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

Phlébotomies et saignements peropératoires dans les cas de transplantation hépatique : une étude de cohorte historique et une analyse causale

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.

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.

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Author contributions

François Martin Carrier participated in research design, research performance, data acquisition, data analysis, and writing the manuscript. Steve Ferreira Guerra participated in research design, data analysis, and writing the manuscript. Janie Coulombe participated in research design, data analysis, and writing the manuscript. Éva Amzallag and Luc Massicotte participated in data acquisition and writing the manuscript. Michaël Chassé and Helen Trottier participated in data analysis and writing the manuscript.

Acknowledgements

We would like to thank Ms. Claudia Bouchard who helped collect transfusion data, Dr. Cédric Zaouter for his insights regarding the manuscript, and all anesthesiologists from the CHUM who contributed to data collection over the years. Finally, we would like to thank reviewers from the Canadian Journal of Anesthesia/Journal canadien d’anesthésie who conducted very careful and diligent reviews that improved the manuscript.

Disclosures

None.

Funding statement

This work was funded by the Centre de recherche du CHUM. Dr Chassé and Dr Carrier are recipients of a Career Award from the Fonds de la Recherche du Québec – Santé.

Editorial responsibility

This submission was handled by Dr. Philip M. Jones, Deputy Editor-in-Chief, Canadian Journal of Anesthesia/Journal canadien d’anesthésie.

Data availability statement

Due to national regulations in the Province of Quebec (Canada), health medical data cannot be made available publicly. Nevertheless, complete access to the research data set is possible for research purposes after appropriate privacy agreements between research parties have been made. Data access requests may be sent to the corresponding author (francois.martin.carrier@umontreal.ca), or directly to the CHUM REB (ethique.recherche.chum@ssss.gouv.qc.ca). The R code will be available upon request to the corresponding author.

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Correspondence to François Martin Carrier MD, MSc.

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Carrier, F.M., Ferreira Guerra, S., Coulombe, J. et al. Intraoperative phlebotomies and bleeding in liver transplantation: a historical cohort study and causal analysis. Can J Anesth/J Can Anesth 69, 438–447 (2022). https://doi.org/10.1007/s12630-022-02197-1

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  • DOI: https://doi.org/10.1007/s12630-022-02197-1

Keywords

  • liver transplantation
  • bleeding
  • red blood cell transfusion
  • phlebotomy
  • causal inference