Preeclampsia and Eclampsia

Preeclampsia and Eclampsia

Ravindra Prasad, M.D.

UNC-Chapel HillMorning ConferenceNov. 7 and 8, 1996

HTN during pregnancy:

• Preeclampsia– HTN, generalized edema, proteinuria– after 20th week gestation (mostly after 24th)– (hyperreflexia)

• Eclampsia– Preeclampsia + grand mal seizure unrelated to other neurologic disease

• Chronic HTN– HTN before 20th wk, or > 6 wks. postpartum

• Chronic HTN with superimposed (Pre)eclampsia

• Gestational HTN– Isolated HTN (no edema, proteinuria) late in pregnancy (last wks)– Resolves within 2 wks postpartum

• PIH– all of above associated with pregnancy

Preeclampsia/eclampsia

• BP– inc. in SBP 30 mmHg, or SBP > 140– inc. in DBP 15 mmHg, or DBP > 90– inc. in MAP 20 mmHg, or MAP > 105– (measured in lateral position, at least 6 hrs apart)

• Proteinuria– > 300 mg protein/liter in 24 hr urine collection– >1 gm protein/liter (1+ or 2+ dipstick) in two samples >6 hrs apart

• Edema– generalized, not just dependent

• Gestational age– > 20 wks– earlier than 20wks if molar pregnancy

Preeclampsia/eclampsia, severe

• SBP > 160

• DBP > 110

• MAP > 120

• Proteinuria: > 5 gm/24 hrs (3+ or 4+ dipstick)

• oliguria: <500 ml urine/24 hrs

• HA or CNS changes

• epigastric (liver) pain

• pulmonary edema or cyanosis

• HELLP Syndrome (hemolysis, elevated liver enzymes, low platelets)

Incidence

• Preeclampsia: 2.6-7 % of all pregnancies• Eclampsia: 0.02-0.07 % of all pregnancies

– onset before (44, 17%), during (37, 52%), or after (19, 34%) delivery

– if after, 43% within 4 hrs., 86% within 24 hrs

• Risk factors– <20 yo vs. >20 yo: 5x incidence– Unmarried > married– Medicaid > private insurance

Morbidity/mortality: Maternal

• leading cause of maternal death (20-40%) in US, England, and Scandinavia

• intracranial hemorrhage (#1 cause of mortality)

• CHF with pulmonary edema

• aspiration of gastric contents

• postpartum hemorrhage

• DIC

• ARF

• ruptured liver

• septic shock

Morbidity/mortality: Fetal

• intrauterine mortality– *placental infarction– retarded placental growth– abruptio placentae– acute infection of amniotic fluid

• morbidity– severe maternal HTN assoc. with inc. incidence of

mental retardation, global and motor dysfunction•mortality > 93% if severe preeclampsia develops before 24 wks gestation

Perinatal morbidity/mortality

• related to preterm birth– respiratory distress– intracranial hemorrhage– SGA– meconium aspiration

Morbidity/mortality: Eclampsia

• maternal mortality 0.4-11.9% (higher with greater age and parity and number of seizures)

• perinatal mortality 20-30%

Etiology

• Unknown• The normal balance is lost between vasodilators /

anticoagulants (PGE2, prostacyclin, NO, tissue plasminogen activator) and vasoconstrictors / procoagulants (thromboxane, angiotensin, tissue plasminogen inhibitor)

• Imbalance may be related to endothelial cell injury, or to placental trophoblastic production of thromboxane

Etiology

dec vasoconstriction dec plt aggregation dec uterine activity inc uteroplacental blood flow

inc vasoconstriction inc platelet aggregation inc uterine activity dec uteroplacental blood flow

Normal Pregnancy

Preeclampsia/eclampsia

prostacyclin PGE2

nitric oxide tissue plasminogen

activator

thromboxane tissue plasminogen inhibitor angiotensin

decreased synthesis increased synthesis

endothelial cell damage

release of factors, eg fibronectin

decreased placental perfusion

spiral arteries maintain muscular wall, remain constricted

loss of capillary endothelial integrity

chronically hyperdynamic heart

prolonged hyperperfusion

Microvilli may slough off (maternal blood is in direct contact with placental syncytiotrophoblast)

Activated decidual PMNs (decidua is mostly lymphoid tissue)

cytokines, oxygen-free radicals

leukotrienes

inc. vascular permeability vasoconstriction further PMN activation

Pathophysiology: Airway

• excess sodium and water retention

• decreased colloid oncotic pressure from proteinuria

• inc. upper airway/laryngeal edema

• magnesium, sedatives, narcotics can ==> hypoxia, hypercarbia

Pathophysiology: Coagulation

• thrombocytopenia (platelets < 150,000 in 11-50%) – (?due to consumption at sites of endothelial damage or

immune mechanism)

• altered platelet function (prostaglandin imbalance)• increased platelet turnover (more immature

platelets)• slight inc. in PTT (statistically, but not clinically

significant - 29.8±6.6 vs 26.4±1.8)

Pathophysiology: Cardiovascular 1

• inc BP

– widespread vasoconstriction

– Plasma volumes markedly decreased, RBC mass unchanged• inc. blood viscosity

– normal-hyperdynamic LV function

– inc. in BP related to inc. CO more than to inc. SVR

Pathophysiology: Cardiovascular 2

• inc. response to vasoactive drugs• CVP tends to be low (except, if pulmonary

edema, almost always 6)

• PCWP tends to be normal, but IVF supplementation can cause pulmonary edema in some patients

• inc. levels of renin, angiotensin, catecholamines, and atrial natriuretic factor

Pathophysiology: Pulmonary edema

• 2.9-5% of patients• more likely older multiparae with preexisting cHTN• may be related to

– Colloid oncotic pressure may be decreased

– capillary endothelial damage

• usually assoc. with sepsis, DIC, abruptio, preexisting cHTN, and/or excessive IVF

• usually in first few postpartum days

Pathophysiology: Renal

• dec renal blood flow (renal artery vasospasm vs. volume overload with cardiac dysfunction)

• loss of protein (proteinuria)

• ARF (8%) with oliguria may occur (even with normo- or hypervolemia), esp. if abruptio placentae with DIC, HELLP, or cHTN also present

• inc. uric acid levels

• renal changes may reverse with resolution of disease (not known), though preeclampsia + cHTN often ==> permanent renal damage

Pathophysiology: Hematologic

• left shift of hemoglobin dissociation curve (= dec O2 unloading to fetus) (mechanism: ? inc. catabolism of RBCs ==> inc. carboxyhemoglobin)

• hemolysis (intense vasospasm ==> endothelial disruption ==> platelet adherence, fibrin deposition)

Pathophysiology: CNS

• cerebral edema and/or change in CBF may cause sx (HA, visual changes, irritability)

• cerebral hemorrhage may occur, though BPs rarely are beyond limits of cerebral autoregulation

• 45% of eclamptics will have some CT abnormality

• 90% of eclamptics will have abnormal EEG

Pathophysiology: HELLP Syndrome

• usually before 36 wks gestation• symptoms:

– malaise 90%

– epigastric pain 90%

– N/V 50%

– some with flu-like symptoms

• rapidly progressive, to DIC, liver failure, renal failure: requires immediate delivery

• platelet count nadir 24-48 hrs postpartum

Pathophysiology: Hepatic

• usually little involvement• if severe preeclampsia or HELLP, can have more

involvement:– periportal hemorrhages

– ischemic lesions

– generalized swelling

– subcapsular hematoma

– hepatic swelling ==> epigastric pain

– hyperreflexia

– inc. CNS irritability

Pathophysiology: Uteroplacental

• uterine and placental blood flow dec 50-70%, due to:– vasospasm from decreased uterine prod of vasodilators

– inc. viscosity

– catecholamines can cause exaggerated vasospastic response

• hyperactive uterus

• inc. sensitivity to oxytocin– rapid labor, painful contractions common

– PTL frequent

• placenta often small, with infarcts, fibrin deposition, calcification, and abruption

• inc. incidence of abruptio placentae (10%)

Pathophysiology: other

• Total plasma albumin decreased

• inc. fibrin split products

• dec levels plasma cholinesterase

Therapy

• Delivery of fetus

• Pregnancy allowed to continue until it becomes a danger to fetus (unable to support fetal growth) or mother

• Vaginal delivery not contraindicated if fetus tolerates

• C-section indicated if– markedly premature, but viable fetus

– significant compromise of intrauterine environment:• falling BPP

• fetal distress

– mother rapidly deteriorating

Therapy, continued pregnancy

• Goals

– minimize vasospasm

– inc. circulation (esp. to uterus, placenta, and kidneys)

– inc. intravascular volume

– correct acid-base and electrolyte abnormalities

– dec CNS hyperactivity

• Bed rest, lateral decubitus position may dec BP

• Normal diet (no sodium or fluid restriction)– adequate hydration and intravascular volume expansion may lower

BP

Magnesium: Beneficial effects 1

• (therapeutic = 4-6 mEq/L, toxicity if >10 mEq/L)• Anticonvulsant (CNS depressant)• Vasodilation (mild: decreases smooth muscle

contraction, depresses catecholamine release)– inc. uterine blood flow

– inc. renal blood flow

– dec BP (not reliable)

• inc. prostacyclin release by endothelial cells

Magnesium: Beneficial effects 2

• dec plasma renin activity

• dec ACEs

• dec vascular response to pressors

• dec platelet aggregation

• bronchodilation

• tocolysis– improves uterine blood flow– decreases uterine hyperactivity

Magnesium: Detriments 1

• tocolysis– prolonged labor

– inc. postpartum hemorrhage

• dec FHR variability

Magnesium: Detriments 2

• myoneural blocking effects– generalized muscle weakness

– inc. sensitivity to muscle relaxants, esp. NDMRs (decreases the amount of ACh released, the depolarizing effect of ACh, and the muscle membrane excitability)

• neonatal effects– lower Apgar scores

– dec muscle tone, respiratory depression, apnea (only with maternal overdose)

Magnesium overdose

• weakness

• respiratory insufficiency

• cardiac failure

• usually after decrease in DTRs

• symptoms may be partially overcome by iv calcium (in mom, this will antagonize the anticonvulsant effects of Mg also)

Antihypertensives

• Indicated if SBP>160 or DBP>110 despite Mg therapy

Antihypertensives: Hydralazine

• decreases precapillary arteriolar resistance ==> dec BP

• however, assoc. inc. CO and inc. HR may counterbalance BP effect

• increases renal blood flow

• maximum effect 20-30 min. after iv dose

• duration 2-3 hrs

• may dec uterine blood flow

• assoc. with fetal distress

• may be assoc. with neonatal thrombocytopenia

Antihypertensives: Labetolol

• nonselective beta blockade

• selective post-synaptic alpha-1 blockade

• beta:alpha = 3:1 (oral) or 7:1 (iv)

• may also cause beta-2 related vasodilation

• more rapid onset than hydralazine

• lacks hydralazine’s side effects (inc. HR, nausea, HA, excessive dec BP, dec uterine blood flow)

Antihypertensives: Calcium channel blockers

• vascular smooth muscle relaxants ==> dec SVR• potent uterine relaxants (may inc. risk of

postpartum hemorrhage if given close to delivery time)

• inc. renal blood flow, UOP• nifedipine preferred (lacks associated tachycardia)• caution if also using magnesium - hypotension,

respiratory difficulty, and additive cardiac toxicity (Mg may also be working as a CCB)

Antihypertensives

• Methyldopa– esp. if cHTN

• alpha-1 blockers– Clonidine

– Prazosin

• Propanolol– clinically, appears safe for mom and fetus

• Esmolol– Beta-1 selective

– ewe studies: fetal beta blockade, hypoxemia - additional studies needed

• Trimethaphan, SNP, NTG– usually for acute control of BP on induction and emergence, GA

Convulsions: treatment 1

• Must control seizure, then deliver baby

• mortality increased by # of seizures

• STP 50-100 mg, Diazepam 2.5-5 mg, midazolam 1-2 mg, magnesium 2-4 gm

• Then, to prevent additional seizure, magnesium 2-4 gm/hr, or other anticonvulsant

• If seizure continue, may indicate additional CNS pathology– venous thrombosis– intracerebral hemorrhage– cerebral edema

Convulsions: treatment 2

• Give O2• If cannot control quickly, RSI - protect airway and

prevent aspiration• postictal depression may require ventilation

(prevent hypoxia, hypercarbia)• Give bicarbonate if metabolic acidosis develops• If CHF or pulmonary edema, diurese• If cerebral edema, consider mannitol (if adequate

UOP only) and/or dexamethasone 10-16 mg

Monitoring 1

• Frequent BP - NIBP usually OK

• Foley - monitor UOP, protein excretion

• FHR and uterine contraction monitoring– preeclampsia: dec uterine and placental blood

flow, uterine hyperactivity (long, frequent contractions) - fetus may not tolerate; may need to section

• SpO2 (early sign of pulmonary edema)

Monitoring 2

• ABP if pulmonary edema, ventilated, or require freq. ABGs, or if on vasodilator gtts

• CVP if severe disease, esp. if marked HTN or oliguria, or major conduction analgesia

• PAC if LV failure or other cardiac disease present or refractory oliguria

Monitoring: Indications for PAC

• Unresponsive or refractory HTN: inc. SVR vs. inc. CO?

• Pulmonary edema: LV failure vs. inc. SVR vs. volume overload vs. dec colloid oncotic pressure (can try to dec. PCWP to less than oncotic pressure, in effort to minimize pulmonary fluid shifts)?

• Persistent arterial desaturation: cardiac vs. noncardiac?

• Oliguria unresponsive to modest fluid loading: low preload vs. severe inc. in SVR with low CO vs. selective renal artery vasoconstriction?

General considerations 1

• avoid rapid infusion of dextrose-containing fluids (maternal hyperglycemia is assoc. with fetal hypoglycemia, hyperbilirubinemia)

• use balanced salt solutions (giving free water may lead to water intoxication)

• volume-loading for epidural– NS/LR - rapid dosing of 2L BSS may lower colloid

oncotic pressure for 24 hrs

– 5% albumin - in severe preeclamptics, 500-1000cc increases CO, dec SVR with minimal lowering of MAP

General considerations 2

• monitor CVP/UOP/signs of pulmonary edema if giving large volumes quickly

• maintain left lateral position

• give O2 during delivery

Vaginal delivery

• narcotics - give early, small dose to minimize neonatal depression

• 30-40 % N2O in O2 for first stage of labor - augment with pudendal block or local for forceps delivery– may add 0.3-0.5% isoflurane for additional analgesia

– or may add ketamine (up to 0.75 mg/kg) incrementally for additional analgesia

– not ideal obstetric conditions

Vaginal delivery - CLE 1

• contraindications– significant coagulation abnormalities

(decreasing platelet count, esp if < 100,000 may be a relative contraindication)

– ±septicemia– marked untreated hypovolemia


• benefits– ideal conditions for vaginal delivery, including

forceps/vacuum

– can be used for c-section

– decreases O2 requirements during labor

– prevents pain-related hyperventilation during labor (which can dec uterine blood flow and cause maternal metabolic acidosis)

– significantly decreases circulating catecholamines

– improves intervillous blood flow


• potential problems– sudden hypotension may dec intervillous blood flow

– local anesthetics may dec beat-to-beat variability (slightly) and thus impede diagnosis of fetal hypoxia and distress (occurs with lidocaine, not bupivacaine

– local anesthetic may predispose to convulsions

– can avoid problems• avoid aortocaval compression• ensure adequate hydration - may monitor CVP• small doses ephedrine

– dec intervillous blood flow only occurs if dec BP (if managed correctly, actually increase uterine artery and intervillous blood flow)

– other analgesics cause great(er) loss of beat-to-beat variability


• Preparation– control BP; DBP<110– confirm coagulation times OK– monitors (as above)– prehydrate, CVP up to 6 cm water (500 cc usually

enough for CLE; 1-2L for c/s, and may want to substitute some colloid)

• Place early (avoid narcotic-related fetal depression)

Vaginal delivery - CLE 5: details

• T10-L1 for Stage I: pain from uterine contraction, cervical dilation (T11-12)

• if BP OK, extend block slowly to cover T8-S5 for rest of labor and delivery– Stage II: pain from distention of lower vagina, vulva, and

perineum, S2-4

– analgesia for forceps delivery, episiotomy

– perineal analgesia• prevents uncontrollable bearing down by the mother, which is assoc.

with sudden changes in CV and CNS systems

• minimizes likelihood of precipitous delivery of preterm or SGA neonate, which is assoc. with neonatal intracerebral hemorrhage

Vaginal delivery - CLE 6: details

• may add fentanyl/epinephrine to inc. quality/duration of block

• For c-section, extend block to T4 (going from T8 ==> T4 causes less hypotension than if start with lower level)

Vaginal delivery - SAB 1

• if delivery imminent, saddle block to T10 level• BP usually maintained if

– block no higher than T10

– maintain LUD

– prehydrate

• hyperbaric lidocaine 35-50 mg, bupivacaine 5-7.5 mg, or tetracaine 4-6 mg

• add fentanyl 15-25 µg for better quality/duration

Vaginal delivery - SAB 2

• disadvantages– risk of PDPH - use small gauge, pencil point

needles– cannot extend block if need to do c-section

Cesarean Section

• often indicated b/c of deterioration of intrauterine environment or mother’s condition

• If there is time (may need 30 minutes to slowly raise level), and no contraindications, epidural anesthesia is technique of choice

C-section - Epidural anesthesia

• may add fentanyl 50-75 µg to speed onset, prolong duration, improve quality of block, and dec visceral discomfort from uterine exteriorization and interiorization, and peritoneal retraction

• advantages of epidural– as above for CLE

– maternal bonding

– epidural morphine for 24 hrs excellent analgesia, or post-op infusion

– avoid GA/RSI/aspiration risk/sudden inc. in BP (which is assoc. with pulmonary edema, cerebral edema, and intracranial hemorrhage)

C-section - SAB

• sudden establishment of T4 level often assoc. with sudden, profound sympathectomy

• prophylactic ephedrine may be risky• still preferable to GA for some (controversial)• hyperbaric lidocaine 70-80 mg, bupivacaine 12-15

mg, tetracaine 9-11 mg with epinephrine 100-200 µg• may add fentanyl of morphine to improve quality,

dec. visceral discomfort, and provide post-op pain relief

C-section - General Anesthesia 1

• considerations– upper airway edema– drug interactions (e.g. magnesium)– marked hypertensive responses to intubation,

surgical stimulation, extubation


• airway– usual pre-op evaluation

– look for dysphonia, dysphoria, dyspnea, respiratory distress

– small diameter ETT

– be prepared for difficult intubation

– consider awake intubation

– do not traumatize nasal passages (suction, airway, ...) • can cause difficult-to-control epistaxis (and don’t use nasal

phenylephrine)


• magnesium– more sensitive to muscle relaxants

– succinylcholine 1.5 mg/kg, up to 120 mg

– no other relaxants unless surgeons require it and nerve stimulator indicates need

– may give 5-10 mg succinylcholine boluses (not infusion - pseudocholinesterase levels significantly decreased in preeclamptics)

– if use NDMR, give v small doses, e.g. vecuronium 1-2 mg

– can usually avoid additional muscle relaxants if give 2/3 MAC volatile agent + 60-70% N2O after delivery


• stimulation– can cause marked inc. in BP, HR, and circulating catecholamines– multips age > 25 at greatest risk– pre-treatment with lidocaine d/n work– can pre-treat with opioids, though this may cause neonatal depression– decrease DBP to about 95 mmHg– labetolol - give incrementally, up to 0.5-1 mg/kg prior to induction– NTG - may improve placental gas exchange– SNP - in preeclamptics, an altered response to SNP-induced vasodilation can

cause sudden hypotension at very low doses (0.3 µg/kg/min)– Trimethaphan– CCBs– see table for advantages/disadvantages


• Anesthetic– up to 2/3 MAC volatile agent (0.5% halothane,

0.75% isoflurane) in oxygen alone until delivery - higher concentrations may be assoc. with inc. uterine bleeding (atony), neonatal depression

– prevent hypoxia (maternal left-shift of hemoglobin curve)

– keep ETCO2 >25 mmHg before delivery (alkalosis ==> further left-shift)

Documents

Preeclampsia and Eclampsia