The Effects of MELD Scoring on Liver Transplant Anesthesia
Cynthia Wang, MD and Victor W. Xia, MD
Department of Anesthesiology, Ronald Reagan UCLA Medical Center, David Geffen School of
Medicine, University of California, Los Angeles, Los Angeles, California, the United States
Corresponding author: Victor W. Xia, MD,
Department of Anesthesiology, Ronald Reagan UCLA Medical Center, David Geffen School of
Medicine, University of California, Los Angeles, Los Angeles, California, the United States
Email: vxia@mednet.ucla.edu
The Model for End-Stage Liver Disease (MELD) is a scoring system adopted in the United
States in February 2002 to prioritize recipients on the liver transplant waiting list. Originally, the
MELD score was intended to predict short term outcomes after transjugular intrahepatic
portosystemic shunt placement and later, to predict 3 month mortality rate in patients who are
cirrhotic.(1, 2) Many studies have confirmed that the MELD score is as an excellent indicator of
severity for various liver diseases.(3) In patients undergoing orthotopic liver transplantation
(OLT), studies have shown that a higher preoperative MELD score is associated with higher
morbidity and mortality.(4) Recently, studies also suggest that higher MELD scores are
associated with increased intraoperative risks.(3, 5) Here we review the evidence on MELD
scoring and its potential effects on postoperative morbidity and mortality as well as on
intraoperative anesthetic management.
The MELD score and the effects of its components on the perioperative outcomes
The MELD score is a composite of three laboratory values: serum creatinine, serum
bilirubin, and international normalized ratio (INR). MELD = 9.6 X loge(creatinine) + 3.78 X
loge(bilirubin) + 11.2 X loge(INR) + 6.43.(6) When broken down into its individual components,
abnormally elevated values of any one of these laboratory tests may suggest greater severity of
disease. It is well known, for instance, that renal dysfunction prior to liver transplantation
confers greater intraoperative risks and is a predictor for worse postoperative outcomes.(7)
Patients with pre-existing renal dysfunction are at risk for presenting to the operating room at the
time of surgery with fluid overload; depending on when the patient may have last been dialyzed.
It is sometimes difficult to assess whether the patient is hypovolemic, euvolemic, or
hypervolemic.
Furthermore, this patient population is particularly at risk for presenting with and/or
developing significant electrolyte abnormalities and acidosis. If severe, these abnormalities may
lead to a need for intraoperative renal replacement therapy (RRT). In a study involving 102 liver
transplant candidates receiving RRT, Wong, et al demonstrated that overall mortality was
increased to 30% compared to 9.7% for all other liver transplant recipients, reflective of
worsened 3-month and 1-year survival. As creatinine is a significant component of the MELD
score, the patients requiring RRT in this study exhibited higher MELD scores, which was
predictive of death after liver transplantation.
The study group also found that patients who required RRT prior to transplantation had
lower mean arterial pressures (58 vs. 67.3), higher mean APACHE II scores (31.2 vs. 24.1), were
more likely to be need postoperative ventilation (59% vs. 8%), and were more likely to be on
vasopressors (62% vs. 14%) (Table 1). Of note, the study excluded patients who were receiving
outpatient hemodialysis prior to surgery; therefore, one could assume that the patients included
in the study not only had more advanced renal dysfunction, but that they might also suffer from
more advanced liver and/or systemic disease, preventing them from tolerating the hemodynamic
shifts involved with single pass dialysis.(8) Renal dysfunction that continues into the
postoperative period also has an impact on morbidity. In a retrospective review of 144 liver
transplant recipients, Oberkofler, et al identified the need for post-operative renal replacement
therapy as an independent predictor of mortality. Even mild renal failure in the posttransplantation period was associated with longer hospital stays, an increased incidence of
infections, and increased overall mortality. In fact, mortality was observed to be up to 60% in
patients requiring RRT at 30 days following surgery. Of note, the study did include patients with
preserved renal function preoperatively, and whose renal dysfunction only presented after
transplantation. However, the authors also note that hepatorenal syndrome prior to
transplantation along with RRT post-transplantation is a strong predictor for mortality and
increased ICU length of stay.(9)
It has been hypothesized that it is possible to predict the degree of intraoperative blood
loss and transfusion requirements based on the severity of preoperative coagulopathy, one of the
MELD components. Investigators have found positive correlations between preoperative INR
and platelet counts with intraoperative blood transfusions.(10) These assumptions have been
challenged by some including the same authors in previous studies who argue that the presence
and degree of portal hypertension and the history of prior abdominal surgeries, not preoperative
coagulopathy, is more predictive of blood loss.(11)
The MELD score has been modified to better predict pre- or post-transplant mortality. In
addition to the 3 laboratory values mentioned above, several new components such as the serum
sodium have been proposed in various studies. If added to the MELD formula, they have the
potential to influence intra- and post-operative outcomes and anesthesia management as well.
The effects of the MELD score on the postoperative outcomes
As an overall marker for disease severity, the MELD score has been used to predict
postoperative morbidity and mortality following OLT. Several groups have demonstrated that
high pretransplant MELD scores predicted worse survival rates.(12, 13) A MELD score of
greater than 24 was associated with worse 1-year survival when compared to patients with
MELD scores of less than 24.(4) Another study suggests that an increase of the MELD score by
one point increases the possibility of death by 1.2 times.(14) Similarly , others have associated
elevated MELD scores with more hospital admission days in the 3 month post-operative period
in the living donor liver transplant population.(15)
Even amongst cirrhotic patients undergoing non-liver transplant surgery, MELD scores
are correlated with outcomes. In a retrospective analysis, Northrup, et al found the MELD score
to be a statistically significant predictor of 30-day mortality, with an approximate 1% increase in
mortality for each one point increase in MELD score from 5 to 20, and a 2% increase in
mortality for each one point increase in MELD score above 20.(16) Similarly, Kim, et al found a
positive association between MELD score and mortality in 160 patients undergoing non-liver
transplant surgery.(17)
Even studies that have not demonstrated a difference in survival post-liver transplantation
in patients with elevated MELD scores, there is data to suggest that these patients may
experience greater morbidity. Patients with higher MELD scores in a study involving 178 liver
transplants had longer hospital stays. Mean hospital length of stay in patients with mean MELD
scores of 34 was 24 days, compared to a mean hospital stay of 15.55 days in patients with a
mean MELD score of 16. Parallel with the increased hospital stays were the ICU stays, with
higher MELD patients staying an average of 12.6 days in the ICU versus 5.13 ICU days in the
lower MELD group.(18) However, this study did not demonstrate a difference in overall
survival. Others have also shown that patients with higher MELD scores undergoing liver
transplantation incur higher healthcare costs due to greater resource utilization during their care,
implying greater complexity and severity of their disease, in spite of exhibiting no significant
differences in overall outcomes.(19)
The MELD score has also been associated with several other perioperative risks that may
alter perioperative care and increase the acuity of this patient population. Postoperative
pulmonary complications have been identified as a significant source of increased mortality. In a
study involving 107 patients undergoing liver transplantation, mortality was 18.5% in patients
who developed postoperative pulmonary complications versus 4.8% in those who did not. The
MELD score was identified as an independent risk factor for the development of postoperative
pulmonary complications. Those with a MELD score greater than 25 were at higher risk of
developing these complications.
Other risk factors included intraoperative fluid administration of greater than 10L and
intraoperative blood transfusion volume of greater than 4L. These complications prolonged
hospital stays and/or contributed to overall morbidity and mortality.(20) The MELD score has
also been linked to alterations in cerebral perfusion, possibly contributing to the incidence of
perioperative neurological complications, another major contributor to morbidity and mortality
after liver transplant surgery.
Patients with higher MELD scores have been shown to be at greater risk for developing
mental status changes post OLT.(21) Others have demonstrated a significant difference in
cerebral tissue oxygenation and hemoglobin indices intraoperatively, suggestive of clinically
significant alterations in cerebral perfusion. These changes were demonstrated to be more
exaggerated in patients with higher MELD scores. Cerebral hyperperfusion episodes in this
patient population, some of whom demonstrate a functional loss in CBF autoregulation, may
contribute to cerebral hypertensive episodes, predisposing cerebral vascular accidents and
cerebral edema.(22)
As the liver transplant population is evolving, the transplant community is also
encountering more candidates with underlying cardiac diseasePatients with cirrhosis may present
with cardiomyopathy, further increasing their chances of developing post-operative cardiac
complications. In addition to adverse intraoperative cardiovascular events and a history of preexisting cardiac disease, advanced liver disease as quantified by a modified MELD score has
been shown to be predictive of postoperative cardiac complications. In a study involving 197
patients, the MELD score, MELD-Na score, and (Integrated MELD) i-MELD1 score were all
associated with the incidence of cardiac events. However the i-MELD, a score that incorporates
1
MELD-Na = MELD + 1.59(135-serum Na) where minimum serum Na is 120mmol/L and maximum serum Na is 135mmol/L
i-MELD = MELD + (age X 0.3) – (serum Na X 0.7) + 100
the age as well as the serum sodium, was the most strongly correlated. Presumably, this is due to
the link between degree of liver failure and extent of cardiovascular anomalies such as cirrhotic
cardiomyopathy, peripheral vasodilatation, and hyperdynamic circulation.
Cardiac complications have been reported to be the third leading cause of death post OLT,
following infection and rejection. It has been estimated to be the cause of 22% of all late
mortalities. Thus, the increased risk for these events in the perioperative period in patients with
higher MELD scores creates a need for more vigilant perioperative care, particularly since the
overall severity of disease is great in this patient population.(23)It should be noted that despite
many studies suggesting an association between the MELD score and postoperative mortality,
the overall mortality in the U.S. has not changed since the adoption of the MELD system in
organ allocation in 2002.
.
The effects of the MELD score on the intraoperative management
In the MELD based organ allocation system, the available graft will go a patient with the
highest MELD score. In a study comparing low vs. high MELD scores, Xia, et al (5) found that
patients with higher MELD scores have more comorbidities and require a higher level of
pretransplantation care. Specifically, patients with high MELD scores have lower starting
hemoglobin and fibrinogen concentrations. In addition, patients with higher MELD scores more
frequently require hemodialysis, mechanical ventilation, and hemodynamic support.
Intraoperatively, patients with higher MELD scores require on average 5 more units of red blood
cells (RBC) and 7 more units of FFP during OLT compared to those with lower MELD
scores.(5) Other blood products such as platelets and cryoprecipitate have very similar patterns.
Although the higher MELD score is generally correlated with higher transfusion requirements,
these patterns are particularly noticeable when the MELD score exceeds 30 (Table 2).
In another retrospective review of 26 living donation transplants and 69 cadaveric
donation transplants, Frasco, et al (24) found significant associations between the MELD score
and preoperative coagulation tests with intraoperative transfusion of blood and component
therapy. Specifically, the MELD score was associated with the total number of transfusions
required, while aberrancies in individual coagulation and hematologic tests were associated with
the need for component therapy transfusions. On average, an increase in 3 MELD score points
correlated with one additional blood product transfusion.
The factors most strongly associated with the number of transfusions in this study were
the MELD score, starting fibrinogen concentration, and hemoglobin concentration. Although the
fibrinogen value is not integral in the calculation of the MELD score, many have associated high
MELD scores with decreased fibrinogen levels. Thissuggests that high INR values contributing
to elevated MELD scores may be an overall indicator of severity of coagulopathy. As a case in
point, others have associated high MELD scores with decreased starting hematocrit and
fibrinogen levels. Subsequently, the same study correlates high MELD scores with increased
intraoperative transfusion requirements and an increased intraoperative vasopressor
administration.
Mangus, et al (25) conducted a retrospective review of 526 liver transplants and also
found that MELD score and initial fibrinogen, along with low preoperative hemoglobin and
overall anesthesia care time, were strongly predictive of RBC usage. Those with increased
transfusion requirements experienced longer postoperative hospital stays and lower 90-day and
1-year graft and patient survival. Of note, this study only included transplants that used the
piggyback hepatectomy technique. In another retrospective study involving 90 patients,
increased MELD scores were associated with increased intraoperative blood loss.
Although other studies have failed to show a statistically significant link between MELD
score and blood transfusion requirements, there still remains a trend toward greater transfusion
requirements with increasing MELD scores.(26) Greater transfusion requirements in this patient
population have been associated with an increase in mortality and increased post-operative ICU
stays. Oberkofler, et al (9) identified RBC transfusions of greater than 7 units intraoperatively as
an independent risk factor for post-operative mortality. Likewise, the study group also identified
FFP transfusion of greater than 10 units as an independent risk factor for post-operative
morbidity. Similarly, Wiederkehr et al associated the need for blood transfusions and higher
MELD scores with worse survival rates.(27)
Intraoperatively, patients with higher MELD scores have also been shown to have more ascites, a
potential new addition to the MELD calculation. Independently, the presence of pretransplantation ascites has been associated with increased transfusion requirements.(28) Patients
with high MELD scores may present with other anesthetic risks as well.(5) Intraoperatively,
requirements of vasopressor, both in boluses and in continuous infusion, are significantly greater
in patients with higher MELD score than in those with lower MELD score.(5) Analysis after
exclusion of those patients who require vasopressors before transplantation shows the similar
results (Table 3). Although the analyses fail to show that the MELD score is an independent for
intraoperative hyperkalemia, MELD-related transfusion is a significant contributor to
intraoperative hyperkalemia.(29)
Conclusion
It is prudent to note that although there have been many studies correlating MELD scores with
various perioperative findings such as blood product transfusions, vasopressor requirements,
hospital stays, and overall morbidity and mortality, utilization of the MELD score to predict
perioperative risks has its shortcomings. First, the MELD score is designed to predict
pretransplant mortality, not intra- or post-operative outcomes. Therefore, it is not surprising to
see inconsistent and sometimes conflicting results from various studies. Second, the MELD
scores utilized across these studies are not uniform. The definition of what constitutes a “high”
MELD score is disparate and ranges from values as low as 18 to those as high as 30 and above.
A 12 point difference (or more) in MELD score may very well have significant implications on
severity of illness and, as a result, on overall outcomes. Nevertheless, as a widely available
index for severity of liver disease, the MELD score may be used by anesthesiologists to predict
those who present with more complex comorbidities and require additional resources,
monitoring, and higher level of care during the perioperative period.
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Table 1. Survival for pretransplant RRT liver recipients versus all other liver recipients
Initiated RRT
All other OLT
Initiated RRT
pretransplant
patients
posttransplant
P values
3-month
mortality
1-yr mortality
(n=32)
(n=220)
(n=28)
5/32 (15.6%)
9/220 (4.1%)
6/28 (21.4%)
0.02
9/30 (30.0%)
20/206 (9.7%)
7/27 (33.3%)
0.0045
From Wong LP, et al. Survival of liver transplant candidates with acute renal failure receiving
renal replacement therapy. Kidney International 2005; 68:362-370. With permission.
Table 2. Requirements of Total Transfusion in 5 Groups (in units, MSD)
MELD Scores
6-20
21-25
26-30
31-35
36-40
25
24
24
23
28
RBC
10.68.4
9.76.4
11.59.5
14.17.5
17.310.9 0.29
0.001
FFP
14.58.7 14.88.3 16.212.1 19.311.9 24.416.0 0.26
0.004
Platelets
0.70.7
1.01.0
0.90.9
1.30.8
1.41.0
0.26
0.004
Cryoprecipitate
0.60.7
0.50.7
0.50.9
1.00.8
1.11.0
0.26
0.004
Patients (n)
rs
p values
From Xia VW, et al. Preoperative characteristics and intraoperative transfusion and vasopressor
requirements in patients with low vs high MELD scores. Liver Transpl 2006; 12:614-620, p. 618,
with permission.
Table 3. Requirements for Intraoperative Vasopressors
Low MELD Group
High MELD Group
Before Exclusion
73
51
Infusion
14 (19.2)
27 (52.9)
<0.001
Bolus
12 (16.4)
21 (41.2)
0.007
Infusion or Bolus
20 (27.4)
32 (62.8)
<0.001
73
44
Infusion
14 (19.2)
22 (50.0)
0.001
Bolus
12 (16.4)
18 (40.9)
0.011
Infusion or Bolus
20 (27.4)
27 (61.4)
<0.001
After Exclusion
P Values
From Xia VW, et al. Preoperative characteristics and intraoperative transfusion and vasopressor
requirements in patients with low vs high MELD scores. Liver Transpl 2006; 12:614-620, p. 618,
with permission.
Multiple choice questions
1) The MELD score was initially developed to predict outcomes in
a. Patients with hepatorenal syndrome
b. Patients who have received transjugular intrahepatic portosystemic shunts (TIPS)
c. Patients with cirrhosis
d. B and C
e. A and C
2) Liver transplant candidates with co-existing renal dysfunction often arrive to the OR
a. Euvolemic
b. Hypervolemic
c. Hypovolemic
d. None of the above
e. All of the above
3) Studies suggest that liver transplant patients in renal failure have
a. A 5 % increase in overall mortality compared to those with normal renal function
b. A 10% increase in overall mortality compared to those with normal renal function
c. A 20% increase in overall mortality compared to those with normal renal function
d. A 30% increase in overall mortality compared to those with normal renal function
e. A 40% increase in overall mortality compared to those with normal renal function
4) Studies suggest that liver transplant candidates on RRT prior to transplantation exhibit
a. Lower mean arterial pressures
b. Greater need for pre-operative transfusions
c. Higher incidence of vasopressor infusions
d. B and C
e. A and C
5) Studies have indicated that patients with MELD scores greater than 30 may require on
average
a. 3 more units of RBC and 5 more units of FFP
b. 7 more units of RBC and 5 more units of FFP
c. 5 more units of RBC and 3 more units of FFP
d. 3 more units of RBC and 7 more units of FFP
e. 5 more units of RBC and 7 more units of FFP
6) Studies suggest that the following are predictive of intraoperative transfusion
requirements
a. MELD score and fibrinogen
b. MELD score and INR
c. MELD score and bilirubin
d. MELD score and creatinine
e. MELD score and PTT
7) Studies have shown that a MELD above what value is correlated with worsened 1-year
survival?
a. 18
b. 20
c. 24
d. 30
e. 35
8) Studies have suggested that patients with elevated MELD scores are
a. Approximately 5% more likely than those with low MELD scores to develop postoperative pulmonary complications
b. Approximately 10% more likely than those with low MELD scores to develop postoperative pulmonary complications
c. Approximately 15% more likely than those with low MELD scores to develop postoperative pulmonary complications
d. Approximately 20% more likely than those with low MELD scores to develop postoperative pulmonary complications
e. Approximately 25% more likely than those with low MELD scores to develop postoperative pulmonary complications
9) Studies have suggested that patients with higher MELD scores may be at increased risk
for developing post-operative mental status changes due to
a. Increased propensity for cerebral AVM’s
b. Disruption in cerebral autoregulation
c. Increased CMRO2
d. B and C
e. B only
10) Which of the following, alone with elevated MELD scores, have been shown to be
predictive of postoperative cardiac complications?
a. Adverse intraoperative cardiac events
b. Abnormal preoperative angiogram
c. Abnormal preoperative stress test
d. A and B
e. A only