Anesthesia Considerations for the Critically Ill Parturient with Cardiac Disease 649 atheromatous changes, narrowing of the arterial bed, and in situ thrombosis. Diagnosis of pulmonary hypertension is confi rmed by various diagnostic modalities (Table 45.17 ). A word of caution is needed when relying on non - invasive measurements of pulmonary artery pressure in pregnancy. A recent study has revealed that echocardiography signifi cantly overestimates pulmonary artery pressures compared with cathe- terization in pregnant patients with suspected pulmonary hyper- tension. Thirty - two per cent of pregnant patients with normal pulmonary artery pressures may be misclassifi ed as having pul- monary artery hypertension when measured by echocardiogra- phy alone [41] . For this reason we suggest right heart catheterization in such women before making the diagnosis of pulmonary hypertension. Maternal mortality in the setting of severe pulmonary hyper- tension is over 50% [42,43] and primary pulmonary hyperten- sion is a contraindication to pregnancy. Most fatalities occur during labor and the early postpartum period. Management of these patients is challenging, and invasive hemodynamic moni- toring during labor and delivery is recommended [44] . Despite improvements in medical, obstetric, anesthetic, and intensive care, mortality rates have remained stable over the past decades. Pharmacologic t herapies Pharmacologic therapies include calcium channel blockers, angiotensin - converting enzyme (ACE) inhibitors, adenosine, cardiac glycosides, anticoagulants, diuretics, and supplemental oxygen, but no combination has resulted in increased surviv- ability or a long - term response. Diuretics are frequently used to treat excessive edema that compromises the patient ’ s current condition, and must be used with caution to avoid signifi cant abuse, and severe hemorrhage. The mortality rate is as high as 50% in the event of a myocardial infarction [38] . Delivery should be avoided for 2 weeks postinfarction if at all possible since the mortality rate is extremely high. Early diagnosis, consultation with a cardiologist, and aggressive therapy are the keys to reduc- ing morbidity and mortality. One study showed that patients with severe postpartum hemorrhage admitted to the ICU had elevated troponin levels and myocardial injury, and that tachycardia and hypotension were independent predictors of myocardial ischemia [39] . Spontaneous coronary dissection can occur in the immedi- ate postpartum period and usually involves the left anterior descending coronary artery. Interventions such as coronary stent- ing and angioplasty have been successful in pregnant patients. Tissue plasminogen activator has been administered for throm- bolysis; it has a short half - life of about 5 minutes and does not cross the placenta. Anesthetic m anagement Hemodynamic monitoring, oxygen supplementation, heart rate control with β - blockade, assisted vaginal delivery and effective pain control with epidural analgesia are all effective strategies to reduce the myocardial work and oxygen consumption. Epidural anesthesia has been used successfully for labor and delivery in these patients as it reduces the pain and consequent tachycardia. Successful pregnancy outcomes have been reported after myocar- dial infarction with close monitoring and multidisciplinary man- agement [40] . Pulmonary h ypertension Pathophysiology Pulmonary hypertension is a condition characterized by chronic elevation of mean pulmonary artery pressure > 25 mmHg at rest, or > 30 mmHg with exercise, and it is associated with a pulmonary capillary wedge pressure lower than 12 mmHg diagnosed by right heart catheterization (Table 45.16 ). The World Health Organization has also recently defi ned pulmonary hypertension to be present when a systolic pulmonary artery pressure is > 40 mmHg. This level of pulmonary hypertension can be esti- mated non - invasively by using the velocity of the tricuspid jet seen when assessing tricuspid regurgitation, and corresponds to a velocity of 3 – 3.5 m/s. Pulmonary hypertension is self - perpetu- ating, and causes structural changes in the pulmonary vascula- ture, including intimal proliferation, smooth muscle hypertrophy, Table 45.16 Criteria for pulmonary hypertension. 1. Chronic elevation of mean PAP > 25 mmHg at rest 2. Mean PAP > 30 mmHg with exercise 3. PCWP < 12 mmHg PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure. Table 45.17 Diagnosis of pulmonary hypertension. Diagnostic modalities Changes seen in pulmonary hypertension Electrocardiogram Right axis deviation, right ventricular hypertrophy, right ventricular strain or right atrial enlargement Chest X - ray May show enlargement of the central pulmonary arteries with peripheral tapering Transthoracic echocardiography May show evidence of tricuspid regurgitation, right ventricular and right atrial enlargement, paradoxic motion of the interventricular septum, and a reduction in left ventricular size Right heart catheterization Reveals elevated pulmonary artery pressures and normal pulmonary capillary wedge pressure Chapter 45 650 The degree of pulmonary hypertension and right ventricular failure must be assessed before proceeding with anesthesia. The reactivity of the pulmonary vasculature should also be examined to determine if pharmacologic pulmonary vasodilata- tion is feasible. Preoperatively, drugs likely to produce depression of ventilation should be avoided. Excessive doses of systemic analgesics can cause respiratory depression resulting in hypercar- bia and acidosis, which further exacerbates the pulmonary hypertension. ECG, pulse oximetry, and invasive arterial blood pressure monitoring is advocated at the time of delivery. Transesophageal echocardiography has been used intraoperatively during cesarean section. Continuous invasive monitoring for instrumental or sur- gical delivery allows frequent determinations of arterial blood gases and subsequent adjustments in inspired oxygen concentra- tions and minute ventilation. A right atrial catheter can give important information such as abrupt increases in right atrial pressure, which may signal right ventricular dysfunction and increased pulmonary vascular resistance. The optimum mode of delivery and anesthetic management remain unclear. Methods of delivery should be discussed with the delivery team and the patient because of the deleterious effects of anesthesia. The literature reports a mortality rate of 37% for vaginal delivery and almost 63% for cesarean section [45] , which should be reserved for accepted obstetric indications. The most serious anesthetic complication in women with pul- monary hypertension is right ventricular dysfunction. Monitoring the central venous pressure can warn of early dysfunction. If the central venous pressure gradually increases, hypercarbia, acidosis, hypoxia, and light anesthesia should be excluded as causal and if present should be immediately corrected. Inotropic therapy or pulmonary vasodilator therapy intraoperatively usually requires intraoperative consultation with a cardiologist. Intravenous opioids, inhalational analgesia, intrathecal mor- phine, and paracervical and pudendal nerve blocks are recom- mended for labor and vaginal delivery. Vaginal delivery using segmental epidural analgesia with local anesthetics (low - dose bupivacaine and fentanyl) [46] has been reported. Low - dose epi- dural analgesia alone does not have any signifi cant deleterious hemodynamic effect, and it considerably decreases the adverse hemodynamic consequences of labor. If a continuous epidural technique with local anesthetic agents is used, a very cautious and slow titration of local anesthetics is recommended with careful attention to venous capacitance and resistance. Continuous intravenous fl uid titration is necessary and only marked decreases in systemic vascular resistance should be corrected using careful ephedrine titration. Breen and Janzen [47] have described the successful use of epidural anesthesia as a safe alternative to general anesthesia for cesarean section in a patient with pulmonary hypertension, car- diomyopathy, and a patent foramen ovale. Duggan and Katz [45] described the successful use of a combined spinal/epidural tech- nique, using both intrathecal morphine and fentanyl, followed by epidural local anesthetic for the cesarean section, in a patient with reductions in preload and electrolyte abnormalities. Long - term oral therapy with calcium channel blockers has produced sus- tained improvement in approximately 25 – 30% of patients. In patients whose condition responds to calcium channel blockers, the 5 - year survival rate approximates 95% [9] . Vasodilators are the most important new development in the treatment of primary pulmonary hypertension. Continuous epo- prostenol (prostacyclin 12, PG12) infusion lowered pulmonary vascular resistance and improved right ventricular function in several series of primary pulmonary hypertension and secondary vascular pulmonary hypertension patients [44] . Short - term application of aerosolized PG12 or its analogue iloprost more effectively reduced pulmonary artery pressure as compared to intravenous PG12 and inhaled nitric oxide in patients. Oral or long - acting transdermally delivered prostacyclin analogues, endothelin receptor antagonists and converting enzyme inhibi- tors, thromboxane inhibitors and antagonists, or new angioten- sin - converting enzyme inhibitors with specifi c affi nity for the pulmonary vasculature might be expected to further improve the effi cacy of treatment and life expectancy in patients with pulmonary vascular disease. These therapies, however, remain experimental. Sildenafi l is a new class of medication being utilized in the treatment of acute and chronic pulmonary hypertension. It is at least as effective as inhaled nitric oxide in relaxing the pulmonary vasculature, and may have fewer side effects . Coadministration of sildenafi l with nitric oxide also leads to less rebound pulmonary hypertension. An atrial balloon septostomy is an optional postpartum inter- vention for cases that are resistant to treatment. Congenital or iatrogenic intra - atrial communication may postpone the occur- rence of right heart failure or acutely decompress the right heart at the expense, of course, of the right - to - left shunt blood fl ow. Surgical pulmonary thrombendarterectomy is indicated in patients with chronic thromboembolic disease involving the proximal pulmonary arteries. Excellent results have been reported after surgery, including moderate morbidity rates, survival of small for gestational age neonates, and excellent maternal survival rates [9] . Perioperative m anagement While the literature on the management of the non - pregnant patient with primary pulmonary hypertension is extensive, infor- mation on pregnant patients is very limited. In a recent study, the authors reviewed the charts of all preg- nant women with severe pulmonary hypertension who were fol- lowed up at their institution during the past 10 years, to assess the multidisciplinary treatment and outcome of these patients. They concluded that despite the most modern treatment efforts, the maternal mortality was 36% [44] . Pain, anxiety, stress, hypercarbia, hypoxia, and acidosis during labor and delivery further complicate the management of a patient with pulmonary hypertension by increasing pulmonary vascular resistance. These avoidable factors should be minimized. Anesthesia Considerations for the Critically Ill Parturient with Cardiac Disease 651 changes. Echocardiography confi rms the diagnosis by revealing new left ventricular systolic dysfunction. Endomyocardial biopsy demonstrates myocarditis in up to 76% of patients. Persistent cardiomegaly results in a poor prognosis [49] . Perioperative m anagement The treatment of peripartum cardiomyopathy, particularly in patients with severe systolic dysfunction, involves the use of diuretics, salt restriction, and afterload reduction with vasodila- tors. Hydralazine, nitrates or calcium channel blockers like amlo- dipine are some of the drugs that have been recommended for afterload reduction. ACE inhibitors are generally contraindicated in the antepar- tum period due to the risk of teratogenicity, neonatal anuric renal failure and neonatal death [50] . However, these drugs may be used under specifi c circumstances where maternal condition mandates them. This clearly involves a clear informed consent discussion. ACE inhibitors are used effectively postpartum even if the mother is breastfeeding. Newer therapy includes pooled polyclonal antibodies [45] which have been shown to improve overall survival in pregnant patients with dilated cardiomyopathy. Atrial arrhythmias can be treated with digoxin and other indi- cated anti - arrhythmia drugs as required. Drug choice in such patients is best made in consultation with a cardiologist. Anticoagulation with unfractionated or low molecular weight heparin should be considered in patients with very low ejection fraction due to the risk of thromboembolism. Oral anticoagulation with warfarin is useful in the postpartum period. The mode of delivery in patients with peripartum cardiomy- opathy is usually determined by obstetric indications and the maternal functional status. A multidisciplinary approach helps with delivery planning and in most cases vaginal delivery is appropriate in a well compensated and medically optimized mother [51] . The advantages of vaginal delivery are greater hemodynamic stability, decreased blood loss, minimal surgical stress and lower risk of postoperative infection. Epidural analge- sia with slow titration of low concentrations of local anesthetic has the advantages of decreasing preload and afterload, and helps in accommodating volume from uterine autotransfusion after delivery. It also provides excellent pain control and minimizes the primary pulmonary hypertension who failed to respond to nitric oxide. Some authors have described the use of general anesthesia for cesarean section with good maternal outcome. However, others have reported increased pulmonary arterial pressure during laryngoscopy and tracheal intubation, and that positive - pressure ventilation may reduce venous return and ultimately lead to cardiac failure. Low tidal volumes of 5 – 10 mL/kg are recom- mended. Intermittent positive pressure breathing is most often selected for the intraoperative management of ventilation in patients with cor pulmonale. Marked decreases in venous return caused by lung infl ation, aortocaval compression, or by conduc- tion anesthesia must be minimized. Excessive reductions in the P a CO 2 during controlled ventilation should be avoided because metabolic alkalosis causes hypokalemia; this is particularly important in patients on digitalis therapy. There are now an increasing number of case reports highlight- ing the use of regional anesthesia with good outcome. However, a single - shot spinal anesthesthetic is contraindicated in these patients. Therefore, epidural anesthesia with incremental doses is currently regarded as the best regional technique. Nonetheless, the dense and extended block needed to prevent pain during cesarean delivery may have signifi cant hemodynamic consequences. The postpartum period is critical in women with primary pul- monary hypertension because dramatic increases in pulmonary vascular resistance generally precede irreversible right ventricular failure and death. After placental extraction, oxytocin must be infused slowly, because direct intravenous boluses of large doses can be fatal in patients with an unstable hemodynamic status [48] . Symptomatic therapy during the postpartum period includes inhaled nitric oxide and epoprostenol infusion or inhaled ilo- prost. Many advocate long - term anticoagulation as part of the postpartum therapy. Postoperative management in an intensive care unit is critical and close observation in a high - dependency unit should continue for at least 1 week postpartum because of the high incidence of sudden death during this period. Peripartum c ardiomyopathy The primary criteria for peripartum cardiomyopathy are listed in Table 45.18 . Secondary criteria include multiparity, black race, older maternal age, multiple gestation, tocolytic therapy with β - agonists, and viral myocarditis. A notable feature is its tendency to recur in subsequent pregnancies. Signs and symptoms include dyspnea, extensive lower extremity edema, fatigue, nocturnal cough, paroxysmal nocturnal dyspnea, pulmonary edema, ele- vated jugular venous pressure, hepatomegaly and new regurgitant murmurs, all of which are indicative of congestive heart failure. Chest X - ray needs to be done to determine the presence of car- diomegaly. The ECG fi ndings usually include tachycardia, dys- rhythmias, left ventricular hypertrophy, and/or ST segment Table 45.18 Criteria for peripartum cardiomyopathy. Heart failure in the last month of pregnancy or within 5 months post partum Absence of identifi able cause Absence of prior heart disease Echocardiography shows left ventricle dysfunction with ejection fraction < 45% and/or fractional shortening < 30% and end - diastolic dimension > 2.7 cm/sq m body surface area Chapter 45 652 Electrical cardioversion is generally safe during pregnancy. Firm application of paddles, adequate sedation, and aspiration prophylaxis are all important considerations. Fetal ventricular arrhythmias have been reported after cardioversion. The energy needed for defi brillation is unchanged in pregnancy. In maternal paroxysmal supraventricular tachycardia, adenos- ine can be administered if vagal maneuvers are unsuccessful. Cardioselective β - blockers may also be useful. Esmolol is associ- ated with a higher incidence of fetal bradycardia and may cause fetal acidosis. It should be avoided unless clearly indicated. Amiodarone should also be avoided as a fi rst line of therapy and reserved for resistant cases. Ventricular arrhythmias can be treated with intravenous lidocaine, procainamide or cardiover- sion. In patients with long QT syndrome and torsades de pointes, β - blockade should be continued into the postpartum period. Pregnancy in patients with an implantable cardioversion defi - brillator (ICDs) has had favorable maternal and fetal outcomes. Pregnancy and the t ransplanted h eart Pathophysiology Pregnancy in heart transplant recipients is generally tolerated provided the transplanted heart was functioning well before the onset of the pregnancy [53] . A transplanted heart is denervated and the response to the hemodynamic demands of pregnancy is atypical because of the adaptive mechanisms. The increased cir- culating blood volume leads to an increased preload and an increased stroke volume response as defi ned by the Frank Starling relationship. There is also a delayed increase in cardiac output in response to increased demands because it is only mediated by the release of catecholamines from the adrenal medulla and not via the sympathetic nerves [54] . Anesthetic c onsiderations Spontaneous labor and vaginal delivery is well tolerated and cesarean section is reserved for obstetric indications. In a case series of pregnancies after heart transplantation, 16 out of 22 pregnancies resulted in live births, and 10 out of the 22 pregnan- cies delivered vaginally. Five patients had cesarean section for labor complications and one was for pre - eclampsia. Neuraxial anesthesia was used in fi ve cesarean deliveries and four vaginal deliveries without any adverse maternal or fetal outcomes [55] . Complications seen in these pregnancies include gestational hypertension, pre - eclampsia, renal insuffi ciency, and infections. Most infections are consequent to immunosuppressive therapy [56] . Episodes of acute rejection can occur. Fetal/neonatal mor- bidity is generally the result of spontaneous abortion, premature- birth and low birth weight, and intrauterine growth restriction. Cesarean sections are associated with a higher risk of infection in these patients due to use of immunosuppressive therapy [57] . Ventricular assist devices are usually used as a bridge to trans- plantation in patients with cardiogenic shock. They are designed to provide full hemodynamic support to patients with severe effect of sympathetic responses on the heart as a consequence of pain. Combined spinal/epidural anesthesia with very low dose infusion of bupivacaine (0.0625 – 0.04%) as a continuous epidural has also been used with success. Contraindications to regional anesthesia include the presence of an anticoagulated state. Cesarean delivery may be performed under general anesthesia or neuraxial anesthesia. The principles of anesthetic management in patients undergoing general anesthesia include maintenance of a low to normal heart rate and avoidance of large changes in blood pressure. An opioid - based technique for induction is helpful. This avoids the myocardial depression and vasodilata- tion caused by large doses of agents such as thiopental and propofol. There should be adequate preparation for neonatal resuscita- tion following high - dose narcotic induction in mothers undergo- ing general anesthesia. Use of sufentanil and low - dose thiopental for induction in a diabetic obese parturient with peripartum car- diomyopathy has been described [52] . In patients with severe cardiac dysfunction inotropic support can be provided along with general anesthesia. A recent review by the National Heart, Lung and Blood institute suggests that patients with EF < 35% benefi t from anticoagulation therapy [49] . Monitoring usually includes an arterial line and a pulmonary artery catheter. Transesophageal echocardiography is a very useful tool to assess ventricular function and wall motion when general anesthesia is used. Regional anesthesia for cesarean delivery has been performed with a combined spinal/epidural technique, but such a choice should be made on a case - by - case basis. Arrhythmias d uring p regnancy and m anagement Signifi cant supraventricular and ventricular arrhythmias are very uncommon in healthy parturients. The additional circulatory burden of pregnancy, and enhanced adrenergic receptor excit- ability mediated by progesterone and estrogen can promote mild arrhythmias (PACs and PVCs) but these are usually self - limited and not hemodynamically signifi cant. In clinically relevant arrhythmias the usual causes are structural cardiac defects or residual defects after repair, and most of these arrhythmias are supraventricular in origin. Management of arrhythmias includes the following. • Avoidance of stimuli including smoking, caffeine, and sub- stance abuse including amphetamines, ephedrine and cocaine. • Correction of electrolyte abnormalities if present. • Vagal maneuvers for paroxysmal supraventricular arrhythmias can be attempted. Echocardiography for structural cardiac defects and 24 - hour monitoring should be considered. Drug therapy should be avoided in the fi rst trimester unless arrhythmias result in severe symptoms or in patients with severe ventricular hypertrophy or dysfunction. Anesthesia Considerations for the Critically Ill Parturient with Cardiac Disease 653 Cardiopulmonary b ypass in p regnancy This has been dealt with in Chapter 14 and will not be covered here except to say that the pros and cons of intraoperative fetal monitoring must be assessed on a case - by - case basis [72] . Fetal bradycardia, sinusoidal patterns, and late decelerations may occur during CPB soon after initiation or emergence from CPB [73] . The reasons include reduced systemic vascular resistance, low uteroplacental blood fl ow, hemodilution, particulate or air embolism, obstruction of venous drainage during inferior vena caval cannulation, prolonged bypass, or maternal administration of high - dose narcotics. Fetal protection strategies in such condi- tions include hyperoxygenation, maintenance of the hematocrit above 28%, high CPB perfusion pressures, high pump fl ow, nor- mothermic CPB, minimization of aortic cross - clamp, and CPB duration, and tocolytic therapy. Pulsatile perfusion seems to offer theoretical benefi t but still controversial [74] . References 1 Bitsch M , Johansen C , Wennevold A , Osler M . Maternal heart disease. A survey of a decade in a Danish university hospital . Acta Obstet Gynecol Scand 1989 ; 68 ( 2 ): 119 – 124 . 2 Shime J , Mocarski EJ , Hastings D , Webb GD , McLaughlin PR . Congenital heart disease in pregnancy: short - and long - term implica- tions . Am J Obstet Gynecol 1987 ; 156 ( 2 ): 313 – 322 . 3 Siu SC , Sermer M , Harrison DA , Grigoriadis E , Liu G , Sorensen S , et al. Risk and predictors for pregnancy - related complications in women with heart disease . Circulation 1997 ; 96 ( 9 ): 2789 – 2794 . 4 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 47. Prophylactic antibiotics in labor and deliv- ery . Obstet Gynecol 2003 ; 102 ( 4 ): 875 – 882 . 5 Malhotra S , Yentis SM . Reports on Confi dential Enquiries into Maternal Deaths: management strategies based on trends in maternal cardiac deaths over 30 years . Int J Obstet Anesth 2006 ; 15 ( 3 ): 223 – 226 . 6 Elkayam U , Ostrzega E , Shotan A , Mehra A . Cardiovascular problems in pregnant women with the Marfan syndrome . Ann Intern Med 1995 ; 123 ( 2 ): 117 – 122 . 7 Wong CA , Scavone BM , Peaceman AM , McCarthy RJ , Sullivan JT , Diaz NT , et al. The risk of cesarean delivery with neuraxial analgesia given early versus late in labor . N Engl J Med 2005 ; 352 ( 7 ): 655 – 665 . 8 Saberski LR , Kondamuri S , Osinubi OY . Identifi cation of the epidural space: is loss of resistance to air a safe technique? A review of the complications related to the use of air . Reg Anesth 1997 ; 22 ( 1 ): 3 – 15 . 9 Weiss BM , Zemp L , Seifert B , Hess OM . Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996 . J Am Coll Cardiol 1998 ; 31 ( 7 ): 1650 – 1657 . 10 Martin JT , Tautz TJ , Antognini JF . Safety of regional anesthesia in Eisenmenger ’ s syndrome . Reg Anesth Pain Med 2002 ; 27 ( 5 ): 509 – 513 . 11 Reimold SC , Rutherford JD . Clinical practice. Valvular heart disease in pregnancy . N Engl J Med 2003 ; 349 ( 1 ): 52 – 59 . heart decompensation but their limitations include operative risks, infections and other device - related morbidity such as thromboembolism [58,59] . Even though the ventricular assist devices are used mostly as a bridge to heart transplantation, several successful cases of their use for bridge to recovery have been reported [60] . Cardiac transplantation should be considered in patients with severe end - stage failure, especially in women with postpartum cadiomyopathy. The survival rates are similar to those with idio- pathic dilated cardiomyopathy. However patients with postpar- tum cardiomyopathy have higher rates of early rejection and infection. Intra - aortic balloon pumps have also been used during cardio- pulmonary bypass (CPB) in pregnancy (see Chapter 14 ). The authors claimed that the balloon pump provided an effective pulsatile fl ow pattern throughout CPB, and they postulated that the balloon pump may benefi t maternal circulation and second- arily help fetal hemodynamics [61] . Cardiopulmonary r esuscitation in p regnancy Cardiopulmonary resuscitation has been dealt with in detail in Chapter 7 and will not be dealt with further here .There are a number of excellent reference articles for those interested in this subject [62 – 67] . Cardiovascular s urgery d uring p regnancy Cardiac surgery during pregnancy, particularly with cardiopul- monary bypass, is associated with very high fetal and maternal mortality [68,69] . Medical therapy remains the treatment of choice. Interventional cardiology procedures and cardiac surgery should be reserved as an option only for the extremely critically ill parturients who are not candidates for medical or palliative therapy. Recent studies have suggested maternal mortality as high as 8 – 10%, especially in pregnant patients with NYHA class III or IV disease undergoing emergency cardiac surgery [70] . Hospitalization in late pregnancy, and surgery performed immediately postpartum, signifi cantly worsened the outcome. Cardiovascular surgery is better tolerated in early pregnancy [71] . A prolonged interval between surgery and pregnancy, and deliv- ery before reaching term seem to improve maternal outcome. A systematic review of the outcome of cardiovascular surgery and pregnancy in the period 1984 – 1996 showed maternal morbidity and mortality of 24% and 6% respectively. Fetal/neonatal risks of maternal surgery during pregnancy can be high and unpredict- able. Fetal morbidity is around 9% and fetal mortality is as high as 30%. Hospitalization after 27 weeks of pregnancy and emer- gency surgery contributed to poor maternal outcome. In contrast fetal outcome was better when the gestational age was higher. The duration of the surgery and CPB, and the temperature of CPB blood did not affect outcomes [28] . Chapter 45 654 31 Xia VW , Messerlian AK , Mackley J , Calmes SH , Matevosian R . Successful epidural anesthesia for cesarean section in a parturient with severe aortic stenosis and a recent history of pulmonary edema – a case report . J Clin Anesth 2006 ; 18 ( 2 ): 142 – 144 . 32 Batson MA , Longmire S , Csontos E . 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Am J Obstet Gynecol 2001 ; 184 ( 7 ): 1568 – 1570 . 42 Abboud TK , Raya J , Noueihed R , Daniel J . Intrathecal morphine for relief of labor pain in a parturient with severe pulmonary hyperten- sion . Anesthesiology 1983 ; 59 ( 5 ): 477 – 479 . 43 Easterling TR , Ralph DD , Schmucker BC . Pulmonary hypertension in pregnancy: treatment with pulmonary vasodilators . Obstet Gynecol 1999 ; 93 ( 4 ): 494 – 498 . 44 Bonnin M , Mercier FJ , Sitbon O , Roger - Christoph S , Jais X , Humbert M , et al. Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases . Anesthesiology 2005 ; 102 ( 6 ): 1133 – 1137 . 45 Duggan AB , Katz SG . Combined spinal and epidural anaesthesia for caesarean section in a parturient with severe primary pulmonary hypertension . Anaesth Intens Care 2003 ; 31 ( 5 ): 565 – 569 . 46 Slomka F , Salmeron S , Zetlaoui P , Cohen H , Simonneau G , Samii K . 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Beta - adrenergic receptor blockade in the management of preg- nant women with mitral stenosis . Am J Obstet Gynecol 1990 ; 163 ( 1 Pt 1 ): 37 – 40 . 26 Clark SL , Phelan JP , Greenspoon J , Aldahl D , Horenstein J . Labor and delivery in the presence of mitral stenosis: central hemodynamic observations . Am J Obstet Gynecol 1985 ; 152 ( 8 ): 984 – 988 . 27 Naidoo DP , Moodley J . Management of the critically ill cardiac patient . Best Pract Res Clin Obstet Gynaecol 2001 ; 15 ( 4 ): 523 – 544 . 28 Weiss BM , von Segesser LK , Alon E , Seifert B , Turina MI . Outcome of cardiovascular surgery and pregnancy: a systematic review of the period 1984 – 1996 . Am J Obstet Gynecol 1998 ; 179 ( 6 Pt 1 ): 1643 – 1653 . 29 Goertz AW , Lindner KH , Schutz W , Schirmer U , Beyer M , Georgieff M . I n fl uence of phenylephrine bolus administration on left ventricu- lar fi lling dynamics in patients with coronary artery disease and patients with valvular aortic stenosis . Anesthesiology 1994 ; 81 ( 1 ): 49 – 58 . 30 Patharkar M , Cohen S , Wang M , Solina A . Epidural anesthesia for cesarean section in a parturient with subaortic stenosis . Int J Obstet Anesth 2007 ; 16 ( 3 ): 294 . Anesthesia Considerations for the Critically Ill Parturient with Cardiac Disease 655 62 Syverson CJ , Chavkin W , Atrash HK , Rochat RW , Sharp ES , King GE . Pregnancy - related mortality in New York City, 1980 to 1984: causes of death and associated risk factors . Am J Obstet Gynecol 1991 ; 164 ( 2 ): 603 – 608 . 63 Rees GA , Willis BA . Resuscitation in late pregnancy . Anaesthesia 1988 ; 43 ( 5 ): 347 – 349 . 64 Lindsay SL , Hanson GC . Cardiac arrest in near - term pregnancy . Anaesthesia 1987 ; 42 ( 10 ): 1074 – 1077 . 65 Sanders AB , Kern KB , Ewy GA . Time limitations for open - chest car- diopulmonary resuscitation from cardiac arrest . Crit Care Med 1985 ; 13 ( 11 ): 897 – 898 . 66 Greiss FC Jr . Uterine vascular response to hemorrhage during preg- nancy, with observations on therapy . Obstet Gynecol 1966 ; 27 ( 4 ): 549 – 554 . 67 European Resuscitation Council . Part 8: advanced challenges in resuscitation. Section 3: special challenges in ECC. 3F: cardiac arrest associated with pregnancy . Resuscitation 2000 ; 46 ( 1 – 3 ): 293 – 295 . 68 Kole SD , Jain SM , Walia A , Sharma M . Cardiopulmonary bypass in pregnancy . Ann Thorac Surg 1997 ; 63 ( 3 ): 915 – 916 . 69 Parry AJ , Westaby S . Cardiopulmonary bypass during pregnancy . Ann Thorac Surg 1996 ; 61 ( 6 ): 1865 – 1869 . 70 Arnoni RT , Arnoni AS , Bonini RC , de Almeida AF , Neto CA , Dinkhuysen JJ , et al. Risk factors associated with cardiac surgery during pregnancy . Ann Thorac Surg 2003 ; 76 ( 5 ): 1605 – 1608 . 71 Pomini F , Mercogliano D , Cavalletti C , Caruso A , Pomini P . Cardiopulmonary bypass in pregnancy . Ann Thorac Surg 1996 ; 61 ( 1 ): 259 – 268 . 72 Lamb MP , Ross K , Johnstone AM , Manners JM . 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J Extra Corpor Technol 2005 ; 37 ( 2 ): 189 – 191 . 656 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 46 The Organ Transplant Patient in the Obstetric Critical Care Setting Calla Holmgren & James Scott Department of Obstetrics and Gynecology, University of Utah Medical Center, Salt Lake City, UT, USA Background Successful pregnancies have been reported in women with virtu- ally all types of organ and tissue allografts now used clinically. However, all transplant patients have signifi cant underlying medical disorders that can adversely affect the outcome. Problems may occur unpredictably, and each group of organ recipients has its own array of specifi c issues. Pregnancy in transplant patients also represents a natural experiment in immunologic aspects of gestation. The implanted conceptus is itself a graft of living tissue, and it is still not clear how the developing semiallogeneic placenta and fetus survive the normal immunocompetent maternal envi- ronment. Pregnancy in allograft recipients takes place in a relative state of generalized immune defi ciency because of the immuno- suppressive agents these women must take. This combination of factors presents unique management challenges to the physician. Organ and tissue transplantation have evolved from a clinical experiment into a contemporary treatment which restores many patients to near - normal life styles. The fi rst reported post - trans- plant pregnancy was in a woman who had received a kidney from her identical twin sister in 1958 [1] . Since then, the number of young women with allografts has dramatically increased and thousands have become pregnant (Table 46.1 ). There are no ran- domized trials that have investigated pregnancy management options for transplant patients, but a great deal has been learned through experience. The largest experience is with patients receiv- ing living donor or cadaver kidney transplants, but many recipi- ents of liver, heart, lung and pancreas allografts and bone marrow transplants have also become pregnant. Potential problems in these women include adverse effects of immunosuppressive drugs, medical and obstetric complications, and the psychologi- cal stress of being both transplant recipient and an expectant mother. Although the prognosis for a live birth is usually good, it is clear that these are high - risk pregnancies that require expert obstetric care. Prepregnancy e valuation Preconception counseling is desirable for all transplant patients, but it is often diffi cult to decide how to advise these couples [2 – 4] . Any woman contemplating pregnancy after transplantation should be in good health with no evidence of graft rejection (Table 46.2 ). Medical problems, such as diabetes mellitus, recur- rent infections, and serious side effects from the immunosuppres- sive drugs make pregnancy inadvisable. Most transplantation centers advise that it is safe to attempt pregnancy after the second post - transplantation year. This is with the condition that the graft is performing well [5] . An assessment of the patient ’ s family support as well as a tactful but honest discussion of the potential pregnancy problems is important. Those who have followed many of these patients are aware that the literature can be overly optimistic about pregnancy and long - term prognosis. It needs to be appreciated that the long - term organ allograft survival rates are not 100%, and many transplant recipients will not live to raise their children to adulthood [6] . Prenatal c are Much of the information regarding pregnancy and transplanta- tion is from experience with renal transplant patients. However, antepartum care is similar with essentially all other organ allografts. Early diagnosis of pregnancy is important, and a fi rst - trimester ultrasound examination is valuable to establish an accu- rate date of delivery. Antenatal management should be meticulous and includes serial assessment of maternal allograft function, detection of graft rejection episodes, and prompt diagnosis and treatment of infections, anemia, hypertension, and pre - eclampsia. Close fetal surveillance is also necessary, and the The Organ Transplant Patient in the Obstetric Critical Care Setting 657 pressed women has also caused congenital CMV in the infant [8] . HBV and HCV are usually acquired through dialysis and blood transfusions prior to transplantation. Hepatitis B immune globu- lin (HBIG) and HBV vaccine should be given to the newborn and are 90% effective in preventing chronic hepatitis. Acyclovir as prophylaxis or treatment of HSV can be used safely during pregnancy. The management of antepartum obstetric complications is similar to that for non - transplant patients. However, the risk of infection warrants a more aggressive approach and avoidance of invasive procedures when possible. Immunosuppression d uring p regnancy This is a class of drugs that not all obstetricians are familiar with, but it is crucial that they become aware of the impact on preg- nancy and potential side effects when caring for these women. Most maintenance immunosuppressive regimens in transplant patients include combinations of daily corticosteroids, azathio- prine, cyclosporine, tacrolimus (FK 506) and mycophenolate mofetil. Multiple drug regimens are common, and both the dose and timing of drug administration require close monitoring during pregnancy. The potential fetal risks for each drug catego- rized by the US Food and Drug Administration are shown in Table 46.3 . Corticosteroids have been used by physicians for immunosup- pression in renal transplant patients since the 1950s [9] . Prednisone is the corticosteroid used in most transplant patients, and intravenous glucocorticoids are used to treat acute rejection reactions. These anti - infl ammatory medications inhibit both humoral and cell - mediated immune responses. Maternal adverse effects include glucose intolerance, hirsutism, acne, weight gain, cushingoid appearance, striae formation, osteonecrosis, osteopo- rosis, fl uid retention, hypertension, severe infections, impaired wound healing, and mood changes. Since prednisone is largely metabolized by placental 11 - hydroxygenase to the relatively inac- tive 11 - keto form, the fetus is exposed to only 10% of the mater- nal dose of the active drug. [10] Most patients are maintained on moderate doses of prednisone (10 – 30 mg/day) that are relatively safe with few fetal effects. However, it is uncertain whether the increased incidence of premature rupture of membranes, preterm birth, pre - eclampsia and fetal growth restriction are due exclu- sively to the underlying condition or whether prednisone might contribute to these complications [11,12] . There is also evidence that prolonged exposure to other glucocorticoids, such as beta- methasone used to accelerate fetal lung maturation, may lead to decreased fetal and neonatal somatic brain growth, adrenal sup- pression, neonatal sepsis, chronic lung disease, psychomotor delay and behavioral problems [12 – 17] . Two doses of 12 mg 24 h apart have been shown to improve fetal outcomes without expo- sure of the fetus to the complications listed above [12,13] . Azathioprine and its more toxic metabolite 6 - mercaptopurine is a purine analogue whose principal action is to decrease delayed known risk for fetal growth restriction is monitored by serial ultrasound examinations. Dysplastic cervical lesions can occur in up to 9% of renal transplant recipients and the risk of cervical carcinoma has been estimated to be 3 – 16 times higher for renal transplant recipients than for the general population [7] . This is related to the increased risk for human papillomavirus in the immunosuppressed popu- lation. At present, it is recommended that all women greater than age 18 and girls less than 18 who are sexually active undergo pelvic examinations, with pap smears, annually. The effect of HPV vaccination on this rate has yet to be assessed but there may be a reduction in women previously vaccinated. Urinary tract infections are particularly common in kidney transplant patients, with up to a twofold increase in the incidence of pyelonephritis. Asymptomatic bacteriuria should be treated for 2 weeks with follow - up urine cultures, and suppressive doses of antibiotics may be needed for the rest of the pregnancy. Other bacterial and fungal infections may be associated with immunosuppression including endometritis, wound infections, skin abscesses, and pneumonia often with unusual organisms such as Aspergillus , Pneumocystis , Mycobacterium tuberculosis , and Listeria . Some patients have become Rh - sensitized from the allograft, and commonly acquired viral infections such as cytomegalovirus (CMV), herpes genitalis (HSV), human papillovirus (HPV), human immunodefi ciency virus (HIV) and hepatitis B (HBV) and C (HCV) pose a risk for both the mother and her fetus. The transplanted graft is a source of CMV, and patients typically receive prophylaxis against CMV for 1 – 3 months postoperatively when the risk for infection is highest. The greatest risk of con- genital infection in the fetus is with primary CMV infection during pregnancy, but recurrent CMV infection in immunosup- Table 46.1 Pregnancies in female transplant recipients reported to the National Transplantation Pregnancy Registry ( NTPR ). 37 Kidney 1097 Liver 187 Heart 54 Pancreas - kidney 56 Lung 15 Heart - lung 3 Table 46.2 Important prognostic factors for optimum pregnancy outcome in transplant patients. Two years since transplant Good general health and prognosis Satisfactory graft function with no evidence of rejection No or minimal hypertension and proteinuria Family support Stable immunosuppressive regimen No or minimal hypertension and proteinuria Chapter 46 658 limus is 11 – 20%; the median time to onset is 68 days, but it is reversible in up to 50% of patients after 2 years [25,26] . Nephrotoxicity and hyperkalemia develop in at least one - third of patients, and neurotoxicities such as headache, tremor, change in motor function, mental status or sensory function have also been described. Cord blood concentrations are approximately 50% of maternal levels [27] , but there is no proven association with congenital malformations to date. Mycophenolate mofetil is another medication more recently utilized to prevent organ rejection, and approximately 79.6% of patients receiving renal transplantation in the United States are placed on this medication. In animal studies, fetal developmental abnormalities have been noted, but there are limited data regard- ing human teratogenicity. One case report demonstrated major congenital malformation while on mycophenolate mofetil during the organogenesis period of pregnancy. The anomalies were similar to those described in animal models [28] . In 2002, the US National Transplantion Pregnancy Registry reported a total of 14 pregnancies in 10 women with mycophenolate mofetil exposure during pregnancy. Of these, there were six spontaneous abor- tions. Of the eight live births, there were two newborns with congenital anomalies [29] . Given concerning animal studies and the lack of human data, the use of this medication in pregnancy should be approached with caution. In general, it is recom- mended that treatment with mycophenolate mofetil should be stopped 6 weeks prior to conception [28] . It is apparent that all immunosuppressive drugs cross the pla- cental barrier and diffuse into the fetus during the development of its own immune system. Yet, there is no convincing evidence that prednisone, azathioprine, cyclosporine or tacrolimus produce congenital abnormalities in the human fetus, and they remain the drugs of choice during pregnancy. Other than fetal growth restriction and preterm birth, the majority of offspring hypersensitivity and cellular cytotoxicity. The primary maternal hazards of azathioprine administration are an increased risk of infection and neoplasia. Maternal liver toxicity and bone marrow depression with anemia, leucopenia and thrombocytopenia have occurred but usually resolve with a decrease in dose. Between 64% and 90% of azathioprine crosses the placenta in human pregnancies, but the majority is the inactive form, thiouric acid [18] . Classifi cation of azathioprine as Category D is based largely on two early series that reported an incidence of congenital anomalies of 9% and 6.4% [19,20] . No specifi c pattern has emerged, and further experience has shown that azathoiprine is not associated with more congenital malformations than seen in the normal population. [21,22] . Other fetal effects that have occa- sionally occurred include fatal neonatal anemia, thrombocytope- nia, leucopenia, and acquired chromosome breaks. One approach suggested recently to minimize neonatal effects is to adjust doses to keep the maternal leukocyte count within normal limits for pregnancy [23] . Cyclosporine is a fungal metabolite whose major inhibitory effect is on T cell - mediated responses by preventing formation of interleukin - 2 (IL - 2). Cyclosporine has improved survival in transplant recipients and is a standard component of many immunosuppressant regimens. Bone marrow depression is infre- quent, but the drug has a propensity for nephrotoxicity and hypertension. Other side effects include hirsutism, tremor, gingi- val hyperplasia, viral infections, hepatotoxicity and an increased risk of neoplasia such as lymphomas. Cyclosporine levels drop during pregnancy, but graft function has remained stable in most patients despite decreases in trough levels [24] . Cyclosporine readily crosses the placenta, but there is no evidence of teratoge- nicity of cyclosporine in the human. Tacrolimus (FK 506) is a macrolide obtained from streptomy- ces. The incidence of post - transplant diabetes mellitus with tacro- Table 46.3 Classifi cation and fetal risks for immunosuppressive drugs used in transplantation. Medication Pregnancy category Associated fetal risks Corticosteroids B Premature rupture of membranes, preterm birth, fetal growth restriction, adrenal suppression, neonatal sepsis, chronic lung disease, psychomotor delay, behavioral problems Azathioprine (Imuran) D Fatal neonatal anemia, thrombocytopenia, leukopenia, acquired chromosome breaks Cyclosporine C Unknown Tacrolimus (Prograf) C Unknown Sirolimus, rapamycin C Unknown Mycophenolate mofetil (CellCept) D Possible problems with organogenesis; no structural malformations have been noted in offspring exposed to this drug Antithymocyte globulin (ATGAM, ATG, thymoglobulin) C Unknown Muromonab - CD3 (Othroclone OKT3) C Unknown Basilizimab (Simulect) B None Daclizumab (Zenapax) C Unknown A, controlled studies, no risk; B, no evidence of risk in humans; C, risks cannot be ruled out; D, positive evidence of risk; X, contraindicated. . Publishing Ltd. 46 The Organ Transplant Patient in the Obstetric Critical Care Setting Calla Holmgren & James Scott Department of Obstetrics and Gynecology, University of Utah Medical Center,. Postoperative management in an intensive care unit is critical and close observation in a high - dependency unit should continue for at least 1 week postpartum because of the high incidence of. anesthesia for cesarean section in a parturient with subaortic stenosis . Int J Obstet Anesth 2007 ; 16 ( 3 ): 294 . Anesthesia Considerations for the Critically Ill Parturient with Cardiac Disease 655