hypertension in pregnancy
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Hypertension in pregnancy. Tom Archer, MD, MBA UCSD Anesthesia. Hypertension in pregnancy. Pre-eclampsia (HBP, proteinuria, edema) Gestational hypertension (HBP, no proteinuria) Chronic hypertension (HBP antedating preg.). Three causes of death in pregnancy:. #1 Thromboembolism - PowerPoint PPT PresentationTRANSCRIPT
Hypertension in pregnancy
Tom Archer, MD, MBAUCSD Anesthesia
Hypertension in pregnancy
• Pre-eclampsia (HBP, proteinuria, edema)
• Gestational hypertension (HBP, no proteinuria)
• Chronic hypertension (HBP antedating preg.)
Three causes of death in pregnancy:
#1 Thromboembolism
#2 Hemorrhage
#3 Hypertensive disorders / pre-EStrokeSeizuresDIC
Traditional pre-eclampsia triad:
• Hypertension
• Proteinuria
• Edema
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.
Ayten Elvan-Tas¸ pinar, Arie Franx, Michiel L. Bots,Hein W. Bruinse, and Hein A. KoomansAm J Hypertens2004;17:941–946
Visual example of increased augmentation index in pre-eclampsia.
Normotensive 29 yo pregnant woman
Pre-eclamptic patient, 29 yo.
Pre-E and CHTN show increased atrial and BNP– peptides produced by heart when it is under strain due to volume overload. These peptides eliminate sodium and increase vascular permeability.
VEGF also contributes to vascular permeability.
Tihtonen KM, Kööbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196:328.e1-328.e7.
Central thesis of pre-eclampsia: symptoms are due to arterial,
arteriolar and capillary endothelial damage.
Q: Damage by what?A: Chemical mediators from
placenta
Pre-E: endothelial damage
• Deranged smooth muscle function, due to damaged endothelium overlying smooth muscle.
• Leaky capillary endothelium (no smooth muscle).
vasodilatory signals (NO, prostacyclin)
vasoconstrictive signals (thromboxane, endothelin)
Endothelial cells send molecular signals to surrounding smooth muscle
Vessel lumen
Insulin makes endothelium produce
Pre-eclampsia mediators (and glucose) make endothelium produce
Archer TL 2006 unpublished, Idea from Dandona P 2004
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.
vasodilatory signals (NO, prostacyclin)
vasoconstrictive signals (thromboxane, endothelin)
Endothelial cells send molecular signals to surrounding smooth muscle
Vessel lumen
Insulin makes endothelium produce
Pre-eclampsia mediators (and glucose) make endothelium produce
Archer TL 2006 unpublished, Idea from Dandona P 2004
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).
Obesity, hyperglycemia, sepsis or pre-eclampsia
WBC
Platelet
Protein (edema)
WBC
Platelets
Archer TL 2006 unpublished
Capillary endothelium (no underlying smooth muscle)
Pre-E: disorder of endothelium
• Genetic polymorphism of endothelial NO synthase predisposes certain Japanese women to pre-E.
• In other words, generation of vasodilatory signal from endothelium to underlying smooth muscle is messed up.
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)
Wave reflection comes from muscular arteries (larger than arterioles).
Strong, early wave reflection increases heart’s systolic workload (augmentation index).
MT, 22 yo, healthy, in labor, epidural in place and she is comfortable.
AIx = -1%.
JM, 21 yo, in labor, recent onset lupus, on prednisone and plaquenil. Could see this in Pre-E. AIx = 6%
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
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2000
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100
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0 10 20 30 40
A minutes B
Nominal cardiac output L/min
Nominal systemic vascular resistance dyn.sec.cm-5
Blood pressure mm Hg
Heart rate beats/min and nominal stroke volume mL
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, BeauchampRadioGraphics 1998; 18:353-36ı‘
Edema– imagine same process in liver and brain!
Central thesis of pre-eclampsia: signs and symptoms are due to arterial, arteriolar and capillary
endothelial damage.
Damage by what?Chemical mediators from
placenta.
Pre-eclampsia:
Probably adisorder of placentation.
www.siumed.edu/~dking2/erg/images/placenta.jpg
Say “OUCH!”
Pre-E
mediators
Poor placentation
Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.
What are the pre-E mediators?
• Pre-E: imbalance between proangiogenic factors (VEGF and PlGF) and anti-angiogenic factors (sVEGFR-1, also known as sFLt1, and soluble endoglin, s-Eng)
Angiogenic factors:
VEGF and PlGFAnti-angiogenic factors:
sENG and sVEGFR1
Does pre-eclampsia involve an imbalance in angiogenic and anti-angiogenic factors?
Romero R et al, The Journal of Maternal-Fetal and Neonatal Medicine, January 2008; 21(1): 9–23
Unhealthy endothelium
Healthy endothelium
Proper placentation:• Syncytiotrophoblast invades and denervates
maternal spiral arterioles to ensure a LOW RESISTANCE AV fistula in the intervillous spaces.
• This proper placentation FAILS in pre-eclampsia, leading to release of endothelium-damaging mediators from ischemic placenta
• Result is hypertension, proteinuria and edema, plus IUGR (poor O2 and nutrient transfer to fetus).
http://pharyngula.org/images/preeclampsia_model.jpg
Poor-placentation theory of pre-E:
Synciotrophoblast invades myometrium but does not denervate spiral arteries of mother properly.
Hence, intervillous flow is sub-optimal.
Chorionic villi are ischemic and release mediators (VEGF, etc) which damage maternal endothelium.
www.siumed.edu/~dking2/erg/images/placenta.jpg
Say “OUCH!”
Pre-E
mediators
Poor placentation
Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.
http://members.aol.com/wayneheim/vegf.jpg
VEGF– vascular endothelial growth factor.
Is it good, or bad? Both, of course. Helps to build new blood vessels and breaks down basement membrane in the process.
What do we observe in pre-E?
• Evidence of vasoconstriction
– Increased wave reflection from muscular arteries (augmentation index).
– Increased SVR of arterioles (late in pre-E), decreased CO
– Increased cardiac natriuretic peptides (heart tries to compensate for increased wall stretch (afterload).
Ayten Elvan-Tas¸ pinar, Arie Franx, Michiel L. Bots,Hein W. Bruinse, and Hein A. KoomansAm J Hypertens2004;17:941–946
Visual example of increased augmentation index in pre-eclampsia.
Normotensive 29 yo pregnant woman
Pre-eclamptic patient, 29 yo.
Mats Ro¨ nnback, M.D.,1, 2,* Katja Lampinen,2,3 Per-Henrik Groop,1,2 and Risto Kaaja3Hypertension in Pregnancy, 24:171–180, 2005
Pre-eclampsia is associated with an increase in augmentation index.
Cite this article as: Tihtonen KM, Kööbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196:328.e1-328.e7.
In pre-eclampsia, we see increased SVR (arteriolar constriction), MAP and decreased CO. Atria and ventricles respond by increasing natriuretic peptide secretion.
Bosio 1999
Hemodynamics of normal pregnancy:
CO rises early, plateaus at 28-32 weeks and falls slightly after that.
SVR falls early, plateaus at 28-32 weeks and rises slightly after that.
Bosio 1999
In pre-eclampsia, early phase (28-36 weeks) may involve an increased CO.
After 36 weeks, CO falls and SVR rises.
Hyperdynamic early phase of pre-eclampsia, followed by arteriolar constriction (high SVR)?
Bosio 1999
Gestational hypertension (no proteinuria), by contrast, appears to involve persistent high CO and low-normal SVR.
So, hemodynamically, gestational hypertension and pre-eclampsia are different diseases.
Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli
Italian study of hemodynamics of pre-eclampsia: early onset pre-E (<34weeks) is predicted at 24 weeks by high SVR and low CO. Late onset (>34 weeks) is predicted at 24 weeks by low SVR and high CO.
Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli
Italian study of hemodynamics of pre-eclampsia: early onset pre-E (<34weeks) is predicted at 24 weeks by high SVR and low CO. Late onset (>34 weeks) is predicted at 24 weeks by low SVR and high CO.
Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli
Italian study of hemodynamics of pre-eclampsia: early onset pre-E (<34weeks) is predicted at 24 weeks by high SVR and low CO. Late onset (>34 weeks) is predicted at 24 weeks by low SVR and high CO.
Rang S, van Montfrans GA, Wolf H. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growthrestriction. Am J Obstet Gynecol 2008;198:519.e1-519.e9.
Fetal growth restriction, with or without pre-eclampsia or gestational hypertension, is associated with high SVR and low CO.
Pre-eclampsia and GH, without fetal growth restriction, ar associated with low SVR and high CO.
Hence: fetal growth restriction is associated with high SVR.
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Nominal cardiac output L/min
Nominal systemic vascular resistance dyn.sec.cm-5
Blood pressure mm Hg
Heart rate beats/min and nominal stroke volume mL
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Etomidate induction in preE and lupus– severe HBP and vasoconstriction
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Nicardipine lowers SVR and increases CO in patient with pre-E.
BP control in pre-E:
• BP control is distinct from seizure prophylaxis. No evidence (RCT) to support BP control. Modest reduction only!
• We use hydralazine or labetalol for HBP in pre-E.
• Mg will tend to lower BP, but that is not why it is used.
Hemodynamics in pre-E:• Progression from high CO, normal SVR to low CO, increased
SVR?
• CVP not reliable as index of volume status! Colloid osmotic pressure is down in pre-E (leaky capillaries?).
• Keep down the fluids! Use colloid if you want to volume expand.
• Pre-E patients probably do NOT drop their pressure with SAB/ epidural more than normal pregnant women.
• OBs worry about post-op / delivery pulmonary edema.
Mean BP in 30 normals and 30 preeclamptic (preterm) women for C/S under SAB
Practical management of pre-E:• Mg is anticonvulsant. Mg use in mild pre-E
is controversial!
• Mg use in severe pre-E is well established (MAGPIE Trial and others).
• Mg in severe pre-E reduces seizures by about 60% (1.9% 0.8%, NNT 91), so the effect is NOT overwhelming and NNT is high.
Mg++ toxicity• Ca++ influx into nerve terminal releases Ach for N-M
transmission. Mg++ will counteract this, so Mg++ toxicity can be N-M blockade. Mg++ potentiates non-depolarizing NMBs.
• Respiratory depression (sedation + weakness)• • Rx symptomatic hypermagnesemia with IV Ca++.
• Poor man's Mg++ levels: patellar reflexes. Hold Mg++ if reflexes disappear.
• If epidural in place, check DTRs in arms!
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 >75K.
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.
HELLP syndrome
• Can be seen without proteinuria.
• Often worse at 24-48h after delivery.
• Relationship with pre-E is unclear.
Renal in pregnancy and pre-E
• GFR normally increases in pregnancy.
• Creatinine greater than 1.0 is probably pathological!
• Elevated uric acid is another index of pre-E severity.
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).
Pre-E is associated with long-term CV problems
• OB needs to counsel pre-E patients about increase in CV complications in women with Hx of pre-E.
• OBs need to counsel them about avoiding other CV stressors such as DM, obesity, smoking and hyperlipidemia.
Van Pampus long term outcomes after preE CLINICAL OBSTETRICS AND GYNECOLOGYVolume 48, Number 2, 489–494
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• Endothelial dysfunction in pre-eclampsia is due
to “junk” coming from an ischemic placenta.
• The “junk” may involve anti-angiogenic factors which inactivate angiogenic factors.
• 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).
• Applanation tonometry can be used to evaluate “augmentation index”, which is a measure of extra work that the heart has to do in systole.
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.
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.
The End