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Intraoperative blood and fluid administration differences in primary liver transplantation versus liver retransplantation
Acta Anaesthesiologica Taiwanica 49 (2011) 50e53
Contents lists available at ScienceDirect
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Original Article
Intraoperative blood and fluid administration differences in primary liver transplantation versus liver retransplantation Sheng-Chun Yang 1, Chao-Long Chen 2, Chih-Hsien Wang 1, Chia-Jung Huang 1, Kwok-Wai Cheng 1, Shao-Chun Wu 1, Bruno Jawan 1 * 1 2
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. Liver 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
a b s t r a c t
Article history: Received 15 March 2011 Received in revised form 10 May 2011 Accepted 13 May 2011
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 deviation. 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 neosynephrine 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 Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved.
Key words: anesthesia, general; blood loss, surgical; fluid therapy; liver transplantation
1. Introduction Liver transplantation (LT) is the standard surgical therapy for terminal liver failure.1 One and 5-year survival rates as reported are higher than 80% and higher than 70%, respectively, in experienced centers.2e5 In biliary atresia patients, the 5-year survival rate after LT was 98%.5 However, 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).6 The outcome of Re-LT as reported is significantly inferior to that of primary LT.7e9 This
* 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: [email protected] (B. Jawan).
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 in primary LT and Re-LT during the surgical procedure. 2. Methods 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 by the Institutional Review Board for Human Studies of Chang Gung Memorial Hospital. The anesthesia records were analyzed retrospectively. Preoperative hemoglobin (Hb), coagulation profile, renal
1875-4597/$ e see front matter Copyright Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.aat.2011.05.011
Intraoperative fluid management in primary liver transplant versus retransplant
51
Table 1 Characteristics of 16 patients. No.
Sex
Diagnosis
Previous abdominal surgery
Age at primary LT (mo)
Interval between primary LT and Re-LT (d)
Indication for Re-LT
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
F M M M F M M M F F F F M M M F
BA HBV/HCC Fulminate HBV BA HBV HCV/HCC HBV/HCC HCV Fulminant Alagille BA GSD HBV/HCC HBV/HCV/HCC HCV/HCC
Kasai operation
14 624 14 408 66 528 660 456 612 324 12 31 156 492 648 708
2059 673 186 419 479 939 434 1475 1883 44 16 4243 1121 1072 1045 5
PVT, 2nd cirrhosis Recurrent HBV VOD Chronic rejection PVT Chronic rejection VOD Cryptogenic Recurrent HCV HAT HAT De novo HBV Idiopathic HAT, 2nd cirrhosis 2nd cirrhosis, biliary stricture HAT with massive graft infraction
Kasai operation
Cesarean section Laparotomy Kasai operation Hepatectomy Hepatectomy Hepatectomy, cholecystectomy
BA ¼ biliary atresia; F ¼ female; GSD ¼ glycogen storage disease; HAT ¼ hepatic artery thrombosis; HBV ¼ hepatitis B virus; HCC ¼ hepatocellular carcinoma; HCV ¼ hepatitis C virus; LT ¼ liver transplantation; M ¼ male; PVT ¼ portal vein thrombosis; Re-LT ¼ liver retransplantation; VOD ¼ veno-occlusive disease of liver.
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 anesthesia was induced with propofol and fentanyl and maintained with isoflurane in an O2/air mixture combined with fentanyl when required. Atracurium or cisatracurium was used as muscle relaxant. The LT operation was performed pursuant to standard surgical technique without venovenous bypass. Dopamine 2 mg/kg/hr was given continuously throughout the operation. Blood recirculating apparatus was not used and antifibrinolytics were not given during operation. During the LT procedure, based on the findings and recommendations by Massicotte et al,10 coagulation profile monitoring was not routinely performed. Arterial blood gas analysis was done at least five times throughout the procedure (after induction of anesthesia, 2nd and/or 4th hour 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 posttransfusion 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 abdominal 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 presented 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 significant when the p value was less than 0.05.
3. Results 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’ preoperative data. There was no intraoperative mortality in this series. One patient developed intraoperative cardiac arrest that required cardiopulmonary 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. leukocytepoor packed red cells and platelets) were also significantly greater in GII than GI. There was 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 Table 2 Comparison of demographic data, baseline laboratory values, and intraoperative parameters between primary liver transplantation (Group I) and liver retransplantation (Group II). Parameter
Group I
Group II
p
Age (mo) Weight (kg) Height (cm) Preoperative hemoglobin (g/dL) Preoperative platelet (1000/mL) Preoperative INR Preoperative aPPT Preoperative creatine (g/dL) Anesthesia time (h)
360 268 44.6 25.2 135.5 38.5 11.1 2.6 16.7 15.7 1.49 0.89 41.8 21.9 0.75 0.50 14.9 3.8
392 261 48.4 21.6 146.4 31.1 9.8 2.3 35.0 61.9 1.71 0.81 52.8 19.3 0.93 0.37 13.4 3.3
0.008 0.140 0.343 0.04 0.91 0.315 0.173 0.086 0.208
aPPT ¼ activated partial prothrombin time; INR ¼ international normalized ratio.
52
S.-C. Yang et al
Table 3 Blood loss and intraoperative transfusion requirements in the 16 primary liver transplantation (Group I) and liver retransplantation (Group II) recipients. Parameter
Group I
Group II
p
Ascites (mL/kg) Blood loss (mL/kg) LPR (mL/kg) FFP (mL/kg) Platelet (mL/kg) 5% Albumin (mL/kg) Crystalloid (mL/kg) Urine output (mL/kg/h) Hemoglobin end op (g/dL) Extubation time (h) 7% NaHCO3 (mL/kg) 5% Calcium chloride (mL/kg) Lasix (mg/kg) Epinephrine (mg/kg) Neosynephrine (mg/kg)
9.6 12.9 48.9 106.6 29.6 59.5 12.5 21.0 0.85 3.29 42.1 36.8 175.1 110.0 3.19 1.83 9.1 1.9 20.6 17.3 (n ¼ 16) 3.6 2.8 0.8 0.9
25.8 50.5 251.5 242.5 151.8 115.9 62.8 107.6 6.17 4.72 77.3 56.6 321.7 175.1 1.98 1.40 9.3 2.5 30.1 35.3 (n ¼ 11) 7.9 5.5 2.3 1.9
0.515 0.007 0.007 0.02 0.003 0.05 0.026 0.023 0.730 0.496 0.031 0.026
0.2 0.2 (n ¼ 8/16) 0.0 0.0 (n ¼ 0/16) 0.0001 0.0005 (n ¼ 1/16)
0.4 0.6 (n ¼ 8/16) 0.05 0.2 (n ¼ 2/16) 0.012 0.019 (n ¼ 7/16)
0.228 0.287 0.029
FFP ¼ fresh frozen plasma; LPR ¼ leucocyte poor red blood cell.
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). 4. Discussion Our results show that the circumstance of anesthesia management 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 bicarbonate, and calcium chloride for maintaining hemodynamics were also more in GII than in GI. Despite the relatively unstable hemodynamics 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.7 Because red blood cell and platelet transfusions have negative impact on survival after LT,12,13 we consider giving blood transfusion only when the Hb level is lower than 6e7 g/dL. Normovolemic anemia is Table 4 Blood loss and intra-operative transfusion requirements in GIA and GIB patients. Parameters
GIA (n ¼ 8)
GIB (n ¼ 8)
p
Blood loss (mL/kg) LPR (mL/kg) Crystalloids (mL/kg) 5% albumin (mL/kg) FFP (mL/kg)
26.5 24.2 14.4 9.2 130.3 80.0 34.4 28.1 8.24 18.6
71.2 150 44.8 83.5 214.2 122.1 48.7 43.8 16.17 23.5
0.674 0.958 0.189 0.779 0.361
FFP ¼ fresh frozen plasma; LPR ¼ leucocyte poor red blood cell.
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 function of vital organs, such as the brain, heart, lungs, and kidneys, and the recovery of the liver graft.14 Table 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.15 It is even reported to be a predictor of poor prognosis in living donor LT recipients.16 Massive 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 to that of our previous primary LT in biliary atresia patients.5 Likewise, 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.16,17 In our pediatric LT, 42% did not require intraoperative blood transfusion.14 Similarly, Massicotte et al10 reported 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.10,19 Neither preoperative nor intraoperative clotting parameters were predictor for the intraoperative blood loss and blood products used.10,19 Hence, what is the primary reason why Re-LT was associated with significantly more blood loss than primary LT as 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.10,19 It 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.20 Because 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 LT can, 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 al21 found 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.22,25 Eight 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 abdominal 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
Intraoperative fluid management in primary liver transplant versus retransplant
indicate that previous abdominal surgery may be a factor that causes more blood loss and blood product consumption as previously 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 LT and 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 underwent 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-LT series 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. 5. Conclusion 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 bicarbonate, 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 intensive fluid resuscitation and close monitoring because of increased perioperative bleeding. References 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 1995;59:31e40. 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.
53 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. Retransplantation for late liver graft failure: predictors of mortality. Liver Transpl 2000;6:174e9. 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 prognostic 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: 1083e91. 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. Transplantation 2004;77:1394e8. 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 recipients 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: 2789e91. 18. Boylan JF, Klinck JR, Sandler AN, Arellano R, Greig PD, Nierenberg H, et al. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 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 Engl 1993;75:339e44. 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 preoperative risk factors. Anesth Analg 1995;81:1142e7. 22. Carlier M, Van Obbergh LJ, Veyckemans F, de Kock M, de Beys CC, LavennePardonge 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.
Contents lists available at ScienceDirect
Acta Anaesthesiologica Taiwanica journal homepage: www.e-aat.com
Original Article
Intraoperative blood and fluid administration differences in primary liver transplantation versus liver retransplantation Sheng-Chun Yang 1, Chao-Long Chen 2, Chih-Hsien Wang 1, Chia-Jung Huang 1, Kwok-Wai Cheng 1, Shao-Chun Wu 1, Bruno Jawan 1 * 1 2
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. Liver 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
a b s t r a c t
Article history: Received 15 March 2011 Received in revised form 10 May 2011 Accepted 13 May 2011
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 deviation. 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 neosynephrine 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 Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved.
Key words: anesthesia, general; blood loss, surgical; fluid therapy; liver transplantation
1. Introduction Liver transplantation (LT) is the standard surgical therapy for terminal liver failure.1 One and 5-year survival rates as reported are higher than 80% and higher than 70%, respectively, in experienced centers.2e5 In biliary atresia patients, the 5-year survival rate after LT was 98%.5 However, 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).6 The outcome of Re-LT as reported is significantly inferior to that of primary LT.7e9 This
* 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: [email protected] (B. Jawan).
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 in primary LT and Re-LT during the surgical procedure. 2. Methods 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 by the Institutional Review Board for Human Studies of Chang Gung Memorial Hospital. The anesthesia records were analyzed retrospectively. Preoperative hemoglobin (Hb), coagulation profile, renal
1875-4597/$ e see front matter Copyright Ó 2011, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.aat.2011.05.011
Intraoperative fluid management in primary liver transplant versus retransplant
51
Table 1 Characteristics of 16 patients. No.
Sex
Diagnosis
Previous abdominal surgery
Age at primary LT (mo)
Interval between primary LT and Re-LT (d)
Indication for Re-LT
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
F M M M F M M M F F F F M M M F
BA HBV/HCC Fulminate HBV BA HBV HCV/HCC HBV/HCC HCV Fulminant Alagille BA GSD HBV/HCC HBV/HCV/HCC HCV/HCC
Kasai operation
14 624 14 408 66 528 660 456 612 324 12 31 156 492 648 708
2059 673 186 419 479 939 434 1475 1883 44 16 4243 1121 1072 1045 5
PVT, 2nd cirrhosis Recurrent HBV VOD Chronic rejection PVT Chronic rejection VOD Cryptogenic Recurrent HCV HAT HAT De novo HBV Idiopathic HAT, 2nd cirrhosis 2nd cirrhosis, biliary stricture HAT with massive graft infraction
Kasai operation
Cesarean section Laparotomy Kasai operation Hepatectomy Hepatectomy Hepatectomy, cholecystectomy
BA ¼ biliary atresia; F ¼ female; GSD ¼ glycogen storage disease; HAT ¼ hepatic artery thrombosis; HBV ¼ hepatitis B virus; HCC ¼ hepatocellular carcinoma; HCV ¼ hepatitis C virus; LT ¼ liver transplantation; M ¼ male; PVT ¼ portal vein thrombosis; Re-LT ¼ liver retransplantation; VOD ¼ veno-occlusive disease of liver.
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 anesthesia was induced with propofol and fentanyl and maintained with isoflurane in an O2/air mixture combined with fentanyl when required. Atracurium or cisatracurium was used as muscle relaxant. The LT operation was performed pursuant to standard surgical technique without venovenous bypass. Dopamine 2 mg/kg/hr was given continuously throughout the operation. Blood recirculating apparatus was not used and antifibrinolytics were not given during operation. During the LT procedure, based on the findings and recommendations by Massicotte et al,10 coagulation profile monitoring was not routinely performed. Arterial blood gas analysis was done at least five times throughout the procedure (after induction of anesthesia, 2nd and/or 4th hour 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 posttransfusion 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 abdominal 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 presented 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 significant when the p value was less than 0.05.
3. Results 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’ preoperative data. There was no intraoperative mortality in this series. One patient developed intraoperative cardiac arrest that required cardiopulmonary 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. leukocytepoor packed red cells and platelets) were also significantly greater in GII than GI. There was 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 Table 2 Comparison of demographic data, baseline laboratory values, and intraoperative parameters between primary liver transplantation (Group I) and liver retransplantation (Group II). Parameter
Group I
Group II
p
Age (mo) Weight (kg) Height (cm) Preoperative hemoglobin (g/dL) Preoperative platelet (1000/mL) Preoperative INR Preoperative aPPT Preoperative creatine (g/dL) Anesthesia time (h)
360 268 44.6 25.2 135.5 38.5 11.1 2.6 16.7 15.7 1.49 0.89 41.8 21.9 0.75 0.50 14.9 3.8
392 261 48.4 21.6 146.4 31.1 9.8 2.3 35.0 61.9 1.71 0.81 52.8 19.3 0.93 0.37 13.4 3.3
0.008 0.140 0.343 0.04 0.91 0.315 0.173 0.086 0.208
aPPT ¼ activated partial prothrombin time; INR ¼ international normalized ratio.
52
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Table 3 Blood loss and intraoperative transfusion requirements in the 16 primary liver transplantation (Group I) and liver retransplantation (Group II) recipients. Parameter
Group I
Group II
p
Ascites (mL/kg) Blood loss (mL/kg) LPR (mL/kg) FFP (mL/kg) Platelet (mL/kg) 5% Albumin (mL/kg) Crystalloid (mL/kg) Urine output (mL/kg/h) Hemoglobin end op (g/dL) Extubation time (h) 7% NaHCO3 (mL/kg) 5% Calcium chloride (mL/kg) Lasix (mg/kg) Epinephrine (mg/kg) Neosynephrine (mg/kg)
9.6 12.9 48.9 106.6 29.6 59.5 12.5 21.0 0.85 3.29 42.1 36.8 175.1 110.0 3.19 1.83 9.1 1.9 20.6 17.3 (n ¼ 16) 3.6 2.8 0.8 0.9
25.8 50.5 251.5 242.5 151.8 115.9 62.8 107.6 6.17 4.72 77.3 56.6 321.7 175.1 1.98 1.40 9.3 2.5 30.1 35.3 (n ¼ 11) 7.9 5.5 2.3 1.9
0.515 0.007 0.007 0.02 0.003 0.05 0.026 0.023 0.730 0.496 0.031 0.026
0.2 0.2 (n ¼ 8/16) 0.0 0.0 (n ¼ 0/16) 0.0001 0.0005 (n ¼ 1/16)
0.4 0.6 (n ¼ 8/16) 0.05 0.2 (n ¼ 2/16) 0.012 0.019 (n ¼ 7/16)
0.228 0.287 0.029
FFP ¼ fresh frozen plasma; LPR ¼ leucocyte poor red blood cell.
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). 4. Discussion Our results show that the circumstance of anesthesia management 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 bicarbonate, and calcium chloride for maintaining hemodynamics were also more in GII than in GI. Despite the relatively unstable hemodynamics 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.7 Because red blood cell and platelet transfusions have negative impact on survival after LT,12,13 we consider giving blood transfusion only when the Hb level is lower than 6e7 g/dL. Normovolemic anemia is Table 4 Blood loss and intra-operative transfusion requirements in GIA and GIB patients. Parameters
GIA (n ¼ 8)
GIB (n ¼ 8)
p
Blood loss (mL/kg) LPR (mL/kg) Crystalloids (mL/kg) 5% albumin (mL/kg) FFP (mL/kg)
26.5 24.2 14.4 9.2 130.3 80.0 34.4 28.1 8.24 18.6
71.2 150 44.8 83.5 214.2 122.1 48.7 43.8 16.17 23.5
0.674 0.958 0.189 0.779 0.361
FFP ¼ fresh frozen plasma; LPR ¼ leucocyte poor red blood cell.
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 function of vital organs, such as the brain, heart, lungs, and kidneys, and the recovery of the liver graft.14 Table 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.15 It is even reported to be a predictor of poor prognosis in living donor LT recipients.16 Massive 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 to that of our previous primary LT in biliary atresia patients.5 Likewise, 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.16,17 In our pediatric LT, 42% did not require intraoperative blood transfusion.14 Similarly, Massicotte et al10 reported 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.10,19 Neither preoperative nor intraoperative clotting parameters were predictor for the intraoperative blood loss and blood products used.10,19 Hence, what is the primary reason why Re-LT was associated with significantly more blood loss than primary LT as 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.10,19 It 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.20 Because 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 LT can, 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 al21 found 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.22,25 Eight 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 abdominal 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
Intraoperative fluid management in primary liver transplant versus retransplant
indicate that previous abdominal surgery may be a factor that causes more blood loss and blood product consumption as previously 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 LT and 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 underwent 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-LT series 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. 5. Conclusion 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 bicarbonate, 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 intensive fluid resuscitation and close monitoring because of increased perioperative bleeding. References 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 1995;59:31e40. 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.
53 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. Retransplantation for late liver graft failure: predictors of mortality. Liver Transpl 2000;6:174e9. 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 prognostic 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: 1083e91. 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. Transplantation 2004;77:1394e8. 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 recipients 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: 2789e91. 18. Boylan JF, Klinck JR, Sandler AN, Arellano R, Greig PD, Nierenberg H, et al. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 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 Engl 1993;75:339e44. 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 preoperative risk factors. Anesth Analg 1995;81:1142e7. 22. Carlier M, Van Obbergh LJ, Veyckemans F, de Kock M, de Beys CC, LavennePardonge 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.