Dexmedetomidine Versus Midazolam for Facilitating Extubation

This study is unique because midazolam or dexmedetomidine will be added, in a blinded
fashion, to existing sedation and analgesia in an effort to decrease or possibly discontinue
these therapies.

Objectives:

The objectives of this study are to determine if transitioning conventional sedation to
dexmedetomidine safely facilitates tracheal extubation after study initiation; alters the
amounts of sedative and analgesic agents required after study initiation; influences the
levels of sedation and analgesia; alters the adverse event profile (neurologic, hemodynamic,
or gastrointestinal) during and after discontinuing sedation; and impacts the total cost of
sedation during and after discontinuing sedation.

Hypothesis 1: Transitioning conventional sedation to dexmedetomidine expedites tracheal
extubation to shorten ventilator time.

Specific Aim 1: Comparatively determine the time from study initiation to tracheal
extubation with midazolam and dexmedetomidine when the practice of daily awakenings is used.

Hypothesis 2: Transitioning conventional sedation to dexmedetomidine reduces the doses of
conventional sedatives and analgesics while maintaining equivalent levels of sedation and
analgesia and not incurring adverse events.

Specific Aim 2a: Comparatively determine the hourly, daily, and cumulative doses of
conventional sedatives and analgesics from study initiation to sedation discontinuation with
midazolam and dexmedetomidine when the practice of daily awakenings is used.

Specific Aim 2b: Comparatively evaluate the quality of sedation and analgesia of midazolam
and dexmedetomidine by determining the proportion of Riker sedation scores at 3 - 4 (desired
level of sedation) and ≤ 2 or ≥ 5 (undesired levels of sedation) and the proportion of Pain
Assessment Behavioral Scores (PABS) ≤ 3 (comfortable) and ≥ 4 (pain).

Specific Aim 2c: Comparatively evaluate sedation-related adverse effects (neurologic,
hemodynamic, or gastrointestinal) of midazolam and dexmedetomidine when the practice of
daily awakenings is used.

Hypothesis 3: Transitioning conventional sedation to dexmedetomidine increases the cost of
administering sedation but minimizes the incidental costs associated with sedation to
counterbalance and possibly reduce the total cost of sedation (sum of administration costs
and incidental costs).

Specific Aim 3a: Comparatively determine the hourly, daily, and cumulative administration
costs of midazolam and dexmedetomidine when the practice of daily awakenings is used.

Specific Aim 3b: Comparatively determine the hourly, daily, and cumulative incidental costs
of conventional sedatives and dexmedetomidine; including neurologic dysfunction,
antipsychotic requirements, cardiovascular dysfunction, constipation or ileus, differences
in times to ventilator discontinuation, personnel time, and patient transfer from the ICU
after sedation discontinuation.

Inclusion Criteria:

1. Patients requiring mechanical ventilation in the medical or surgical ICUs and
currently receiving lorazepam or midazolam by continuous infusion for the purpose of
sedation therapy. 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 .

2. 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.

3. 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.

4. 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.