Clinical trial NCT00744380: Dexmedetomidine Versus Midazolam for Facilitating Extubation
Official title: Dexmedetomidine vs. Midazolam for Facilitating Extubation in Medical and Surgical ICU Patients: A Randomized, Double-Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Keywords: Analgesia
Mechanical ventilation
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2008-09-01
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this randomized, double-blind study is to evaluate the utility, safety, and cost of transitioning benzodiazepine sedation to dexmedetomidine in medical or surgical intensive care unit (ICU) patients requiring sedation when tracheal extubation is nearing. Fifty medical or surgical ICU patients requiring sedation with existing benzodiazepine therapy and qualifying for daily awakenings will be randomized in a double-blind manner to receive additional midazolam or dexmedetomidine.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time From Study Drug Initiation to Tracheal Extubation
timeFrame: Duration of ICU stay, for up to 24 weeks
Secondary outcomes:
measure: Cumulative Doses of Conventional Sedatives and Analgesics
timeFrame: Duration of ICU stay, for up to 24 weeks
measure: The Quality of Sedation (Assessed by the Riker Sedation-Agitation Score) and Analgesia (Assessed by the Pain Assessment Behavioral Score)
timeFrame: Duration of ICU stay, for up to 24 weeks
measure: Sedation-related Adverse Effects
timeFrame: Duration of ICU stay, up to 24 weeks
measure: ICU Experiences by Administering ICU Stressful Experiences Questionnaire (ICU-SEQ)
timeFrame: Duration of hospital stay, up to 24 weeks
measure: Duration of Study Drug Administration
timeFrame: Duration of ICU stay, up to 24 weeks
measure: Manifestations of Acute Stress Disorder by Impact of Event Scale - Revised (IES-R)
timeFrame: Duration of hospital stay, up to 24 weeks
measure: Hospital Anxiety and Depression Scale (HADS) Score
timeFrame: Duration of hospital stay, up to 24 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
name: Robert MacLaren, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: MacLaren R, Preslaski CR, Mueller SW, Kiser TH, Fish DN, Lavelle JC, Malkoski SP. A randomized, double-blind pilot study of dexmedetomidine versus midazolam for intensive care unit sedation: patient recall of their experiences and short-term psychological outcomes. J Intensive Care Med. 2015 Mar;30(3):167-75. doi: 10.1177/0885066613510874. Epub 2013 Nov 12.