Th e fi rst documented use of cardiopulmonary bypass in pregnancy was in 1959 for a pulmonary valvotomy and atrial septal defect closure at 6 weeks of gestation.
[ 5 , 6 ] Th e mother survived but the fetus miscarried aft er the procedure. Th is pattern of good maternal result but signifi cant fetal loss was to repeat itself over the follow- ing fi ve decades.
A systematic review in 2012 described maternal mortality rates ranging from 3% to 13%, and fetal mor- tality rates ranging from 14% to 38%.[ 7 ] Th ese data are summarized in Table 8.1 . Th e 2011 US series of 21 patients over 33 years reported a maternal mortality rate of 5% and a fetal mortality rate of 14%.[ 8 ] In general, maternal mortality rates are similar to those reported for emergency procedures in nonpregnant patients . Fetal loss is related to gestational age,[ 8 – 10 ] with improved survival as the fetus becomes more mature.
In general, cardiopulmonary bypass includes a number of components: hypothermia, chemical car- dioplegia, hemodilution, extracorporeal circulation, and oxygenation. Hypothermia was introduced to reduce myocardial and systemic oxygen demand and to increase ischemic tolerance for the increasing com- plexity of surgeries.[ 11 ] Hypothermia also allowed the use of hemodilution, which reduces the need for large volumes of blood in the circuit . Th e use of concomitant chemical cardioplegia permitted surgery on a nonbeat- ing fl accid heart, thus improving the ease and success of
Table 8.1 Fetal and maternal mortality rates associated with cardiopulmonary bypass procedures during pregnancy, based on reported series and systematic literature reviews
Reference Patients ( n ) Fetal mortality (%) Maternal mortality (%)
Weiss (1998) [ 9 ] 59 29 5
Salazar (2000) [ 66 ] 15 33 13
de Souza (2001) a [ 53 ] 24 33 4
Immer (2003) b [ 73 ] 20 15 5
Arnoni (2003) [ 16 ] 74 18.6 7
Avila (2003) [ 2 ] 25 16 4
John (2011) [ 8 ] 21 14 5
Elassy (2014) [ 10 ] 14 26 9
Elkayam (2014) c [ 81 ] 14 7 0
a Only open mitral commissurotomy b Only aortic dissection
c Bypass surgery in acute MI
complex cardiac surgery.[ 12 ] Support of the rest of the circulation, as well as oxygenation, is provided through a mechanical pump-oxygenator system that has seen signifi cant technological advances in recent years but is still based on principles similar to those of 60 years ago . From the physiological point of view, cardiopulmo- nary bypass during pregnancy can be considered a form of “controlled cardiocirculatory shock” that is generally better tolerated by the mother than by the fetus.[ 13 ] Th e cardiovascular changes of pregnancy result in an increase in circulating volume, an increase in cardiac output, a decrease in hematocrit, and an increase in oxygen consumption. Th e placental blood vessels are maximally dilated. Th erefore, uterine blood fl ow is not autoregulated: it is directly proportional to maternal mean arterial pressure and inversely proportional to uterine vascular resistance. A mean arterial pressure of 70 mmHg is required for adequate placental perfusion and a higher pressure is needed during uterine contrac- tions.[ 6 ] Furthermore, cardiopulmonary bypass brings further hemodilution, hypotension, hypothermia, and nonpulsatile blood fl ow, as well as complement acti- vation and the risks of particulate and air embolism.
[ 14 ] Th e activation of complement and cytokines by the cardiopulmonary bypass circuit may even have the potential to bring about a direct deleterious eff ect on the placenta and fetus. Moreover, the well-established procoagulant eff ect of pregnancy would be expected to increase these risks further. Maternal hypotension aft er initiation of cardiopulmonary bypass can be caused by a decrease in systemic vascular resistance due to hemodilution and the release of vasoactive sub- stances.[ 13 , 14 ] Th e use of high doses of heparin for anticoagulation during cardiopulmonary bypass and the consequent need for neutralization with protamine can cause further diffi culties in both intraoperative and postoperative hemostasis, as well as hemodynamic instability and bronchospasm related to protamine.
[ 15 ] All of these factors can result in decreased blood fl ow to the placenta and a reduction in oxygen supply to the fetus, with consequent fetal distress .
Uterine contractions occur frequently during car- diopulmonary bypass and are an important predic- tor of poor fetal outcome. Th ey occur more frequently with increasing gestational age.[ 5 ] Th ey may be caused by the dilutional eff ect of cardiopulmonary bypass on hormone levels, resulting in increased uterine excitabil- ity.[ 14 ] Uterine contractions are most common in the rewarming phase aft er hypothermia.[ 13 , 16 ] Th e con- tractions decrease placental blood fl ow and therefore
contribute to fetal hypoxia. To reduce this deleterious eff ect on the fetus, it is important to monitor and control uterine contractions. Adjusting perfusion parameters may be successful. If not, the use of tocolytic agents has been suggested.[ 17 ] However, the use of these drugs (e.g. beta-adrenergic agonists, calcium blockers, mag- nesium, ritodrine, ethanol, nitroglycerine, atosiban) in any setting of preterm labor has been controversial and has been associated with adverse cardiovascular eff ects;
in general, it is not recommended .[ 18 ]
Th e common fetal response to cardiopulmonary bypass is bradycardia. Th is is thought to be due to fetal hypoxia or acidosis, and may be related to maternal hypothermia. It may be transient or persistent, may show late decelerations or sinusoidal patterns, and is usually noted just aft er initiation of, or emergence from, cardiopulmonary bypass.[ 6 , 17 ] Fetal bradycardia usu- ally improves within 2–3 h postoperatively, suggesting that inadequate placental perfusion had resulted in fetal hypoxia and the bradycardic response. Th e bradycardia has been shown to respond to measures that increase the perfusion rate and to worsen with uterine contrac- tions that compromise placental fl ow.[ 8 ] Hypothermia has also been implicated as a factor in such fetal brady- cardia. [ 19 ] and has been used as one of the justifi ca- tions for normothermic arrest. Unfortunately, return to a normal fetal heart rate (HR)aft er cardiopulmonary bypass is no guarantee of a good fetal outcome. A sig- nifi cant cause of fetal bradycardia is the use of high-dose opioids for maternal anesthesia. Th is is reversible and transient, and should be considered if fetal bradycar- dia does not respond to increasing cardiopulmonary bypass fl ow .[ 14 ] Th e potentially damaging eff ect of hyperkalemic cardioplegia on the fetus has not been fully studied,[ 13 ] but potassium ions can easily cross the placenta and lead to fetal cardiac depression or even arrest. Maternal hyperkalemia must be avoided, with close monitoring of maternal potassium levels.[ 20 , 21 ]
A number of modifi cations to cardiopulmo- nary bypass techniques for pregnant women have been proposed. Pulsatile cardiopulmonary bypass is thought to reduce uterine contractions by releasing endothelium-derived growth factor from the vascular endothelium and to further maintain placental perfu- sion by preserving fetal/maternal endothelial nitric oxide synthesis and decreasing activation of the fetal renin–angiotensin pathway.[ 22 ] However, there is no consensus on whether there are enough clinical data to recommend pulsatile cardiopulmonary bypass for these women .[ 7 , 8 ]
Section 2: Antenatal Care: General Considerations
Th e extent of the deleterious eff ect on the fetus of hypothermia in cardiopulmonary bypass is diffi cult to gage. Pomini et al. reported a fetal mortality rate of 24%
with hypothermia and 0% with normothermia.[ 13 ] Other reports have not confi rmed such a strong rela- tionship.[ 9 , 23 ] Experimental studies on pregnant ewes have demonstrated a number of eff ects of hypothermia on the fetus.[ 24 ] In all the animals, fetal temperature decreased in parallel with maternal cooling. Th e pla- centa acted as a heat exchanger, with a gradient of tem- perature during all phases of cooling. During cooling, there was a direct eff ect on the fetal sinus node, with an average reduction in the fetal HR of 7 beats/min for each degree of fetal cooling. Maternal temperatures of ≥18°C, corresponding to a fetal temperature of ≥25°C, were associated with fetal survival. At very low temperatures, profound fetal bradycardia led to a critical reduction in cardiac output and consequently reduced feto–placental exchange, with irreversible fetal acidosis and hypoxia.
At 20°C or higher, the fetus returned to normal pH and partial pressure of oxygen. More profound hypothermia resulted in poor perinatal outcome or fetal death. Such fi ndings have led to a variety of recommendations on hypothermia in cardiopulmonary bypass during preg- nancy, ranging from avoidance of deep hypothermia to the use of normothermic cardiopulmonary bypass.
[ 5 – 7 , 13 , 14 , 19 , 20 , 22 ] So-called “warm heart surgery” is gaining acceptance for cardiovascular surgery in gen- eral,[ 11 , 12 ] and has been used successfully in aortic valve replacement for a pregnant woman .[ 21 ]
Th ere have been reports of two cases in which intra-aortic balloon pumping was used with cardio- pulmonary bypass to improve uterine blood fl ow and benefi t fetal hemodynamics, but the effi cacy of its rou- tine use in this setting remains to be determined.[ 25 ]
Of course, there are alternative techniques for car- diac surgery that do not require the use of cardiopul- monary bypass. Aortocoronary bypass surgery has been performed without cardiopulmonary bypass in pregnant women.[ 26 , 27 ] Closed mitral valvotomy has a long history and continues to be used in many developing countries, where it has been successfully applied to pregnant women.[ 28 ] In developed coun- tries, PBMV and other percutaneous techniques have obviated the need for a number of surgeries with car- diopulmonary bypass, but these come with their own special risks (see the radiation and contrast-agent risks to fetus and mother in the section below).
In summary, the risk of cardiopulmonary bypass to a pregnant woman is similar to that of a nonpregnant
patient, but there is a high percentage of fetal loss. It has been suggested that fetal risk can be minimized if the bypass is supervised by a highly experienced team.
When there is no alternative to an intervention and an appropriate gestational age has been achieved, consid- eration should be given to delivering the baby before the intervention.[ 8 , 29 ] Such a decision will clearly need to balance the risks of preterm delivery against those of fetal loss during cardiopulmonary bypass surgery.[ 8 , 30 ]
Key points regarding cardiopulmonary bypass in pregnancy
1. Consider cardiac surgery only if the woman is deteriorating and has failed optimal medical therapy and there are no suitable percutaneous options for interventional therapy.
2. Refer the woman early to a center with experience in intervention during pregnancy.
3. Avoid aortocaval compression by the gravid uterus by positioning the woman with the right hip elevated at 15°.
4. Avoid cannulation of the femoral vein and artery, if possible. Femoral artery cannulation may result in hypoperfusion of the uterus. Venous return through a femoral vein cannula may be reduced by pressure on the inferior vena cava from the uterus.
5. Although there is no risk of fetal hemorrhage from the heparin required during cardiopulmonary bypass, heparin may increase the risk of uterine hemorrhage and must be carefully monitored. Th is is especially true if the fetus has been delivered by cesarean section just prior to cardiopulmonary bypass.
6. Th e use of high-fl ow rate, high-pressure (mean arterial pressure >70 mmHg) cardiopulmonary bypass to match expected maternal cardiac output (cardiac index of 2.6–3 l/min/m 2 ) is recommended.
Th e necessity of pulsatile perfusion remains controversial.
7. Avoid deep hypothermia. Th e maternal temperature should not be allowed to fall below 30°C.
8. Avoid hyperkalemia by using cardioplegia recovery techniques and close monitoring of maternal potassium levels.
9. Continuous monitoring of uterine contractions and fetal HR are recommended. Intraoperative fetal echocardiography should be considered.
10. Th e presence of an experienced obstetric team is required for fetal monitoring and to deal with precipitous delivery or the need for cesarean section (surgical equipment for cesarean section must be readily available).
11. Consideration should be given to postponing the surgery for as long as possible to allow fetal maturity. Delivery of the fetus prior to cardiopulmonary bypass avoids the risk of fetal loss but incurs the risks of prematurity for the child. Careful consultation with the obstetrician and neonatologist are necessary before
considering such a preterm delivery .