CONTINUOUS VENOVENOUS HEMOFILTRATION WITH DIALYSIS IN COMBINATION WITH TOTAL HEPATECTOMY AND PORTOCAVAL SHUNTING

Bridge to Liver Transplantation

Abstract

Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

Children who experience acute liver failure following liver transplantation(LT*) have a high rate of mortality unless emergency retransplantation can be performed. These patients develop refractory coagulopathy, metabolic acidosis, and respiratory, circulatory and renal failure. Despite their listing as United Network for Organ Sharing status 1, a second liver graft may not become available to these patients for several days or longer. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in such patients and in patients with fulminant hepatic failure (FHF) who have not undergone LT ^{(1, 2)}. In addition, continuous hemofiltration may be used in patients with FHF to facilitate fluid, circulatory and metabolic balance ⁽³⁾. We used continuous venovenous hemofiltration with dialysis (CVVH-D) following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve control of serum electrolytes, pH, and ammonia levels as well as fluid and circulatory hemeostasis prior to successful retransplantation.

The patient was a 3½-year-old boy with FHF due to giant cell hepatitis who underwent LT. Coagulopathy, metabolic acidemia, hyperammonemia, hypoglycemia, and renal failure developed on the first postoperative day (POD) due to liver graft nonfunction (Table 1). His neurologic status deteriorated and he became unresponsive to noxious stimulation. Severe circulatory failure ensued, including cardiac arrest, necessitating administration of inotropic drug infusions. Exploratory laparotomy showed the liver to be indurated, suggestive of primary allograft nonfunction. Transplant hepatectomy and portocaval shunting were performed at that time, after which the patient's circulatory status improved. CVVH-D was then initiated on POD 1 via an 8-Fr double lumen catheter inserted into the left femoral vein. An Amicon 20 filter and custom dialysate fluid with bicarbonate were used. The dialysate flow rate was 500 ml/hr and the ultrafiltration rate was 200 ml/hr. Heparin was infused at 0-10 U/kg/hr to maintain an activated clotting time of 180-200 sec. Within 12 hr of initiating CVVH-D, the patient's neurologic status improved, with spontaneous eye opening. Fresh-frozen plasma was infused intermittently to minimize bleeding from the indwelling surgical drain. Fluid, circulatory, and metabolic stability as well as neurologic responsiveness were maintained for the ensuing 56 hr until a donor liver became available, at which time successful LT was performed. CVVH-D was discontinued immediately before surgery. Following retransplantation, the patient had gradual normalization of hepatic and renal function without the need for CVVH-D. His trachea was extubated on POD 3, at which time the results of his neurological examination were normal. He was discharged home 28 days after his second LT with normal liver function and normal values for liver enzymes, serum blood urea nitrogen, and creatinine.

Acute liver failure is associated with a high rate of mortality in patients who have undergone LT with graft nonfunction and in patients with fulminant liver failure who have not received transplants. Ringe et al.⁽²⁾ observed clinical improvement in patients following removal of failing livers, reporting that “in exceptional situations it is advantageous to have a patient who is anhepatic (rather) than to leave a necrotic liver in situ, which has extremely high mortality.” The authors refer to the clinical sequelae of severe metabolic acidosis and multiple organ failure in patients with acute liver failure as “toxic liver syndrome.” Contributing factors may include release of toxic compounds by the necrotic liver, including lactic acid. Removal of the liver resulted in significant improvement in metabolic and circulatory status in the majority of patients, who were then treated with hemodialysis or continuous arteriovenous hemofiltration (CAVH).

So et al. ⁽¹⁾ reported their experience with two children with primary graft nonfunction in whom hepatectomy and portocaval shunting were performed as a bridge to retransplantation. Both patients had developed severe metabolic acidosis, coagulopathy, and circulatory failure in association with liver graft failure. In these cases, dramatic resolution of these processes was noted following hepatectomy. Intravenous infusions of dextrose and fresh-frozen plasma were continued, as well as were antibiotics and antacids. Hemodialysis was utilized in one patient. Both patients had successful retransplant surgery after anhepatic periods of 26 and 48 hr.

Several innovative therapies have been utilized to support the patient with acute liver failure awaiting LT. These include hemoperfusion, plasmapheresis, hemodialysis, hemofiltration, isolated hepatocyte perfusion, auxiliary liver transplantation, and extracorporeal liver transplantation^(3-5). Because many patients with acute liver failure also develop renal failure, techniques that facilitate dialysis and fluid removal may be especially beneficial. Both hemodialysis and hemofiltration are widely available techniques which have been used in patients with end-stage liver disease and renal failure awaiting LT. These modalities, however, have associated risks related to vascular cannulation and circulatory instability which may limit their use in patients with acute liver failure.

Hemodialysis may produce hypotension in patients with liver failure⁽⁶⁾. In addition, hemodialysis has been associated with the development of cerebral edema. Refractory increases in intracranial pressure have been observed in patients with fulminant liver failure undergoing hemodialysis ⁽⁷⁾. Continuous modes of renal replacement therapy, including continuous arteriovenous hemofiltration with dialysis (CAVH-D) and CVVH-D, have been reported to result in greater circulatory stability, less change in intracranial pressure, and less cerebral edema when compared with standard hemodialysis ⁽⁸⁾.

CAVH has been used in the United States since 1982. CAVH is an extracorporeal ultrafiltration technique designed to remove plasma water, urea, and other toxins from the intravascular space. In contrast to conventional hemodialysis, CAVH is performed continuously, 24 hr per day, commonly for several days or longer. Blood passes from the patient's arterial circulation via an arterial catheter through a hemofilter, composed of several thousand hollow-fiber capillaries, and re-enters the circulation via a venous catheter (Fig. 1A). The blood is driven through the hemofilter by the patient's arteriovenous pressure gradient, resulting in the passage of water and small- and medium-sized solute molecules across the capillary membrane by “convection.” The effluent, or ultrafiltrate, then passes from the extracapillary space through the ultrafiltrate port into a drainage reservoir. The ultrafiltrate has a solute and electrolyte concentration identical to that of the patient's plasma. To achieve enhanced filtration of water and solute by “diffusion,” countercurrent dialysate flow may be added. This technique is called CAVH-D(Fig. 1B). To prevent thrombosis in the hemofilter, heparin or other anticoagulants may be infused into the arterial limb of the extracorporeal circuit. To achieve the desired fluid and electrolyte balance, replacement fluid is infused into the venous limb of the circuit. Alternatively, the replacement fluid may be infused via the arterial limb, serving as a prefilter diluent. As an alternative to CAVH-D, CVVH-D may be instituted by utilizing an extracorporeal circuit that includes a roller pump to drive blood through the hemofilter. Two venous catheters or, more commonly, a double-lumen venous catheter may be used (Fig. 1C).

CAVH-D requires the insertion of large-bore venous and arterial catheters. Commonly, the femoral vessels are utilized in children. Arterial cannulation may be associated with significant hemorrhage and hematoma formation⁽⁹⁾. In addition, low flow through the hemofilter occurs in patients with relatively low arterial blood pressure and therefore a small arteriovenous pressure gradient. This condition, common in critically ill infants and small children, results in poor hemofiltration and frequent clotting of the hemofilter. CVVH-D offers the advantages of single vessel cannulation with a double-lumen catheter, avoidance of arterial cannulation, and the use a pump to drive the patients blood through the filter, resulting in a stable rate of filtration and, theoretically, less frequent clotting of the filter. A relative disadvantage of CVVH-D, however, is the additional technical requirement represented by the pump. Despite this, CVVH-D was determined to be the more favorable technique in a prospective, comparative study of CAVH-D and CVVH-D in critically ill patients, and has become the preferred modality for pediatric patients in our institution⁽¹⁰⁾.

CVVH-D was used to facilitate fluid, circulatory, and metabolic balance in a 3½-year-old boy who was anhepatic for 66 hr. He had undergone hepatectomy with portocaval shunting following graft failure after LT. Fifteen months after retransplantation, he is healthy with normal liver, kidney, and neurologic function. The combination of hepatectomy with portocaval shunting and CVVH-D may be beneficial in selected patients with acute liver failure as a bridge to LT.

Figure 1: Technical features of three continuous hemofiltration procedures.(A) For CAVH, the inflow to and outflow from the hemofilter are connected to catheters in the femoral artery and vein, respectively. A heparin infusion is added to the prefilter circuit to prevent clotting of the filter. Ultrafiltration occurs due to the arteriovenous pressure difference. The ultrafiltrate is drained into a collection bag and measured hourly. Replacement fluid is added to the postfilter circuit to maintain the desired fluid and electrolyte balance. Solute clearance is achieved by ultrafiltration alone (convection). (B) For CAVH-D, ultrafiltration is augmented by countercurrent dialysate flow through the hemofilter compartment (diffusion).(C) For CVVH-D, a double-lumen catheter is inserted into a central vein. Blood flow through the hemofilter is driven by a roller pump. D = dialysate; RF = replacemeent fluid.