DOI: 10.31038/JCCP.2020316

Introduction

In a patient presenting with severe acute chest or back pain, aortic dissection is a concerning etiology and requires immediate attention due to its profound morbidity and mortality. Less common presentations include altered mental status, stroke symptoms, and syncope, which represent less than 30% of aortic dissections. Risk factors have been well described, and include history of uncontrolled hypertension, connective tissue disease, and vasculitis. We present a case of acute Stanford Type A aortic dissection in a patient without risk factors but with recent history of bevacizumab treatment, who also presented with atypical symptoms.

Case Description

The patient is a 60 year old female with past medical history of colon cancer metastatic to liver and lung, who woke from sleep with severe chest pain, followed by right facial droop and right upper extremity weakness. Stroke code was called and Glasgow Coma Scale was 5 on admission, but CT Head was negative for hemorrhage or large-territory infarct. CT angiography of the brain and neck partially showed a Stanford type A aortic dissection, and CT aneurysm study confirmed the dissection, which extended from the aortic valve to the femoral arteries and included the great vessels, celiac trunk, and superior mesenteric artery. She was in shock on admission, was intubated and sedated. Based on the patient’s frailty she was a poor surgical candidate, and the family stated she would have declined repair. She lived for another day in the ICU before transitioning to comfort care.

Postmortem review revealed no classic risk factors for aortic dissection. The patient had no history of hypertension, connective tissue disease, or vasculitis, prompting further evaluation of her extensive history of chemotherapy. She was originally diagnosed with moderately-differentiated colon cancer in 2012 and subsequently underwent multiple resections of the primary tumor and metastasis (liver and peritoneum). Bilateral pulmonary nodules were found and treated medically. Multiple antitumor agents were used since 2012, the majority of which involved many iterations of fluorouracil and bevacizumab. The last chemotherapy regimen consisted of FOLFIRI and bevacizumab, which was resumed four months prior to the dissection.

Discussion

This case illustrates the broad range of presentations of aortic dissection, including altered mental status or stroke symptoms, as well as devastating complications of certain antitumor regimens. Cardiovascular side effects can be the most profound, especially in the use of fluoropyrimidines (e.g. fluorouracil) and vascular endothelial growth factor (VEGF) pathway inhibitors (e.g. bevacizumab). In the absence of typical risk factors, repetitive vascular toxicity from these agents likely represents the causative pathophysiology for the acute dissection. While aortic dissection is an uncommon complication of these therapies, it is incumbent on providers to recognize this possibility and recall the variable presentations of the pathology.

Figure 1. Sagittal view showing Stanford type A aortic dissection extending from aortic valve
into abdomen

Figure 2. Axial view showing aortic dissection involving arch and all three arch arterial
branches.

DOI: 10.31038/JCCP.2020315

Summary

Cardiac surgery-related morbidity and mortality may be higher in patients with malignant neoplastic disease. Inflammatory phenomena and immunological alterations secondary to the use of cardiopulmonary bypass may also increase tumor recurrence. The aging population favors the early diagnosis of cancer and new therapies that increase the survival of patients with malignant neoplasms. emergence of cancer patients who at the same time have a cardiomyopathy that requires surgery. The benefits, especially in terms of long-term survival and risks, have not yet been clearly established. This study evaluated the characteristics of cancer patients undergoing cardiac surgery with Cardiopulmonary Bypass (CPB) indicated for a different cause of the tumor: type of procedure required, morbidity and mortality, long-term survival and incidence of tumor recurrence. To carry out this study, we used bibliographic research, performing a review on the topic.

Keywords

Cardiac surgery, Extracorporeal circulation, Splenic changes

Introduction

Controversy over the appropriateness of cardiac surgery in cancer patients, especially if they are not in complete remission, is increasing in daily clinical practice. As there are no objective reasons to justify higher mortality in these patients, the interest of the procedure focuses on the prospects for long-term survival and the risks arising from the use of CPB through direct alteration of the immune system, may exacerbate the tumor and favor dissemination and / or relapse [1]. Since the 1990s, studies on cancer patients undergoing cardiac surgery have been published. Some exclude newly diagnosed or untreated cancers and others refer exclusively to the association of cardiac surgery and the simultaneous or deferred surgical excision of lung tumors. A third group describes the results of surgical treatment of cancers that affect the heart as a primary tumor or metastasis and require CPB for resection [2]. Finally, a final group includes patients affected by tumors with special characteristics, such as hematologic malignancies. The publications are few and far between and the series are limited and heterogeneous due to the low number of operated patients. The risk of selection bias is difficult to avoid and, in addition, the different origins, stages and degrees of tumor differentiation and spread make it difficult to compare results [3]. Although clinical treatment of heart disease progresses from year to year and the less invasive approach is expanding rapidly, cardiac surgery is the preferred intervention in some cases of heart disease [4]. Therefore, this study deals with cardiopulmonary bypass and cardiac surgery, considering the main theoretical findings on the subject.

Cardiopulmonary Bypass

Supportive cardiopulmonary bypass during cardiac surgery is unique because blood exposed to foreign surfaces of nonendothelial cells is collected and continuously recirculated throughout the body. This contact with synthetic surfaces within the perfusion circuit, as well as open tissue surfaces within the wound, trigger a defensive reaction involving at least five plasma protein systems and five circulating blood cell types [5]. This inflammatory response to cardiopulmonary bypass initiates a powerful thrombotic stimulus and the production, release, and circulation of vasoactive and cytotoxic substances that affect all organs and tissues of the body. Because of this, open-heart surgery using cardiopulmonary bypass is not possible without anticoagulation, which is usually with heparin; thus, the inflammatory response to cardiopulmonary bypass involves the consequences of exposure of heparinized blood to foreign surfaces uncoated with endothelial cells [6]. During Cardiopulmonary Bypass (CPB) for cardiac surgery, blood is typically severely drained into the venous reservoir of the heart-lung machine through cannulae placed in the superior and inferior vena cava or a single cannula placed in the right atrium. Specialized cannulae can also be placed in the inferior vena cava through a femoral approach [7].

The blood from the reservoir is then pumped through a hollow fiber oxygenator after appropriate gas exchange that occurs in the systemic arterial system through a cannula placed in the distal ascending aorta, femoral artery or axillary artery. This basic extracorporeal perfusion system can be adapted to provide partial or full circulatory and respiratory support or partial support for the left or right heart or lungs separately [8]. That is, Cardiopulmonary Bypass (CPB) is used to maintain the patient’s blood circulation and / or pulmonary function outside the body. Oxygen-depleted blood is diverted out of the body and enriched with oxygen, passing it through an artificial lung (oxygenator) before being pumped back into the patient’s circulation for up to six hours [9].

Results Analysis and Discussion

Heart Disease And Cardiopulmonary Bypass (CPB)

In order to perform different types of cardiac surgeries, Cardiopulmonary Bypass (CPB) remains a frequent procedure, aiming to provide a clean surgical field, preserve the functional characteristics of the heart and provide safety to the surgical team [10]. Cardiopulmonary Bypass (CPB) is a form of circulation in which the patient’s blood is diverted from the heart and lungs out of the body. The normal physiological functions of the heart and lungs, including blood circulation, oxygenation and ventilation, are temporarily taken over by the ECC machine [7,11]. In most cases, the heart is also separated from the circulation (eg, aortic clamping) and the cardioplegia solution is administered to allow the cardiac surgeon to operate on a heart not beating in a bloodless field while other end organs they are adequately oxygenated and perfused [12].

General Principles

Equipment and Physiology

CPB components include pumps, tubing, and gas exchange (oxygenator) and heat exchange units. Modern CPB machines are also equipped with systems that continuously monitor line or circuit pressure, temperature and blood parameters (eg, oxygen saturation, blood gases, hemoglobin [Hgb], potassium) as well as safety features such as air and fluid level detection. Systems and a blood filter in the arterial line [10,12,13]. During cardiopulmonary bypass, venous blood is drained from the right atrium and is diverted through the venous line of the CPB circuit to a venous reservoir [14]. CPB machines are typically equipped with vacuum assisted technology that facilitates drainage to maintain a bloodless surgical field and allows the use of smaller venous cannulas and reduced CPB circuit volumes. The arterial pump acts as an artificial heart by drawing blood from this reservoir and propelling it through a heat exchanger, an artificial lung (oxygenator or gas exchanger) and, finally, an arterial line filter [15]. The blood is then returned to the patient through an arterial cannula positioned in the ascending aorta or other major artery. Additional cardiopulmonary bypass pumps or other components are employed as needed to suck blood from the surgical field, provide cardioplegia solution to produce cardiac electromechanical silence, decompress the heart through a vent and remove fluid (ultrafiltration) [9,16]. Thus, the cardiopulmonary machine temporarily assumes the functions of the heart, lungs and, to a lesser extent, the kidneys [17].

The contact of blood with non-endothelial surfaces of the CPB circuit induces an intense inflammatory response. This results in platelet activation and initiation of the coagulation cascade with decreased levels of circulating coagulation factors. Endothelial cells and leukocytes are activated, releasing mediators that may contribute to capillary leakage and tissue edema. Many of the challenges encountered during weaning from CPB and in the postoperative period are considered consequences of this inflammatory sequence [17]. In addition, the CPB circuit priming solution (typically 1 to 2 liters of a balanced crystalloid solution) results in hemodilution with anemia and temporary or persistent coagulopathy [18].

Protocol

Surgical procedures that require CPB follow a predictable sequence of events including CPB circuit initiation and testing, anticoagulation, vascular cannulation, CPB initiation and maintenance, and finally CPB weaning and termination. Myocardial arrest with myocardial protection and myocardial reperfusion are additional considerations when a stationary heart and a bloodless field are desired. Protocols established for the management of CPB parameters approaching normal physiology [19].

• In adults, the target flow rate during CPB is 2.2 to 2.4 Liters / min / m² in normothermic patients to approach a normal cardiac index; cardiac index is appropriately decreased if hypothermia is induced [6,20].
• Mean arterial pressure (MAP) is usually directed to ≥65 mmHg, but the goal may be higher in elderly patients and those with cerebrovascular disease. MAP should not exceed 100 mmHg [20,21].
• The adequacy of target organ perfusion is determined by the analysis of arterial blood gases and mixed venous oxygen saturation (SvO2), which is continuously monitored and maintained ≥75 percent throughout CPB. Arterial blood gas analysis, baseline deficit and lactate levels are intermittently checked (approximately every 30 minutes) [22].
• ECB weaning preparations and checklists to ensure readiness for weaning are described separately [9,18].

Cardiopulmonary Bypass

Objectives during CPB include maintenance of general anesthesia, anticoagulation, and parameters that approximate normal physiology for optimal end-organ function [23]. Arterial oxygenation, ventilation and blood gas – Arterial pO 2 is maintained at 150 to 250 mmHg during CPB. A continuous arterial blood pressure monitoring system is located on the arterial line of the CPB circuit, and a continuous venous oximeter is located on the venous return line. Arterial blood gas values are checked in the laboratory or by point-of-care testing approximately every 30 minutes, which also allows intermittent recalibration of the continuous blood gas monitor in the arterial line [24]. More specific oxygenation strategies (eg targeting hyperoxia) have not been shown to be clinically beneficial. A 2018 systematic review of 12 randomized trials noted little evidence of differences in the outcome of a hyperoxic rather than normoxic oxygenation strategy used during cardiac surgery, but the studies were small and heterogeneous [21,22,8]. Two studies [9,25] reported a reduction in postoperative myocardial enzymes and one study reported a reduction in mechanical ventilation time in normoxic groups. Alpha-stat management of arterial blood gases without temperature correction is used to maintain a normal range for pCO 2 (35 to 45 mmHg [4.7 to 6 kPa]) and pH (7.35 to 7.45) [25]. Maintaining PaCO 2 and pH within this physiological range during CPB is important to preserve cerebral self-regulation [26].

Ventilation of the lungs during CPB has not been shown to improve lung function and may increase the technical difficulty for the surgeon. Some doctors use continuous positive airway pressure (CPAP) during CPB. In a meta-analysis of seven small randomized trials, the use of 5 to 15 cmH20 CPAP improved the postoperative alveolar-arterial oxygen gradient (Aa gradient) by a weighted average difference of approximately 31 mmHg [23]. Pump flow and mixed venous oxygen saturation – CPB flow rates are set at 2.2 to 2.4 Liters / min per m² in a normothermic patient to provide adequate blood flow for optimal brain and other end organ perfusion. . These rates may be slightly decreased if hypothermia is employed [27]. Acute decreases in Mean Arterial Pressure (MAP) or increases in Central Venous Pressure (CVP) may indicate a sharp reduction in venous return due to the surgeon’s lifting of the heart (causing a reduction in flow), a misplaced or twisted arterial or venous cannula, or obstruction of blood flow by an air blockage. With severe reduction in venous return, the perfusionist may need to administer volume to the CPB reservoir or reduce arterial flow. Persistent reductions in arterial line flow and / or venous return should be urgently addressed, identifying and correcting the cause [2,5,24]^.

Mixed venous oxygen saturation (SvO2) is maintained ≥75% throughout CPB as a peripheral perfusion adequacy monitor. Persistent SvO 2 values <75% may indicate inadequate oxygen supply and are associated with worse outcomes, including postoperative delirium and decreased long-term survival [27]. In addition, lactate and baseline deficit values are measured when arterial blood gases are obtained approximately every 30 minutes. Although absolute lactate values are multifactorial, increasing levels during CPB represent anaerobic metabolism at the cellular level due to inadequate tissue oxygen delivery and may reflect hypoperfusion during CPB, particularly if maintained or associated with low mixed venous saturation. oxygen (SvO 2 <70%) [28]. Treatment for SvO 2 <75 percent, baseline deficit less than -5, or lactate level> 4 mEq / L is directed to increasing CPB flow rate as well as ensuring that blood gas and hemoglobin levels ( Hgb) are suitable. It is common practice to administer sodium bicarbonate for a baseline deficit below -5, or lactate level> 4 mEq / Liter, but excessive administration of sodium bicarbonate may cause postoperative hypernatremia [19,20]. Although increased lactate level during CPB is more often the result of inadequate tissue perfusion, persistent postoperative lactic acidosis may occur due to other factors (eg, beta-adrenergic metabolic effects of epinephrine infusion) [28]. Mean blood pressure – In the context of acceptable CPB flow rates, MAP is generally directed to ≥ 65 mmHg; a higher target may be selected in elderly patients and in those with cerebrovascular disease [28].

In a retrospective study30 of nearly 7500 patients, postoperative stroke was associated with prolonged periods with MAP <65 mmHg, with an adjusted odds ratio (OR) of 1.13 for each 10-minute period that was 55 to 64 mmHg during and after surgery. After CPB (95% CI 1.05–1.21) and adjusted OR of 1.16 for each 10-minute period when MAP was <55 mmHg (95% CI 1.08–1.23) Other factors associated with stroke in this study were advanced age, history of hypertension, combined procedures of valvular myocardial revascularization, prolonged CPB duration, emergency surgery, and new onset of postoperative atrial fibrillation [11,29]. However, a randomized study in 197 patients showed no reduction in the number or volume of cerebral infarcts in those who received vasopressor therapy to maintain a nearly physiological MAP target (70 to 80 mmHg) compared to those who had a smaller target. MAP (40 to 50 mmHg) [30]. Episodes of low or high blood pressure during CPB have been associated with the risk of brain events and other adverse outcomes, although a causal relationship has not been established [21]. A retrospective study [31] observed that impaired cerebral self-regulation is common, occurring in almost one third of patients undergoing cardiac surgery with CPB. In this study, impaired self-regulation was associated with small brain vessel disease (identified with brain magnetic resonance imaging) but was not associated with large vessel disease (identified by transcranial Doppler). However, it is not yet clear how these data inform the management of blood pressure in individual patients.

During attempts to increase MAP, it is important to ensure adequate pump flow and to maintain clear communication between the anesthesiologist (who may be adjusting the systemic vascular resistance of the vasopressor patient) and the perfusionist (who may be adjusting the flow rate) effective heart rate with changes in pump flow) [34]. MAP should not exceed 100 mmHg, in most patients a range of MAP from 65 to 100 mmHg allows for self-regulation of cerebral circulation and other target organs throughout CPB, although it is not possible to determine an accurate range of self-regulation for each patient. Individual [3,25].

Hypotension

Moderate hypotension – In the context of acceptable CPB flow rates, if MAP is below the target range, the perfusionist may increase pump flow (equivalent to increasing cardiac output), particularly if <2.4 L / min / m². If hypotension persists after increased pump flow, a vasopressor may be administered as an intravenous (IV) bolus or by continuous infusion. In many institutions, small bolus doses of phenylephrine (eg 40 to 100 mcg) are administered directly into the CPB reservoir to treat hypotension. Phenylephrine infusions at 10 to 200 mcg / min, vasopressin at 0.04 units / min or norepinephrine at 0.02 to 0.06 mcg / kg / min are also commonly employed [22]. Severe vasoplegia – systemic vasodilation, characterized by markedly decreased systemic vascular resistance (SVR) and low MAP during and after CPB, occurs in 5 to 25 percent of patients undergoing cardiac surgery. Risk factors include the preoperative use of agents such as angiotensin converting enzyme (ACE) inhibitors, heparin or calcium channel blockers, as well as hemodynamic instability before passage [17]. Before treating low blood pressure near the end of the CPB period, it is important to verify that radial blood pressure is not markedly underestimating central aortic pressure. A significant central pressure gradient associated with end-CPB rewarming is often present during cardiac surgery. Attaching a pressure transducer to the side port of the aortic cannula after CPB is complete, or the use of a surgeon-inserted femoral intraarterial catheter in the field will usually provide an accurate estimate of true central aortic pressure [33].

If hypotension due to vasoplegia (low SVR) is confirmed, a continuous vasopressor infusion is usually necessary. Although an optimal approach for vasopressor selection during CPB has not been established, observations in the distributive shock scenario suggest that administration of vasopressin or a combination of vasopressin with noradrenaline or phenylephrine is associated with lower atrial fibrillation rates compared to administration. isolated from norepinephrine [34]. If these agents are ineffective, methylene blue 1 to 2 mg / kg IV for 20 minutes may be administered to reduce the responsiveness of nitric oxide resistance vessels. Notably, methylene blue should be avoided in patients receiving chronic serotonin therapy (eg, fluoxetine) because of the risk of serotonin syndrome and may interfere with monitors employing oximetry to measure oxygen saturation (pulse oximetry and cerebral oximetry) [5,29]. Hypertension – If MAP increases to> 90 mmHg during CPB, treatment includes increasing the concentration of volatile anesthetic administered through the CPB circuit and / or administering additional IV anesthetic. Occasionally, administration of a vasodilator may be required. For brief periods, pump flow may be reduced while these pharmacological interventions are effective [35]. Anticoagulation Maintenance – The adequacy of heparin anticoagulation is measured with point-of-care tests such as activated whole blood clotting time (ACT) every 30 minutes to maintain a target value during CPB (typically above 480 seconds). If available, plasma heparin concentrations may also be determined by treatment point assays such as Hepcon with target heparin concentration ≥4 units / mL. Protocols in some institutions emphasize the treatment of heparin concentrations <4 units / mL, even if ACT values are adequate [36].

Special Population Management

Specific management strategies are employed during CPB for patients with aortic insufficiency, cerebrovascular disease, renal failure, or vasoplegia and for those undergoing a period of elective deep hypothermic circulatory arrest (DHCA) [6,30]. Pre – existing Aortic Regurgitation (AR) can be diagnosed and its severity characterized by intraoperative Transesophageal Echocardiography (TEE) examination in the pre – reception period. During CPB, the presence of AR may limit the effectiveness of administration of anterograde cardioplegia solution to the coronary artery ostia after the ascending aorta is crossed [37]. Much of the cardioplegia solution will regurgitate through the incompetent aortic valve to the Left Ventricle (LV). The severity of RA can be influenced by the increased aortic root pressure that occurs during attempted delivery of anterograde cardioplegia and surgical manipulations that further distort the normal aortic root and valve geometry [38]. In addition, cardioplegia solution that flows back through the incompetent aortic valve may cause LV distention as the ventricle is not ejecting regularly due to bradycardia, asystole or ventricular fibrillation. Distension causes increased LV wall tension. In combination with inadequate coronary delivery of anterograde cardioplegia solution, this may result in inadequate myocardial protection and severe LV dysfunction. In this situation, a LV ventilator is placed by the surgeon to keep the ventricle in an uncompressed state [4,15,28].

Correct ventilation placement and effective LV decompression are confirmed with the TEE examination. Subsequently, continuous monitoring of TEE and Pulmonary Artery Pressure (PAP) supplement the surgical detection of a displaced LV output or recurrence of LV distension [28]. If the administration of anterograde cardioplegia is inadequate due to RA, the cardiac surgeon usually minimizes the attempted delivery by this route, opting for retrograde cardioplegia provided by the coronary sinus. In selected aortic valve or aortic root procedures, it may be necessary to implant cardioplegia solution directly into the coronary ostia after aortic clamping and opening of the aortic root [36]. Rapid and severe LV distension may occur in a patient with significant RA, even before aortic clamping, if ventricular fibrillation occurs at the onset of CPB and on cooling. In this situation, the CPB flow rate may be temporarily reduced to allow the surgeon to manually decompress the LV, since defibrillation is more likely if the heart is empty (not distended). Defibrillation is performed with internal paddles applied directly to the heart to provide 10 to 20 joules of electricity. Subsequently, if LV distension recurs after the application of aortic cross forceps, a left ventricular opening may be inserted [39].

Cerebrovascular disease is common in patients undergoing cardiac surgery. A study that used preoperative magnetic resonance imaging observed a major brain vessel disease in 25% and small vessel disease present in 35% of 346 patients undergoing cardiac surgery with CPB. Considerations for patients with known cerebrovascular disease and / or evidence of severe aortic atherosclerosis include maintaining a higher mean arterial pressure than patients without these comorbidities, with careful attention to maintaining hemoglobin (Hb) and hematocrit (Hct) levels. and the prevention of cerebral hyperthermia. The use of intraoperative oximetry and the maintenance of regional cerebral oxygen saturation (rSO2) in 20% of baseline values has been advocated by patients at high risk of adverse neurological outcomes, including those with known cerebrovascular disease [23,39].

Conclusion

Cardiopulmonary Bypass (CPB) is a form in which the patient’s blood is diverted from the heart and lungs out of the body. Normal physiological functions of the heart and lungs, including blood circulation, oxygenation, and ventilation, are temporarily taken over by the CPB machine. Most studies do not show a significant increase in the morbidity and mortality of CPB cardiac surgery in cancer patients, even at an active stage, compared to the normal population. It appears that the survival of cancer patients undergoing cardiac surgery is more related to tumor progression than to the surgical procedure. Medium-term survival is acceptable, although less in active cancer patients at the time of intervention and in those <2 years between cancer diagnosis and surgery. Readmission rates are higher than in the general population and are mainly due to the need for cancer treatment and / or complications arising from it. Typical parameters during CPB in adults include controlled flow rate of 2.2 to 2.4 Liters / min / m², maintenance of mean arterial pressure (MAP) ≥ 65 mmHg and mixed venous oxygen saturation ≥ 75%. Maintaining renal blood flow is achieved by maintaining adequate CPB pump flow throughout CPB to minimize the risk of Acute Kidney Injury (AKI). Inadequate anesthetic depth is treated by increasing the volatile anesthetic concentration administered by the CPB circuit or by the administration of additional Intravenous (IV) anesthetic agents. It is reasonable to monitor processed EEG indices (eg bispectral index) or unprocessed EEG to provide data that may detect inadequate anesthesia during CPB. Decreasing the dose of the selected Neuromuscular Blocking Agent (NMBA) may be adequate during the hypothermic CPB period; however, additional NMBA is usually required during reheat. Individual assessment of each case should consider both the tumor stage and the chances of complete remission (even in active cancers) before discounting cardiac surgery. Larger studies are needed to allow comparison of morbidity and mortality outcomes and survival with and without CPB to identify their influence on these variables and long-term recurrence.

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DOI: 10.31038/JCCP.2020314

Summary

The need for cardiac surgery during pregnancy is rare. Only 1% to 4% of pregnancies are complicated by maternal heart disease and most of them can be treated with medical therapy and lifestyle changes. Occasionally, whether due to the natural progression of underlying heart disease or precipitated by cardiovascular changes in pregnancy, cardiac surgical therapy should be considered. Cardiac surgery is inherently dangerous for both mother and fetus with mortality rates close to 10% and 30%, respectively. For some conditions, percutaneous cardiac intervention offers effective therapy with much less risk for the mother and her fetus. For others, cardiac surgery, including procedures that require the use of cardiopulmonary bypass, should be considered to save the mother’s life. Given the extreme risks to the fetus, if the patient is in the third trimester, serious consideration should be given to pre-operative delivery involving cardiopulmonary bypass. At earlier gestational ages, when this is not feasible, modifications to the infusion protocol, including higher flow rates, normothermic perfusion, pulsatile flow, and the use of intraoperative monitoring of the external fetal heartbeat should be considered.

Keywords

Cardiac surgical procedures, Cardiopulmonary bypass, Cardiovascular, Surgery, Complications of pregnancy, Heart defects congenital, Pregnancy

Introduction

Cardiovascular adaptations during pregnancy are usually well tolerated in healthy women. However, 2% to 4% of women of childbearing age have some degree of concomitant heart disease, and these changes may compromise cardiac function. Of these, some who do not respond to medical treatment may require surgical correction. In this scenario, the maternal mortality rate improved to levels similar to non-pregnant women. However, the fetal mortality rate remains high (up to 33%). Factors contributing to the high rates of fetal mortality include the timing of the operation, the urgency of the operation, and the fetal / fetoplacental response to cardiopulmonary bypass. Modulation of the fetoplacental response to cardiopulmonary bypass may prevent placental dysfunction and sustained uterine contractions that underlie fetal hypoxia and acidosis. In this article, we reviewed the cardiovascular adaptations to pregnancy and the pathophysiological effects of cardiopulmonary bypass on the mother, fetus and fetoplacental unit, and talked about whether manipulating these responses can help improve fetal outcome. Finally, approaches to perfusion management and cardiac surgical techniques without extracorporeal circulation in pregnancy were made.

Khandelwal et al [1] points out that approximately 2% to 4% of women of childbearing age have concomitant heart disease. According to Abbas [2], Congenital Heart Disease (CHD) is responsible for most structural heart diseases that affect women of childbearing age. Abbas [2] also points out that the acquired heart disease observed during pregnancy is mainly valvular in nature, usually a consequence of rheumatic fever. Although rheumatic fever is decreasing in developed countries, it remains a serious problem in the developing world. Immigrants also form a high-risk population, especially those who are unaware of the risks inherent in heart disease during pregnancy or unaware of the presence of any heart disease. In this regard, mitral stenosis is the most commonly found lesion. Abbas [2] further states that although its incidence is declining, aortic valve disease is less common: aortic incompetence is usually a consequence of endocarditis (1 in 8,000 pregnancies) or aortic dissection, in which case there may be tissue disease. underlying connective tissue such as Marfan syndrome. Thus, significant aortic stenosis is uncommon in this age group. Parry [3] points out that ischemic events during pregnancy are rare. The incidence of myocardial infarction is approximately 1 in 10,000 pregnancies. Mabie [4] states that infarction is usually secondary to underlying coronary artery disease, although spontaneous coronary artery dissection appears to be more common during pregnancy and accounts for 30% of all myocardial infarctions seen in pregnancy.

Maternal and Fetal Predictors

Siu [5] highlights that heart disease in the mother is the leading cause of maternal death during pregnancy. Of these patients, 25% have congenital heart disease. In a large prospective multicenter study on pregnancy outcomes among women with heart disease, adverse cardiovascular events were observed in 13% of patients. Independent predictors of maternal cardiac complications included previous cardiac events, functional class III / IV, left heart obstruction, and left ventricular systolic dysfunction. Neonatal complications were observed in 20% and were associated with functional class or poor cyanosis, left heart obstruction or smoking. Klairy [6] says that a recent prospective observational study in pregnant patients with congenital heart disease found that both cardiac complication and neonatal complication rates were considerable in these women. In mothers, right subpulmonary ventricular systolic dysfunction and severe pulmonary regurgitation were predictors of an adverse fetal outcome

Drenthen [7], in his bibliographic review, describes that the results of 2,491 pregnancies among women with structural heart disease (congenital heart disease), were observed substantial cardiac complications in 11% of pregnancies. Obstetric complications do not appear to be more prevalent except for hypertensive disorders and thromboembolic events. In patients with complex CHD, rates of preterm delivery ranged from 22% to 65%, and neonates were lower than normal for gestational age.

Maternal Cardiovascular Changes During Pregnancy

In the presence of maternal heart disease, circulatory changes in pregnancy may result in decompensation and death of the mother or fetus. Pregnancy produces changes in the cardiovascular system that have profound implications for heart surgery. Cardiac output increases markedly by the end of the first trimester, followed by a more gradual increase of 30% to 40% above baseline until the third trimester partly due to an increase in stroke volume and heart rate. In most patients, this hyperdynamic situation results in mild midsystolic murmur [8]. Diastolic murmurs may be normal, but deserve further investigation. At the end of pregnancy, compression of the lower uterine vena cava in the supine position decreases venous return and reduces cardiac output. Relief of vena cava compression is easily achieved by positioning the patient in the left lateral position. Systemic and pulmonary vascular resistance falls due to the effects of circulating prostaglandins in addition to other hormones and the poor resistance of the placental circulation. This lowers blood pressure during the first half of pregnancy, but pressure tends to increase in the second half [9].

Blood volume increases with a concomitant increase in plasma volume and red blood cell volume. Plasma volume expands by approximately 40% at term, when red cell mass increases by about 20%. Consequently, there is a drop in hematocrit and blood viscosity [10]. Hemoglobin’s oxygen carrying capacity is increased by a right shift on the oxygen dissociation curve. Pregnancy induces a procoagulant state with a 2-fold increase in fibrinogen level and an increase in factors V, VII, VIII, IX, and X, which has teleological advantage as it helps in hemostasis and reduces blood loss. during childbirth. In addition, this state ensures the optimal supply of oxygen and nutrients to the mother and fetus

Responses to Cardiopulmonary Bypass

Maternal

As the circulation of pregnant women has already undergone significant changes, the additional effect of Cardiopulmonary Bypass (CPB) induces a non-physiological hemodynamic state that may adversely affect the mother during cardiac surgery. This effect is amplified by simultaneous changes in the cellular and protein components of the blood. Hemodilution and changes in coagulation, complement activation, release of vasoactive substances by leukocytes, gas embolism and hypotension during CPB are further added to the deleterious effect. However, these effects are relatively well tolerated by the mother, as the maternal mortality rate associated with CPB in pregnant women is similar to that of non-pregnant women undergoing CPB-like cardiac procedures [3].

Uterine

Sustained uterine contractions during cardiac surgery and CPB are accepted as the most important cause of fetal death. Sustained uterine contractions reduce uterine blood flow and interventional perfusion, resulting in fetoplacental insufficiency and subsequent fetal hypoxia. Cardiopulmonary bypass has other potentially deleterious effects on the uterus during pregnancy. Both cooling and reheating phases are associated with increased sustained uterine contractions. This observation is supported by the fact that there is a noticeably higher fetal mortality rate with hypothermic CPB than with normothermic CPB [3]. Uterine muscle excitability is probably increased by hormonal dilution, especially by progesterone dilution. Postoperative progesterone administration successfully eliminated preterm labor.

Fetoplacental shunt

Experimental studies of fetal CPB provided much information on the fetoplacental response, which could shape future management of CPB in pregnant women. Studies in sheep have repeatedly shown that standard non-pulsatile flow perfusion rapidly causes severe placental dysfunction dominated by a strong vasoconstrictor reaction. Vasodilators have been used with some success to overcome this increase in placental vascular resistance, producing improvement in both placental blood flow and acidosis [11]. A study of the human placenta under physiological conditions reveals that an active fetal renin-angiotensin system can modulate placental perfusion in vivo. Endothelial dysfunction is a cause or an effect of excessive renin-angiotensin activity that has yet to be resolved. Lactate levels during CPB pulsatile flow were stable, while a continuous increase is observed with non-pulsatile CPB. Manipulation of the fetal lamb during CPB has been shown to produce significant lactic acidosis; this was considered as a result of metabolic debt of fetal stress, and anesthesia. Since lactate release into the maternal circulation was similar between the beginning and the end of CPB, the increase in fetal lactate probably originated from within the fetus. The placenta plays an important role in regulating circulating lactate levels under hypoxic conditions, thus allowing the fetus to maintain stable lactate levels. However, a reduction in placental perfusion prevents lactate clearance in the fetal circulation [11].

Fetal

The fetal mortality rate during maternal cardiac surgery with CPB ranges from 16% to 33%. Increased gestational age and increased hypothermia are factors known to increase fetal morbidity during CPB. Unfortunately, little experimental evidence is available on the fetal response to maternal CPB. Fetal cardiac monitoring usually shows that the onset of CPB is bradycardia, which in most cases reverts to sinus rhythm immediately after CPB cessation [13]. Alternatively, an initial tachycardia may occur, accompanied by an increase in blood pressure. Fetal bradycardia observed after the onset of CPB is corrected by increased blood flow and the restoration of maternal circulation upon CPB discontinuation. The mechanism of this bradycardic response is unknown, but several causes have been postulated, including fetoplacental dysfunction, fetal hypoxia and acidosis, maternal hypothermia, and drugs that cross the placental barrier, such as β-adrenergic blockers [14]. Fetal hypoxia during CPB may be a consequence of hemodilution, as hemodilution reduces the oxygen content in the maternal blood. Other causes of fetal hypoxia include reduced uterine perfusion pressure and increased uterine vascular resistance [14] Because placental blood vessels are maximally dilated during pregnancy, uterine blood flow is not self-regulating but directly depends on maternal mean arterial pressure and uterine vascular resistance.

Decreased maternal blood pressure may result in fetal bradycardia shortly before the onset of CPB. Maternal hypotension soon after cardiopulmonary bypass is caused by decreased systemic vascular resistance caused by reduced flow rate, hemodilution, and release of vasoactive substances, which may result in a significant reduction in placental perfusion. Cardiac fetal decelerations observed during CPB are probably caused by reduced blood flow to the interventional spaces and the resulting fetal hypoxia. Factors such as non-pulsatile flow, uterine arteriovenous bypass, and obstruction of venous drainage by cannulation of the inferior vena cava, particulate and gas emboli, and spasm of the uterine artery may reduce placental circulation and lead to fetal hypoxia. When CPB is prolonged, there is a significant risk that the fetus will develop a prolonged bradycardic response. Changes in fetal heart rate may be observed even when maternal circulation, acid-base balance and perfusion pressure are stable. Therefore, it has been postulated that these changes are related to the narcotic effect of drugs used during anesthesia. Vasoconstrictors may reduce uteroplacental flow (direct evidence of this is lacking) and should be avoided, although phenylephrine and ephedrine are considered safe during pregnancy.

Surgical Issue

The principles for the management of pregnant patients undergoing cardiac surgery with CPB are similar to those of pregnant women undergoing surgical intervention. These include: attention to maternal well-being, prevention of teratogenic drugs, prevention of intrauterine hypoxia and prevention of premature labor. In addition, strong consideration should be given to the administration of maternal corticosteroids to initiate endothelial membrane stability and fetal lung maturation, which can substantially improve fetal outcome if delivery occurs after CPB. In summary, the main concerns in optimal management of pregnant patients undergoing CPB are temperature control, perfusion pressure, and the nature of bypass flow. Current evidence favors the maintenance of normothermic CPB, avoiding the use of vasoconstrictors (which may have a profound effect on the placental unit) and maintaining high hematocrit rates and high blood flow rates. Fetal hypoperfusion and hypoxia may also be alleviated by the use of pulsatile perfusion. Other adjuncts, such as the use of arterial line filters or leukocyte depletion filtration, have not been evaluated in the specific context of pregnant patients [15].

Extracorporeal Circulation

Aggarwal and coauthors [16] reported that closed mitral valvotomy offers excellent results, comparable to non-surgical treatments; It is still the procedure of choice in certain parts of the world. Myocardial revascularization without cardiopulmonary bypass is a safe and accepted technique for coronary revascularization; However, its role in pregnancy needs further evaluation. The current medical literature contains only 1 documented case of myocardial revascularization during pregnancy – that of a 32-year-old woman at the 22nd week of gestation who had a spontaneous dissection of the left anterior descending artery and subsequently delivered a healthy baby at term. Hemodynamic instability during unsupported myocardial revascularization (CABG) surgery – involving a decrease in mean systemic blood pressure and an increase in mean pulmonary pressure during distal anastomosis construction and heart manipulation to gain access to the lateral and posterior branches – may not be well tolerated by pregnant patients and could cause significant placental malfunction. However, if only one anterior target (such as the anterior descending coronary artery territory) is grafted, this can usually be accomplished with minimal hemodynamic compromise and avoid all risks inherent to CPB, such as hemodilution, systemic inflammatory response to CPB and increased risk of bleeding [17].

To deepen our understanding of the placental and fetoplacental response to off-pump myocardial revascularization surgery, it is useful to look at how other vascular beds, such as splanchnic circulations, behave during off-pump coronary artery bypass grafting (CABG). If we hypothesize that splanchnic and fetoplacental circulations will respond similarly to hemodynamic insults during CPB myocardial revascularization surgery, much can be learned by observing splanchnic and gastrointestinal physiology during cardiac operations. L-lactate concentration has been significantly higher in the intestinal mucosa of patients undergoing myocardial revascularization with CPB than without CPB [17]. This supports the view that without CPB produces less dysfunction in these vascular beds than CPB. When Fiore et al. [18] examined upper mesenteric blood flow during myocardial revascularization, they found that cardiac manipulation to gain access to the lower and lateral walls caused hemodynamic changes that resulted in significant mesenteric hypoperfusion. Such information can help us plan the approach to revascularization we want to perform in pregnant patients who develop spontaneous coronary artery dissection.

Conclusion

Spontaneous single vessel or two vessel dissections, particularly in the anterior descending territory or right coronary artery territory, are probably the best candidates for off-pump surgery: the use of CPB in these instances avoids manipulation of the heart to reach the posterior artery. and inferior, thus avoiding hemodynamic instability and its effects on fetoplacental circulation More observational data should be collected in the context of myocardial revascularization in pregnancy, with particular attention to responses. fetal and maternal cardiovascular diseases, before myocardial revascularization can be safely recommended as the ideal therapy for this challenging group of patients.

References

1. Khandelwal M, Rasanen J, Ludormirski A, Addonizio P, Reece EA (2015) Avaliação da hemodinâmica fetal e uterina durante a circulação extracorpórea materna. Obstet Gynecol 88: 667–671.
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DOI: 10.31038/JCCP.2020313

Summary

Right Thromboses Floating (RHT) are in transit from the legs to the pulmonary arteries and are therefore a severe form of Venous Thromboembolism (VTE) with a high early mortality rate without treatment. There is a lack of evidence-based recommendations for its management, which is why, motivated the accomplishment of this study, dealing with the subject, addressing the surgical treatment of pulmonary arterial thrombosis, considering professional experiences in the surgical management of the thrombus in transit and Pulmonary Embolism (PE).

Keywords

Pulmonary arterial thrombosis, Pulmonary embolism, Surgical treatment

Introduction

The presence of thrombi in right heart chambers may be a consequence of Venous Thromboembolism (VTE) or may develop in situ as a consequence of cardiac conditions. Transient Thrombus (TT) or floating thrombus is defined as a thrombus temporally located in the right cardiac chambers en route to the Pulmonary Artery (AP). It is, therefore, a severe manifestation of VTE and very often (more than 90%) is associated with Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE). Given the high mortality rate without treatment (90%) and being very early (in the first 24 hours), monitoring in critical units and urgent treatment (including systemic fibrinolysis or surgical embolectomy, in addition to conventional anticoagulation) is justified. TT is an uncommon manifestation of symptomatic PE, with an approximate frequency of 4%. Currently, there is insufficient evidence on the best treatment option, and the recommendations are based on conclusions drawn from case series. The objective of this study is to discuss theoretical findings and experience of early surgical treatment of patients with TT and PE.

Discussion on the Topic

The presence of thrombi in the right cardiac chambers may be a consequence of VTE or may develop in situ as a consequence of cardiac conditions. This differentiation is of great importance considering that they have different treatment and prognosis [1]. TT or floating thrombus is defined as thrombus temporarily located in the right cardiac chambers en route to the PA. It is, therefore, a severe manifestation of VTE and with very high frequency (more than 90%) is associated with DVT or PE [2]. Thus, the presence of a TT confirms the diagnosis of PE and implies the desire for immediate treatment without the need for additional diagnostic tests. Three types of right thrombus were described using the Transthoracic Echocardiogram (TTE): type A thrombi are the most common and tend to be large, free floating masses with a high propensity for distal embolization; Type B thrombi are small clots of immobile right chambers attached to walls originating in situ; finally, type C thrombi are rare and have great mobility mimicking atrial myxomas. TT is an uncommon manifestation of symptomatic PE, with an approximate frequency of 4%.

Although coexisting Right Heart Thrombus (RHT) does not commonly occur in patients with acute symptomatic PE, studies have validated THR as a predictor of poor prognosis [3]. Despite anticoagulation, the mortality rate has been reported high (23.2-44.7%), especially in the first 24 hours [3]. In a recent meta-analysis, which included 15,220 patients with symptomatic acute PE, patients with detectable RHT concomitantly with echocardiography had a three-fold increased risk of short-term death compared to patients without RHT [4]. Similar results were found in a study of patients with PE from the Computerized Registry of the Thrombotic Infirmary (RIETE), which included 12,441 patients with PE, of which 325 had RHT.

Severe hypoxemia and the occurrence of cardiac arrest were significantly related to in-hospital mortality in patients with concomitant acute and concurrent PH. For these reasons, early diagnosis and treatment are essential. However, some studies have shown that clinical prognostic scores (PESI, simplified PESI) have demonstrated excellent accuracy for the identification of patients with low risk of short-term complications and have shown that coexisting TT in normotensive patients with PE did not lead to greater all-cause mortality. However, the data suggest an increased risk of mortality for patients with TT and RV dysfunction. On the other hand, the prognosis is generally good after discharge.

Most TT is detected by TTE in patients diagnosed or suspected of acute PE. Therefore, TTE is an important tool for early recognition. In case of doubt, it would be necessary to perform a transesophageal echocardiogram, which is also useful in the detection of thrombi in PA and in the coexistence of Patent Foramen Ovale (FOP). The presence of FOP should be taken into account as it is a source of paradoxical embolism (emboli originating within the venous system, which passes through a FOP and enters the systemic circulation) and may be a site for the clot to be lodged. Some authors such as Barrios et al  and Bodia favor the surgical removal of these thrombi with simultaneous pulmonary embolectomy due to the imminent risk of displacement, which can lead to massive PE or paradoxical systemic embolism. Despite its prognostic importance, current guidelines do not propose that echocardiography be performed routinely in all patients with acute PE or in all patients with a low-risk PESI assessment. However, they stimulate the evaluation of right ventricular function by echocardiography and / or measurement of cardiac biomarkers if, after clinical evaluation, there is uncertainty about whether patients need more intensive monitoring or thrombolytic therapy [4].

Current guidelines suggest that patients with acute hypotension (ie systolic BP <90 mmHg for 15 min) and no high risk of bleeding should be treated with thrombolytic therapy. The development of hypotension suggests that thrombolytic therapy is indicated. Deterioration that has not resulted in hypotension may also lead to the use of thrombolytic therapy. For example, there may be a progressive increase in HR, a decrease in systolic BP (which remains> 90 mmHg), increased jugular venous pressure, worsening of gas exchange, shock signals (eg, cold sweat, diuresis reduction, confusion ), progressive dysfunction of the right heart on echocardiography, or increase in cardiac biomarkers [4]. However, few studies, only series of cases and retrospective studies, have compared thrombolysis with surgical therapy in acute PE and have recommended considering surgical pulmonary embolectomy in case of hypotension and contraindication for thrombolysis or life-threatening situations such as thrombolysis failure, RV failure, cardiogenic shock and TT.

According to current guidelines, in patients with TT, the therapeutic benefits of thrombolysis remain controversial. Surgical embolectomy is justified in some cases of TT, for example, those with coexistence of FOP. The ideal treatment for concomitant acute and concurrent PH is not currently defined due to the absence of randomized clinical trials and should be considered on a case-by-case basis by multidisciplinary teams following a risk-benefit assessment [4]. Patients who did not receive therapy had a mortality rate of 90 to 100%. In addition, the mortality rate is high (21.1%) in the first 24 hours, which justifies an immediate treatment. Thus, inotropic support with catecholamine infusion should be prepared immediately after the diagnosis of TT and administered as soon as the patient’s blood pressure drops below 100 mm Hg or there is suspicion of cardiogenic shock. It may be preferable to admit patients to an ICU because sudden death is a risk and mechanical ventilation may also be required. Different therapeutic approaches have been reported for acute PE with concomitant TT: anticoagulation with Unfractionated Heparin (UFH), systemic thrombolysis with Recombinant Tissue Plasminogen Activator (RTPA), surgical embolectomy with exploration of the right chambers and pulmonary arteries in complete extracorporeal circulation, and endovascular thrombectomy.

According to Marti (2014), systemic thrombolysis and surgical embolectomy were more likely to survive (81.5% and 70.45%, respectively) than anticoagulation (47.7%). However, there are contradictory data regarding the management of TT; a recent study that included patients with acute RI associated with TT from the RIETE registry showed that there were no significant differences in mortality and bleeding between reperfusion (thrombolysis, surgery) and anticoagulation therapy. Regarding the superiority of thrombolysis or surgical thrombectomy, [4] say that both are effective strategies, with a slight increase in the probability of survival with thrombolysis in some studies. They were, however, plagued by selection bias, small numbers and lack of comparable groups. A prospective, randomized, well-planned study is needed to determine the optimal treatment of acute PD and concomitant TT.

Conclusion

Transit thrombus is an uncommon and severe manifestation of VTE. The high rate of early mortality ensures rapid and effective treatment. Surgical embolectomy in patients with PE and concomitant thrombus in transit may be an effective treatment in selected patients, although the current evidence to support this approach is not definitive.

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