Skip to main content
Top
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2022

01-04-2022 | Liver Transplantation | Reports of Original Investigations

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

Authors: François Martin Carrier, MD, MSc, Steve Ferreira Guerra, MSc, Janie Coulombe, PhD, Éva Amzallag, MSc, Luc Massicotte, MD, Michaël Chassé, MD, PhD, Helen Trottier, PhD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 4/2022

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ozier Y, Klinck JR. Anesthetic management of hepatic transplantation. Curr Opin Anaesthesiol 2008; 21: 391-400.PubMed Ozier Y, Klinck JR. Anesthetic management of hepatic transplantation. Curr Opin Anaesthesiol 2008; 21: 391-400.PubMed
2.
go back to reference Feltracco P, Brezzi M, Barbieri S, et al. Blood loss, predictors of bleeding, transfusion practice and strategies of blood cell salvaging during liver transplantation. World J Hepatol 2013; 5: 1-15.PubMedPubMedCentral Feltracco P, Brezzi M, Barbieri S, et al. Blood loss, predictors of bleeding, transfusion practice and strategies of blood cell salvaging during liver transplantation. World J Hepatol 2013; 5: 1-15.PubMedPubMedCentral
3.
go back to reference Sabaté A, Dalmau A, Koo M, Aparicio I, Costa M, Contreras L. Coagulopathy management in liver transplantation. Transplant Proc 2012; 44: 1523-5.PubMed Sabaté A, Dalmau A, Koo M, Aparicio I, Costa M, Contreras L. Coagulopathy management in liver transplantation. Transplant Proc 2012; 44: 1523-5.PubMed
4.
go back to reference Massicotte L, Sassine MP, Lenis S, Seal RF, Roy A. Survival rate changes with transfusion of blood products during liver transplantation. Can J Anesth 2005; 52: 148-55.PubMed Massicotte L, Sassine MP, Lenis S, Seal RF, Roy A. Survival rate changes with transfusion of blood products during liver transplantation. Can J Anesth 2005; 52: 148-55.PubMed
5.
go back to reference de Boer MT, Christensen MC, Asmussen M, et al. The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation. Anesth Analg 2008; 106: 32-44.PubMed de Boer MT, Christensen MC, Asmussen M, et al. The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation. Anesth Analg 2008; 106: 32-44.PubMed
6.
go back to reference Murad MH, Stubbs JR, Gandhi MJ, et al. The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010; 50: 1370-83.PubMed Murad MH, Stubbs JR, Gandhi MJ, et al. The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010; 50: 1370-83.PubMed
7.
go back to reference Rana A, Petrowsky H, Hong JC, et al. Blood transfusion requirement during liver transplantation is an important risk factor for mortality. J Am Coll Surg 2013; 216: 902-7.PubMed Rana A, Petrowsky H, Hong JC, et al. Blood transfusion requirement during liver transplantation is an important risk factor for mortality. J Am Coll Surg 2013; 216: 902-7.PubMed
9.
go back to reference Real C, Sobreira Fernandes D, Sá Couto P, et al. Survival predictors in liver transplantation: time-varying effect of red blood cell transfusion. Transplant Proc 2016; 48: 3303-6.PubMed Real C, Sobreira Fernandes D, Sá Couto P, et al. Survival predictors in liver transplantation: time-varying effect of red blood cell transfusion. Transplant Proc 2016; 48: 3303-6.PubMed
10.
go back to reference Massicotte L, Carrier FM, Karakiewicz P, et al. Impact of MELD score-based organ allocation on mortality, bleeding, and transfusion in liver transplantation: a before-and-after observational cohort study. J Cardiothorac Vasc Anesth 2019; 33: 2719-25.PubMed Massicotte L, Carrier FM, Karakiewicz P, et al. Impact of MELD score-based organ allocation on mortality, bleeding, and transfusion in liver transplantation: a before-and-after observational cohort study. J Cardiothorac Vasc Anesth 2019; 33: 2719-25.PubMed
11.
go back to reference Shehata N, Mistry N, da Costa BR, et al. Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis. Eur Heart J 2019; 40: 1081-8.PubMed Shehata N, Mistry N, da Costa BR, et al. Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis. Eur Heart J 2019; 40: 1081-8.PubMed
12.
go back to reference Zuckerman J, Coburn N, Callum J, et al. Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: long-term outcomes from a population-based cohort. Surgery 2021; 170: 870-9.PubMed Zuckerman J, Coburn N, Callum J, et al. Association of perioperative red blood cell transfusions with all-cause and cancer-specific death in patients undergoing surgery for gastrointestinal cancer: long-term outcomes from a population-based cohort. Surgery 2021; 170: 870-9.PubMed
13.
go back to reference Bezinover D, Dirkmann D, Findlay J, et al. Perioperative coagulation management in liver transplant recipients. Transplantation 2018; 102: 578-92.PubMed Bezinover D, Dirkmann D, Findlay J, et al. Perioperative coagulation management in liver transplant recipients. Transplantation 2018; 102: 578-92.PubMed
14.
go back to reference Taura P, Martinez-Palli G, Blasi A, Rivas E, Beltran J, Balust J. Intraoperative management of high-risk liver transplant recipients: concerns and challenges. Transplant Proc 2016; 48: 2491-4.PubMed Taura P, Martinez-Palli G, Blasi A, Rivas E, Beltran J, Balust J. Intraoperative management of high-risk liver transplant recipients: concerns and challenges. Transplant Proc 2016; 48: 2491-4.PubMed
15.
go back to reference Molenaar IQ, Warnaar N, Groen H, TenVergert EM, Slooff MJ, Porte RJ. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007; 7: 185-94.PubMed Molenaar IQ, Warnaar N, Groen H, TenVergert EM, Slooff MJ, Porte RJ. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007; 7: 185-94.PubMed
16.
go back to reference Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Reduction of blood product transfusions during liver transplantation. Can J Anesth 2005; 52: 545-6.PubMed Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Reduction of blood product transfusions during liver transplantation. Can J Anesth 2005; 52: 545-6.PubMed
17.
go back to reference Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl 2006; 12: 117-23.PubMed Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl 2006; 12: 117-23.PubMed
18.
go back to reference Massicotte L, Perrault MA, Denault AY, et al. Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation. Transplantation 2010; 89: 920-7.PubMed Massicotte L, Perrault MA, Denault AY, et al. Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation. Transplantation 2010; 89: 920-7.PubMed
19.
go back to reference Martel G, Baker L, Wherrett C, et al. Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility. Br J Surg 2020; 107: 812-23.PubMed Martel G, Baker L, Wherrett C, et al. Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility. Br J Surg 2020; 107: 812-23.PubMed
20.
go back to reference Al Khaldi M, Gryspeerdt F, Carrier FM, et al. Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study. Can J Anesth 2021; 68: 980-90.PubMed Al Khaldi M, Gryspeerdt F, Carrier FM, et al. Effect of intraoperative hypovolemic phlebotomy on transfusion and clinical outcomes in patients undergoing hepatectomy: a retrospective cohort study. Can J Anesth 2021; 68: 980-90.PubMed
21.
go back to reference Mukhtar A, Lotfy A, Hussein A, Fouad E. Splanchnic and systemic circulation cross talks: implication for hemodynamic management of liver transplant recipient. Best Pract Res Clin Anaesthesiol 2020; 34: 109-18.PubMed Mukhtar A, Lotfy A, Hussein A, Fouad E. Splanchnic and systemic circulation cross talks: implication for hemodynamic management of liver transplant recipient. Best Pract Res Clin Anaesthesiol 2020; 34: 109-18.PubMed
22.
go back to reference Massicotte L, Carrier FM, Denault AY, et al. Development of a predictive model for blood transfusions and bleeding during liver transplantation: an observational cohort study. J Cardiothorac Vasc Anesth 2018; 32: 1722-30.PubMed Massicotte L, Carrier FM, Denault AY, et al. Development of a predictive model for blood transfusions and bleeding during liver transplantation: an observational cohort study. J Cardiothorac Vasc Anesth 2018; 32: 1722-30.PubMed
23.
go back to reference Massicotte L, Capitanio U, Beaulieu D, Roy JD, Roy A, Karakiewicz PI. Independent validation of a model predicting the need for packed red blood cell transfusion at liver transplantation. Transplantation 2009; 88: 386-91.PubMed Massicotte L, Capitanio U, Beaulieu D, Roy JD, Roy A, Karakiewicz PI. Independent validation of a model predicting the need for packed red blood cell transfusion at liver transplantation. Transplantation 2009; 88: 386-91.PubMed
25.
go back to reference Carrier FM, Chassé M, Wang HT, et al. Restrictive fluid management strategies and outcomes in liver transplantation: a systematic review. Can J Anesth 2020; 67: 109-27.PubMed Carrier FM, Chassé M, Wang HT, et al. Restrictive fluid management strategies and outcomes in liver transplantation: a systematic review. Can J Anesth 2020; 67: 109-27.PubMed
26.
go back to reference Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 2011; 46: 399-424. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 2011; 46: 399-424.
27.
go back to reference Shrier I, Redelmeier A, Schnitzer ME, Steele RJ. Challenges in interpreting results from ‘multiple regression’ when there is interaction between covariates. BMJ Evid Based Med 2021; 26: 53-6.PubMed Shrier I, Redelmeier A, Schnitzer ME, Steele RJ. Challenges in interpreting results from ‘multiple regression’ when there is interaction between covariates. BMJ Evid Based Med 2021; 26: 53-6.PubMed
28.
go back to reference Rubin DB. For objective causal inference, design trumps analysis. Ann Appl Stat 2008; 2: 808-40. Rubin DB. For objective causal inference, design trumps analysis. Ann Appl Stat 2008; 2: 808-40.
29.
go back to reference Carrier FM, Chassé M, Sylvestre MP, et al. Effects of intraoperative fluid balance during liver transplantation on postoperative acute kidney injury: an observational cohort study. Transplantation 2020; 104: 1419-28.PubMed Carrier FM, Chassé M, Sylvestre MP, et al. Effects of intraoperative fluid balance during liver transplantation on postoperative acute kidney injury: an observational cohort study. Transplantation 2020; 104: 1419-28.PubMed
31.
go back to reference Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247-54.PubMed Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247-54.PubMed
32.
go back to reference von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61: 344-9. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61: 344-9.
34.
go back to reference Hernán MA, Robins JM. Causal Inference: What If, 1st Edition. Boca Raton: Chapman & Hall/CRC; 2020. Hernán MA, Robins JM. Causal Inference: What If, 1st Edition. Boca Raton: Chapman & Hall/CRC; 2020.
35.
go back to reference Tran A, Heuser J, Ramsay T, McIsaac DI, Martel G. Techniques for blood loss estimation in major non-cardiac surgery: a systematic review and meta-analysis. Can J Anesth 2021; 68: 245-55.PubMed Tran A, Heuser J, Ramsay T, McIsaac DI, Martel G. Techniques for blood loss estimation in major non-cardiac surgery: a systematic review and meta-analysis. Can J Anesth 2021; 68: 245-55.PubMed
36.
go back to reference Ashworth A, Klein AA. Cell salvage as part of a blood conservation strategy in anaesthesia. Br J Anaesth 2010; 105: 401-16.PubMed Ashworth A, Klein AA. Cell salvage as part of a blood conservation strategy in anaesthesia. Br J Anaesth 2010; 105: 401-16.PubMed
37.
go back to reference Sabaté A, Dalmau A. Fibrinogen: a clinical update on liver transplantation. Transplant Proc 2015; 47: 2925-8.PubMed Sabaté A, Dalmau A. Fibrinogen: a clinical update on liver transplantation. Transplant Proc 2015; 47: 2925-8.PubMed
38.
go back to reference Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-70.PubMed Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-70.PubMed
39.
go back to reference Feng ZY, Xu X, Zhu SM, Bein B, Zheng SS. Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation. World J Surg 2010; 34: 1864-73.PubMed Feng ZY, Xu X, Zhu SM, Bein B, Zheng SS. Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation. World J Surg 2010; 34: 1864-73.PubMed
40.
go back to reference Kim JH. Should low central venous pressure be maintained during liver transplantation? Open Anesthesiol J 2017; 11: 17-28. Kim JH. Should low central venous pressure be maintained during liver transplantation? Open Anesthesiol J 2017; 11: 17-28.
41.
go back to reference Imbens GW. Nonparametric estimation of average treatment effects under exogeneity: a review. Rev Econ Stat 2004; 86: 4-29. Imbens GW. Nonparametric estimation of average treatment effects under exogeneity: a review. Rev Econ Stat 2004; 86: 4-29.
43.
go back to reference Barrera-Gómez J, Basagaña X. Models with transformed variables: interpretation and software. Epidemiology 2015; 26: e16-7.PubMed Barrera-Gómez J, Basagaña X. Models with transformed variables: interpretation and software. Epidemiology 2015; 26: e16-7.PubMed
45.
go back to reference Parikh A, Washburn KW, Matsuoka L, et al. A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era. Liver Transpl 2015; 21: 1160-8.PubMed Parikh A, Washburn KW, Matsuoka L, et al. A multicenter study of 30 days complications after deceased donor liver transplantation in the model for end-stage liver disease score era. Liver Transpl 2015; 21: 1160-8.PubMed
46.
go back to reference Austin PC. The performance of different propensity-score methods for estimating differences in proportions (risk differences or absolute risk reductions) in observational studies. Stat Med 2010; 29: 2137-48.PubMedPubMedCentral Austin PC. The performance of different propensity-score methods for estimating differences in proportions (risk differences or absolute risk reductions) in observational studies. Stat Med 2010; 29: 2137-48.PubMedPubMedCentral
47.
go back to reference Lash TL, VanderWeele TJ, Haneuse S, Rothman KJ. Modern Epidemiology, Fourth Edition. Wolters Kluwer; 2021. Lash TL, VanderWeele TJ, Haneuse S, Rothman KJ. Modern Epidemiology, Fourth Edition. Wolters Kluwer; 2021.
Metadata
Title
Intraoperative phlebotomies and bleeding in liver transplantation: a historical cohort study and causal analysis
Authors
François Martin Carrier, MD, MSc
Steve Ferreira Guerra, MSc
Janie Coulombe, PhD
Éva Amzallag, MSc
Luc Massicotte, MD
Michaël Chassé, MD, PhD
Helen Trottier, PhD
Publication date
01-04-2022
Publisher
Springer International Publishing
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 4/2022
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-022-02197-1

Other articles of this Issue 4/2022

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2022 Go to the issue