Acute Respiratory Failure, Anxiety
Conditions
Keywords
sedation, mechanical ventilation, anxiety, respiratory failure
Brief summary
Mechanical ventilation (MV) is the most frequently used life-support modality in intensive care units (ICUs). To reduce anxiety, stress and promote tolerance of MV, nurses frequently administer a variety of sedative medications to their patients based on subjective observations. The investigators hypothesize that patient-controlled sedation, compared to clinician-directed sedation, will decrease sedative exposure while decreasing patient anxiety during the episode of mechanical ventilation.
Detailed description
A study to determine whether critically ill patients, during a substantial portion of their time on mechanical ventilation, can reduce anxiety symptoms better with PCS than their caregivers while reducing over-sedation, duration of mechanical ventilation and length of ICU stay will require hundreds of subjects enrolled on a multi-day protocol. However, patient-controlled sedation has been used in less than 20 patients and only for less than 24 hours. Therefore this study is designed to: 1. Establish the feasibility of subject recruitment and protocol adherence in a randomized pilot trial that compares patient-controlled sedation (PCS) using dexmedetomidine to usual sedation practice in mechanically ventilated patients. Feasibility will be defined by: a) number and proportion of patients or proxies who consent to enrollment, b) proportion of eligible subjects enrolled on Days 1,2,3,4 etc, of mechanical ventilation, c) number of days on protocol, up to five days, that subjects successfully use the PCS device, d) ability of ICU nurses to adjust the pump and adhere to the infusion rates of the PCS protocol. 2. Develop and refine the study protocol including: a) improving the proportion of patient daily assessments actually completed such as anxiety and delirium scales, b) develop a protocol to reliably determine when the subject is not able to self-manage their sedation due to weakness, confusion or severe illness; c) create rules for suspending PCS therapy and d) develop a post-ICU symptom interview. 3. Estimate effect sizes on key variables to inform the design of a future randomized trial to compare: a) sedative exposure, anxiety levels, and delirium occurrence between groups, b) adverse event rates and protocol violations related to the drug, pump or both; and c) duration of mechanical ventilation and ICU stay.
Interventions
DRUGDexmedetomidine
loading dose (0.5 mcg/kg i.v.), followed by a continuous basal infusion (0.2-0.7 mcg/kg/hr) with 3 allowable patient-controlled self-boluses per hour (0.25 mcg/kg) each with a 20-minute lock-out. Study infusion up to 5 days.
Sponsors
National Institute of Nursing Research (NINR)
Hospira, now a wholly owned subsidiary of Pfizer
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult intubated patients with respiratory failure expected to require mechanical ventilation for at least an additional 48 hours * subjects have to have at least a 50% chance of being able to operate the PCS machine (i.e., adequate hand strength and cognition)
Exclusion criteria
* aggressive ventilatory support such as positive end expiratory pressure \> 15 cm of water, prone ventilation, use of high-frequency oscillator ventilator * hypotension requiring vasopressors (systolic blood pressure \< 85 mmHg), second or third degree heart block or bradycardia (heart rate \< 50 beats/min.) * permanent condition preventing the use of push button device (e.g., paralysis) * pregnancy or lactation * acute hepatitis or liver failure * general anesthesia 24 hours prior * acute stroke or uncontrolled seizures * acute MI * severe cognition or communication problems (e.g., coma as main reason for intubation, deafness without signing literacy, dementia or severe delirium)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aggregate Sedative Exposure During PCS Use (up to 5 Days). | 5 days after enrollment | Will use the sedation intensity score Scale is based on a score of 1 (full arousal) to 4 (no arousal) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | During 5 days of study protocol | arterial hypotension, bradycardia, self-extubations, and protocol violations related to drug, pump or both. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual Sedative Practice Subjects will have usual care sedation directed by their patient care team with no protocolized restriction on drug doses, selection or duration. | 7 |
| Patient Controlled Sedation Subjects will be given the hand actuator connected to a Lifecare PCA Infusion System in the PCA + continuous mode with the syringe filled with 4 ucg/ml of dexmedetomidine. A loading dose (0.5 mcg/kg) will be given followed by a continuous basal infusion (0.2-0.7 mcg/kg/hr) with 3 allowable patient-controlled self-boluses per hour (0.25 mcg/kg) each with a 20-minute lock-out. Bedside RNs will adjust the basal rate to a maximum of based on the number of bolus requests in the prior two hours. Subjects can also receive bolus supplemental sedative medications (benzodiazepines and/or opioids)if needed in the judgment of the patient-care nurse.
Dexmedetomidine: loading dose (0.5 mcg/kg i.v.), followed by a continuous basal infusion (0.2-0.7 mcg/kg/hr) with 3 allowable patient-controlled self-boluses per hour (0.25 mcg/kg) each with a 20-minute lock-out. Study infusion up to 5 days. | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Usual Sedative Practice | Patient Controlled Sedation | Total |
|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 13.2 | 66.5 years STANDARD_DEVIATION 13.2 | 66.5 years STANDARD_DEVIATION 13.2 |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 7 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 |
Outcome results
Primary
Aggregate Sedative Exposure During PCS Use (up to 5 Days).
Will use the sedation intensity score Scale is based on a score of 1 (full arousal) to 4 (no arousal)
Time frame: 5 days after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Sedative Practice | Aggregate Sedative Exposure During PCS Use (up to 5 Days). | 4 units on a scale |
| Patient Controlled Sedation | Aggregate Sedative Exposure During PCS Use (up to 5 Days). | 3.5 units on a scale |
Secondary
Number of Participants With Adverse Events
arterial hypotension, bradycardia, self-extubations, and protocol violations related to drug, pump or both.
Time frame: During 5 days of study protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Sedative Practice | Number of Participants With Adverse Events | 7 participants |
| Patient Controlled Sedation | Number of Participants With Adverse Events | 8 participants |