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