Please select the eligibility criteria that correspond to the clinical trial below.
Title: The BRAIN ICU Study: Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors
Brief Summary: The primary purpose of this proposal will be to identify potentially modifiable risk factors of long-term cognitive impairment (i.e. development of delirium and exposure to sedative and analgesic medications) in ICU patients. The investigators will quantify the independent contribution of these risk factors to the incidence of long-term cognitive impairment, controlling for other established risk factors including age, pre-existing cognitive impairment, and apolipoprotein E (apoE) genotype. Quantifying the contributions of these modifiable risk factors will pave the way for the development of preventive and/or treatment strategies to reduce the incidence, severity and/or duration of long-term cognitive impairment and improve functional recovery for patients with critical illness.


Options:
A: Inclusion Criteria:

1. Critically ill patients ≥18 years of age
2. Anticipated ICU stay of \>48 hours
3. Able to receive enteral administration of study drug (i.e. by mouth or any feeding tube = naso- or oro- or percutaneous gastric or post-pyloric feeding tube)
4. Consent to participate.

Exclusion Criteria:

1. ICU admission of \>48 hours prior to screening
2. Unable to assess for delirium (e.g. comatose defined as SAS 1 or 2 or either 'No Response' Score A or B on ICDSC, chemically paralyzed with neuromuscular blocking drugs)
3. Screened delirium positive prior to randomization (ICDSC score ≥4 out of 8)
4. Anticipated withdrawal in next 48 hours
5. Known history of severe cognitive or neurodegenerative disease (e.g. dementia, Parkinson's disease) or severe structural brain injury (e.g. traumatic brain injury, intracranial hemorrhage) as the ICDSC assessment tool has not been validated in these patient populations
6. Unable to communicate in English or French (Montreal site)
7. Contraindications to receiving any enteral medication (defined as absolute contraindication to enteral nutrition such as gastrointestinal obstruction, perforation, recent upper GI surgery, no enteral access)
8. Active seizures
9. Known pregnancy
10. Legal blindness
11. Known allergy to melatonin
B: 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)
C: Inclusion Criteria:

* Adult patients admitted to the medical or surgical ICU who are receiving treatment for respiratory failure, cardiogenic shock, hemorrhagic shock, and/or septic shock.

Exclusion Criteria:

* Moderate to severe dementia on ICU admission based on a standardized surrogate assessment (as this would prohibit patients from functioning independently at home);
* Moderate or severe physical dysfunction that precludes performance of independent activities of daily living based on a standardized surrogate assessment;
* Live greater than 120 miles from Nashville;
* Blind, deaf, or unable to speak English;
* Prisoners;
* Homelessness and no secondary contact person available
D: Inclusion Criteria:

* 18 years of age or over
* Mechanically ventilated, with anticipated need for MV ≥48 hrs
* ICU team has decided to initiate continuous sedative/analgesic infusion(s)
* informed consent from patient and/or SDM

Exclusion Criteria

* Admission after resuscitation from cardiac arrest
* Traumatic brain injury
* Currently receiving neuromuscular blocking agents
* Allergy to midazolam and lorazepam
* Lack of commitment to aggressive treatment
* Previous enrolment in SLEAP, or current enrolment in related trial

Answer: B