EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Anesthesia management, Hepatopulmonary syndrome, Pulmonary arteriovenous fistula

Doublecortin domain-containing protein 2 (DCDC2) gene mutations can cause neonatal sclerosing cho-langitis (NSC), a rare and serious progressive biliary fibrosis that eventually progresses to end-stage liver disease (ESLD), necessitating liver transplant (LT) in childhood.¹ The vital clinical findings in NSC include hyperbilirubinemia, jaundice, hepatosplenomegaly, cholestasis, pale stools, and elevated serum gamma-glutamyl transferase activity.^1,2 Extrahepatic findings, involving nephronophthisis, renal cysts, vascular malformations, neurological manifestations, and sensorineural hearing loss, have been described in previous case series.^1-3 In NSC, the bile duct is patent but strictured, and there is no biliary atresia. Children with the DCDC2 variant experience rapidly progres-sive portal hypertension and variceal bleeding within the first 5 years of life. Varicose vein eradication is often difficult in these patients, with only 27.3% eradicated, and recurrent bleeding rates are high. Response to endotherapy is the sole determinant of long-term liver survival, and LT is the only treatment option for those who do not respond.⁴

Hepatopulmonary syndrome (HPS) is a serious complication of ESLD that progresses gradually, and the mortality rate of HPS can be up to 48%. Charac-teristic findings of HPS include hypoxemia, increased alveolar-arterial oxygen gradient at rest in a sitting position breathing room air due to intrapulmonary vascular dilatation (IPVD), and hepatic cirrhosis.^5,6 Although previously contraindicated in patients with HPS due to ESLD because of potential perioperative complications, LT has recently become the gold standard treatment for these patients. Furthermore, the risk of developing arteriovenous fistula (AVF) in patients with HPS is high, which may contribute to the development of hypoxemia; therefore, factors that trigger hypoxemia should be avoided as much as possible.⁶

We report the successful anesthetic management of a deceased donor LT in a patient with ESLD, HPS, and pulmonary AVF due to a DCDC2 mutation. Verbal and written informed consent was obtained from the patient’s parents for publication of our case.

An 8-year-old female patient (height 125 cm, weight 26 kg, body mass index 16.6 kg/m²) with HPS and pulmonary AVF diagnosis, who developed NSC due to a DCDC2 mutation, was admitted to the intensive care unit for LT. The patient was tested by the pediatric metabolism department after birth at aged 3 years. The patient developed portal hypertension, hypersplenism, jaundice, ascites, esophageal varices, tubulopathy, and metabolic acidosis due to cirrhosis. The patient underwent band ligation twice because of esophageal varices. The patient presented with dyspnea, orthodeoxia, platypnea, cyanosis, and weakness.

Transthoracic echocardiography revealed micro-bubbles in the left atrium, but no pulmonary hyper-tension was detected. Lung perfusion scintigraphy showed a 20% intrapulmonary right-to-left shunt, and pulmonary arteriography demonstrated diffuse IPVD and pulmonary AVF. The liver computed tomography angiography revealed a diffuse hepatoportal shunt and splenomegaly in irregular areas of the liver parenchyma (Figure 1).

During follow-up, the patient was scheduled for living donor LT due to reduced arterial oxygen saturation (83%), dyspnea, orthodeoxia, platypnea, increasing cyanosis, and hypoxemia. On room air in the supine position, venous oxygen pressure was 59.5 mm Hg and O₂ saturation was 85%; in the sitting position, venous oxygen pressure was 45.7 mm Hg and O₂ saturation was 68.9%. Preoperative hemog-lobin (11.3 g/dL), hematocrit (33.9%), platelets (66 × 10³/mL), alanine aminotransferase level (126 IU/L), aspartate transaminase level (107 IU/L), gamma-glutamyl transferase (107 IU/L), total bilirubin (1.9 mg/dL), direct bilirubin (1.2 mg/dL), albumin (2.7 g/dL), and international normalized ratio (1.1) were normal.

The patient’s Child-Pugh-Turcotte score was B, and the Pediatric End-Stage Liver Disease score was 6.4. The patient’s physical classification, as deter-mined by the American Society of Anesthesiologists, was class III, and the Mallampati score was II.

The deceased donor was a 13-year-old male patient (weight 50 kg, height 168 cm); cause of death was subarachnoid hemorrhage due to a traffic accident. Standard monitoring tests, including elec-trocardiogram, peripheral oxygen saturation (SpO₂), noninvasive blood pressure, capnography (end-tidal carbon dioxide), temperature, and bispectral index, were performed. After 3 minutes of preoxygenation with 80% O₂, anesthesia was induced with lidocaine, propofol, fentanyl, and rocuronium. Intubation was performed without complications using a size 6.0 cuffed endotracheal tube, and the patient was connected to a ventilator. The mean arterial pressure was targeted as >60 mm Hg throughout the surgery, and norepinephrine infusion (0.02-0.5 mg/kg/min) was initiated for hypotension.

A 1050-g liver tissue was extracted from the patient (Figure 2), and a 1000-g deceased donor liver was implanted (Figure 3). After the dissection phase, anastomosis of the great vessels was completed during the anhepatic phase, which lasted about 68 minutes. The clamp on the portal vein was removed, and reperfusion was started. The patient’s blood pressure dropped to 60/32 mm Hg 2 minutes after reperfusion, and norepinephrine infusion dose was raised; ephedrine and calcium chloride were administered twice.

Doppler ultrasonography performed at the end of the surgery revealed normal perfusion in the portal vein, hepatic artery, and hepatic venous system (Figures 4, 5, and 6). Postoperatively, the patient was intubated and ventilated, with fraction of inspired oxygen (FiO₂) at 40% and SpO2 between 85% and 92%. On day 2, SpO₂ ranged from 89% to 94%.

With resolution of hypoxemia, the patient was extubated, and SpO₂ remained normal on room air. The patient’s hemodynamic state, condition, and consciousness were stable, and blood gas and lactate values, as well as liver transaminases, returned to reference values within a few days. Immunosup-pressive medications, steroids, and other necessary treatments were administered. The patient was transferred to the hospital ward on day 4 of follow-up and discharged 14 days after surgery without any postoperative complications.

To our knowledge, we have described for the first time in the literature the anesthetic management of LT in a patient who developed NSC due to a DCDC2 mutation. Our patient had many clinical and physical disorders as a result of NSC and because of HPS and pulmonary AVF, which made LT quite challenging for us in terms of both anesthesia and surgery.

Although any NSC arising from a patient with a DCDC2 mutation is complex, we recommend that the anesthesiologist’s plans of anesthesia management during LT primarily consider the disease’s pathophys-iology and associated comorbidities. The mortality rate as a result of HPS is quite high in these children without LT, with pulmonary and intracranial hemorrhage, portal vein thrombosis, infection, sepsis, and multiorgan failure being the most significant causes of death.5 The mortality rate is 30% in LT candidates with severe preoperative hypoxemia (partial arterial oxygen pressure <50 mm Hg). Even after successful LT, these patients may require prolonged mechanical ventilation.^5,6 Hypoxemia in patients with HPS who have intrapulmonary right-to-left shunts and pulmonary AVFs can worsen the clinical picture during surgery. Therefore, to safely anesthetize patients with HPS, whether with or without a pulmonary AVF, situations that could worsen hypoxemia and increase pulmonary vaso-dilation should be avoided as much as possible.⁶

Our patient had platypnea, orthodeoxia, and dyspnea before surgery. In the supine position, venous oxygen pressure was 59.5 mm Hg and SpO₂ was 85%; in the sitting position, venous oxygen pressure was 45.7 mm Hg and SpO₂ was 68.9%. We successfully performed LT in our patient (8-year-old girl with HPS due to NSC caused by the DCDC2 mutation and pulmonary AVF) who had room air SpO₂ of 84% to 88% and intrapulmonary right-to-left shunt of 20%.

Postreperfusion syndrome can trigger and worsen hypoxia by increasing the shunt fraction in patients with pulmonary AVF and HPS.⁶ In our case, after the development of postreperfusion syndrome, short-term hypoxemia occurred intraoperatively due to HPS and pulmonary AVF. Our anesthesia plan aimed to minimize factors that could trigger hypoxemia and hypercarbia. We attempted to treat this by increasing inspiratory pauses and mechanical ventilator pressures. Patients with HPS and pulmonary AVF are at rise risk for paradoxical embolism. We were careful to prevent air from entering the surgical field during the operation and to prevent air bubbles from forming during fluid or drug administration.^5-7 We attempted to keep pulmonary end-expiratory pressure at 4 to 6 mm Hg. Because our patient had HPS and AVF, we used pulse contour cardiac output to closely monitor for potential hemodynamic and oxygenation difficulties.

Lee and colleagues⁸ reported a 9-year-old girl with HPS and diffuse pulmonary AVF due to ESLD caused by biliary atresia who underwent living donor LT. The investigators used total intravenous anesthesia as an anesthetic management method to prevent further shunting and hypoxemia and successfully performed LT. We successfully performed deceased donor LT in our 8-year-old female (Child-Pugh-Turcotte class B, Pediatric End-Stage Liver Disease score 6.0) with HPS, pulmonary AVF, a 20% intra-pulmonary right-to-left shunt, and diffuse IPVD due to the DCDC2 mutation. Our anesthesia plan aimed to minimize factors that could trigger hypoxemia, hypercarbia, and shunting.

Postoperative hypoxemia and intrapulmonary shunt recovery time are related to the severity of preoperative hypoxemia. In most cases, HPS-related hypoxemia resolves within 1 year after LT.⁶ After transplant, our patient was intubated and ventilated, with fraction of inspired oxygen of 40% and SpO₂ between 85% and 92%. On day 2, SpO₂ ranged from 89% to 94%. With hypoxemia resolved, the patient was extubated after weaning. After 2 days of 2 L/min mask oxygen supplementation, SpO2 remained normal on room air.

Our patient had multiple clinical abnormalities (HPS and pulmonary AVF due to NSC resulting from the DCDC2 mutation), making LT quite challenging from both the anesthesia and surgical perspectives. Liver transplant performed with successful anesthesia and surgical management can lead to improved oxygenation, shunt regression, and improved outcomes, improving prognosis, reducing mortality rates, and enhancing quality of life. Anesthesiologists and surgeons should be knowledgeable about comprehensive preoperative evaluation, underlying pathophysiology, and close intraoperative moni-toring in patients with HPS and pulmonary AVF due to NSC from the DCDC2 mutation.

Volume: 24 Issue: 5 May 2026

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