C.G. is a 39-year-old pregnant woman presenting with increased blood pressure and swelling. At 28 weeks gestation, her blood pressure was 180/100. She was diagnosed with preeclampsia based on her gestational hypertension and proteinuria. Preeclampsia is a hypertensive disorder of pregnancy affecting 7-10% of pregnancies. It is characterized by new onset hypertension and proteinuria after 20 weeks of gestation. Symptoms can range from mild to severe, including headaches, visual disturbances, RUQ pain, and others. Progression of preeclampsia must be closely monitored to determine optimal timing of delivery to prevent maternal and fetal complications.

1. Hypertensive Disorders With
Pregnancy
Hisham M. Gamal, MD
lecturer of Anaesthesia and postoperative
ICU
Alexandria Faculty Of Medicine
[hisham.gamal83@yahoo.com]

2. • C.G. is a 39 year old married white female gravida 2, para 0,
with one spontaneous abortion who presented for prenatal care
at 14 weeks gestation. Blood pressure at that time was 130/80.
The patient had no significant medical history and her
gynecologic history was significant only for oral contraceptive
use several years ago.
• The pregnancy had been unremarkable until approximately one
month ago when the patient noted increased swelling of her
hands and feet. A 6 Kg. weight gain in two weeks time was
noted. Blood pressure at that time was 124/78. There was no
urinary protein. On the day prior to admission, at 28 weeks, the
patient presented with a blood pressure of 160/98 and had
been sent home to bedrest with instructions to take a single
baby aspirin daily. On the day following, the patient was noted
at home to have a persistent blood pressure of 180/100.

3. Avant propos…
• Complicates 7-10% of pregnancies
– 70% Preeclampsia-eclampsia
– 30% Chronic hypertension
– Eclampsia 0.05% incidence
• 20% of Maternal Deaths
• Cause of 10% of Preterm birth
• Etiology unknown

4. • Young female 3 fold increased risk
• African American 2 fold increased risk
• Multifetal pregnancies
– Twins
– Triplets
• Hypertension
• Diabetes Mellitus
• Renal Disease
• Collagen Vascular Disease

6. Hypertension during Pregnancy: Classification
• Pregnancy-induced hypertension
– Hypertension without proteinuria/edema
– Preeclampsia
• mild
• severe
– Eclampsia
• Coincidental HTN: preexisting or persistent
• Pregnancy-aggravated HTN
– superimposed preeclampsia
– superimposed eclampsia
• Transient HTN: occurs in 3rd trimester, mild

7. Preeclampsia: Risk Factors
• Nulliparity (or, more correctly, primipaternity)
• Chronic renal disease
• Angiotensinogen gene T235
• Chronic hypertension
• Antiphospholipid antibody syndrome
• Multiple gestation
• Family or personal history of preeclampsia
• Age > 40 years
• African-American race
• Diabetes mellitus

8. Etiology and Prevention
• Etiology is unknown.
• Many theories:
– genetic
– immunologic
– dietary deficiency (calcium, magnesium, zinc)
• supplementation has not proven effective
– placental source (ischemia)

9. Dr.Hisham

11. Etiology and Prevention
• A major underlying defect is a relative
deficiency of prostacyclin vs. thromboxane
• Normally (non-preeclamptic) there is an 8-10
fold  in prostacyclin with a smaller  in
thromboxane
– prostacyclin salutatory effects dominate
• vasodilation,  platelet aggregation,  uterine tone
• In preeclampsia, thromboxane’s effects
dominate
–  thromboxane (from platelets, placenta)
–  prostacyclin (from endothelium, placenta)

12. Preeclampsia Prophylaxis: Aspirin
• Aspirin has been extensively studied as a
targeted therapy to  thromboxane
production
• CLASP study, A multicenter RCT
[CLASP Collaborative Group, Lancet 1994;343:619-29]
– 9364 women, risk factors for PIH or IUGR or who
had PIH or IUGR
– 60 mg ASA daily vs. placebo
– Small reduction (12%) in occurrence of PIH
– Small reduction in preterm deliveries: 20 vs 22%
– No difference in neonatal outcome

13. Preeclampsia Prophylaxis: Aspirin
• NIH study of high-risk patients, RCT, 60 mg
aspirin daily vs. placebo [Caritis, et al., N Engl J Med
1998;338:701-5]
– pre-gestational DM (471 patients)
– chronic hypertension (774 patients)
– multifetal gestations (688 patients)
– prior history of preeclampsia (606 patients)
• No reduction in development of preeclampsia
in any subgroup or groups in aggregate
• No difference in perinatal death, preterm
delivery, IUGR, maternal or fetal hemorrhagic
complications

15. Preeclampsia: Mechanism
• At this time the most widely accepted
proposed mechanism for preeclampsia is:
Global Endothelial Cell Dysfunction
• Endothelial cell dysfunction is just one
manifestation of a broader intravascular
inflammatory response
– present in normal pregnancy
– excessive in preeclampsia
– Proposed source of inflammatory stimulus:
placenta

16. Pathophysiology
Of importance, and distinguishing preeclampsia
from chronic or gestational hypertension, is
that preeclampsia is more than hypertension; it
is a systemic syndrome, and several of its
“non-hypertensive” complications can be life-
threatening when blood pressure elevations
are quite mild.

17. Pathophysiology: Cardiovascular
• In severe preeclampsia, typically
hyperdynamic with normal-high CO, normal-
mod. high SVR, and normal PCWP and CVP.
• Despite normal filling pressures,
intravascular fluid volume is reduced (30-
40% in severe PIH)
• Variations in presentation depending on
prior treatment and severity and duration of
disease
• Total body water is increased (generalized
edema)

18. Pathophysiology: Cardiovascular
• Preeclamptic patients are prone to develop
pulmonary edema due to reduced colloid
oncotic pressure (COP), which falls further
postpartum:
Colloid oncotic pressure:
Antepartum Postpartum
Normal pregnancy: 22 mm Hg 17 mm Hg
Preeclampsia: 18 mm Hg 14 mm Hg

19. Pathophysiology
• Respiratory:
– Airway is edematous; use smaller ET tube (6.5)
–  risk of pulmonary edema; 70% postpartum
• Renal:
– Renal blood flow & GFR are decreased
– Renal failure due to  plasma volume or renal
artery vasospasm
– Proteinuria due to glomerulopathy
• glomerular capillary endothelial swelling w/subendothelial
protein deposits
– Renal function recovers quickly postpartum

20. Pathophysiology: Hepatic
• RUQ pain is a serious complaint
– warrants imaging, especially when
accompanied by  liver enzymes
– caused by liver swelling, periportal
hemorrhage, subcapsular hematoma, hepatic
rupture (30% mortality)
• HELLP syndrome occurs in ~ 20% of
severe preeclamptics.

21. Pathophysiology
• Coagulation:
– Generally hypercoagulable with evidence of
platelet activation and increased fibrinolysis
– Thrombocytopenia is common, but fewer than
10% have platelet count < 100,000
– DIC may occur,
• Acutely esp. with placental abruption
• Neurologic:
– Symptoms: headache, visual changes, seizures
– Hyperreflexia is usually present
– Eclamptic seizures may occur even w/out BP
• Possible causes: hypertensive encephalopathy, cerebral edema,
thrombosis, hemorrhage, vasospasm

22. Classification
• Chronic hypertension
• Preeclampsia-eclampsia
• Preeclampsia Superimposed upon
chronic hypertension or Renal Disease
• Gestational hypertension (only during pregnancy)
• Transient hypertension (only after pregnancy)

23. Chronic Hypertension
Defined as hypertension diagnosed
• Before pregnancy
• Before the 20th week of gestation
• During pregnancy and not resolved
postpartum

24. Gestational Hypertension
• Gestational Hypertension:
–Systolic >140
–Diastolic>90
–No Proteinurea
–25% Develop Pre-eclampsia

25. Gestational Hypertension
Diagnosis of gestational hypertension:
• Detected for first time after midpregnancy
• No proteinuria
• Only until a more specific diagnosis can be
assigned postpartum
If:
• BP returns to normal by 12 weeks postpartum,
diagnosis is transient hypertension.
• BP remains high postpartum, diagnosis is
chronic hypertension.
• Proteinurea develops Superimposed
Preeclampsia is diagnosed (25% incidence)

26. Preeclampsia-Eclampsia
• Occurs after 20th week (earlier with
trophoblastic disease)
• Increased BP (gestational BP elevation)
with proteinuria
• ‘LL’ Edema is NOT part of this definition

27. Diagnosis of Preeclampsia-Eclampsia
• Gestational Hypertension:
–Systolic >140
–Diastolic>90
• Proteinuria is defined as urinary
excretion
– 0.3 g protein or greater in a 24-hour
– +2 or greater on urine dip specimen

28. Classification of Preeclampsia-
Eclampsia
• Mild Pre-eclampsia
• Severe Pre-eclampsia

29. Classification of Preeclampsia-Eclampsia
• Criteria for Severe Preeclampsia (one or
more)
– Blood Pressure: >160 systolic, >110
diastolic
– Proteinurea: >5gm in 24 hours, over 3+
urine dip
– Oligurea: less than 400ml in 24 hours
– CNS: Visual changes, headache, scotomata,
mental status change
– Pulmonary Edema
– Epigastric or RUQ Pain: Usually indicates
liver involvement

30. Classification of Preeclampsia-
Eclampsia
• Criteria for Severe Preeclampsia (one or
more)
– Impaired Liver Function tests
– Thrombocytopenia: <100,000
– Intrauterine Growth Restriction: With or
without abnormal doppler assessment
– Oligohydramnios

31. Clinical Implications of
Preeclampsia
• Preeclampsia ranges from mild to severe.
• Progression may be slow or rapid – hours to
days to weeks.
For clinical management, preeclampsia should
be over diagnosed to prevent maternal and
perinatal morbidity and mortality – primarily
through timing of delivery.

32. Symptoms of Preeclampsia
• Visual disturbances typical of preeclampsia are
scintillations and scotomata. These disturbances are
presumed to be due to cerebral vasospasm.
• Headache is of new onset and may be described as
frontal, throbbing, or similar to a migraine
headache. However, no classic headache of
preeclampsia exists.
• Epigastric pain is due to hepatic swelling and
inflammation, with stretch of the liver capsule. Pain
may be of sudden onset, it may be constant, and it
may be moderate-to-severe in intensity.

33. Symptoms of preeclampsia
• While mild lower extremity edema is common in
normal pregnancy, rapidly increasing or
nondependent edema may be a signal of
developing preeclampsia. However, this signal
theory remains controversial and recently has
been removed from most criteria for the
diagnosis of preeclampsia.
• Rapid weight gain is a result of edema due to
capillary leak as well as renal sodium and fluid
retention.

34. Physical Findings in Preeclampsia
• Blood Pressure
• Proteinurea
• Retinal vasospasm or Retinal edema
• Right upper quadrant (RUQ) abdominal
tenderness stems from liver swelling
and capsular stretch

35. Physical findings in Preeclampsia
– Brisk, or hyperactive, reflexes are common
during pregnancy, but clonus is a sign of
neuromuscular irritability that raises concern.
– Among pregnant women, 30% have some lower
extremity edema as part of their normal
pregnancy. However, a sudden change in
dependent edema, edema in nondependent
areas such as the face and hands, or rapid
weight gain suggests a pathologic process and
warrants further evaluation

36. Eclampsia
• Women older than 40 years with preeclampsia
have 4 times the incidence of seizures compared to
women in their third decade of life.
– Twenty-five percent of eclampsia cases occur before
labor (ie, antepartum).
– Fifty percent of eclampsia cases occur during labor (ie,
intrapartum).
– Twenty-five percent of eclampsia cases occur after
delivery (ie, postpartum).
– Patients with severe preeclampsia are at greater risk to
develop seizures.
– Twenty-five percent of patients with eclampsia have only
mild preeclampsia prior to the seizures

37. Causes:
The cause of the seizures is not clear,
although several processes have been
implicated in their development.
– Areas of cerebral vasospasm may be severe
enough to cause focal ischemia, which may in
turn lead to seizures.
– Pathologic alterations in cerebral blood flow and
tissue edema induced by vasospasm may result
in headaches, visual disturbances, and
hypertensive encephalopathy, resulting in a
seizure.

38. Eclamptic seizure
– The patient may have 1 or more seizures.
– Seizures generally last 60-75 seconds.
– The patient's face initially may become
distorted, with protrusion of the eyes.
– The patient may begin foaming at the
mouth.
– Respiration ceases for the duration of the
seizure.

39. • The seizure may be divided into 2 phases:
– Phase 1 lasts 15-20 seconds and begins with facial twitching. The
body becomes rigid, leading to generalized muscular
contractions.
– Phase 2 lasts approximately 60 seconds. It starts in the jaw,
moves to the muscles of the face and eyelids, and then spreads
throughout the body. The muscles begin alternating between
contracting and relaxing in rapid sequence.
• A coma or a period of unconsciousness follows phase 2.
– Unconsciousness lasts for a variable period.
– Following the coma phase, the patient may regain some
consciousness.
– The patient may become combative and very agitated.
– The patient has no recollection of the seizure.
• A period of hyperventilation occurs after the tonic-clonic
seizure. This compensates for the respiratory and lactic
acidosis that develops during the apneic phase.
• Seizure-induced complications may include tongue biting,
head trauma, broken bones, or aspiration.

43. Laboratory Tests
High-risk patients presenting with normal
BP:
• Hematocrit
• Hemoglobin
• Serum uric acid
• If 1+ protein by routine urinalysis (clean catch)
present obtain a timed collection for protein and
creatinine
• Accurate dating and assessment of fetal growth
• Baseline sonogram at 25 to 28 weeks

44. Laboratory Tests
Patients presenting with hypertension
before gestation week 20:
• Same tests as described for high-risk
patients presenting with normal BP
• Early baseline sonography for dating
and fetal size

45. Laboratory Tests
Patients presenting with hypertension
after midpregnancy:
• Quantification of protein excretion
• Hemoglobin and hematocrit and platelet
count
• Serum creatinine, uric acid, and
transaminase level
• Serum albumin, LDH, blood smear, and
coagulation profile

46. Preeclampsia: Treatment
• Goal is to prevent eclampsia and other severe
complications.
• Attempts to treat preeclampsia by natriuresis
or by lowering BP may exacerbate pathologic
changes.
• Palliate maternal condition to allow fetal
maturation and cervical ripening.

47. Preeclampsia: Treatment
Maternal Evaluation
• Goals:
– Early recognition of preeclampsia
– Observe progression, both to prevent
maternal complications and protect well-
being of fetus.
• Early signs:
– BP rises in late second and early third trimesters.
– Initial appearance of proteinuria is important.

48. Preeclampsia: Treatment
• Maternal Evaluation…When To Hospitalize?
– Often, hospitalization recommended with new-onset
preeclampsia to assess maternal and fetal conditions.
– Hospitalization for duration of pregnancy indicated for
preterm onset of severe gestational hypertension or
preeclampsia.
– Ambulatory management at home or at day-care unit
may be considered with mild gestational hypertension
or preeclampsia remote from term

49. Preeclampsia

50. Indication of Delivery

51. Preeclampsia
• Antepartum Management of Preeclampsia
– Little to suggest therapy alters the underlying
pathophysiology of preeclampsia.
– Restricted activity may be reasonable.
– Sodium restriction and diuretic therapy appear
to have no positive effect.

52. Obstetric Management
• Classically “stabilize and deliver”

53. Preeclampsia
• The “cure” for preeclampsia is
delivery
– The “cure” is always beneficial for the
mother, although c-section might be
needed
– The “cure” may be deleterious for the
fetus

54. Preeclampsia
• Route of Delivery
– Vaginal delivery is preferable.
– Aggressive labor induction (within 24 hours).
– Neuraxial (epidural, spinal, and combined
spinal-epidural) techniques offer advantages.
– Hydralazine, nitroglycerin, or labetalol may be
used as pretreatment to reduce significant
hypertension during delivery.

55. Obstetric Management
• Medical management while awaiting
delivery:
– use of steroids X 48 hours if fetus < 34 wks
– antihypertensives to maintain DBP < 105-110
– magnesium sulfate for seizure prophylaxis
– monitor fluid balance, I/O, daily weights,
symptoms, reflexes, HCT, plts, LFT’s, proteinuria

56. Obstetric Management
• Indications for expedited delivery:
– fetal distress
–  BP despite aggressive Rx
– worsening end-organ function
– development or worsening of HELLP syndrome
– development of eclampsia

57. Antihypertensive Therapy
• Most commonly, for acute control: hydralazine,
labetolol
• Nifedipine may be used, but unexpected
hypotension may occur when given with MgSO4
• For refractory hypertension: nitroglycerin or
nitroprusside may be used
– Nitroprusside dose and duration should be limited
to avoid fetal cyanide toxicity
– Usually require invasive arterial pressure monitoring
• Angiotensin-converting enzyme (ACE) inhibitors
contraindicated due to severe adverse fetal
effects

58. Hydralazine
• Dose: 5-10 mg every 20 minutes
• Onset: 10-20 minutes
• Duration: 3-8 hours
• Side effects: headache, flushing,
tachycardia, lupus like symptoms
• Mechanism: peripheral vasodilator

59. Labetalol
• Dose:
– IV:20mg, then 40, then 80 every 20 minutes, for a
total of 220mg
– Oral 100 mg bid to be increased up to 200 mg qid.
( maximum 2400mg daily)
• Onset: 1-2 minutes
• Duration: 6-16 hours
• Side effects: hypotension
• Mechanism: Alpha and Beta block

60. Nifedipine
• Dose: 10 mg po, not sublingual(potent
generalized vasodilatation)
• Onset: 5-10 minutes
• Duration: 4-8 hours
• Side effects: chest pain, headache,
tachycardia
• Mechanism: CA channel block

61. Clonidine
• Dose: 1 mg po
• Onset: 10-20 minutes
• Duration: 4-6 hours
• Side effects: unpredictable, avoid rapid
withdrawal
• Mechanism: Alpha agonist, works
centrally

62. Nitroprusside
• Dose: 0.2 – 0.8 mg/min IV
• Onset: 1-2 minutes
• Duration: 3-5 minutes
• Side effects: cyanide accumulation,
hypotension
• Mechanism: direct vasodilator

63. Preeclampsia
• Anticonvulsive Therapy
– Indicated to prevent recurrent
convulsions in women with eclampsia
or to prevent convulsions in women
with preeclampsia.
– Parenteral magnesium sulfate
reduces the frequency of eclampsia
and maternal death. (Caution in renal
failure.)

64. Seizure Prophylaxis & Treatment
• Magnesium sulfate vs. phenytoin for seizure
prophylaxis in preeclampsia
Lucas, et al., N Engl J Med 1995;333:201-5.
– 2138 patients (75% had mild PIH)
– Maternal & fetal outcomes similar except 10
seizures in the phenytoin group (0 in MgSO4)
• Mg vs. diazepam & Mg vs. phenytoin for
preventing recurrent seizures in eclamptics
Eclampsia Trial Collaborative Group, Lancet 1995;345:1455
– Mg pts were 52% or 67% less likely to have a
recurrent seizure than diazepam or phenytoin pts

65. Seizure Prophylaxis
• Evidence is strong that magnesium
sulfate is indicated for
– seizure treatment in eclamptics
– seizure prophylaxis in severe preeclamptics
• Role of magnesium prophylaxis in mild
preeclamptics is less clear
– awaits large, prospective, randomized,
placebo-controlled trial

66. Magnesium Sulfate
• Magnesium sulfate has many effects; its
mechanism in seizure control is not clear.
– NMDA (N-methyl-D-aspartate) antagonist
– vasodilator
• Brain parenchymal vasodilation demonstrated in
preeclamptics by Doppler ultrasonography
– increases release of prostacyclin
• Potential adverse effects:
– toxicity from overdose (respiratory, cardiac)
–  bleeding
–  hypotension with hemorrhage
–  uterine contractility

67. Magnesium Sulfate
• Renally excreted
• Preeclamptics prone to renal failure
• Magnesium levels must be monitored frequently
either clinically (patellar reflexes, urinary output) or
by checking serum levels q 6-8 hours
• Therapeutic level: 4-7 meq/L
• Patellar reflexes lost: 8-10 meq/L
• Respiratory depression: 10-15 meq/L
• Respiratory paralysis: 12-15 meq/L
• Cardiac arrest: 25-30 meq/L
• Treatment of magnesium toxicity:
– stop MgSO4, IV calcium, manage airway

68. Treatment of Eclampsia
• Seizures are usually short-lived.
• If necessary, small doses of barbiturate or
benzodiazepine (STP, 50 mg, or midazolam, 1-2 mg)
and supplemental oxygen by mask.
• If seizure persists or patient is not breathing, rapid
sequence induction with cricoid pressure and
intubation should be performed.
• Patient may be extubated once she is completely
awake, recovered from neuromuscular blockade, and
magnesium sulfate has been administered.

69. 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
– intracerebral hemorrhage
– renal failure
– pulmonary edema
– eclampsia
• To be able to rapidly provide anesthesia for
C/S

70. Regional vs. General Anesthesia
in Preeclampsia
• Epidural anesthesia would probably be
preferred by many anesthesiologists in a
severely preeclamptic pt in a non-urgent
setting
• For urgent cases it is reassuring to know
that spinal is also safe
• This allows us to avoid general anesthesia
with the potential for encountering a
swollen, difficult airway and/or labile
hypertension

71. Regional vs. General
Anesthesia in Preeclampsia
• General anesthesia is a well-known
hazard in obstetric anesthesia:
– 16X more likely to result in anesthetic-
related maternal mortality
– Mostly due to airway/respiratory
complications, which would only be
exaggerated in preeclampsia
Hawkins, Anesthesiology 1997;86:273

72. Platelets & Regional Anesthesia
in Preeclampsia
• Prior to placing regional block in a preeclamptic it is
recommended to check the platelet count.
• No concrete evidence at to the lowest safe platelet
count for regional anesthesia in preeclampsia
• Any clinical evidence of DIC would contraindicate
regional anesthesia.

73. Hazards of General Anesthesia
in Preeclampsia
• Airway edema is common
– Mandatory to reexamine the airway soon before
induction
– Edema may appear or worsen at any time during the
course of disease
• tongue & facial, as well as laryngeal
• Laryngoscopy and intubation may  severe BP
– Labetolol & NTG are commonly used acutely
– Fentanyl (1 mcg/kg), alfentanil (10 mcg/kg), lidocaine
may be given to blunt response

74. Hazards of General Anesthesia
in Preeclampsia
• Magnesium sulfate potentiates depolarizing &
non-depolarizing muscle relaxants
– Initial dose of succinylcholine is not reduced.
– Neuromuscular blockade should be monitored &
reversal confirmed.

75. Invasive Central Hemodynamic
Monitoring in Preeclampsia
• Usually reserved for patients with
complications
– oliguria unresponsive to modest fluid challenge
(500 cc LR X 2)
– pulmonary edema
– refractory hypertension
• may have increased CO or increased SVR
• Poor correlation between CVP and PCWP in
PIH
– However, at most centers anesthesiologists
would begin with CVP & follow trend
• not arbitrarily hydrate to a certain number
– If poor response, change to PA catheter

80. Conclusions
• Preeclampsia is a serious multi-organ system
disorder of pregnancy that continues to defy
our complete understanding.
• It is characterized by global endothelial cell
dysfunction.
• The cause remains unknown.
• There is no effective prophylaxis.

81. Conclusions
• Delivery is the only effective cure.
• Magnesium sulfate is now proven as the
best medication to prevent and treat
eclampsia.
• Epidural analgesia for labor pain
management & regional anesthesia for C/S
have many beneficial effects & are
preferred.

82. Postpartum Counseling and
Followup
• Counseling for Future Pregnancies
• Risk of recurrent preeclampsia
increases with
– Preeclampsia before 30 weeks (40%)
– Multiparas as compared with nulliparas or
new father
– Risk of recurrent preeclampsia may be
substantially greater in African Americans.