Illuminating Neuropsychological Dysfunction and Systemic Inflammatory Mechanisms Gleaned After Hospitalization in Trauma-ICU Study

Cognitive skills are the crucial abilities required to manage money, maintain employment, and
live independently. Long-term cognitive impairment (LTCI) is a disabling loss of these skills
that can persist for months to years. LTCI frequently occurs after primary brain injury
(e.g., traumatic brain injury, hypoxia), but older LTCI research has not characterized
primary brain injury using NIH Common Data Elements in Imaging, the contributions of
polytrauma, and the time-course of the critical illness, including secondary brain injury
(i.e., delirium). In our recent large study of ICU patients without primary brain injury,
over 50% of patients had LTCI and nearly 50% were newly unemployed at one-year
post-discharge. In-hospital delirium was the major independent risk factor for LTCI.
Surprisingly, this delirium-related LTCI was similar to the LTCI seen in past studies after
moderate traumatic brain injury. Thus, both primary and secondary brain injury are associated
with LTCI, yet they have not been studied together. There is an unmet need to define the
independent risks of primary brain injury and delirium in LTCI. The trauma ICU patient is at
combined risk for primary brain and/or multisystem injuries, secondary brain injury, and
critical illness; these critically injured patients are the unique population to address this
knowledge gap.

Therefore, our FIRST HYPOTHESIS is that delirium duration is an independent risk for the
severity of LTCI, controlling for confounders of co-morbidities, socioeconomic status,
pre-injury employment, primary brain injury, polytrauma, and critical illness. AIM 1 will
address this hypothesis by defining the independent risks of primary and secondary brain
injury on the severity of LTCI among 900 trauma ICU subjects.

But, LTCI's real-world impact on employment has not been explained or adjusted for the above
confounders and social factors. Accordingly, our SECOND HYPOTHESIS is that LTCI severity is
an independent risk for lower level of employment, adjusting for similar confounders. AIM 2
will delineate the independent risk of LTCI severity on employment among trauma ICU
survivors. Lastly, LTCI pathogenesis may be related to persistent inflammation.

So, our THIRD HYPOTHESIS is that hospital discharge biomarkers of persistent inflammation
will be independent risks for LTCI severity, adjusting for similar confounders. AIM 3 will
explore the mechanistic role of plasma inflammatory biomarkers on LTCI severity among trauma
ICU survivors.

Inclusion Criteria:

• Adult trauma and/or burn patients, injury from any mechanism, requiring admission to an
Adult ICU for the treatment of shock (any type), respiratory failure, and/or neurologic
failure, including monitoring for deteriorating brain function.

Exclusion Criteria:

- Inability to obtain informed consent within the 72 hours following injury

- Attending physician refusal

- Patient and/or surrogate refusal

- 72-hour period of eligibility was exceeded before the patient was screened

- Patient unable to consent and no surrogate available within the 72-hour period

- Residence > 200 miles from study site and do not regularly visit the Nashville area.

- Patients who are homeless and have no secondary contact person available.

- Severe prior cognitive or neurodegenerative disorder that prevents a patient from
living independently at baseline

- Inability to understand English or Spanish or bilateral deafness or bilateral vision
loss

- Inability to co-enroll with other studies

- Prisoners

- Substance abuse requiring treatment, known psychotic disorder (e.g., schizophrenia or
schizoaffective disorder), or recent (within the past 6 months) serious suicidal
gesture necessitating hospitalization

- Expected death within 24 hours of enrollment or lack of commitment to aggressive
treatment by family or the medical team (e.g., likely to withdraw life support
measures within 24 hours of screening).