Reoxygenation After Cardiac Arrest (REOX Study)

Specific Aim 1: Test if the degree and duration of hyperoxia following ROSC from cardiac
arrest is associated with the degree of in vivo oxidative stress during the
post-resuscitation phase of therapy.

Approach: We will conduct a multicenter prospective observational study of adult patients
resuscitated from cardiac arrest. We will record data pertaining to oxygenation parameters
and other factors and measure biomarkers of oxidative stress (isoprostanes and isofurans) in
the plasma at 0 and 6 hours after ROSC using gas chromatography negative ion chemical
ionization mass spectrometry. We will determine the exposure to post-ROSC hyperoxia by
calculating the time-weighted average PaO2 and SaO2 for the post-resuscitation phase of
therapy, and will test the association with plasma isoprostane and isofuran levels.

Specific Aim 2: Test if the degree and duration of hyperoxia following ROSC from cardiac
arrest is associated with the degree of neurological disability at hospital discharge.

Approach: In the study described above, we will determine the Modified Rankin Scale at
hospital discharge. We will perform multivariable analyses adjusted for numerous covariates
known to be associated with outcome in post-cardiac arrest patients to determine if
post-ROSC hyperoxia exposure is independently associated with neurological disability.

Specific Aim 3: Test if the degree and duration of hyperoxia following ROSC from cardiac
arrest is associated with neuropsychological outcomes among survivors at 180 days.

Approach: In the study described above, we will assess neuropsychological outcome among
survivors at 180 days. Neuropsychological testing will use validated instruments across five
cognitive domains (attention, Wechsler Adult Intelligence Scale-IV-digit span; (2)
reasoning, Wechsler Adult Intelligence Scale-IV-similarities; (3) immediate and delayed
memory, Wechsler Memory Scale-III-logical memory I and II; (4) verbal fluency, Controlled
Oral Word Association Test; and (5) executive functioning, Hayling Sentence Completion
Test). We will perform multivariable analyses to determine if post-ROSC hyperoxia exposure
is independently associated with neuropsychological deficits.

Inclusion Criteria:

- Age >17 years

- Cardiac arrest

- Return of spontaneous circulation

- Not following commands immediately after ROSC

- Endotracheal intubation

- Clinician intent to treat with therapeutic hypothermia (or absence of clinician
intent to withhold therapeutic hypothermia)

Exclusion Criteria:

- Presumed etiology of arrest is trauma

- Presumed etiology of arrest is hemorrhage

- Presumed etiology of arrest is sepsis

- Permanent resident of nursing home or other long-term care facility

- Any other condition, that in the opinion of the investigator, would preclude the
subject from being a suitable candidate, e.g. end stage chronic illness with no
reasonable expectation of survival to hospital discharge