Severe pre-eclampsia.
Tom Archer, MD, MBA
Director, OB Anesthesia
UCSD Hillcrest
March 28, 2012
Hypertension in pregnancy
• Pre-eclampsia (HBP, proteinuria, edema, after 20
weeks ega)
• Gestational hypertension (HBP after 20 weeks ega,
no proteinuria). Old term: “pregnancy-induced
hypertension”.
• Chronic hypertension (HBP antedating pregnancy).
• “Superimposed” pre-eclampsia– pre-eclampsia on
top of chronic hypertension
Three causes of death in
pregnancy:
#1 Pulmonary thromboembolism
#2 Hemorrhage
#3 Hypertensive disorders / pre-E
Stroke
Seizures
DIC
Pre-eclampsia variants
• Eclampsia– pre-eclampsia with seizures
• HELLP syndrome (hemolysis, elevated
liver enzymes and low platelets)
Severe pre-eclampsia
• SBP > 160 or DBP > 110, X2, 6 hours
apart.
• Proteinuria > 5 gm / 24 hours (Hence 24hour urine collection)
• Oliguria < 500 mL / 24 hours
Severe pre-eclampsia
• Cerebral or visual disturbances: HA,
blurred vision or altered consciousness.
• Pulmonary edema (or low Sp02).
• Epigastric or RUQ pain (liver edema or
rupture)
Severe pre-eclampsia
• Increased liver enzymes-- common.
• Prolonged PT or PTT or decreased
fibrinogen implies DIC– fortunately rare.
• Thrombocytopenia
• Fetal growth restriction
Traditional pre-eclampsia triad:
• Hypertension
• Proteinuria
• Edema
New understanding of traditional
pre-eclampsia triad:
• Hypertension arteriolar constriction
(endothelial dysfunction).
• Proteinuria leaky glomerulus (capillary)
(endothelial dysfunction).
• Edema leaky capillaries in skin, muscle, liver,
brain, airway, nose. (endothelial dysfunction).
“4th component” of endothelial
dysfunction in pre-eclampsia
• Muscular artery spasm increased
arterial wave reflection back to heart
• Increased “augmentation index” (AIx)
• Increased AIx extra work for heart
muscle
• LVH, increased BNP release CHF.
Modern concept of pre-eclampsia:
symptoms are due to arterial,
arteriolar and capillary endothelial
damage.
Q: Damage by what?
A: Chemical mediators from
placenta
“Toxemia of pregnancy”
• The old-fashioned term is actually very
descriptive!
• The ischemic placenta gives off toxins
which damage the mother’s vascular
endothelium throughout her body.
Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.
Say “OUCH!”
Pre-E
mediators
Poor placentation
www.siumed.edu/~dking2/erg/images/placenta.jpg
Pre-E: endothelial damage
• Deranged smooth muscle function, due to
damaged endothelium overlying smooth
muscle.
• Leaky capillary endothelium (no smooth
muscle).
Endothelial cells send molecular signals to surrounding smooth muscle
Pre-eclampsia
mediators (and
glucose) make
endothelium
produce
Insulin makes
endothelium
produce
Vessel lumen
vasoconstrictive
signals (thromboxane,
endothelin)
Archer TL 2006 unpublished, Idea from Dandona P 2004
vasodilatory
signals (NO,
prostacyclin)
Endothelial factors in pre-E:
• In health, there is a balance between
– vasodilatory factors: NO, PGI2 (Prostacyclin) and
– vasoconstrictive factors: thromboxane, endothelin.
• This normal balance is messed up in pre-E.
Obesity, hyperglycemia, sepsis and pre-eclampsia all “activate”
(damage) endothelium, white cells and platelets, leading to
white cell adhesion and infiltration, thrombosis and edema
(inflammation).
WBC
WBC
Obesity, hyperglycemia,
sepsis or pre-eclampsia
Platelet
Platelets
Capillary endothelium (no underlying
smooth muscle)
Protein (edema)
Archer TL 2006 unpublished
Endothelial damage causes problems
in 3 sizes of blood vessels:
• Muscular arteries increased wave
reflection (heart work, augmentation
index).
• Arterioles increased SVR
• Capillaries proteinuria and tissue edema
(glomerulus, liver, skin, muscle, brain)
Figure 1. Pt HB, PreE for CS, superimposed on CHTN and CRF, 33 weeks. Hemodynamic parameters before and after treatment
with antihypertensive medication A. Labetalol 25 mg and hydralazine 5 mg, B. Nicardipine 250 μ total in divided doses
Nominal cardiac output L/min
8
4
0
Nominal systemic vascular resistance dyn.sec.cm-5
3000
2000
1000
0
Blood pressure mm Hg
200
100
0
150
Heart rate beats/min and nominal stroke volume mL
100
50
0
0
10
A
20
minutes
30
B
40
Posterior reversible
encephalopathy
syndrome (PRES):
Occipital-parietal
cortical and white
matter changes in
pre-eclampsia.
Is this due to capillary
damage in the brain?
Port JD,
Beauchamp
RadioGraphics
1998; 18:353-36ı
‘
Figure 1b
Figure 1c
Edema– imagine
same process in
liver and brain!
Pre-eclampsia:
Probably a
disorder of placentation.
Poor-placentation theory of pre-E:
Synciotrophoblast invades
myometrium but does not
denervate spiral arteries of mother
properly.
Hence, intervillous flow is suboptimal.
Chorionic villi are ischemic and
release mediators (VEGF, etc)
which damage maternal
endothelium.
http://pharyngula.org/images/preeclampsia_model.jpg
Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.
Say “OUCH!”
Pre-E
mediators
Poor placentation
www.siumed.edu/~dking2/erg/images/placenta.jpg
Hemodynamic review:
MAP = SVR x CO.
We ignore CVP since it is small compared
to MAP.
Hemodynamic issues
in pre-eclampsia
• We could work on CO or SVR, since
MAP = CO x SVR.
We usually work on both CO and SVR, but
different drugs affect the two components
to different degrees.
SAB / epidural cause
sympathectomy
www.cvphysiology.com/Blood%20Pressure/BP019.htm
Post-partum BP control
• Hydralazine – arteriolar vasodilator.
Decreases SVR. Tendency is to cause
tachycardia. 5 mg IV q15 minutes
• Labetalol – alpha and beta blocker. Dilates
arterioles (dec SVR) and slows heart rate
and reduces contractility (dec CO). 10-20
mg IV q 10 minutes.
Why treat BP in pre-eclampsia?
• Decrease stroke, CHF, renal damage?
• This has never been proven by RCT.
• But we do it anyway!
• Goal is modest decrease in BP. DBP 90100 mm Hg.
Other BP meds in pre-eclampsia
• Nitroglycerin– venodilator, can be given sublingually or
IV.
• Sodium nitroprusside– IV. Needs arterial line.Primarily
arteriolar dilator.
• Nifedipine– Ca++ channel blockers. Arteriolar dilator.
Can be used for BP control and also as a tocolytic.
Caution should be used when used with Mg++.
• Esmolol– sort acting beta blocker. Adjunct to decrease
HR in BP control.
Pre-eclampsia complication:
pulmonary edema
• Fluid overload / pulmonary edema–
– respiratory distress
– Low SpO2 (“low sats”)
– Rales on auscultation
• Can progress to ARDS
• May need intubation
• Call anesthesia for evaluation
Pre-eclampsia complications:
pulmonary edema
• Fluid overload / pulmonary edema–
– Albumin (oncotic pressure) decreases in
normal pregnancy.
– Lower in pre-eclampsia due to protein loss
into interstitial space
Respiratory function
in pre-eclampsia
• Edema of the airway
Pre-eclampsia complications:
blindness and seizures
• Blindness / blurred vision
– Edema in occipital cortex (retina is normal)
– Disorientation / fear
– Visual impairment usually resolves completely
Pre-eclampsia complications:
blindness and seizures
• Seizure: neurological event but also a
respiratory event!
• Remember: suction, oxygen, ambu bag, IV
access, call anesthesiologist to help.
• Ante-partum, fetal oxygenation is at risk.
MgSO4 seizure prophylaxis
• Mg++ in severe pre-E reduces seizures by
about 60% (from 1.9% 0.8%)
• Mg++ use in mild pre-eclampsia is
controversial but it is used at UCSD.
Magnesium toxicity
• 1.7-2.4 mg / dL– Normal
• 5-9 mg / dL– therapeutic range for seizure
prevention
• Loss of patellar reflexes (but watch out for
epidural)– 12 mg / dL
• Respiratory arrest – 15-20 mg / dL
• Asystole– 25 mg / dL
• Mg++ levels OK, but try clinical
assessment!
Magnesium toxicity
• Multiple blood draws– think central or arterial line or
blue valve from IV catheter. Avoid repeated sticks?
• Treatment:
• Stop Mg++
• Give Ca++ (1 gm Ca gluconate or 300 mg CaCl2
• Assist ventilation (Ambu bag). Intubation if
necessary.
Magnesium toxicity
• Uterine atony (Mg++ is a uterine relaxant)
Hematologic aspects of pre-E:
• Exacerbated normal hypercoagulability of
normal pregnancy.
If DIC occurs, fibrinolysis will occur as well (+
Fibrin dimer test)
Platelet activation and adhesion / consumption.
We commonly follow trend of platelets.
Regional OK if > 50-100K.
Prolongation of PT / PTT or
decreased fibrinogen in pre-E
• Uncommon (thrombocytopenia is common).
• Low fibrinogen implies DIC.
• Liver damage decreased synthesis of
fibrinogen and clotting factors?
• Bottom line: if fibrinogen or PT/PTT are
abnormal, patient has a more serious problem
than “just” thrombocytopenia.
Pre-eclampsia complications
• Disseminated intravascular coagulation
(“DIC”)
– Consumption of platelets and clotting factors
d/t damaged endothelium
– Diffuse ooze from incision, IV sites
– Major emergency
– IV access, pRBCs, FFP, cryoprecipitate
– Will need ICU, ?intubation, arterial line
Hemolysis from fibrin stands
www.nejm.org/.../2005/20050804/images/s19.jpg
Liver in pre-eclampsia
• Elevated liver enzymes (AST, ALT)
• Edema– swelling– epigastric / RUQ pain
• Hemorrhage into liver (hematoma)
• Rupture of hematoma through liver
capsule (“liver rupture”).
Factitious thrombocytopenia
• Platelet clumping due to EDTA
anticoagulant or cold
www.nejm.org/.../2005/20050804/images/s19.jpg
Renal function in pre-eclampsia
• Normal pregnancy involves increased
GFR and decreased creatinine, e.g.
0.80.6 mg/dL.
• Renal dysfunction in pre-eclampsia may
be associated with a “normal” creatinine,
eg. 1.0.
• Increased uric acid in pre-eclampsia
Renal failure after pre-E
• Oliguria almost always gets better after
delivery.
• Renal failure due to pre-E is rare
(unless there is pre-existing renal
disease).
Oliguria
• Urine output less than 30 mL / hr for more
than 3 hours, despite crystalloid boluse(s)
of 300-500 mL.
• Is the Foley in the bladder? Is it kinked?
Summary
• Pre-eclampsia is associated with
endothelial dysfunction.
• Normal balance between vasodilation and
vasoconstriction tips toward constriction.
• Capillaries become leaky– edema (and
proteinuria) everywhere.
Summary
• Old-fashioned term “toxemia of pregnancy”
is very accurate!
• Placenta is ischemic because implantation
has not gone well.
• Pre-eclampsia: a disorder of implantation.
Summary
• Pre-eclampsia may involve an early
hyperdynamic phase (increased CO),
followed by a vasoconstrictive phase (high
SVR).
• Later on, pre-eclampsia involves intense
arteriolar constrictive, with high BPs and
reflected pressure waves leading to heart
strain and possible CHF.
Summary
• The endothelial damage of pre-eclampsia
can activate the coagulation system.
• Thrombocytopenia occasionally occurs but
hypofibrinogemia and prolonged PT/PTT
are rare and very worrisome.
Overall management
•
•
•
•
•
Seizure prophylaxis
Hemodynamic state—invasive monitoring
Fluid restriction (but boluses for oliguria).
Review of platelets, PT, PTT, fibrinogen
Evaluation of airway (swelling) and
pulmonary status (edema)
• Pulmonary edema most common after
delivery (mobilization of edema fluid).
Neonatal issues in pre-eclampsia
• IUGR
• Prematurity
• Hypoxia
• Mother will be afraid for the baby!
Maternal CNS issues
in pre-eclampsia
• Confusion or somnolence due to cerebral
edema
• Somnolence due to MgSO4 therapy
• Post-ictal state (has patient had a
seizure?)
• Is patient afraid?
Summary care for patient with
severe pre-eclampsia
• Emotional support– anxiety for self,
neonate, CNS changes due to disease
and therapy.
• Pain from surgery– helped by neuraxial
anesthesia and neuraxial opioids.
Summary of care for patient with
severe pre-eclampsia
• Follow BP– may increase as spinal wears
off. This is normal.
• Goal of BP control is high normal– don’t
overshoot.
• Treat pain, not just give antihypertensives.
Summary of care for patient with
severe pre-eclampsia
• Judicious fluid restriction (unless postpartum hemorrhage).
• Continue magnesium sulfate.
• Monitor urine output.
Summary of care for patient with
severe pre-eclampsia
• Monitor for post-partum hemorrhage
• Prolonged labor, MgSO4 can predispose
to uterine atony.
• Monitor for DIC. Oozing at IV and other
venipuncture sites.
How can anesthesiologist help the
patient in the PACU?
• IV access: central line or arterial line for
repeated blood draws and BP monitoring?
• IV med assistance: what to give? How fast
will it work?
• Monitor for pulmonary / cardiac
dysfunction– rales, low Sp02.
How can anesthesiologist help the
patient in the PACU?
• Manage seizing patient– airway, vomiting.
• Have suction, ambu bag, crash cart
nearby.
The End