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Severe preeclampsia complicating mitral valve stenosis
Regional Anesthesia and Pain Medicine 23(2): 204-209, 1998
Severe Preeclampsia Complicating Mitral Valve Stenosis Beatrice Afrangui, M.D. and A.M. Malinow, M.D.
Background and Objectives. We present a report of a parturient with severe mitral valve stenosis diagnosed during a previous pregnancy who developed severe preeclampsia. Methods: Labor and subsequent abdominal delivery were managed with epidural analgesia and anesthesia. The clinical management was guided by invasive hemodynamic monitoring, including a flow-directed pulmonary artery catheter. Conclusions: Peripartum maternal and neonatal outcomes were satisfactory. Postpartum complications included pulmonary edema as well as peripartum heart failure and pulmonary thromboembolism 4 weeks postpartum. Reg Anestlt Pain Med 1998: 23: 204-209. Key words: mitral valve stenosis, pulmonary hypertension. severe preeclampsia. epidural anesthesia, cesarean delivery, pulmonary artery catheter.
Mitral valve stenosis is the most common rheumatic valvular lesion found during pregnancy (I). It is associated with a fixed, maximal cardiac output because of limitations in diastolic filling and stroke volume (2). Gravidae with moderate-to-severe mitral valve stenosis often cannot increase their cardiac output to meet the normal physiologic demands of pregnancy (2). The physiologic stress of labor and delivery can lead to an acute decompensation, including pulmonary edema and right ventricular failure (2). Any superimposed disease state associated with added cardiac stress may result in further deterioration. Preeclampsia is a disease associated with vasospasm (3), circulating hypovolemia (4), and evidence of organ hypoperfusion (5,6). Patients with severe preeclampsia may manifest both cardiogenic and noncardiogenic pulmonary edema (7,8), malignant hypertension (9), and oliguria (9). From the Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland. Accepted for publication September 13, 1997. Reprint requests: Beatrice Afrangui, M.D., University of Maryland Women's Center, Sl 1C04, UMMC, 22 South Greene Street, Baltimore, MD 21201. Copyright © 1998 by the American Society of Regional Anesthesia. 0146- 521X/98/2302-00 16$ 5.00/0
Therapy used to optimize cardiac function in patients with mitral valve stenosis (e.g., diuretics) may lead to uteroplacental hypoperfusion in a parturient with severe preeclampsia. Therapy used to optimize placental perfusion in certain subsets of parturients with severe preeclampsia (e.g., arterial vasodilatation, aggressive intravascular hydration), may lead to cardiac decompensation because of coexisting mitral valve stenosis. We report on our management of a multiparous parturient with a history of moderate-to-severe mitral valve dysfunction who presented at 34 weeks estimated gestational age with severe preeclampsia.
Case Report A 26-year-old gravida 3 para I abortus I was transported to the University of Maryland Women's Center at 34 weeks estimated gestational age from an outlying hospital. The patient had complaints of headache, scotomata, and increasing pedal edema. The patient had mitral valve stenosis diagnosed earlier during the second trimester of her last pregnancy (four years prior), at which time she also developed pulmonary edema. Her echocardiogram demonstrated a calculated mitral valve area of 1.3
Severe Preeclampsia Complicating Mitral Valve Stenosis •
crrr', a dilated left atrium, a left ventricular ejection fraction >60%, and trivial mitral, aortic, and pulmonic valve regurgitation. At that time, her pregnancy progressed to term, resulting in a spontaneous vaginal delivery, and she was discharged home on the fourth postpartum day after recovering from postpartum pulmonary edema. At 27 weeks gestation during this pregnancy, the patient was admitted to the hospital with complaints of dyspnea and radiographic evidence of pulmonary edema. M-mode Doppler echocardiography estimated pulmonary artery systolic pressure at 50 mm Hg with a left ventricular ejection fraction >70%. Her systemic arterial blood pressure was not elevated, but she was tachycardic. After resolution of her symptoms, the patient was discharged home with atenolol to control the maternal heart rate. On her admission to the labor and delivery suite, her systemic arterial blood pressure was 150n 02 mm Hg. and she had (I +) proteinuria. Auscultation of her chest revealed clear breath sounds, and her heart rate was 95 beats/min with an audible IIIlV presystolic murmur. She had moderate-to-severe nondependent edema and no hyperreflexia. Laboratory investigation revealed platelet count, 255,000/ nL; blood urea nitrogen, 12 mg/dL; serum creatinine, 1.0 mg/dL; serum uric acid, 7.7 mg/dL; serum LDH, 801 UlL; serum ALT, 106 U/L; and serum AST, 137 UlL. A 12-lead electrocardiogram revealed sinus rhythm with evidence of left atrial enlargement and a right ventricular conduction delay. A chest radiograph showed small bilateral pleural effusions, but no other abnormalities. She had I-em cervical dilatation, 0% effacement, and the fetal vertex not in the pelvis. Analysis of the electronicfetal heart rate tracing demonstrated a fetal heart rate of 130-140 beats/min, adequate beat-to-beat variability without periodic changes. Tocodynamometry showed no uterine contractions. An intravenous bolus of 6 g magnesium sulfate was followed by a continuous infusion at 2 g/h, In this near-term gestation with known severe mitral valve stenosis and with acute onset of severe preeclampsia that might cause critical cardiac decompensation, an intravenous oxytocin induction was begun. A radial arterial and pulmonary artery thermodilution catheter were inserted. Initial hemodynamic measurements showed: heart rate (HR), 95 beats/min; blood pressure (BP), 130/98 mm Hg; pulmonary artery pressure (PAP), 80135 mm Hg; central venous pressure (CVP), 8 mm Hg; cardiac output (CO), 3.5 Lrmin: and systemic vascular resistance (SVR) 2600 dynes/cm/s5. After an epidural test dose injection of 3 mL of 0.25% bupivacalne, 10 mL 0.125% bupivacaine
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and 50 p.g fentanyl were incrementally injected, producing a T8 sensory level. Repeated 100 mL intravenous boluses of lactated Ringer's were administered to maintain systemic arterial blood pressure within 20% of preinduction values. Immediately, epidural analgesia was begun. At that point, the heart rate was 95 beats/min, BP, 145/90 mm Hg; PAP, 77/30 mm Hg; CVP, 12 mm Hg; CO, 3.8 Umin; and SVR, 2100 dynes/cm/s5. Labor analgesia was maintained with a continuous epidural infusion of 0.0625% bupivacaine, fentanyl I p.g/mL, and epinephrine I:600,000. There were no changes in variability or evidence of periodic changes in the electronic fetal heart rate tracing. To optimize cardiac output with minimal chronotropic effect, an intravenous infusion of dobutamine was started at 0.5 p.g/kg/min and incrementally increased to 2 p.g/kg/min. Maternal heart rate increased to 115 beats/min; BP, 145/90 mm Hg; PAP, 88/35 mm Hg; and with a small increase in cardiac output to 4.2 Umin. The dobutamine infusion was discontinued, and the maternal heart rate returned to 100 beats/min with a cardiac output of 3.7 Lzrnin. After 12 hours of oxytocin-stimulated labor (and 6 hours of epidural analgesia), without progression of labor, and with evidence of worsening preeclampsia an abdominal delivery was planned. To produce surgical anesthesia, 9 mL of 0.5% buplvacaine was incrementally injected, followed by an additional 10 mL of 2% lidocaine with freshly added epinephrine (1: 400,000) and 50 p.g fentanyl. A T2 sensory dermatome level of surgical anesthesia was obtained. Cesarean delivery yielded a live preterm neonate with Apgar scores of 6 at I minute and 8 at 5 minutes, respectively, Umbilical cord blood revealed an umbilical artery pH 7.23/pC0256/p0222!HC0321/BD-6.6 and umbilical vein pH 7.26/pC0247/p02 39/HC0 323/ BD-4.7. Preservative-free morphine (3.5 mg) was injeered via the epidural catheter for postoperative pain relief. Incremental Injections of phenylephrine (20 p.g) and crystalloid solution were intravenously infused to maintain systemic arterial blood pressure above 100 mm Hg systolic. Surgical blood loss was estimated at 1,000 mL. A total of 1,300 mL of lactated Ringer's and 250 mL of 5% albumin was intravenously infused over the 8-hour duration of labor and abdominal delivery. Two hours postpartum the HR was 85 beats/min; BP 130170 mm Hg; CVP, 10 mm Hg; PAP, 69/32 mm Hg; CO, 5.5 Umin; and SVR, 1150 dynes/em/ s5/ The rate of intravenous crystalloid solution infusion was 75 mUh. On the first postoperative day, the patient developed dyspnea and radiographic evidence of pulmo-
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nary edema which was treated with an intravenous injection of 20 mg furosemide and supplemental administration of oxygen. Over the next 24 hours, the pulmonary edema resolved and maternal systemic arterial blood pressure returned to early antenatal values while the liver function tests were returning to normal levels. Magnesium sulfate therapy was then discontinued. The rate of the intravenous fluid infusion was maintained at 75 mLlh. On the third postoperative day, the patient developed oliguria with a concomitant rise in serum creatinine (to 1.2 mg/dL) and uric acid (10 mg/dl.). The platelet count decreased to 77,000/nI. With unexpectedly slow resolution of her preeclampsia, intravenous magnesium sulfate therapy (4 g followed by an infusion of 2 g/h) was reinitiated. Calculation of the patient's 24-hour fluid balance revealed the patient had 500 mL more input than output. The HR was 100 beats/min; BP, 145/90 mm Hg; PAP, 68/30 mm Hg; CVP, 12 mm Hg; CO, 2.9 Llmin; and SVR 2700 dynes/cm/s5. Intravenous digoxin (0.5 mg followed by two doses of 0.25 mg over the next 16 hours) was injected in an attempt to maximize cardiac output without chronotropy. Over the next 24 hours, the signs of preeclampsia again resolved. Cardiac output increased to 3:8 Llmin. Urinary output increased to 1 mLlh. The patient continued to improve and magnesium sulfate therapy was again discontinued. The pulmonary artery catheter was also removed. On the twelfth postoperative day, an echocardiogram revealed a left ventricular ejection fraction estimated at >60%. Pulmonary artery systolic pressure was estimated at 65 mm Hg with moderate-tosevere tricuspid regurgitation. The consultant cardiologist recommended a subsequent admission for mitral valvuloplasty which the patient refused. She was discharged to home on enalapril 5 mg orally every day. Four weeks postpartum, the patient was readmitted to the hospital with acute onset of dyspnea. A diagnosis of pulmonary thromboembolism (as diagnosed by radionuclide ventilation/ perfusion scan and confirmed by pulmonary angiography) and dilated cardiomyopathy (ejection fraction = 20%) was made. The patient was discharged after 25 hospital days on isosorbide, coumadin, and furosemide. Three years after her last hospital admission, the patient is still doing "reasonably well" and has since refused mitral valve replacement.
Discussion In patients with mitral valve stenosis right- and bi-ventricular failure occur when the physiologic demand to increase cardiac output cannot be met (2). Ventricular failure is therefore a risk in the postpartum period (10,11). Mortality in pregnant women with mitral valve stenosis may be as high as 5-15% (1). In the past, labor was not recommended for gravidae with moderate-to-severe mitral valve stenosis (12). Recently, however, a trial of labor has been advocated (2). It is believed that labor and vaginal delivery carry little additional risk provided that the clinicians properly use appropriate maternal hemodynamic monitoring, provide intrapartum analgesia and use intensive care resources appropriately (1,2). Hemodynamic goals in the parturient with symptomatic mitral valve stenosis include: maintenance of sinus rhythm (with prompt and aggressive treatment of atrial fibrillation), attenuation of maternal tachycardia, and maintenance of adequate right ventricular preload without causing pulmonary edema (1,2). Epidural analgesia blunts stress-induced maternal tachycardia in the parturient with mitral valve stenosis. This is important because maternal tachycardia decreases left ventricular stroke volume as there is inadequate time for left ventricular filling (1). Epidural labor analgesia is advocated for preeclamptic parturients only after adequate vascular hydration is used to attempt to decrease the uterine vasoconstrictive effects of stress-induced cathecholamines (13). Maintenance of adequate circulating volume during induction of epidural analgesia minimizes reflex maternal tachycardia, maintains right and left ventricular preload, maintains or improves uteroplacental perfusion (14), and decreases the need for exogenous vasopressors. We thought that epidural labor analgesia was most appropriate in the anesthetic and obstetric management of this patient's preeclampsia and mitral valve stenosis. Continuous spinal analgesia or combined spinal and epidural analgesia with injections of opioids could have been used for labor analgesia. Some clinicians suggest that these techniques minimize the sudden onset sympathectomy and possible acute cardiac decompensation which is occasionally seen with epidural analgesia. We believed that the high probability of abdominal delivery would mandate that we eventually use anesthetic concentrations of spinal or epidural local anesthetic, inducing the same cardiovascular effects as seen with the de IlOVO induction of epidural analgesia. Using a noncontinuous technique for labor
Severe Preeclampsia Complicating Mitral Valve Stenosis
analgesia (e.g.. intrathecal opioid with pudendal and paracervical blocks) obligates anesthesiologists to use general anesthesia for urgent or emergent abdominal deliveries in these high-risk patients. General anesthetic agents for pregnant cardiac (15) and preeclamptic patients (16) are well described elsewhere in the literature. Blocking the pressor and tachycardiac response to tracheal intubation in this severely preeclamptic patient would have been of prime concern, especially in a patient with severe mitral valve disease. Another choice for this preeclamptic patient was single-shot spinal anesthesia. Some clinicians believe that any type of regional anesthesia is safer than the induction of general anesthesia in the pregnant patient (especially the preeclamptic patient) (17). We believe this point to be, at the very least, controversial, and, in our patient with mitral valve stenosis, the use of single-shot spinal anesthesia was not considered part of the anesthetic plan. We believed the use of a dilute bupivacaine and fentanyl solution to induce analgesia allows for a more gradual onset of sympathectomy and venodilation as compared to a more concentrated local anesthetic solution. The gradual onset of venodilation allows additional time to recognize signs of relative circulating hypovolemia, such as increasing maternal heart rate, decreasing central venous pressure, decreasing cardiac output, or subtle signs of placental hypoperfusion. Small bolus volumes of intravenous fluids were infused to replenish intravascular volume, thus avoiding the injection of vasopressors or the empirical infusion of large volumes of intravenous fluid that might lead to cardiogenic pulmonary edema. We chose to use a nonepinephrine containing local anesthetic to induce labor analgesia because the unintentional intravascular injection of epinephrine (15 Ilg) could cause abrupt maternal tachycardia. Although intravenous epinephrine might induce hypertension in a preeclamptic patient, epinephrine-induced tachycardia in the patient with a stenotic valve might cause an abrupt decrease in maternal cardiac output leading to maternal hypotension. Intravenous injection of epinephrine (15 Ilg) also induces uterine artery vasoconstriction (18). Once the function of the epidural catheter was confirmed, our standard anesthetic solution for laboring patients [bupivacaine (1/16%)/ fentanyl (1 Ilg/mL)/epinephrine (1:600,000)] was infused. We did not believe that epidural infusion of a dilute epinephrine-containing local anesthetic solution would increase maternal heart rate because it did not significantly increase maternal heart rate when intravenously infused in the gravid ewe model (19).
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Epidural injection of 0.5% bupivacaine was used initially to extend the rostral level of surgical anesthesia to allow gradual onset of venodilation with the epidural anesthetic-induced sympathectomy. Epinephrine was again omitted from the initial bolus injection. The surgical level of anesthesia was intensified with the local anesthetic mixture (2 % lidocaine with freshly added 1:400,000 epinephrine and 50 Ilg fentanyl) that we routinely inject in preparation for abdominal delivery. Again, we did not believe that epidural injection of epinephrinecontaining local anesthetic would acutely increase maternal HR. Maternal HR remained constant until 30 minutes after injection of the last local anesthetic. At that time, there was an abrupt increase in maternal HR to 115 beats/min as the patient was moved into the operating room. We believed that the patient's tachycardia was not due to systemic absorption of epinephrine in the epidural anesthetic, but instead caused by her anxiety. Maternal cardiac output did not decrease and the fetal heart rate tracing did not change. We decided not to inject beta-adrenergic blocking drugs. Maternal tachycardia could have been attenuated by the intravenous infusion of esmolol. However, esmolol has been associated with a decrease in fetal heart rate (20). Perhaps the onset of fetal side effects could have been delayed by slowly decreasing the rate of esmolol infusion until onset of fetal bradycardia precluded its use. The patient tolerated the abdominal delivery without complication. Intravenous phenylephrine was chosen as the vasopressor to be injected for maternal hypotension or change in fetal heart rate tracing. Dilute intravenous doses of phenylephrine have been used instead of ephedrine as a pressor drug in obstetric anesthesia with maternal efficacy and without fetal compromise in routine pregnancies (21). If a patient with either preeclampsia or mitral valve stenosis presented for abdominal delivery, it could be argued that a pulmonary artery thermodilution catheter would have been unnecessary in the management of her anesthesia. Central venous or pulmonary artery catheterization could be initiated if indicated by cardiac decompensation, which would most probably occur in the postpartum period. However, we believed that the initial obstetric plan to induce labor in anticipation of vaginal delivery (especially in a patient with an unfavorable cervix) extended the period during which the patient would be exposed to physiologic stress. Pulmonary artery thermodilution catheter-generated hemodynamic profiles have proved useful in the management of the severely preeclamptic parturient with oliguria unresponsive to aggressive intra-
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vascular hydration or in those parturients who manifest pulmonary edema (22). Therefore, because of this patient's mitral valve stenosis, we thought it optimal to measure central pressures (thereby estimating right ventricular preload and right ventricular afterload) and cardiac output in response to intravascular hydration, alterations in (the awake and often anxious parturient's) HR, and response to drug therapy (such as vasopressor drugs, inotropic drugs, and magnesium sulfate). Intravenous dobutamine was infused as a right ventricular inotrope in an attempt to optimize cardiac output during labor. Dobutamine was chosen because it is associated with less chronotropy than dopamine. We believed that the relatively short duration of action of dobutamine (as compared to a phosphodiesterase inhibitor such as milrinone) might be more desirable if in fact maternal cardiac or fetal decompensation occurred. The trial of dobutamine was abandoned because the cardiac output did not significantly increase but the maternal HR did. However, the trial of dobutamine did demonstrate that the patient could withstand at least a short period of tachycardia (II 5-120 beats/min) without acute cardiac decompensation. Pulmonary vascular resistance is increased by relative hypoxemia, hypercarbia, acidosis, environmental cold and postoperative pain (IS); all to be avoided in the operating room as well as in the postpartum period. The patient manifested pulmonary edema on the first postoperative day, and we believe that this was cardiogenic in etiology. In fact, this episode of pulmonary edema was easily treated with furosemide and supplemental oxygen. With apparent resolution of her preeclampsia, the magnesium sulfate infusion was stopped. One day later, she manifested oliguria. Her central venous pressures were elevated, her systemic vascular resistance was high, and her cardiac output was relatively low as compared to earlier measurements. We did not believe she was hypovolemic. Intravenous magnesium sulfate therapy was restarted in a trial attempt to decrease vasospasm as well as to provide seizure prophylaxis. At the same time, the patient was digitalized to provide inotropic support. The patient's further immediate postpartum course was uneventful. Her renal function returned to normal. Her left ventricular function was echocardiographically estimated to be normal. She was discharged on an angiotensin-converting enzyme inhibitor. The patient presented 4 weeks postpartum with a dilated cardiomyopathy and pulmonary thromboembolism (PTE). Pulmonary thromboem-
bolism is reported in 0.05% of all pregnancies (23). The diagnosis of PTE at 4 weeks postpartum was not entirely unexpected because pregnancy increases the risk of PTE five- to sixfold (24). In addition, abdominal delivery increases the risk of PTE as compared to vaginal delivery (25). Pulmonary thromboembolism is associated with mitral stenosis, especially in patients with atrial fibrillation (l). Pulmonary thromboembolism occurs in approximately 50% of women with peripartum cardiomyopathy (I). In retrospect, it might have been prudent to have anticoagulated the patient before discharge from the labor and delivery suite. In summary, we report on a gravida with moderate-to-severe mitral valve stenosis whose pregnancy was complicated by pulmonary edema, severe preeclampsia, peripartum heart failure, and pulmonary thromboemoblism. She withstood a trial of labor followed by abdominal delivery during epidural analgesia and anesthesia. Her obstetric outcome was satisfactory and guided by the use of invasive hemodynamic monitoring. At 4 weeks postpartum she presented with a dilated cardiomyopathy and pulmonary thromboembolism. She survives and continues to do well.
References 1. Clark SL. Structural cardiac disease in pregnancy. In:
2.
3.
4.
5.
6.
7.
Clark SL, Cotton DB, Hankins GDV, Phelan JR, eds. Critical care obstetrics, 2nd ed. Boston, Blackwell, 1991: 115-124. Clark SL, Phelan JR, Greenspoon J, Aldahl D, Horenstein J. Labor and delivery in the presence of mitral stcnsosi: Central hemodynamic observations. Am J Obstet Gynecol 1985: 152: 948-958. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensinogen II pressor response throughout primigravid pregnancy. J Clin Invest 1973: 51: 2682-2689. Chesley LC, Lindhcimer MD. Renal hemodynamics and intravascular volume in normal and hypertensive pregnancy. In: Rubin PC, ed. Handbook of hypertension in pregnancy. In: Rubin PC, ed. Handbook of hypertension in pregnancy. Vol. 10. Amsterdam, Elsevier, 1988: 38-65. Kaar K, Joupilla P, Kuikka J, Luotola H, Toivanen J, Rekonen A. Intervillous blood flow in normal and complicated late pregnancy by means of a 133Xe method. Acta Obstet Gynecol Scand 1980: 59: 7-10. Groenendijk R, Trimbos JB, Wallenburg HC. Hemodynamic measurements in preeclampsia: Preliminary observations. Am J Obstet Gynecol 1984: 150: 232-236. Desai DK, Moodley J, Naidoo DP, Bhorat I. Cardiac abnormalities in pulmonary oedema associated
Severe Preeclampsia Complicating Mitral Valve Stenosis •
8.
9.
10.
11.
12.
13.
14.
15.
with hypertensive crises in pregnancy. Br J Obstet Gynaecol 1996: 103: 523-528. Mabie We, Hackman BB, Sibai BM. Pulmonary edema associated with pregnancy: Echqcardiographic insights and implications for treatment, Obstet Gynecol 1993: 81: 227-234. American College of Obstetricians and Gynecologists. Management of preeclampsia. ACOG Technical Bulletin, No. 219, 1996. Ueland K. Hansen JM. Maternal cardiovascular hemodynamics Ill. Labor and delivery under local and caudal anesthesia. Am J Obstet Gynecol 1969: 103: 8-18. James CF, Banner T, Caton D. Cardiac output in women undergoing cesarean section with epidural or general anesthesia. Am J Obstet Gynecol 1989: 160: 1178-1184. Ueland K, Hansen J, Eng M, Kalappa R, Parer JT. Maternal cardiovascular dynamics vs. cesarean section under thiopental, nitrous oxide and succinylcholine anesthesia. Am J Obstet Gynecol 1970: 108: 615-622. Gutsche B. The expert's opinion: Is epidural block for labor and delivery and for cesarean section a safe form of analgesia in severe preeclampsia or eclampsia? Surv Anesth 1986: 30: 304-311. Joupilla P, Joupilla R, Hollman A, Koivula A. Lumbar epidural analgesia to improve intervillous blood flow during labor in severe preeclampsia. Obstet Gynecol 1982: 59: 158-161. Thornhill ML, Camann WR. Cardiovascular disease. In: Chestnut DH, ed., Obstetric anesthesia: Principles and practice, St Louis, Mosby, 1994: 759-760.
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16. Boxer LM, Malinow AM. Preeclampsia and eclampsia. Curr Opin Anaesthesiol 1997: 10: 188-198. 17. Writer D. Hypertensive disorders. In: Chestnut DH, ed. Obstetric anesthesia: Principles and practice. S1. Louis, Mosby, 1994: 872. 18. Chestnut DR, Weiner CP, Martin JG, Herring JE, Wang JP. Effect of intravenous epinephrine on uterine artery blood flow velocity in the pregnant guinea pig. Anesthesiology 1986: 66: 688-691. 19. Norris MC, Grieco W, Arkoosh VA. Does continuous intravenous infusion of low-concentration epinephrine impair uterine blood flow in pregnant ewes? Reg Anesth 1995: 20: 206-211. 20. Eisenach Je, Castro Ml: Maternally administered esrno101 produces beta-adrenergic blockade and hypoxemia in sheep. Anesthesiology 1989: 71: 718-722. 21. Moran D, Perillo M, La Porta RF, Bader AM, Datta S. Phenylephrine in the prevention of spinal hypotension following spinal anesthesia for cesarean delivery. J Clin Anesth 1991: 3: 301-305. 22. Clark SL, Horenstein JM, Phelan JP, Montag TW, Paul RH. Experience with the pulmonary artery catheter in obstetrics and gynecology. Am J Obstet Gynecol1985: 152: 374-378. 23. Weiner CPo Diagnosis and management of thromboemoblism disease during pregnancy. Clin Obstet Gynecol 1985: 28: 107-118. 24. Bolan JC. Thromboemoblic complications of pregnancy. Clin Obstet Gynecol 1981: 26: 913-922. 25. Bergqvist A, Bergqvist D, Hallbrook T. Acute deep vein thrombosis after cesarean section. Acta Obstet Gynaecol Scand 1979: 58: 473-476.
Severe Preeclampsia Complicating Mitral Valve Stenosis Beatrice Afrangui, M.D. and A.M. Malinow, M.D.
Background and Objectives. We present a report of a parturient with severe mitral valve stenosis diagnosed during a previous pregnancy who developed severe preeclampsia. Methods: Labor and subsequent abdominal delivery were managed with epidural analgesia and anesthesia. The clinical management was guided by invasive hemodynamic monitoring, including a flow-directed pulmonary artery catheter. Conclusions: Peripartum maternal and neonatal outcomes were satisfactory. Postpartum complications included pulmonary edema as well as peripartum heart failure and pulmonary thromboembolism 4 weeks postpartum. Reg Anestlt Pain Med 1998: 23: 204-209. Key words: mitral valve stenosis, pulmonary hypertension. severe preeclampsia. epidural anesthesia, cesarean delivery, pulmonary artery catheter.
Mitral valve stenosis is the most common rheumatic valvular lesion found during pregnancy (I). It is associated with a fixed, maximal cardiac output because of limitations in diastolic filling and stroke volume (2). Gravidae with moderate-to-severe mitral valve stenosis often cannot increase their cardiac output to meet the normal physiologic demands of pregnancy (2). The physiologic stress of labor and delivery can lead to an acute decompensation, including pulmonary edema and right ventricular failure (2). Any superimposed disease state associated with added cardiac stress may result in further deterioration. Preeclampsia is a disease associated with vasospasm (3), circulating hypovolemia (4), and evidence of organ hypoperfusion (5,6). Patients with severe preeclampsia may manifest both cardiogenic and noncardiogenic pulmonary edema (7,8), malignant hypertension (9), and oliguria (9). From the Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland. Accepted for publication September 13, 1997. Reprint requests: Beatrice Afrangui, M.D., University of Maryland Women's Center, Sl 1C04, UMMC, 22 South Greene Street, Baltimore, MD 21201. Copyright © 1998 by the American Society of Regional Anesthesia. 0146- 521X/98/2302-00 16$ 5.00/0
Therapy used to optimize cardiac function in patients with mitral valve stenosis (e.g., diuretics) may lead to uteroplacental hypoperfusion in a parturient with severe preeclampsia. Therapy used to optimize placental perfusion in certain subsets of parturients with severe preeclampsia (e.g., arterial vasodilatation, aggressive intravascular hydration), may lead to cardiac decompensation because of coexisting mitral valve stenosis. We report on our management of a multiparous parturient with a history of moderate-to-severe mitral valve dysfunction who presented at 34 weeks estimated gestational age with severe preeclampsia.
Case Report A 26-year-old gravida 3 para I abortus I was transported to the University of Maryland Women's Center at 34 weeks estimated gestational age from an outlying hospital. The patient had complaints of headache, scotomata, and increasing pedal edema. The patient had mitral valve stenosis diagnosed earlier during the second trimester of her last pregnancy (four years prior), at which time she also developed pulmonary edema. Her echocardiogram demonstrated a calculated mitral valve area of 1.3
Severe Preeclampsia Complicating Mitral Valve Stenosis •
crrr', a dilated left atrium, a left ventricular ejection fraction >60%, and trivial mitral, aortic, and pulmonic valve regurgitation. At that time, her pregnancy progressed to term, resulting in a spontaneous vaginal delivery, and she was discharged home on the fourth postpartum day after recovering from postpartum pulmonary edema. At 27 weeks gestation during this pregnancy, the patient was admitted to the hospital with complaints of dyspnea and radiographic evidence of pulmonary edema. M-mode Doppler echocardiography estimated pulmonary artery systolic pressure at 50 mm Hg with a left ventricular ejection fraction >70%. Her systemic arterial blood pressure was not elevated, but she was tachycardic. After resolution of her symptoms, the patient was discharged home with atenolol to control the maternal heart rate. On her admission to the labor and delivery suite, her systemic arterial blood pressure was 150n 02 mm Hg. and she had (I +) proteinuria. Auscultation of her chest revealed clear breath sounds, and her heart rate was 95 beats/min with an audible IIIlV presystolic murmur. She had moderate-to-severe nondependent edema and no hyperreflexia. Laboratory investigation revealed platelet count, 255,000/ nL; blood urea nitrogen, 12 mg/dL; serum creatinine, 1.0 mg/dL; serum uric acid, 7.7 mg/dL; serum LDH, 801 UlL; serum ALT, 106 U/L; and serum AST, 137 UlL. A 12-lead electrocardiogram revealed sinus rhythm with evidence of left atrial enlargement and a right ventricular conduction delay. A chest radiograph showed small bilateral pleural effusions, but no other abnormalities. She had I-em cervical dilatation, 0% effacement, and the fetal vertex not in the pelvis. Analysis of the electronicfetal heart rate tracing demonstrated a fetal heart rate of 130-140 beats/min, adequate beat-to-beat variability without periodic changes. Tocodynamometry showed no uterine contractions. An intravenous bolus of 6 g magnesium sulfate was followed by a continuous infusion at 2 g/h, In this near-term gestation with known severe mitral valve stenosis and with acute onset of severe preeclampsia that might cause critical cardiac decompensation, an intravenous oxytocin induction was begun. A radial arterial and pulmonary artery thermodilution catheter were inserted. Initial hemodynamic measurements showed: heart rate (HR), 95 beats/min; blood pressure (BP), 130/98 mm Hg; pulmonary artery pressure (PAP), 80135 mm Hg; central venous pressure (CVP), 8 mm Hg; cardiac output (CO), 3.5 Lrmin: and systemic vascular resistance (SVR) 2600 dynes/cm/s5. After an epidural test dose injection of 3 mL of 0.25% bupivacalne, 10 mL 0.125% bupivacaine
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and 50 p.g fentanyl were incrementally injected, producing a T8 sensory level. Repeated 100 mL intravenous boluses of lactated Ringer's were administered to maintain systemic arterial blood pressure within 20% of preinduction values. Immediately, epidural analgesia was begun. At that point, the heart rate was 95 beats/min, BP, 145/90 mm Hg; PAP, 77/30 mm Hg; CVP, 12 mm Hg; CO, 3.8 Umin; and SVR, 2100 dynes/cm/s5. Labor analgesia was maintained with a continuous epidural infusion of 0.0625% bupivacaine, fentanyl I p.g/mL, and epinephrine I:600,000. There were no changes in variability or evidence of periodic changes in the electronic fetal heart rate tracing. To optimize cardiac output with minimal chronotropic effect, an intravenous infusion of dobutamine was started at 0.5 p.g/kg/min and incrementally increased to 2 p.g/kg/min. Maternal heart rate increased to 115 beats/min; BP, 145/90 mm Hg; PAP, 88/35 mm Hg; and with a small increase in cardiac output to 4.2 Umin. The dobutamine infusion was discontinued, and the maternal heart rate returned to 100 beats/min with a cardiac output of 3.7 Lzrnin. After 12 hours of oxytocin-stimulated labor (and 6 hours of epidural analgesia), without progression of labor, and with evidence of worsening preeclampsia an abdominal delivery was planned. To produce surgical anesthesia, 9 mL of 0.5% buplvacaine was incrementally injected, followed by an additional 10 mL of 2% lidocaine with freshly added epinephrine (1: 400,000) and 50 p.g fentanyl. A T2 sensory dermatome level of surgical anesthesia was obtained. Cesarean delivery yielded a live preterm neonate with Apgar scores of 6 at I minute and 8 at 5 minutes, respectively, Umbilical cord blood revealed an umbilical artery pH 7.23/pC0256/p0222!HC0321/BD-6.6 and umbilical vein pH 7.26/pC0247/p02 39/HC0 323/ BD-4.7. Preservative-free morphine (3.5 mg) was injeered via the epidural catheter for postoperative pain relief. Incremental Injections of phenylephrine (20 p.g) and crystalloid solution were intravenously infused to maintain systemic arterial blood pressure above 100 mm Hg systolic. Surgical blood loss was estimated at 1,000 mL. A total of 1,300 mL of lactated Ringer's and 250 mL of 5% albumin was intravenously infused over the 8-hour duration of labor and abdominal delivery. Two hours postpartum the HR was 85 beats/min; BP 130170 mm Hg; CVP, 10 mm Hg; PAP, 69/32 mm Hg; CO, 5.5 Umin; and SVR, 1150 dynes/em/ s5/ The rate of intravenous crystalloid solution infusion was 75 mUh. On the first postoperative day, the patient developed dyspnea and radiographic evidence of pulmo-
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nary edema which was treated with an intravenous injection of 20 mg furosemide and supplemental administration of oxygen. Over the next 24 hours, the pulmonary edema resolved and maternal systemic arterial blood pressure returned to early antenatal values while the liver function tests were returning to normal levels. Magnesium sulfate therapy was then discontinued. The rate of the intravenous fluid infusion was maintained at 75 mLlh. On the third postoperative day, the patient developed oliguria with a concomitant rise in serum creatinine (to 1.2 mg/dL) and uric acid (10 mg/dl.). The platelet count decreased to 77,000/nI. With unexpectedly slow resolution of her preeclampsia, intravenous magnesium sulfate therapy (4 g followed by an infusion of 2 g/h) was reinitiated. Calculation of the patient's 24-hour fluid balance revealed the patient had 500 mL more input than output. The HR was 100 beats/min; BP, 145/90 mm Hg; PAP, 68/30 mm Hg; CVP, 12 mm Hg; CO, 2.9 Llmin; and SVR 2700 dynes/cm/s5. Intravenous digoxin (0.5 mg followed by two doses of 0.25 mg over the next 16 hours) was injected in an attempt to maximize cardiac output without chronotropy. Over the next 24 hours, the signs of preeclampsia again resolved. Cardiac output increased to 3:8 Llmin. Urinary output increased to 1 mLlh. The patient continued to improve and magnesium sulfate therapy was again discontinued. The pulmonary artery catheter was also removed. On the twelfth postoperative day, an echocardiogram revealed a left ventricular ejection fraction estimated at >60%. Pulmonary artery systolic pressure was estimated at 65 mm Hg with moderate-tosevere tricuspid regurgitation. The consultant cardiologist recommended a subsequent admission for mitral valvuloplasty which the patient refused. She was discharged to home on enalapril 5 mg orally every day. Four weeks postpartum, the patient was readmitted to the hospital with acute onset of dyspnea. A diagnosis of pulmonary thromboembolism (as diagnosed by radionuclide ventilation/ perfusion scan and confirmed by pulmonary angiography) and dilated cardiomyopathy (ejection fraction = 20%) was made. The patient was discharged after 25 hospital days on isosorbide, coumadin, and furosemide. Three years after her last hospital admission, the patient is still doing "reasonably well" and has since refused mitral valve replacement.
Discussion In patients with mitral valve stenosis right- and bi-ventricular failure occur when the physiologic demand to increase cardiac output cannot be met (2). Ventricular failure is therefore a risk in the postpartum period (10,11). Mortality in pregnant women with mitral valve stenosis may be as high as 5-15% (1). In the past, labor was not recommended for gravidae with moderate-to-severe mitral valve stenosis (12). Recently, however, a trial of labor has been advocated (2). It is believed that labor and vaginal delivery carry little additional risk provided that the clinicians properly use appropriate maternal hemodynamic monitoring, provide intrapartum analgesia and use intensive care resources appropriately (1,2). Hemodynamic goals in the parturient with symptomatic mitral valve stenosis include: maintenance of sinus rhythm (with prompt and aggressive treatment of atrial fibrillation), attenuation of maternal tachycardia, and maintenance of adequate right ventricular preload without causing pulmonary edema (1,2). Epidural analgesia blunts stress-induced maternal tachycardia in the parturient with mitral valve stenosis. This is important because maternal tachycardia decreases left ventricular stroke volume as there is inadequate time for left ventricular filling (1). Epidural labor analgesia is advocated for preeclamptic parturients only after adequate vascular hydration is used to attempt to decrease the uterine vasoconstrictive effects of stress-induced cathecholamines (13). Maintenance of adequate circulating volume during induction of epidural analgesia minimizes reflex maternal tachycardia, maintains right and left ventricular preload, maintains or improves uteroplacental perfusion (14), and decreases the need for exogenous vasopressors. We thought that epidural labor analgesia was most appropriate in the anesthetic and obstetric management of this patient's preeclampsia and mitral valve stenosis. Continuous spinal analgesia or combined spinal and epidural analgesia with injections of opioids could have been used for labor analgesia. Some clinicians suggest that these techniques minimize the sudden onset sympathectomy and possible acute cardiac decompensation which is occasionally seen with epidural analgesia. We believed that the high probability of abdominal delivery would mandate that we eventually use anesthetic concentrations of spinal or epidural local anesthetic, inducing the same cardiovascular effects as seen with the de IlOVO induction of epidural analgesia. Using a noncontinuous technique for labor
Severe Preeclampsia Complicating Mitral Valve Stenosis
analgesia (e.g.. intrathecal opioid with pudendal and paracervical blocks) obligates anesthesiologists to use general anesthesia for urgent or emergent abdominal deliveries in these high-risk patients. General anesthetic agents for pregnant cardiac (15) and preeclamptic patients (16) are well described elsewhere in the literature. Blocking the pressor and tachycardiac response to tracheal intubation in this severely preeclamptic patient would have been of prime concern, especially in a patient with severe mitral valve disease. Another choice for this preeclamptic patient was single-shot spinal anesthesia. Some clinicians believe that any type of regional anesthesia is safer than the induction of general anesthesia in the pregnant patient (especially the preeclamptic patient) (17). We believe this point to be, at the very least, controversial, and, in our patient with mitral valve stenosis, the use of single-shot spinal anesthesia was not considered part of the anesthetic plan. We believed the use of a dilute bupivacaine and fentanyl solution to induce analgesia allows for a more gradual onset of sympathectomy and venodilation as compared to a more concentrated local anesthetic solution. The gradual onset of venodilation allows additional time to recognize signs of relative circulating hypovolemia, such as increasing maternal heart rate, decreasing central venous pressure, decreasing cardiac output, or subtle signs of placental hypoperfusion. Small bolus volumes of intravenous fluids were infused to replenish intravascular volume, thus avoiding the injection of vasopressors or the empirical infusion of large volumes of intravenous fluid that might lead to cardiogenic pulmonary edema. We chose to use a nonepinephrine containing local anesthetic to induce labor analgesia because the unintentional intravascular injection of epinephrine (15 Ilg) could cause abrupt maternal tachycardia. Although intravenous epinephrine might induce hypertension in a preeclamptic patient, epinephrine-induced tachycardia in the patient with a stenotic valve might cause an abrupt decrease in maternal cardiac output leading to maternal hypotension. Intravenous injection of epinephrine (15 Ilg) also induces uterine artery vasoconstriction (18). Once the function of the epidural catheter was confirmed, our standard anesthetic solution for laboring patients [bupivacaine (1/16%)/ fentanyl (1 Ilg/mL)/epinephrine (1:600,000)] was infused. We did not believe that epidural infusion of a dilute epinephrine-containing local anesthetic solution would increase maternal heart rate because it did not significantly increase maternal heart rate when intravenously infused in the gravid ewe model (19).
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Epidural injection of 0.5% bupivacaine was used initially to extend the rostral level of surgical anesthesia to allow gradual onset of venodilation with the epidural anesthetic-induced sympathectomy. Epinephrine was again omitted from the initial bolus injection. The surgical level of anesthesia was intensified with the local anesthetic mixture (2 % lidocaine with freshly added 1:400,000 epinephrine and 50 Ilg fentanyl) that we routinely inject in preparation for abdominal delivery. Again, we did not believe that epidural injection of epinephrinecontaining local anesthetic would acutely increase maternal HR. Maternal HR remained constant until 30 minutes after injection of the last local anesthetic. At that time, there was an abrupt increase in maternal HR to 115 beats/min as the patient was moved into the operating room. We believed that the patient's tachycardia was not due to systemic absorption of epinephrine in the epidural anesthetic, but instead caused by her anxiety. Maternal cardiac output did not decrease and the fetal heart rate tracing did not change. We decided not to inject beta-adrenergic blocking drugs. Maternal tachycardia could have been attenuated by the intravenous infusion of esmolol. However, esmolol has been associated with a decrease in fetal heart rate (20). Perhaps the onset of fetal side effects could have been delayed by slowly decreasing the rate of esmolol infusion until onset of fetal bradycardia precluded its use. The patient tolerated the abdominal delivery without complication. Intravenous phenylephrine was chosen as the vasopressor to be injected for maternal hypotension or change in fetal heart rate tracing. Dilute intravenous doses of phenylephrine have been used instead of ephedrine as a pressor drug in obstetric anesthesia with maternal efficacy and without fetal compromise in routine pregnancies (21). If a patient with either preeclampsia or mitral valve stenosis presented for abdominal delivery, it could be argued that a pulmonary artery thermodilution catheter would have been unnecessary in the management of her anesthesia. Central venous or pulmonary artery catheterization could be initiated if indicated by cardiac decompensation, which would most probably occur in the postpartum period. However, we believed that the initial obstetric plan to induce labor in anticipation of vaginal delivery (especially in a patient with an unfavorable cervix) extended the period during which the patient would be exposed to physiologic stress. Pulmonary artery thermodilution catheter-generated hemodynamic profiles have proved useful in the management of the severely preeclamptic parturient with oliguria unresponsive to aggressive intra-
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vascular hydration or in those parturients who manifest pulmonary edema (22). Therefore, because of this patient's mitral valve stenosis, we thought it optimal to measure central pressures (thereby estimating right ventricular preload and right ventricular afterload) and cardiac output in response to intravascular hydration, alterations in (the awake and often anxious parturient's) HR, and response to drug therapy (such as vasopressor drugs, inotropic drugs, and magnesium sulfate). Intravenous dobutamine was infused as a right ventricular inotrope in an attempt to optimize cardiac output during labor. Dobutamine was chosen because it is associated with less chronotropy than dopamine. We believed that the relatively short duration of action of dobutamine (as compared to a phosphodiesterase inhibitor such as milrinone) might be more desirable if in fact maternal cardiac or fetal decompensation occurred. The trial of dobutamine was abandoned because the cardiac output did not significantly increase but the maternal HR did. However, the trial of dobutamine did demonstrate that the patient could withstand at least a short period of tachycardia (II 5-120 beats/min) without acute cardiac decompensation. Pulmonary vascular resistance is increased by relative hypoxemia, hypercarbia, acidosis, environmental cold and postoperative pain (IS); all to be avoided in the operating room as well as in the postpartum period. The patient manifested pulmonary edema on the first postoperative day, and we believe that this was cardiogenic in etiology. In fact, this episode of pulmonary edema was easily treated with furosemide and supplemental oxygen. With apparent resolution of her preeclampsia, the magnesium sulfate infusion was stopped. One day later, she manifested oliguria. Her central venous pressures were elevated, her systemic vascular resistance was high, and her cardiac output was relatively low as compared to earlier measurements. We did not believe she was hypovolemic. Intravenous magnesium sulfate therapy was restarted in a trial attempt to decrease vasospasm as well as to provide seizure prophylaxis. At the same time, the patient was digitalized to provide inotropic support. The patient's further immediate postpartum course was uneventful. Her renal function returned to normal. Her left ventricular function was echocardiographically estimated to be normal. She was discharged on an angiotensin-converting enzyme inhibitor. The patient presented 4 weeks postpartum with a dilated cardiomyopathy and pulmonary thromboembolism (PTE). Pulmonary thromboem-
bolism is reported in 0.05% of all pregnancies (23). The diagnosis of PTE at 4 weeks postpartum was not entirely unexpected because pregnancy increases the risk of PTE five- to sixfold (24). In addition, abdominal delivery increases the risk of PTE as compared to vaginal delivery (25). Pulmonary thromboembolism is associated with mitral stenosis, especially in patients with atrial fibrillation (l). Pulmonary thromboembolism occurs in approximately 50% of women with peripartum cardiomyopathy (I). In retrospect, it might have been prudent to have anticoagulated the patient before discharge from the labor and delivery suite. In summary, we report on a gravida with moderate-to-severe mitral valve stenosis whose pregnancy was complicated by pulmonary edema, severe preeclampsia, peripartum heart failure, and pulmonary thromboemoblism. She withstood a trial of labor followed by abdominal delivery during epidural analgesia and anesthesia. Her obstetric outcome was satisfactory and guided by the use of invasive hemodynamic monitoring. At 4 weeks postpartum she presented with a dilated cardiomyopathy and pulmonary thromboembolism. She survives and continues to do well.
References 1. Clark SL. Structural cardiac disease in pregnancy. In:
2.
3.
4.
5.
6.
7.
Clark SL, Cotton DB, Hankins GDV, Phelan JR, eds. Critical care obstetrics, 2nd ed. Boston, Blackwell, 1991: 115-124. Clark SL, Phelan JR, Greenspoon J, Aldahl D, Horenstein J. Labor and delivery in the presence of mitral stcnsosi: Central hemodynamic observations. Am J Obstet Gynecol 1985: 152: 948-958. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensinogen II pressor response throughout primigravid pregnancy. J Clin Invest 1973: 51: 2682-2689. Chesley LC, Lindhcimer MD. Renal hemodynamics and intravascular volume in normal and hypertensive pregnancy. In: Rubin PC, ed. Handbook of hypertension in pregnancy. In: Rubin PC, ed. Handbook of hypertension in pregnancy. Vol. 10. Amsterdam, Elsevier, 1988: 38-65. Kaar K, Joupilla P, Kuikka J, Luotola H, Toivanen J, Rekonen A. Intervillous blood flow in normal and complicated late pregnancy by means of a 133Xe method. Acta Obstet Gynecol Scand 1980: 59: 7-10. Groenendijk R, Trimbos JB, Wallenburg HC. Hemodynamic measurements in preeclampsia: Preliminary observations. Am J Obstet Gynecol 1984: 150: 232-236. Desai DK, Moodley J, Naidoo DP, Bhorat I. Cardiac abnormalities in pulmonary oedema associated
Severe Preeclampsia Complicating Mitral Valve Stenosis •
8.
9.
10.
11.
12.
13.
14.
15.
with hypertensive crises in pregnancy. Br J Obstet Gynaecol 1996: 103: 523-528. Mabie We, Hackman BB, Sibai BM. Pulmonary edema associated with pregnancy: Echqcardiographic insights and implications for treatment, Obstet Gynecol 1993: 81: 227-234. American College of Obstetricians and Gynecologists. Management of preeclampsia. ACOG Technical Bulletin, No. 219, 1996. Ueland K. Hansen JM. Maternal cardiovascular hemodynamics Ill. Labor and delivery under local and caudal anesthesia. Am J Obstet Gynecol 1969: 103: 8-18. James CF, Banner T, Caton D. Cardiac output in women undergoing cesarean section with epidural or general anesthesia. Am J Obstet Gynecol 1989: 160: 1178-1184. Ueland K, Hansen J, Eng M, Kalappa R, Parer JT. Maternal cardiovascular dynamics vs. cesarean section under thiopental, nitrous oxide and succinylcholine anesthesia. Am J Obstet Gynecol 1970: 108: 615-622. Gutsche B. The expert's opinion: Is epidural block for labor and delivery and for cesarean section a safe form of analgesia in severe preeclampsia or eclampsia? Surv Anesth 1986: 30: 304-311. Joupilla P, Joupilla R, Hollman A, Koivula A. Lumbar epidural analgesia to improve intervillous blood flow during labor in severe preeclampsia. Obstet Gynecol 1982: 59: 158-161. Thornhill ML, Camann WR. Cardiovascular disease. In: Chestnut DH, ed., Obstetric anesthesia: Principles and practice, St Louis, Mosby, 1994: 759-760.
Afrangui and Malinow
209
16. Boxer LM, Malinow AM. Preeclampsia and eclampsia. Curr Opin Anaesthesiol 1997: 10: 188-198. 17. Writer D. Hypertensive disorders. In: Chestnut DH, ed. Obstetric anesthesia: Principles and practice. S1. Louis, Mosby, 1994: 872. 18. Chestnut DR, Weiner CP, Martin JG, Herring JE, Wang JP. Effect of intravenous epinephrine on uterine artery blood flow velocity in the pregnant guinea pig. Anesthesiology 1986: 66: 688-691. 19. Norris MC, Grieco W, Arkoosh VA. Does continuous intravenous infusion of low-concentration epinephrine impair uterine blood flow in pregnant ewes? Reg Anesth 1995: 20: 206-211. 20. Eisenach Je, Castro Ml: Maternally administered esrno101 produces beta-adrenergic blockade and hypoxemia in sheep. Anesthesiology 1989: 71: 718-722. 21. Moran D, Perillo M, La Porta RF, Bader AM, Datta S. Phenylephrine in the prevention of spinal hypotension following spinal anesthesia for cesarean delivery. J Clin Anesth 1991: 3: 301-305. 22. Clark SL, Horenstein JM, Phelan JP, Montag TW, Paul RH. Experience with the pulmonary artery catheter in obstetrics and gynecology. Am J Obstet Gynecol1985: 152: 374-378. 23. Weiner CPo Diagnosis and management of thromboemoblism disease during pregnancy. Clin Obstet Gynecol 1985: 28: 107-118. 24. Bolan JC. Thromboemoblic complications of pregnancy. Clin Obstet Gynecol 1981: 26: 913-922. 25. Bergqvist A, Bergqvist D, Hallbrook T. Acute deep vein thrombosis after cesarean section. Acta Obstet Gynaecol Scand 1979: 58: 473-476.