Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cognitive Impairment in the ICU: Evaluation and Outcomes
Brief Summary: The purpose of this study is to determine the impact of a new RN/RRT (Registered Nurse/Registered Respiratory Therapist) directed 2-step protocol to wean patients off of a ventilator. This protocol involves daily attempts to halt sedation (spontaneous awakening trials) combined with daily assessments of patients while they are breathing on their own (spontaneous breathing trials).


Options:
A: Inclusion Criteria:

1. Patients requiring mechanical ventilation in the medical or surgical ICUs.
2. Currently receiving lorazepam or midazolam by continuous infusion for the purpose of sedation therapy.
3. Sedation in these ICUs is provided using an ICU-wide order form that preferentially uses either lorazepam or midazolam with the infusion rate titrated by the bedside nurse to the desired Riker sedation-agitation score(s). Continuous analgesia is provided with fentanyl only with the infusion rate titrated by the bedside nurse to PABS ≤ 3 .
4. Anticipated duration of continuous sedation \> 12 hours with the level of sedation expected to be maintained at Riker sedation-agitation score(s) of 3 - 4.
5. Patients qualifying for daily awakenings as determined by all of the following:

   * fraction of inspired oxygen (FiO2) ≤ 70% or
   * positive end expiratory pressure (PEEP) ≤ 14 cmH2O,
   * hemodynamically stable, and
   * NOT receiving pharmacologic neuromuscular blockade.
6. Informed consent and HIPAA authorization within 24 hours of qualifying for daily awakenings.

Exclusion Criteria:

1. Patients \< 18 years of age or \> 85 years of age.
2. Patients receiving intermittent or "as needed" administration of lorazepam or midazolam.
3. Patients receiving lorazepam or midazolam for purposes other than sedation (e.g. seizure control).
4. Patients receiving epidural administration of medication(s).
5. Patients with Childs-Pugh class C liver disease.
6. Comatose patients by metabolic or neurologic affectation.
7. Patients with active myocardial ischemia or second- or third-degree heart block.
8. Moribund state with planned withdrawal of life support.
9. Patients with known or suspected severe adverse reactions to midazolam (or any other benzodiazepine) or dexmedetomidine (or clonidine).
10. Patients with alcohol abuse within six months of study eligibility.
11. Pregnant females or females suspected of being pregnant.
B: Inclusion Criteria:

1. Subject is ≥18 years of age.
2. If female, subject is non-lactating, and is either:

   1. Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
   2. Of childbearing potential but is not pregnant as confirmed by negative serum pregnancy test at time of screening, and is practicing one of the following methods of birth control: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.
3. Subject is initially intubated and mechanically ventilated, or is planned for imminent intubation and mechanical ventilation, sedation is anticipated to be required during mechanical ventilation, and mechanical ventilation is anticipated to continue for at least 72 hours.
4. Subject or subject's legally authorized representative has voluntarily signed and dated an informed consent form, approved by the applicable Institutional Review Board (IRB), after the nature of the study has been explained and the subject or subject's legally authorized representative has had the opportunity to ask questions. The informed consent must be signed before any study specific procedures are performed.
5. Subject is sedated within a Richmond Agitation-Sedation Scale (RASS) range of -2 to +1 at the time of initiation of study drug

Exclusion Criteria:

1. Subject has been intubated for greater than 96 hours prior to the initiation of study drug (thus, the attainment of consent, screening evaluations, and randomization must all have been completed by the 96th hour post-intubation, so that the actual initiation of the study drug infusion may start by the end of the 96 hour window).
2. Subject has serious central nervous system pathology/trauma that, per clinical judgment of the Investigator, precludes responsiveness or survival.
3. Subject for whom opiates, benzodiazepines, or dexmedetomidine are contraindicated, or who has known or suspected serious allergy to any drug that might be administered during the course of the study.
4. Subject for whom alpha-2 agonists are contraindicated.
5. Subject requires neuromuscular blocking agents during the study for use other than intubation.
6. Subject requires epidural or spinal analgesia during the study.
7. Subject meets any of the following cardiovascular criteria:

   * Acute unstable angina (defined during current hospital stay).
   * Suspicion of acute myocardial infarction.
   * Considered to have a left ventricular ejection fraction of less than 30%. Decision to exclude is predicated on the Investigator's opinion, and may be based on any combination of acute presentations, recently performed diagnostic studies, or a history that suggests poor cardiac function. Pulmonary congestion of a non-cardiac origin or mild congestive failure primarily attributable to etiologies other than poor ventricular function are not exclusion criteria.
   * Heart rate \<50 bpm prior to infusion start.
   * Systolic blood pressure \<90 mmHg prior to infusion start.
   * Conduction abnormalities except 1st degree AV block and rate-controlled atrial fibrillation; subjects with functional pacemaker capacity may be enrolled.
8. Subject is hospitalized primarily due to trauma and/or burns, has received general anaesthesia within the 24 hours prior to the start of study drug infusion, or is anticipated to require general anaesthesia within 24 hours after the start of the infusion.
9. Subject has participated in a trial with any experimental drug within 30 days prior to enrollment in the study, or has ever been enrolled in this study.
10. Subject is unable to undergo any procedure required by the protocol.
11. Subject has laboratory results indicating the presence of liver disease consistent with a Child-Pugh score \>9 (Grade C).
12. Subject has acute hepatitis, history or presence of chronic hepatitis, and/or has had a positive result for Hepatitis B Surface Antigen Test.
13. Subject requires dialysis (eg, hemodialysis, peritoneal dialysis, Continuous Venovenous Hemodialysis \[CVVHD\]).
14. Subject has a known, uncontrolled seizure disorder.
15. Subject has, per the Investigator's judgment, a known or suspected physical or psychological dependence on an abused drug, other than alcohol.
16. Subject has a known psychiatric illness that could confound a normal response to sedative treatment.
17. Subject is incarcerated.
18. Subject is terminally ill with a life duration expectancy of ≤60 days.
19. Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.
C: Inclusion Criteria:

* Recently on mechanical ventilation (less than 2 weeks prior to enrollment)
* Require mechanical ventilation for more than 12 hours
* Over 18 years old
* Under the services of medicine, cardiology, and neurology

Exclusion Criteria:

* Admission after cardiopulmonary arrest
* Inability to obtain informed consent
* Existence of an extubation order at the time of the evaluation
* Dependence upon mechanical ventilation for 2 weeks prior to enrollment
D: Inclusion Criteria:

* Clinical need for sedation and mechanical ventilation
* Receiving full intensive care life support
* Expected stay in ICU of at least 48 hours (h) from time of admission
* Expected requirement for sedation of at least 24h from time of randomisation
* Written informed consent within 36h of ICU admission

Exclusion Criteria:

* Acute severe neurological disorder
* Acute uncompensated circulatory failure at time of randomisation
* Severe bradycardia
* Atrioventricular (AV) conduction block (II-III) unless pacemaker fitted
* Severe hepatic impairment
* Need for muscle relaxation at time of randomisation
* Loss of hearing or vision or any condition interfering significantly with RASS assessment
* Positive pregnancy test or currently lactating

Answer: C