Lynda Thibeault

Coagulation Defects Do Not Predict Blood Product Requirements During Liver Transplantation

Background. In our experience, correction of coagulation defects with plasma transfusion does not decrease the need for intraoperative red blood cell (RBC) transfusions during liver transplantation. On the contrary, it leads to a hypervolemic state that result in increased blood loss. A previous study has shown that plasma transfusion has been associated with a decreased 1-year survival rate. The aim of this prospective study was to evaluate whether anesthesiologists could reduce RBC transfusion requirements during liver transplantation by eliminating plasma transfusion. Methods. Two hundred consecutive liver transplantations were prospectively studied over a 3-year period. Patients were divided into two groups: low starting international normalized ratio (INR) value <1.5 and high INR ≥1.5. Low central venous pressure was maintained in all patients before the anhepatic phase. Coagulation parameters were not corrected preoperatively or intraoperatively in the absence of uncontrollable bleeding. Phlebotomy and auto transfusion of blood salvaged were used following our protocol. Independent variables were analyzed in both univariate and multivariate fashion to find a link with RBC transfusions or decreased survival rate. Results. The mean number of intraoperative RBC units transfused was 0.3±0.8. Plasma, platelet, albumin, and cryoprecipitate were not transfused. In 81.5% of the patients, no blood product was used during their transplantation. The average final hemoglobin (Hb) value was 91.2±15.0 g/L. There were no differences in transfusional rate, final Hb, or bleeding between two groups (low or high INR values). The overall 1-year survival rate was 85.6%. Logistic regression showed that avoidance of plasma transfusion, phlebotomy, and starting Hb value were significantly linked to liver transplantation without RBC transfusion. The need for intraoperative RBC transfusion and Pughs score were linked to the decreased 1-year survival rate. Conclusion. The avoidance of plasma transfusion was associated with a decrease in RBC transfusions during liver transplantation. There was no link between coagulation defects and bleeding or RBC or plasma transfusions. Previous reports indicating that it is neither useful nor necessary to correct coagulation defects with plasma transfusion before liver transplantation seem further corroborated by this study. We believe that this work also supports the practice of lowering central venous pressure with phlebotomy to reduce blood loss, during liver dissection, without any deleterious effect.

Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center.

Background Orthotopic liver transplantation (OLT) has been associated with major blood loss and the need for blood product transfusions. During the last decade, improved surgical and anesthetic management has reduced intraoperative blood loss and blood product transfusions. A first report from our group published in 2005 described a mean intraoperative transfusion rate of 0.3 red blood cell (RBC) unit per patient for 61 consecutive OLTs. Of these patients, 80.3% did not receive any blood product. The interventions leading to those results were a combination of fluid restriction, phlebotomy, liberal use of vasopressor medications, and avoidance of preemptive transfusions of fresh frozen plasma. This is a follow-up observational study, covering 500 consecutive OLTs. Methods Five hundred consecutive OLTs were studied. The transfusion rate of the first 61 OLTs was compared with the last 439 OLTs. Furthermore, multivariate logistic regression was used to determine the main predictors of intraoperative blood transfusion. Results A mean (SD) of 0.5 (1.3) RBC unit was transfused per patient for the 500 OLTs, and 79.6% of them did not receive any blood product. There was no intergroup difference except for the final hemoglobin (Hb) value, which was higher for the last 439 OLTs compared with the previously reported smaller study (94 [20] vs. 87 [20] g/L). Two variables, starting Hb value and phlebotomy, correlated with OLT without transfusion. Conclusions In our center, a low intraoperative transfusion rate could be maintained throughout 500 consecutive OLTs. Bleeding did not correlate with the severity of recipient’s disease. The starting Hb value showed the strongest correlation with OLT without RBC transfusion.

Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation.

Background. A regimen of fluid restriction, phlebotomy, vasopressors, and strict, protocol-guided product replacement has been associated with low blood product use during orthotopic liver transplantation. However, the physiologic basis of this strategy remains unclear. We hypothesized that a reduction of intravascular volume by phlebotomy would cause a decrease in portal venous pressure (PVP), which would be sustained during subsequent phenylephrine infusion, possibly explaining reduced bleeding. Because phenylephrine may increase central venous pressure (CVP), we questioned the validity of CVP as a correlate of cardiac filling in this context and compared it with other pulmonary artery catheter and transesophageal echocardiography-derived parameters. In particular, because optimal views for echocardiographic estimation of preload and stroke volume are not always applicable during liver transplantation, we evaluated the use of transmitral flow (TMF) early peak (E) velocity as a surrogate. Methods. In study 1, the changes in directly measured PVP and CVP were recorded before and after phlebotomy and phenylephrine infusion in 10 patients near the end of the dissection phase of liver transplantation. In study 2, transesophageal echocardiography-derived TMF velocity in early diastole was measured in 20 patients, and the changes were compared with changes in CVP, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and calculated systemic vascular resistance (SVR) at the following times: postinduction, postphlebotomy, preclamping of the inferior vena cava, during clamping, and postunclamping. Results. Phlebotomy decreased PVP along with CO, PAP, PCWP, CVP, and TMF E velocity. Phenylephrine given after phlebotomy increased CVP, SVR, and arterial blood pressure but had no significant effect on CO, PAP, PCWP, or PVP. The change in TMF E velocity correlated well with the change in CO (Pearson correlation coefficient 95% confidence interval 0.738–0.917, P≤0.015) but less well with the change in PAP (0.554–0.762, P≤0.012) and PCWP (0.576–0.692, P≤0.008). TMF E velocity did not correlate significantly with CVP or calculated SVR. Conclusion. Phlebotomy during the dissection phase of liver transplantation decreased PVP, which was unaffected when phenylephrine infusion was used to restore systemic arterial pressure. This may contribute to a decrease in operative blood loss. CVP often increased in response to phenylephrine infusion and did not seem to reflect cardiac filling. The changes in TMF E velocity correlated well with the changes in CO, PAP, and PCWP during liver transplantation but not with the changes in CVP.

Aprotinin versus tranexamic acid during liver transplantation: impact on blood product requirements and survival.

Background. Historically, orthotopic liver transplantation (OLT) has been associated with major blood loss and the need for blood product transfusions. Activation of the fibrinolytic system can contribute significantly to bleeding. Prophylactic administration of antifibrinolytic agents was found to reduce blood loss. Methods. The efficacy of two antifibrinolytic compounds—aprotinin (AP) and tranexamic acid (TA)—was compared in OLT. Four hundred consecutive OLTs were studied: 300 patients received AP and 100 received TA. Multivariate logistic regression analysis was used to identify independent predictors of intraoperative transfusion requirement and 1-year patient mortality. Results. There was no intergroup difference in intraoperative blood loss (1082±1056 vs. 1007±790 mL), red blood cell transfusion per patient (0.5±1.4 vs. 0.5±1.0), final hemoglobin (Hb) concentration (93±20 g/L vs. 95±22 g/L), the percentage of OLT cases requiring no blood product administration (80% vs. 82%), and 1-year survival (85.1% vs. 87.4%). Serum creatinine concentrations were also the same (116±55 vs. 119±36 &mgr;mol/L) 1 year after surgery. Two variables, starting Hb and phlebotomy, correlated with the two primary outcome measures (transfusion and 1-year survival). Conclusions. In our experience, administration of AP was not superior to TA with regards to blood loss and blood product transfusion requirement during OLT. In addition, we found no difference between the groups in the 1-year survival rate and renal function. Furthermore, we suggest that starting Hb concentration should be considered when prioritizing patients on the waiting list and planning perioperative care for OLT recipients.

Evaluation of cell salvage autotransfusion utility during liver transplantation

BACKGROUND Orthotopic liver transplantation (OLT) may be associated with massive blood loss and the need for allogenic blood product transfusions. Cell salvage autotransfusion (CS) is an attractive alternative to allogenic red blood cell (RBC) transfusion. However, controversy surrounds its usefulness during OLT; some studies stated that CS decreased transfusions of allogenic blood products and others stated that blood loss was increased. The aim of this study was to evaluate the efficiency of the CS during OLT. PATIENTS AND METHODS After approval by the institutional ethics committee, a prospective survey was undertaken. A total of 150 consecutive OLTs were included in the study. Two groups of patients were formed. Period 1 included patients 1-75 with no CS use. Period 2 comprised patients 76-150 with systematic CS use. RESULTS Patients from both periods were comparable. CS was used in all cases in period 2, and there was enough salvaged blood to retransfuse 65% of these OLTs. The mean volume of retransfused blood was 338+/-339 ml. The transfusion rate did not change from period 1 to period 2. The mean number of RBC units transfused per patient was 0.4+/-0.9 vs 0.4+/-1.2 with 78.7% vs 81.3% of cases not receiving transfusion of any blood product. The threshold for RBC transfusions was the same. The length of surgery and blood loss were greater in period 2 than in period 1 (associated with the arrival of two junior surgeons), but the hemoglobin (Hb) value was also higher at the end of surgery (93.8+/-19.3 g/L vs 85.2+/-17.8 g/L, p<0.0001). CONCLUSION Despite increased blood loss in period 2, CS saved 21 g/L of Hb per patient or two RBC unit transfusions. As long as we cannot predict with accuracy which patients will bleed, we will continue to use the CS for all OLTs.

Con: Low Central Venous Pressure During Liver Transplantation

S l RTHOTOPIC LIVER TRANSPLANTATION (OLT) has been associated with major blood loss and the need for llogeneic blood product transfusions. A few years ago, the uthors had the impression that their transfusion rate was ower than other liver transplantation centers. Therefore, the uthors decided to undertake a retrospective study of more han 200 consecutive OLTs to look further into their perforance.1 The findings were interesting. The transfusion rate or red blood cell units (RBCs) was 2.8 3.5 units per atient with 4.1 4.1 units of plasma. Despite the fact that he patients’ severity of disease and threshold for RBC ransfusions were exactly the same according to each aneshesiologist, there was a great disparity in blood product ransfusions according to each anesthesiologist. Some would ransfuse 3 times more blood products than others (4.7 v 1.6 BC units per patient and 6.2 v 2.0 units of plasma per atient). Furthermore, this study showed that the transfusion of lasma for the purpose of correcting coagulation defects was ot associated with a reduction in RBC transfusion. In fact, the pposite occurred. The anesthesiologists who transfused the ost plasma also transfused the most RBCs, and the ones who id not transfuse plasma did not transfuse RBCs. Intraoperative lasma transfusion was the variable with the strongest link to BC transfusion. In this study, a significant link was found between the ntraoperative transfusion of 1 or more units of plasma, more han 4 RBC units, and the 1-year survival rate. The patients ho did not receive any blood products had a 1-year survival ate of 97.4%. This survival rate decreased significantly to 6.9% when patients received only plasma. Twenty-seven varibles were analyzed by univariate and multivariate methods to nd variables linked to a decreased 1-year survival rate. The ogistic regression analysis showed that 2 variables were assoiated significantly with the 1-year survival rate: the number of BCs transfused and the number of units of plasma transfused. he association between RBCs or plasma transfusion and the -year survival rate was significant whether the independent ariables (RBCs or plasma) were studied as categories (mean, edian, or subgroups of RBCs or plasma [low v high transfuion]) or as continuous variables. All other studied variables age, sex, weight, height, starting hemoglobin [Hb] value, startng international normalized ratio value, starting platelet count, ugh’s score, Model of End-Stage Liver Disease (MELD) core, and starting creatinine value) did not influence the 1-year urvival rate. In summary, the risk of dying within a year was 4.2 times igher in patients transfused with more than 4 RBC units ompared with those who received 4 or less RBC units. atients who received 1 or more units of plasma had a risk .1 times higher than those receiving no plasma. In patients eceiving more than 4 RBC units, the risk increased 4.4 times n the ones who also received plasma. The risk further inreased to 5.3 times in patients receiving more than 4 units of oth RBC and plasma compared with patients receiving 4 or ess units of RBCs and plasma. Patients receiving more than 4 nits of both RBCs and plasma had a 1-year survival rate of s

Reply: Reduction of blood product transfusion requirements during liver transplantation

We thank Dr. E. Pivalizza et al. for their interest in our work. Only 44.5% of our patients underwent phlebotomy, and all patients in both series had aprotinin according to the Hammersmith protocol. Phlebotomy was one of the 3 variables linked to no red blood cell (RBC) transfusion during orthotopic liver transplantation (OLT) from logistic regression. We gave the odds ratio from the 304 patients studied; when we performed phlebotomy, the risk of transfusing RBC decreased from 79% to 13%. Moreover, we did not conclude that there was a causal relationship between phlebotomy and no RBC transfusions. Phlebotomy is a tool to decrease the central venous pressure (CVP), but it is not an end in itself. We believe that maintaining a low CVP is the most important clinical factor that permits OLT without transfusion. Regardless of which technique is used (phlebotomy or fluid restriction), it is the lowering of the CVP during liver dissection, before the anhepatic phase, that contributes to limit blood loss and hence leads to a decreased transfusion rate. Phlebotomy results in a faster decrease of the CVP when compared with fluid restriction. The purpose of our study was not to compare the level of morbidity between our patients and patients from other centers. We wanted to evaluate ways to transfuse less blood products in patients with comparable disease severity. Our patients, when compared with patients in other series, seem to be as sick, if not sicker. The patients of Frasco et al., with a RBC transfusion rate of 2.9 2.7 units per patient, had the same severity of disease for their patients as ours. The patients of Ramos et al., who had the same transfusion rate for RBC, had a starting international normalized ratio of 1.2 0.2. What is more, 40% of the patients in the last series received a diagnosis of hepatocellular carcinoma as a result of hepatitis C, vs. 7% in our series. A total of 73% of their patients came from their home. Finally, in our series, 13 patients had undergone a previous OLT, and some had undergone OLT and a renal transplant. We can add that after more than 200 OLTs performed at our center using this strategy, the transfusion rate is still the same. With this transfusion rate, it is very difficult to study strategies aimed at decreasing blood loss or transfusion rate. We are limited to observational studies or historical controls. We hope that other liver transplantation centers would undertake the study of these new concepts of not correcting coagulation defects, lowering CVP, or performing phlebotomy during OLT.