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CASE REPORTS

ANESTHETIC MANAGEMENT DURING COMBINED LIVER AND


KIDNEY TRANSPLANTATION
Amr El Kouny1*, Mohammed Al Harbi1**, Hesham Ismail1*,
Chadi Abouras1***, Abdulatif Basha1*, Ibrahim Abojeesh1****,
Annas Naeim1*****, Sami Kashkoush2*, Abdullah Khalid2**,
Wael Ohali2*** and Vassilios DimitRIOU1******

Abstract

Combined liver and kidney transplantation is a highly demanding and challenging procedure
for anesthesiologists due to the lengthy and complicated nature of the procedure, the critical patient
condition and the need to balance the intravascular volume to maintain the venous outflow of the
hepatic allograft and also the diuresis of the renal allograft. Intravascular volume management
and coagulation control, seem to be the most important issues during combined liver and kidney
transplantation. There is sparsity of data in the literature concerning the anesthetic and fluid
management in CLKT. We present and discuss the anesthetic management in a case series in three
patients, who underwent combined liver and kidney transplantation in our institution during the
last two years.

Keywords: Liver Transplantation; Kidney Transplantation; coagulation management; fluids


management; Prothrombin Complex Concentrate; antifibrinolytic agents.

1 Department of Anesthesia, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Kingdom of Saudi
Arabia:
* Consultant, Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
** FRCPC, Assistant Professor, Department of Anesthesiology, King Saud University for Health Sciences, Deputy Chairman,
Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
*** Associate Consultant, Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
**** Assistant Consultant, Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
***** Staff Physician, Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
****** Professor of Anesthesia, Consultant, Department of Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
2 Department of Hepatobilliary Science and Liver Transplant, King Abdulaziz Medical City, National Guard Health Affairs,
Riyadh, Kingdom of Saudi Arabia:
* Consultant, Department of Hepatobiliary Surgery and Organ Transplantation, King Abdulaziz Medical City, Riyadh,
Saudi Arabia.
** Chairman, Department of Hepatobiliary Surgery and Organ Transplantation, King Abdulaziz Medical City, Riyadh, Saudi
Arabia
*** Deputy Chairman, Department of Hepatobiliary Surgery and Organ Transplantation, King Abdulaziz Medical City,
Riyadh, Saudi Arabia.
 Corresponding author: Vassilios Dimitriou, Professor of Anesthesia, Consultant, Department of Anesthesia, King
Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. P.O Box: 22490, Riyadh
11426 Phone: +9661180111 ext 19432. E-mail address: vaskdimi58@gmail.com

549 M.E.J. ANESTH 23 (5), 2016


550 Amr E. K. et. al

Introduction and 2 mcg.kg-1 fentanyl. Endotracheal intubation


was facilitated with 0.2 mg mg.kg-1 cis-atracurium.
With advancements in anesthetic techniques, The patients were mechanically ventilated with
surgical skills and perioperative management, patient oxygen/air mixture keeping arterial carbon dioxide
survival following liver transplant has been increased and oxygen tension between 35-40 mmHg and
considerably, showing a 10 years liver and patient 100-200 mmHg, respectively. Anesthesia was
survival above 50%1. It was found that about 18% of maintained with sevoflurane, continuous infusion of
the liver transplant patients would suffer from kidney intravenous fentanyl, and neuromuscular blockade
insufficiency requiring dialysis 13 yr after the surgery with continuous infusion of cis-atracurium. The
2
.This deterioration of kidney function was attributed left internal jugular vein was cannulated, using a
to calcineurin inhibitor-induced nephrotoxicity. triple lumen-central venous catheter for continuous
Furthermore, the adverse influence of decompensated infusion of intravenous medications, bolus fluid
liver on the kidney function among patients waiting administration and continuous central venous
for liver transplant has resulted in chronic renal pressure (CVP) monitoring. A Swan-Ganz catheter
insufficiency in 10-20% of them, and up to 8% introducer was placed also through the left internal
receive hemodialysis prior to liver transplant3,4. Pre jugular vein for massive volume replacement. The
liver transplant renal dysfunction is an important risk right internal jugular was avoided because of the
factor for post-operative sepsis, poor outcome and also presence of a dialysis line in the right subclavian vein.
it will increase the overall cost of transplantation3,5,6. The left femoral artery and the left radial artery were
Moreover, the incidence of renal failure following cannulated for continuous arterial blood pressure
liver transplant ranges from 12% to 70%7, and if a monitoring, arterial blood gases and laboratory
renal replacement therapy is needed, the mortality rate sampling. Cell saving was performed and salvaged
increases up to 40-90%8. To overcome these problems, blood was retransfused to the patients.
there is a more trend to perform combined liver kidney Pharmacologic hemodynamic management was
transplant (CLKT). achieved with norepinephrine infusion.
The United Network for Organ Sharing (UNOS)
data revealed that from 2001 to 2006, the number
Case 1
of performed CLKT was almost tripled reaching
about 400 CLKT in 20061. This was attributed to the
Female patient (44 years, 149 cm height, 67 kg
introduction of Model for End-Stage Liver Disease
weight, BMI 30kg/m2) with end stage liver disease
(MELD) scoring system, to allocate donor livers to the
(ESLD) due to hepatitis C liver cirrhosis. The
patients with a higher risk of mortality on the waiting
patient’s MELD score was 17. A cadaveric hepatic
list of liver transplant, due to the heavily weighted
allograft became available but she refused surgery.
serum creatinine value used in its calculation.
Renal function rapidly deteriorated, and dialysis was
required for 2 months, fitting the criteria for CLKT.
Anesthetic management The MELD score deteriorated to 40. Another liver
and kidney allografts were available, and CLKT
Standardized anesthetic technique including was planned. Preoperative laboratory findings were
general anesthesia and tracheal intubation was hemoglobin 89 g/L, platelet count 39,000/mm3,
used in our patients with some modifications done white blood cell count 3,400 cells/mm3, international
on case by case basis. After the patient’s informed normalized ratio (INR) 3.2, PTT 85 seconds,
consent was obtained they were taken to the fibrinogen 0.4 g/L, creatinine 163 µmol/l, electrolytes
operating room. Upon arrival, standard monitoring (K+, Na+, Cl-) within normal range, fasting blood
consisting of electrocardiogram, pulse oximetry, and sugar 5.2 mmol/l, and albumin 24 g/l. Preoperative
noninvasive blood pressure was established. General echocardiography and electrocardiogram were
anesthesia was induced with 2 mg.kg-1 propofol unremarkable.
ANESTHESIA FOR COMBINED LIVER AND KIDNEY TRANSPLANTATION
551

Continuous veno-venous hemodialysis with an procedure. During kidney transplant the CVP was
output of 250 ml/hour was initiated with the start of allowed to rise gradually till it reached 17 mmHg,
surgery. The baseline CVP reading was 9 mm Hg. before renal allograft reperfusion with crystalloid
It was maintained between 5 - 8 mmHg during the fluid administration. The CVP was kept at this level
preanhepatic, anhepatic phase and neohepatic phases until urine output was noted and then it was allowed
of liver transplant till the start of the renal transplant to decrease to 12 mmHg till the end of the procedure.
procedure. Then the continuous veno-venous Blood loss was 500 ml. Patient received one liter of
hemodialysis was stopped and the CVP was slowly 5% Albumin, 4 liters of normal saline and no blood
increased to 15 mmHg until renal allograft reperfusion products. Pharmacologic coagulation management
using crystalloid hydration with normal saline, and
was achieved with 1gr of tranexamic acid.
it was kept at this value until urine production was
noted. CVP was then gradually decreased again to
approximately 10 mmHg until completion of the Case 3
surgery. Total blood loss was 14 liters. Throughout
the surgery, the patient received 21 units (7350 ml) Male patient (61 years, weight 65 kg, height
of packed red blood cells, 17 units (3400 ml) of fresh 168 cm, BMI 23 Kg/m2) with ESLD secondary to
frozen plasma(FFP), 18 units (1260 ml) of platelets, cryptogenic cirrhosis, ESRD on hemodialysis for
50 units (1500 ml) of cryoprecipitate, 2500 ml of 3years, type 2 diabetes mellitus and hypertension.
cell saver blood and 15 liters of normal saline, and The patient’s MELD score was 23. The laboratory
produced 120 ml of urine. Additional coagulation evaluation showed hemoglobin 107 g/L, platelets
management was achieved with single doses of count 183,000/mm3, INR 1.3, fibrinogen 2.5 g/L, PTT
desmopressin (0.3 mcg/kg) and recombinant factor 37.3, electrolytes (K+, Na+, Cl-) within normal range,
VIIa (rFVIIa) (90 mcg/kg). fasting blood sugar 7.4 mmol/l and creatinine 476
µmol/l. The patient had mild mitral valve regurgitation
Case 2 and mild left atrial dilatation on echocardiographic
examination.
Female patient (54 years, weight70 kg, height Continuous veno-venous hemodialysis was on
154cm, BMI 29.5 kg/m2) with ESLD secondary to standby. The baseline CVP was 7 mmHg. CVP was
cryptogenic cirrhosis, type 2 diabetes mellitus (insulin maintained between 7-10 mmHg throughout the 3
treated), hypertension, dyslipidemia, hypothyroidism
phases of liver transplant. Then CVP was gradually
and end stage renal disease (ESRD). The patient’s
increased to 18 mmHg one hour before kidney allograft
MELD score was 25. The laboratorary evaluation
reperfusion and remained at this level till the end of
showed hemoglobin 128 g/L, platelet count 103,000/
surgery. Blood loss was 3 liters. The patient received 8
mm3, fibrinogen 2.1 g/L, INR 1.1, PTT 30.9, albumin
units (2800 ml) of packed red blood cells, 4 units (800
31 g/l, electrolytes (K+, Na+, Cl-) within normal
ml) of FFP, 10 units (300 ml) of cryoprecipitate, 500
range, fasting blood sugar 5.3 mmol/l and creatinine
ml of albumin 5%, and 13 liters of plasmalyte. Two
738 µmol/l. Electrocardiogram showed prolonged
QT interval, and echocardiography showed a right grams of tranexamic acid were given intraoperatively.
ventricular systolic pressure of 40-50 mm Hg with After completion of the surgery, the patients
mild tricuspid valve regurgitation. were transferred to surgical intensive care unit in a
Continuous veno-venous hemodialysis was on stable condition. They all had a smooth post-operative
standby. The baseline CVP reading was 12 mmHg. course,with good function of the liver and kidney
Despite fluid restriction, diuresis with mannitol and grafts,except case 2 whose kidney graft did not
initial temporary use nitroglycerin infusion, which work properly requiring hemodialysis, but she was
was stopped due to development of hypotension, CVP discharged home,and only comes to the hospital for
remained 10-12mmHg throughout liver transplant her dialysis sessions.
M.E.J. ANESTH 23 (5), 2016
552 Amr E. K. et. al

Discussion creatinine levels, more frequent need for dialysis and


increased mortality due to sepsis and graft failure16-1
Fluid volume management and coagulation In contrast, previous studies that Instead of decreasing
control seem to be the most important issues during CVP to an absolute numeric value range, they found
CLKT. There is sparsity of literature discussing the that decreasing CVP value 40% from baseline during
anesthetic and fluid management in CLKT9. In our the anhepatic phase of liver transplant, protected liver
cases, in agreement with previous study we tried to function, reduced intraoperative blood loss, and had no
make fluid management based on literature of isolated detrimental effects on renal function14,19.
liver transplant and kidney transplant10.
In another study comparing CVP above 10
During kidney transplant, a liberal hydration policy mmHg with CVP below 10 mmHg in the neohepatic
optimizing the cardiac output and renal blood flow is phase of liver transplant, the investigators did not find
usually employed intraoperatively targeting a CVP any difference in terms of immediate postoperative
between 10 - 15 mm of Hg to decrease the incidence of allograft function, graft survival, or patient survival.
postoperative renal graft acute tubular necrosis11,12. This may support our practice of gradually increasing
In contrast, it is believed that maintaining a the CVP in the neohepatic phase in preparation for
low CVP limits blood loss during liver resection and kidney transplant20.
orthotopic liver transplant, reducing the need for blood During kidney transplant, hemodynamic stability,
product transfusion and its associated negative impact better intraoperative renal allograft turgidity, earlier
on postoperative patient outcomes13-15. Although there diuresis, and rapid improvement of postoperative renal
is no clear evidence for the ideal level during liver function, were accomplished with maximal hydration
transplantation, the CVP is generally maintained targeting a CVP of 15 mmHg within an hour before
between 5-10 mmHg16,17. However, keeping the CVP renal allograft reperfusion, followed by replacement of
in the desired range is very difficult in cases where urine output targeting a CVP of 8 to 10 mmHg12.
there is both coagulopathy and a need to administer
Although the CVP was low in case 1, the patient
blood products14. Additionally, in the CLKT this is
presented significantly increased intraoperative blood
obviously controversial, since keeping the CVP low
loss and increased blood products transfusion. However,
seems to be critical for anesthesia management during
the patient had a MELD score 40. This supports
liver transplantation, while it has to be increased during
considering many factors affecting intraoperative blood
renal transplantation.
loss other than the isolated CVP, like the preoperative
More controversy comes from that, it has been patient condition, surgical technique and also the donor
demonstrated that CVP values <5mmHg could parameters (donor risk index)20,21.
be a reason for hypotension and deterioration of
It is important to note that the CVP is being replaced
microperfusion in liver grafts14,16,17.
with newer hemodynamic parameters, such as stroke
In our cases we tried to keep the CVP below 10 volume variation (SVV)22,23, which may be used to guide
mmHg during the preanhepatic and the anhepatic phases fluid management in the patients receiving mechanical
in accordance with other studies14-16 and then CVP was ventilation. Despite the superiority of SVV to CVP, the
increased to 10 mmHg between the neohepatic phase promising results of its use in the patients undergoing
and 1 hour before the renal allograft reperfusion, where liver or kidney transplant are still evolving24,25.
the patients were fully hydrated with crystalloids, with
According to the European Renal Best Practice
a maximum CVP of 15 mmHg, 17 mmHg and 18
(ERBP) Transplantation guidelines there is no
mmHg, in cases 1, 2 and 3 respectively.
evidence to prefer one type of solution for intravenous
During preanhepatic and anhepatic phases, CVP volume management of the recipient during kidney
was not allowed to decrease below 5 mmHg. There is transplant surgery, with recommendation to monitor
increased evidence indicating that CVP values <5 mmHg for metabolic acidosis when normal saline is used as
should be avoided during the anhepatic phase until the the only intravenous fluid in the perioperative period26.
end of surgery, since this is associated with elevated In our case series we used normal saline for crystalloid
ANESTHESIA FOR COMBINED LIVER AND KIDNEY TRANSPLANTATION
553

volume replacement in cases 1 and 2, and Plasmalyte catastrophic bleeding, when coagulopathy is evident.
in case 3. There is a report comparing normal saline, Although the available data on safety in this population
lactated Ringer's and Plasmalyte, in kidney transplants does not suggest an increased risk of thrombotic,
of living related donors. The conclusion was that all thromboembolic and ischaemic events associated with
three crystalloid solutions can be safely used during PCC and fibrinogen concentrate use, the data are scarce
uncomplicated, short-duration renal transplants; and need to be confirmed in large trials35,36. Currently
however, better metabolic profile was maintained in the first two multicentre, randomized, double-blinded
patients who received Plasmalyte27. trial comparing the routine use of prothrombin complex
Transfusion and coagulation management during concentrate (PCC) or fibrinogen concentrate with a
CLRT is challenging and coagulopathy is usually placebo in patients undergoing LT are still pending37,38.
multifactorial28. Clinical strategies to reduce blood Recombinant factor VIIa (rFVIIa) was used
loss during CLRT include the use of blood products by Busani et al., in a series of seven patients with
to correct pre-existing or intraoperative coagulopathy. persistent severe bleeding after application of a standard
This is achieved by transfusion of fresh frozen plasma transfusion protocol, in a dose similar to what we
(FFP), platelet concentrate, cryoprecipitate and used in case 1 (90 mcg/kg). Blood losses and need for
antifibrinolytic agents to correct hyperfibrinolysis platelets transfusion significantly decreased after rFVIIa
that may occur during the procedure28. In our administration; a non-significant decrease in red blood
cases the coagulation management was guided by cell and fresh frozen plasma transfusions also occurred.
thromboelastography (TEG), performed hourly In six patients treatment with rFVIIa was effective;
during the surgical procedure, as well as conventional only one patient died because of haemorrhagic shock,
coagulation parameters. The use of TEG for coagulation and no thromboses were detected among the treated
management constitutes the more recent trend in patients. The study suggested that in some challenging
coagulation monitoring29-31. A major disadvantage of cases of massive bleeding rFVIIa should be considered
transfusion of blood products such as FFP is volume
as a useful option to control bleeding39.
overload. To correct a prolonged PT during CLRT
several units of FFP are needed, which will result in an Tranexamic acid was administrated in case
increase in CVP and portal (splanchnic) venous blood 2, it was given also in case 3. It seems to be the
pressure and in fact will increase the bleeding risk. antifibrinolytic agent of choice in liver transplantation,
being equally efficacious as the currently unavailable
Prothrombin complex concentrate (PCC) are
aprotinin. As opposed to a blind prophylaxis with
hemostatically active highly purified concentrates,
antifibrinolytics in liver transplantation a goal directed
prepared from pooled plasma32. They contain all four
therapy, by using thrombelastometry to assess
vitamin K-dependent clotting factors (II, VII, IX and
fibrinolysis, has been suggested31,40.
X). In contrast to the traditional infusion of FFP to
stimulate coagulation in cirrhotic patients, PCC does Desmopressin acetate (DDAVP) was used in case
not add to the intravascular volume and therefore may 1.Desmopressin increases the levels of factor VIII,
be, theoretically, more effective in reducing bleeding vWF, and plasminogen. DDAVP appears to improve
complications than FFP infusion32. blood coagulability during liver transplantation in vitro,
possibly by activating coagulation factors and platelets41.
It has been demonstrated that hypofibrinogenemia
is associated with increased hemorrhage during liver In conclusion, CLKT is a highly demanding and
transplantation28. Fibrinogen concentrate is also challenging procedure for anesthesiologists due to the
produced from pooled human plasma. It is stored as lengthy and complicated nature of the procedure, the
a lyophilised powder at room temperature and can be critical patient condition and the need to balance the
reconstituted quickly with sterile water and infusion intravascular volume to maintain the venous outflow
volumes are low, allowing for rapid administration of the hepatic allograft and also the diuresis of the renal
without delays for thawing or cross-matching33,34. In allograft. Appropriate intraoperative fluid management
many centers, PCC and fibrinogen concentrate are tailored to each phase of CLRT surgery and targeted
used “off-label” during LT as a rescue therapy during coagulation management may have favorable results.
M.E.J. ANESTH 23 (5), 2016
554 Amr E. K. et. al

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