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© Borgis - Anaesthesiology Intensive Therapy 1/2001
Cezary Pakulski, Roman Kostyrka, Grażyna Michalska-Krzanowska, Krystyna Dybkowska, Maciej Wójcicki, Tomasz Zawada, Wiesław Szewczuk, Elżbieta Pikuła, Romuald Bohatyrewicz, Stanisław Zieliński
Orthotopic liver transplantation: a retrospective analysis of 16 cases
Head: R. Bohatyrewicz M.D., Ph.D. IInd Department of General and Transplantation Surgery,
Head: prof. S. Zieliński Pomeranian Medical Academy, Szczecin
Summary
We have analyzed retrospectively sixteen orthotopic liver transplantations performed over three years in fifteen adult patients, aged 23-58 yrs (mean 40). The most common indication was cirrhosis.
All recipients were anaesthetized with sufentianil, vecuronium and isoflurane. Mean time of anaesthesia was 12 hours (8-20). Mean RBC transfusion volume was 6000 ml (1950 - 13350). Reperfusion syndrome has occured in seven cases. Five patients suffered acute rejection and four were infected with the CM virus. Three patients died: one from massive haemorrhage, one from the septic shock due to the acute liver abscess and another one at home, from cerebral haemorrhage. Intraoperative porto-caval anastomosis and preservation of the lower caval vein have limited number of circulatory complications.
We conclude that presented surgical and anaesthetic techniques are optimal for liver transplantation surgery.
Liver transplant is the world-wide accepted method of treatment of terminal liver insufficiency. Both for surgeons and anaesthesiologists this procedure constitutes the greatest possible challenge. The transplanted liver must resume its function as quickly as possible, as the retrieval of the organ for re-transplantation is, in our country, practically impossible. According to the State Transplant Agency "Poltransplant" about 240 potentially available livers are not transplanted each year for different reasons.
The first liver transplantation in an adult patient in Poland took place in 1987 in the State Clinical Hospital No. 2 in Szczecin. From this time, 19 liver transplants have been performed in this centre.
The beginning of the liver transplantat programme in our hospital was difficult. The first three patients operated on in 1987-1994 died between the 5th and 35th postoperative days. Retrospective analysis revealed that this was a consequence of incorrect qualification for the procedure as well as different surgical/anaesthetic complications. After modification of the surgical and anaesthetic techniques, from May 1996 to December 1998, 16 liver transplants were performed in 15 patients (1 retransplant). Up till now, 12 of them are alive, 3 having returned to work. The period of observation ranges from 4 to 32 months. Apart from our centre, liver transplants in Poland are successfully performed only in the Department of General and Liver Surgery (Medical University, Warsaw) in adults and in the "Child Health Centre -Memorial" Institute (Międzylesie near Warsaw) in children.
The aim of the study was to present the schema of anaesthesia accepted in our centre, the problems of the perioperative period and our own results of liver transplanting.
METHODS
Medical documentation of 15 patients (16 liver transplants) treated from May 1996 to December 1998 was analysed retrospectively. In one female patient, 82 days after transplant, a successful re-transplant was performed because of hepatic artery thrombosis. The decision to qualify a patient for transplantation was made by a multi-discipinary medical team, consisting of anaesthesiologists, surgeons and infectious disease specialists. In all patients the operative risk/hepatic functional reserve were assessed according to the Child-Turcotte scale modified by Pough [1]. One of the qualification criteria was the securing of blood and blood products for surgery: 60 units of packed red blood cells, 60 units of fresh frozen plasma, 6 units of platelets concentrate and cryoprecipitate obtained from 12 units of plasma. Preoperative treatment of the recipient was begun after the acceptance of the organ, announced available by "Poltransplant". Apart from the typical preoperative surgical preparation, the recipient received blood products transfusions to supplement the morphotic and coagulation deficits, omeprazole 40 mg i.v. and the first dose of antibiotics. According to the accepted scheme, about an hour before operation, the patient received piperacilline 4 g and ciprofloxacine 200 mg of. The next dose of antibiotics (2 g and 100 mg, respectively) was administered 8 hours later, during surgery. If necessary, fluconazole 100 mg was also infused. Premedication was individualised, based on the liver function according to the Child's scale. Patients qualified as Child's group B received midazolam 7.5 mg p.o., and group C - fentanyl 0.1 mg i.v. after the transfer to the operating room.
To minimise the risk of patient cooling, the temperature in the operating room was maintained at 28°C. The patient was placed on a warming mattress (Medi-Therm, Gaymar Industries, USA) and during anaesthetic preparation additionally covered with a warming blanket. The sufficient volume of crystalloids, 5 and 20% albumin and gelafundin were kept pre-warmed in a water bath.
After precurrarisation with vecuronium 0.02 mg/kg anaesthesia was induced with thiopentone 3 -5 mg/kg, suxamethonium 1 mg/kg and fentanyl 4-5 mg/kg. After oro- tracheal intubation an additional dose of vecuronium up to total of 0.08-0.1 mg/kg was administered. Mechanical ventilation was carried on with Sulla 909V or Julian (Dräger, Germany) anaesthetic apparatus. An air / oxygen mixture was used (FiO2 0.4-0.5; VT- 8 ml/kg, f - 12/min). The breathing circuit was equipped with an antibacterial filter, which additionally diminished the heat loss from the respiratory tract. Anaesthesia was maintained with izoflurane 0.4-1.0 vol%, and sufentanyl 0.8-1.0 mg/kg/h and vecuronium 0.05-0.07 mg/kg/h in continuous infusion. In three patients isoflurane was supplemented with alfentanyl and rocuronium (0,18 mg/kg/h and 5-8 mg/kg/h, respectively).
After checking the blood flow to the hands, according to the Allen's test, two arterial lines were connected to radial arteries. A heparinised line served to arterial blood pressure monitoring, a non-heparinised - to draw blood samples for laboratory tests. The veins of both upper extremities were cannulated with 4-6 large lumen catheters (12 or 14G, Ohmeda). A triple lumen dialyse catheter (8Fr, Arrow, USA) was introduced to the left subclavian vein to secure the route for rapid, large-volume transfusion of blood and blood products. Additionally a double - or triple lumen catheter (Arrow, USA) was introduced to the right internal jugular vein (for drug infusion). The same vein was also catheterised with an 8Fr Desilet-Hoffman catheter (Ohmeda, USA), by which a Swan-Ganz catheter (Ohmeda, USA) was introduced for haemodynamic monitoring. The preparation of the patient ended with insertion of a nasogastric tube (TRIP NGS Catheter, Tonometrics Division, Finland) and catheterisation of urinary bladder.
Continuous monitoring of vital signs included: ECG, heart rate, pulsoximetry, capnography, invasive blood pressure, central venous pressure and internal body temperature (Swan-Ganz catheter and rectal probe). At hourly intervals, the haemodynamic profile was assessed, including cardiac output and pulmonary arterial wedge pressure. At the same time intervals the degree of muscle relaxation, urine output and the volume of lost body fluids were also noted. Laboratory tests, determined every hour, consisted of: haematocrite value, platelet count, arterial blood gasometry, haemoglobin, albumin, total protein, glucose, creatinine and electrolyte concentrations (Na+, K+, ionised Ca++ and Mg++), coagulation parameters: prothrombin time, kaolin-kefalin time and fibrinogen concentration.
During the procedure, packed red blood cells, full blood and plasma were transfused with the use of an i.v. fluid warmer equipped with a micro-aggregation filter (Level 1 Technologies, USA). When indicated, the platelets concentrate was infused by slow drip infusion and cryoprecypitate with an automatic syringe at the rate of 10-20 ml/h. During surgery the patients received aprotinine (initial dose: 15000 U/kg during 30 minutes, then 7000 U/kg/h in the continuous infusion) [2].
The fluid balance was calculated at hourly intervals. Maintenance of diuresis above 1.5 ml/kg/min was observed. Apart from i.v. fluids, these required dopamine 2-3 mg/kg/min infusions, as well as administration of mannitol and diuretics (furosemide, spironolactone).
Surgery was performed without a veno-venous bypass. In 12 out of 16 transplants, a temporary end-to-side porto-caval shunt was used. After hepatectomy the recipient caval vein was anastomosed side-to-side with the graft vein. Then the temporary porto-caval shunt was closed, and portal venous anastomosis performed. In the retransplant case, no temporary porto-caval shunt was used. A side-to-side cavo-caval anastomosis was created between the inferior caval vein of the second donor and the inferior vena cava of the first graft. In the remaining 3 patients caval and portal veins were totally clamped during the anhepatic phase. To prevent an early immunological reaction, methylprednisolone 10 mg/kg was given prior to the reperfusion of the grafted liver. The reperfusion was started after performing venous anastomoses, before the hepatic arterial reconstruction. In the treatment of reperfusion syndrome, increased doses of catecholamines (dopamine, norepinephrine and epinephrine), calcium preparations and sodium bicarbonate were used. Biliary reconstruction was done as choledocho-choledocho end-to-end anastomosis with T-tube (Kehr) drainage in 8 patients, side-to side anastomosis without T-tube drainage in 7 patients. In one patient choledocho-jejunal anastomosis with a Roux-Y loop was performed. The control of haemostasis, abdominal drainage and abdominal wall in-layers suture ended the procedure.
In all patients a uniform scheme of post-transplant imunosuppression was employed: azathioprine 0.5-1.0 mg/kg, methylprednizolone in the gradually decreasing doses (starting from 40mg/kg x 4 p.d.) and cyclosporine 2-3 mg/kg (in the presence of satisfactory diuresis). Acute rejection episodes, refractory to high-dose steroids, were treated with OKT3 monoclonal antibodies or FK506. If cytomegalovirus infection occurred, ganciclovir was employed [3, 4].
The differences between the assessed parameters (mean ± standard deviation) were analysed with the Student's t-test for dependent series (p value accepted as significant <0.05).
RESULTS
Liver transplants were performed in 10 women and 6 men aged from 23 to 58 years (mean 40.3 ± 10.7). The indications for transplantation are presented in Tab. I. According to the Child-Turcotte classification, modified by Pough, ten patients were classified as grade B and six as grade C. At the beginning of surgery 2 patients were in hepatic coma.
Table I. Indications for liver transplantation
DiagnosisNo. of patients
Postinflamattory type b cirrhosis1
Postinflammatory type c cirrhosis3
Chronic autoimmunologic hepatitis2
Primary biliary cirrhosis3
Postalcoholic cirrhosis1
Primary sclerosing cholangitis1
Cryptogenic cirrhosis4
Hepatic artery thrombosis1 (retransplant)
Total: 16 transplants in 15 patients
Preparation for, and induction of anaesthesia were in all cases uneventful and lasted from 80 to 200 minutes (mean 118 ± 31 min). The duration of surgery ranged from 6 to 18 hours (mean 9h 52 min ± 31 min).
Apart from massive haemorrhagic episodes, the haemodynamic parameters were stable. After the construction of portocaval shunt a significant increase in cardiac output was noted. Reperfusion syndrome was observed in 7 patients, in whom the values of blood pressurre and cardiac index diminished by 20-40% as compared with the values before reperfusion.
During surgery, hourly diuresis was maintained at 1.5-2.5 ml/kg with the administration of diuretics. In one patient, during 10hours of surgery (with clamping of caval and portal veins), 750 ml of 20% mannitol solution and furosemide 600 mg were used.
Crystalloid fluids, blood and blood products transfused are presented in table II. The total volume transfused ranged from 10.1 to 35.9 l (mean 19.5 ± 7.2). Platelets concentrate was administered in 3 patients, cryoprecipitate in 9 patients.
Table II. Volume of transfused packed red blood cells (PRBC), fresh frozen plasma (FFP), crystalloids and colloids during liver transplantation
FluidMean ± SDRange
PRBC (units)19.7±10.66.5-44.5
FFP (units)29.0±12.315-54
Crystalloids (liters)4.8±1.42.8-8.1
Colloids (liters)2.9±1.50.5-6.25
1 unit of PRBC = 300 ml
1 unit of FFP = 200 ml

Seven patients were extubated after 24 hours, 2 - at 48 hours, 4 - at 72 hours and 1 - at 96 hours from the end ofsurgery. In one patient respiratory insufficiency persisted (this patient died). In 8 patients, the return of peristalsis enabled the early oral feeding (48h). In the remaining patients peristalsis returned 3 to 6 days after the operation. Table III presents the anaesthetic and surgical complications observed in the early and late postoperative period. These include acute graft rejection in 5 patients and cytomegalovirus infection in 4 persons. In 2 patients after the long lasting infusion of 10% calcium chloride to the peripheral vein, skin necrosis developed, requiring later skin grafting.
Table III. Anaesthetic and surgical complications in the perioperative period
Transplantation numberAnaesthetic complicationsSurgical complicationsDeath
1-Pneumothorax 
2Fluid balance: - 3000 ml- 
3Pulmonary oedema (1st postoperative day)Biliary leak around the T-tube 
4-Relaparotomy (3X) for subhepatic fluid pool; biliary leak around the T-tube - death 71 days after transplantx
5Multiple organ failure as a result of surgical complicationIntraoperative haemorrhage - death 14 days after transplantx
6Skin necrosis (right thenar) as the effect of peripheral infusion of CaCl2- 
7Prolonged artificial ventilation (interaction between anaesthetic drugs)- 
8Intraoperative pulmonary oedema (not resulting from fluid inbalance). Prolonged artificial ventilation (interaction of anaesthetic drugs)Drainage of ascitic fluid pools 
9-- 
10-Hepatic artery thrombosis 6 days after transplant treated with urokinase. Retransplant at 82 day 
11-- 
Retransplant-- 
13Skin necrosis (distal left forerarm) as the result of peripheral infusion of CaCl2- 
14Fluid balance: + 4700 mlDrainage of ascitic fluid pools 
15-- 
16-Relaparotomy for postoperative bleeding, DIC, septic shock - death 8 days after transplantx
From 15 patient in whom 16 liver transplants were performed, 3 patients died (2 in the early postoperative period - 8th and 14th postoperative day). In all of them the indication for liver transplant was hepatic postinfection cirrhosis type C. The first patient's death was attributed to multiorgan failure provoked by massive intraoperative bleeding. In the second patient an irreversible septic shock developed 7 days after transplantation. Histologic examination of the native liver removed during surgery revealed the presence of micro-abscesses. It can be recognised as an erroneous qualification. The third patient died 71 days after transplant, living a month at home, from cerebral haemorrhage. The most probable cause was bacterial sepsis originating from the perihepatic abscess. In 2 dead patients the anhepatic phase proceeded with caval and portal occlusion, in one - a temporary porto-caval shunt was constructed.
The remaining 13 transplants in 12 patients were successful. The patients were discharged home about 30 days after surgery in good or excellent general condition, One patient had to be retransplanted (82 days after the first transplant) because of hepatic arterial thrombosis. At present, 12 patients are alive, the time of observation ranging from 3 to 31 months.
DISCUSSION
Liver transplantating poses many more difficulties than any other surgical procedure. Choosing the method of anaesthesia requires careful evaluation of the influence of different drugs on liver function. All anaesthetic techniques diminish the hepatic blood flow, limiting the supply of blood and oxygen to the organ. The degree of blood flow reduction is a consequence of diminished cardiac output and lowered arterial blood pressure. Among anaesthetic techniques the least harmful for the liver function is general anaesthesia with isoflurane and total intravenous anaesthesia (midazolam + sufentanyl) [5]. In all our patients the first of these methods was employed. Nitrous oxide is contraindicated in liver transplantation. It easily diffuses to the closed spaces causing distension of the guts, which can be cumbersome for the operating team. Toxicity of N2O to haemopoietic system during massive bleeding and the danger of gas emboli during preparation of the veins of the liver additionally exclude this gas from anaesthesia in hepatic surgery. The standard technique of orthotopic liver transplant includes donor hepatectomy with the portion of retrohepatic inferior vena cava, which necessitate clamping of portal and caval veins. Total occlusion of these vessels causes the significant haemodynamic disturbances (diminished venous return, cardiac output and arterial blood pressure), lowers renal blood flow, increases (in most patients) portal pressure, causes hyperaemia of the intestinal wall (fluid loss to the third space, translocation of bacteria and their toxins) [6, 7]. These processes are especially manifested in recipients in whom collateral portal circulation has not developed (fulminant hepatitis), in patients with limited circulatory sufficiency and pulmonary hypertension [7]. In these patients a temporary veno-venous bypass (femoral vein / portal vein Ţ axillary vein) is necessary.
Creating a veno-venous bypass prevents adverse haemodynamic reactions and the stasis of blood in the splanchnic and renal vascular bed during the anhepatic phase of operation. This limits hyperaemic lesions to the intestinal wall, as well as reduces intraoperative bleeding [6,7]. Most centres, with a bio-pump (centrifugal pump) available, use veno-venous by-pass routinely or depending on the intraoperative assessment of haemodynamic tolerance to the occlusion of portal and inferior caval vein [9, 11]. The use of a bio-pump, however, prolongs the time of surgery, increases the procedure cost and is not free from complications [12, 13]. According to our data, only in 3 centres in Poland a bio-pump is available (Kraków, Warsaw and Wrocław).
Our alternative to the two operative techniques described above was a construction of a temporary porto-caval shunt at the first stage of transplanting. This technique was used for the first time in recipients without developed collateral portal circulation. The construction of the shunt is not time - consuming (in the authors' experience: 4-10 minutes) [14, 15]. In all patients with a porto-caval shunt, a transient hyperaemia and blood stasis in the intestinal wall and mesentery was observed during performing of porto-caval and porto-portal anastomosis. This regressed spontaneously after restoration of portal flow. In the authors' opinion, the temporary porto-caval shunt limits the extent of hyperaemic lesions of the intestinal wall, reduces blood loss from collateral vessels by reducing portal hypertension, and markedly ameliorates the results of liver transplantation. Owing to this manoeuvre no renal complications were observed in our recipients, which allowed the early beginning of immunosuppressive therapy with cyclosporine. By reducing the risk of hyperaemic intestinal lesions an early return of peristalis was observed in majority of patients. This allowed early enteral feeding and oral medical therapy, and shortening the period of intravenous administration of cyclosporine (the form of the drug has a strong nephrotoxic effect) to 2-3 days.
The most difficult stage of hepatic transplanting is hepatectomy in the recipient. Blood loss during laparotomy and preparing of the liver hilus is difficult to predict. The risk of massive bleeding results from the abundant network of collateral vessels both in abdominal wall, and in higly vascularised adhesions formed in peritoneum. The risk of bleeding is further increased by previous abdominal surgery and coagulation deficits.
The anhepatic phase lasts until the construction of caval donor-recipient anastomosis, closing of the porto-caval shunt and anastomosing the portal vein. Lack of hepatic function leads to decreased activity of antithrombine III, plasma coagulation prothrombin factors, lowered ionized calcium concentration, all of which promote coagulation disorders. Increased fibrinolysis tends to dominate, as the effect of the lack of a-2 antiplasmine production.
The opening of the porto-portal anastomosis begins the shortest stage of liver transplantating - the reperfusion phase. The inclusion of the transplanted liver into circulation washes out the remaining preserving solution, which leads to transient hiperkalemia, hipocalcemia, metabolic acidosis and hypothermia. The reaction of circulatory system to the reperfusion syndrome manifests itself by cardiovascular instability, characterised by bradycardia, hypotension, lowered cardiac index and diminished blood oxygen saturation [16, 17]. The correction of ionized calcium deficits before reperfusion is of special importance, as its concentration below 1.1 mmol/l increases the risk of severe reperfusion syndrome. We observed that in patients with a temporary porto-caval shunt, the course of the reperfusion phase was milder. As a preventive measure, graft lavage with 500 ml of 5% albumin solution, before portal declamping, was also undertaken.
In the analysed group of patients only a few serious complications were observed in the immediate postoperative period. Seven patients were extubated at 24, and 3 others - at 48 hours after transplant. This may be a result of minimal traumatization of the diaphragm and diaphragmatic nerves during surgery, as well as limited volume of fluids infused before hepatectomy [18, 19]. Malnutrition could be the cause of prolonged artificial ventilation in one of 4 patients extubated 3 days after transplantation [20]. In the remaining 3 patients, prolonged ventilation could result from the residual effect of rocuronium [21] (in these patients a different scheme of anaesthesia was employed: rocuronium, alfentanyl, isoflurane). One patient, reoperated twice for postoperative bleeding, was extubated on the 4th day. In one patient with massive intraoperative bleeding no signs of spontaneous ventilation were observed. In 2 patients, during the immediate postoperative period oliguria and increase in plasma creatinine concentration occured.
The final therapeutic result of a liver transplant depends on the participation of doctors of different medical specialities. The correct qualification of the recipient, preoperative care, histological assessment of the graft, are as important for the patient, as the skills of anaesthetic and surgical teams. The need to develop the liver transplantat programme in Poland is unquestionable. As this procedure, the most difficult in transplant practice, is also the most expensive, several specialised centres should further obtain financial guarantees from the State budget.
CONCLUSIONS
1. Liver transplant, also in Poland, is the only effective method of therapy in acute and chronic diseases leading to hepatic failure.
2. A temporary porto-caval shunt and preserving the recipient vena cava enables hepatectomy in relatively stable haemodynamic conditions.
3. General anaesthesia with isoflurane, fentanyl and vecuronium provides an adequate depth of anaesthesia, and early return of respiratory function.

Originally published in Anestezjologia Intensywna Terapia 31; (4), 241-246, 1999.
Received from:
Department of Anaesthesiology and Intensive Therapy
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Adres do korespondencji:
Hrubieszowska Str. 16/15; 71-047 SZCZECIN, Poland

Anaesthesiology Intensive Therapy 1/2001