Association of Phlebotomy on Blood Product Transfusion Requirements During Liver Transplantation: An Observational Cohort Study on 1000 Cases.

Background: During the past 2 decades, transfusion requirements have decreased drastically during orthotopic liver transplantation (OLT), and transfusion-free transplantation is nowadays increasingly common. Understanding that liberal intravenous volume loading in cirrhotic patients may have detrimental consequences is key. In contrast, phlebotomy is a method to lower central venous pressure and portal venous pressure. The objective of this study was to determine the effectiveness and safety of phlebotomy in the early phase of blood transfusion, blood loss, renal function, and mortality. Methods: The present study evaluated the impact of phlebotomy on bleeding, transfusion rate, renal dysfunction, and mortality in 1000 consecutive OLTs. Two groups were defined and compared using phlebotomy. Multivariate logistic and linear regression models were used to determine predictors of bleeding, red blood cell (RBC) transfusion, renal dysfunction, and mortality. Results: A mean of 0.7 ± 1.5 RBC units was transfused per patient for 1000 OLTs, 75% did not receive any RBCs, and the median and interquartile range (25-75) were 0 for all blood products transfused. The phlebotomy was associated with decreased transfusion (RBCs, plasma, platelets, cryoprecipitate, albumin), with less bleeding, and with an increased survival rate, both 1 mo and 1 y. Phlebotomy was not associated with renal dysfunction. Conclusions: The practice of phlebotomy to lower portal venous pressure was associated with reduced blood product transfusions and blood loss during liver dissection without deleterious effect on renal function.

Validation of 5 models predicting transfusion, bleeding, and mortality in liver transplantation: an observational cohort study.

BACKGROUND: Historically, orthotopic liver transplantation (OLT) has been associated with massive blood loss, blood transfusion and morbidity. In order to predict such outcomes five nomograms have been published relating to transfusions and morbidity associated with OLTs. These nomograms, developed on the basis of three cohorts of patients consisting of 406, 750, and 800 having undergone OLTs, aimed to predict a transfusion of ≥1 red blood cell unit (RBC), a transfusion of >2 RBC units, a blood loss of >900 ml, as well as one-month and one-year survival rates. The aim of this study was to validate these five nomograms in a contemporary, independent cohort of patients. METHODS: Five nomograms were previously developed based on 406, 750, and 800 OLTs. In this study we performed a temporal validation of these nomograms on contemporary patients that consisted of three cohorts of 800, 250, and 200 OLTs. Logistic regression coefficients from the historic development cohorts were applied to the three contemporary temporal validation cohorts. RESULTS: The most accurate nomogram was able to predict transfusion of ≥1 RBC units with an area under the curve (AUC) was 0.91. The second-best nomogram was able to predict bleeding of >900 ml with an AUC of 0.70. T he AUC of the third nomogram (transfusion of >2 RBC units) was 0.70. However, is temporal validation was suboptimal, due to a low prevalence of OLTs transfused with >2 RBC units. The last 2 nomograms exhibited clearly suboptimal AUC values of 0.54 and 0.61. CONCLUSION: Two of the five nomograms predict blood transfusion and blood loss with excellent accuracy. Transfusion of ≥1 RBC unit and blood loss of >900 ml can be predicted on the basis of these nomograms. However, these nomograms are not accurate to predict one-month and one-year survival rates. These results should be further cross-validated, ideally prospectively, in additional external independent cohorts.

Making sense of what exactly public health does: a typology of public health interventions.

SETTING: Montréal. INTERVENTION: The lack of common knowledge about what public health does is a hindrance to its recognition and capacity to act. Montréal's regional public health department set an explicit goal to clarify and better communicate its specific contributions when it developed its 2016-2021 action plan. This article briefly describes the efforts made to classify public health practice, introduces a typology of public health interventions and discusses its application and benefits. OUTCOMES: The typology that was developed defines 29 types of interventions grouped into four categories: direct action targeting the population; advocacy (persuading partners to take action); support (helping partners take action); collaboration (taking action with partners). The analysis of Montreal's most recent action plan, completely drafted in terms of the typology, provides an insightful characterization of public health practice. Globally, four out of five interventions target partners (indirect), with more than half falling within the support category. Other indirect interventions are divided almost equally between advocacy and collaboration. Following a rigorous planning process and enforcing the use of the typology also had a significant structuring effect on the organization and its teams and enabled greater synergy with partners from other sectors. IMPLICATIONS: Very few people are familiar with everything public health does, sometimes not even the responsible political decision-makers. This situation poses a threat to the survival of its prevention mission. The typology of public health interventions is an innovative tool that can be used to better inform the public and decision-makers.

Impact of MELD Score-Based Organ Allocation on Mortality, Bleeding, and Transfusion in Liver Transplantation: A Before-and-After Observational Cohort Study.

OBJECTIVE: The goal of this study was to evaluate the effect of the Model for End-Stage Liver Disease (MELD)-based allocation system on mortality, bleeding, and transfusion requirement in orthotopic liver transplantation (OLT). DESIGN: OLTs were studied for this observational study (before-and-after observational cohort study). SETTING: One community hospital. PARTICIPANTS: The study comprised 686 patients who underwent 750 consecutive OLTs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients who underwent OLT in the MELD era had an adjusted lower 1-year mortality (adjusted odds ratio 0.45 [0.24-0.83]) compared with patients who underwent OLT the pre-MELD era. No significant difference in 1-month mortality was observed. Other variables with a significant effect on 1-year mortality in multivariate analysis were preoperative international normalized ratio, intraoperative use of a phlebotomy, total intraoperative volume of crystalloid infused, and retransplantation. Blood loss was greater in the MELD era (median difference 200 mL; p < 0.001), as were red blood cell, fresh frozen plasma, and cryoprecipitate transfusions. More patients in the MELD era received at least 1 transfusion (27% v 20%; p = 0.024). CONCLUSION: The MELD allocation system did not affect 1-month mortality, but a decrease in 1-year mortality was demonstrated. Blood loss and transfusions increased during OLTs performed in the MELD era. The role of other variables should be explored further to explain postoperative morbidity and mortality.

Development of a Predictive Model for Blood Transfusions and Bleeding During Liver Transplantation: An Observational Cohort Study.

OBJECTIVE: Orthotopic liver transplantation (OLT) frequently is associated with major blood loss and considerable transfusion requirements. The goal of this study was to define the risk factors for multiple transfusions and major bleeding during OLT and to help identify higher risk patients that could benefit from targeted interventions. DESIGN: OLTs were studied for this observational cohort study. SETTING: Community hospital. PARTICIPANTS: A total of 800 consecutive OLTs were studied. INTERVENTION: No intervention. MEASUREMENTS AND MAIN RESULTS: Baseline and intraoperative data were gathered. Multivariate logistic regression analyses were performed to find variables associated with 2 outcomes: transfusion of more than 2 units of red blood cells (RBC) and bleeding ≥900 mL. Two nomograms were developed to predict individual risks. The overall intraoperative RBC transfusion was 0.6 ± 1.4 units on average, and 61 surgeries (7.6%) received more than 2 units of RBC (4.5 ± 1.9). Some variables were associated with the outcomes: 5 were associated with transfusion of more than 2 units of RBC (patient's height, starting hemoglobin concentration, starting bilirubin value, the use of a phlebotomy, and central venous pressure [CVP] at the time of vena cava clamping) and 3 with blood loss of ≥900 mL (starting hemoglobin value, Child-Turcotte-Pugh score, and CVP at the time of vena cava clamping). Preclamping CVP showed the strongest association with both outcomes. Nomograms were developed to predict the individual OLT recipients' risk of requiring more than 2 units RBC and suffering from major bleeding. Among the variables associated with multiple RBC transfusions and major bleeding, 3 can lead to interventions: baseline hemoglobin value, the use of a phlebotomy, and the preclamping CVP. CONCLUSION: Some variables were able to predict the risk of multiple transfusions and major bleeding in this low bleeding liver transplantation population. Further studies based on these variables should be done to better define the role of targeted interventions in higher risk liver transplant recipients.

Classical Notions of Coagulation Revisited in Relation with Blood Losses, Transfusion Rate for 700 Consecutive Liver Transplantations.

During the last decade, improved surgical and anesthetic management, such as better understanding of coagulation defects and the use of the phlebotomy, has reduced intraoperative blood product transfusions during orthotopic liver transplantation (OLT). The goal of this study was to look at the impact of initial conventional coagulation tests on blood loss and blood product requirement and to evaluate the role of the phlebotomy during liver transplantations. A total of 700 consecutive OLTs were studied. The group of patients was split into two according to the median of starting international normalized ratio to study blood losses and transfusion rate. Logistic regression was used to determine the main predictors of blood loss, intraoperative blood transfusion, and survival. There was no intergroup difference for demographic characteristics. The mean blood loss was 1,184 mL with a median of 920 mL. Overall, 77.4% of the patients did not receive any blood product and the mean transfusion rate of red blood cells (RBCs) was 0.5 ± 1.4 units per patient. Severity of recipients' disease did not correlate with blood loss or transfusion rate. Starting hemoglobin value was the only biochemical variable linked to RBC transfusions. Phlebotomy was linked to decrease in blood loss, RBC transfusions, and increased survival rate. It is concluded that bleeding did not correlate with traditional coagulation defects or the severity of recipient's disease. Preemptive phlebotomy was linked to a decreased blood loss, a decreased transfusion rate, and an increased 1-year survival rate.

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.

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 µmol/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.

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< or =0.015) but less well with the change in PAP (0.554-0.762, P< or =0.012) and PCWP (0.576-0.692, P< or =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.

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 > or =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 Pugh's 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.

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.

Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations.

Correction of coagulation defects with plasma transfusion did not decrease the need for intraoperative red blood cells (RBC) transfusions during liver transplantations. On the contrary, it led to a hypervolemic state that resulted in an increase of shed blood. As well, plasma transfusion has been associated with a decreased one-year survival rate. The aim of the present prospective survey was to evaluate whether anesthesiologists could reduce intraoperative RBC transfusions during liver transplantations by changing their anesthesia practice, more specifically by maintaining a low central venous pressure (CVP), through restriction of volume replacement, elimination of all plasma transfusion and by using intraoperative phlebotomy during the transplantation. One hundred consecutive liver transplantations were prospectively studied during a two-year period and were compared to a retrospective series (1998-2002). A low CVP was maintained in all patients prior the anhepatic phase. Coagulation disorders were not corrected preoperatively, intraoperatively, or post-operatively unless uncontrollable bleeding. Phlebotomy and Cell Saver (CS) were used following pre-established criteria. Independent variables were analyzed in a univariate and multivariate fashion. The mean number of intraoperative RBC units transfused was 0.4 +/- 0.8. No plasma, platelets, albumin, or cryoprecipitate were transfused. Seventy-nine percent of the patients received no blood products during their liver transplantation. The average final hemoglobin value was 85.9 +/- 17.8 g/L. In 57 patients (58.2%), intraoperative phlebotomy and CS were used either together or separately. The one-year year survival rate was 89.1%. Logistic regression showed that avoidance of plasma transfusion, starting hemoglobin value and phlebotomy were significantly linked to liver transplantation without RBC transfusion. In conclusion, the avoidance of plasma transfusion and maintenance of a low CVP prior to the anhepatic phase were associated with a decrease in RBC transfusions during liver transplantations. Previous reports indicating that it is neither useful nor necessary to correct coagulation defects with plasma transfusion prior to liver transplantation are further corroborated by this prospective survey. We believe that this work also supports the practice of lowering CVP with phlebotomy in order to reduce blood loss, during liver dissection, without any deleterious effect.