Managing severe heart failure in a pregnant patient undergoing cardiopulmonary bypass: case report and review of the literature

Managing Severe Heart Failure in a Pregnant Patient Undergoing Cardiopulmonary Bypass: Case Report and Review of the Literature ¨ ztu¨rk, MD,† Ufuk Yetkin, MD,‡ Levent Yilik, MD,‡ Nagihan Karahan, MD,* Tu¨lin O Ali Baloglu, MD,§ and Ali Gu¨rbu¨z, MD,‡

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ECAUSE OF INCREASES in cardiac output and intravascular volume that occur in pregnancy, previously asymptomatic structural heart disease in women will often cause symptoms for the first time or present with worsening symptoms. In this report, the authors describe a woman at 28 weeks gestation, presenting with acute heart failure, who was noted to have severe mitral stenosis and underwent emergency mitral valve replacement. CASE PRESENTATION A 28-year-old pregnant patient (G4, P2, at 26 weeks gestation) was admitted to this hospital with a diagnosis of congestive heart failure (New York Heart Association functional class III).1 Echocardiography showed a very fibrotic mitral valve and extremely thick subvalvular tissues. The mitral orifice area was 1.2 cm2, and her pulmonary arterial pressure (PAP) was 93 mmHg. She was managed for 2 weeks with bed rest, digoxin, enalapril, isosorbide dinitrate, and furosemide. Despite optimal doses of medications, her clinical and hemodynamic condition did not normalize over the course of 2 weeks; she continued to be dyspneic with exertion and to have bouts of acute pulmonary edema, whereas her repeat PAP remained high at 89 mmHg. Obstetricians determined that fetal development was within normal limits. After the unsuccessful 2-week trial of medical therapy, urgent mitral valve replacement was considered. The patient was counseled about the perioperative and postoperative risks to herself and the fetus and consented to the procedure. On the day of surgery, premedication was not administered. In the operating room, with the patient in the left lateral decubitus position and sitting at a 45° angle, her oxygen saturation (SpO2), cardiac rhythm, and blood pressure (invasive) were monitored. The external fetal heart rate and uterine contractions were also followed (Maternal/ Fetal Monitor, model 118; Corometrics Inc, Wallingford, CT). The patient had rapid atrial fibrillation (heart rate: 122), an invasive mean arterial pressure (MAP) of 92 mmHg, and a respiratory rate of 21 with an SpO2 of 97% while on 5 L/min of oxygen by mask. The initial recording of the fetal heart rhythm was normal rate with good variability. A single dose of intravenous (IV) methylprednisolone (500 mg) was administered preoperatively. In the operating room, while waiting in the left lateral decubitus position at a 45° angle for anesthetic induction, the patient’s condition worsened, developing systemic hypotension, right ventricular failure, and acute pulmonary edema. Her atrial fibrillation rate was 156/min, MAP 58 mmHg, and tachypneia (35/min) with an SpO2 of 82%. Continuous positive airway pressure (CPAP) was unavailable, and mask ventilation was performed with 100% oxygen but was very difficult because of decreasing lung compliance. While nitroglycerin (NTG), dopamine, beta-blocker, and furosemide were given emergently to reduce pulmonary vascular resistance (PVR) and PAP while maintaining mean arterial pressure, anesthesia was induced with thiopental (5 mg/kg), fentanyl (5 ␮g/kg), and pancuronium (0.1 mg/kg). On intubation, the endotracheal tube flooded with edema fluid and the peak airway pressure was 45 mmHg. The patient was ventilated by pressurecontrolled ventilation (Penlon AV 900, Penlon, Abingdon, UK), with an FIO2 of 1.0. A pulmonary arterial catheter was placed. Her temperature was also monitored. About 20 minutes later, her SaO2 was 100% and MAP was 104 mmHg. Anesthesia was maintained with sevoflurane, dry air:O2 (50%:50%), fentanyl (5 ␮g/kg), and pancuronium. MAP was maintained at about 90 mmHg, with a mean pulmonary

arterial pressure of 64 mmHg. Fetal heart rate (FHR) remained within normal limits during and postinduction (149-156 beats/min). Pulsatile cardiopulmonary bypass (CPB) was initiated after cannulation of the aorta and vena cava, and the system was primed with lactated Ringer’s solution, which contained the following additives (per liter): 80 mmol of sodium bicarbonate, 150 mg of mannitol, and 50 mg (5,000 IU) of heparin. Mean flows were set to be greater than 2.5 L/min/m2. Moderate systemic hypothermia (32°C) was accomplished. After the aortic cross-clamp was applied, hyperkalemic, isothermic buffered blood cardioplegia was infused in an antegrade fashion at 10 mL/kg. As CPB was initiated, the FHR remained the same, but a decrease in FHR variability and increase in the tone of uterine contractions were observed. After surgical examination, her mitral valve was replaced with a 29-mm St. Jude mechanical valve. The patient’s MAP ranged between 68 and 89 mmHg and pulse pressure was maintained at approximately 40 mmHg during bypass. Immediately before releasing the aortic cross-clamp, the MAP suddenly decreased to 45 mmHg and the fetus became bradycardic then asystolic. Uterine contraction tone had increased to 60 mmHg. At this time, the maternal rectal temperature was 32°C and warming was initiated. The position of the cardiotocograph probe was checked and monitoring continued. Maternal hypotension was treated with 5 mg of ephedrine and by increasing the pump flow. The FHR spontaneously returned to a sinusoidal pattern of 50 beats/min after 9 minutes. On completion of the mitral valve replacement, maternal cardiac activity resumed spontaneously and the patient was weaned from CPB without inotropic support. The aortic cross-clamp time was 27 minutes, CPB time 37 minutes, and the operation was completed 55 minutes after bypass. On transfer to the intensive care unit (ICU), FHR was 50 to 58/min in a sinusoidal pattern, and uterine contractions continued to be elevated, although at lower levels than before (40-60 mmHg). After the patient was taken to the ICU, in addition to the NTG infusion (5-10 ␮g/kg/min), indomethacin (100 mg, rectally, every day) was started. The FHR returned to normal within 3 hours, whereas FHR variability did not return to normal until 16 hours after the operation. Uterine contractions returned to baseline 24 hours after the operation. Heparin was infused intravenously to maintain a partial thromboplastin time between 2.0 and 2.5 times the control value. The mother’s postoperative course was unremarkable while in the ICU and on the hospital ward. Before hospital discharge, the patient learned to give self-injections of subcutaneous heparin, 5,000 units every 8 hours. On follow-up, no maternal or fetal complications caused by heparin, such as thrombocytopenia, were observed. At 39 weeks of gestation, heparin was stopped 6 hours before planned delivery. The patient subsequently underwent elective Cesarean section under general anesthesia. She

From the Departments of *Cardiovascular Anaesthesiology, †Anaesthesiology, ‡Cardiovascular Surgery, and §Obstetrics and Gynecology, Atatu¨rk Training and Research Hospital, Izmir, Turkey. ¨ ztu¨rk, MD, Mustafa Kemal Sahil Address reprint requests to Tu¨lin O Bulvarı. No: 41/1, Narlıdere, Izmir 35320, Turkey. E-mail: ozturktulun@ yahoo.com © 2004 Elsevier Inc. All rights reserved. 1053-0770/04/1803-0017$30.00/0 doi:10.1053/j.jvca.2004.03.017 Key words: mitral stenosis, pregnancy, cardiopulmonary bypass, heart failure

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delivered a healthy female infant, with Apgar scores of 9 at 1 minute, and 9 at 5 minutes postdelivery. At delivery, hemostasis was deemed adequate, and heparin was again started by IV infusion for 24 hours. To breast-feed, the patient then continued with subcutaneous heparin (5,000 IU, 2-3 times daily) for 1 month. Warfarin was started 1 month after delivery. Mother and child were followed by cardiovascular surgeons and pediatricians as outpatients, and at last check-up the child at 9 months was developing normally. CASE DISCUSSION

Cardiac operations have been performed on pregnant women with varying degrees of success since the late 1950s. Previous limited reports showed the risk to the mother to be similar to that of nonpregnant female patients (3% overall), but fetal mortality remained high (20%).2,3 Because of the fetal risk, cardiac surgery has been advised only in extreme emergencies.3-5 The circumstances necessitating emergency surgery are significant predictive factors of maternal and fetal outcome. Weiss et al,6 in their summary of case reports and series, found that sudden decompensation, fetal immaturity, and the high hemodynamic load of late pregnancy result in a poor maternal and fetal outcome of cardiovascular procedures during pregnancy. Salazar et al4 also report high maternal and fetal mortality rates when a mother with severe acute heart failure because of a dysfunctional valve is urgently operated on and are related to the severity of the patient’s preoperative condition.4 The basic principles for the perioperative management of the gravid patient undergoing cardiac surgery and CPB are identical to those for gravidae requiring any type of surgery: attention to maternal safety, avoidance of teratogenic drugs, avoidance of intrauterine asphyxia, and prevention of preterm labor.7,8 Mild-to-moderate mitral stenosis in pregnancy can result in many complications including pulmonary venous congestion, pulmonary edema, atrial fibrillation, and venous thromboembolism.9 In the pregnant woman with mitral stenosis, the physiologic increases in heart rate and blood volume of pregnancy can cause even greater left atrial pressures, which results in atrial flutter or fibrillation. If atrial fibrillation occurs with a rapid ventricular response, pulmonary edema can occur suddenly and cause sudden deterioration, as happened in this patient.10-12 The chief concern in the anesthetic management of patients with mitral stenosis is to avoid tachycardia and prevent any increases in PAP. Conditions or substances that increase pulmonary vascular resistance (eg, hypercarbia, hypoxia, and nitrous oxide) are to be avoided to maintain cardiac output. Although inadequate sedation may lead to anxiety (and resultant tachycardia) in the preoperative period, oversedation because of extreme sensitivity to even small doses of narcotics, and sedative hypnotics has also been observed.7,12 Thus, sedative agents need to be individually titrated in light of their potential risks and benefits. Patients with a high risk of pulmonary edema usually have thermodilution pulmonary artery and radial artery catheters placed before induction. Through the pulmonary artery catheter readings, the effects of vasoactive and anesthetic agents on

overall ventricular function can be assessed, and the anesthesiologist can obtain an optimum balance of preload and afterload before induction.7,12,13 The plan for sedation and induction of anesthesia must take into account the pathophysiology of the underlying disease and volume status. The agents to be used must combine to maintain a stable adrenergic and hemodynamic state. Sympathetic stimulation during tracheal intubation induces tachycardia and hypertension that may be harmful to patients, especially those with severe cardiac disease. This hemodynamic reaction is often followed by a period of drug-induced hypotension.14 Awake fiberoptic endotracheal intubation under deep conscious sedation in patients with severe cardiac disorders avoids both tachycardia caused by sympathetic stimulation and pharmacologically induced hypotension.14,15 In this patient, conventional intubation had been planned because of the unavailability of fiberoptic equipment. Besides medications, treatment of severe pulmonary edema often requires oxygen at higher pressures than nonrebreather masks can deliver. Mechanical positive-pressure ventilation with positive end-expiratory pressure reduces venous return and improves alveolar ventilation and the ventilation-perfusion relationship.16 Noninvasive positive-pressure ventilation tecniques such as continuous positive airway pressure and bilevel positive pressure lead to early physiologic and clinical improvement in patients with acute cardiogenic pulmonary edema and is a valuable alternative in those failing treatment with a high-flow rebreather oxygen mask.17-19 These methods were not available; thus, this patient’s severe pulmonary edema was managed with medications and intubation with positive endexpiratory pressure. Although dopamine was used to maintain MAP, NTG was used to decrease PVR and mean PAP; it has also been shown to increase cardiac output in patients with elevated PVR secondary to mitral valve disease.20,21 Drugs used appropriately during anesthesia do not appear to cause congenital fetal abnormalities but carry an increased risk of miscarriage and growth retardation.22,23 Fentanyl and sufentanil may decrease FHR and beat-to-beat variability and thus simulate the bradycardia of fetal distress.24 Alpha-adrenergic agents (eg, dopamine, epinephrine) are not ideal agents for treating maternal hypotension because, although maternal blood pressure may increase, uterine blood flow may decrease.22,25 In contrast, Pomini et al26 stated that dopamine and epinephrine are safe agents to use for the prevention of intraoperative hypotension in pregnant patients. Phenylephrine and ephedrine have also been recommended as vasopressors for treating maternal hypotension.27 Rosen22 reported ephedrine to be the agent of choice in the initial pharmacologic management of maternal hypotension, with phenylephrine as second choice when ephedrine is ineffective or when the mother is tachycardic, has a stenotic valvular cardiac lesion, or is receiving ␤-agonist therapy. For the treatment of maternal hypertension, NTG and nitroprusside are recommended, but long-term nitroprusside infusions should be avoided because of the inability of the immature fetal hepatobilliary system to metabolize the cyanide metabolite.28 Heparin does not cross the placenta and thus heparin and protamine may be used for cardiac surgery as needed.29 Both mannitol and furosemide cross the placenta and

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may induce diuresis in the fetus. However, an experimental study showed that maternally administered furosemide did not augment fetal urine production.30 A routine recommendation for cardioplegic solutions in the gravid patient is not found in the literature7; thus, various solutions have been used.5,31,32 Similar to the recommendation of Gopal et al,32 a routine infusion of high-potassium blood cardioplegia was administered. Maternal diuresis was enough to maintain normokalemia during CPB. Neither hyperkalemia nor deleterious effects on the fetus were noted during the procedure. To preserve placental flow and avoid a hypotension-induced increase in vascular resistance in the placenta, high flow rates (⬎2.5 L/min/m2) and high perfusion pressures (MBP ⬎70 mmHg) have been recommended for CPB during pregnancy.31-34 In addition, maternal pulsatile flow may better preserve placental hemodynamic function.3,5,33,35 Experimental studies in fetal lambs showed nonpulsatile perfusion to result in a vasoconstrictive response of the fetal placental circulation.36 This response is believed to be mediated by prostaglandins and/or inhibition of tonic production of the endothelium-derived relaxation factor nitric oxide.36,37 In the same studies, pulsatile flow did not cause an increase in placental vascular resistance.36,37 CPB may have several deleterious effects on the uterus and fetus. Uterine contractions during CPB are presumably related to hypothermia and rewarming.2 Hypothermia during CPB decreases fetal oxygen requirements but provokes uterine contractions, thus reducing placental oxygen exchange.26,38 The rewarming period is a cause of fetal distress and premature labor. Pomini et al26 reported the CPB-related embryo fetal mortality to be higher with hypothermia than normothermia (24% v 0%, n ⫽ 40). Therefore, normothermic perfusion during CPB is recommended.2,3,36,37 CPB-associated dilution reduces hormone levels (progesterone in particular), which might increase uterine excitability. Uterine contractions reduce uterine blood flow, which results in diminished placental blood flow. External FHR and uterine monitoring are essential to notice fetal distress in its early stages.2,3,32 Routine tocolytic treatment is controversial,34,39,40 but some suggest aggressive treatment with commonly used tocolytics (eg, ␤-sympathomimetics, progesterone, magnesium sulfate, ritodrine, and ethanol) to delay delivery.3,38,41 To decrease this patient’s uterine tone, the tocolytic effect of NTG was used during the intraoperative period, indomethacin was added for the first 2 postoperative days. NTG is reported to be an effective tocolytic with minimal complications, and its use during obstetric procedures has been described.42 On the other hand, Duckitt et al43 found that NTG did not delay delivery or improve neonatal outcome when compared with placebo or alternative tocolytics such as ritodrine, albuterol, and magnesium sulphate. Fetal bradycardia (persistent or transient), with or without late decelerations, and sinusoidal patterns have been reported to occur just after initiation of CPB or emergence from CPB and return to normal within 2 to 3 hours in the postoperative period.26,28,33,44 Fetal distress with resultant bradycardia may occur because of reduced systemic vascular resistance, low

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uterine blood flow, and uterine artery spasm as a result of hemodilution and/or secreted vasoactive substrates in pregnancy; particulate and bubble embolism; or obstruction of venous drainage because of cannulation of the inferior vena cava during CPB.3,45 In addition, persistent fetal bradycardia may be caused by prolonged bypass, fetal acidosis, or highdose narcotic analgesics.3,44,46 Bradycardia with a sinusoidal pattern and subsequent loss of the fetal heart beat was noted for 9 minutes in this patient, with decreased FHR variability and increased uterine tone just before discontinuation of CPB. FHR changes gradually resolved over the following 3 hours. The authors believe this problem was because of maternal rewarming from hypothermia. During this period, sufficient heat may not have been transferred to the fetus because of vasoconstriction in the umbilical vessels as well as the peripheral vessels.33,47 Uterine tone and FHR tracings are commonly assessed by anesthesiologists, but if preoperative fetal distress is observed or if an emergency cesarean section during cardiac surgery is anticipated, having a perinatologist or an obstetrician present during cardiac surgery may be desirable.22,48 This institution has no perinatologist on its staff; thus, such intraoperative monitoring is done by either an obstetrician or anesthesiologist. Because pregnancy is a hypercoagulable state, an increased risk of thrombosis of the cardiac valve prosthesis with systemic embolism and death have been documented.49,50 For these reasons, long-term anticoagulation is mandatory to prevent thromboembolic phenomena in pregnant patients with mechanical valve prostheses. All treatment choices have risks, and the ideal medication and dosages for these patients are uncertain.51,52 Warfarin provides adequate protection against thromboembolism and should be used in patients with mechanical prosthetic valves. However, to prevent warfarin-induced embryopathy and intracranial bleeding, warfarin is replaced by heparin from before the 6th until the end of the 12th week of gestation and after the 35th week.31,51,52 Because heparin does not cross the placental barrier, it is an obvious choice to avoid the teratogenic effects of warfarin. But subcutaneous unfractionated heparin has been found to be inadequate prophylaxis against thromboembolism in women with mechanical valves.51,52 Low–molecular-weight heparin therapy has been noted to be both an excellent choice by some authors53 and inadequate for thromboembolism prophylaxis in women with mechanical heart valves by others.50,54,55 Successful CPB for cardiac surgery during pregnancy has been reported, but experience is still limited.40 In this pregnant patient undergoing mitral valve replacement, successful perioperative management included careful selection of anesthetic and supportive agents, prevention of pulmonary edema, intensive treatment of congestive heart failure just before and during induction, continuous cardiotocographic monitoring, high CPB perfusion pressures, pulsatile high flow during CPB, avoidance of deep hypothermia, and minimization of the aortic crossclamp and CPB duration. A sinusoidal fetal bradycardia lasting several hours was not avoided, however. Techniques still need to be further refined to avoid danger to the fetus in these situations.

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50. Oles D, Berryessa R, Campbell K, et al: Emergency redo mitral valve replacement in a 27-year-old pregnant female with a clotted prosthetic mitral valve, preoperative fetal demise and postoperative ventricular assist device: a case report. Perfusion 16:159-164, 2001 51. Vural KM, Ozatik MA, Uncu H, et al: Pregnancy after mechanical mitral valve replacement. J Heart Valve Dis 12:370-376, 2003 52. Salazar E, Izaguirre R: Heart disease, anticoagulants and pregnancy. Rev Esp Cardiol 54:8-16, 2001 53. Arnaout MS, Kazma H, Khalil A, et al: Is there a safe anticoagulation protocol for pregnant women with prosthetic valves? Clin Exp Obstet Gynecol 25:101-104, 1998 54. Leyh RG, Fischer S, Ruhparwar A, et al: Anticoagulation for prosthetic heart valves during pregnancy: Is low-molecular-weight heparin an alternative? Eur J Cardiothorac Surg 21:577-579, 2002 55. Mahesh B, Evans S, Bryan AJ: Failure of low-molecular-weight heparin in the prevention of prosthetic mitral valve thrombosis during pregnancy: Case report and a review of options for anticoagulation. J Heart Valve Dis 11:745-750, 2002