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Anaesthetic Implications and Management in Preeclampsia &
EclampsiaDr. Shilpa Agarwal
Moderator: Dr. JP Sharma
www.anaesthesia.co.in email: [email protected]
University College of Medical Sciences & GTB Hospital, Delhi
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Contents
• Classification of hypertensive disorders of pregnancy• Diagnosis of preeclampsia• Risk factors• Obstetric and Anaesthetic management• Complications of preeclampsia• Diagnosis and risk factors of Eclampsia• Obstetric and Anaesthetic management in Eclampsia• Complications of Eclampsia
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Introduction
• Hypertensive disorders complicate nearly 5-10% of all pregnancies
• Deadly triad with infection and haemorrhage• In developed countries, 16% of maternal deaths due to
hypertensive disorders• Preeclampsia – a multifactorial, multi-system hypertensive
disorder of pregnancy ,is most dangerous• etiology remains unknown• evidence-based management
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History Year Milestones
1903 Chesley -Preeclampsia word included in books
1961 Chesley -Preeclampsia-eclampsia restricted to obstetric definition.
1966 Eastman and Hellmann
-Toxemia of pregnancy-Diagnostic criteria of preeclampsia: hypertension, proteinuria, edema after 24 weeks
1976 Pritchard and Mc Donald
-Hypertensive disorders of pregnancy-Diagnostic criteria of preeclampsia: hypertension, proteinuria, edema after 20 weeks
1988 Hibbard -Under classification Hypertensive disorders of pregnancy, preeclampsia grouped into Pregnancy induced Hypertension-Classified into mild-moderate and severe preeclampsia
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Classification
• In 2000, National High Blood Pressure Education Program classified hypertensive disorders complicating pregnancy as:
Gestational hypertensionPreclampsia- eclampsiachronic hypertensionchronic hypertension with superimposed preeclampsia
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Gestational Hypertension
• Blood Pressure ≥ 140/90 on two or more occasions - in a previously normotensive patient
- after 20 weeks gestation - without proteinuria
- returning to normal 12 weeks after delivery
• Almost half of these develop preeclampsia syndrome
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Chronic Hypertension
• Blood Pressure ≥ 140/90 before 20 weeks of gestationOr
• Persistence of hypertension beyond 12 weeks after delivery.
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Preeclampsia superimposed on Chronic Hypertension
• New-onset proteinuria ≥ 300 mg/24 hours in hypertensive women but no proteinuria before 20 weeks’ gestation
• A sudden increase in proteinuria or blood pressure or platelet count <1 lakh/mm3 in women with hypertension and proteinuria before 20 weeks’ gestation
• More adverse outcome than preeclampsia alone
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Preeclampsia
• New onset of hypertension & proteinuria in a previously normotensive woman – after 20 weeks of gestation– Returning to normal after 12 weeks of pregnancy.
• Edema not a part of diagnosis now.• A retrospective diagnosis• Eclampsia : new onset of seizures or unexplained coma during
pregnancy or postpartum period in patients with pre-existing
preeclampsia and without pre-existing neurological disorder.
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PREECLAMPSIA
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Epidemiology
• Preeclampsia complicates nearly 6% - 10% of all pregnancies.• maternal ICU admission• Leading cause of preterm delivery-NICU• Birth of LBW babies- economic, social and medical burden• Leading cause of maternal and fetal morbidity and mortality.
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Classification of PreeclampsiaMild PE Severe PE
Blood pressure >140/90 >160/110
ProteinuriaOn 2 occasions, >4hrs
apart
>0.3gm/ 24 hrsDip stic > 1+
>5gm/24 hrsDipstic > 3+
S. creatinine normal elevated
Pulmonary edema _ +
oliguria _ +
IUGR _ +
headache _ +
Visual disturbance _ +
Epigastric pain _ +
HELLP syndrome _ +
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Risk Factors
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Risk factors contd..
-Maternal disease related Obesity, BMI>35 doubles the
risk Hypertension Diabetes Thrombotic vascular diseases
-Behaviour- Smoking : - preventive
-Pregnancy associated- Multiple gestation Molar pregnancy
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ETIOPATHOGENESIS
• Exact mechanism unknown, disease of theories.1. ABNORMAL PLACENTATION
• Stage1: failure of trophoblastic invasion into myometrium Penetrates only decidua
superficial placentation ↓placental perfusion
• stage2 : endothelial damage systemic manifestations of Preeclampsia
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1.Abnormal placentation
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2. Inflammatory mediators
↓PGI2 ↑TXA2
VasoconstrictionPlatelet aggregation↑Vasopressor response↑uterine activity
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3. GENETIC
Early onset Late onset
onset < 34 wks POG > 34 wks POG
frequency 20% 80%
Association with IUGR High negligible
Familial component yes no
Placental morphology abnormal normal
etiology placental maternal
Risk factos Family history DM, HTN, Maternal age, ↑BMI, CVS disorder
Risk of adverse outcome high negligible
Family history of pre eclampsia: genetic originMutations in Complement Regulatory Protein geneGenes assoc.: MTHFR, F5 leiden, AGT, HLA, NOS3, F2(prothrombin), ACE
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4. IMMUNOLOGIC
• Exposure to sperms of different partner • long term exposure to paternal antigen in sperms of same
partner- protective• activated auto antibodies to angiotensin receptor-1 AA-
AT1activate AT1 receptorsincreased sensitivity to angiotensins
hypertension
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5.ANTIANGIOGENIC PROTIENS
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Markers of Preeclampsia
• ↑ plasma Homocystiene• ↑ serum sFlt1(soluble fms-like tyosine kinase)• ↓serum and urinary Platelet Growth Factor• ↓ Vascular Endothelial Growth Factor
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Pathophysiology
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Respiratory
– Airway is edematous;– ↓ internal diameter of trachea– Pharyngolaryngeal edema– risk of pulmonary edema; 3% women with preeclampsia.
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CNS
• CNS manifestations include:headache,
visual disturbances, hyperexcitability, hyperreflexia, coma,seizures
Cause: cerebral edema and hypoperfusion
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CVS
• Vasospasm and exaggerated responses to catecholamines• Increased vascular permeability• ↓ Colloid Oncotic Pressure
hypertension endorgan ischemia Intravascular volume deficit
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Haematology• Hemoconcentration (pts with anemia may appear to have
normal hematocrit)• Thombocytopaenia most common• Platelet count correlates with disease severity and incidence
of abruptio placentae• DIC due to activation of coagulation
cascadeoverconsumption of coagulants and platelets spontaneous haemorrhage.
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Hepatic
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Renal
Decreased GFR - oliguria - renal failure
- uric acid, creatinine is elevated
Glomerulopathy - proteinuria
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Uteroplacental circulation
• Uteroplacental insufficiency• Fetal complications: - hypoxia -IUGR -Prematurity -IUD -Placental abruptio
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Prediction of Preeclampsia
No screening test is really helpfulVarious screening methods are:• Diastolic notch at 24weeks by doppler ultrasonography• Absence or reversal of end diastolic flow• Average mean arterial pressure ≥ 90 mmHg in second
trimester• Angiotensin infusion test: angiotensin infusion required to
raise the blood pressure >20 mm Hg from baseline• Roll over test: rise in blood pressure >20 mmHg from baseline
on turning supine at 28-32 weeks gestation is positive.
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Prevention • Regular Antenatal checkup:
rapid gain in weightrising blood pressureedemaproteinuria/deranged liver or renal profile
• Low dose Aspirin in High risk group: ↑PGs and↓TXA2 • Calcium supplementation: no effects unless women are
calcium deficient• Antioxidants- Vitamin C and E• Nutritional supplementation: zinc, magnesium, fish oil, low
salt diet
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Obstetric Management
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Obstetrics management
1. Maternal evaluation : Hemoglobin and hematocrit
platelet count : decreased, if < 1 lakh coagulation profile
LFTs : indicated in all patientsKFTs : raised (S.urea creatinine is decresaed in Normal pregnancy) Urine Routine : proteinuria
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Obstetrics management contd..
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Obs. Manag contd..
3. Treatment of Acute Hypertension:
• Goal: to prevent adverse maternal sequalae
• Aim: to keep DBP below 100 mm Hg and to lower MAP not >15-25%
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Anti Hypertensive DrugsDRUGS MOA SIDE EFFECTS C/I & PREVENTION
Methyldopa 250mg-1g tds or 250-500mg iv
Central and pripheral anti adrenergic action
Maternal-postural hypotension, hemolytic anemia, sodium retention, excessive sedationFetal-intestinal ileus
Hepatic disorders, psychic pts., CCF
LabetalolOral-100mg tds till 800mg/dIv- 20 mg till desired effect (max. 220mg)
Alpha + beta blocker Maternal-tachycardia, hypotensionFetal-bradycardia, hypotension
Hepatic disorders
HydralazineOral-100mg/d in 4 divided doses
Peripheral vasodilation Maternal-hypotension, tachycardia, arrythmia, palpitations, lupus like syndromeFetal- safeNeonate- thrombocytopenia
Causes sodium retention so use diuretic
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Anti Hypertensives contd..DRUGS MOA SIDE EFFECTS C/I & PREVENTION
NifedipineOral: 5-10mg tds
Arteriolar vasodilation Flushing, hypotension, tachycardia, inhibition of labor
With MgSO4 and NMBs
Nitroprusside0.25-8 mcg/kg/min
Direct vasodilator Maternal- nausea, vomitting, severe hypotensionFetal- cyanide toxicity
Bed restAvoid Diuretics, ACE inhibitors, ARBsAvoid uterotonics
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Obs Manag contd..
4. Seizure Prophylaxis Routinely used in severe PE Magnesium sulphate: most commonly used Initiated with onset of labor till 24h postpsrtum For caesarean, started 2hrs before the section till 12hrs
postpartum
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Recommended regime for MgSO4
– Zuspan or sibai regime: 4-6 gm i.v over 15 min f/b
infusion of 1-2 gm/hr
– Pritchard regime: 4 gm i.v over 3-5min f/b 5 gm in each buttock with maintenance of 5 gm i.m in alternate buttock 4 hrly
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Side effects of MgSO4
• Maternal : flushing, perspiration, headache, muscle weakness, pulmonary edema
• Neonatal: lethargy, hypotonia, respiratory depression
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Magnesium levels Monitoring
• Normal Serum levels- 1.7- 2.4 mg/dl• Therapeutic range- 5- 9mg/dl• Patellar reflex lost- >12mg/dl• Respiratory depression- 15-20 mg/dl• Cardiac arrest- >25mg/dl
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Management of MgSO4 Toxicity
• Stop infusion• Intravenous Calcium 10 ml 10% over 10 minutes• Endotracheal intubation in respiratory depression
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Anaesthetic implications during MgSO4 therapy
o MgSO4 potentiate and prolong the action of both depolarizing
non-depolarizing muscle relaxants
o At higher doses Mg2+ rapidly crosses the placental barrier, has
been found to significantly ↓ FHR variability
o Should be given cautiously with Ca2+ as may antagonize the
anticonvulsant effect of MgSO4
o Also be cautious in patients with renal impairment
o May ↑ the possibility of hypotension during regional block
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Obs. Manag. Contd..
5. Delivery • The only definitive treatment• Preeclamptic patients divided into 3 categories
A- Preeclampsia features fully subsideB- partial control, but BP maintains a steady high levelC- persistently increasing BP to severe level or
addition of other features
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Management:Gp A: can wait till spontaneous onset of labor
don’t exceed Expected Date of Delivery Gp B: >37wk terminate w/o delay
<37wk, expectant management at least till 34wksGp C: terminate irrespective of POG, start seizure prophylaxis and steroids if<34wks
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Anaesthetic management
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Pre anaesthetic Evaluation
1.Airway 2. Haemodynamic monitoring :
blood pressure, ECG, Pulse oxymetry3. Fluid status: volume depleted patients
higher risk of hypotension with induction of anaesthesia
4. BP control5. Coagulation status
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Invasive Haemodynamic monitoring
• Invasive central blood pressure monitoring not routinely indicated
• Does not improve patient outcome• Indications:
-oliguria patients-pulmonary edema-poorly controlled maternal blood pressure- massive hemorrhage-frequent arterial blood gas measurements
• Poor correlation between central venous and pulmonary capillary wedge pressure
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Anesthetic Goals of Labor Analgesia in Preeclampsia
• To establish & maintain hemodynamic stability (control hypertension & avoid hypotension)
• To provide excellent labor analgesia• To prevent complications of preeclampsia– Pulmonary edema– Eclampsia– Intracerebral haemorrhage– Renal failure
• To be able to rapidly provide anesthesia for Caesarean Section
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Analgesia For Labor & delivery• Neuraxial analgesia:
Lumbar Epidural-
gradual onset of sympathetic blockadecardiovascular stability↓ stress responsemaintains uteroplacental circulationavoids neonatal depression extended analgesia if cesarean requiredexcellent post op analgesia
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Neuraxial analgesia contd..
Combined Spinal Epidural Analgesia- advantages of both
Spinal - rapidityrequires only small dose of LA↑vasopressor response-better control
of hypotensiondisadvantage: immediate verification of
catheter function not possible
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Anaesthesia for Caesarean• Epidural anaesthesia
• Spinal anaesthesia:advantage: rapidity
requires only small dose of LA↑vasopressor response-better control of
hypotension• Combined Spinal Epidural Anaesthesia – Indications:• Patient preference• Contraindications to general anaesthesia• Hemodynamically stable patient
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Anaesthesia for caesarean contd..
General anaesthesia:Indications
- coagulopathy -sustained fetal bradycardia with reassuring maternal airway - severe ongoing maternal hemorrhage - contraindications to neuraxial technique
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Concerns with neuraxialanaesthesia
• Adequate hydration:- risk of pulmonary edema-Lower concentration of local anesthetics: hypotension
less common• Treatment of hypotension if any:
- small doses of vasopressors • Epinephrine containing test dose should be avoided• Coagulation status
-mild preeclampsia-: hypercoagulable-severe preeclampsia-: hypocoagulable -bleeding time poor indicator of platelet function
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Platelets and neuraxial anaesthesia
• platelets >1lakh/mm3, coagulation profile not indicated
• Platelets <1 lakh/mm3
-clinical evidence of bleeding-platelet trend-Every 6hourly if stable, every 1-3hrly if declining
-coagulation profile: PT/PTTK/INR-quality of platelets-risk vs benefit
• Platelets <50,000: contraindication
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Platelets contd..
- remove epidural catheter only when platelet count returns normal (at least 75000-80000/mm3)
- emergency imaging studies and neurologic evaluation if epidural hematoma suspected
- In various studies, it has been found that low dose aspirin doesn’t significantly affect bleeding time, neuraxial analgesia can be given safely without any complication
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Coagulopathy and Neuraxial Anaesthesia
ASRA guidelines• Frank coagulopathy is an absolute contraindication• Subcutaneous (minidose) heparin thromboprophylaxis: not a
contraindication, however– Assess platelet count before needle placement and
removal of catheter, if > 4days heparin therapy– Stop heparin 4-5 days prior to needle placement
• With Low Molecular Weight Heparin:- needle placement and catheter removal 10-12 hours after
last dose, at higher doses after 24h- first post operative dose after 6-8 hours-repeat dose after at least 2hours of catheter removal
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Hazards of General Anaesthesia1.Difficult intubation-
-smaller size tube-difficult airway cart ready
2. Exaggerated and prolonged hypertensive response to laryngoscopy and intubation: -risk of intracranial hemorrhage.
-labetalol(5-10 mg), local anesthetics, esmolol( 2mg/kg ), nitroglycerine(200mcg/ml), nitroprusside 0.5mcg/kg/min, remifentanyl (1mcg/kg) used before intubation and
extubation
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Hazards contd..
3.MgSO4 with neuromuscular blockers, calcium channel blockers, uterotonics and uterine relaxants
4. Uterotonics avoided: risk of acute hypertension and eclampsia
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General Anaesthesia administration in severe Preeclampsia
Place a radial canula for continuous BP monitoring i.v line secured Arrange smaller size endotracheal tubes Antacids and perinorm given 30 minutes before 100% oxygen for 3 min. Labetalol 10 mg iv bolus and titrate to effect before
induction, while monitoring fetal heart rate Rapid Sequence Induction Labetalol 5-10 mg before extubation Give opioids or BZDS after delivery .
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Post op concerns
• Post op analgesia:intravenous opioids, neuraxial opioidsconcern : monitor for respiratory depression
• Post partum management: risk of pulmonary edema, sustained
hypertension, stroke, Venous thromboembolism, seizures,
HELLP, postpartum hemorrhage.
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Complications• CVA: main leading cause of death in pts with PE
absolute risk is low reversible cerebral edema is m/c
• Pulmonary edema, pleural effusion, ARDS:head end elevationoxygen therapyrestrict fluidsdiureticsmechanical ventilation
• laryngeal edema• Placental abruptio
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Complications contd..
• Renal failure: oliguria most commonhaemodynamic monitoringdiuretics
• Liver:Subcapsular liver hematoma: avoid trauma to liver, HELLP Syndrome, hepatic rupture with shock : surgical emergency
• DIC: treat the causeplatelets/Fresh Frozen Plasma/cryoprecipitate
• Eclampsia• Maternal death
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HELLP syndrome
Diagnosis:1. Hemolysis: – Peripheral smear– ↑bilirubin >1.2mg/dL, – LDH>600 IU/L
2. Elevated liver enzymes: – SGOT> 70 IU/L– LDH>600 IU/L
3. Low platelets: <1 lakh /mm3
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Management of HELLP syndrome
• Immediate hospitalisation• Stabilise mother– antihypertensives– anti seizure prophylaxis– correct coagulation abnormalities
• Assess fetal condition- FHR, doppler ultrasound, biophysical profile
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HELLP contd..
• Ultimate goal: – >34 wks gestation deliver– <34wks expectant management if stable maternal and
fetal conditions• Platelet transfusion if: <40,000/mm3 before cesarean
<20,000/mm3 before delivery
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Eclampsia
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ECLAMPSIA
• Is the new onset of seizures or unexplained coma during pregnancy or postpartum period in patients with pre-existing PE and without pre-existing neurological disorder.
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Epidemiology
• 0.1- 5.5 per 10,000 pregnancies• Decreasing incidence with time• Antepartum(50%): mostly in third trimester• Intrapartum(30%): • Postpartum(20%): usually within 48hours, fits beyond 7days
generally rules out eclampsia
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Risk factors
Maternal age less than 20 yearsMultigravidaMolar pregnancyTriploidyPre-existing hypertension or renal diseasePrevious severe Preeclampsia or EclampsiaNonimmune hydrops fetalisSystemic Lupus Erythematosus
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Clinical features• Eclamptic convulsions are epileptiform and consist of four
stagesPremonitory stage: twitching of muscles of face, tongue,
limbs and eye. Eyeballs rolled or turned to one side, 30sTonic stage: opisthotonus, limbs flexed, hands clenched,
30sClonic stage: 1-4 min, frothing, tongue bite, stertorous
breathing Stage of coma: variable period.
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Physical Examination
• Sustained rise in blood pressure• Tachycardia, Tachyponea • Rales • Mental status changes • Hypereflexia • Clonus • Papilloedema • Oliguria or anuria • Right upper quadrant or epigastric abdominal tenderness • Generalized edema • Small fundal height for the estimated gestational age
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Pathogenesis
• Loss of normal cerebral auto regulatory mechanisms cerebral hyperperfusion Edema & ↓cerebral blood flow
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Differential Diagnosis
• meningitis• encephalitis• space occupying lesion• electrolyte disturbance• vasculitis• amniotic fluid embolism• medications• organ failure• stroke
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Prediction and Prevention
• Early detection and judicious treatment with termination of pregnancy in Preeclamptic patients
• Adequate sedation, Anti hypertensives and prophylactic Anticonvulsant in peripartum period
• Observe for 24-48 hrs postpartum
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Management of Eclampsia
1. Prevention of seizures2. Control of seizures
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Prevention of convulsions• MgSO4 therapy:
DOC for prophylaxis of eclamptic convulsions
M.O.A:
blocks Ca2+ ion influx into neurons
leading to cerebral vasodilatation
Other actions: -lowers endothelin-1 levels
- ↑ production of PG I2
- tocolytic action
- attenuates the release of Ach and sensitivity to
Ach at myoneuronal junction
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Control of seizures
-turn patient head to one side, -apply jaw thrust if airway compromised- nasopharyngeal airway- Adequate oxygenation
- ensure adequate breathing , bag and mask ventilation can be done - secure an i.v line - Drugs- Antiepileptics Antihypertensives - Delivery
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Anticonvulsants Drugs Mechanism of action Contraindications Side effects
MgSO4Zuspan or sibai regime: 4-6g iv over 15 min f/b infusion of 1-2g/hPitchard regime: 4g i.v over 3-5min f/b 5g in each buttock with maintenance of 5g i,.m in alternate buttock 4hrly
Competitive inhibition of calcium ions at motor end plate or cell membrane, ↓ Ach release & sensitivity
Patients with MG and impaired renal function, heart block, digitalis
Maternal : flushingPerspiration, headache, muscle weakness, pulmonary edemaNeonatal: lethargy, hypotonia, respiratory depression
Diazepam 10-20 mg I.V f/b 40 mg diazepam in 500ml normal saline at 30 drops per minute
Cerebral muscle relaxant and anticonvulsants
Maternal : hypotension Fetal : respiratory depression, may last even 3 weeks after delivery
Phenytoin 10 mg/kg IV at not more than 50 mg/min f/b 2 hrs later by 5 mg/kg for 12 hrs, thereafter 200mg orally till 48hours
Centrally acting anticonvulsants
Maternal: hypotension, cardiac arrythmias, phlebitis, hyperglycemia, respiratory arrest, cardiac arrest, bradycardiaFetal: Fetal hydantoin syndrome
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Refractory seizures
• Thiopentone sodium 0.5 g in 20 ml of 5% Dextrose intravenously slowly
• Propofol infusion• Midazolam infusion• if fails then General Anaesthesia• Seizures still not controlled then termination of pregnancy
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Delivery in Eclampsia
Unless contraindicated: Eclamptic women should undergo normal vaginal delivery
Indications for cesarean section - Fetal distress
Placental abruption
Extreme prematurity
Unfavorable cervix
Failed induction of labor
Recurrent seizures
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Anaesthetic Management1. Assess seizure control and neurologic function2. Fluids : 75-100 ml/hr
avoid cerebral edema, CVP guided fluid therapy 3. BP control : appropriate anti hypertensives4. Monitoring :Pulse oxymeter , ECG, Fetal Heart Rate, Urine output,
NM monitoring, Mg monitoring,5. Lab inv: CBC, Bld sugar, Bld urea, S.creatinine, S.uric acid level
with S.E, LFTs, Coagulation profile, 24 hrs specimen for protein 6. Choice of anaesthesia: GA preferred with thiopentone or propofol
(both decreases ICP)7. Avoid hypo or hyperglycaemia, hypoxia, hyperthermia8. Peripartum : manage for shock, sepsis, psychosis
thrombocytopenia, DIC, coagulopathy
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Choice of Anaesthesia in Eclampsia
• Neuraxial: - indications - seizures controlled
- no coagulopathy - patient cooperative
• GA: -Indications -seizures not controlled
-coagulopathy -reassuring airway
-uncooperative patients
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General anesthesia in eclamptic pt.o Careful preanesthetic evaluation to be doneo Aspiration prophylaxis to be giveno Secure an i.v lineo Small endotracheal tubes ( 6 and 6.5mm) should be readyo Difficult airway cart should be readyo All monitors to be attachedo Start preoxygenation with100% oxygen via well fitting mask for 3-5 minutes
o Exaggerated CVS response should be pretreated with either lignocaine or beta blockers
o Induces anesthesia with : inj. Thiopentone 4-5mg/kg inj Sch 1-1.5mg/kg RSI #If pt. is on MgSo4
therapy, the usual fasciculation following Sch may not occur and it may take 60 sec.
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General anesthesia in eclamptic pt.
o Maintain anesthesia with 50% N2o+50% O2 +0.5% isoflurane until delivery of neonate, with inj. Vecuronium
#Neuromuscular monitoring to be done and dosage of NDMR to be titrated accordingly
o Extubation: Should be done after 24-48 hrs later in view of-
Postpartum seizure, Cerebral edema, Aspiration pneumonia, Hypertensive crisis, Pulmonary edema, ARDS
DIC, HELLP syndrome
Persistent oliguria
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Summary
• Preeclampsia is a multisystem disorder.• Management is supportive, delivery is the only definitive.• Preeclampsia patients: High risk for difficult intubation.• Hypertensive response to laryngoscopy intracranial
hemorrhage.• Spinal Anaesthesia not contraindicated in severe
Preeclampsia• Eclampsia can be prevented by prophylactic MgSO4 therapy• Eclamptic patients should be monitored for at least 24 hrs
post partum.
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References • Chestnut’s Obstetric Anaesthesia: Principles and Practice,
“Hypertensive disorders” 4th Ed, Ch 45, 975-1008 • Miller’s Anaesthesia, “Anaesthesia for Obstetrics” 7th Ed,Ch
69, 2227-2230• Wylie and Churchill Davidson’s A Practice of Anaesthesia,
“Obstetric Anaesthesia” 7th Ed, Ch57, 934• Morgan’s Clinical Anaesthesiology, “Obstetric Anaesthesia”
4th Ed, Ch 43, 910-912• Textbook of Obstetrics, D.C. Dutta, “Hypertensive Disorders in
Pregnancy” 6th Ed, Ch 17, 221-242• William obstetrics, “Pregnancy Hypertension” Ch34, 706-748• Bell M.J, BSN, RN, A Historical Overview of Preeclampsia-
Eclampsia J Obstet Gynecol Neonatal Nurs. 2010 September ; 39(5): 510–518
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