Extracorporeal membrane oxygenation (ECMO) is used in cases of severe cardiac and/or respiratory dysfunction. End-stage liver disease is sometimes associated with hepatopulmonary syndrome (HPS), which is due to excess pulmonary vasodilators.1 The excess pulmonary vasodilators cause intrapulmonary shunting and abnormal gas exchange. Pulmonary angiogenesis also occurs and exacerbates the pulmonary vasodilation and ultimately pulmonary vascular remodeling.1 Hepatopulmonary syndrome can lead to severe hypoxemia either before or after liver transplant and is associated with a poor prognosis. Liver transplantation is the only curative intervention. However, the medical management of HPS following liver transplantation is difficult due to what some believe is the abrupt cessation of intrinsic production of pulmonary vasodilators and the impact of the pulmonary vascular remodeling that has occurred.1 This pulmonary vascular remodeling and cessation of pulmonary vasodilator production can lead to increased ventilation and perfusion mismatching in the early postoperative period. Nayyar et al.1 suggest that the posttransplant management of HPS include initiation of inhaled pulmonary vasodilators (nitric oxide [iNO] and epoprostenol), then followed by intravenous pulmonary vasoconstrictors (methylene blue). The administration of inhaled vasodilators to well-ventilated areas of the lungs and administration of intravenous vasoconstricting medications to well-perfused areas of the lungs may allow the medications to work synergistically. However, the optimal medical management of HPS is unclear.1 Previous case reports in adults and children report the successful use of ECMO support for severe HPS when medical management has failed.2–7
This is a 19-month-old female who presented from an outside hospital to our transplant center with end-stage liver disease secondary to biliary atresia. She was born at 3.8 kg, at 37 weeks gestation, and delivered by Cesarean section. At 119 days of life, she underwent Kasai portoenterostomy, which did not drain. Her liver disease progressed, and she developed jaundice, portal hypertension, hematochezia, and a persistent oxygen requirement after multiple admissions for bronchopneumonia. Following her admissions, she had pulmonary vascular dilation demonstrated by the appearance of agitated saline contrast in the left atrium within three cycles on transthoracic echocardiogram and transesophageal echocardiogram. With these findings in the setting of end-stage liver disease, she was diagnosed with HPS. At the time of evaluation, at our transplant center, she weighed 6.9 kg and was in her baseline state of health. She required high-flow nasal cannula at 8 liters per minute and fraction of inspired oxygen 0.8 to keep her oxygen saturation greater than 80% (Table 1 details laboratory values at major events in her clinical course including preoperative evaluation). During the evaluation, the patient was noted to have an interrupted inferior vena cava (Figure 1). She was deemed an appropriate candidate for transplant and underwent orthotopic living donor liver transplantation utilizing a left lateral graft (Figure 2). She remained intubated following the procedure and oxygenation initially improved. On postoperative day 3, her respiratory function acutely worsened and her clinical condition was managed with increased positive end-expiratory pressure, inhaled epoprostenol, and iNO. Due to concern of ventilation-perfusion mismatching leading to hypoxemia, the patient was given a trial of pulmonary vasodilators. She transiently responded to pulmonary vasodilators with improved oxygenation consistent with HPS exacerbation. Her chest radiograph at that time was not consistent with pneumonia, acute respiratory distress syndrome, pulmonary edema from cardiomyopathy or volume overload, or sepsis. She acutely deteriorated on postoperative day 7, so a trial of methylene blue was instituted. She was then on a mean airway pressure of 19, a fraction of inhaled oxygen of 1.0, and a PaO2 of 34 mm Hg for an oxygenation index of 55.9. After failing maximal medical efforts to correct her hypoxemia, she was taken to the operating room for initiation of ECMO.
The interrupted inferior vena cava and recent anastomosis just below the level of the right atrium increased the risk of placing a bi-caval cannula, the preferred method in children at our institution. Given our patient’s unique anatomy and recent surgical history, our team felt that a right internal jugular approach with a mid-right atrial dual lumen venovenous cannula (Origen Biomedical, Austin, TX) would provide the best approach to cannulation and extracorporeal life support (Figure 3).
The patient had bleeding complications during the ECMO course. Due to her postoperative state, the initial anti-factor Xa (aXa) goal was set at 0.3 IU/mL (normal institutional goal of 0.3–0.6 IU/mL). The heparin infusion was titrated reaching a maximum dose of 53 u/kg/hr, within the set aXa goal parameter. On postoperative day 4, the patient abruptly dropped her hemoglobin levels, had a change in quality of the intra-abdominal drain output, and blood from her endotracheal tube. The heparin infusion was stopped. Therapeutic bronchoscopy to remove obstructing clots from her airway and re-exploration of the abdomen to remove clot and place additional drains were performed. There was no evidence of surgical bleeding, only oozing from raw surfaces. At this point, her coagulation panels had normalized, thromboelastography was normal, and clinical suspicion for heparin-induced thrombocytopenia was low and anti-PF4 antibodies were undetectable. We hypothesized that ongoing bleeding was likely related to the large raw surface area from the explanted liver and coagulopathy from the newly generated coagulation factors from the allograft leading to dysfunctional clotting cascade. She continued to have slow oozing from multiple sites and ongoing transfusion requirements without medical anticoagulation. On ECMO day 8, hemorrhage stopped with the administration of activated factor VII (aFVII) (45 mcg/kg per dose for two doses 9 hours apart) and aminocaproic acid. On ECMO day 10, hemostasis was achieved, and low-dose heparin infusion (15 u/kg/hr) was restarted. On ECMO day 11, the rate of heparin infusion was increased based on a lower therapeutic aXa target level of 0.2 IU/mL. The patient had another episode of medical hemorrhage on ECMO day 15, which required cessation of heparin and additional doses of aFVII (45 mcg/kg/dose every 6 hours for four doses) and aminocaproic acid. Heparin was not restarted for the remainder of the ECMO run, and there were no thrombotic or mechanical circuit complications.
The patient improved and weaned from ECMO support and was decannulated on ECMO day 17. She remained on mechanical ventilator support for an additional 2 days. Then she was extubated to high-flow nasal cannula and weaned to room air over the subsequent 2 weeks and was discharged home off oxygen on postoperative day 77. Since discharge, she continues to gain weight, remains off oxygen, and is without signs of rejection.
Previous authors describe the successful use of ECMO in pre- and posttransplant adult patients.2–6 This is only the third pediatric patient with HPS requiring ECMO identified in the literature, and only the second using venovenous ECMO.3,4 In this case, we describe a unique indication for ECMO and approach to cannulation. Additionally, this report describes the youngest and smallest patient treated with ECMO for HPS.3,4 The use of a mid-right atrial dual lumen venovenous cannulation approach for HPS is also unique to this case. The cannula functioned well and provided sufficient flow to support the patient during a 17-day ECMO run with minimal recirculation. Although we experienced bleeding complications, this is common in postlaparotomy patients on ECMO.8 With close attention to therapeutic anticoagulation targets, replacement of blood products, temporary cessation of heparin, reversal of anticoagulation with aFVII, and surgical evaluation of hemorrhage, we were able to control the bleeding and successfully provided the extracorporeal life support. Posttransplant ECMO may provide patients with HPS and severe posttransplant hypoxemia a period of support for their pulmonary vessels to remodel and allow for recovery from HPS.
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