EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Primary hyperoxaluria type 1 is an autosomal recessive disorder that is responsible for the overproduction of oxalate and has an incidence of 1 in 120 000 live births. Indications for combined liver and kidney transplant are still debated. However, combined liver and kidney transplant is preferred in various conditions, including primary hyperoxaluria, liver-based metabolic abnormalities affecting the kidney, and structural diseases affecting both the liver and the kidney, such as congenital hepatic fibrosis and polycystic kidney disease. When compared with sequential liver and kidney transplant, the rejection rate of both liver and kidney allografts was reported to be lower than with combined liver and kidney transplant. With proper anesthesia management, the probable increased complications with combined liver and kidney transplant can be prevented. In this report, we present the anesthesia care of a 22-year-old patient with primary hyperoxaluria type 1 who had deceased-donor combined liver and kidney transplant.

Key words : Primary hyperoxaluria, Combined liver and kidney transplant, Anesthesia

Indications for combined liver and kidney transplant (CLKT) include primary hyperoxaluria (PH) and other liver-based metabolic abnormalities affecting the kidney and structural diseases affecting both the liver and kidney, such as congenital hepatic fibrosis and polycystic kidney disease.¹ Patients with primary hyperoxaluria, a rare autosomal recessive disorder, have overproduction of oxalate. Primary hyperoxaluria type 1 is the most common, with an incidence of about 1 in 120 000 live births.² In those with PH type 1, the liver-specific paroxysmal alanine-glyoxylate aminotransferase enzyme does not catalyze the conversion of glyoxylate and alanine to pyruvate and glycine and does not convert serine to hydroxypyruvic acid. As a result, glyoxylate accumulates, there is an excess production of both oxalate and glyoxylate, and renal deficiency occurs.³ In 90% of patients with PH type 1, nephrocalcinosis, hyperoxaluria, and urolithiasis leading to end-stage kidney disease from the accumulation of oxalate are observed.^2,4,5 Because the main concern for patients is the enzyme deficiency, replacement of the enzyme-deficient organ, as well as the damaged target organ, is needed. Therefore, CLKT or sequential liver and kidney transplant has been beneficial for these patients.

Anesthesia management is of special concern because patients undergo longer surgical times during CLKT. Some of the concerns that may arise are low body temperature (< 32°C), increased risk of cardiac arrhythmias, and hyperkalemia (> 5.2 mEq/L).6 Because few patients with PH have received CLKT, reports regarding the anesthesia care of these patients are scarce. The aim of our case report was to describe the anesthetic care of a 22-year-old man who underwent a deceased-donor CLKT for PH type 1.

A 22-year-old male patient was diagnosed at the age of 3 years with PH with high serum oxalate levels, marked hyperoxaluria, and recurrent stone formation despite treatment with vitamin B6, which ultimately led to end-stage renal disease requiring hemodialysis. Renal insufficiency progressed secondary to PH type 1. One year ago, he received a renal transplant from his father, with rejection occurring 6 months later, at which time he was admitted to the hospital for CLKT.

Preoperative laboratory tests showed the following values: serum creatinine, 7.2 mg/dL; serum blood urea nitrogen, 46 mg/dL; serum albumin, 2 g/dL; alanine aminotransferase, 6 IU/L; aspartate aminotransferase, 94 IU/L; γ-glutamyltranspeptidase, 23 IU/L; serum C-reactive protein, 78 IU/L; serum sodium, 142 g/dL; serum potassium, 3.6 g/dL; serum calcium, 8.4 g/dL; hemoglobin, 13 g/dL; hematocrit, 42 g/dL; platelet count, 79 000 (10 000/μL); leucocyte count, 9400/μL; prothrombin time (PT), 14 seconds; international normalized ratio (INR), 1.06; and activated partial thromboplastin time (aPTT), 25 seconds. Model for End-Stage Liver Disease score was 35. Preoperative intermittent hemodialysis was done 6 to 24 hours before surgery to adjust electrolyte balance and to optimize intravascular volume.

After 8 hours of starving period, he received an intravenous preoperative dose of 2 mg of midazolam. Intraoperative monitoring included electrocardiogram with 5 leads, pulse oximetry, capnography, urine output, invasive arterial blood pressure of both the left radial and right femoral arteries, two 14-gauge peripherally intravenous lines, and a right subclavian central venous catheter (18 cm, 12-F catheter). A pulse index contour cardiac output (Pulsion PiCCO, München, Germany) catheter was used to monitor cardiac output and other parameters.

Anesthesia induction was performed with propofol (1.5 mg/kg), fentanyl (3 μg/kg), and atracurium (0.4 mg/kg), and the trachea was intubated with a 7.5-mm cuffed endotracheal tube. Anesthesia was maintained with sevoflurane (1-1.5 minimum alveolar concentration) in a mixture of 50% oxygen and 50% air, remifentanil (0.05- 0.3 μg/kg/min), and rocuronium (0.3 mg/kg/h) infusions. Antibiotic prophylaxis with 1 g of ampicillin and 1 g of cefotaxime was administered during the induction of anesthesia. The initial blood gas and blood analyses showed the following results: pH 7.41; partial pressure of carbon dioxide (pCO₂), 26 mm Hg; partial pressure of oxygen (pO₂), 372 mm Hg; sodium, 139 mmol/L; potassium, 3.6 mmol/L; calcium, 1.06 mg/dL; lactate, 1.5 mmol/L; hematocrit, 35.4%; hemoglobin, 11.5 g/dL; bicarbonate concentration, 19.6 mEq/L; base excess, -5.3 mmol/L; and blood glucose, 90 mg/dL. The PiCCO catheter showed the following results before anhepatic phase: cardiac output, 7.25 L/min; cardiac index, 2.8 L/min/m2; global end-diastolic volume, 2585 mL/m²; extravascular lung water, 13 mL/kg; and stroke volume variation, 3%.

Continuous venovenous hemodiafiltration was started after induction of anesthesia and continued for 2 hours to remove oxalate crystals. During the transplant procedure, arterial blood pressure showed a maximum of 130/80 mm Hg and a minimum of 70/40 mm Hg. The oxygen saturation did not decrease below 97%. Minimum central venous pressure was 8 cm H₂O, and maximum was 16 cm H2O. Minimum body temperature was minimum 35.6°C, and the maximum was 36.6°C. Sodium chloride (0.9%, crystalloid) and albumin (5%) were used as maintenance fluids. The total fluid administered was 8300 mL (5450 mL of crystalloid, 2400 mL of albumin, 300 mL of erythrocyte suspension, and 150 mL of mannitol), with 950 mL given from the cell saver. Total fluid loss was 8300 mL (800 mL of urine output, 700 mL of blood loss, 5020 mL of incidental loss).

In accordance with our institutional protocol, 25 mg of heparin was given before anastomosis and bolus methylprednisolone (1 mg/kg) and infusion of basiliximab (1 mg/kg for 1 hour) were administered at the induction of anesthesia. Mannitol (0.5 g/kg) and furosemide (1 mg/kg) were given intravenously during the vascular anastomosis.

The total duration of the transplant procedure was 600 minutes (anhepatic phase of 65 min, liver transplant of 7 h, and renal transplant of 3 h). To avoid hyperkalemia before reperfusion, intravenous insulin and calcium chloride were administered. After reperfusion, 100 mg of furosemide and 30 mg of mannitol were given. At the end of the transplant procedure, the arterial blood gas and blood analyses showed the following results: pH 7.30; pCO₂, 30.8 mm Hg; pO₂, 166 mm Hg; sodium, 136 mmol/L; potassium, 4.8 mmol/L; calcium, 1.15 mg/dL; lactate, 2.2 mmol/L; hemoglobin, 9.3 g/dL; hema-tocrit, 28.7; base excess, -10 mmol/L; and blood glucose, 106 mg/dL. After reperfusion, the patient’s coagulation tests showed the following: INR, 1.94; aPTT, 38.7 seconds; and PT, 22.7 seconds.

At the end of the surgical procedure, the patient was taken to the intensive care unit intubated and hemodynamically stable. Analgesic management included controlled analgesia and morphine. Intermittent daily hemodialysis was performed to enhance oxalate removal. The functions of both grafts remained stable throughout the entire 2-month posttransplant period. Three months after transplant, the transplanted kidney failed and was resected from the patient.

Transplant anesthesiologists play important roles in the perioperative assessment of patients undergoing combined organ transplants because of the range of metabolic and systemic concerns during their intraoperative and postoperative care. Anesthesiologists have a critical role, especially in combined organ transplants, because of the prolonged surgical times and intensive care periods.

A CLKT for simultaneous treatment of metabolic defect and renal failure was first attempted in Cambridge, England in 1984. Since then, CLKT has been increasingly common, and clinical studies have reported good outcomes.⁷ In one study, 11 CLKT cases among 541 patients (483 adult and 58 pediatric) were examined between 1996 and 2006. In the adult patients, reasons for the combined transplant included polycystic kidney and liver disease in 3 patients (27%), cryptogenic liver disease with renal failure in 1 patient (9%), alcohol-related cirrhosis with renal failure in 2 patients (18%), hepatitis C virus-related cirrhosis and renal disease in 4 patients (37%), and recurrent hepatitis C virus-related cirrhosis with associated renal failure 6 years after first liver transplant in 1 patient (9%). In the pediatric patients, reasons for combined transplant included alpha-1 antitrypsin deficiency in 1 patient (25%) and primary hyperoxaluria in 3 patients (75%).⁸

In a French study, data were collected from 10 centers on 54 patients who had undergone transplant between May 1976 and June 2010. Each patient had one or several transplants during this period, with 75 renal allografts and 47 liver allografts. Of the 54 patients, 33 had CLKT and 21 had kidney transplant alone. The diagnosis of PH type 1 was confirmed by liver biopsy in 30 patients (55.6%) and by molecular biology in 13 patients (24%). Nine patients presented with the classic symptoms of hyperoxalemia, hyperoxaluria, and hyperglycolic aciduria.⁷ Opelz and associates also reported better kidney allograft survival when the kidney was implanted simultaneously with a liver.9 On the other hand, some studies consider CLKT as a high-risk surgical procedure leading to increased morbidity and mortality versus kidney transplant alone.^10,11 However, both liver and kidney allograft rejections were lower in combined transplant procedures versus sequential transplant procedures, as shown in a study that compared CLKT and sequential liver and kidney transplant. However, these results did not mean that patient or graft survival was increased.¹²

Our patient had a previous kidney transplant due to PH type 1 before he received the CLKT. During the surgical procedure, we preferred to monitor the patient with an advanced invasive cardiac output monitor (PiCCO) because of the recurrent and prolonged surgery. PiCCO is a cardiac output monitor that combines pulse contour analyses and transpulmonary thermodilution techniques. This technology is easy, less invasive, and cost effective for determining the main hemodynamic parameters (cardiac preload, calibration of cardiac output, volumetric preload parameters instead of filling pressure, afterload, contractility, and volume responsiveness). We have been using PiCCO as a standard monitoring technique during solid-organ transplant procedures in our clinic.

Serious coagulation problems can be expected in patients with liver and kidney dysfunction. Thromboelastography measures the viscoelastic and mechanical properties of the developing clot and allows a differential diagnosis of the coagulopathy and separation of surgical and nonsurgical bleeding. Carneiro and associates reported that thromboelastography for monitoring coagulation status during an orthotopic liver transplant in a patient with PH type 1 who underwent twice renal transplant was useful.¹³ The use of thromboelastography in patients with serious coagulation deficiencies reduces the amount of blood product transfusion and thrombosis of the anastomoses and protects the patient from the risks associated with blood transfusion.

During the intraoperative and early postoperative period of CLKT, hemodialysis was applied to prevent oxalate accumulation. An approach that combines preoperative hemodialysis and intraoperative continuous venovenous hemodiafiltration is especially relevant for patients with high systemic oxalate loads because of the expected rebound of oxalate levels during transplant procedure. In a previous study, the effect of intraoperative continuous venovenous hemodiafiltration therapy during CKLT was shown to be technically feasible, effectively clearing oxalate accumulation and completely preventing the postdialysis rebound of plasma oxalate levels in PH type 1 patients who had extensive systemic oxalate accumulation.¹⁴

Our patient was hemodynamically stable and did not receive vasopressors or massive blood and fluid resuscitation. We did not observe intractable hypothermia and cardiac arrhythmia after the anhepatic phase. As a result, we decreased the early postoperative morbidity and mortality rates by using invasive monitoring techniques, protecting the body temperature, and administering intraoperative renal replacement therapy in our patient. The anesthesiologist plays an important role, by providing safe general anesthesia, maintaining an acceptable hemodynamic profile and ensuring sufficient perfusion to the vital organs of the patient.¹⁵

In this case report, we present the anesthesia care of a 22-year-old patient with PH type 1 who had deceased cadaveric donor CLKT. Complications can be prevented or decreased when proper anesthesia management during surgery for CLKT is used.

Volume: 13 Issue: 3 November 2015 - Supplement - 3

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