Liver Failure
Conditions
Keywords
liver transplantation, vasopressin, renal function, hypotension, creatinine, urine output, diuretics, vasopressors, hemodynamic stability
Brief summary
The purpose of this study is evaluate the medication vasopressin for its ability to preserve kidney function in patients undergoing liver transplantation.
Detailed description
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.
Interventions
DRUGVasopressin
Patients randomly assigned to the experimental arm of the study will receive vasopressin 0.5U/hr IV (20 U vasopressin in 250mL of 0.9% NaCL to infuse at a rate of 6.25mL/hr) via internal jugular catheter. Vasopressin infusion is started at the time of incision and is stopped at the time abdominal closure is completed
DRUGNormal saline placebo
Patients randomly assigned to the placebo arm of the study will receive placebo (0.9% NaCl to infuse at a rate of 6.25 mL/hr) via internal jugular catheter
Sponsors
Emory University
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* \> 18 years of age * undergoing liver transplant * ability to provide informed consent. If patient is unable to give informed consent i.e. hepatic encephalopathy, consent may be obtained from the patient's legally authorized representative
Exclusion criteria
* \< 18 years of age * renal failure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Creatinine Levels | baseline to 48 hours postop |
| Change in Urine Output | 24 hours to 48 hours postop |
Secondary
| Measure | Time frame |
|---|---|
| Count of Participants Who Needed Diuretics Postoperatively | 48 hours |
| Count of Patient Who Need Vasopressers in the Perioperative Period | 48 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vasopressin Vasopressin: Patients randomly assigned to the experimental arm of the study will receive vasopressin 0.5U/hr IV (20 U vasopressin in 250mL of 0.9% NaCL to infuse at a rate of 6.25mL/hr) via internal jugular catheter. Vasopressin infusion is started at the time of incision and is stopped at the time abdominal closure is completed | 8 |
| Normal Saline Placebo Normal saline placebo: Patients randomly assigned to the placebo arm of the study will receive placebo (0.9% NaCl to infuse at a rate of 6.25 mL/hr) via internal jugular catheter | 10 |
| Total | 18 |
Baseline characteristics
| Characteristic | Normal Saline Placebo | Vasopressin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 7 Participants | 16 Participants |
| Age, Continuous | 55.1 years | 58 years | 56.4 years |
| Region of Enrollment United States | 10 participants | 8 participants | 18 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 0 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 |
Outcome results
Primary
Change in Creatinine Levels
Time frame: baseline to 48 hours postop
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vasopressin | Change in Creatinine Levels | 0.5 MG/DL |
| Normal Saline Placebo | Change in Creatinine Levels | 0.55 MG/DL |
Primary
Change in Urine Output
Time frame: 24 hours to 48 hours postop
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vasopressin | Change in Urine Output | 1353 mL |
| Normal Saline Placebo | Change in Urine Output | 731 mL |
Secondary
Count of Participants Who Needed Diuretics Postoperatively
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vasopressin | Count of Participants Who Needed Diuretics Postoperatively | 4 Participants |
| Normal Saline Placebo | Count of Participants Who Needed Diuretics Postoperatively | 1 Participants |
Secondary
Count of Patient Who Need Vasopressers in the Perioperative Period
Time frame: 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vasopressin | Count of Patient Who Need Vasopressers in the Perioperative Period | 3 Participants |
| Normal Saline Placebo | Count of Patient Who Need Vasopressers in the Perioperative Period | 4 Participants |