Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind Trial in Ventilated ICU Patients Comparing Treatment With an Alpha2 Agonist Versus a Gamma Aminobutyric Acid (GABA)-Agonist to Determine Delirium Rates, Efficacy of Sedation, Analgesia and Discharge Cognitive Status
Brief Summary: Delirium has recently been shown as a predictor of death, increased cost, and longer length of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain, but may contribute to patients' transitioning into delirium. It is possible that modifying the paradigm for sedation using novel therapies targeted at different receptors, such as dexmedetomidine targeting alpha2 receptors and sparing the GABA receptors, could provide efficacious sedation yet reduce the development, duration, and severity of acute brain dysfunction (delirium).


Options:
A: Inclusion Criteria:

* Male or female adult patients admitted to the medical and surgical ICU for critical illnesses requiring mechanical ventilation with expectation of being mechanically ventilated for greater than 24 hours

Exclusion Criteria:

* Subjects who are less than 18 years of age
* Subjects who are pregnant (a pregnancy test will be performed on all women of child bearing age)
* Inability to obtain informed consent from the patient or his/her surrogate
* Subjects in the ICU due to a lack of beds elsewhere in the hospital, triage issues, or withdrawal of care decisions rather than severity of illness
* Subjects admitted with alcohol or drug overdoses, suicide attempts, or alcohol/delirium tremens
* Subjects who are physiologically benzodiazepine dependent, and at risk for withdrawal syndromes
* Subjects with chronic pain syndromes on maintenance narcotics
* Subjects treated within the last 30 days with a drug or device that has not received regulatory approval as of study entry
* Subjects with a psychiatric history for which they are on neuroleptic treatment
* Subjects with documented moderate to severe dementia
* Subjects with anoxic brain injuries, strokes, neurotrauma, or neuromuscular disorders such as myasthenia gravis or Guillain Barre syndrome
* Medical team following patient unwilling to use the sedation regimens
* Subjects whose family and/or physician have not committed to aggressive support for 72 hours or who are likely to withdraw within 72 hours
* Subjects who are moribund and not expected to survive 24 hours
* Subjects not expected to survive hospital discharge due to preexisting uncorrectable medical condition
* Documented allergy to study medications
* Subjects who have either Child-Pugh Class B or C cirrhosis
* Subjects with active coronary artery disease at time of screening as defined by any recent evidence of ischemia, documented myocardial infarction, or coronary intervention within the past 6 months.
* Subjects with advanced heart block at time of screening
B: 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
C: 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.
D: Inclusion Criteria:

* Age more than 18 years
* Clinical need for sedation of an initially intubated (or tracheotomised) and ventilated (with inspiratory assistance) patient
* Prescribed light to moderate sedation (target RASS = 0 to -3) using propofol
* Patients should be randomised within 72 hours from ICU admission and within 48 hours of commencing continuous sedation in the ICU
* Patients should have an expected requirement for sedation more than 24 hours from time of randomisation
* Written informed consent must be obtained according to local regulations before starting any study procedures other than pre-screening

Exclusion Criteria:

* Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
* Uncompensated acute circulatory failure at time of randomisation (severe hypotension with mean arterial pressure \[MAP\] \< 55 mmHg despite volume and pressors)
* Severe bradycardia (heart rate \[HR\] \< 50 beats/min)
* AV-conduction block II-III (unless pacemaker installed)
* Severe hepatic impairment (bilirubin \> 101 µmol/l)
* Need for muscle relaxation at the time of randomisation (may only be used for intubation and initial stabilization)
* Loss of hearing or vision, or any other condition which would significantly interfere with the collection of study data
* Burn injuries requiring regular anaesthesia or surgery
* Use of centrally acting α2 agonists or antagonists at the time of randomisation, notably clonidine
* Patients who have or are expected to have treatment withdrawn or withheld due to poor prognosis
* Patients receiving sedation for therapeutic indications rather than to tolerate the ventilator (e.g. epilepsy)
* Patients who are unlikely to require continuous sedation during mechanical ventilation (e.g. Guillain-Barré syndrome)
* Patients who are unlikely to be weaned from mechanical ventilation e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or advanced amyotrophic lateral sclerosis)
* Distal paraplegia
* Positive pregnancy test or currently lactating
* Received any investigational drug within the preceding 30 days
* Concurrent participation in any other interventional study (any study in which patients are allocated to different treatment groups and/or non-routine diagnostic or monitoring procedures are performed)
* Previous participation in this study
* Any other condition which, in the investigator's opinion, would make it detrimental for the subject to participate in the study

Answer: A