Hypertensive Disorders of Pregnancy

Question 1

Epidemiology of PreE

Answer 1

• Complicates 2-8% of pregnancies
• Contributes to 16% of maternal deaths (26% in Latin Amer & 9% in Africa/Asia)
• Increasing in the US and contributing to billions in cost

Question 2

Risk Factors of PreE (high)

Answer 2

(most cases occur in healthy nulliparous women with no obvious risk factors)
HIGH (recommend LDA if pt has 1 or more)
•	Multifetal gestations
•	PreE in a previous pregnancy
•	Chronic HTN
•	Pregestational DM (type 1 or 2)
•	Kidney/renal disease
•	Autoimmune disease (SLE, APS) Systemic lupus erythematosus, Antiphospholipid syndrome

Question 3

Risk Factors of PreE (moderate and low)

Answer 3

MODERATE (consider LDA if pt has more than one)
• Nulliparity
• Obesity/BMI (prepregnancy) greater than 30
• Family h/o PreE (mother/sis)
• Sociodemographic (African American, low socioeconomic status)
• AMA >35 years old
• Personal history factors (low birth, SGA, prev adverse pregnancy outcome, >10-year interpregnancy interval)
• Gestational DM
• Thrombophilia
• Assisted reproductive technology
• Obstructive sleep apnea
LOW (do not rec LDA)
Previous uncomplicated full term delivery

Question 4

Definition of Preeclampsia

Answer 4

• BLOOD PRESSURE - New onset HTN after 20 weeks gestation
o (>140/90 on 2 occasions more than 4 hours apart when BP was previously nml)
o 160/110 (severe htn)
• AND…
• w/ proteinuria
o 300 mg in 24 hr urine or higher
o Protein:creatinine of 0.3 or higher
o Dipstick of 2+ protein
• OR WITHOUT PROTEINURIA AND ONE OF THE FOLLOWING (new onset):
• Thrombocytopenia (less than 100 X10^9/L)
• Renal insufficiency (serum creatinine >1.1mg/dL or doubling of baseline creatinine)
• Impaired liver function (LFTs double the normal concentration)
• Pulmonary edema
• Headache (new onset, not responsive to meds, no other alternative diagnosis)
• RUQ pain, epigastric pain (severe and persistent)

Question 5

Differential of PreE if < 20 weeks

Answer 5

• Thrombotic thrombocytopenic purpura
• Hemolytic-uremic syndrome
• Molar pregnancy
• Renal disease
• Autoimmune disease

Question 6

Definition of Preelampsia w/severe features

Answer 6

• 160/110 on 2 occasions >4 hours apart
• Thrombocytopenia (platelet less than 100X10^9/L)
• Renal insufficiency (serum creatinine >1.1mg/dL or doubling of baseline creatinine)
• Impaired liver function (LFTs double the upper limit of normal) w/RUQ/epigastric pain
• Pulmonary edema
• Headache (new onset, not responsive to meds, no other alternative diagnosis)
• Visual disturbances (blurred vision, scotomata, hyper reflexia)

Question 7

Definition of Gestational Hypertension

Answer 7

• BLOOD PRESSURE - New onset HTN after 20 weeks gestation
o (>140/90 on 2 occasions more than 4 hours apart when BP was previously nml)
o 160/110 (severe GHTN)
o *occurs when hypertension without proteinuria or severe features develops and BPs return to normal in the postpartum period
o Up to 50% of women w/GHTN will develop proteinuria or other end-organ dysfunction consistent with the diagnosis of preeclampsia
 More likely if GHTN occurs before 32 weeks

Question 8

HELLP (Hemolysis, elevated liver enzymes, and low platelet count syndrome)

Answer 8

• More severe form of preeclampsia
o Increased rates of maternal morbidity and mortality
o Mostly in the 3rd TM but 30% of cases expressed/progress postpartum
o Patients may lack HTN and proteinuria
• Diagnosed by:
o LDH (lactate dehydrogenase) over 600 IU/L
o AST (aspartate aminotransferase) and ALT (alanine aminotransferase) elevated more than twice the upper limit of normal
o Platelets less than 100 X10^9/L
• Presents with:
o RUQ pain/malaise – 90%
o N/V – 50%

Question 9

HELLP treatment

Answer 9

 Watch for sudden deterioration in mom/fetus
 Women with help should be delivered regardless of gestational age
 Need NICU and ICU (obstetric ICU) – transfer to tertiary care center
 Tx with corticosteroids helps improve platelets
o Does not improve maternal death, morbidity in mom or fetus
 Close monitoring with labs q 12 hours
 AST > 2000 and LDH >3000 show increased mortality risk
 Supportive care and labs should begin to improve within 4-7 days of delivery

Question 10

Eclampsia

Answer 10

o Convulsive manifestation of hypertensive disorders of pregnancy
o Defined by new-onset tonic-clonic, focal or multifocal seizures in the absence of other causative conditions (epilepsy, drug use, cerebral arterial ischemia/infarction, intracranial hemorrhage)
o Preceded by persistent occipital/frontal headaches, blurred vision, photophobia, altered mental status in 78-83% of cases
o Preeclampsia evolves to eclampsia in only 1.9% of cases
o Severe preeclampsia evolves to eclampsia in 3.2 % of cases
o Others have no signs preceding eclampsia

Question 11

Eclampsia treatment

Answer 11

Eclampsia treatment
 Supportive measures (eclamptic seizures are usually self-limited)
o Call for help
o Prevent maternal injury
o Place in left lateral decubitus position
o Prevent aspiration
o Administer oxygen
o Monitor vitals
 Mag sulfate does not arrest current seizure but prevents them from recurring
o Better than phenytoin, diazepam or lytic cocktail (chlorpromazine, promethazine and pethidine) – less maternal and neonatal morbidity

Question 12

Refractory treatment for Eclampsia

Answer 12

 During seizure – likely to observe prolonged decelerations/bradycardia
 After seizure – recurrent decels, tachycardia, diminished variability
 When maternal hemodynamic stabilization occurs, proceed with delivery
o Heart tracing should also normalize
o C-section is likely but not a must; consider clinical scenario
 May consider:
o Clonazepam 1mg IV
o Diiazepam 10 mg
o Midaazolam
 These inhibit laryngeal reflexesinc aspiration risk; use with caution
 If pt continues to seize
o Another bolus of magnesium sulfate 2-4 g IV over 5 min X2 doses
 If pt continues to seize for 20 min
o Sodium amobarbital 250 mg IV in 3 minutes
o Thiopental
o Phenytoin 1250 mg IV at 50 mg/min (over 15 min)
o Likely need endotracheal intubation, assisted ventilation, ICU, head imaging

Question 13

Screening for PreE

Answer 13

 Biochemical and biophysical markers in 1st and 2nd TM have low PPV
o Those who screen positive will not develop the disease
o A large number of pts would be exposed to testing and not benefit from intervention
o Uterine artery Doppler studies, angiogenic factors, placental growth factor
 No single test reliably predicts preeclampsia

Question 14

Prevention of PreE

Answer 14

 No intervention to date has been proven to unequivocally eliminate the risk of preE.
 Have tried; VitC, VitE, fish oil, garlic, Vit D, folic acid, sodium restriction, Ca++, bed rest
 Imbalance in prostacyclin and thromboxane A2 metabolism
o Aspirin preferentially inhibits thromboxane A2 at lower doses
o Modest risk reduction of PreE when beginning ASA after 16 weeks gestation
 Begin LDA 91 mg 12-26 wks until delivery
o More significant reductions in severe PreE and growth restriction
 Current studies on metformin, sildenafil and statins
o Not recommended outside of clinical trials

Question 15

Treatment

Answer 15

 Labs
o CBC (platelets), creatinine, LDH, AST, ALT and testing for proteinuria
 Consider uric acid if superimposed on chronic HTN
 Comprehensive clinical maternal and fetal evaluation
o Ultrasound of fetus
 Estimated fetal weight (EFW) and amniotic fluid index (AFI)
• Serial growth US (every 3-4 wks)
 Antepartum testing (NST or BPP)
• Weekly to twice weekly
• AFI weekly
 Close monitoring of BPs and weekly labs
• Progression from GHTN to PreE w/severe 1-3 weeks
• Progression from PreE to PreE w/severe could happen in days
 Decision to deliver balances maternal and fetal risk
 May continue pregnancy if diagnosis is GHTN or PreE without severe features
o Until 37 0/7
o HYPITAT trial
 After 36 weeks IOL group had reduction in adverse maternal outcome and no differences in rates of neonatal complciations

Question 16

Balance the risks

Answer 16

o	Risks for delayed delivery
o	Severe HTN
o	Eclampsia
o	HELLP syndrome
o	Placental abruption
o	Fetal growth restriction
o	Fetal death

o Benefits for delayed delivery
o Avoid prematurity
o Avoid NICU admission
o Avoid neonatal respiratory complications

Question 17

Maternal complications in Preeclampsia with severe features

Answer 17

o	Pulmonary edema
o	Myocardial infarction
o	Stroke
o	Acute respiratory distress syndrome
o	Coagulopathy
o	Renal failure
o	Retinal injury
Thus delivery in the setting of severe features at or beyond 34 0/7

Question 18

Conditions precluding expectant management

Answer 18

o Maternal
o Uncontrolled severe range blood pressures (160/110 not responsive to tx)
o Persistent headaches (refractory to treatment)
o Epigastric pain or RUQ pain unresponsive to repeat analgesics
o Visual disturbances, motor deficit or altered sensorium
o Stroke
o Myocardial infarction
o HELLP syndrome
o New or worsening renal dysfunction (serum creatinine greater than 1.1 or twice baseline)
o Pulmonary edema
o Eclampsia
o Suspected acute placental abruption or vaginal bleeding in the absence of previa
o Fetal
o Abnormal fetal testing
o Fetal death
o Fetus without expectation for survival at time of diagnosis (lethal anomaly, extreme prematurity)
o Persistent reversed end diastolic flow in the umbilical artery

Question 19

Proper way to check a blood pressure

Answer 19

o Appropriate sized cuff
o Cuff length 1.5 X the circumference of the arm or bladder encircles 80% of arm
o Taken in an upright position (sitting or in left lateral recumbent)
o After 10 minutes or more of rest
o No tobacco or caffeine in the previous 30 minutes

Question 20

Intrapartum management

Answer 20

1 Prevent seizures

#2 Control of hypertension
o Magnesium sulfate (smooth muscle relaxant)
o Cuts rate of eclampsia by more than half (in preE w/severe)
• Seizure rate of PreE w/severe 4/200 (4 times higher)
• Treat 36 patients to prevent 1 seizure
 Uncertain effect when used in GHTN and PreE without severe)
• Seizure rate of PreE without 1/200
o Reduces the risk of placental abruption
o Slight reduction in the risk of maternal mortality
o Therapeutic range
o 4.8-9.6 mg/dL or 4-8 mEq/L
o Beware of mag toxicity

Question 21

Magnesium sulfate dosing

Answer 21

o 4-6 g IV loading dose over 20-30 min (10 g IM (5 g in each buttock))
o 1-2 g/hr IV maintenance dose (5 g IM every 4 hours)
 Use 1 mL xylocaine 2% due to painful injection
o Continue during surgery (if needed) and for 24 hours postpartum
o REVERSAL with calcium gluconate 10% solution 10 mL IV over 3 min
 Add furosemide IV to accelerate urinary excretion

Question 22

Magnesium sulfate reactions and side effects

Answer 22

o Respiratory depression (12 mg/dL or 10 mEq/L)
o Cardiac arrest (30 mg/dL or 25 mEq/L)
o Loss of deep tendon reflexes (lost at mag level of 9 mg/dL or 7 mEq/L)
o Hot flushes (25%)
o Increased rate of c-section (inc by 5%)
o Measure urine output
 (if creatinine 1-1.5 then use only 1 g/hr maintenance)
 Serum mag levels every 4 hours
o Follow deep tendon reflexes
o Mag sulfate is the drug of choice
o More effective than phenytoin, diazepam or nimodipine

Question 23

Contraindications to mag sulfate use

Answer 23

o	Myasthenia gravis
o	Hypocalcemia
o	Moderate to severe renal failure
o	Cardiac ischemia
o	Heart block
o	Myocarditis

Question 24

Labetalol

Answer 24

o 10-20 mg IV
o Onset of action in 1-2 min
o Then 20-80 mg IV every 10-30 min
o Max dose of 300 mg (may give constant infusion of 1-2 mg/min IV)
o SE
o Less tachycardia than others
o Avoid in asthma, myocardial dz, heart block, bradycardia, decompensated cardiac function

Question 25

Outpatient labetalol

Answer 25

o Initiate expeditiously (within 30-60 min) if severe range pressure 160/110 are persistent (>15 min)
o Begin labetalol 200 mg orally every 12 hrs
o Increase up to 800 mg every 8-12 hrs
o Maximum total daily dose of 2400 mg
o If this does not adequately control the pressure then add oral nifedipine

Question 26

Hydralazine

Answer 26

o 5 mg IV or IM
o Onset of action 10-20 min
o Then 5-10 mg IV every 20-40 min
o Max dose of 20 mg (may give constant infusion of 0.5-10 mg/hr
o SE
o When dosing is higher/more frequent, it leads to maternal hypotension, headaches, abnormal fetal heart rate tracings (more common than others)

Question 27

Nifedipine

Answer 27

o	10-20 mg orally
o	Onset of action 5-10 min
o	Repeat 10-20 mg orally in 20 min
o	Then10-20 mg every 2-6 hours
o	Max daily dose of 180 mg
o	SE
o	May observe reflex tachycardia and headaches

Question 28

Anesthesia for PreE

Answer 28

o Regional anesthesia is the preferred technique for women with preE w/severe and eclampsia
o Epidural does not increase c-sec rate, pulmonary edema or renal failure
o Spinal has > hypotension than epidural (51% vs 23%)
o General anesthesia has greater risk
o Aspiration
o Failed intubation due to pharyngolaryngeal edema
o Stroke due to increased intracranial pressures (intubation/extubation)
o But epidural/spinal may not be appropriate due to coagulopathy
 Thrombocytopenia increases risk of epidural hematoma
 No safe lower-limit for platelets exist but higher than 70 X 10^9 shows low risk of epidural hematoma
o Mag sulfate prolongs nondepolarizing muscle relaxants
 ½ life of mag sulfate is 5 hours
 Does not help to shut off the mag for the c-section (it should continue)

Question 29

Subsequent risk of cardiovascular disease

Answer 29

With recurrent preeclampsia, the risk is 4-8 times higher than a normal pregnancy
 Increased risk of:
o Hypertension (5 times higher)
o Cardiovascular disease (2 times higher)
o Myocardial infarction
o Congestive heart failure
o Cerebrovascular events/ stroke
o Peripheral vascular disease
o Cardiovascular related mortality
 Endothelial dysfunction is liked to atherosclerosis
 Manage risk factors (achieve healthy weight, exercise, diet, quit smoking)