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JOBNAME: AUTHOR QUERIES PAGE: 1 SESS: 3 OUTPUT: Fri Apr 8 06:39:04 2011
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Semmelweis University, Department of Transplantation and Surgery, Budapest, Hungary
Our reference: TPS 22977
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Volumetric Hemodynamic Changes and Postoperative Complications
in Hypothermic Liver Transplanted Patients
J. Fazakas, A. Doros, A. Smudla, S. Tth, B. Nemes, and L. Kbori
ABSTRACT
Introduction. Hepatic diseases decrease the livers involvement in thermoregulation.
Removal of the liver during transplantation increases the incidence of hypothermia during
the surgery. The aims of the present study were to analyze the hemodynamic changes
among hypothermic liver transplantations and to determine its relationship to postoper-
ative complications.
Methods. Conventional and volumetric hemodynamic monitoring and intramucosal pH
measurements were performed during 54 liver transplantations. According to the core
temperature until graft reperfusion, patients were classied into group A, hypothermic
patients (temperature 35C; n 25) versus group B, normothermic patients (temper-
ature 36C; n 29). We examined the relationships between central venous pressure
(CVP), intrathoracic blood volume index, cardiac index (CI), and oxygen delivery index,
oxygen consumption index, as well as the uctuation of the mean arterial pressure (MAP)
and gastric intramucosal pH and activated clotting time. We recorded prolonged ventila-
tion time, vasopressor and hemodialysis requirements, occurrence of infections, and
intensive care days.
Results. There were no signicant differences in the MELD scores. More ChildPugh
class C patients (P .01) showed signicantly higher APACHE II scores (P .02) among
group A. During hepatectomy and at the same intrathoracic blood volumes, the hypother-
mic group showed signicantly higher CVP levels (P .02). During the anhepatic and
postreperfusion phases, the decreased CI levels (P .05) were associated with increased
MAP values (P .05). Without differences in oxygen delivery, the oxygen consumption
was lower in group A (P .05). The intramucosal pH levels were the same in the both
groups during the whole examination period. More instances of infection, intensive care,
and hemodialysis treatment days, were observed as well as signicantly longer vasopressor
requirements and coagulopathy among the hypothermic group (P .007).
I
NTRAOPERATIVE hypothermia can be benecial dur-
ing neurosurgery and cardiac surgery. Monitoring for
maintenance of normothermia is generally necessary during
other types of surgery, because perioperative hypothermia
is a common complication of anesthesia and surgery.
1
Hepatic disease decreases the livers involvement in ther-
moregulation; in addition, excision of the liver during the
anhepatic phase and implantation of a cold graft during
transplantation produce mild core hypothermia.
2
Prospec-
tive, randomized trials have demonstrated hypothermia to
induce complications. The degree of hypothermia corre-
lates with increased plasma norepinephrine levels and
intraoperative blood loss with transfusion requirements.
Several studies have shown hypothermia to be associated
with perioperative cardiac events and increased rates of
surgical wound infections as well as longer hospital stays.
Altered drug pharmacokinetics during hypothermia may
increase postanesthetic recovery and ventilation times.
3,4
The purpose of the present study was to determine whether
From the Semmelweis University, Department of Transplanta-
tion and Surgery, Budapest, Hungary.
Address reprint requests to Jnos Fazakas, Semmelweis
University, Department of Transplantation and Surgery, Baross
utca 23. H-1082 Budapest, Hungary. E-mail: jancsidora@gmail.
com
2011 Published by Elsevier Inc. 0041-1345/see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.03.088
Transplantation Proceedings, xx, xxx (2011) 1
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hypothermia induced negative consequences by applying
volumetric hemodynamic monitoring and intramucosal pH
measurements. We also sought to determine its relationship
with postoperative complications among liver transplanted
patients.
METHODS
Fifty-four liver transplant patients were examined during this study.
According to their core temperature changes until venous reper-
fusion of the graft, we classied the patients into 2 groups. Group
A displayed mild core hypothermia despite intraoperative warming
(temperature 35C; n 25), whereas group B showed normo-
thermia with warming procedures (temperature 36C; n 29).
For detailed volumetric hemodynamic measurements, we placed a
femoral artery catheter and the PiCCO system (Pulsion, Germany).
A gastric air tonometer (TRIP; Tonometrics) was placed after
induction of anesthesia to measure intramucosal pH using a
Tonocap monitor (TC-200, Datex, Finland). The goal of hemody-
namic management was to optimize cardiac output, preload pa-
rameters, perfusion pressure, and systemic oxygen delivery. For
intraoperative warming, we used a full-length circulating water
mattress (Blanketroll II Thermoregulator CSZ) and an upper body
forced air cover blanket (Bair Hugger, Model 505 Temperature
Management Unit). Volume replacement therapy was delivered by
a fast ow blood and uid warmer (Automated Pressure Infusion
system, Level 1 Inc.) and we used an articial respiration Heat and
Moisture Exchangers (HME) lter. During transplantation, we
measured these parameters: hemodynamic (cardiac index [CI]
central venous pressure [CVP], intrathoracic blood volume index
[ITBI], extravascular lung water index [EVLWI], mean arterial
pressure [MAP], oxygenation [oxygen delivery, DO
2
]; oxygen con-
sumption, [VO
2
]; oxygen extraction rate, [O
2
ER]; pulmonary shunt
fraction, [Qs/Qt]; splanchnic perfusion (intramucosal pH [pHi]),
and activated clotting time (ACT). The measurement periods were
before surgery (BS); 1 and 2 hours during hepatectomy (H
12
),
anhepatic phase (AH), 10 minutes after reperfusion and arterial
anastomosis (Rep, Art) as well as end of surgery (ES). We analyzed
conventional liver and renal function parameters over the rst 5
postoperative days. We noted the underlying disease, age, Model
for End-Stage Liver Disease (MELD) and ChildPugh scores,
surgical time, packed blood cell transfusions and operative dura-
tion. The major postoperative complications were recorded: venti-
lation time, hemodialysis, and vasopressor requirements as well as
infections. We used the same protocol during anesthesia and
during transplantations employing the piggy back technique. The
study was performed in accordance with ethical standards of the
1975 Declaration of Helsinki. For statistical analysis we used Stat
View software (Abacus Concepts) for Students t-test, Wilcoxon
rank test, and the chi square test, considering a signicant differ-
ence to be a P .05.
RESULTS
There were no important differences between the 2 groups
regarding preoperative characteristics. The underlying dis-
ease distribution was similar (group A, hepatitis C virus
[HCV, n 9], alcoholic liver disease [ALD, n 5], primary
biliary cirrhosis [PBC, n 5], and primary sclerotising
cholangitis [PSC, n 1], autoimmune hepatitis [AIH, n
1], retransplantation [reTx, n 2], and cryptogenic etiolo-
gies [n 2]. Among group B, they were HCV (n 15),
ALD (n 3), PBC (n 2), PSC (n 3), hemangioma
(n 2), Wilsons disease (n 1), Budd-Chiari (n 2), and
congenital brosis (n 1; Table 1). There were no differ-
ences in the MELD scores. Group A included more Child
Pugh class C cirrhotic patients (P .01) with signicantly
higher APACHE II scores (P .02; Table 1). At the same
intrathoracic blood volumes, higher central venous pressure
levels were observed during hepatectomy in hypothermic
patients (P .02). In the anhepatic and postreperfusion
phases, decreased CI levels (P .05) were associated with
increased MAP values in group A (P .05). Without
differences in oxygen delivery, oxygen consumption was
lower in group A (P .05; Fig 1). The intramucosal pH
levels were similar in both groups during the whole exam-
ination period. Liver graft function was optimal in both
groups, but there were more azotemic patients among the
hypothermic group albeit not a signicant difference. Al-
though Group A subjects experienced more infection, and
more hemodialysis treatments, the values in group A were
signicantly worse only for vasopressor and transfusion
requirements and for coagulopathy (P .007; Table 1). No
arrhythmic or acute ischemic event was detected. There was
no difference in the duration of residence in the intensive
care unit between the 2 groups.
DISCUSSION
The risk of hypothermia may increase with the progression
of cirrhosis.
4
Global and regional circulation parameters
uctuate during transplantation because of bleeding or
Table 1. Demographic Data and Postoperative Complications
in Hypothermic and Normothermic Liver Transplanted Patients
Group A Group B P
Age (y) 45 7 42 8 NS
Male/female 10/15 17/12 NS
Apache II score 24 1.4 23 1.7 .02
Child-Pugh score A 1 (10.7%) 3 (5.8%) NS
Child-Pugh score B 12 (42.8%) 21 (41.2%) .06
Child-Pugh score C 12 (28.6%) 5 (29.4%) .01
MELD score 23 6 26 9 NS
Surgical time (min) 513 100 439 68 NS
Fresh frozen
plasma (U)
12 8 16 7 NS
Packet blood cell
(U)
18 8 10 6 .01
Vasopressor
therapy (12 h)
7 1 .007
Renal replacement
therapy
9 4 NS
Respiration time (h) 204 135 86 74 .05
Urinary infection 3 1 NS
Catheter related
infection
2 5 NS
Pneumonia 2 0 NS
ICU treatment (d) 4 1 4 1.3 NS
Hypothermic group A (n 25) and normothermic group B (n 29).
P .05.
2 FAZAKAS, DOROS, SMUDLA ET AL
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T1
F1
circulatory redistribution during the anhepatic phase.
5
Dur-
ing hypothermia, the increased serum norepinephrine con-
centration induces peripheral vasoconstriction with central-
ization of the circulation into the thoracic and abdominal
cavities.
3
The consequence of this shift is a higher CVP at
relative thoracic normovolemia, which may be disadvanta-
geous during hepatectomy because of increased bleeding.
There were no differences between the hypothermic and
normothermic groups in the ITBVI, SVR, DO
2
I parameters.
During transplantation, there were no signicant differences in
pH
i
between the 2 groups, because the redistribution of
circulation ensured better conditions for splanchnic perfusion,
with lower metabolic activity.
6,7
Transient organ dysfunction
and severe postoperative complications can occur when intra-
operative hypothermia is present because of more packed red
cells transfusions and longer postoperative vasopressor re-
quirements.
8
In conclusion, the incidence of hypothermia correlated
with the severity of liver disease. Hemodynamic changes in
hypothermic patients resulted in more unfavorable opera-
tive conditions. The need for intraoperative transfusions
was greater also due to hemodynamic changes and reduced
coagulation parameters. The hypothermic alterations in
hemodynamic and coagulation parameters seemed to be
related to postoperative complications.
REFERENCES
1. Leslie K: Perioperative hypothermia in high-risk surgical
patient. Best Pract Clin Anaesthesiol 17:485, 2003
2. DAmico DF, Vitale A, Cillo U, et al: Thermal homeostasis
and liver transplantation. Acta Bio Medica 74(suppl 2):30, 2003
3. Doufas AG: Consequences of inadvertent perioperative hy-
pothermia. Best Pract Clin Anaesthesiol 17:535, 2003
4. Janicki PK, Stoica C, Chapman WC, et al: Water warming
garment versus forced air warming system in prevention of intra-
operative hypothermia during liver transplantation: a randomized
controlled trial. BMC Anaesthesiol 2:7, 2002
5. Della Rocca G, Costa MG, Coccia C, et al: Preload and
hemodynamic assessment during liver transplantation: a compari-
son between pulmonary artery catheter and transpulmonary indi-
cator dilutional techniques. EJA 19:868, 2002
6. Russell SH, Freeman JW: Prevention of hypothermia during
orthotropic liver transplantation: comparison of three intraopera-
tive warming methods. Br J Anest 74:415, 1995
7. Okano N, Hiraoka H, Owada R, et al: Hepatosplanchnic
oxygenation is better preserved during mild hypothermic than normo-
thermic cardiopulmonary bypass. Can J Anesth 48:1011, 2001
8. Sessler DI: Complications and treatment of mild hypother-
mia. Anesthesiology 95:531, 2001
Fig 1. Hemodynamic, oxygenation, and coagulation changes
in hypothermic and normothermic liver transplanted patients
during transplantation (hypothermic group A [n 25] and
normothermic group B [n 29]. *P .05.
HYPOTHERMIC PATIENTS 3
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