Use of Direct Peritoneal Resuscitation in High-risk Liver Transplant Recipients

Study Overview
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Brief Summary
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This study is being conducted to assess the safety of Direct Peritoneal Resuscitation (DPR) in high-risk liver transplant patients. The investigators want to also identify if this method of recovery after large surgery has the same benefits in liver transplant patients as have been appreciated in other surgical patients. The combination of elevated BMI and impaired kidney function increases the risk of 1) needing intensive care unit (ICU) admission after surgery, 2) slow function of the new liver [technically termed Early Allograft Dysfunction (EAD)] and 3) need for more than one operation. The study team also aims to identify if DPR can reduce these risks and not cause other unexpected complications following surgery. DPR involves the infusion of a solution into the abdomen and has been shown to reduce edema and improve blood flow in organs. The solution used in this study is a commercially available peritoneal dialysate, a dextrose containing solution that is infused into the abdominal cavity and is routinely used in patients with end-stage renal disease requiring dialysis.

Detailed Description
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The central hypothesis of this study is that direct peritoneal resuscitation is a safe therapy following liver transplantation and is associated with a reduced rate of return to the operating room. AIM 1: Determine the safety profile of direct peritoneal resuscitation on liver transplant recipients at risk of return to the operating room and ICU admission. Hypothesis: Liver transplant recipients that receive DPR will have comparable complication rates to historic controls of liver transplant recipients with similar demographics. AIM 2: Identify if direct peritoneal resuscitation demonstrates a trend towards a reduced rate of return to the operating room compared to historic controls. Hypothesis: DPR will demonstrate a trend of a reduce rate of return to the operating room of liver transplant patients after index operation compared to historic controls. AIM 3: Identify if direct peritoneal resuscitation reduces the rate of early allograft dysfunction and other organ failure following liver transplantation with interval improvement in post-operative fibrinolysis activity. Hypothesis: DPR will reduce the rate of EAD of liver transplant patients compared to historic controls and is associated with increased fibrinolysis in the post-operative period.

Official Title
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Phase I Clinical Trial Utilizing Direct Peritoneal Resuscitation in Liver Transplant Recipient Population at Increased Risk of Return to the Operating Room and Early Allograft Dysfunction

Conditions
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End Stage Liver DIsease, Obesity, Acute Kidney Injury

Intervention / Treatment
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* Procedure: Direct Peritoneal Resuscitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult liver transplant recipients ≥18 y/o Ability to consent Pre-operative Creatinine ≥1.1 (or on dialysis) and BMI ≥30 Exclusion Criteria: Diaphragmatic injury Active spontaneous bacterial peritonitis (SBP) with initiation of antibiotic treatment within 72 hours of surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: All study subjects will be enrolled to the treatment arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Direct Peritoneal Resuscitation (DPR) Group<br>At the time of abdominal closure and determination that the patient will either go to extended stay or the intensive care unit, three drains will be placed per standard of care. An additional 19 French drain will be placed at the ligament of Treitz at the base of the mesentery. Following abdominal closure DPR will be initiated with commercially available 2.5% glucose-based peritoneal dialysis solution at a rate of 1.5 cc/kg/hr based on previously reported therapy in trauma. Drains will be connected to continuous wall suction. This infusion will continue for the duration the patients stay in extended stay (8 hours) if they are deemed eligible for hospital ward admission, or for 24 hours if requiring ICU care. These patients will then be observed for their hospital course and monitored for outcomes listed above. | Procedure: Direct Peritoneal Resuscitation<br>* Direct peritoneal resuscitation involves the abdominal infusion and drainage of a peritoneal dialysate in high-risk liver transplant patients, for up to 24 hours after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients that complete DPR infusion without reaching stopping criteria |  | Up to 24 hours after initiation of direct peritoneal resuscitation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of return to the operating room after index operation | Amount of patients that require a re-operation after their transplant | Up to 7 days after transplant | 
| Abdominal compartment syndrome requiring reoperation | Number of patients that develop increased intraabdominal pressure as a consequence of dialysate infusion | Events that occur during the duration of the DPR infusion, which will last no more than 24 hours after the participant's transplant surgery. | 
| Percent of patients that complete DPR infusion |  | Up to 24 hours after initiation of DPR | 
| Percent of patients that are transferred to hospital ward | Patients that are admitted to the hospital ward after surgery, not requiring ICU admission | Up to 24 hours after surgery | 
| Rate of early allograft dysfunction | Patients who experience slow function of their transplanted liver after their transplant | Up to 7 days after transplant | 
| Number of blood product units required during first 24 hours postoperatively | The study team will record the number of units of blood product (i.e. bags of red blood cells, platelets, etc.) required by the participant in the first day after liver transplantation. | Up to 24 hours after transplant | 
| Number of participants that require renal replacement therapy (i.e. hemodialysis) during the first 7 days after liver transplant. | Researches will record whether the participant developed renal failure requiring renal replacement therapy (i.e. hemodialysis) | Up to 7 days after transplant | 
| Hourly urine output for first 24 hours |  | Up to 24 hours after transplant | 
| Rate of early infection after transplant | Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia. | <7 days postoperatively | 
| Rate of late infection after transplant | Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia. | 7-30 days postoperatively | 
| Rate of mechanical bowel obstruction | Constipation caused by compression from inside or outside of the bowel lumen | Up to 30 days after transplant | 
| Ileus/time to oral intake | Time to return of normal bowel function and food tolerance after transplant | Up to 30 days after transplant | 
| Duration of insulin infusion post-operatively | Insulin requirements after transplant surgery | Up to 7 days after transplant | 
| Ventilator free days | Outcome measurement that looks into rate of respiratory failure requiring prolonged mechanical ventilation after transplant surgery | Up to 28 days post-op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplant, Obesity, Renal failure