Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02548130 |
| Other study ID # |
Centre CHUM |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 29, 2015 |
| Est. completion date |
July 21, 2019 |
Study information
| Verified date |
August 2021 |
| Source |
Centre hospitalier de l'Université de Montréal (CHUM) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The goal of this observational study was to evaluate the impact of the adoption of the MELD
system to prioritize patients on the waiting list for OLT on survival for 1000 consecutive
liver transplantations. Survival was evaluated on the waiting list, one month, and one year
after the transplantation. Another goal was to look at blood losses and transfusion
requirement after the adoption of the MELD score. The hypothesis was the MELD system will
ameliorate the survival rate on the waiting, but the post-OLT will be worse. Blood losses and
transfusions could be worse with the MELD system.
Description:
IMPACT OF THE INTRODUCTION OF THE MELD SCORE TO PRIORITIZE THE WAITING LIST ON SURVIVAL,
BLOOD LOSSES, AND TRANSFUSION REQUIREMENT FOR 1000 CONSECUTIVE LIVER TRANSPLANTATIONS,
OBSERVATIONAL STUDY
INTRODUCTION
Orthotopic liver transplantation (OLT) has been classically associated with coagulation
defects, blood loss, and the need for massive blood product transfusions .
Transfusion of blood products may contribute to morbidity and mortality. Ironically, one
third of patients for OLT had acquired their diseases through transfusion of blood products.
The Child-Turcotte score was developed to predict complications for Porto-cave shunt surgery.
This classification was used after to prioritize patients on the waiting for OLT. This
classification which includes 3 subjective variables (nutrition, encephalopathy, ascites
control) was improved by replacing nutrition by the international normalized ratio (INR) .
The Model of End-Stage Liver Disease (MELD) score was initially created to predict survival
in patients with complications of portal hypertension undergoing elective placement of
transjugular intrahepatic porto-systemic shunts (TIPS) . The MELD score may be an improvement
of the Child-Turcotte-Pugh score as it includes 3 objectives laboratory test results:
bilirubin (mg/dL), creatinine (mg/dL), and INR. More recently, MELD score has been validated
both retrospectively and prospectively as an accurate predictor of mortality for patients who
have chronic end-stage liver disease . After, the MELD system was adopted to reduce the
ever-increasing mortality of patients on the waiting list for OLT.
The MELD score is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill). The MELD
system is constantly being scrutinized and revised. So it's difficult to compare patients'
MELD from different periods. Some authors have tried to use the MELD score to predict blood
product requirements or survival after OLT . Although the MELD system reduces the mortality
of patients on the waiting list, prioritizing the sickest patient raises a number of
concerns. One of the main concerns is that the MELD may worsen the post-OLT outcomes
resulting in futile transplantation. Many studies suggest that patients with high MELD score
have worse post-OLT outcomes than patients with low MELD score.
The MELD system was adopted in the province of Quebec in July 2009. Before that the
allocation system was: first priority was for intubated patients in an intensive care unit.
The second priority was for patients in intensive care unit. The third priority was for
hospitalized patients, and the final priority was for patients at home.
The goal of this observational study was to evaluate the impact of the adoption of the MELD
system to prioritize patients on the waiting list for OLT on survival for 1000 consecutive
liver transplantations. Survival was evaluated on the waiting list, one month, and one year
after the transplantation. Another goal was to look at blood losses and transfusion
requirement after the adoption of the MELD score. The hypothesis was the MELD system will
ameliorate the survival rate on the waiting, but the post-OLT will be worse. Blood losses and
transfusions could be worse with the MELD system.
METHODS
After approval of the Ethic committee of the Centre hospitalier de l'Université de Montréal
(CHUM) (15.113) and registration on Clinical Trials.gov a non-experimental comparative study
was conducted. 1000 consecutive liver transplantations were studied. Prioritization for the
first 300 OLTs was as Quebec's allocation system at that time. The last 700 OLTs were
prioritized according to the MELD system (since July 9th, 2009).
Surgery Protocol:
Eight hepatobiliary surgeons performed all the OLTs, and more than 25 anesthesiologists were
involved throughout the study period. Monitoring was standardized in all patients, as was the
anesthesia technique (arterial canula, pulmonary artery catheter, sufentanil, propofol,
rocuronium, desflurane). In the absence of uncontrollable bleeding coagulation disorders were
not corrected before or at the time of transplantation. No fresh frozen plasma (FFP),
platelets or cryoprecipitate were given and a "wait-and-see" approach of rescue therapy was
used instead of a prophylactic or preventive interventions. The triggering Hb level for RBC
transfusion was set between 60 and 70 g/L. An effort was made to start a RBC transfusion
after the blood loss was controlled. In the presence of diffuse oozing (any clinical evidence
of coagulation) plasma (10-15 ml/kg) were transfused if the international normalized ratio
(INR) value was higher than 1.5 to 2.0. Platelets were also transfused (5-10 units) if
platelets count was lower than 30 X 109 pl/L, and cryoprecipitate (5 units) if fibrinogen was
lower than 1.3-2.0 g/L. Aprotinin was administered in every case for the first 300 OLTs
according to the Hammersmith protocol (37). The last 700 OLTs received tranexamic acid as
antifibrinolytic according to the BART protocol.
Each anesthesiologist tried to lower the central venous pressure (CVP) before the anhepatic
phase by one third using a restricting intravenous fluid infusion approach, phlebotomy
without volume replacement or by a combination of both techniques. Phlebotomy consisted of
withdrawing blood (from the introducer of the pulmonary artery catheter) at the beginning of
the cas without any crystalloid or colloid volume replacement. Criteria for phlebotomy were:
Hb concentration above 85 g/L, and a normal renal function. The quantity of blood withdrawn
was guided by the patient's body mass (7-10 ml/kg). The phlebotomy was interrupted if the
arterial blood pressure dropped by more than 20% of the baseline value in spite of
vasopressor (phenylephrine or norepinephrine) administration. The CVP was slowly corrected
after unclamping the inferior vena cava to avoid hepatic congestion. The previously withdrawn
whole blood was returned to the patient at the end of surgery of before as needed. A cell
saver (CS) was used for every case except for the initial 75 OLTs.
Two surgeons were involved in each procedure. Neither venovenous bypass nor piggyback
technique was used except for very few cases where the piggyback technique was used. During
dissection, bleeding was controlled almost exclusively by electrocautery and metallic clips.
All livers were harvested from brain dead donors and where ABO-Rh compatibles.
Statistical Analysis The MELD score was determined for each patient according to the
equation: 0.957 X Loge creatinine mg/dL + 0.378 X Loge bilirubin mg/dL + 1.120 X Loge INR X
10 (14). The MELD score was adjusted according to the period (14). The data are expressed as
mean ± standard deviation of the mean or as a percentage. Statistical analysis was performed
using the Student'S T test, Welch T test as appropriate. The chi-square test served to
compare percentages.
