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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.61 no.3 Campinas May/June 2011
Bruno Salomé de Morais, TSAI, Marcelo Dias SanchesII; Daniel Dias RibeiroIII; Agnaldo Soares LimaII; Teresa Cristina de Abreu FerrariIV; Malvina Maria de Freitas DuarteV; Guilherme Henrique Gomes Moreira CançadoVI
IM.Sc., Ph.D. in Medicine from UFMG; Member of SBA Organ Transplant Commitee, Anesthesiologist of the Grupo de Transplante of Instituto Alfa de Gastroenterologia/UFMG and Hospital Lifecenter
IIM. D. from UFMG; Surgeon of the Grupo de Transplantes of Instituto Alfa de Gastroenterologia (IAG)/UFMG, Professor of Surgery/UFMG
IIIM. D. in Medicine from UFMG; Hematologist and Clinical Pathologist
IVM. D. from UFMG; Professor of Internal Medicine of UFMG
VM.Sc. Student in Medicine at UFMG; Nursing Professor of PUC-MG and Nurse of the Grupo de Transplantes of Hospital das Clínicas da UFMG
VIMedical Student/UFMG; Scholarship from FAPEMIG
BACKGROUND AND OBJECTIVES: Liver transplant (LT) surgery is associated with significant bleeding in 20% of cases, and several authors have demonstrated the risks related to blood components. The objective of the present study was to evaluate the impact of using blood components during hospitalization in five-year survival of patients undergoing LT.
METHODS: One hundred and thirteen patients were evaluated retrospectively. Several variables, including the use of blood components intraoperatively and throughout hospitalization, were categorized and evaluated by univariate analysis using Fisher's test. A level of significance of 5% was adopted. Results with p < 0.2 underwent multivariate analysis using multinomial logistic regression.
RESULTS: Parenchymal diseases, preoperative renal dysfunction, and longer stay in hospital and ICU are associated with greater five-year mortality after LT (p < 0.05). Unlike the intraoperative use of blood components, the accumulated transfusion of packed red blood cell, frozen fresh plasma, and platelets during the entire hospitalization was associated with greater five-year mortality after liver transplantation (p < 0.01).
CONCLUSIONS: This study emphasizes the relationship between the use of blood components during hospitalization and increased mortality in five years after LT.
Keywords: Blood Component Transfusion; Liver Transplantation; Fatal Outcome.
Liver transplantation (LT) is the only definitive treatment for end-stage liver disease. Even with the great advance and improvement of surgical results, since it was first described in 1963 by Starzl, LT still has high morbidity because it is a complex surgery performed in patients with multisystem involvement and poor functional reserve.
In recent years, a considerable reduction in the use of blood components has been observed in LT 1-5. However, the surgery is associated with significant bleeding in 20% of cases 6.
Some authors 7-10 have correlated the intraoperative use of blood components with a reduction in one-year survival after LT. However, there is a lack of studies evaluating the total impact of blood components received during hospitalization and survival after LT.
The main objective of the present study was to evaluate the association of blood transfusion from surgery to hospital discharge with five-year survival of patients undergoing LT.
This is a retrospective study of 113 patients undergoing orthotopic liver transplantation at the Hospital das Clínicas (HC) of Universidade Federal de Minas Gerais (UFMG) between 2001 and 2004. After exclusion of patients younger than 18 years of age (n = 11), live donor liver transplantation (n = 3), retransplantation (n = 2), surgery due to fulminant hepatitis (n = 2), and death intraoperatively or within the first 24 hours after surgery (n = 2), the data from 93 patients were analyzed. Follow-up was terminated in September 2009. The piggyback surgical technique was used in all patients.
Several variables regarding the receiver were evaluated: age, sex, baseline liver disease (Model of End-stage Liver Disease - MELD), calculated c eatinine clearance (Cockcroft-Gault equation), duration of surgery, length of stay in the intensive care unit (ICU), and duration of hospitalization. Patients were separated according to the use of blood components and they were also classified according to the sum of blood components transfusion (Table I).
Patients were classified into four groups according to MELD at the time of surgery: < 10, 11 to 18, 19 to 24, and > 25. This categorization followed the standardization of the Health Ministry for the validity of exams in order to be placed in the waiting list.
Regarding baseline liver disease, the classification was made into categories: parenchymatous, cholestatic, and others.
Preoperative renal dysfunction was characterized according to a creatinine clearance lower than 70 mL.min-1.
The initial data analysis as well as the results obtained in the literature guided the categorization of continuous variables.
Based on from database, a descriptive analysis was performed on sex, age, primary diagnosis, preoperative renal function, CTP, MELD, duration of surgery, length of stay in ICU, duration of hospitalization, transoperative transfusion of packed red blood cell (PRBC), frozen fresh plasma (FFP), platelets, and cryoprecipitate (CRIO), as well as transfusion of PRBC, FFP, platelets, and CRIO during the entire hospitalization period. Fisher's test was used to determine the association between survival and descriptive variables. A level of significance of 5% was used. The results of univariate analysis with p < 0.2 underwent multivariate analysis. Multinomial logistic regression was used in the multivariate analysis. The SPPP, version 10.0, and StatXact, version 4, were the statistical software used.
Of the 93 patients, 60 (64.5%) were male. Their age ranged from 18 to 75 years, with a mean of 48.8 ± 10.97 years. Regarding the baseline liver disease, 77 (82.8%) were parenchymatous, 10 (10.8%) cholestatic, and 6 (6.5%) were classified as others.
Twelve (12.9%) patients were classified as CTP A, 65 (69.9%) as B, and 16 (17.2%) as C. The MELD ranged from 9 to 36, with a median of 16. Preoperative renal dysfunction had an incidence of 27.6%.
Table II shows the use of blood components intraoperatively and during hospitalization.
During surgery, 26.9% of patients did not receive any blood transfusion, while 10.8% did not receive blood products during hospitalization.
The duration of the surgery ranged from 4 hours and 20 minutes to 12 hours, with a mean of 7:02h ± 1:32h. The length of stay in ICU ranged from 3 to 19 days, with a mean of 4.29 ± 3.37 days, while the length of postoperative hospitalization ranged from 7 to 90 days, with a mean of 19.32 ± 13.81 days.
Twenty-two patients (23.7%) died within five years, with survival ranging from 2 to 1,495 days, with a mean of 189.77 ± 357.06 days and median of 25 days. The causes of death were cardiovascular in three patients (3.2%), surgical in six patients (6.5 %), infectious in eight patients (8.6%), and other in five patients (5.4%). The 30-day, and 1- and 5-year survival was 86%, 81%, and 76%, respectively.
The results of univariate analysis are shown in Table III. All variables with p < 0.2 underwent multivariate analysis, but none of them was proven to be an independent predictor of survival.
The Model of End-stage Liver Disease, the severity criteria for allocation in the waiting list of LT, was not associated with mortality after transplant at the HC of UFMG in the studied period. Several studies have shown contradictory results regarding the capacity of the MELD to predict mortality after liver transplant 11-14.
Survival rate after LT in patients with cholestatic liver disease was lower than that of patients with parenchymatous disease (p = 0.048), which is similar to the results reported in literature 15.
Although relatively frequent in LT, with an incidence that ranges from 10.0% to 33.0% 16,17, preoperative renal dysfunction is difficult to define. Serum creatinine, the most frequently used test, is not a good method for cirrhotic patients since it overestimates the renal function of these patients 16. The calculated creatinine clearance (Cockcroft-Gault) estimates the glomerular filtration rate, taking into account the sex, weight, and age of the patient, besides the serum creatinine. In patients with liver disease the normal limit should be over 70 mL.min-1. Preoperative renal dysfunction is associated with increased need for postoperative hemodialysis, primary liver dysfunction, and increased mortality 16,18, having great influence on quality of life and survival of patients after transplants. Similar to other studies, preoperative renal dysfunction was associated with lower survival after LT (p = 0.008).
A large variation in the use of blood products, both intraoperatively and during hospitalization was observed. This variation was probably due to a wide heterogeneity in the severity of patients undergoing LT and to risk factors, such as prior abdominal surgeries, coagulopathies, central venous pressure, preoperative levels of hemoglobin, and greater duration of surgery or hospitalization 19. The mean rate of transfusion in our institution was similar or lower than that reported by other authors 1,20-22.
In the last 20 years, an important reduction in transfusion has been observed, from a mean of 43 PRBC and 41 FFP per patient to only 0.3 units of PRBC per patient without FFP 9. The greater knowledge of transfusion-related complications, associated with improvements in surgical-anesthetic techniques, has contributed for a more rational use of blood components.
Several studies have shown the association between transfusion of PRBC and reduction of survival after LT 1,2,7,8,24. At the same time, physicians are increasingly aware of the immunomodulatory effects caused by transfusion in almost all patients. These effects may increase the risk of nosocomial infections, acute lung injury, and the development of longterm autoimmune disorders 25. This has been attributed to depression of the immune system, known as transfusion-related immune modulation (TRIM), and changes in blood products that can occur during storage 28.
The syndrome known as transfusion-related acute lung injury (TRALI) is a non-cardiogenic acute pulmonary edema that can be seen in up to 6 hours after transfusion of plasmacontaining blood components 27. Patients undergoing LT are at increased risk of developing TRALI, and it has been suggested that ischemia and reperfusion of the graft would represent predisposing conditions 28.
Univariate analysis, performed by Fisher's test, found an association between the transfusion of PRBC, FFP, and platelets during hospitalization with the 5-year mortality after LT. The same was observed with the total amount of blood components during hospitalization. Unlike other studies, we did not observe an association between the intraoperative use of blood components and mortality. There is no study in the literature that correlates the use of blood components during hospitalization with the 5-year survival rate after LT. The mean operation time in the present study reflects a small percentage (1.5%) of the mean total length of hospitalization of these patients.
During hospitalization, several other variables can influence the results of LT and the need for blood transfusions. During LT, better monitoring of coagulopathies and adoption of judicious transfusion protocols have reduced the use of blood components despite the great surgery-related hemodynamic repercussions. It is possible that the lack of postoperative protocols might have exposed patients to unnecessary blood transfusions, therefore leading to an association with a reduction in the survival of this population.
Although the association between the use of blood components during hospitalization and the lower 5-year survival suggests causality, these observations might be due to the fact that the need for blood transfusion is a marker of greater disease severity. Multivariate analysis was performed with some confounding variables; however, none of them proved to be an independent predictive factor of mortality after LT.
The retrospective nature of this study has limitations. Despite these limitations, however, the outcomes of the study represent an alert for the judicious analysis of the risk-benefit ratio when indicating transfusion of blood products in LT.
Future prospective studies may assess whether the adoption of postoperative conducts in LT to reduce the use of blood components will be associated with increased survival.
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Correspondence to: Submitted on July 14, 2010. Received from Hospital das Clínicas da Universidade Federal de Minas Gerais (UFMG), Brazil.
Dr. Bruno Salome de Morais
Avenida do Contorno, 4747/19º andar Funcionários
30110060 - Belo Horizonte, MG, Brazil
Approved on December 7, 2010.
Submitted on July 14, 2010.
Received from Hospital das Clínicas da Universidade Federal de Minas Gerais (UFMG), Brazil.