Neonatal ECMO Study of Temperature

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Neonatal ECMO Study of Temperature

• NEST

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Basic ECMO circuit
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ECMO Study follow-up at four
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Outcome classification

• Normal
• Impairment No functional loss
• Disability
• Mild Little or no support
• Moderate Needs aids or assistance
• Severe Constant supervision

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Results Cognitive
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Results Cognitive
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Results - Neuromotor
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Results General health
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Results Behaviour
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Results Hearing
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Outcome at four years of age
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Results Overall
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Overall outcome
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Concept

• Infants receiving ECMO represent a high risk
  group for cerebral injury
• Mild hypothermia appears to be a promising means
  of offering neuroprotection following hypoxic
  ischaemic injury

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Pilot Study Progress

• Stage I 1998 -1999
• Twenty neonates recruited
• Cooled for first 12 hours of ECMO
• No significant problems found.
• Stage II 2000 -2001
• Twenty neonates recruited
• Cooled for the first 24 hours of ECMO
• Stage III 2001
• Five neonates recruited
• Cooled to 340c core temperature for the
• first 48 hours of ECMO

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Methods

• 25 consecutive neonates referred for ECMO (n
  5 per group)
• Group 1 (Control) Core temp at 370c for five
  days
• Group 2 360c for 24 hours
• Group 3 350c for 24 hours
• Group 4 340c for 24 hours
• Group 5 340c for 48 hours

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MethodProtocol Blood Sampling Points
ECMO Cannulation (VA or VV-DLC)
37 0C
Cooling
48 H
Baseline
2 H
12 H
24 H
Day 3
Day 4
Day 5
36 H
Infants were carefully assessed clinically and
biologically Blood Samples were drawn from the
ECMO circuit sampling port at the times shown
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Measurements

• Serum Assays
• Cytokines IL6 and IL8
• Molecular Markers of Coagulation
• Thrombin-Antithrombin III, Antithrombin III,
  Plasmin ?2 plasminogen
• Complement C3a

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Measurements

• Heparin and Platelet Transfusion Requirements
• Oxygenator resistance calculated 2, 12 and 24
  hourly thereafter using the formula
• Pre-oxygenator pressure - post-oxygenator
  pressure(mmHg)
• circuit blood flow
  (ml/min)

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Summary of Demographic Data for Study Groups
Comparison of groups by Kruskal-Wallis test (df
4) values are median (range)
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Median Group Core Temperature During Study Period

• Comparing groups 1-5, median rectal temperature
  SD at 24 hours
• (Kruskal-Wallis chi-squared 23.3,
  df 4, plt0.001)

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Progress and Complications During the Study

Comparison of groups by Kruskal-Wallis (df
4) Bleeding at cannula site due to heparin bolus
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Cardiovascular Data During Cooling and Rewarming
Denotes patients not cooled
Values are median (range)
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Results

• No systemic difference between groups for
• Molecular markers of coagulation
• Complement C3a
• Cytokines IL6 and IL8
• Platelet transfusion requirements
• Oygenator resistance

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Mean IL6 (Temperature Groups)
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Mean C3a (Temperature Groups)
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Conclusions

• Applying mild hypothermia (340C) for 24 or 48
  hours of neonatal ECMO appears feasible and safe
• No major complications related to mild
  hypothermia were observed in this study.

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The next steps

• A randomised controlled trial

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Trial outline

• Research question to be addressed Does cooling
  neonates (neonate less than or equal to 28 days
  of age) requiring ECMO to 34oC for the first 48
  to 72 hours of their ECMO run result in improved
  Bayley scores at 2 years of age?
• Trial design Pragmatic multi-centre randomised
  controlled trial.

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Trial outline

• Eligibility
• Meeting standard ECMO criteria but no congenital
  diaphragmatic hernias and no post cardiac ECMO

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Trial outline

• Blinding
• Randomisation
• Consent

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Trial outline

• Minimisation by approach to ECMO (VV or VA).

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Trial outline

• ECMO management
• Organisation

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Trial outline

• Trial end points
• Primary outcome MDI of the Bayley scales (34) at
  age of 2 years (24 - 27 months).
• Note Where the MDI cannot be assessed because of
  severe disability or death, a score of either 40
  or 0 will be recorded respectively.

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Trial outline

• Secondary outcomes
• Death
• Outcome of a structured neurological assessment
• Results of simple questionnaire completed by
  parents about their childs health at two years
  of age.
• PDI of the Bayley scales
• Visuospatial assessment
• Testers rating of child behaviour

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Trial Size
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Analysis

• Intention-to-treat analysis
• Pre specified secondary analyses by disease
  severity and diagnosis

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Other issues

• Timescale
• aEEG
• MRI

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Thank you