Reoxygenation After Cardiac Arrest II (REOX II Study)

Specific Aim 1: Test if initiation of the rapid FiO2 optimization protocol 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 interventional study (FiO2 optimization protocol) 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 (IsoPs) and isofurans (IsoFs)] in the plasma at 0 and 6 hours after ROSC using
gas chromatography negative ion chemical ionization mass spectrometry. We will compare
plasma IsoPs/IsoFs at each time point between subjects enrolled in REOX II (i.e. receive the
study intervention, rapid FiO2 optimization) and REOX I (i.e. do not receive the study
intervention) using t-test or Mann-Whitney U as appropriate with corrections for multiple
comparisons.

Specific Aim 2: Test if initiation of the rapid FiO2 optimization protocol following ROSC
from cardiac arrest is associated with a decrease in neurological disability at hospital
discharge.

Approach: In the study described above, we will determine the Modified Rankin Scale (mRS) at
hospital discharge. We will compare proportions of good neurological outcome [defined as a
mRS ≤ 3] between subjects enrolled in REOX II (i.e. receive the study intervention, rapid
FiO2 optimization) vs. those enrolled in REOX I (i.e. do not receive the study
intervention), using binomial test.

Specific Aim 3: Test if initiation of the rapid FiO2 optimization protocol 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). Among survivors, we will compare the 180-day neuropsychological measures (composite
z-scores for each cognitive domain) between the same two groups using t-test or Mann-Whitney
U as appropriate with corrections for multiple comparisons. We will also compare the
proportions of patients able to return to work between the two groups using binomial test

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