Intraoperative blood and fluid administration differences in primary liver
transplantation versus liver retransplantation
Sheng-Chun Yang1, Chao-Long Chen2, Chih-Hsien Wang1, Chia-Jung Huang1, Kwok-Wai Cheng1,
Shao-Chun Wu1, Bruno Jawan1*
1Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.
2Liver Transplant Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.
a r t i c l e i n f o
Received 15 March 2011
Received in revised form
10 May 2011
Accepted 13 May 2011
blood loss, surgical;
a b s t r a c t
Objectives: Liver retransplantation (Re-LT) is the effective therapy for irreversible liver graft failure after
primary liver transplantation (LT). The challenges faced by the operative team in the Re-LT setting have
been seldom elucidated. Our aim is to analyze the differences in fluid management in primary LT and
Re-LT during the surgical procedure.
Methods: The anesthesia charts of 16 patients who underwent both primary LT and Re-LT at our center in
the space from October 1995 to May 2009 were analyzed. Group 1 (GI) consisted of patients who
underwent primary LT, whereas patients in Group 2 (GII) were patients in GI but underwent Re-LT. GI
was further divided into two subgroups depending on whether they had previous abdominal surgery
before primary LT (GIB) or not (GIA). Wilcoxon signed-ranks test was used to compare GI and GII, and GIA
and GIB. A p value less than 0.05 was regarded as significant. Data were given as mean ?standard
Results: Blood loss was significantly increased from 48.9 ?106 mL/kg in GI to 251.5?242 mL/kg in GII.
Consequently more blood products, crystalloids, sodium bicarbonate, calcium chloride, and neo-
synephrine were required to support the hemodynamics in GII. In GI, GIB tended to bleed more and
required more blood transfusions than GIA.
Conclusion: More bleeding is expected in Re-LT than primary LT. Additional anesthetic personnel, more
intravenous lines, and blood and blood products should be readily available to deal with the emergent
fluid and hemodynamic resuscitations in anesthesia for Re-LT.
Copyright ? 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights
Liver transplantation (LT) is the standard surgical therapy for
terminal liver failure.1One and 5-year survival rates as reported are
higher than 80% and higher than 70%, respectively, in experienced
centers.2e5In biliary atresia patients, the 5-year survival rate after
LT was 98%.5However, despite successful LT, the liver graft may be
subject to complications, damage from operative insults, or disease
recurrence, which may lead to irreversible graft dysfunction that
necessitate liver retransplantation (Re-LT).6The outcome of Re-LT
as reported is significantly inferior to that of primary LT.7e9This
may implicate that Re-LT is more challenging for the transplant
team. Anesthesia management in LT is already a challenge to most
anesthesiologists but whether Re-LT is a much bigger challenge
remains to be elucidated. There is still limited information about
the comparison of the anesthesia management in LT and Re-LT in
the same patients. The purpose of this study is to analyze the
differences in fluid management inprimary LTand Re-LT during the
Between October 1995 and May 2009, there were 16 patients
who underwent both primary LT and Re-LT at Kaohsiung Chang
Gung Memorial Hospital, Taiwan. The study protocol was approved
bythe Institutional Review Board for Human Studies of Chang Gung
Memorial Hospital. The anesthesia records were analyzed retro-
spectively. Preoperative hemoglobin (Hb), coagulationprofile, renal
* Corresponding author. Department of Anesthesiology, Kaohsiung Chang Gung
Memorial Hospital, Chang Gung University College of Medicine, No. 123, Ta-Pei
Road, Niao-Sung, Kaohsiung 833, Taiwan, R.O.C.
E-mail: firstname.lastname@example.org (B. Jawan).
Contents lists available at ScienceDirect
Acta Anaesthesiologica Taiwanica
journal homepage: www.e-aat.com
1875-4597/$ e see front matter Copyright ? 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved.
Acta Anaesthesiologica Taiwanica 49 (2011) 50e53
function, and albumin were recorded. All patients were monitored
on electrocardiography, continuous arterial blood pressure, and
pulse oximetry. Central venous pressure, end-tidal CO2, body
temperature, and urine output were, likewise, monitored. General
anesthesiawas induced with propofol and fentanyl and maintained
with isoflurane in an O2/air mixture combined with fentanyl when
Atracurium or cisatracurium was used as muscle relaxant. The
LT operation was performed pursuant to standard surgical tech-
nique without venovenous bypass. Dopamine 2 mg/kg/hr was given
continuously throughout the operation. Blood recirculating appa-
ratus was not used and antifibrinolytics were not given during
operation. During the LT procedure, based on the findings and
recommendations by Massicotte et al,10coagulation profile moni-
toring was not routinely performed. Arterial blood gas analysis was
done at least five times throughout the procedure (after induction
of anesthesia, 2ndand/or 4thhour through the operation, during
anhepatic phase,10 minutes after portal reperfusion, and at the end
of the operation). Metabolic acidosis was corrected with 7% sodium
bicarbonate when the base excess was greater than ?5%, and 5%
calcium chloride was administered to treat ionized hypocalcemia
when the serum ionized calcium was lower than 0.8 mmol/L.11
Crystalloid and 5% albumin as colloid, rather than blood products,
were used as blood loss replacement to maintain normovolemia.
Blood transfusion was started when the Hb level was lower than
6e7 g/dL. When blood transfusion was required, leukocyte-poor
red blood cells were given in amounts calculated to give a post-
transfusion target Hb of 9 g/dL. Fresh frozen plasma and platelets
were transfused only when blood clotting was not appreciated in
the surgical field. The total amount of crystalloid solutions, 5%
albumin, leukocyte-poor red blood cells, fresh frozen plasma, and
platelets given were recorded, analyzed, and compared.
The patients were divided into two groups: Group 1 (GI, Primary
LT) and Group 2 (GII, Re-LT). GI patients were further divided into
two subgroups depending on whether they had previous abdom-
inal surgery before primary LT (GIB) or not (GIA).
Because both pediatric and adult patients were included in this
series, the data on amount of blood loss, fluid replacements, and
blood and blood product transfusions given were converted into
milliliter/kilogram for statistical comparison. All data were pre-
sented as mean?standard deviation. Because the continuous data
could not fit the assumption of normal distribution, Wilcoxon
signed-ranks test was used. The difference was considered signifi-
cant when the p value was less than 0.05.
Sixteen patients underwent primary LT (3 deceased donor LT,13
living donor LT). There were nine male and seven female patients.
Table 1 shows the characteristics of the 16 patients. Eight patients
had abdominal surgery before primary LT, which included Kasai
operation, hepatectomy, cholecystectomy, and cesarean section.
The indications for Re-LT are shown in Table 1. Table 2 shows the
demographical data, baseline laboratory values, and intraoperative
parameters of the 16 patients at primary LT (GI) and at re-LT (GII).
There were no significant differences found in the patients’
There was no intraoperative mortality in this series. One patient
developed intraoperative cardiac arrest that required cardiopul-
monary resuscitation. In the very same patients who underwent
primary LT and then Re-LT, blood loss was significantly increased.
Blood loss in Re-LT was almost five times that of primary LT
(48.9?106 mL/kg in primary LT vs. 251.5?242 mL/kg in Re-LT)
(Table 2). All in all, the blood loss in GI was less than 50% of the
blood volume, whereas in the 13 of 16 patients in GII, the blood loss
was more than one blood volume.
The mean volume of crystalloids used in GI and GII was
175.1?110 mL/kg and 321.7?175 mL/kg, respectively. The mean
volume of crystalloid used was greater in GII and was statistically
significant (Table 3). The blood and blood products (i.e. leukocyte-
poor packed red cells and platelets) were also significantly greater
in GII than GI. Therewas no significant difference in the Hb levels at
the end of the operation between GI and GII. GII patients required
more sodium bicarbonate to buffer intraoperative metabolic
Characteristics of 16 patients.
No.SexDiagnosisPrevious abdominal surgery Age at primary LT (mo)Interval between primary LT and Re-LT (d)Indication for Re-LT
De novo HBV
2ndcirrhosis, biliary stricture
HAT with massive graft infraction
BA¼biliary atresia; F¼female; GSD¼glycogen storage disease; HAT¼hepatic artery thrombosis; HBV¼hepatitis B virus; HCC¼hepatocellular carcinoma; HCV¼hepatitis C
virus; LT¼liver transplantation; M¼male; PVT ¼portal vein thrombosis; Re-LT ¼liver retransplantation; VOD¼veno-occlusive disease of liver.
Comparison of demographic data, baseline laboratory values, and intraoperative
parameters between primary liver transplantation (Group I) and liver retrans-
plantation (Group II).
Parameter Group I Group II
Preoperative hemoglobin (g/dL)
Preoperative platelet (1000/mL)
Preoperative creatine (g/dL)
Anesthesia time (h)
aPPT¼activated partial prothrombin time; INR¼international normalized ratio.
Intraoperative fluid management in primary liver transplant versus retransplant51
acidosis and more calcium chloride to treat ionized hypocalcemia.
In GII, seven patients required neosynephrine and another two
patients required epinephrine to support their hemodynamics. In
contrast, only one patient required neosynephrine and epinephrine
was not used in any patient in GI (Table 3).
The blood loss in GIA and GIB was 26.5?24.2 mL/kg and
71.2 ?150.3 mL/kg, respectively, the blood and fluids replacement
were tended to be more in GIB (Table 4).
Our results show that the circumstance of anesthesia manage-
ment centered on blood loss and fluid replacement of the same
patients undergoing primary LT and Re-LT was significantly
different. The main cause of difference was in the blood loss. The
blood loss was significantly more in GII than in GI. The mean blood
loss of GII was almost five times more than the mean blood loss in
GI (251.5?242 mL/kg GII vs. 48.9?106 mL/kg GI). No patient in GI
had an episode of massive bleeding but 13 of the 16 patients in GII
had blood loss greater than their blood volume. It also indicated
that the hemodynamics of GII patients were more unstable than GI
and required more concentrated monitoring. From the results, the
requirements in fluid replacement, neosynephrine, sodium bicar-
bonate, and calcium chloride for maintaining hemodynamics were
also more in GII than in GI. Despite the relatively unstable hemo-
dynamics encountered in GII, sufficient urine output could still be
generated and maintained (Table 3).
In major abdominal surgery, blood loss should be appropriately
replaced. The initial bleeding is usually replaced by crystalloids in
three- to fourfold the volume of blood lost. When larger amounts of
bleeding are encountered or more than 20% of the total blood
volume is lost, blood product(s) transfusion is indicated.7Because
red blood cell and platelet transfusions have negative impact on
survival after LT,12,13we consider giving blood transfusion only
when the Hb level is lower than 6e7 g/dL. Normovolemic anemia is
allowed to occur in the recipient intraoperatively by allowing the
Hb to decrease naturally through surgical bleeding to as low as
6e7 g/dL and, then, maintain it at about 9 g/dL postoperatively.14
This level of Hb seemed to have no negative effect on the func-
tion of vital organs, such as the brain, heart, lungs, and kidneys, and
the recovery of the liver graft.14Table 3 shows that the Hb levels at
the end of the operation between groups were similar at around
9 g/dL indicating that both groups were not overtransfused.
Massive blood loss followed by massive blood transfusion and
fluid resuscitation is associated with increased mortality and
morbidity.15It is even reported to be a predictor of poor prognosis
in living donor LT recipients.16Massive bleeding had a negative
impact in patient survival after Re-LT in our series. One patient had
cardiac arrest during the procedure and the conditions of 5 of 16
patients in GII were critical during the postoperative period and all
5 patients died. The outcome of our Re-LT was inferior tothat of our
previous primary LT in biliaryatresia patients.5Likewise,significant
higher morbidity and mortality in Re-LT setting in comparison to
primary LT were also reported by other centers.7e9
In the LT setting, blood loss may vary from minimal to
massive.16,17In our pediatric LT, 42% did not require intraoperative
blood transfusion.14Similarly, Massicotte et al10reported that 79%
of their patients did not receive blood transfusion during LT. But LT
associated with massive blood loss are more often reported.16,18
Analyses show that it is difficult to predict blood loss before an LT
operation.10,19Neither preoperative nor intraoperative clotting
parameters were predictor for the intraoperative blood loss and
blood products used.10,19Hence, what is the primary reason why
Re-LT was associated with significantly more blood loss than
primary LTas shown by our results? Table 2 shows that both GI and
GII had prolonged international normalized ratio, activated partial
prothrombin time, and thrombocytopenia but only GII had massive
bleeding. These findings corroborate that preoperative coagulation
profile is not a predictor and does not correlate with intraoperative
blood loss.10,19It is, however, possible that technical factors rather
than patient-related factors are more important in the control of
intraoperative bleeding in the Re-LT setting.20Because the primary
LT and Re-LT operations were performed by the same surgical and
anesthesia teams where the only difference between the groups is
the previous LT, a history of primary LTcan, therefore, be deemed as
a contributing factor that caused five times more bleeding in GII.
The issue of whether previous abdominal surgery affects the
intraoperative blood loss or not is not settled. Ozier et al21found
that previous abdominal surgery was not a factor correlated with
blood loss, but other authors noted its relation to blood loss.22e24
The increase in blood loss is often attributed to surgical technical
problems associated with the presence of adhesions and collateral
vessels after previous abdominal surgery.22,25Eight patients in GI
had previous abdominal surgery (Table 1). When GI was divided
into two subgroups, analysis showed that patients with previous
abdominal surgery in the subgroup GIB tended to bleed more
(71.2 ?150.3 mL/kg in GIB vs. 26.5?24.2 mL/kg in GIA) and
required relatively more red blood cell (44.8?83.5 mL/kg in GIB vs.
14.4? 9.2 mL/kg in GIA) transfusion. It is expected that the surgical
technique to deal with problems related to adhesions in the inferior
vena cava (IVC) and hepatic veins from previous LT are more
challenging than adhesions after Kasai operation or other abdom-
inal surgeries not involving the IVC. Our results showed that blood
loss in patients without previous abdominal surgery (GIA), patients
with previous non-LT abdominal surgery (GIB), and patients after
LT surgery (GII) were in increasing order with blood loss at
26.5?24.2 mL/kg, 71.2?150.3 mL/kg, and 251.5?242.5 mg/kg,
respectively. The blood product transfusion requirements were
consequently in increasing order at 14.4? 9.2 mL/kg, 44.8?
83.5 mL/kg, and 151.8 ?115.9 mL/kg, respectively. These findings
Blood loss and intraoperative transfusion requirements in the 16 primary liver
transplantation (Group I) and liver retransplantation (Group II) recipients.
Parameter Group IGroup II
Blood loss (mL/kg)
5% Albumin (mL/kg)
Urine output (mL/kg/h)
Hemoglobin end op (g/dL)
Extubation time (h)
5% Calcium chloride
20.6?17.3 (n ¼16)
30.1 ?35.3 (n¼11)
0.2?0.2 (n ¼8/16)
0.0?0.0 (n ¼0/16)
0.4 ?0.6 (n¼8/16)
0.05 ?0.2 (n¼2/16)
FFP¼fresh frozen plasma; LPR¼leucocyte poor red blood cell.
Blood loss and intra-operative transfusion requirements in GIA and GIB patients.
Parameters GIA (n ¼8)
GIB (n ¼8)
Blood loss (mL/kg)
5% albumin (mL/kg)
FFP¼fresh frozen plasma; LPR¼leucocyte poor red blood cell.
S.-C. Yang et al52
indicate that previous abdominal surgery may be a factor that Download full-text
causes more blood loss and blood product consumption as previ-
ously reported by other authors.22,25
But not all Re-LT is associated with significantly more blood loss
than primary LT. The time interval between primary LTand Re-LT in
most GII patients was longer than 6 weeks (Table 1). There were
two patients who underwent Re-LT within 3 weeks (5 days and 16
days, respectively) because of hepatic artery thrombosis. The blood
loss during Re-LT was 13.5 mL/kg and 74 mL/kg, respectively. In
contrast, two patients with hepatic artery thrombosis but under-
went Re-LT beyond 6 weeks (44 days and 1072 days, respectively)
had massive bleeding during Re-LT with blood loss of 336 mL/kg
and 892 mL/kg, respectively. Primary LT per se, therefore, may not
be the sole cause of more bleeding during Re-LT. The presence of
adhesion in the great vessels and collateral vessels after primary LT
is probably another contributing factor for increased bleeding
during Re-LT. Because the number of our Re-LTseries was small and
only two patients underwent early Re-LT before adhesion in IVC or
collateral vessels might have set in, our findings would require
further validation with more cases over time.
Re-LT is associated with significantly more blood loss than
primary LT. Significantly, more fluids and blood and blood product
replacements are required. Greater amounts of sodium bicar-
bonate, calcium chloride, and neosynephrine are given in Re-LT
patients to maintain hemodynamics. Our report suggests that
more anesthetic personnel, more intravenous lines, and blood and
blood products should be readily available when conducting
anesthesia in Re-LT patients as these patients require more inten-
sive fluid resuscitation and close monitoring because of increased
1. Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, et al.
Evolution of liver transplantation in Europe: report of the European Liver
Transplant Registry. Liver Transpl 2003;9:1231e43.
2. Neuhaus P, Blumhardt G, Bechstein WO, Platz KP, Jonas S, Mueller AR, et al.
Comparison of FK506- and cyclosporine-based immunosuppression in primary
orthotopic liver transplantation. A single center experience. Transplantation
3. Busuttil RW, Farmer DG, Yersiz H, Hiatt JR, McDiarmid SV, Goldstein LI, et al.
Analysis of long-term outcomes of 3200 liver transplantations over two decades:
a single-center experience. Ann Surg 2005;241:905e16 [discussion 916e8].
4. Jain A, Reyes J, Kashyap R, Dodson SF, Demetris AJ, Ruppert K, et al. Long-term
survival after liver transplantation in 4,000 consecutive patients at a single
center. Ann Surg 2000;232:490e500.
5. Chen CL, Concejero A, Wang CC, Wang SH, Lin CC, Liu YW, et al. Living donor
liver transplantation for biliary atresia: a single-center experience with first
100 cases. Am J Transplant 2006;6:2672e9.
6. Chen GH, Fu BS, Yang Y, Cai CJ, Lu MQ, Li H, et al. Early liver retransplantation
versus late liver retransplantation: analysis of a single-center experience. Chin
Med J (Engl) 2008;121:1992e6.
7. Facciuto M, Heidt D, Guarrera J, Bodian CA, Miller CM, Emre S, et al. Retrans-
plantation for late liver graft failure: predictors of mortality. Liver Transpl
8. Bilbao I, Figueras J, Grande L, Cleries M, Jaurrieta E, Visa J, et al. Risk factors for
death following liver retransplantation. Transplant Proc 2003;35:1871e3.
9. Yao FY, Saab S, Bass NM, Hirose R, Ly D, Terrault N, et al. Prediction of survival
after liver retransplantation for late graft failure based on preoperative prog-
nostic scores. Hepatology 2004;39:230e8.
10. Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Effect of low
central venous pressure and phlebotomy on blood product transfusion
requirements during liver transplantations. Liver Transpl 2006;12:117e23.
11. Jawan B, de Villa V, Luk HN, Chen YS, Chiang YC, Wang CC, et al. Ionized
calcium changes during living-donor liver transplantation in patients with and
without administration of blood-bank products. Transpl Int 2003;16:510e4.
12. Pereboom IT, de Boer MT, Haagsma EB, Hendriks HG, Lisman T, Porte RJ.
Platelet transfusion during liver transplantation is associated with increased
postoperative mortality due to acute lung injury. Anesth Analg 2009;108:
13. de Boer MT, Christensen MC, Asmussen M, van der Hilst CS, Hendriks HG,
Slooff MJ, et al. The impact of intraoperative transfusion of platelets and red
blood cells on survival after liver transplantation. Anesth Analg 2008;106:
32e44 [table of contents].
14. Jawan B, de Villa V, Luk HN, Wang CS, Huang CJ, Chen YS, et al. Perioperative
normovolemic anemia is safe in pediatric living-donor liver transplantation.
15. Busani S, Semeraro G, Cantaroni C, Masetti M, Marietta M, Girardis M.
Recombinant activated factor VII in critical bleeding after orthotopic liver
transplantation. Transplant Proc 2008;40:1989e90.
16. Yuasa T, Niwa N, Kimura S, Tsuji H, Yurugi K, Egawa H, et al. Intraoperative
blood loss during living donor liver transplantation: an analysis of 635 recip-
ients at a single center. Transfusion 2005;45:879e84.
17. Cheng KW, Chen CL, Cheng YF, Tseng CC, Wang CH, Chen YS, et al. Dextrose in
the banked blood products does not seem to affect the blood glucose levels in
patients undergoing liver transplantation. World J Gastroenterol 2005;11:
18. Boylan JF, Klinck JR, Sandler AN, Arellano R, Greig PD, Nierenberg H, et al.
Tranexamic acid reduces blood loss, transfusion requirements, and coagulation
1996;85:1043e8 [discussion 30Ae31A].
19. Gerlach H, Slama KJ, Bechstein WO, Lohmann R, Hintz G, Abraham K, et al.
Retrospective statistical analysis of coagulation parameters after 250 liver
transplantations. Semin Thromb Hemost 1993;19:223e32.
20. Deakin M, Gunson BK, Dunn JA, McMaster P, Tisone G, Warwick J, et al. Factors
influencing blood transfusion during adult liver transplantation. Ann R Coll Surg
21. Ozier YM, Le Cam B, Chatellier G, Eyraud D, Soubrane O, Houssin D, et al.
Intraoperative blood loss in pediatric liver transplantation: analysis of preop-
erative risk factors. Anesth Analg 1995;81:1142e7.
22. Carlier M, Van Obbergh LJ, Veyckemans F, de Kock M, de Beys CC, Lavenne-
Pardonge E, et al. Hemostasis in children undergoing liver transplantation.
Semin Thromb Hemost 1993;19:218e22.
23. Cuervas-Mons V, Millan I, Gavaler JS, Starzl TE, Van Thiel DH. Prognostic value
of preoperatively obtained clinical and laboratory data in predicting survival
following orthotopic liver transplantation. Hepatology 1986;6:922e7.
24. Steib A, Freys G, Lehmann C, Meyer C, Mahoudeau G. Intraoperative blood
losses and transfusion requirements during adult liver transplantation remain
difficult to predict. Can J Anaesth 2001;48:1075e9.
25. Cuervas-Mons V, Julio Martinez A, Dekker A, Starzl TE, Van Thiel DH. Adult liver
transplantation: an analysis of the early causes of death in 40 consecutive
cases. Hepatology 1986;6:495e501.
Intraoperative fluid management in primary liver transplant versus retransplant53