Preoperative Fibrinogen Level and Bleeding in Liver Transplantation for End-stage Liver Disease: A Cohort Study.

BACKGROUND: Liver transplantation is a high-risk surgery associated with important perioperative bleeding and transfusion needs. Uncertainties remain on the association between preoperative fibrinogen level and bleeding in this population. METHODS: We conducted a cohort study that included all consecutive adult patients undergoing a liver transplantation for end-stage liver disease in 1 center. We analyzed the association between the preoperative fibrinogen level and bleeding-related outcomes. Our primary outcome was intraoperative blood loss, and our secondary outcomes were estimated perioperative blood loss, intraoperative and perioperative red blood cell transfusions, reinterventions for bleeding and 1-y graft and patient survival. We estimated linear regression models and marginal risk models adjusted for all important potential confounders. We used restricted cubic splines to explore potential nonlinear associations and reported dose-response curves. RESULTS: We included 613 patients. We observed that a lower fibrinogen level was associated with a higher intraoperative blood loss, a higher estimated perioperative blood loss and a higher risk of intraoperative and perioperative red blood cell transfusions (nonlinear effects). Based on an exploratory analysis of the dose-response curves, these effects were observed below a threshold value of 3 g/L for these outcomes. We did not observe any association between preoperative fibrinogen level and reinterventions, 1-y graft survival or 1-y patient survival. CONCLUSIONS: This study suggests that a lower fibrinogen level is associated with bleeding in liver transplantation. The present results may help improving the selection of patients for further studies on preoperative fibrinogen administration in liver transplant recipients with end-stage liver disease.

[The Development Process of the New Quebec Digital Suicide Prevention Strategy: Suicide.ca]. / Processus d'élaboration de la nouvelle Stratégie québécoise numérique en prévention du suicide : Suicide.ca.

In Quebec, nearly 3 persons still take their own lives every day, even though this number has been declining since 2000. Several institutional and community actors are involved in suicide prevention and several initiatives have contributed to the reduction of suicide rates. Despite this hard work, additional efforts are needed to intensify service offers and resource access to better reach people at risk of suicide not reached by actual services. For many years, several countries have been implementing digital technologies to reach them. In Quebec, there were delays in adoption of digital technologies for suicide prevention. In this context, the Health and Social services Ministry mandated Association québécoise de prévention du suicide (AQPS) to develop a Digital Strategy for Suicide Prevention (DSPS). From the beginning, AQPS wanted to anchor DSPS's development in a decision-making process based on scientific, contextual and experiential evidence. A process, derived from implementation science, was therefore put in place to actualize this intent. Implementation science is defined as the science of implementing programs in real-world settings. It is recognized as contributing to the successful implementation of new programs while promoting a rigorous evaluation of their impacts and outcomes. Objectives This article aims to: 1) present the process that was put in place to facilitate DSPS design, implementation, and evaluation; and 2) describe the DSPS action model and the DSPS. Method The Knowledge to Action (KTA) framework is central to the design, implementation, and evaluation of DSPS. This framework proposes a cyclical process in 7 iterative phases, each with its own methodological aspects and data collections Results The results section illustrates the concrete actions taken at each phase of the KTA process and the highlights that emerge from the analysis of the data collected. This section also presents the DSPS. Conclusion Optimal conditions to promote the implementation of DSPS, its use and its sustainability have been put in place. The current implementation and evaluation of this implementation and its impacts will allow to assess the capacity of DSPS to achieve its main objectives: to provide information about suicide, to identify suicidal individuals, to increase the visibility of resources, and to offer help to suicidal individuals who respond less to traditional resources.

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.

Intraoperative phlebotomies and bleeding in liver transplantation: a historical cohort study and causal analysis.

BACKGROUND: Liver transplantation is associated with major bleeding and red blood cell (RBC) transfusions. No well-designed causal analysis on interventions used to reduce transfusions, such as an intraoperative phlebotomy, has been conducted in this population. METHODS: We conducted a historical cohort study among liver transplantations performed from July 2008 to January 2021 in a Canadian centre. The exposure was intraoperative phlebotomy. The outcomes were blood loss, perioperative RBC transfusions (intraoperative and up to 48 hr after surgery), intraoperative RBC transfusions, and one-year survival. We estimated marginal multiplicative factors (MFs), risk differences (RDs), and hazard ratios by inverse probability of treatment weighting both among treated patients and the whole population. Estimates are reported with 95% confidence intervals (CIs). RESULTS: We included 679 patients undergoing liver transplantations of which 365 (54%) received an intraoperative phlebotomy. A phlebotomy did not reduce bleeding, transfusion risks, or mortality when estimated among the treated but reduced bleeding and transfusion risks when estimated among the whole population (MF, 0.85; 95% CI, 0.72 to 0.99; perioperative RD, -15.2%; 95% CI, -26.1 to -0.8; intraoperative RD, -14.7%; 95% CI, -23.2 to -2.8). In a subgroup analysis on 584 patients with end-stage liver disease, slightly larger effects were observed on both transfusion risks when estimated among the whole population while beneficial effects were observed on the intraoperative transfusion risk when estimated among the treated population. CONCLUSION: The use of intraoperative phlebotomy was not consistently associated with better outcomes in all targets of inference but may improve outcomes among the whole population. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04826666); registered 1 April 2021.

RéSUMé: CONTEXTE: La transplantation hépatique est associée à des saignements importants et à de multiples transfusions de globules rouges (GR). Aucune analyse causale bien conçue sur l'effet d'interventions servant à réduire les transfusions, comme une phlébotomie peropératoire, n'a été menée dans cette population. MéTHODE: Nous avons mené une étude de cohorte historique incluant toutes les transplantations hépatiques réalisées dans un centre canadien de juillet 2008 à janvier 2021. L'exposition d'intérêt était une phlébotomie peropératoire. Les critères d'évaluation étaient le saignement peropératoire, les transfusions de GR périopératoires (peropératoires et jusqu'à 48 heures après la chirurgie), les transfusions de globules rouges peropératoires et la survie à un an. Des facteurs multiplicatifs (FM), des différences de risque (DR) et des rapports de risques instantanés marginaux ont été estimés en utilisant une pondération par l'inverse de la probabilité de traitement parmi les patients traités et parmi l'ensemble de la population. Les effets estimés ont été rapportés avec des intervalles de confiance (IC) à 95 %. RéSULTATS: Nous avons inclus 679 transplantations hépatiques dont 365 (54 %) ont bénéficié d'une phlébotomie peropératoire. La phlébotomie n'a pas réduit les saignements, le risque de transfusion ou la mortalité lorsque ses effets ont été estimés parmi les patients traités, mais a réduit les risques de saignement et de transfusion lorsque ses effets ont été estimés parmi l'ensemble de la population (FM = 0,85 (IC 95 %, 0,72 à 0,99); DR périopératoire = −15,2 % (IC 95 %, −26,1 % à −0,8 %); DR peropératoire = −14,7 % (IC 95 %, −23,2 % à −2,8 %)). Dans une analyse de sous-groupe portant sur 584 patients atteints d'une hépatopathie terminale, des effets légèrement plus importants ont été observés sur les deux risques transfusionnels lorsqu'estimés dans l'ensemble de la population, tandis que des effets bénéfiques ont été observés sur le risque transfusionnel peropératoire lorsqu'estimés parmi les patients traités. CONCLUSION: L'utilisation de la phlébotomie peropératoire n'a pas été systématiquement associée à de meilleurs résultats dans toutes les populations cibles, mais semble améliorer les résultats lorsque les effets sont estimés dans l'ensemble de la population. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04826666); enregistrée le 1er avril 2021.

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.

Association between intraoperative fluid balance, vasopressors and graft complications in liver transplantation: A cohort study.

INTRODUCTION: Biliary complications following liver transplantation are common. The effect of intraoperative fluid balance and vasopressors on these complications is unknown. MATERIALS AND METHODS: We conducted a cohort study between July 2008 and December 2017. Our exposure variables were the total intraoperative fluid balance and the use of vasopressors on ICU admission. Our primary outcome was any biliary complication (anastomotic and non-anastomotic strictures) up to one year after transplantation. Our secondary outcomes were vascular complications, primary graft non-function and survival. RESULTS: We included 562 consecutive liver transplantations. 192 (34%) transplants had a biliary complication, 167 (30%) had an anastomotic stricture and 56 had a non-anastomotic stricture (10%). We did not observe any effect of intraoperative fluid balance or vasopressor on biliary complications (HR = 0.97; 95% CI, 0.93 to 1.02). A higher intraoperative fluid balance was associated with an increased risk of primary graft non-function (non-linear) and a lower survival (HR = 1.40, 95% CI, 1.14 to 1.71) in multivariable analyses. CONCLUSION: Intraoperative fluid balance and vasopressors upon ICU admission were not associated with biliary complications after liver transplantation but may be associated with other adverse events. Intraoperative hemodynamic management must be prospectively studied to further assess their impact on liver recipients' outcomes.

Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study.

BACKGROUND: There is no consensus on how to best achieve a low central venous pressure during hepatectomy for the purpose of reducing blood loss and red blood cell (RBC) transfusions. We analyzed the associations between intraoperative hypovolemic phlebotomy (IOHP), transfusions, and postoperative outcomes in cancer patients undergoing hepatectomy. METHODS: Using surgical and transfusion databases of patients who underwent hepatectomy for cancer at one institution (11 January 2011 to 22 June 2017), we retrospectively analyzed associations between IOHP and RBC transfusion on the day of surgery (primary outcome), and with total perioperative transfusions, intraoperative blood loss, and postoperative complications (secondary outcomes). We fitted logistic regression models by inverse probability of treatment weighting to adjust for confounders and reported adjusted odds ratio (aOR). RESULTS: There were 522 instances of IOHP performed during 683 hepatectomies, with a mean (standard deviation) volume of 396 (119) mL. The IOHP patients had a 6.9% transfusion risk on the day of surgery compared with 12.4% in non-IOHP patients (aOR, 0.53; 95% confidence interval [CI], 0.29 to 0.98; P = 0.04). Total perioperative RBC transfusion tended to be lower in IOHP patients compared with non-IOHP patients (14.9% vs 22.4%, respectively; aOR, 0.72; 95% CI, 0.44 to 1.16; P = 0.18). In patients with a predicted risk of ≥ 47.5% perioperative RBC transfusion, 24.6% were transfused when IOHP was used compared with 56.5% without IOHP. The incidence of severe postoperative complications (Clavien-Dindo scores ≥ 3) was similar in patients whether or not IOHP was performed (15% vs 16% respectively; aOR, 0.97; 95% CI, 0.53 to 1.54; P = 0.71). CONCLUSIONS: The use of IOHP during hepatectomy was associated with less RBCs transfused on the same day of surgery. Trials comparing IOHP with other techniques to reduce blood loss and transfusion are needed in liver surgery.

RéSUMé: CONTEXTE: Il n'existe pas de consensus quant à la meilleure façon d'obtenir une pression veineuse centrale basse pendant une hépatectomie dans le but de réduire les pertes et les transfusions sanguines. Nous avons analysé les associations entre la phlébotomie hypovolémique peropératoire, les transfusions, et les résultats cliniques postopératoires chez les patients qui subissent une hépatectomie pour cancer. MéTHODE: À l'aide de bases de données chirurgicales et transfusionnelles de patients ayant subi une hépatectomie pour cancer dans un seul établissement (du 11 janvier 2011 au 22 juin 2017), nous avons rétrospectivement analysé les associations entre la phlébotomie hypovolémique peropératoire et les transfusions érythrocytaires le jour de la chirurgie (critère d'évaluation principal) et avec les transfusions périopératoires totales, les pertes sanguines peropératoires, et les complications postopératoires (critères d'évaluation secondaires). Nous avons utilisé des modèles de régression logistique avec pondération de probabilité inverse de traitement afin de tenir compte des facteurs de confusion et rapporté les rapports de cotes ajustés (RCa). RéSULTATS: Il y a eu 522 phlébotomies hypovolémiques peropératoires exécutées au cours de 683 hépatectomies, avec un volume moyen (écart type) de 396 (119) mL. Les patients ayant eu une phlébotomie hypovolémique peropératoire avaient un risque transfusionnel de 6,9 % le jour de la chirurgie, comparativement à 12,4 % pour les patients sans phlébotomie (RCa, 0,53; intervalle de confiance [IC] de 95 %, 0,29 à 0,98; P = 0,04). Les transfusions périopératoires totales d'érythrocytes tendaient à être moins fréquentes chez les patients ayant subi une phlébotomie hypovolémique peropératoire par rapport aux patients sans phlébotomie (14,9 % vs 22,4 %, respectivement; RCa, 0,72; IC 95 %, 0,44 à 1,16; P = 0,18). Pour les patients présentant un risque prédit de transfusion périopératoire d'érythrocytes ≥ à 47,5 %, 24,6 % de ceux qui ont eu une phlébotomie hypovolémique peropératoire ont été transfusés, comparativement à 56,5 % sans phlébotomie. L'incidence des complications postopératoires graves (scores de Clavien-Dindo ≥ 3) était semblable chez tous les patients, avec ou sans phlébotomie hypovolémique peropératoire (15 % vs 16 % respectivement; RCa, 0,97; IC 95 %, 0,53 à 1,54; P = 0,71). CONCLUSIONS: L'utilisation de la phlébotomie hypovolémique peropératoire pendant une hépatectomie était associée à un moins grand nombre de transfusions érythrocytaires le jour de la chirurgie. Des études qui compareront la phlébotomie hypovolémique peropératoire à d'autres techniques visant à réduire les pertes et les transfusions sanguines sont nécessaires en chirurgie hépatique.

Association between intraoperative rotational thromboelastometry or conventional coagulation tests and bleeding in liver transplantation: an observational exploratory study.

INTRODUCTION: Liver transplantation is associated with major blood loss and transfusions. Our objective was to evaluate the association between coagulation results (rotational thromboelastometry (ROTEM) and conventional coagulation tests) and intraoperative bleeding or perioperative red blood cell (RBC) transfusions in liver transplantation. METHODS: We measured ROTEM values and conventional coagulation tests at the beginning of surgery, after graft reperfusion and at the end of surgery. We did bivariate correlation and multivariable regression analyses to explore the association between test results and either intraoperative bleeding or perioperative RBC transfusions. RESULTS: We enrolled 75 consecutive patients. Median [Q1-Q3] intraoperative blood loss was 1400 mL [675-2300] and 59% of patients did not receive any RBC transfusion either intraoperatively or postoperatively. In multivariable analyses, FIBTEM maximal clot firmness (MCF) measured at the beginning of surgery was associated with lower intraoperative blood loss (ß = -106 mL for each mm; 95% CI, -203 to -9 mL). Both a higher haemoglobin concentration (multiplicative factor = 0.89 for each g/L; 95% CI, 0.84 to 0.95) and FIBTEM MCF measured at the end of surgery (multiplicative factor = 0.68 for each mm; 95% CI, 0.48 to 0.95) were associated with fewer postoperative RBC transfusions. CONCLUSION: FIBTEM MCF was strongly associated with intraoperative blood loss and postoperative transfusions while other coagulation results were not. This study might inform future clinical trials on ROTEM-based interventions in liver transplantation. STUDY REGISTRATION: Clinical Trials.gov: NCT02356068.

Effects of intraoperative hemodynamic management on postoperative acute kidney injury in liver transplantation: An observational cohort study.

BACKGROUND: Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. METHODS: We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the effect of vasopressors infused at admission in the intensive care unit (ICU) and total intraoperative fluid balance. Our primary outcome was 48-hour acute kidney injury (AKI) and our secondary outcomes were 7-day AKI, need for postoperative renal replacement therapy (RRT), time to extubation in the ICU, time to ICU discharge and survival up to 1 year. We fitted models adjusted for confounders using generalized estimating equations or survival models using robust standard errors. We reported results with 95% confidence intervals. RESULTS: We included 532 patients. Vasopressors use was not associated with 48-hour or 7-day AKI but modified the effects of fluid balance on RRT and mortality. A higher fluid balance was associated with a higher need for RRT (OR = 1.52 [1.15, 2.01], p<0.001 for interaction) and lower survival (HR = 1.71 [1.26, 2.34], p<0.01 for interaction) only among patients without vasopressors. In patients with vasopressors, higher doses of vasopressors were associated with a higher mortality (HR = 1.29 [1.13, 1.49] per 10 µg/min of norepinephrine). CONCLUSION: The presence of any vasopressor at the end of surgery was not associated with AKI or RRT. The use of vasopressors might modify the harmful association between fluid balance and other postoperative outcomes. The liberal use of vasopressors to implement a restrictive fluid management strategy deserves further investigation.

Effects of Intraoperative Fluid Balance During Liver Transplantation on Postoperative Acute Kidney Injury: An Observational Cohort Study.

BACKGROUND: Liver transplant recipients suffer many postoperative complications. Few studies evaluated the effects of fluid management on these complications. We conducted an observational cohort study to evaluate the association between intraoperative fluid balance and postoperative acute kidney injury (AKI) and other postoperative complications. METHODS: We included consecutive adult liver transplant recipients who had their surgery between July 2008 and December 2017. Our exposure was intraoperative fluid balance, and our primary outcome was the grade of AKI at 48 hours after surgery. Our secondary outcomes were the grade of AKI at 7 days, the need for postoperative renal replacement therapy, postoperative red blood cell transfusions, time to first extubation, time to discharge from the intensive care unit (ICU), and 1-year survival. Every analysis was adjusted for potential confounders. RESULTS: We included 532 transplantations in 492 patients. We observed no effect of fluid balance on either 48-hour AKI, 7-day AKI, or on the need for postoperative renal replacement therapy after adjustments for confounders. A higher fluid balance increased the time to ICU discharge, and increased the risk of dying (hazard ratio = 1.21 [1.04,1.40]). CONCLUSIONS: We observed no association between intraoperative fluid balance and postoperative AKI. Fluid balance was associated with longer time to ICU discharge and lower survival. This study provides insight that might inform the design of a clinical trial on fluid management strategies in this population.

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.

Preliminary Experience in Combined Somatic and Cerebral Oximetry Monitoring in Liver Transplantation.

OBJECTIVE: The use of cerebral near-infrared spectroscopy (NIRS) has become widespread in cardiac surgery after research demonstrated an association between perioperative cerebral desaturations and postoperative complications. Somatic NIRS desaturation also is associated with an increased risk of postoperative complications and mortality. The objective of this study was to explore the trends of both somatic and cerebral NIRS during liver transplantation. DESIGN: A prospective, single-site, observational case series. SETTING: Tertiary care center. PARTICIPANTS: The study comprised 10 patients undergoing liver transplantation. INTERVENTIONS: NIRS sensors were placed on the forehead (cerebral regional oxygen saturation [rSO2]) and on the right arm and right leg (somatic rSO2) to measure tissue perfusion. Desaturation was defined as a 20% decrease of baseline values for 15 seconds. MEASUREMENTS AND MAIN RESULTS: In all patients, parallel changes in both cerebral and somatic rSO2 values were observed during phlebotomy, bleeding, transfusion, portal vein clamping, and the use of vasoactive agents. Induction of anesthesia increased cerebral rSO2 more than it did somatic values. However, ascites removal, abdominal manipulation, and clamping of the inferior vena cava (IVC) were associated with nonparallel changes in cerebral and somatic rSO2. Ascites removal was associated with increased somatic leg rSO2, and IVC clamping and abdominal hypertension were associated with a significant reduction in somatic leg rSO2. Somatic leg desaturation instead of arm or cerebral desaturation was associated with more postoperative complications. CONCLUSIONS: The use of combined NIRS monitoring allows for the identification of the source of somatic or cerebral desaturation. Compromised venous flow from the IVC from clamping or abdominal compartment syndrome typically is associated with the appearance of more pronounced leg than arm desaturation.

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.

Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial.

BACKGROUND: We have always been searching for the ideal local anesthetic for outpatient spinal anesthesia. Lidocaine has been associated with a high incidence of transient neurological symptoms, and bupivacaine produces sensory and motor blocks of long duration. Preservative-free 2-chloroprocaine (2-CP) seems to be a promising alternative, being a short-acting agent of increasing popularity in recent years. This study was designed to compare 2-CP with bupivacaine for spinal anesthesia in an elective ambulatory setting. METHODS: A total of 106 patients were enrolled in this randomized double-blind study. Spinal anesthesia was achieved with 0.75% hyperbaric bupivacaine 7.5 mg (n = 53) or 2% preservative-free 2-CP 40 mg (n = 53). The primary endpoint for the study was the time until reaching eligibility for discharge. Secondary outcomes included the duration of the sensory and motor blocks, the length of stay in the postanesthesia care unit, the time until ambulation, and the time until micturition. RESULTS: The average time to discharge readiness was 277 min in the 2-CP group and 353 min in the bupivacaine group, a difference of 76 min (95% confidence interval [CI]: 40 to 112 min; P < 0.001). The average time for complete regression of the sensory block was 146 min in the 2-CP group and 329 min in the bupivacaine group, a difference of 185 min (95% CI: 159 to 212 min; P < 0.001). Times to ambulation and micturition were also significantly lower in the 2-CP group. CONCLUSION: Spinal 2-chloroprocaine provides adequate duration and depth of surgical anesthesia for short procedures with the advantages of faster block resolution and earlier hospital discharge compared with spinal bupivacaine. (ClinicalTrials.gov number, NCT00845962).

Evaluation of the addition of bupivacaine to intrathecal morphine and fentanyl for postoperative pain management in laparascopic liver resection.

BACKGROUND: Optimal modality of pain management after liver resection has been controversial. Epidural analgesia is often avoided because of transient coagulopathy and the associated risk of epidural hematoma. Single-dose intrathecal morphine has been shown to be an effective alternative in open liver resection. The purpose of this trial was to compare the analgesic efficacy of intrathecal morphine and fentanyl versus intrathecal bupivacaine 0.5%, morphine, and fentanyl for patients undergoing laparoscopic liver resection. METHODS: This prospective randomized controlled double-blind trial compared morphine consumption between control (CTRL) group receiving a spinal injection of fentanyl 15 µg and morphine 0.4 mg and bupivacaine (BUPI) group receiving the same medications in addition to bupivacaine 0.5% (15 mg). Forty patients scheduled for laparoscopic liver resection were enrolled. Primary outcome was intravenous patient-controlled analgesia morphine consumption measured at 6, 9, 12, 18, 24, 36, and 48 hrs after spinal injection. Secondary outcomes were pain scores at rest and with movement, sedation, nausea, pruritus, and respiratory rate. RESULTS: Cumulative doses of morphine were significantly lower for all time intervals in the BUPI group: 54 (30) versus 94 (47) mg (P = 0.01) at 48 hrs. Morphine consumption was significantly lower for each time interval up to 18 hrs. Pain scores with movement were significantly lower in the BUPI group up to 24 hrs after injection. Pain score at rest was significantly lower in the BUPI group 9 hrs after injection. There were no differences in adverse effects. CONCLUSIONS: The addition of bupivacaine to intrathecal morphine and fentanyl significantly reduced intravenous morphine consumption after laparoscopic liver resection.

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.