 
CARDIOPULMONARY BYPASS IN PREGNANT PATIENTS.Maria Helena L. Souza, CCP (BR)* & Decio O. Elias, MD*** Perfusionist / ** Pediatric Cardiac Surgeon(Posted on January 10, 2001)
|
|
ABSTRACT
INTRODUCTION Some specific situations such as pregnancy, can substantially modify the physiology of the female organism. Cardiac surgery with extracorporeal support in a pregnant patient constitutes a more complex endeavor, because it represents the sum of anesthetic, surgical and cardiopulmonary bypass effects on two organisms under biologically distinct situations, the maternal and the fetal organisms. It is not unusual for a cardiac team to be required to manage opposite or conflicting interests between both of those organisms. The coincidence of cardiovascular disease and pregnancy has decreased over the last two decades in developed areas such as North America and Europe. Less developed countries still present a higher incidence of heart diseases, specially rheumatic valvular disease, among pregnant women. An average international figure can be represented by an incidence of 1 to 4% of maternal cardiovascular disease during pregnancy [1,2]. Rush [3] and coworkers retrospectively reviewed the records of 697 women with heart disease who were delivered between 1972 and 1976 (0,83% of all deliveries) of a large obstetric hospital in South Africa. Rheumatic heart disease comprised 65% of total patients, while congenital heart diseases accounted for 14%. Twelve percent have had cardiac surgery in the past and 9% presented a miscellaneous of cardiac conditions. The maternal mortality rate in these women was 7,17/1000 deliveries, compared to 0,46/1000 in the non-cardiac patients. Cardiac disease was the most important cause of non-obstetric maternal death. Although the incidence of cardiac diseases in pregnant women varies in different countries, most specialists agree that heart disease is the leading cause of death during pregnancy and delivery [4]. The pregnant woman with cardiac disease even if well compensated, can be affected by heart failure in face of the increased cardiorespiratory requirements during pregnancy. Medical therapy is not always sufficient to drive a heart with a reduced functional reserve or acute complications, in a pregnant woman. Three to four decades ago, the regular advice to a woman with heart disease was to avoid pregnancy. With improved cardiac care, including cardiac surgery, it is not unusual for cardiac women to have a normal pregnancy to deliver a healthy baby. Still in our days, in many circumstances the heart disease is identified only during the pregnancy. Considerations as to interrupt or proceed with the pregnancy are far from settled and are, most commonly a matter of individual evaluation and decision. These and other particular aspects of the combination of heart disease and pregnancy and the medical management of a pregnant cardiac patient will not be discussed in this work. Generally speaking, if and when the clinical conditions of a pregnant woman with cardiac disease deteriorates despite maximal medical therapy, surgical correction is the only alternative to restore cardiovascular function, and create conditions for the pregnancy to evolve normally. Closed mitral valvotomy has been frequently used in the past to carry the mother through the pregnancy. Percutaneous balloon valvuloplasty may develop a role when adequate imaging can be obtained by echocardiography [1]. Cardiopulmonary bypass was first used during pregnancy in 1959 [4]. Ten years later a series of 24 cases was reported with an overall maternal mortality of 4.2% and a fetal mortality of 29.2% [5]. Most published material on cardiac surgery and pregnancy refers to isolated case reports, small series of procedures and an occasional review of surgical aspects and outcome. Very few reports deal specifically with cardiopulmonary bypass in the pregnant women. In this paper we review the published reports on cardiac surgery and cardiopulmonary bypass during pregnancy, from 1966 to the current year. Our objective was to identify:
1. The influence of cardiopulmonary bypass factors on the maternal organism; MATERIAL AND METHODS The publications describing a cardiovascular surgical or a cardiopulmonary bypass procedure during pregnancy were identified in the database of the National Library of Medicine (MEDLINE) during the interval from 1966 to December 2000. Key words used for the search were cardiac surgery and pregnancy, cardiopulmonary bypass and pregnancy, and cardiac surgery, cardiopulmonary bypass and pregnancy. We collected a total of 246 publications, which were initially reviewed. Most papers deals with case reports, surgical and anesthetic considerations and the evaluation of small series. Sixty publications were reviewed in detail and 40 of them form the basis for the present study. Recent books and reviews (5) were also consulted for additional information and references. HISTORICAL SERIES The first series of cardiac surgery during pregnancy was reported in 1969 by Zitnik [5] and collaborators. In their 20 cases, the maternal mortality was 5% and the fetal mortality was 33%. Becker [6] in 1983 reported the results of a survey performed by the Society of Thoracic Surgeons (STS). From a total of 101 cases, 68 consisted of open cardiac repair, mostly mitral comissurotomy or replacement. Maternal mortality had fallen to 1.47% but fetal mortality remained as high as 20%. Almost all operations were performed during the second trimester of pregnancy and the almost universal indication was progressive congestive heart failure unresponsive to medical treatment. This and several other studies are subjected to the intrinsic bias characteristic of self-reporting surveys, namely an underreporting of adverse outcomes; therefore, the actual maternal and fetal mortalities could have been higher. The authors stated that whenever possible hypothermia should be avoided, and monitoring of fetal heart beats and uterus activity should be routinely adopted. Pomini and collaborators analysed the cases reported between 1958 and 1991 [7] while Born [8], Parri [1] and Weiss [9] also contributed with a few collective reviews of reported cases or series. Born [8] has reported a single center study of 30 cases and documented a maternal mortality of 13% and a fetal mortality of 33% among patients with rheumatic valvular disease operated on during pregnancy in the period 1981-1992. Most recently, Weiss and coworkers [9] reviewed the outcome of cardiovascular operations during pregnancy, at delivery, and postpartum, from 161 cases reported between 1984 and 1996. Surgery during pregnancy resulted in fetal-neonatal morbidity and mortality of 9% and 30%, respectively. The maternal morbidity and mortality found were of 24% and 6%, respectively (Table 1).
Table 1 illustrates seven collective series reported from 1958 to 1996. We should note that most papers reported before 1970 included a large percentage of young women with a predominant diagnosis of mitral stenosis. Maternal gross mortality has been consistently acceptable and has a close relationship with the cardiac disease involved [9]. A closer analysis indicates that pregnancy per se does not constitute an isolated risk factor for maternal mortality. Fetal mortality, on the contrary, appears to remain high in all series. It is possible that historical reviews may not identify the actual risks of cardiovascular surgery during pregnancy. A few more recent articles may better delineate current indications, management and outcome, based on the physiopathological aspects involved. CARDIAC OPERATION AND FETAL OUTCOME While maternal mortality for a particular operation is similar to that for nonpregnant women of the same age group, a relationship could be observed between the operation performed and fetal outcome. This has been suggested by data collected from a few authors. However, these data should be evaluated with great caution, because of the influence of many other variables involved. Table 2 summarizes those findings. Even considering that data in table 2 constitute a few small samples, it is clear that fetal mortality for valve replacements (mitral and aortic) is 3 to 4 times higher than fetal mortality observed in mitral comissurotomy. This can be accounted for by the longer bypass time, the use of concomitant hypothermia and by some other factors related to the cardiopulmonary bypass. Detrimental effects of anesthesia, surgery and perfusion directly influence fetal mortality. It is higher in valve replacement, specially in the presence of bacterial endocarditis, closure of left-to-right shunts and the correction of aortic aneurysms. CARDIOPULMONARY BYPASS AND PREGNANCY Cardiopulmonary bypass involves several factors that can compromise the delicate biological equilibrium between the fetus and the placenta. Potentially adverse effects of CPB include changes in coagulation, alterations in the function of cellular and protein components of the blood, release of vasoactive substances from leukocytes, complement activation, particulate and air embolism, nonpulsatile flow, hypothermia and hypotension [16]. If we consider only the short operations, such as a mitral comissurotomy, we can conclude that the detrimental effects of CPB may be better tolerated by the fetus. During more prolonged operations, such as valve replacements or repair of aneurysms, the deleterious effects of CPB act longer and their injury may be more pronounced. This may cause an increase of fetal mortality from 5 to 22% (Table 2). Weiss [9] reported an average fetal mortality of 30% during the period 1984-1996.
PHYSIOLOGIC CHANGES OF PREGNANCY The usual 38-40 weeks of human pregnancy are divided into trimesters. The first trimester begins at the first day of the last menstruation and terminates at the end of the 13th week. Second trimester goes from the 14th to the 27th week of gestation and the third and last trimester extends from the 28th to the 40th week of gestation. Pregnancy produces numerous physiological adaptative changes on the female organism. Intravascular volume increases 30% to 50% and oxygen consumption rises from 25% to 30% above nonpregnant levels. In response to this preload, cardiac output increases proportionately by changes in stroke volume and heart rate. Systemic and pulmonary resistances decrease with pregnancy, which may particularly affect patients with right-to-left shunts. A relative state of hypercoagulability increases the risks of thrombotic events [17]. Uterine blood flow is approximately 3% of the total cardiac output during the first trimester and increases to approximately 10 to 15% during the third trimester. These changes, in addition to a decrease in systemic vascular resistance , results in an increased cardiac output that reaches a level about 30 to 40% above the nonpregnant values [16]. All of these physiological changes create a greater demand on the cardiovascular system during pregnancy, compared to the nonpregnant state. These changes are necessary to allow the maternal organism to cope with the new and increased metabolic demands represented by the fetoplacental unit. Clark [18] and coworkers have measured several adaptative cardiovascular changes that occur during pregnancy. Table 3 summarizes their main comparative findings that illustrate the cardiovascular overload typical of the pregnant state.
Peak gestational changes occur from the 20th to the 32th weeks. A prospective study of 30 pregnant patients with mitral stenosis in the NYHA functional class I and II has shown that 86.7% evolved to the functional class III/IV, during the second trimester [19]. These findings well illustrate the severe circulatory overload of pregnancy. PLACENTA During gestation, the embryo is a parasite that survives at the expenses of its mother. Early in gestation, the embryo is small and has correspondingly small requirements for nutrients and for waste disposal systems - it subsists by taking up endometrial secretions and dumping its metabolic wastes into the lumen of the uterus. This situation changes rapidly. As the embryo grows and develops a vascular system, it needs to establish a more adequate means of obtaining nutrients and eliminating waste products, and does so by establishing an efficient interface between its vascular system and that of its mother. That interface is the placenta. In addition to its primary goal of allowing transport between mother and fetus, the placenta functions as a major endocrine organ. Human chorionic gonadotropin (HCG) is a hormone exclusive of pregnancy that can be detected in the blood or urine early after fecundation. The placenta is a major source of HCG during all pregnancy. HCG levels peak at about 8-10 weeks of pregnancy and then decline, remaining at lower levels for the rest of the pregnancy. The placenta also synthesizes and secretes steroid hormones - progestins, lactogen and estrogens, and a number of protein hormones. The placenta is a fundamental support for fetal development; a pregnancy simply cannot proceed without a placenta. Soon after its formation the placenta takes over the hormonal control of maternal organism [20,21]. Under the circulatory point of view, the placenta functions as a large arterio-venous fistula, which considerably reduces the vascular resistance of the maternal organism while fetal vascular resistance remains stable. The placenta has a somewhat flat shape; in one side it adheres to the internal surface of the uterus while the other side (external face) links to the fetus by the umbilical cord. It is important to consider that the placenta does not directly connect mother and fetus. To the contrary, its main function is to serve as an interface between the maternal and the fetal circulations. The fetal surface of placenta is smooth, glistening and is covered by the amnion which is reflected on the cord. The umbilical cord is inserted near or at the center of this surface and its radiating branches can be seen beneath the amnion. The maternal surface is dull greyish red in colour and is divided into 15-20 cotyledons. The placental circulation originates in the uterine arteries which branches and constitute several spaces as "blood lakes" with a large volume and low pressure, in order to favor exchange with fetal blood. About 75% of uterine blood perfuses those spaces. The fetal blood reaches the placenta through the two umbilical arteries which branches to constitute a large capillary surface to exchange gases and nutrients with the maternal blood. Fetal capillaries converge into a large amount of veins which ultimately constitute the umbilical vein. The umbilical vein follows the umbilical cord, enters fetal abdomen and joins the fetal portal vein and the inferior vena cava. Fetal and maternal blood do not mix at the placenta. They flow separately and isolated by the placental interface. Under the gas exchange point of view, the placenta can be considered as working very similarly to a true membrane oxygenator. This concept is helpful to understand the mechanisms by which we can adjust fetal oxygenation during maternal cardiopulmonary bypass and preserve the functional integrity of fetoplacental unit. The perfusionist can modify the flow, pressure and oxygenation of placental blood and thus contribute to improve fetal exchanges. INFLUENCE OF FETAL AGE The gestational age at the time of operation has been sought in order to determine the influence on fetal development, morbidity and mortality. Although there is no proven relationship between the gestational age of the fetus and mortality, several reports point to the more common occurrence of congenital malformations when cardiopulmonary bypass is performed during the first trimester [5, 22]. The risks of teratogenesis due to drug administration and possibly due to cardiopulmonary bypass during the first trimester of pregnancy are always of concern. Surgical interventions should be avoided when possible, during this time [1, 9]. This recommendation does not imply a universally unfavorable outcome. There have been reported a few instances of CPB performed early in the first trimester, before the patients were aware they were pregnant, followed by completely successful pregnancies [6]. In order to avoid these circumstances it is advisable to search for pregnancy on any women at reproductive age during the preoperative work up. Cardiopulmonary bypass during the first half of the second trimester has been associated with less complications. Fetal development is completed and the chances of fetal malformations are reduced. Also uterine excitability seems to be at its lowest levels during the second trimester of pregnancy. There are now many reports of fetal survival to term after operations performed in the second or third trimesters [23, 24]. Operations with the use of CPB performed during the third trimester have been associated with a high incidence of premature labor. At this stage the maternal hemodynamic overload is also of a greater magnitude. Recent progress in neonatal care have improved survival of premature infants with gestational age over 28 weeks. For this reason a few authors have performed a cesarean section to deliver the infant after heparinization and cannulation of the mother but before commencing CPB. In our days, at the third trimester, delivery before cardiopulmonary bypass can be advocated in order to avoid fetal distress from perfusion [1, 25, 26]. When the operation cannot be delayed until the third trimester, it becomes essential a clear understanding of the physiologic changes that occur in the mother during pregnancy and the physiology of the fetoplacental unit, in order to reduce the CPB insult to a minimum. INFLUENCE OF ANESTHESIA In animal studies certain anesthetic agents are known to have untoward effects on the completion of pregnancy, but investigators have been unable to correlate human maternal or fetal mortality with any one surgical or anesthetic technique [Conroy, Pedersen]. It is believed that outcome reflects instead the severity of the underlying maternal disease state. Mechanical ventilation can profoundly affect uterine blood flow and the fetus. Mechanical hyperventilation resulted in a decrease in uterine blood flow of 25% during hypocarbia and, with the addition of carbon dioxide to the respiratory gases, during normocarbia and hypercarbia, in experimental animal studies. Maternal blood pressure remained unchanged during hyperventilation, and the adverse effect on uterine blood flow was atributed to the mechanical effects of positive-pressure ventilation - that is, a decrease in venous return and cardiac output [16, 27, 28]. Maternal hyperventilation and respiratory alkalemia also decrease fetal arterial oxygen tension and oxygen content despite increases in maternal oxygenation. This diminished fetal arterial oxygen tension is probably due to a left shift on the maternal oxygen-hemoglobin dissociation curve [29]. Concerns about fetal development and teratogenicity exists whenever any drug is administered to a pregnant woman, especially during the first trimester when fetal organogenesis occur. The effect of isolated exposures to various anesthetics in pregnant humans have not, for the most part, been elucidated. Some anesthetic agents have produced untoward effects in laboratory studies. However, these results were not confirmed or reproduced in the clinical settings. It appears that most anesthetic agents, venous and inhalatory, and paralyzing drugs are devoided of teratogenic effects and can be safely employed in a pregnant patient [30]. Strickland [16 ] and coworkers, from the Mayo Clinic, have extensively reviewed the effects of anesthetic agents on the fetal organism during cardiac surgery and CPB for pregnant women. INFLUENCE OF CPB The effects of cardiopulmonary bypass on the fetoplacental unit are multiple and complex, and constitute the main determinants of fetal outcome. Potentially detrimental effects of CPB include coagulation changes, functional changes of blood cells and proteins, liberation of vasoactive substances from leukocytes, complement activation, air and particulate microembolism, linear nonpulsatile flow, hypotension and hypothermia [17, 23]. Placental function is dependent not only on the maternal side of the circulation but also on the fetal side with its responses to interventions. On the experimental animal, thirty to sixty minutes after discontinuing CPB, a progressive respiratory acidosis develops on the fetus, which is possibly due to a vasoactive phenomenon. Sodium nitroprusside infusion reverses this acidosis by preventing the elevation in placental vascular resistance. It has been postulated that the underlying cause is activation of eicosanoid products (prostaglandin E2 and thromboxane) as indomethacin and corticosteroids can prevent this respiratory acidosis. A later and more intractable metabolic acidosis develops 6 to 8 hours after CPB is discontinued [31], probably due to low cardiac output secondary to an increase in systemic vascular resistance, due to an increase in cathecolamine levels, which occurs as part of fetal response to stress. The immature fetal myocardium tolerate poorly the increase in the systemic vascular resistance. In the clinical setting, alternative forms of anesthesia or specific drugs that block the fetal stress response to prevent fetal systemic vascular resistance changes are required and may prevent the late metabolic acidosis [1]. It is of fundamental importance the understanding that most of detrimental agents of CPB do not act directly on the fetal organism. Their influence is exerted on the placenta and the uterus. Only a few agents such as hyperkalemia may directly affect the fetal myocardium. EFFECTS OF CPB ON THE PREGNANT UTERUS Uterine contractions occur frequently during cardiopulmonary bypass and are considered to be the most important predictor of fetal death. The contractions are more prone to occur during the rewarming phase after moderate or profound hypothermia and are more frequent with increasing gestational age. Hypothermia can produce acid-base changes, arrhythmias and uterine contractions [6, 32]. This is an indication that whenever possible normothermic cardiopulmonary bypass should be the first choice for a pregnant patient. Contractions are prone to occur during the third trimester. The cause is still unknown but it is speculated that the contractions result from dilution of progesterone and other gestational hormones. Supplemental progesterone has been suggested to stabilize the uterus around the time of bypass [1, 32]. Some other authors have recommended the use of beta2-agonists agents such as ritodrine or isoxsuprine to cease the uterine contractions. Uterine contractions in association with the nonpulsatile flow of cardiopulmonary bypass can produce insufficient irrigation of the placenta and determine the development of fetal hypoxia. Monitoring uterine activity during CPB is essential to detect any increase and allow for an early intervention, before the development of fetal hypoxia and bradycardia [9]. In some occasions the use of deep hypothermia is mandatory as reported by Buffolo [33]. The author corrected an aortic arch aneurysm ruptured into the left lung on a 28 years old woman in the 21th week of pregnancy, with deep hypothermic circulatory arrest. Circulation was arrested for 37 minutes at a temperature of 19 degrees C and both mother and fetus survived. Fetal heart beats disappeared at 24 degrees during cooling and terbutaline was administered to the patient to inhibit the uterine contractions during the immediate postoperative period. Hypothermia, in this particular case was protective of the maternal and the fetal organisms. FETAL RESPONSE TO CPB There are few studies of fetal response to cardiopulmonary bypass. Most reports of cardiopulmonary bypass in pregnant patients indicate some fetal changes. These are dependent upon alterations in the placenta such as hypotension and vasoconstriction, both capable of reducing fetal oxygenation. The most common fetal reaction is bradycardia, which very often occurs after a few minutes of CPB [34, 35]. Most of times the bradycardia is an indication of fetal distress and should be criteriously identified and managed. What causes bradycardia at the beginning of bypass is unknown but it may be related to a decreased fetal oxygenation secondary to placental hypotension or to acid-base changes. Hypothermia is another cause for bradycardia, but it can also occurs during normothermic CPB. It has been postulated that starting normothermic CPB with a high perfusion flow avoids the occurrence of fetal bradycardia [7]. Fetal bradycardia has consistently been related to hemodynamic changes and reduced efficiency of gas exchange at the placental interface. The adequate perfusion of placental tissue can avoid changes in fetal cardiac rate. The transition from pulsatile to linear flow of the arterial pump, the lower mean arterial pressure, and hemodilution, at the beginning of CPB occasionally associated with uterine contractions or increased tonus, can all contribute to reduce the placental blood flow. The lack of an arterial pulse in addition to the arterial hypotension develops a state of placental hypoperfusion which reduces the efficiency of gas exchange with fetal blood [36]. The fetus becomes hypoxic and the first manifestation is bradycardia. Fetal heart rate is usually 135-140 bpm. A range of 120-160 bpm is accepted as normal. Frequently during CPB the fetal heart rate decreases to 100-115 bpm but, occasionally this drop may be accentuated and heart rates of 70-80 bpm are encountered. This level of bradycardia represents a considerable degree of fetal distress. A reduction of fetal heart rate to below 110-120 bpm can frequently be corrected by elevating the perfusion flow. Increasing maternal blood PO2 to 300-400 mmHg can also contribute to correct fetal bradycardia. Both, increasing perfusion flow and increasing arterial PO2 favor oxygen exchange at the placental interface. Hypothermia may increase the affinity of fetal hemoglobin by the oxygen. Excessive circulating cathecolamines elevates fetal peripheral vascular resistance, which is not well tolerated by the immature fetal myocardium[1, 7]. This is a clear evidence of the fetal vulnerability to the excess of cathecolamines which accompanies CBP. Fetal response to the stress of CPB also contributes to elevate the levels of fetal cathecolamines. Some anesthetic agents such as halothane produce maternal and fetal anesthesia but fail to block the fetal response to the excess of circulating cathecolamines and some other vasoactive agents. UTERINE AND FETAL MONITORING DURING CPB Cardiopulmonary bypass effects on the fetoplacental unit can contribute to interrupt pregnancy and to determine fetal death. In order to prevent fetal bradycardia and distress it is a good recommendation to add fetal monitoring to the CBP monitoring protocol. Since uterine contractions or increased tonus contribute to fetal discomfort and distress, uterine activity should also be monitored during CPB. Monitoring uterine activity and fetal heart rate can offer valuable information to the perfusionist as to the placental blood flow and perfusion [34]. These last parameters can be optimized by adjustments of perfusion flow and arterial PO2. CARDIOTOCOGRAPHY Cardiotocography has been used to monitor uterine activity and fetal heart beats during surgical treatment of a pregnant patient since 1975 [7]. Cardiotocography is based on the surface detection of electrical activity much like the conventional electrocardiography. Usually an abdominal belt contains two sets of electrodes; one to monitor the uterine activity and a second to monitor the fetal heart beats. The detection of increased uterine activity and contractions should prompt the administration of beta2 agonists in order to promote uterine relaxation, which favors placental perfusion [37, 38]. Uterine monitoring and treatment should obviously be performed by an obstetrician that becomes part of the team in charge of any operation on a pregnant patient. Detection of fetal bradycardia should prompt the perfusionist to increase perfusion flow and arterial PO2 which usually contribute to maintain fetal heart rate within an acceptable range. Those measures increase the placental perfusion and enhance oxygen exchange, and both contribute to abort or revert fetal hypoxia. ULTRASONOGRAPHY AND DOPPLER MONITOR A few Doppler transducers are available to monitor fetal heart beats from the surface of maternal abdominal wall. These probes are difficult to maintain in place during the procedure. Smaller probes have also been used transvaginally to monitor fetal heart beats and umbilical cord flow, but they have not gained a wide popularity at the present time. RECOMMENDATIONS FOR CPB IN THE PREGNANT PATIENT It has been demonstrated that CPB can reduce placental blood flow and thus interfere with fetal well being. A reduced fetal heart rate is a common finding during CPB, and does not necessarily indicates any increased risk for the development of fetal distress or death. Severe fetal bradycardia, on the other side, is a clear indication of fetal distress and should be avoided or aggressively treated. During CPB the perfusionist's attention should be directed at the placental blood flow, which can be optimized to offer the fetus the best conditions for oxygen exchange and thus maintain its viability. Cardiopulmonary bypass during pregnancy must be conducted according to the specific physiology of pregnancy. The circulatory and respiratory functions of the placenta to maintain fetal life should be the main focus in order to decrease the detrimental effects of CPB on the fetoplacental unit. Our review has shown that an individual discussion of some specific aspects of CPB can contribute to a better understanding and a more appropriate protocol for a pregnant patient. POSITIONING ON THE OPERATING TABLE Particularly during the third trimester, after induction of anesthesia, the patient should be positioned with 30 to 60 degrees right lateral pelvic tilt, in order to eliminate the inferior vena cava compression by the relaxed uterus, which can reduce venous return and cause arterial hypotension [37, 39]. ANTICOAGULATION Heparin does not cross fetoplacental barrier and cannot exert any anticoagulant effect on the fetus. However there exists a small potential risk of placental hemorrhage and fetal abortion or premature labor. Heparin monitoring should be closely followed and an ACT between 480 and 600 seconds is a common recommendation for CPB on a pregnant patient. PRIMING A certain degree of anemia is always present and is considered a physiologic change of pregnancy, due to the combination of increased body water and reduced production of red cells, as well as reduced levels of iron and vitamin B12. There is also a 10 to 20% reduction in oncotic pressure. Due to this, the perfusate volume should be a minimum necessary to initiate bypass. Crystalloid hemodilution was used with success but there has been reports of fetal distress with low hematocrit. A better environment for the fetus is obtained when perfusion hematocrit is higher than 25%. Ideal hematocrit for a normothermic bypass is between 30 to 34% and packed red cells should be used to attain those values. Plasma, albumin or colloids can favor tissue perfusion and contribute to avoid interstitial edema. Mannitol crosses the placental barrier and can stimulate fetal diuresis on amniotic fluid [40]. Diuretics should be very cautiously used during CPB. They should not be part of any "routine" protocol but should be used to stimulate maternal diuresis if necessary. Furosemide is preferred to mannitol for its less dramatic effect on fetal diuresis. An oncotically adjusted prime makes addition of mannitol or furosemide unnecessary and can avoid untoward effects of diuretics on the fetus. Perfusate pH and temperature should be adjusted before starting bypass to avoid sudden reduction of placental blood flow and preserve optimal fetal-maternal exchanges. PUMP FLOW Higher perfusion flow rates are unanimously recommended for CPB during pregnancy and objectives to sustain an adequate fetoplacental gas exchange during nonpulsatile flow. Pump flow varies between 2.5 and 2.7 l/min/m2 which should be equivalent to about 60 to 80 ml/kg/min. Arterial flow should essentially be 20-40% higher than flows used for routine CPB [7, 23]. Pump flow should be sufficient to maintain a mean arterial pressure above 70 mmHg (70-90 mmHg), although a few authors have suggested higher levels [1, 7]. However, the best demonstration of an adequate pump flow and arterial pressure is the fetal response to CPB. Fetal bradycardia is an indication to elevate perfusion flow and pressure in order to increase placental blood flow. During the average CPB on a pregnant patient, high perfusion flow, high mean arterial pressure and a normal cardiotocography usually present a clear correlation. GAS FLOW CPB during pregnancy has to be conducted with a higher FiO2 to produce an arterial PO2 of at least 200 mmHg. If fetal bradycardia occurs arterial PO2 should be elevated to about 400 mmHg along with other measures such as increasing perfusion flow and pressure [16, 41]. All these technical adjustments will allow for a better perfusion of placental tissue and favor fetoplacental gas exchange which frequently corrects the bradycardia. One should note that this high maternal arterial PO2 does not affect fetal organs. Fetal arterial saturation will remain normal, according to the fetal pattern and will not contribute to produce any ill effect. HYPOTHERMIA There are numerous experimental and clinical evidences that even mild degrees of hypothermia can increase uterine tone and contractions and elevate uterine vascular resistance. However no effect has clearly been demonstrated on fetal survival by some studies[17], while others suggest a tendency for a higher fetal mortality when CPB is conducted with hypothermia [7]. Maternal bradycardia, ventricular arrhythmias, and fibrillation are more common during hypothermia. Significant hypothermia should be avoided unless extended aortic clamp times are anticipated or a circulatory arrest period is required [17, 33, 42]. Experimental studies have demonstrated that during hypothermia there is reduced gas exchange at the placental level and reduced placental and fetal blood flows [24, 30]. Rewarming has also been associated with increased uterine contractions and increased amniotic fluid pressure [33]. VASOACTIVE DRUGS Under a few circumstances it may become necessary to administer vasoactive drugs in order to adjust certain maternal parameters. This should be done very cautiously. Blood flow to the uterus is under a strong alfa-adrenergic control. Vasopressor with alfa-adrenergic receptors effect can reduce uterine and placental blood flow. Efedrin does not appear to influence uterine flow as well as a low-dose infusion of dopamine (< 5 mcg/kg/min) and can be used as necessary. Administration of isoproterenol has been recommended as the inotrope of choice, soon after bypass. This drug has also a positive effect on maternal and fetal heart rate [38]. Whenever a peripheral vasodilatory effect is required during CPB, an infusion of hidralazine can be administered without any untoward effect. This drug can produce a 20-30% reduction on mean arterial pressure and at the same time increase renal, uterine and placental blood flow [16]. Recommended initial dose is 1.5 mcg/kg/min, to be adjusted according to the hemodynamic response. ACID-BASE MANAGEMENT Acid-base disturbances are not well tolerated by the fetus as they alter gas exchange efficiency at the placental level. Normothermic CPB favors monitoring and managing acid-base status and significant changes are less prone to occur. Metabolic acidosis as a consequence of reduced tissue perfusion and respiratory alkalosis secondary to excessive gas flow in the oxygenator are about the only changes seen. Both can easily be corrected by adjusting perfusion and gas flow without having to resort to any drugs. During hypothermic CPB, acid-base disturbances can be more pronounced. There is no consensus regarding pH management during pregnancy. Most cases are performed under normothermia or mild hypothermia and it is a good practice to manage pH according to an alpha-stat protocol. No recommendation has been found to add CO2 to the ventilating gas in order to keep a stable pH. MYOCARDIAL PROTECTION As for nonpregnant patients, a variety of methods have been used to protect the myocardium during aortic crossclamping. More recent literature concentrates on the use of crystalloid and blood cardioplegia. As most operations are for valve reconstruction or replacement or ASD closure, a crystalloid cardioplegia should be adequate to protect myocardium. Complex procedures or individual preferences may require a blood cardioplegia system to be prepared. In all circumstances it is important to note that regardless of the type of cardioplegia and the administration route (antegrade, retrograde or combined), the cardioplegia efluent should be aspirated from the right atrium (or coronary ostia) to avoid its mixing to the perfusate. The hyperkalemia secondary to the cardioplegia infusion can affect fetal myocardium and produce bradycardia, conduction disturbances or cardiac arrest. High potassium levels in maternal blood accentuates diffusion to fetal blood at the placental corionic villi and originates fetal hyperkalemia. This is particularly important during long procedures and with continuous cardioplegia [7, 39]. MANAGEMENT OF FETAL BRADYCARDIA During pregnancy and labor, fetal bradycardia is always an indication of distress, except in the presence of congenital AV block. During CPB the occurrence of fetal bradycardia has the same significance. Monitoring fetal heart beats is essential to determine the general status of the fetus and and to determine any changes in the CPB management. At the start of CPB, the transition from normal to extracorporeal circulation almost consistently produces some reduction of fetal heart rate. This bradycardia is self limited; it usually disappears in a few minutes and is probably related to maternal hypotension, reduction of peripheral vascular resistance and to hemodilution [9, 43]. Fetal heart rate under these circumstances drops to 100-120 bpm. Several agents have been incriminated as a cause of fetal bradycardia such as hypotension, hypothermia and metabolic acidosis. Occasional bradycardia may be severe with heart rates under 80 bpm. Such extreme bradycardia is always an expression of fetal distress and is a consequence of reduced gas exchange at the placenta. Increasing arterial pump flow and FiO2 usually is all that is necessary to correct the bradycardia. If, despite those measures fetal heart rate remains low, a small drip of efedrin may be required. Correcting any degree of metabolic acidosis will have the same result. In a few cases, despite all management, fetal bradycardia persists for the duration of CPB and reverts when normal circulation is resumed. When the bradycardia prolongs to the immediate postoperative period, the risk of fetal death is substantially increased. MANAGEMENT OF UTERIN CONTRACTIONS Cardiopulmonary bypass is a strong stimulus to increase the uterine tonus and to develop contractions, as observed by several authors [5, 6, 7, 33]. Prolonged and intense contractions are associated with a higher incidence of fetal death. Dilution of pregnancy hormones, such as progesterone has been suggested to be responsible for the increase uterine activity. Arterial hypotension, hypothermia and rewarming can also induce uterine contractions. Excessive uterine activity produces placental insufficiency and fetal hypoxia and distress. The correction of causative factors can minimize and eventually abolish uterine contractions. When uterine activity persists despite all adjustment of perfusion parameters, tocolytic agents are recommended and should be used under obstetric orientation. Some beta-agonist agents can cease uterine contractions [33]. Ritodrin is commonly indicated in those circumstances and is very effective to abolish uterine contractions, as an infusion of 50-150 mcg/min and should be maintained for at least 12 hours. Another effective agent is terbutaline in the dose of 10 mcg/min which can be increased as necessary up to 80 mcg/min and should be continued for 4 hours. Venous infusion of alcohol is effective to abolish uterine contractions in the experimental setting but has not been clinically used [44, 45]. CONCLUSIONS Cardiopulmonary bypass during pregnancy carries a high risk of fetal morbidity and mortality. Preparation and management of CPB for a pregnant patient should be oriented towards the avoidance of any sudden changes of placental blood flow. The physiology of the placenta has to be maintained as close to the normal as possible. Managing the perfusion flow and pressure and arterial oxygen tension can provide the fetal blood with an optimum environment for gas exchange. Fetal bradycardia is the earliest indication of fetal distress and must be aggressively managed. Uterine contractions can also be detrimental to the optimal placental perfusion and should be abolished by tocolytic agents if necessary. Modern neonatal therapy can optimally care for a premature newborn. This favors a cesarean section prior to the start of CPB when gestational age is superior to 28 weeks in order to eliminate any deleterious effect of CPB on the fetus and thus contribute to reduce fetal morbidity and mortality. REFERENCES 1. Parry AJ, Westaby S. Cardiopulmonary Bypass during Pregnancy. Ann Thor Surg 61: 1865-9, 1996. 2. Conroy JM, Bailey MK, Hollon MF, Cooke JE, Baker III JD. Anesthesia for Open Heart Surgery in the Pregnant Patient. Current Concepts in Therapy. Southern Medical Journal 82, 492-495, 1989. 3. Rush RW, Verjans M, Spracklen FH. Incidence of heart disease in pregnancy. A study done at Peninsula Maternity Services hospitals. S Afr Med J 55, 808-10, 1979. 4. Dubourg G, Broustet H, Bricaud H, Fontan F, Tarieux M, Fontanille P. Correction complete d'une triade de Fallot, en circulation extra-corporelle, chez une femme enceite. Arch Mal Coeur Vaiss 52: 1389-92, 1959. 5. Zitnik RS, Bradenburg RO, Sheldon R, Wallace RB. Pregnancy and open-heart surgery. Circulation 39 (Suppl 1): 257-62, 1969. 6. Becker RM. Intracardiac surgery in pregnant women. Ann Thorac Surg 36, 453-8, 1983. 7. Pomini F, Domenico M, Cavalletti C, Caruso A, Pomini P. Cardiopulmonary bypass in pregnancy. Ann Thorac Surg 61, 259-68, 1996. 8. Born D, Massonetto JC, de Almeida PA et al. Heart surgery with extracorporeal circulation in pregnant women: analysis of materno-fetal outcome. Arq Bras Cardiol 64, 207-11, 1995. 9. 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 179, 1643-53, 1998. 10. Lapiedra OJ, Bernal JM, Ninot S, Gonzales I, Pastor E, Miralles PJ. Open heart surgery for mitral prosthetic thrombosis during pregnancy. Fetal hydrocephalus. J Cardiovasc Surg 27, 217-20, 1986. 11. Bahary CM, Ninio A, Gorodesky IG, Nery A. Tococardiography in pregnancy during extracorporeal bypass for mitral valve replacement. Israel J Med Sci 16, 395-7, 1980. 12. Eilen B, Kaiser IH, Becker RM, Cohen MN. Aortic valve replacement in the third trimester of pregnancy: case report and review of the literature. Obstet Gynecol 57, 119-21, 1981. 13. Madjan JF, Wallinsky P, Cowchock SF, Wapner RJ, Plzak L Jr. Coronary artery bypass surgery during pregnancy. Am J Cardiol 52, 1145-6, 1983. 14. Martin MC, Pernoll ML, Boruszak AN, Jones JW, LoCicero J. Cesarean section while on cardiac bypass: report of a case. Obstet Gynecol 57 (Suppl) 41S-5S, 1981. 15. Windsor HM, Shanahan MX, Golding L. Cardiac surgical emergencies. Med J Aust 1, 476-82, 1973. 16. Strickland RA, Oliver WC, Chantigian RC, Ney JA, Danielson GK. Subject Review. Anesthesia, cardiopulmonary bypass, and the pregnant patient. Mayo Clin Proc 66, 411-29, 1991. 17. Chambers CE, Clark SL. Cardiac surgery during pregnancy. Clin Obstet & Gynecol 37, 316-326, 1994. 18. Clark SL, Cotton DB, Lee W, Bishop C, Hill t, Southwick J. Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 161, 1439-42, 1989. 19. Avila WS, Andrade JA, Born D, Lopes CMC. Terapêutica da estenose mitral durante a gravidez - Tratamento clínico, cirurgia cardíaca e valvotomia. Rev Soc Cardiol Estado de São Paulo 7, 2-5, 1997. 20. Redman C, Sargent I, Starkey P. The human placenta. Blackwell Science, London, 1992. 21. Chamberlain GW, Hamilton-Fairly D. Lecture notes on Obstetrics & Gynaecology. Blackwell Science. London, 1999. 22. Levy DL, Warringer RA III, Burgess GE III. Fetal response to cardiopulmonary bypass. Obstet Gynecol 56, 112-5, 1980. 23. Rossouw GJ, Knott-Craig CJ, Barnard PM, MacGregor LA, van Zyl WP. Intracardiac operations in seven pregnant women. Ann Thorac Surg 55, 1172-4, 1993. 24. Bernal JM, Miralles PJ. Cardiac surgery with cardiopulmonary bypass during pregnancy. Obstet Gynecol Surv 41, 1-6, 1986. 25. Wahlers T, Laas J, Alken A, Borst HG. Repair of acute type A aortic dissection after cesarean section in the thirty-nintn week of pregnancy. J Thorac Cardiovasc Surg 107, 314-5, 1994. 26. Martin MC, Pernoll ML, Boruszak AN, Jones JW, LoCicero J. Cesarean section while on cardiac bypass: report of a case. Obstet Gynecol 57(Suppl), 41S-5S, 1981. 27. Pedersen H, Finster M. Anesthetic risk in the pregnant surgical patient. Anesthesiology 51, 439-51, 1979. 28. Levinson G, Shnider SM, deLorimier AA, Steffenson JL. Effects of maternal hyperventilation on uterine blood flow and fetal oxygenation and acid-base status. Anesthesiology 40, 340-7, 1974. 29. Motoyama EK, Rivard G, Acheson F, Cook D. The effect of changes in maternal pH and PCO2 on the PO2 of fetal lambs. Anesthesiology 28, 891-903, 1967. 30. Duncan PG, Pope WDB, Cohen MM, Greer N. Fetal risk of anesthesia and surgery during pregnancy. Anesthesiology 64, 790-4, 1986. 31. Sabik JF, Heinemann MK, Assad RS, Hanley FL. High dose steroids prevent placental dysfunction after fetal cardiac bypass. J Thorac Cardiovasc Surg 103, 116-25, 1994. 32. Korsten HHM, van Zundert AAJ, Mooji PNM, de Jong PA et al. Emergency aortic valve replacement in the 24th-week of pregnancy. Acta Anaesth Belg 40, 201-5, 1989. 33. Buffolo E, Palma JH, Gomes WJ, Vega H, Born D, Moron AF, Carvalho AC. Successful use of deep hypothermic circulatory arrest in pregnancy. Ann Thor Surg 58, 1532-4, 1994. 34. Trimakos AP, Maxwell KD, Berkay S, Gardner TJ, Achuff SC. Fetal monitoring during cardiopulmonary bypass for removal of a left atrial myxoma during pregnancy. John Hopkins Med J 144, 156-60, 1979. 35. Werch A, Lambert HM. Fetal monitoring and maternal open heart surgery. South Med J 70, 1024-6, 1977. 36. Tripp HF, Stiegel HM, Coyle JP. The use of pulsatile perfusion during aortic valve replacement in pregnancy. Ann Thorac Surg 67, 1169-71, 1999. 37. Lamb MP, Ross K, Johnstone AM, Manners JM. Foetal monitoring during open heart surgery. Two case reports. Br J Obstet Gynaecol 88, 669-74, 1981. 38. Levy DL, Warriner RA III, Burgess GE III. Fetal response to cardiopulmonary bypass. Obstet & Gynecol 56, 112-5, 1980. 39. Souza MHL, Elias DO. Perfusões Especiais. Perfusão em Gestantes. In: Fundamentos da Circulação Extracorpórea. Centro Editorial Alfa Rio, Rio de Janeiro, 1995. 40. Basso A, Fernandez A, Althabe O, Sabini G et al. Passage of mannitol from mother to amniotic fluid and fetus. Obst Gynecol 49, 628-31, 1988. 41. Koh KS, Friesen RM, Livingstone RA et al. Fetal monitoring during maternal cardiac surgery with cardiopulmonary bypass. Can Med Assoc 112, 1102-5, 1975. 42. Assalli NS, Westin B. Effects of hypothermia on uterine circulation and on the fetus. Proc Soc Exp Biol Med 109, 485-8, 1962. 43. Fenton KM, Heinemann MK, Hickey PR, Hanley FL. The stress response during fetal surgery is blocked by total spinal anesthesia. Surg Forum 43, 631-4, 1992. 44. Levinson G, Shnider SM. Anesthesia for surgery during pregnancy. In: Shnider SM, Levinson G eds. Anesthesia for Obstetrics. Williams & Wilkins, Baltimore, 1987. 45. Mora CT. Pregnancy and cardiopulmonary bypass. In: Mora CT, ed. Cardiopulmonary Bypass. Principles and techniques of extracorporeal circulation. Springer-Verlag, New York, 1995.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||