MOnIToR trial

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial

A Ali-Khafaji et al. ICM 2015 Online First January 1-9

Clinical Question

  • In brain-dead organ donors does the use of protocolised fluid therapy compared to usual care improve the number of organs transplanted?

Design

  • Randomised-controlled trial
  • Multi-centre
  • Statistical analysis
    • Designed to enrol 960 subjects – powered to detect a 0.5 difference in organs per donor assuming a mean of 3.1 organs transplanted per donor
    • Planned modified intention-to-treat analysis where only subjects able to receive the intervention were included in the protocolised care arm
    • Terminated early due to lack of resources on the 23rd of March 2013 enrolling 556 subjects

Setting

  • 8 organ procurement organisations (OPO) in the USA
  • 8th October 2009 – 23rd March 2013

Population

  • Inclusion
    • > 16 years of age
    • Declared brain dead
    • Eligible for organ donation
    • Arterial catheter in place or plan to place
  • Exclusion
    • Inability to perform minimally invasive haemodynamic monitoring
    • Receiving lithium therapy
    • Severe aortic regurgitation
    • Intra-cardiac shunt
    • Intra-aortic balloon pump therapy
    • Extracorporeal membrane oxygenation
    • Ventricular assist device
  • 603 screened, 556 randomised (subsequently 18 and 30 aborted by OPO from control and intervention group respectively)
    • 259 control group
    • 249 intervention group

Intervention

  • Protocolised fluid therapy using LiDCO Plus connected to donor’s indwelling arterial catheter. This protocol was followed until transfer to the operating room for organ procurement

Control

  • Managed according to local standard, which DID NOT include functional haemodynamic monitoring
  • Randomisation stratified according to donor’s age ≥65 versus <65

Outcome

  • Primary outcome: Number of organs transplanted per donor – no difference
  • Secondary outcome:
    • Number of organs recovered regardless of whether transplanted
      • No data provided
    •  Observed (O) versus expected (E) organs transplanted (O/E) ratio
      • No data provided
    • Recipient survival to 6 months
      • No data provided at 6 months but no difference in mortality at 12 months post transplant
    • 6-month hospital free survival in recipients
      • No difference

Authors’ Conclusions

  • Compared to usual care, protocolised fluid therapy did not increase the number of organs transplanted from brain-dead organ donors

Strengths

  • Randomised, multi-centre, pragmatic
  • Simple and clear intervention protocol

Weaknesses

  • Unblinded
  • Did not achieve recruitment target and terminated early
    • Nearly 10% of enrolled subject aborted
  • ‘Functional haemodynamic monitoring’ as an exclusion criteria not defined
  • Lack of standardisation of non-cardiovascular intervention
  • Protocol adherence was poor with only a third strictly compliant. Reasons provided in the manuscript were multifactorial
  • Duration of cardiac output monitoring was not specified
  • Results of specified secondary outcomes not available in main paper or supplement

The Bottom Line

  • The use of protocolised fluid therapy resulted in the use of more fluids in the intervention arm but no difference in the use of vasoactive drugs. The lack of benefit may be a result of a number of reasons including being under-powered and protocol violation. I will continue to adhere to local guidelines develop in collaboration with regional transplant teams

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