • MSUto exclude UTI as cause of protein

George Eliot Hospital, Nuneaton


Pre eclampsia and eclampsia

PET

  • Fetal assessment

    • Clinical

    • USS for growth

    • CTGs

  • ?cervical assessment (depending on gestation)

George Eliot Hospital, Nuneaton


Monitoring

Monitoring

  • Monitor BP

    • CMW

    • Day assessment or Triage Unit

  • Monitor bloods

    • Weekly or twice weekly (depends on sitn)

  • Monitor fetus

    • CTG

    • Serial USS

George Eliot Hospital, Nuneaton


Definitive treatment

Definitive treatment

  • Deliver when

    • BP/protein or clinical condition deteriorates so become moderate or severe PET

    • Reaches 41 weeks and no change in condition

    • Fetal condition mandates delivery even if maternal condition stable

George Eliot Hospital, Nuneaton


Severe pre eclampsia

SYSTOLIC 160-180

DIASTOLIC >110

CNS

Headache

Visual disturbances

Disorientation/ irritability

Hyperreflexia

clonus

Hepatic

Abnormal LFTs, dysfunction

RUQ pain

Epigastric pain

Renal

Elevated creatnine, urea, urate

Oliguria

Heavy proteinuria >5g in 24 hrs

Haemtological

Thrombocytopaenia

haemolysis

Severe pre-eclampsia

George Eliot Hospital, Nuneaton


Multisystem disease

Eyes

Arteriolar spasm

Retinal haemorrhages

Blindness

Scotoma

Papilloedema

CNS

Seizures

Encephalopathy

Cerebral haemorrhages

CVA

Respiratory

Pulmonary oedema

ARDS

Liver

Subcapsular haemorrhages

Liver rupture

Kidneys

Acute renal failure

Fetoplacental Unit

IUGR

Abruption

Fetal compromise

Fetal death

Haemotological

DIC

haemolysis

Multisystem disease

George Eliot Hospital, Nuneaton


Symptoms

Symptoms

  • Headache (BP)

  • Flashing lights (lightning) (cerebral oedema)

  • Epigastric pain (stretching of liver capsule)

  • Oedema (albumin/BP)

  • Asymptomatic

George Eliot Hospital, Nuneaton


Management of severe pre eclampsia

Management of severe pre-eclampsia

  • Immediate admission to hospital

  • High dependency care/LW-QUIET

    • Invasive monitoring

    • NICU for baby if early gestation

  • Senior multidisciplinary involvement early-obs and anaesthetics

George Eliot Hospital, Nuneaton


Aims of treatment

Aims of treatment

  • Aims

    • Prevent seizures

    • Control hypertension (to prevent cerebral haemorrhage)

    • Deliver safely (stabilise, +/- IUT, +/- steroids)

George Eliot Hospital, Nuneaton


Maternal assessment

Maternal Assessment

  • BP-check every 15 minutes

  • Urine output-hourly

  • Urinary protein dipstix

  • Strict fluid balance chart

  • Bloods

    • U+E, urea, creatnine, urate

    • FBC esp. platelets (G+S)

    • LFTs

  • Deep tendon reflexes and presence of clonus

  • CTG

George Eliot Hospital, Nuneaton


Control blood pressure

Control blood pressure

  • Antihypertensives – aim for diastolic 85-95

    • IV hydralazine (5mg every 15 minutes to acutely control BP)

    • IV labetolol (Not good if asthmatic or already signs of pulmonary oedema-first line in many places now)

    • Oral nifedipine 10mg NOT SUBLINGUAL

    • Methyldopa TOO SLOW ONSET (24-48 hours) for use in acute situation

    • Titrate IV antihypertensive vs. BP then infusion

George Eliot Hospital, Nuneaton


Key points hypertension

KEY POINTS: Hypertension

Systolic blood pressure of 160 mm/Hg or more = anti-hypertensive treatment.

(irrespective of diastolic)

Consideration starting treatment at lower pressures if the overall clinical picture suggests likely rapid deterioration with anticipation of severe hypertension.

George Eliot Hospital, Nuneaton


Prevent fits

Prevent Fits

  • Magnesium sulphate

    • All severe and moderate PET (MAGPIE)

    • 4g IV over 15 minutes

    • Then infusion 1g/ hour

    • Monitor reflexes (present) urine OP (>30ml/hr) and respiratory rate (>12/minute)

    • Slows neuromuscular conduction and decreases CNS irritability

    • Best anticonvulsant in these circumstances AND IN ECLAMPSIA

    • No effect on BP

    • Tell anaesthetist if GA as potentiates effects of muscle relaxants

George Eliot Hospital, Nuneaton


Magnesium toxicity

If urine OP OK then likely not to accumulate (85% renal excretion)

If urine output falls, reduce dose to 0.5g/hour

If signs toxicity, stop

Antidote = Calcium gluconate 1g IV over 3 minutes

Magnesium levels

Therapeutic 2-4 mmol/l

Warmth, flushing, slurred speech 3.8-5mmol/l

Loss of patellar reflexes >5 mmol/l

Respiratory depression >6 mmol/l

Respiratory arrest 6.3-7mmol/l

Cardiac arrest, asystole >12 mmol/l

Magnesium toxicity

George Eliot Hospital, Nuneaton


Magpie

MAGPIE

  • 10141 women-99% received allocated treatment

  • 24% of women with MgSO4 reported side-effects compared to 5% of women on placebo

  • MgSO4 produced 58% reduced risk of eclampsia (0.8% cf. 1.9%)-across all categories of PET

  • Maternal mortality lower as well RR 0.55, CI 0.26-1.14

  • Only improvement in maternofetal morbidity was reduced risk of abruption (0.67, 99% CI 0.45-0.89)

  • No substantial harmful risks to mother or fetus

    Lancet 2002; 359: 1877-90.

George Eliot Hospital, Nuneaton


Magpie lancet 2002 359 1877 90

MAGPIE Lancet 2002; 359: 1877-90.

George Eliot Hospital, Nuneaton


Deliver baby

Deliver Baby

  • If severe PET, should NOT transfer

  • Ensure SCBU aware if baby premature

  • Give antenatal steroids if time but usually, if require IV therapy, delivery is indicated once stabilised

  • If cervix favourable and patient >36 weeks, consider short trial IOL

  • If cervix unfavourable and/or <36 weeks, deliver by LSCS

  • Anaesthesia epidural vs. general

George Eliot Hospital, Nuneaton


Delivery key points 1

DELIVERY: Key Points 1

Risk of sharp rise of BP on intubation

This may be obtunded by large dose alfentanyl or similar

Need experienced and senior anaesthetist to give GA in these circumstances

George Eliot Hospital, Nuneaton


Delivery key points 2

DELIVERY: Key Points 2

Syntometrine should not be given for the active management of the third stage if the mother is hypertensive, or if her blood pressure has not been checked.

(ergometrine causes vasospasm and a sharp rise in BP which may precipitate hypertensive crisis, fits or cerebral haemorrhage)

George Eliot Hospital, Nuneaton


Eclampsia

Eclampsia

  • Occurrence of fits

    • 44% postpartum

    • 38% antenatal)

    • ALWAYS GRAND MAL

  • Due usually to cerebral vasospasm

  • Do not try to shorten initial convulsion (self-limiting)

  • Prevent maternal injury

  • Maintain oxygenation

  • Prevent aspiration

  • ABC…

George Eliot Hospital, Nuneaton


Eclampsia1

Eclampsia

  • Beware known epileptics

    • If BP normal, no protein, typical for their type of fit-may be epilepsy BUT any fit must be considered as eclampsia until proven otherwise especially of BP slightly up etc

  • Any FOCAL fit is not eclampsia

    • Consider SOL eg cerebral bleed/infarction due to severe PET

    • Arrange head CT urgently

George Eliot Hospital, Nuneaton


Collaborative eclampsia trial

Collaborative Eclampsia Trial

  • Multicentre international trial

    Lancet 1995; 345: 1455-63

  • 1687 women

  • Comparisons:

    • MgSO4 vs. diazepam

      • 52% lower risk recurrent convulsions with MgSO4

    • MgSO4 vs. phenytoin

      • 67% lower risk recurrent convulsions with MgSO4

  • Maternal mortality nonsignificantly lower in MgSO4

  • Less risk of pneumonia, ventilation, ITU with Magnesium

  • Babies less likely to be intubated and go to SCBU

George Eliot Hospital, Nuneaton


Eclampsia2

Eclampsia

  • Treatment is IV magnesium sulphate-4g loading then 1g/hr

  • If recurrent fits or fit already on MgSO4, then further 2g IV bolus/increase infusion to 1.5g/hr

  • If fits persist, check magnesium levels, contact anaesthetists, consider CT, consider intubation and ventilation

  • If antenatal, stabilise and Deliver

George Eliot Hospital, Nuneaton


Following delivery

Following Delivery

  • Watch closely on HDU/LW until diuresis and condition improving

  • Anticipate possible worsening or seizures in first 18-24 hours

  • Continue MgSO4 for 24 hours and then review

  • Do not need to taper off MgSO4

  • Do not feed within 12 hours as significant risk ileus-sips H2O only until next morning then review for bowel sounds

George Eliot Hospital, Nuneaton


Postnatal care

Postnatal care

  • Watch closely on HDU/LW until diuresis and condition improving

  • Anticipate possible worsening or seizures in first 18-24 hours

  • Continue MgSO4 for 24 hours and then review

  • Do not need to taper off MgSO4

  • Do not feed within 12 hours as significant riskileus-sips H2O only until next morning then review for bowel sounds

George Eliot Hospital, Nuneaton


Postnatal care1

Postnatal Care

  • Managing the postnatal pre-eclamptic poses particular challenges

    • Hypertension

    • Fits

    • Fluid management

    • GI management

    • Disease progression

George Eliot Hospital, Nuneaton


Postnatal care mortality

Postnatal care-Mortality

  • Most deaths occur after delivery

George Eliot Hospital, Nuneaton


Causes of death1

Causes of death

George Eliot Hospital, Nuneaton


Postnatal management hypertension

Postnatal Management-Hypertension

  • IV hydralazine or labetolol if severe

  • Oral route if less severe

  • Even mild may develop more marked hypertension after delivery

  • Conversely, BP may settle rapidly after delivery

  • Aim for control with DBP <100

George Eliot Hospital, Nuneaton


Postnatal management hypertension1

Postnatal Management-Hypertension

  • Hypertension may persist for some weeks

  • Switch to oral treatment when feasible

    • Atenolol

    • Nifedipine

  • Polypharmacy may be required to control BP-consult with physicians

  • Ensure regular BP checks arranged on discharge with review and follow-up by GP

George Eliot Hospital, Nuneaton


Postnatal management fits

Postnatal Management-Fits

  • Eclampsia Survey showed 44% of fits occur postpartum

  • High index of suspicion

  • Beware worsening of condition

  • MgSO4 prophylaxis in all severe PET and all eclamptics

  • All women with severe PET should have MgSO4 for 24 hours following delivery or following last fit-whichever is longer

George Eliot Hospital, Nuneaton


Postnatal management fluids

Postnatal Management-Fluids

  • Fluid overload real danger after delivery

    • Relaxed vigilance

    • LSCS

    • PPH

    • Physiological oliguria

  • STRICT FLUID BALANCE

George Eliot Hospital, Nuneaton


Postnatal management fluids1

Postnatal Management-Fluids

  • SHIP audit (1997) showed that many women have oliguria but intervention not required unless UO <100ml in 4 hours

  • Fluid overload carries risks of pulmonary oedema-

    • Reduced plasma oncotic pressure

    • Hypertension thus increased gradient across microvasculature

    • Filtration of fluid into tissues

    • Pulmonary oedema

George Eliot Hospital, Nuneaton


Postnatal management fluids2

Postnatal Management-Fluids

  • Women with PET are very vulnerable to Pulmonary oedema

  • Carries risk of ARDS if severe or not recognised rapidly

  • ARDS may be fatal

  • Fluid restriction is far SAFER

    • Renal function more likely to recover than pulmonary and less likely to kill pt

George Eliot Hospital, Nuneaton


Causes of death2

Causes of death

SHIP

George Eliot Hospital, Nuneaton


Postnatal management fluids3

Postnatal Management-Fluids

  • Fluidrestrict-60-86ml/hour TOTAL from all routes (inc. any MgSO4 and antihypertensives)

  • ICE counts as fluid so measure

  • Strict fluid balance with 1 hourly UO via catheter

  • DO NOT ACT on oliguria unless <100ml urine over 4 hours or no urine at all for 2 hours

  • Do not forget to readjust catheter/flush before trying to intervene

  • DO NOT GIVE FRUSEMIDE unless overt signs heart failure (raised JVP or crepitations)-40mg

  • FRUSEMIDE should always be discussed with consultant

George Eliot Hospital, Nuneaton


Postnatal management fluids4

Postnatal Management-Fluids

  • One fluid challengeONLY-250ml crystalloid over 30 minutes

  • If no response, listen to chest base for crepitations (signs LVF) and insert CVP line before any further challenge

  • If CVP low, can give further fluids under CVP guidance to achieve normal CVP

  • If CVP high, give frusemide 40mg IV

  • If CVP normal, consider dopamine

  • Early transfer HDU/ITU

George Eliot Hospital, Nuneaton


Postnatal management fluids5

Postnatal Management-Fluids

  • Check U+E if concerned about fluid management or if oliguria/anuria

  • If deteriorating, confer with renal team or intensivists

  • Multidisciplinary management is the key

George Eliot Hospital, Nuneaton


Fluid balance

Fluid Balance

  • Take Home messages

    • Fluid restrict as pt already fluid overloaded

    • Scrupulous input and output

    • Do not fluid challenge

    • Do not give frusemide

    • Consider CVP line if urine output poor

    • Seek senior advice early

    • Multidisciplinary Mx-obs/anaesth/renal teams

George Eliot Hospital, Nuneaton


Gi management

GI management

  • Don’t forget stress response to illness-

  • H2 antagonists (eg Ranitidine)

  • Delay feeding until bowel sounds present

    • May develop ileus if v unwell

George Eliot Hospital, Nuneaton


Disease progression

Disease Progression

  • Often improve quickly

  • Some may deteriorate further immediately after delivery –may continue to worsen for 24 + hours

    • Worsening BP

    • Worsening bloods

    • Oliguria/anuria

    • Increased risk fits

  • Consult seniors and manage with multidisciplinary team

George Eliot Hospital, Nuneaton


Hellp syndrome

Haemolysis

Elevated

Liver Enzymes

Low

Platelets

1-12% PET (usually severe end of spectrum)

Commoner in multips

Variable presentation

RUQ pain, epigastric pain, nausea + vomiting

85% hypertensive at presentation

Present: 2/3 antepartum, 1/3 postpartum

mid 2nd trimester to several days postnatal

HELLP syndrome

George Eliot Hospital, Nuneaton


Differential diagnosis in hellp

Any liver problems

Biliary colic

Cholecystitis

Hepatitis

Gatroenteritis or reflux

Pancreatitis

ITP/ TTP

Ureteric colic

Renal calculus

Rare-if severe pain:

Aortic dissection

MI

Differential diagnosis in HELLP

George Eliot Hospital, Nuneaton


Management of hellp

Treat as severe PET

Stabilise

Fluids

Antihypertensives

MgSO4

Anti-thrombotic agents

Coagulation factors (if required)

Assess baby

USS

CTG

(remember 20% risk of abruption)

PLAN DELIVERY ASAP

TRANSFER TO TERTIARY CENTRE IF REQUIRED

IOL or LSCS

Management of HELLP

George Eliot Hospital, Nuneaton


Summary pet eclampsia hellp

Summary-PET, eclampsia, HELLP

  • Serious disease with potential for maternal and fetal mortality

  • Prevention not widespread ? Aspirin for some ? Calcium for all

  • Treatment depends on prevention of complications and timing delivery

  • Senior involvement in severe cases

George Eliot Hospital, Nuneaton


Pre eclampsia and eclampsia

THE

END

George Eliot Hospital, Nuneaton


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