EXPERIMENTAL AND CLINICAL TRANSPLANTATION

In this report, we present a case of successful long-term salvage of a patient with transfusion-related acute lung injury associated with acute respiratory distress syndrome immediately after a liver transplant. The patient was a 29-year-old man with end-stage liver disease due to sclerosing cholangitis who underwent liver transplant. After organ reperfusion, there was evidence of liver congestion, acidosis, coagulopathy, and acute kidney injury. He received 61 units of blood products. Continuous renal replacement therapy was initiated intraoperatively. On arrival to the intensive care unit, the patient was on high-dose pressors, and the patient developed respiratory failure and was immediately placed on veno-arterial extracorporeal membrane oxygenation via open femoral exposure. The patient presented with severe coagulopathy and early allograft dysfunction; therefore, no systemic heparin was administered and no thrombotic events occurred. He required extracorporeal membrane oxygenation support until posttransplant day 4, when resolution of the respiratory and cardiac dysfunction was noted. At 2 years after liver transplant, the patient has normal liver function, normal cognitive function, and stage V chronic kidney disease. We conclude that extracorporeal membrane oxygenation is a valuable therapeutic approach in patients with cardiorespiratory failure after liver transplant.

Key words : Acute kidney injury, Acute lung injury, End-stage liver disease

Acute respiratory distress syndrome (ARDS) presents with noncardiogenic pulmonary edema, dyspnea, and hypoxemia and can complicate the postoperative course in noncardiac surgery. Mortality in patients with ARDS remains high despite the progress made in treatment. One of the risk factors for ARDS is transfusion-related acute lung injury (TRALI).¹ Transfusion-related acute lung injury may arise in critically ill patients within 6 hours of a massive transfusion.² For the past 4 decades, extracorporeal membrane oxygenation (ECMO) has been utilized for refractory respiratory and cardiopulmonary failure when treatment with traditional pressor support and mechanical ventilation fails.³ It can offer a last-means option of resuscitation for the otherwise moribund patient, and evolution of this technology has allowed for temporary or even long-term support of the patient in cardiac and pulmonary collapse.⁴ There are significant reservations about the use of ECMO in postoperative settings after nonthoracic surgery because of the limited survival potential.

One of the rare clinical scenarios in which ECMO is applied is after liver transplant. Intraoperative and postoperative complications of liver transplant may include shock related to multiple factors, including myocardial dysfunction, acute lung injury, hemorrhage, vasodilation, and sepsis. There are fewer than 20 cases reported in the English literature on the use of ECMO in the immediate setting after liver transplant, with more cases reported in the Asian literature.⁵ These reports indicate a dismal rate of survival, but there has been an increasing potential benefit as ECMO technology evolves and liver transplant expands. Here, we present a case of successful long-term recovery of a patient with TRALI-associated ARDS immediately after liver transplant.

The patient was a 29-year-old man with end-stage liver disease caused by sclerosing cholangitis with a Model for End-Stage Liver Disease (MELD) score of 13 who underwent liver transplant. His past medical history was significant for an extrahepatic choledochal cyst resected at 12 days of age, with biliary reconstruction via Roux-en-Y choledochojejunostomy.

The liver donor was a young man in the third decade of life who was diagnosed with brain death after head trauma. Liver biopsy indicated 40% to 50% macrosteatosis. The liver was implanted using a caval interposition technique, with standard portal vein and hepatic arterial reconstructions. Intraoperatively, the liver was noted to be severely congested upon reperfusion. Intraoperative transesophageal echocardiography and ultrasonography revealed severe suprahepatic vena cava stenosis with caval thrombus at and below the hepatic veins, with evidence of intracardiac thrombosis. A caval thrombectomy was performed with revision of the suprahepatic caval anastomosis. After these events, there was clear evidence of liver dysfunction, acidosis, coagulopathy, and acute kidney injury. He received 70 units of blood products (47 packed red blood cells, 15 fresh frozen plasma, 3 platelets, 5 cryoprecipitate). The estimated blood loss was approximately 12.5 L. Continuous renal replacement therapy was initiated intraoperatively. The patient’s biliary tree was exteriorized, and his abdomen was temporarily closed.

On arrival to the intensive care unit, the patient was on high-dose pressors (norepinephrine, epinephrine, vasopressin, phenylephrine) and required mechanical ventilation support (high-pressure-controlled ventilation with positive end-expiratory pressure of 12 and fraction of inspired oxygen [FiO2] at 100% but resultingly low tidal volumes). He was acidotic and in multiorgan failure. He was severely anemic, thrombocytopenic, and coagulopathic. His serum lactate level was 16 mmol/L with associated pH 7.16. He quickly developed disseminated intravascular coagulation (DIC) and ARDS secondary to TRALI (ejection fraction of 15% on echocardiogram). A diagnosis of TRALI was made, considering the large amount of blood products received, dyspnea, hypotensive state, and the lack of primary causes of acute lung injury. He developed a mixture of obstructive, vasodilatory, cardiogenic, and hemorrhagic shock. Clinical evaluation demonstrated copious frothy bronchorrhea from the endotracheal tube, which made mechanical ventilation impossible.

He was immediately placed on veno-arterial (V-A) ECMO via open femoral exposure. An 8-mm graft (Hemashield; Maquet, Rastatt, Germany) was sewn to the femoral artery in an end-to-side fashion for arterial cannula access. A 25F Medtronic venous cannula (Medtronic, Inc.; Minneapolis, MN, USA) was then placed into the right atrium and superior vena cava via the right femoral vein. Initial ECMO settings were as follows: 4.1 L/min, 3700 rpm; sweep, 6 L/min; capillary venous oxygen saturation of 98.5%.

Table 1 demonstrates ECMO parameters over the first 4 days after transplant. No thrombotic events occurred despite a lack of systemic heparinization. The patient required ECMO support until posttransplant day 4, when resolution of the respiratory and cardiac dysfunction was noted (Figure 1 and Figure 2).

He returned to the operating room for biliary reconstruction, definitive abdominal closure, and ECMO decannulation. Final ECMO settings were as follows: 3.5 L/min; 2700 rpm; sweep, 0.8 L/min; and oxygen saturation of 50% (Table 1). He required a tracheostomy, dialysis, and enteral nutrition support. Liver function normalized after a prolonged period of cholestasis, with peak bilirubin of 49.1 mg/dL on posttransplant day 16 (Figure 3).

Extracorporeal membrane oxygenation-specific complications included a cannulation-site lymphocele, multidrug-resistant infection that required operative debridement, femoral arterial patch angioplasty, and local soft-tissue flap coverage. He also developed critical illness-related myopathy and hypoxic brain injury identified on magnetic resonance imaging. He was discharged from the hospital in an ambulatory state 96 days after liver transplant. At 2 years after liver transplant, he has normal liver function, normal cognitive function, and stage V chronic kidney disease and no dialysis dependence.

Extracorporeal membrane oxygenation has been successfully used for cardiac and respiratory failures in recent years.6 According to the Extracorporeal Life Support Organization guidelines, during hypoxic failure, ECMO should be considered when mortality risk is 50% (alveolar oxygen partial pressure [PaO2]/FiO₂ < 150 on FiO₂ > 90%) and is indicated when mortality risk is 80% (PaO2/FiO₂ < 100 on FiO₂ > 90%), as in the presented case.⁶ The selection of V-A versus veno-venous cannulation is dependent on the cardiac function; veno-venous cannulation is preferred with normal cardiac function.6 In our case, we proceeded with V-A cannulation because of the patient’s hemodynamic instability. In liver transplant, reports of successful ECMO utilization with good outcomes are recent, and such reports are scarce. There are inherent complications related to cannula placement, sepsis, cardiac thrombosis, cerebral hypoxia, and mechanical complications.⁷

The liver posttransplant setting adds another layer of complexity to treatment of patients who may require ECMO support for cardiopulmonary failure. There is an inherent risk of bleeding from the postoperative coagulopathy after the obligatory ischemia/reperfusion-related graft injury. In this case, a decision was made to forego the use of heparin during the V-A ECMO run and to use high pump flows to reduce thrombotic complications. Our patient did not experience thrombotic events; this allowed for adequate organ recovery while maintaining oxygenation, as well as rapid weaning from ECMO with resolution of pulmonary edema and acute lung injury. Extracorporeal Life Support Organization guidelines recommend the use of an anticoagulant (unfractionated heparin is most widely used) to prevent thrombosis; however, this has been associated with adverse events of increased bleeding.⁶ The criteria for the use of an anticoagulant during ECMO are difficult to assess. In our case, patient’s coagulopathic state resulting from DIC increased the risk of bleeding. There have been reports, similar to our case, of successful ECMO use without anticoagulants; however, close monitoring is required.⁸

There are 2 clear areas where ECMO is being used in the posttransplant setting: (1) for patient care after cardiopulmonary failure related to shock and systemic inflammatory response and (2) as treatment for persistent hypoxia in the posttransplant setting in patients with severe hepatopulmonary syndrome. A recent US study from the University of California, San Francisco, reported the use of ECMO on 8 patients after liver transplant to treat various etiologies; only 3 survived with durable recovery.⁵ The safe and successful utilization of ECMO has also been shown in posttransplant cardiogenic shock from stress-induced cardiomyopathy.⁹ Other reports have previously shown successful use of ECMO due to TRALI following other abdominal surgeries.^1,10 It has also been utilized to maintain adequate ventilation during the lung’s healing process after more traditional means were unsuccessful.

For patients with hepatopulmonary syndrome, posttransplant hypoxemia can be persistent and may be refractory to other treatments.¹¹ Kumar and colleagues showed safe utilization of ECMO in a patient with hepatopulmonary syndrome after liver transplant.¹² Nayyar and colleagues even proposed a treatment algorithm for patients in the same circumstances; they recommended ECMO only after failed epoprostenol, inhaled nitric oxide, and intravenous methylene blue.¹³

Duration of ECMO is variable and can range from hours to months. In a recent study of 7 patients placed on EMCO support after liver transplant over a period of 5 years,¹⁴ median duration on EMCO was 7 days, with an in-hospital mortality rate of 28.6%.¹⁴ In our case, the patient was weaned from ECMO after 4 to 5 days and the patient remains alive at the 2-year follow-up. Sharma and colleagues published a mortality rate of 50% for liver transplant recipients on ECMO.¹⁵

The patient’s clinical status and our center’s expertise in both transplant and circulatory support technologies are important variables in the decision to use ECMO. We advocate for its use in the setting of reversible organ dysfunction with good long-term life expectancy.

Extracorporeal membrane oxygenation is a valuable therapeutic approach, and its use should be considered with in patients with cardiopulmonary failure after liver transplant when appropriate.

Volume: 20 Issue: 6 June 2022

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