Primary nonfunction is a rare but lethal complication that occurs in a small number of liver transplants. When primary nonfunction occurs, the only definite treatment is retransplant; however, another liver might not be readily available at that time. Hence, a surgeon should be aware of the various options available at hand for patient care during the time interval between the primary nonfunction and retransplant. Here, we describe the management strategy that was devised to take care of an unstable anhepatic patient in the intensive care unit, care of the patient during anhepatic phase, and successful outcome with a second liver transplant. Our index patient was a recipient of a liver donated after cardiac death. While in the operating room, after reperfusion of the liver, the patient had right heart dysfunction leading to hemodynamic instability and congestion of the liver, which culminated in primary nonfunction. Graft hepatectomy had to be done on postoperative day 1 because of deteriorating condition of the patient, and the patient was maintained in anhepatic phase in the intensive care unit for 27 hours.
Key words : Donation after brain death, Donation after cardiac death, Retransplant, Right ventricle systolic function
Primary nonfunction (PNF) is a life-threatening complication after liver transplant known to occur in 4% to 8% of cases.1 In PNF, the nonfunctioning liver can severely compromise recipient hemodynamics and necessitate urgent retransplant. Rescue graft hepatectomy has been described as a means to stabilize recipient hemodynamics. While the anhepatic patient awaits retransplant, meticulous critical care management is essential. A rate of 35% long-term patient survival following rescue hepatectomy with anhepatic time has been reported.2 Here, we describe our management strategy following a recent experience with PNF and a 27-hour anhepatic phase.
Our recipient was a 67-year-old man with hepatitis C cirrhosis and segment VII lesion, radiographically consistent with hepatocellular carcinoma. Preoperative echocardiography was notable for a normal ejection fraction, grade 2 diastolic dysfunction, a hypertrophic septum, and no evidence of pulmonary hypertension.
The original donor was a 35-year-old man, with donation after cardiac death and body mass index (calculated as weight in kilograms divided by height in meters squared) of 36.9, who died from drug overdose with 25 minutes of cardiopulmonary resuscitation time. The terminal value for the aspartate aminotransferase (AST) was 264 IU/dL and alanine aminotransferase ratio (ALT) was 42 IU/dL (peak AST and ALT values were 339 and 123 IU/dL, respectively), total bilirubin was 0.5 mg/dL, and terminal creatinine was 1.2 mg/dL. Total warm ischemia time in the donor was 22 minutes.
Transesophageal echocardiography performed immediately prior to the start of the recipient operation demonstrated a normal left ventricular ejection fraction with mild hypertrophy of the anteroseptal wall. The recipient hepatectomy was uneventful with minimal blood loss (without any blood transfusion) and was performed using standard techniques. Electrolytes, including magnesium and calcium, were corrected prior to the implantation phase. Intravenous heparin (3000 U) was given just before clamping and division of the recipient portal vein. A side-to-side caval anastomosis (piggyback technique) was used for implantation. The recipient remained hemodynamically stable throughout the implantation phase, which lasted for 25 minutes. Just prior to reperfusion, a 500-mL antegrade blood flush through the inferior vena cava was completed. Rapid volume replacement was given, and the mean arterial blood pressure did not deviate more than 20% from preflush values.
Immediately after reperfusion, there was a significant drop in systolic pressure from 116 to 83 mm Hg. Transesophageal echocardiography revealed right ventricular dilatation and mildly reduced right ventricle systolic function. The central venous pressure increased to 32 mm Hg, and the pulmonary artery pressure rose to 65/39 mm Hg. The electrocardiogram first demonstrated widening of the QRS complex and subsequently ventricular tachycardia. The arrhythmia resolved with calcium and amiodarone; however, the pulmonary artery pressure remained significantly elevated, and an epinephrine infusion was started. Right ventricular dysfunction persisted for 20 minutes and then resolved. After reperfusion of the hepatic artery, hyperfibrinolysis was evident in the surgical field, and rotational thromboelastometry (ROTEM) showed severe coagulopathy (EXTEM clotting time of 180 seconds [normal range, 43-82 s] and maximum clot firmness of 7 mm [normal range, 52-80 mm]). Despite vigorous product replacement and administration of aminocaproic acid, the coagulopathy worsened, lactate rose to a peak of 12.1 mg/dL, and there was persistent hypoglycemia. A liver biopsy was performed (Figure 1B). The abdomen was packed, and the patient was transported to the surgical intensive care unit. Lactate rose to > 20 mg/dL and the AST and ALT levels peaked at 13 713 IU/dL and 1650 IU/dL. A bedside laparotomy was required for suspected abdominal compartment syndrome; upon visualization, the liver was congested and ischemic. Continuous veno-venous hemodialysis was started, and the patient was relisted for transplant with a Model for End-Stage Liver Disease score of 27. As the recipient’s clinical status deteriorated, the decision was made to proceed with rescue graft hepatectomy (Figure 1D). An end-to-side portocaval shunt was created, and the patient’s relisting status upgraded to United Network for Organ Sharing (UNOS) status 1A.
After rescue graft hepatectomy, our patient arrived in the surgical intensive care unit on epinephrine (0.05 µg/kg/min) and vasopressin (0.04 U/min).
The following treatment goals were set for management during anhepatic phase: (1) sodium bicarbonate or 3% hypertonic saline to keep the serum sodium between 152 and 157 mg/dL to reduce the risk of intracranial hypertension/herniation; (2) vasopressors as needed for a mean arterial blood pressure goal of 65 mm Hg; (3) continuous venovenous hemodialysis to manage volume and acidosis; (4) continuous fresh frozen plasma administration for an international normalized ratio goal of < 2; (5) continuous dextrose infusion to maintain serum glucose between 110 and 180 mg/dL; (6) initial labs every 2 hours; and (7) therapeutic plasma exchange (the molecular adsorbent recirculating system [MARS] is not currently available at our center).
With these goals met, our patient’s hemodynamics markedly improved. Broad spectrum antimicrobial coverage was provided with ampicillin/sulbactam and fluconazole. Just before retransplant, and after a 27-hour anhepatic phase, the patient was on vasopressin (0.04 µg/kg/min) with mean arterial blood pressure of 70 to 80 mm Hg.
The second donor was a 42-year-old man, with donation after brain death and BMI of 32.7, who died from drug overdose. The terminal AST/ALT values were 141/233 IU/dL (peak AST/ALT, 520/457 IU/dL), total bilirubin was 0.8 mg/dL, and terminal creatinine was 2.2 mg/dL. Total cold ischemic time was 4 hours.
The second transplant was completed expeditiously with a total intraoperative warm time of 20 minutes. Soon after reperfusion, serum lactate dropped from > 20 to 10.1 mg/dL and eventually to 6.6 mg/dL at the completion of the case. Serum glucose rose, coagulopathy resolved, and the surgical field dried. Significant tissue and bowel edema remained, and therefore a staged abdominal closure was completed. The patient was extubated in the surgical intensive care unit on postoperative day 4 and transferred to the transplant floor with serum ALT/AST of 33/20 mg/dL, a total bilirubin of 0.6 mg/dL, serum lactate < 1 mg/dL, international normalized ratio of 1.4, and a fibrinogen of 300 mg/dL. Substantial acute kidney injury occurred and was managed with hemodialysis. The patient was transferred to a skilled nursing facility on postoperative day 17 following the second operation. No neurologic deficits were observed in the postoperative course.
Primary nonfunction is a common cause for early retransplant,3 and often its cause cannot be elucidated. Kulik and colleagues4 have shown that donor hepatic steatosis is an important risk factor for PNF. Steatosis makes livers more vulnerable to ischemia-reperfusion injury.5 In our case, liver biopsy showed 40% macrosteatosis (Figure 1, A and C), and it is likely that donor hepatic steatosis contributed to PNF.
Cardiac dysfunction also contributes to PNF. End-stage liver disease is characterized by a state of high cardiac output and low systemic vascular resistance. During liver transplant, sudden changes in preload and afterload and rapid release of cytokines and other vasoactive mediators into the blood6,7 create significant cardiac stress that frequently unmasks occult cardiac dysfunction.8 Our patient experienced acute and transient right heart dysfunction despite normal preoperative echocardiography and stress testing.
Primary nonfunction is rarely subtle and is diagnosed with progressive lactic acidosis, absence of hepatic glycogenolysis, hypotension, absence of bile production, and prolonged coma. Once PNF is diagnosed, retransplant is the only option for patient survival.
In our patient, recognition of toxic liver syndrome drove our decision to proceed with rescue hepatectomy. The technique of graft hepatectomy with temporary portocaval shunting was first described by Ringe and associates in 1988.9
Goal-oriented critical care management is essential to patient survival in anhepatic phase. Anhepatic patients rapidly develop hypocalcemia, oliguria, renal failure, hypoglycemia, and hypothermia.10,11 Severe hypocalcemia develops because of loss of citrate metabolism in the liver, and hence meticulous replacement is crucial. Continuous dialysis is almost always necessary for management of both acidosis and volume. Fresh frozen plasma and fibrinogen are needed to combat coagulopathy, and continuous glucose infusion is required. Our patient underwent therapeutic plasma exchange with 1.5 times the total plasma volume. Plasmapheresis removes free and protein-bound toxins and provides fresh clotting factors and albumin, thus improving coagulopathy in anhepatic patients.12
In anhepatic patients, broad-spectrum antibacterial and antifungal coverage is indicated and close neurologic monitoring is needed to help ensure that retransplant is not futile. Survival after retransplant is inferior to that after primary transplant, with 64.6% patient survival at 1 year and 47.8% at 5 years.13 Uemura and colleagues14 reported that survival after retransplant for PNF (1 year, 66%; 5 years, 60%; 10 years, 48%) is reduced but not excessive, similar to that after retransplant for other reasons (1 year, 67%; 5 years, 51%; 10 years, 37%) (P = .635).
Transplant hepatectomy can be a life-saving procedure in patients with PNF. Meticulous critical care management with attention to intracranial pressure, glucose, calcium, acidosis, and coagulopathy are essential to facilitate successful retransplant outcomes.
DOI : 10.6002/ect.2020.0129
From the 1Division of Transplantation, Department of Surgery, The Ohio State
University, Wexner Medical Center, Columbus, Ohio, USA; the 2Department of
Anesthesia, The Ohio State University, Wexner Medical Center, Columbus, Ohio,
USA; the 3Department of Pathology, The Ohio State University, Wexner Medical
Center, Columbus, Ohio, USA; and the 4Division of Trauma, Critical Care and
Burn, Department of Surgery, The Ohio State University, Wexner Medical Center,
Columbus, Ohio, USA
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Navdeep Singh, Suite No 160, Comprehensive Transplant Center, 395 W, 12 Avenue, Columbus, Ohio 43210, USA
Figure 1. Images of Postreperfusion Liver Biopsies and Explanted Liver