Intraoperative Dialysis in Liver Transplantation (INCEPTION)

Intra-Operative Continuous Renal Replacement Therapy in Liver Transplantation: A Phase II Randomized Controlled Trial (INCEPTION)

Patient with liver failure waiting for liver transplantation are often hospitalized and commonly supported in an intensive care unit prior to surgery. These patients are sick, and in addition to the complications of a failing liver, other organs such as the kidneys often fail as well. As a consequence, these patients are at an increased risk for complications related to their kidney failure during their liver transplantation procedure. One potential method to diminish the risk of these complications is to provide dialysis support to these patients during their liver transplantation in the operating theater in the form of continuous renal replacement therapy (CRRT). While this is increasingly being performed and is theoretically appealing, there is very little information to support this practice. In addition, the use of CRRT during surgery is not entirely without risk. The investigators have performed two preliminary studies on the use of CRRT during liver transplantation and our data would strongly support the need to conduct further higher-quality studies to better evaluate its feasibility, safety and usefulness. Our proposed study is for a randomized trial comparing the use of CRRT during surgery with standard supportive care in sick patients with liver failure scheduled to receive a liver transplantation.

Liver transplantation (E04.210.650), Renal replacement therapy (E05.196.353), Intra-operative period (E04.614.374), Safety (N06.850.135.060.075), Efficacy

Patients allocated with intraoperative CRRT will have a dialysis catheter inserted and receive CRRT during liver transplantation

Intra-operative (From the induction of anesthesia to trasnfer from the OR to the ICU, average 6-8 hours)

This will be defined by the proportion of patients experiencing intra-operative adverse events, serious adverse events and complications related to the study intervention.

Intra-operative (From the induction of anesthesia to trasnfer from the OR to the ICU, average 6-8 hours)

In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively)

Graft dysfunction will include post-operative ultrasonographic-evidence of vascular ischemia/occlusion or venous occlusion; biliary stricture, obstruction or anastomosis leak; primary non-function; biopsy-proven rejection; or need for surgical re-exploration for any reason.

In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively)

Will be defined as post-operative acute kidney injury, defined by RIFLE criteria; along with encompassing receipt of renal replacement therapy (RRT).

From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days

From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days

From the date of liver transplant after hospital discharge, until the date of first documented re-admission to hospital, assessed until 90-days

Inclusion Criteria: Consent Adult (age > 18 years on the day of assessment of eligibility) Planned cadaveric orthotopic liver transplantation Pre-operative unadjusted (natural) Modification of End-Stage Liver Disease (MELD) score > 25. Pre-operative AKI, defined by a minimum RIFLE-RISK, AND/OR pre-operative estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2, calculated by the Modification of Diet in Renal Disease (MDRD) equation. Exclusion Criteria: Planned living-related donor liver transplantation Pre-operative potassium [K] > 4.5 mmol/L AND urine output < 100 mL in the 6 hrs preceding assessment of eligibility Pre-operative pH < 7.3

Townsend DR, Bagshaw SM, Jacka MJ, Bigam D, Cave D, Gibney RT. Intraoperative renal support during liver transplantation. Liver Transpl. 2009 Jan;15(1):73-8. doi: 10.1002/lt.21650.

Parmar A, Bigam D, Meeberg G, Cave D, Townsend DR, Gibney RT, Bagshaw SM. An evaluation of intraoperative renal support during liver transplantation: a matched cohort study. Blood Purif. 2011;32(3):238-48. doi: 10.1159/000329485. Epub 2011 Aug 9.

Karvellas CJ, Taylor S, Bigam D, Kneteman NM, Shapiro AMJ, Romanovsky A, Gibney RTN, Townsend DR, Meeberg G, Ozelsel T, Bishop E, Bagshaw SM. Intraoperative continuous renal replacement therapy during liver transplantation: a pilot randomized-controlled trial (INCEPTION). Can J Anaesth. 2019 Oct;66(10):1151-1161. doi: 10.1007/s12630-019-01454-0. Epub 2019 Jul 26.