Intrapulmonary Shunting and Paradoxical Air Embolism in Liver Transplantation: A Case Report

Introduction

A paradoxical air embolism (PAE) occurs when air entering the central venous circulation reaches systemic circulation through a right-to-left shunt, which may be due to a cyanotic congenital heart defect, atrial septal defect (ASD), patent foramen ovale (PFO), or intrapulmonary shunting (IPS). Patients presenting for liver transplantation (LT) frequently have some degree of pulmonary arterial vasodilation, which can contribute to right-to-left shunting even in the absence of hepatopulmonary syndrome (HPS) [1]. The incidence of intrapulmonary shunting in patients with end-stage liver disease may be as high as 47% [1]. Subclinical PAE during orthotopic LT is frequently detected using intraoperative transesophageal echocardiography (TEE). PAE can involve the coronary arteries (leading to myocardial ischemia) or cerebral vessels (leading to ischemic stroke), but serious complications or cases of hemodynamic collapse due to PAE are rare [2–4]. Here, we present a case of severe biventricular dysfunction following allograft reperfusion during an orthotopic LT with hemodynamic collapse preceded by detection of transpulmonary air into the left atrium, left ventricle, and ascending aorta using TEE and ST-segment changes on electrocardiography (ECG) monitoring.

Case Report

A 60-year-old man (75 kg, BMI 25) with history of end-stage liver disease secondary to non-alcoholic steatohepatitis (NASH), mild coronary artery atherosclerosis, hypertension, hyperlipidemia, and insulin-dependent type 2 diabetes presented for donation after circulatory death (DCD) orthotopic LT with utilization of normothermic machine perfusion (NMP) of the allograft. His liver disease was complicated by hepatic encephalopathy, ascites, thrombocytopenia, sarcopenia, and esophageal varices with prior banding. His Model for End-Stage Liver (MELD) sodium score was 17.

Preoperative cardiac evaluation included a transthoracic echo-cardiogram (TTE) showing a left ventricular ejection fraction (LVEF) of 62% by three-dimensional echocardiography and a borderline enlarged right ventricle (RV) with normal function, and no significant valvular disease, but moderate IPS was detected. Dobutamine stress echocardiography demonstrated positive apical myocardial ischemia. Further evaluation with coronary catheterization demonstrated diffuse mild coronary artery disease (less than 50% stenosis), requiring no intervention.

Anesthesia was induced with intravenous midazolam, fentanyl, lidocaine, propofol, and rocuronium. Intraoperative monitoring included standard ASA monitors, intra-arterial catheter blood pressure monitoring, central venous pressure monitoring, and TEE. Baseline TEE revealed normal left ventricle (LV) size, LVEF of 53% by three-dimensional echocardiography, normal RV function, mild tricuspid regurgitation, mild mitral regurgitation, trace aortic insufficiency, no PFO by color flow Doppler, and moderate IPS with air bubbles seen coming from the pulmonary veins.

The orthotopic LT proceeded uneventfully throughout the dissection and anhepatic phases. The DCD liver allograft was per-fused for 10 h 14 min using portal vein, hepatic artery, and suprahepatic vena cava cannulas prior to removal from normothermic machine perfusion. The allograft was flushed with 500 ml of circulating blood prior to unclamping of the portal vein and liver reperfusion. Hemodynamics were maintained throughout the initial 5 min after liver reperfusion, with minimal vasopressor requirements, but there appeared to be air bubbles transiting the pulmonary system. Air bubbles were seen in the left atrium and LV and were seen coming from the left upper pulmonary vein (Figure 1), and no interatrial shunting was detected (Figure 2). Air bubbles were seen crossing the aortic valve and into the sinus of Valsalva (Figure 3). Significant ST-segment depression was seen on the V5 ECG lead, and hypotension developed approximately 6 min after reperfusion, with blood pressure decreasing to 63/34 and CVP rising to 30. TEE revealed severe RV dysfunction as well as LV dysfunction with mid- to apical anteroseptal wall motion abnormalities and moderate-to-severe functional mitral regurgitation. After this acute decompensation, which occurred over approximately 1–2 min, it was thought that a PAE to the coronary arteries had led to myocardial ischemia and severe biventricular dysfunction. The patient was ventilated with 100% fractional inspired oxygen and required high doses of vasopressor and inotropic support with epinephrine, vasopressin, and norepinephrine. The patient required increasing doses of inotropic and vasopressor support over a 20-min period from the time of initial hemodynamic decline. Epinephrine was used for ino-tropic support to increase cardiac output to reduce the severe hepatic congestion of the liver allograft. Inhaled nitric oxide (iNO) was initiated to optimize right ventricular function. We considered using an intra-aortic balloon pump to optimize coronary perfusion pressure and potentially drive intracoronary air antegrade to restore coronary blood flow; however, over the course of 30 min, there was significant improvement in biventricular function, resolution of ST-segment changes and substantial reduction in vasopressor and inotropic requirements. The hepatic artery and biliary anastomoses were completed successfully, and the patient’s hemodynamics and ventricular function continued to improve throughout the remainder of the neo-hepatic phase. Intraoperatively, the patient received 12 units of packed red blood cells, 3 units of fresh frozen plasma, 2 units of platelets, 6 pack of cryoprecipitate, 3 liters of crystalloid, and 4 liters of colloid.

Immediately after surgery, he was transferred to the Intensive Care Unit (ICU) for close monitoring and subsequent management. Upon arrival to the ICU, he remained intubated on epinephrine 0.02 mcg/kg/min, vasopressin 0.04 units/min, and 20 parts per million of iNO. Postoperative troponins were elevated at 123 ng/L and increased to 1501 ng/L over the first 12 h after surgery; however, ECG showed normal sinus rhythm with no acute ST-T wave ischemic changes. A postoperative transthoracic echocardiogram revealed a LVEF of 57%, normal RV function, no significant valvular heart disease, normal IVC, and mild apical wall motion abnormalities. The patient was subsequently extubated with no neurologic deficits and did not require any coronary artery intervention. He was discharged to home on postoperative day 7.

Discussion

This case demonstrates the utility of TEE to detect IPS and to diagnosis what was believed to be a PAE to the coronary arteries causing acute severe biventricular dysfunction following reperfusion during orthotopic LT.

It has long been known that IPS can occur with chronic liver disease. In 1966, Berthelot et al reported marked arterial changes and pulmonary arteriovenous shunts in the postmortem lungs of patients with liver disease [5]. Hopkins et al found 47% of patients with end-stage hepatic disease had contrast echocardiographic evidence of intrapulmonary right-to-left shunting [1]. Case reports have also described cerebral emboli secondary to IPS associated with HPS [6].

It seems likely that our patient’s underlying mild diffuse coronary artery disease may have made him especially susceptible to myocardial ischemia due to intracoronary air. Given that the origin of the right coronary artery (RCA) is in an anterior position within the sinus of Valsalva and is most susceptible to air embolism in the supine patient, we suspected a significant burden of air within the RCA as the cause of the RV dysfunction and ST-segment depression in V5. It is difficult to know if the LV dysfunction was caused by a PAE into the left main coronary artery or due to hypoperfusion-mediated ischemia in the setting of hypotension and underlying coronary artery disease. The pattern of LV regional wall abnormalities followed the distribution of the left anterior descending artery, which would be more prone to air than the left circumflex given its more anterior orientation. It seems likely that the improvement in hemodynamics after approximately 30 min represented improved myocardial oxygen delivery as the intracoronary air was absorbed. While an intra-aortic balloon pump was considered as a strategy to maintain coronary perfusion pressure and increase cardiac output, it should be noted that another potential strategy would have been to use peripheral venoarterial extracorporeal membrane oxygenation to provide hemodynamic stability and decrease hepatic venous congestion.

There are a number of clinical scenarios that can occur at the time of liver reperfusion and lead to hemodynamic instability, including systemic vasodilation, hypovolemia, acute right ventricular dysfunction, pulmonary hypertension, intracardiac thrombus formation, cardiac arrhythmias, acute coronary syndrome, or air embolism. The cause of a post-reperfusion syndrome is not always known; however, TEE is a powerful tool to help diagnose the cause of hemodynamic perturbations and guide perioperative management.

At the time of liver perfusion there is often a heavy burden of air bubbles entering the right heart, which is frequently seen during TEE monitoring. Although the source of intracardiac air is not certain, we believe it was likely from entrapment into blood vessels within the allograft during routine handling during procurement and preparation for implantation into the recipient, as this is known to occur during organ transplantation. Other cases of PAE have occurred during the dissection phase, where hepatic veins may be open to the atmosphere, allowing for continued entrapment of venous air and often requires flooding the surgical field with saline. These large air embolisms can also obstruct blood flow in the right ventricular outflow tract due to formation of an air-lock, which can potentially be relieved by placing the patient in a lateral position, although this was not seen during our case. The degree of air burden entering the right atrium in our patient did not exceed that which is typically observed with TEE during reperfusion, and only occurred at the time of reperfusion. It is also worth noting that air embolisms can occur during machine perfusion [7], potentially as a result of intravascular air entrapment from an incompletely sealed intravascular cannula, although machine perfusion can also wash out previously entrapped intravascular air due to continual flow through the allograft during preservation [8]. It is important to recognize the possibility of PAE during the time of reperfusion, which can be due to right-to-left shunting through a PFO or ASD from acute increases in right heart pressure, such as in the case of sudden RV dysfunction, increases in pulmonary vascular resistance, or increased preload. PAE can also occur due to IPS, as in our patient. This case demonstrates the possibility of clinically significant PAE through IPS in a patient without HPS or any documented preoperative hypoxemia and should be considered in cases of hemodynamic instability in LT, especially if air is seen within the left heart.

Conclusions

PAE through intrapulmonary shunting occurs in patients presenting for liver transplantation, even in the absence of a clinically significant hepatopulmonary syndrome. PAE rarely causes hemodynamic collapse during orthoptic liver transplantation, although can involve the coronary arteries and lead to significant myocardial dysfunction. TEE can detect PAE by visualization of air entering the left atrium through pulmonary veins and should be used to guide diagnosis and management. TEE can be useful in diagnosing causes of hemodynamic compromise during liver transplantation, as well as other complications of intracardiac air, such as formation of an air-lock.