Intensive Care Medicine

, Volume 39, Issue 10, pp 1808–1817

Increased perioperative mortality following aprotinin withdrawal: a real-world analysis of blood management strategies in adult cardiac surgery

  • Graham J. Walkden
  • Veerle Verheyden
  • Rosalind Goudie
  • Gavin J. Murphy



To evaluate the effect of aprotinin withdrawal in 2008 on patient outcomes, to assess the likely risks and benefits of its re-introduction, and to consider the relevance of existing evidence from clinical trials to ‘real-world’ practice.


We performed a nested case–control study of two cohorts undergoing adult cardiac surgery in a single tertiary centre. The first group underwent surgery between 1 January 2005 and 30 July 2007 (n = 3,578), prior to aprotinin withdrawal; the second group underwent surgery between 1 January 2009 and 31 December 2010 (n = 3,030), after aprotinin withdrawal. Propensity matching was used to select patients matched for 24 covariates in both groups (n = 3,508). We also estimated the effect of aprotinin withdrawal on a subgroup of high-risk patients (n = 1,002). Results were expressed as adjusted odds ratios (OR) and 95 % confidence intervals (CI) for categorical data and hazard ratios (HR) for time-to-event data.


In propensity-matched cohorts, the withdrawal of aprotinin from clinical use was associated with more bleeding, higher rates of emergency re-sternotomy, OR 2.10 (1.04–4.25), and acute kidney injury (AKI), OR 1.86 (1.53–2.25). In high-risk patients, the increases in bleeding and AKI following aprotinin withdrawal were of a greater magnitude. Aprotinin withdrawal was also associated with a significant increase in 30-day mortality, HR 2.51 (1.00–6.29), in the high-risk group. The results were not altered by sensitivity analyses that adjusted for potential selection bias, time series bias and unmeasured confounders.


Aprotinin withdrawal was associated with increased complication rates and patient deaths following cardiac surgery. These real-world findings are at odds with those of randomised trials and cohort studies that have considered the clinical role of aprotinin.


Aprotinin Cardiac surgery Mortality Blood management 

Supplementary material

134_2013_3020_MOESM1_ESM.doc (340 kb)
Supplementary material 1 (DOC 340 kb)
134_2013_3020_MOESM2_ESM.doc (42 kb)
Supplementary material 2 (DOC 42 kb)
134_2013_3020_MOESM3_ESM.doc (286 kb)
Supplementary material 3 (DOC 285 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Graham J. Walkden
    • 1
  • Veerle Verheyden
    • 2
    • 4
  • Rosalind Goudie
    • 3
  • Gavin J. Murphy
    • 1
    • 4
  1. 1.Bristol Heart InstituteUniversity of BristolBristolUK
  2. 2.Department of Cardiac SurgeryUniversity Hospitals Bristol NHS Foundation TrustBristolUK
  3. 3.School of Social and Community MedicineUniversity of BristolBristolUK
  4. 4.Department of Cardiovascular Sciences, Clinical Sciences Wing, Glenfield General HospitalUniversity of LeicesterLeicesterUK

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