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Hypertension in pregnancy

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

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Hypertension in pregnancy

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  1. Hypertension in pregnancy Tom Archer, MD, MBA UCSD Anesthesia

  2. Hypertension in pregnancy • Pre-eclampsia (HBP, proteinuria, edema) • Gestational hypertension (HBP, no proteinuria) • Chronic hypertension (HBP antedating preg.)

  3. Three causes of death in pregnancy: #1 Thromboembolism #2 Hemorrhage #3 Hypertensive disorders / pre-E Stroke Seizures DIC

  4. Traditional pre-eclampsia triad: • Hypertension • Proteinuria • Edema

  5. 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).

  6. “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.

  7. Visual example of increased augmentation index in pre-eclampsia. Normotensive 29 yo pregnant woman Pre-eclamptic patient, 29 yo. Ayten Elvan-Tas¸ pinar, Arie Franx, Michiel L. Bots, Hein W. Bruinse, and Hein A. KoomansAm J Hypertens 2004;17:941–946

  8. 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.

  9. Central thesis of pre-eclampsia: symptoms are due to arterial, arteriolar and capillary endothelial damage. Q: Damage by what? A: Chemical mediators from placenta

  10. Pre-E: endothelial damage • Deranged smooth muscle function, due to damaged endothelium overlying smooth muscle. • Leaky capillary endothelium (no smooth muscle).

  11. Endothelial cells send molecular signals to surrounding smooth muscle Insulin makes endothelium produce Pre-eclampsia mediators (and glucose) make endothelium produce vasodilatory signals (NO, prostacyclin) Vessel lumen vasoconstrictive signals (thromboxane, endothelin) Archer TL 2006 unpublished, Idea from Dandona P 2004

  12. 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.

  13. Endothelial cells send molecular signals to surrounding smooth muscle Insulin makes endothelium produce Pre-eclampsia mediators (and glucose) make endothelium produce vasodilatory signals (NO, prostacyclin) Vessel lumen vasoconstrictive signals (thromboxane, endothelin) Archer TL 2006 unpublished, Idea from Dandona P 2004

  14. 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

  15. 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.

  16. 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)

  17. Wave reflection comes from muscular arteries (larger than arterioles). Strong, early wave reflection increases heart’s systolic workload (augmentation index).

  18. MT, 22 yo, healthy, in labor, epidural in place and she is comfortable. AIx = -1%.

  19. JM, 21 yo, in labor, recent onset lupus, on prednisone and plaquenil. Could see this in Pre-E. AIx = 6%

  20. 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 Heart rate beats/min and nominal stroke volume mL 150 100 50 0 0 10 20 30 40 A minutes B

  21. 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 ‘

  22. Edema– imagine same process in liver and brain!

  23. Central thesis of pre-eclampsia: signs and symptoms are due to arterial, arteriolar and capillary endothelial damage. Damage by what? Chemical mediators from placenta.

  24. Pre-eclampsia: Probably a disorder of placentation.

  25. 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

  26. 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)

  27. Does pre-eclampsia involve an imbalance in angiogenic and anti-angiogenic factors? Angiogenic factors: VEGF and PlGF Anti-angiogenic factors: sENG and sVEGFR1 Healthy endothelium Unhealthy endothelium Romero R et al, The Journal of Maternal-Fetal and Neonatal Medicine, January 2008; 21(1): 9–23

  28. 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).

  29. 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. http://pharyngula.org/images/preeclampsia_model.jpg

  30. 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

  31. www.hgsi.com/invest/annual99/prod_vegf2.htm

  32. 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. http://members.aol.com/wayneheim/vegf.jpg

  33. www.hgsi.com/invest/annual99/prod_vegf2.htm

  34. 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).

  35. Visual example of increased augmentation index in pre-eclampsia. Normotensive 29 yo pregnant woman Pre-eclamptic patient, 29 yo. Ayten Elvan-Tas¸ pinar, Arie Franx, Michiel L. Bots, Hein W. Bruinse, and Hein A. KoomansAm J Hypertens 2004;17:941–946

  36. Pre-eclampsia is associated with an increase in augmentation index. Mats Ro¨ nnback, M.D.,1, 2,* Katja Lampinen,2,3 Per-Henrik Groop,1,2 and Risto Kaaja3 Hypertension in Pregnancy, 24:171–180, 2005

  37. In pre-eclampsia, we see increased SVR (arteriolar constriction), MAP and decreased CO. Atria and ventricles respond by increasing natriuretic peptide secretion. 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.

  38. 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

  39. 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

  40. 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. Bosio 1999

  41. 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

  42. 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

  43. 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

  44. 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. Rang S, van Montfrans GA, Wolf H. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growth restriction. Am J Obstet Gynecol 2008;198:519.e1-519.e9.

  45. Etomidate induction in preE and lupus– severe HBP and vasoconstriction Nominal cardiac output L/min 10 0 Nominal systemic vascular resistance dyn.sec.cm-5 3000 2000 1000 0 Blood pressure mm Hg 300 200 100 0 Heart rate beats/min and nominal stroke volume mL 150 100 50 0 0A B 5 10 15 C D 20 SV minutes

  46. Nicardipine lowers SVR and increases CO in patient with pre-E.

  47. 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.

  48. 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.

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