Single Center Case Series Highlights Successful Intra-Operative Continuous Renal Replacement Therapy for Pediatric Liver Transplant Recipients

Background:  Pediatric liver transplant and continuous renal replacement therapy

• 17% to 55% of pediatric patients requiring liver transplant have acute kidney injury.
• 33% of adults requiring whole liver transplant first receive continuous renal replacement therapy (CRRT).
• 9 Children’s Hospital Colorado patients in this case series received CRRT during liver transplant.

Pediatric patients with end-stage liver disease commonly experience acute kidney injury (AKI), most often due to sequelae of hepatorenal syndrome, acute tubular necrosis or relative intravascular volume contraction.

Approximately one-third of adults presenting for a whole liver transplant have first required continuous renal replacement therapy (CRRT). This can help stabilize fluid overload from poor urine output, electrolyte imbalances and acid–base and metabolic dysregulation, which can worsen during the liver transplant.

While an attractive option, there has been some controversy surrounding intra-operative CRRT during a liver transplant, including:

• Logistical challenges
• Labor intensive
• Questions around benefits outweighing risks in patients with AKI alone, but with no known chronic kidney disease

Intra-operative CRRT has demonstrated success in the adult population and is currently being used at about one-third of adult liver transplant centers in the U.S. In the pediatric population, literature is limited for intra-operative CRRT in liver transplantation and outcomes data is not well described.

A multidisciplinary team of researchers at Children’s Colorado and University of Colorado School of Medicine reported on a single-center case series of 9 pediatric liver transplant patients. These patients successfully underwent intra-operative CRRT at the Liver Transplant Program at Children’s Colorado.

Study authors from Children’s Colorado included:

• Eliza Blanchette, MD, Pediatric Nephrology
• Dania Brigham, MD, Pediatric Transplant Hepatology, Pediatric Gastroenterology
• Michael Wachs, MD, Chief, Abdominal Transplant Surgery
• Margret Bock, MD, Medical Director, Pediatric Kidney Transplantation
• Megan Adams, MD, Surgical Director, Pediatric Living Donor Transplantation and Pediatric Transplant Clinical Research

This report summarizes center-specific clinical experience developed to manage intra-operative CRRT in pediatric liver transplantation and highlights ongoing collaboration between the transplant and nephrology teams.

Methods: Children’s Colorado liver transplant CRRT recipients 

Study population and data collection

All primary liver transplants recipients who received CRRT at Children’s Colorado  between January 2017 and December 2021 were included in the series. Study authors collected multiple data points. An intra-operative CRRT nursing protocol was established and followed, which included two CRRT nursing specialists present in operating room (OR) for the duration of each case.

Institutional intra-operative CRRT protocol for liver transplantation

The following is prepared before patients enter OR:

• Two identical circuits
• CRRT circuit tubing
• Prismasol bags for dialysate, replacement
• Filters
• Priming solution

An OR walkthrough is completed prior to each case to plan placement of two Prismaflex machines and accessibility to patient catheter without disrupting sterile supplies and equipment.

Participants:

• Anesthesiology
• Transplant surgeons
• Circulating OR nurse
• Nephrologist
• CRRT specialists

Additional preparations:

• Replacement fluids are run split between pre-filter and post-filter to optimize filter life, minimize deaeration chamber clotting.
• Both circuits primed, ready to use at onset of the operative case in case of circuit clotting

Line placement:

• Vascular access catheters preferentially placed in the right internal jugular vein (left secondary option)
• Femoral catheters avoided due to operative clamping of inferior vena cava (IVC)

Once anesthesia begins and lines are placed, a time out occurs to initiate CRRT.

During procedure:

• Anesthesiologist notifies CRRT nursing specialist immediately before cross-clamping IVC
• During cross clamping, circuit blood flow decreased 25% to 50%
  • Ensures acceptable access, return pressures with continued successful pump flow
• Consideration of transitioning to low potassium PrismaSol dialysate/replacement fluids occurs ~30 minutes before IVC unclamped
  • Serum electrolytes checked at least every 30 minutes if low potassium dialysate/fluids used
• Prior to unclamping, fluid removal is decreased to 0 ml/h
  • To avoid hemodynamic compromise during reperfusion

As operation concludes:

• Blood returned to blood prime patients who will stop receiving CRRT
• Circuit recirculated and reinitiated immediately upon return to ICU in patients who will continue CRRT
  • New circuit primed if intra-operative circuit shows signs of clotting

Results:  Liver transplant CRRT recipients experience good outcomes

Study cohort and baseline characteristics

CRRT recipient age and weight

• 39 days to 17.7 years
• 7–49 kg
• Four under 1 year old, less than 10 kg
• Median age, weight not significantly different than patients not requiring CRRT

CRRT recipient PELD and MELD scores

• Significantly higher than in patients not requiring CRRT
• Median 29, range − 10 to 46 vs. median 11, range − 35 to 38

CRRT recipient diagnoses

• 6 cirrhosis at the time of transplant
• 3 acute liver failure
• Diagnoses, match PELD/MELD scores significantly differed among the two groups
• More CRRT recipients transplanted for acute liver failure (44% vs. 6%) and Status 1A exception (45% vs. 3%)
• 3 CRRT recipients underwent simultaneous liver-kidney transplants (SLK) for concomitant end-stage renal disease caused by autosomal recessive polycystic kidney disease
• SLK significantly more common in CRRT group (38% vs. 2%)

Initiation and course of CRRT

CRRT indications in recipients:

• 3 hyperammonemia
• 3 profound acidosis
• 6 fluid overload
• 2 hyperkalemia

Outcomes 

• 3 patients in CRRT group required early reoperation; same rate among both groups
• 1 CRRT recipient experienced death, graft loss over a median of 344 days of follow-up
  • Passed at 9 days post-op (presumed virally induced macrophage activation syndrome, hemophagocytic lymphohistiocytosis)
• 2 no CRRT patient deaths over median 741 days of follow-up
• 0 retransplants among either group
• No significant difference in recipient/graft survival among either group
• 6-day median post-transplant ICU length of stay (LOS) in CRRT group vs. 3 days in no CRRT group
  • Excludes recipient deaths prior to transfer out of ICU
• 15-day median hospital LOS for CRRT group compared to 11 days in no CRRT group
• 8 surviving CRRT recipients had good liver graft function, renal function without needing dialysis at last known follow-up
  • 3 developed sustained post-transplant hypertension
  • 1 had proteinuria
  • 1 treated with ACE inhibitor therapy

Discussion and conclusion: CRRT successful for critically ill liver transplant recipients

Study authors described the successful use of perioperative CRRT as a reliable and feasible option to maximize fluid and metabolic control in nine critically ill children who underwent liver transplant. The report includes the implementation of the successful clinical framework for intraoperative CRRT.

CRRT benefits:

• Treats volume overload in hemodynamically-at risk patients at time of transplant instead of diuretics or intermittent dialysis
• Offers neuroprotection against cerebral edema, hepatic encephalopathy, intracranial hypertension, and mortality from cerebral herniation
• Achieves superior ammonia mass removal
  • Compared to peritoneal dialysis, intermittent hemodialysis, other techniques

CRRT risks:

• Potential for delayed graft function, significant risk factor for mortality, as well as kidney and liver graft failure in combined kidney-liver transplants
  • 3 in cohort experienced transient delayed graft function without long-term sequalae, successfully weaned off CRRT, have 100% liver, graft survival

This report is believed to be one of largest published case series of CRRT in the pediatric liver transplant population to date.

CRRT can be a lifesaving procedure in high-risk pediatric patients undergoing liver transplantation. Unlike extensive literature on CRRT in adult liver transplantation, less attention has been paid to the pediatric population. CRRT is most indicated in pediatric liver recipients with acute kidney injury, chronic kidney disease, or hyperammonemia due to acute liver failure.

The authors conclude CRRT can be used briefly with good outcomes and without compromising long-term liver graft or renal function.