Continuous Renal Replacement Therapy (CRRT) in Surgery Room During Orthotopic Liver Transplantation (OLT) (CRRT-OLT)

The study is interventional, non-pharmacological, single-center. The aim of this study is to test the possible added value of CRRT in the surgery room during liver transplantation, compared to the investigators center current practice in which CRRT is suspended and possibly restarted at the end of the operation. The incidence of some clinical and metabolic alterations that often complicate transplantation in the absence of CRRT will be evaluated, by measuring a series of parameters related to the state of water filling, acid-base balance, general metabolic structure, hemodynamics and supportive drugs.

Some parameters related to patient safety will be evaluated. The results of this exploratory study will be useful to document what was rationally hypothesized, that is, that the continuation of dialysis treatment even during the hours of surgery, in this narrow category of patients, is actually useful to reduce the possible clinical and metabolic complications, intra- and/or post-operative (within 48 hours of transplant), linked to the simultaneous presence of renal failure.

The statistical analysis is aimed at analyzing the behavior of different indicators of clinical complications and comparing them with what was found in the historical series, in the hypothesis that with the new procedure the analyzed parameters are better. In detail, the mean values at the end of treatment will be compared for:

• Central venous pressure
• Potassiemia
• Lactatemia
• pH

The following will also be evaluated:

• dose of vasoconstrictor drugs, defined by the variation between the dose at the beginning of administration during the anhepatic phase and the maximum dose reached
• pulmonary congestion/pulmonary edema, defined by radiological signs of alveolar congestion/edema on chest X-ray in the post-surgery period
• safety parameters: episodes of hypokalemia requiring supplementation (K<3.5 mmol/l), post-surgery hypophosphatemia, number of coagulation events in the extracorporeal circuit, appearance of cardiac arrhythmias.

Study Overview

• Status: Completed
• Conditions: Liver Failure; Acute Kidney Injury; Kidney Disease, Chronic
• Intervention / Treatment: Other: continuous renal replacement therapy

Detailed Description

The study is interventional, non-pharmacological, single-center. The clinical practice adopted to date provides that upon arrival of the liver to be transplanted, dialysis is interrupted before entering the surgery room, and then resumed, if necessary, upon exiting the room. The aim of this study is to test the possible added value of CRRT in the surgery room during liver transplantation, compared to the investigators center current practice. The incidence of some clinical and metabolic alterations that often complicate transplantation in the absence of CRRT will be evaluated, by measuring a series of parameters related to the state of water filling, acid-base balance, general metabolic structure, hemodynamics and supportive drugs. Some parameters related to patient safety will be evaluated.

For each patient enrolled in the study, the following will be collected:

baseline data (taken before entering the operating room), intraoperative data, postoperative data for the first 48 hours, and data at 3 and 6 months after surgery.

Baseline data:

• demographic data: age, sex
• anamnestic data: etiology of liver disease (viral, alcoholic, neoplastic, other); state of liver disease (acute, acute on chronic, cirrhosis, decompensated cirrhosis); etiology of acute kidney injury (sepsis, hypovolemia/hemorrhage, iatrogenic/drugs, hepatorenal syndrome, other); indication for dialysis treatment (uremia, electrolyte imbalance, acidosis, oligo-anuria, fluid overload, other)
• biochemical parameters (as indicated in the "Objectives" paragraph): pH, HCO3, pO2, pCO2, BE, P/F ratio, DO2, SVO2; hemoglobin, hematocrit, sodium, potassium, calcium, lactate, CPK, ammonium, glycemia
• Hemodynamic parameters: heart rate, mean arterial pressure, cardiac output, peripheral vascular resistance, central venous pressure, pulmonary wedge pressure, stroke volume
• Severity scores: MELD and SOFA pre- and post-intervention
• Other clinical data: amine infusion (YES/NO), mechanical ventilation (YES/NO), urine output (volume/minute), radiological signs of pulmonary congestion/edema (YES/NO).

Intra- and post-operative data:

The biochemical, hemodynamic and clinical parameters listed above will be recorded at the following times:

• at the induction of anesthesia
• in the anhepatic phase
• at 5, 30 and 120 and 180 minutes after reperfusion
• at the end of surgery
• at 24 and 48 hours after leaving the operating room The following will also be reported: intraoperative onset of arrhythmia (YES/NO), intraoperative coagulation of the extracorporeal circuit (YES/NO), intraoperative replacement of the extracorporeal circuit for TMP>200 (YES/NO), onset of hypophosphatemia (<2.5 mg\dl) and hypocalcemia (calcium ion <0.9 mmol\l) hypercalcemia (calcium ion <1.3 mmol\l) assessed at the end of surgery.

Data 3 and 6 months post intervention:

• survival
• INR
• Bilirubin
• Creatinine
• GFR

CRRT protocol:

The extracorporeal renal function replacement treatment modality adopted in the population under study is continuous veno-venous hemodiafiltration (CVVHDF) without anticoagulation. The Prismax® Baxter monitor will be used. A commercially available dialysis solution will be used and in particular: Prismasol 2 ® Baxter used both as dialysate and as post-dilution reinfusion, blood flow 150 ml/min; dialysis dose initially prescribed 30-35 ml/min which may be increased during treatment if necessary to obtain better metabolic/electrolytic control.

During the transplant, a dialysis nurse will be present in the surgery room for the entire duration of the operation. At the end of the operation, CRRT will continue in Intensive Care Unit.

The results of this exploratory study will be useful to document what was rationally hypothesized, that is, that the continuation of dialysis treatment even during the hours of surgery, in this narrow category of patients, is actually useful to reduce the possible clinical and metabolic complications, intra- and/or post-operative (within 48 hours of transplant), linked to the simultaneous presence of renal failure.

The statistical analysis is aimed at analyzing the behavior of different indicators of clinical complications and comparing them with what was found in the historical series, in the hypothesis that with the new procedure the analyzed parameters are better. In detail, the mean values at the end of treatment will be compared for:

• Central venous pressure
• Potassiemia
• Lactatemia
• pH

The following will also be evaluated:

• dose of vasoconstrictor drugs, defined by the variation between the dose at the beginning of administration during the anhepatic phase and the maximum dose reached
• pulmonary congestion/pulmonary edema, defined by radiological signs of alveolar congestion/edema on chest X-ray in the post-surgery period
• safety parameters: episodes of hypokalemia requiring supplementation (K<3.5 mmol/l), post-surgery hypophosphatemia, number of coagulation events in the extracorporeal circuit, appearance of cardiac arrhythmias.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients scheduled for ISOLATED LIVER TRANSPLANT with acute or chronic renal failure already undergoing continuous dialysis treatment in Intensive Care at the time of arrival of the organ. If acute renal failure: stage 2-3 of the KDIGO classification (referring to diuresis).
2. Patients scheduled for COMBINED LIVER-KIDNEY TRANSPLANT, whether or not they are already undergoing continuous dialysis treatment in Intensive Care at the time of arrival of the organ to be implanted
3. Patients scheduled for ISOLATED LIVER TRANSPLANT, for acute liver failure and with acute renal failure in stage 3 of the KDIGO classification (referring to diuresis) for which there is an indication for continuous dialysis.
4. Age ≥ 18 years
5. Signature of informed consent

Exclusion Criteria:

• Age < 18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: CRRT during OLT	Other: continuous renal replacement therapy; continuous renal replacement therapy during OLT in surgery room

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
central venous pressure average values at the end of treatment	Central venous pressure (cmH2O)	during surgery
Potassiemia average values at the end of tretment	Potassiemia (mmol/L)	during surgery
Lactatemia average values at the end of treatment	Lactatemia (mmol/L)	during surgery
pH average values at the end of treatment	pH (absolute value)	during surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dose of vasocostrictors drugs	vasoconstrictor drugs, defined by the variation between the dose at the start of administration during the anhepatic phase and the maximum dose reached (mcg/Kg/min)	during surgery
pulmunary congestion	pulmonary congestion/pulmonary edema, defined by radiological signs of alveolar congestion/edema on chest X-ray in the post-surgery period (Yes/NO)	during surgery
safety parameters: episodes of hypokalemia	episodes of hypokalemia - K < 3.5 mmol/L - requiring supplementation (number of episodes)	during surgery
safety parameters: post-surgery hypophosphatemia	onset of hypophosphatemia <2.5 mg\dl (Yes/No)	during surgery
safety parameters: number of coagulation events in the extracorporeal circuit	intraoperative replacement of the extracorporeal circuit for TMP>200 (YES/NO)	during surgery
Safety parameters: appearance of cardiac arrhythmias	appearance of cardiac arrhythmias (Yes/No)	during surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at 3 and 6 months post intervention	Survival (Yes/No)	3 and 6 months post intervention
INR at 3 and 6 months post intervention	INR (International Normalized Ratio)	3 and 6 months post intervention
Bilirubin at 3 and 6 months post intervention	Bilirubin (mg/dL)	3 and 6 months post intervention
Serum Creatinine at 3 and 6 months post intervention	Serum Creatinine (mg/dL)	3 and 6 months post intervention
GFR at 3 and 6 months post intervention	GFR (mL/min/1.73 m2)	3 and 6 months post intervention

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Davide Ricci, Md, Phd, IRCCS Azienda ospedaliero-Universitaria di Bologna Policlinico di S'Orsola

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Actual): June 15, 2024
• Study Completion (Actual): June 15, 2024

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Liver transplant; CRRT
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Digestive System Diseases; Liver Diseases; Renal Insufficiency; Hepatic Insufficiency; Acute Kidney Injury; Kidney Diseases; Renal Insufficiency, Chronic; Liver Failure
• Other Study ID Numbers: CRRT-OLT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No