Self-management of Sedative Therapy by Ventilated Patients

Efficacy of Self-management of Sedative Therapy by Ventilated ICU Patients

The purpose of this randomized clinical trial is to test the efficacy of dexmedetomidine for the self-management of sedative therapy (SMST) in a sample of critically ill patients receiving mechanical ventilator support. The investigators hypothesis is that self-management of sedative therapy by mechanically ventilated patients in the intensive care unit (ICU), tailored to their individual needs will be more efficacious than nurse-administered sedative therapy in reducing anxiety, which may reduce duration of mechanical ventilator support and occurrence of delirium.

Study Overview

• Status: Active, not recruiting
• Conditions: Critical Illness; Respiratory Failure; Anxiety
• Intervention / Treatment: Drug: Dexmedetomidine

Detailed Description

The overall objective of this study is to demonstrate efficacy for conducting a future, pragmatic effectiveness trial to test whether self-management of sedative therapy (SMST) is superior to nurse-administered sedative therapy in day-to-day intensive care unit (ICU) practice. This efficacy trial is powered for the investigators primary, clinically relevant endpoints (anxiety, duration of mechanical ventilation, and delirium presence), and examines patient outcomes adversely affected by sedative administration practices, such as prolonged ICU stays, altered mental status, and diminished post-ICU quality of life. This randomized clinical trial with a total of 190 mechanically ventilated patients enrolled and maintained on protocol will address the following Specific Aims.

The primary aim is to determine the efficacy of SMST compared to nurse-administered sedative therapy on anxiety, duration of mechanical ventilation, and presence of delirium in mechanically ventilated patients (MVPs).

The secondary aim is to compare level of arousal and sedative exposure in mechanically ventilated patients (MVPs) randomized to SMST to those MVPs receiving nurse-administered sedative therapy. The investigators hypothesize that SMST patients will be easily arousable, more alert, and exposed to less sedation than those who receive nurse-administered sedative therapy.

Exploratory aims are to compare post-ICU outcomes (physical/functional status, psychological well-being, and health-related quality of life) and recall of ICU experiences between MVPs randomized to SMST and those receiving nurse-administered sedative therapy.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • School of Medicine, University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is acutely mechanically ventilated during the current hospitalization.
2. Subject is currently receiving a continuous intravenous infusion of a sedative/opioid medication(s) or has received at least one intravenous bolus dose of a sedative/opioid medication in the previous 24 hours (fentanyl, hydromorphone, ketamine, morphine, midazolam, diazepam, lorazepam, propofol, haloperidol, dexmedetomidine).
3. Subject must pass pre-Patient-Controlled Sedation (PCS) screening test and be assessed Richmond Agitation-Sedation Scale (RASS) -2 to +1
4. Subject Age ≥ 18 years
5. Subject or their proxy is capable of providing informed consent

Exclusion Criteria:

1. Aggressive ventilatory support or prone ventilation.
2. Hypotension (systolic blood pressure < 85 mmHg) requiring a vasopressor at a dose greater than norepinephrine or epinephrine 0.15 mcg/kg/min or vasopressin > 2.4 units per hour. Subjects will be excluded if they require more than one continuous infusion of a catecholamine vasopressor medication simultaneously. Subjects will be excluded if the vasopressor dose was higher than norepinephrine or epinephrine 0.15 mcg/kg/min, vasopressin > 2.4 units per hour, phenylephrine >3 mcg/kg/min, dopamine >10 mcg/kg/min or dobutamine at any dose in the prior 6 hours. If dopamine is being used to increase heart rate, rather than as a vasopressor for hypotension, subject will be excluded.
3. Second or third degree heart block or bradycardia (heart rate < 50 beats/min).
4. Paralysis or other condition preventing the use of push button device
5. Positive pregnancy test or lactation
6. Acute hepatitis or liver failure (direct bilirubin >5 mg/dL)
7. Acute stroke or uncontrolled seizures.
8. Acute myocardial infarction within 48 hours prior to enrollment.
9. Severe cognition or communication problems (such as coma, deafness without signing literacy, physician-documented dementia)
10. Assessed RASS -3, -4, -5 or RASS +2,+3, +4
11. Chronic ventilator support in place of residence prior to current hospitalization.
12. Imminent extubation from mechanical ventilator support.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; These patient will get usual care - sedation administered by ICU Nurses as deemed necessary by primary care team
Experimental: Dexmedetomidine; These patients will receive a basal intravenous infusion of medication (Dexmedetomidine) and have access to self-administered sedation medication (Dexmedetomidine) for anxiety.	Drug: Dexmedetomidine; Patient will receive a maintenance intravenous infusion of medication (Dexmedetomidine) and have access to self-controlled sedation medication (Dexmedetomidine) for anxiety.; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in anxiety using the 100mm vertical visual analog scale	Vertical visual analog scale will be used to measure level of state anxiety	7 days
Changes in duration of days receiving mechanical ventilation after study enrollment	Patients' self-management of sedative therapy (SMST) using dexmedetomidine compared to usual sedation practices in mechanically ventilated subjects.	up to 6 months
Changes in delirium using the CAM-ICU tool	Confusion Assessment Method-ICU (CAM-ICU) will be used as a pre-enrollment delirium screening tool and to measure level of alertness and presence of delirium	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of level of arousal and alertness using the Richmond Agitation-Sedation Scale	The Richmond Agitation-Sedation Scale will be used to measure level of arousal and alertness	7 days
Comparison of sedative exposure (sedation frequency + sedation intensity) using electronic health record data of intravenous sedative medications.	Frequency of intravenous sedatives medications sums the number of sedative medication doses administered to participant during each 4-hour time period during a 24-hour day. Sedation intensity is a score derived from aggregate dose frequency and dosing of each sedative medications administered to all study participants each 4-hour time period over the 24-hour study day. Scores are summed for the 24-hour period over the 6, 4-hour time blocks to produce a daily sedation intensity score.	each 24-hour period, up to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of post-ICU physical status using the Katz Activities of Daily Living scale	Physical status will be assessed by the Katz Activities of Daily Living scale to assess basic physical abilities like bathing, feeding with 6 questions	3 and 6 months after ICU discharge over the telephone
Comparison of post-ICU functional status using the Functional Activities Questionnaire	Functional status will be assessed by the Functional Activities Questionnaire that contains 10 questions that assess instrumental activities of daily living such as cooking, driving, managing finances.	3 and 6 months after ICU discharge over the telephone
Comparison of post-ICU psychological well-being status using the Patient Health Questionnaire	Psychological well-being will be assessed by the Patient Health Questionnaire is a 9-item tool that tracks symptoms of major depression	3 and 6 months after ICU discharge over the telephone
Comparison of post-ICU psychological well-being status using the Posttraumatic Stress Disorder Checklist Event Specific scale	Psychological well-being will also be assessed with the Posttraumatic Stress Disorder Checklist Event Specific toll to measure symptoms of posttraumatic stress disorder.	3 and 6 months after ICU discharge over the telephone
Comparison of post-intensive care unit health-related quality of life using the Short-Form 36	Post-intensive care unit health-related quality of life will be assessed by the Short-Form-36	3 and 6 months after ICU discharge over the telephone
Comparison of immediate post-extubation recollections of ICU using the Intensive Care Experience questionnaire	Immediate post-extubation recollection of ICU experiences	24 to 48 hours after extubation, 3 and 6 months after ICU discharge over the telephone
Relationships among cognitive experiences using the Confusion Assessment Method-ICU and awareness using the Richmond Agitation-Sedation Scale with mechanical ventilation complications of device disruption or self-extubation	Relationships among cognitive experiences, awareness, and mechanical ventilation complications	24 to 48 hours after extubation

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Minnesota
• Investigators: Principal Investigator: Linda L Chlan, RN, PhD, Mayo Clinic

Publications and helpful links

General Publications

• Tracy MF, Chlan L, Savik K, Skaar DJ, Weinert C. A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients. Nurs Res. 2019 Jan/Feb;68(1):73-79. doi: 10.1097/NNR.0000000000000322.
• Chlan LL, Weinert CR, Tracy MF, Skaar DJ, Gajic O, Ask J, Mandrekar J. Study protocol to test the efficacy of self-administration of dexmedetomidine sedative therapy on anxiety, delirium, and ventilator days in critically ill mechanically ventilated patients: an open-label randomized clinical trial. Trials. 2022 May 16;23(1):406. doi: 10.1186/s13063-022-06391-w.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 23, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimated): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Disease Attributes; Respiratory Insufficiency; Critical Illness; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 16-000417; R01HL030881 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO