The BRAIN Intensive Care Unit (ICU) Study: Bringing to Light the Risk Factors

Among Intensive Care Unit (ICU) survivors, subsequent cognitive and functional decline are
the greatest threats to meaningful recovery. Six small cohorts indicate that an alarming 30%
to 80% of the increasingly millions of ICU survivors develop an acquired long-term cognitive
impairment (LTCI) functionally equivalent to mild/moderate dementia that may last years.
Additionally, major deficits in health-related quality of life (HRQL), functional status, and
an "ICU accelerated" frailty are common, especially in the elderly. A leading and potentially
modifiable risk factor for these devastating outcomes may be ICU delirium, which is a
predictor of higher mortality, higher cost, and poor cognitive function at discharge.
Additionally, heavy and prolonged exposure to potent psychoactive medications routinely
administered in high doses to ventilated patients may have lasting yet preventable cognitive
and functional effects. In this proposal, Aims 1 and 3 will determine whether delirium is an
independent risk factor for the incidence, severity, and/or duration of LTCI (Aim 1) and
impaired HRQL (Aim 3) in ICU survivors. Likewise, Aims 2 and 4 will determine whether degree
of exposure to sedative and analgesic medications in ICU patients is an independent risk
factor for the incidence, severity, and/or duration of LTCI (Aim 2) and impaired HRQL (Aim
4). The study will be a prospective cohort study enrolling 800 mechanically ventilated
medical and surgical patients from 3 diverse medical centers over a 39 month period with
comprehensive follow-up testing at 3 and 12 months after hospital discharge. This study will
quantify whether delirium and sedative/analgesic exposure are indeed risk factors for LTCI
and HRQL, controlling for other covariates such as age, medical versus surgical ICU
admission, pre-existing cognitive impairment, sepsis, and apoE genotype. This will pave the
way for the development of preventive and/or treatment strategies to reduce long-term
cognitive impairment and improve the functional recovery of older and younger ICU patients
for decades to come. Major threats to recovery for ICU survivors are acquired cognitive and
functional decline that can last years, especially in older patients. To pave the way for
future preventive and interventional strategies, the cohort will determine to what degree
delirium and potent sedatives and analgesics are risk factors for long-term cognitive
impairment and functional decline following critical illness.

Inclusion Criteria:

- Patients will be included if they are adult, patients in a medical and/or surgical ICU
receiving treatment for any of the following: respiratory failure or cardiogenic or
septic shock.

Exclusion Criteria:

Patients who meet the inclusion criteria will be excluded if they meet any of the following
criteria:

- Cumulative ICU time >5 days in the past 30 days, not including the current ICU stay,
as this might create a state of flux regarding patients' cognitive baseline

- Severe cognitive or neurodegenerative diseases that prevent a patient from living
independently at baseline, including mental illness requiring institutionalization,
acquired or congenital mental retardation, known brain lesions, traumatic brain
injury, cerebrovascular accidents with resultant moderate to severe cognitive deficits
or ADL dependency, Parkinson's disease, Huntington's disease, severe Alzheimer's
disease or dementia of any etiology

- ICU admission post cardiopulmonary resuscitation with suspected anoxic injury

- An active substance abuse or psychotic disorder, or a recent (within the past 6
months) serious suicidal gesture necessitating hospitalization. This exclusion will
enrich follow-up rates by avoiding patients with whom it is particularly challenging
to maintain long-term contact

- Blind, deaf, or unable to speak English, as these conditions would preclude our
ability to perform the follow-up evaluation interviews.

- Overly moribund and not expected to survive for an additional 24 hours and / or
withdrawing life support to focus on comfort measures only.

- Prisoners.

- Patients who live further than 200 miles from Nashville and who do not regularly visit
the Nashville area.

- Patients who are homeless and have no secondary contact person available. This
exclusion will enrich follow-up rates by avoiding patients with whom it is
particularly challenging to maintain long-term contact

- The onset of the current episode of respiratory failure, cardiogenic shock, or septic
shock was > 72 hours ago.

- Patients who have had cardiac bypass surgery within the past 3 months (including the
current hospitalization)