Hypertensive Disorders of Pregnancy
Sharon Abramovitz
A 39-year-old woman gravida 1 para 0 at 29 weeks’ gestation was admitted to the hospital because of an elevated blood pressure (BP) (182/111 mm Hg), headache, and proteinuria.
A. Medical Disease and Differential Diagnosis
What is the classification of hypertension disorders in pregnancy as defined by the American College of Obstetricians and Gynecologists?
What is preeclampsia?
What is preeclampsia with severe features?
What is eclampsia?
What are the risk factors for developing preeclampsia?
What is the mortality associated with preeclampsia?
Discuss the pathogenesis of preeclampsia.
Discuss the pathologic alterations of preeclampsia.
Which component of BP best predicts the occurrence of preeclampsia?
What is the significance of increased pulse wave velocity (PWV) during pregnancy? How does this relate to birth weight?
What are some of the complications associated with preeclampsia?
B. Preoperative Evaluation and Preparation
What initial laboratory studies are recommended for patients with preeclampsia?
What are the important routine monitors for patients with preeclampsia? When is a central venous pressure (CVP) monitor indicated?
What conditions mandate immediate delivery, regardless of the gestational age?
Discuss the obstetric management of preeclampsia.
In the United States, what drug therapy is the treatment of choice for seizure prophylaxis?
Discuss the treatment of magnesium sulfate toxicity.
Discuss the mechanism of action of magnesium sulfate.
What are the fetal effects of magnesium sulfate therapy?
Discuss the treatment of eclampsia.
C. Intraoperative Management
What is your choice of analgesia/anesthesia for patients with preeclampsia?
What is the advantage of prehydration?
Discuss bleeding time and platelet count evaluation during preoperative assessment of a patient with preeclampsia requesting epidural analgesia/anesthesia for labor and delivery.
What level of analgesia/anesthesia is required for labor and delivery?
Discuss the commonly used local anesthetics for labor analgesia.
Is the addition of epinephrine to local anesthetics advisable in preeclamptic patients?
What is the treatment for the abnormal fetal heart rate pattern seen with maternal hypotension after epidural analgesia/anesthesia is instituted?
What would you do after an accidental spinal tap? How do you treat postdural puncture headache?
How would you manage total spinal anesthesia?
Should ergonovine be given to preeclamptic patients?
When and how would you give spinal anesthesia?
Discuss a general anesthesia technique for the patient with preeclampsia presenting for cesarean delivery.
What agents can you use to prevent hypertension during the induction of general anesthesia for cesarean delivery?
What is HELLP syndrome?
D. Postoperative Management
Discuss the postpartum management of preeclamptic patients.
A. Medical Disease and Differential Diagnosis
A.1. What is the classification of hypertension disorders in pregnancy as defined by the American College of Obstetricians and Gynecologists?
Hypertensive disorders of pregnancy are classified as follows:
Gestational hypertension
Preeclampsia
Preeclampsia without severe features
Preeclampsia with severe features
Chronic hypertension preceding pregnancy
Chronic hypertension with superimposed preeclampsia
American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122:1122-1131.
A.2. What is preeclampsia?
Preeclampsia is a multiorgan disease characterized by the development of hypertension with proteinuria after the 20th week of gestation. It is a disorder affecting approximately 8% of all pregnancies, with most cases occurring during the first pregnancy, and is unique to humans. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide, particularly in developing countries. Hypertension is defined as a systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg on two occasions at least 4 hours apart in a previously normotensive patient. Proteinuria is defined as 300 mg or more of protein in a 24-hour urine collection, or a protein-creatinine ratio of 0.3 or greater, or 1+ protein on a urine dipstick (if other tests are not readily available because there is variability in this diagnostic test). Edema is no longer part of the diagnostic criteria because it lacks specificity and is found in many healthy pregnant women. In the absence of proteinuria, the diagnosis of preeclampsia can still be made due to the syndromic nature of the disease. Therefore, preeclampsia is diagnosed by the presence of hypertension in association with thrombocytopenia (platelet count less than 100,000 per µL), impaired liver function (elevated blood levels of liver transaminases to twice the normal concentration), the new development of renal insufficiency (elevated serum creatinine greater than 1.1 mg per dL or a doubling of the serum
creatinine in the absence of other renal disease), pulmonary edema, or new-onset cerebral or visual disturbances.
creatinine in the absence of other renal disease), pulmonary edema, or new-onset cerebral or visual disturbances.
American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122:1122-1131.
Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:827-828.
Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol. 2009;200(5):481.e1-481.e7.
A.3. What is preeclampsia with severe features?
Severe preeclampsia includes at least one of the following features:
Blood pressure: systolic BP 160 mm Hg or higher or diastolic BP 110 mm Hg or higher on two occasions at least 4 hours apart while the patient is on bedrest
Thrombocytopenia (platelet count less than 100,000 per µL)
Serum creatinine concentration greater than 1.1 mg per dL or greater than two times the baseline serum creatinine concentration
Pulmonary edema
New-onset cerebral or visual disturbances
Impaired liver function, indicated by elevated blood concentrations of liver enzymes (twice baseline values) and severe persistent right upper quadrant pain or epigastric pain
Fetal growth restriction and severe proteinuria (<5 g in 24 hours) are no longer considered features of severe preeclampsia
American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122:1122-1131.
Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:825-827.
A.4. What is eclampsia?
Eclampsia is defined as convulsions and/or coma not caused by coincidental neurologic disease (e.g., epilepsy), which occurs during pregnancy or the puerperium in a woman whose condition also meets the criteria for preeclampsia.
Broughton Pipkin F. The hypertensive disorders of pregnancy. BMJ. 1995;311:609-613.
Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:850-851.
A.5. What are the risk factors for developing preeclampsia?
The risk factors for developing preeclampsia are as follows:
Hypertensive disease
Previous preeclampsia
Systolic hypertension during early pregnancy
History of chronic hypertension
Family history of hypertension during pregnancy
Increase in pulse pressure during the first trimester
Coexisting vascular and endothelial disease
Diabetes mellitus
Chronic renal disease
Systemic lupus erythematosus
Protein S deficiency
Activated protein C resistance
Antiphospholipid antibody syndrome
Obstetric factors
African American race
Advanced maternal age greater than 35 years
Angiotensinogen gene T235
Nulliparity
Obesity
Increased trophoblastic mass (e.g., multiple gestation, molar pregnancy)
Large for gestational age fetus
Erythroblastosis fetalis
Polyhydramnios, particularly in young primigravidas
Boxer LM, Malinow AM. Pre-eclampsia and eclampsia. Curr Opin Anesth. 1997;10:188-198.
Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:827-829.
A.6. What is the mortality associated with preeclampsia?
Preeclampsia accounts for 15% to 19% of maternal deaths in the United States and the United Kingdom. It is also accounts for 26% of maternal deaths in Latin America and the Caribbean and 9% of deaths in Africa and Asia.
Berg CJ, Atrash HK, Koonin LM, et al. Pregnancy-related mortality in the United States, 1987-1990. Obstet Gynecol. 1996;88:161-167.
Hibbard BM, Anderson MM, Drife JO, et al. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom, 1991-1993. London: Her Majesty’s Stationery Office; 1996:1-31.
Khan KS, Wojdyla D, Say L, et al. WHO analysis of causes of maternal deaths: a systematic review. Lancet. 2006;367:1066-1074.
A.7. Discuss the pathogenesis of preeclampsia.
Preeclampsia is most likely a disease of heterogeneous causes of both maternal and placental origin.
Immunologic Factors
Immunologic disorders may arise from an abnormal maternal-fetal antigen-antibody response or from the contents of seminal fluids; spermatozoa may cause antibody formation, or prostaglandins may initiate uterine vasoconstriction. The fetus acquires 50% of its genes from the father, which represents in part a paternal allograft that interacts with maternal tissue as the fetal trophoblast migrates into the maternal decidua after implantation. Migration normally occurs in two phases. Trophoblasts displace the muscular structure of the maternal spiral arteries before 20 weeks of gestation, causing their adrenergic denervation and converting them from high-resistance to low-resistance vessels. At the same time, biochemical adaptations occur in the maternal vasculature, with an increased dominance of endothelium-dependent vasodilators, prostacyclin (prostaglandin I [PGI]), and nitric oxide (NO). In preeclampsia, the second wave of trophoblastic migration fails. This failure can result in a high-resistance, low-flow uteroplacental circulation and consequent placental ischemia and hypoxia. These changes may represent an aberrant immunologic mechanism.
Genetic Factors
A familial tendency toward preeclampsia exists in some populations, and it may result from a recessive genetic inheritance.
Endothelial Factors
Vascular endothelial damage or dysfunction is the common pathologic feature of preeclampsia and occurs in the placental decidual vessels and renal microvasculature. Endothelial cell dysfunction in response to unknown factors may cause a hormonal imbalance in women with preeclampsia (Fig. 28.1).
The metabolic end products of normal vascular endothelium include PGI2 and endothelium-derived relaxing factor (EDRF), which is either NO or a related nitrosyl substance.
Both PGI2 and EDRF are potent vasodilators. In patients with preeclampsia, the failure of the trophoblast to invade the uteroplacental vascular bed may encourage an increased production of free radicals and lipid peroxides by the decidual lymphoid tissue. As a result, an imbalance occurs between the production of the vasoconstrictor thromboxane A2 (TXA2), which is derived from platelets, and the production of endothelium-derived PGI2. This imbalance results in a reduced perfusion of the intervillous space. Some investigators have concluded that hypoxia-induced impairment of NO production by the syncytiotrophoblast results in uteroplacental insufficiency and production of a toxin responsible for the clinical manifestations of preeclampsia.
Both PGI2 and EDRF are potent vasodilators. In patients with preeclampsia, the failure of the trophoblast to invade the uteroplacental vascular bed may encourage an increased production of free radicals and lipid peroxides by the decidual lymphoid tissue. As a result, an imbalance occurs between the production of the vasoconstrictor thromboxane A2 (TXA2), which is derived from platelets, and the production of endothelium-derived PGI2. This imbalance results in a reduced perfusion of the intervillous space. Some investigators have concluded that hypoxia-induced impairment of NO production by the syncytiotrophoblast results in uteroplacental insufficiency and production of a toxin responsible for the clinical manifestations of preeclampsia.
 FIGURE 28.1 Endothelial cell dysfunction in response to unknown factors may cause a hormonal imbalance in women with pregnancy-induced hypertension. GFR, glomerular filtration rate; HELLP, hemolysis, elevated liver enzymes, low platelets; RBF, renal blood flow. (From Chestnut DH, ed. Obstetric Anesthesia: Principles and Practice. 3rd ed. Philadelphia, PA: Mosby; 2004:798, with permission.) |
It has been shown that production of endothelin 1 (ET-1), which is the most potent endogenous vasoconstrictor and produced mainly by vascular smooth muscle cells as well as by the vascular endothelium, is markedly increased in preeclampsia and correlates inversely with NO production. Therefore, the imbalance between NO and ET-1 may play a significant role in the pathophysiology of preeclampsia.
Fetoplacental blood vessels, namely, the human placental chorionic plate arteries, constrict in response to ET-1. Moreover, there is now some evidence that amniotic concentration of ET-1 is elevated in pregnancies associated with preeclampsia. Margarit et al. found a statistically significant increase in ET-1 concentration in the amniotic fluid of women at 17 weeks’ gestation who developed preeclampsia, as compared to those who did not develop preeclampsia. By the second trimester, higher levels of ET-1 have also been shown in the amniotic fluid of women with preterm premature rupture of the membranes.
Platelet Factors
In mild preeclampsia, serotonin (5-HT) released from aggregating platelets interacts with endothelial 5-HT1 receptors, resulting in the release of prostacyclin and NO (EDRF). The released prostacyclin induces angiotensin II release, improving uteroplacental perfusion. In early-onset severe preeclampsia, damaged uteroplacental vessels cannot respond to 5-HT1 effects. Instead, serotonin interacts with 5-HT2 receptors on vascular smooth muscle cells, inducing vasoconstriction. Platelet-derived serotonin also activates 5-HT2 platelet receptors, establishing a positive feedback loop and intensifying platelet aggregation. The loss of 5-HT1 receptors prevents stimulation of angiotensin II release (Fig. 28.2).
Calcium
In normal pregnancy, the intracellular free calcium concentration increases slowly, but this increase is significantly greater in the third trimester in women with preeclampsia. The increase in cytoplasmic calcium levels is enhanced by angiotensin II, and the enhancement is greater in women with preeclampsia compared with normotensive women. This response to angiotensin II occurs long before signs of preeclampsia become evident and is a sensitive indicator of its subsequent development.
Coagulation Factors
Platelet activation in preeclampsia is surface-mediated. Women with preeclampsia have an increased tendency toward thromboembolism, which may result in part from an alteration in the plasma ratio between von Willebrand factor and factor VIII coagulant activity.
Fatty Acid Metabolism
Altered handling of fatty acids by the liver is a key factor in the pathogenesis of preeclampsia. Both increased hepatic uptake of free fatty acids and hypertriglyceridemia are seen more frequently in women who develop preeclampsia.
 FIGURE 28.2 The loss of 5-HT1 receptors prevents stimulation of angiotensin II release. EDRF, endothelium-derived relaxing factor. (From Chestnut DH, ed. Obstetric Anesthesia: Principles and Practice. 3rd ed. Philadelphia, PA: Mosby; 2004:797, with permission.) |
Markers of Angiogenesis
Preeclamptic patients have elevated plasma levels of endoglin and soluble FLT-1, the receptor for vascular endothelial growth factor, throughout gestation. Recent research suggests that these molecules are not just disease markers but are involved in the pathogenesis of preeclampsia.
Baksu B, Davas I, Baksu A, et al. Plasma nitric oxide, endothelin-1 and urinary nitric oxide and cyclic guanosine monophosphate levels in hypertensive pregnant women. Int J Gynaecol Obstet. 2005;90(2): 112-117.
Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut’s Obstetric Anesthesia: Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:829-833.
Margarit L, Griffiths A, Tsapanos V, et al. Second trimester amniotic fluid endothelin concentration. A possible predictor for pre-eclampsia. J Obstet Gynaecol. 2005;25(1):18-20.
Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12:642-649.
A.8. Discuss the pathologic alterations of preeclampsia.
Cardiovascular Changes
Blood pressure. Increase in BP results from an increase in peripheral vascular resistance secondary to a state of sympathetic overactivity. Alternatively, systolic BP increases as a result of increased cardiac output (increased plasma volume—typical of pregnancy) and a noncompliant aorta. In such cases, the systemic vascular resistance (SVR), which is predominantly determined by the smaller arterioles, is not increased but due to aortic stiffness, the ejected stroke volume causes the systolic component to rise significantly.
Blood volume. Reduction in blood volume causes a greater degree of hemoconcentration.
Hemodynamic Changes
Three hemodynamic subsets exist:
Hyperdynamic with increased cardiac output, normal or slightly increased SVR, and normal or slightly decreased blood volume and filling pressures
High SVR with normal cardiac output and lower filling pressures
Markedly increased SVR with decreased blood volume and depressed left ventricular function
Poor correlation between CVP and pulmonary artery (PA) occlusion pressure
Decreased colloid oncotic pressure in pregnancy with further reduction in preeclampsia. The low colloid oncotic pressure, coupled with increased vascular permeability and the loss of intravascular fluid and protein into interstitial tissues, increases the risk of pulmonary edema.Related posts:
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