Study to Evaluate if the Drug Vasopressin Protects the Kidneys for Patients Undergoing Liver Transplant

• Low dose vasopressin given during liver transplantation prevents renal dysfunction in the perioperative period confirmed by evaluating creatinine postoperatively. [ Time Frame: baseline, 24 hours postop, 48 hours postop ] [ Designated as safety issue: Yes ]
  
• Low dose vasopressin given during liver transplantation prevents renal dysfunction in the perioperative period confirmed by evaluating urine output postoperatively [ Time Frame: baseline, 24 hours postop, 48 hours postop ] [ Designated as safety issue: Yes ]
  

• Low-dose vasopressin given during liver transplantation prevents renal dysfunction in the perioperative period confirmed by evaluating the need for diuretics in the perioperative period. [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  
• Low-dose Vasopressin given during liver transplantation prevents renal dysfunction in the perioperative period confirmed by evaluating hemodynamic stability/requirement of additional vasopressors in the perioperative period. [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  

Renal failure is a common complication of liver disease. Hepatorenal syndrome is caused by a dysfunctional global circulation in the setting of liver disease: Increased flow to the mesenteric circulation is a contributor to decreased blood flow to the kidneys (1). Renal failure often worsens in the perioperative period of liver transplantation since the kidneys are further stressed by reduced flow due to inferior venacava occlusion, decreased blood flow to the kidneys from anesthetics, as well as hypotension from volume shifts, such as when large volumes of ascites are removed. Renal failure is a cause of major morbidity and mortality in patients undergoing liver transplantation.

Vasopressin is a logical choice of therapy in this context as the effects of the drug work to particularly increase renal blood flow and glomerular filtration rate due to the location of specific vasopressin receptors within the renal vasculature. It has been suggested that the use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog) or alpha-1-adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in patients with type 1 Hepatorenal Syndrome.

Six studies (with only one randomized study in a small series of patients) have shown that terlipressin improves renal function in these patients (2-7). This drug is available in Europe, but not in the United States. However, while anesthesiologists commonly use vasopressin during liver transplantation in the setting of hepatorenal syndrome or vasodilatory shock, the validity of this practice for its effects on renal function and outcomes has not been rigorously studied (8-10). Therefore, the purpose of this study is to evaluate the effects of low-dose vasopressin on intraoperative and perioperative renal function in liver transplant patients.

This study will be a randomized, double-blind controlled trial performed in adult liver transplant patients coming to surgery for chronic liver disease; the major end-points of analyses are renal function tests in the perioperative period.