Anxiety, Intensive Care Acquired Cognitive Impairment, Intensive Care Unit Delirium, Pain
Conditions
Keywords
Delirium, Music, Pain, Anxiety, Cognition
Brief summary
Critically ill older adults admitted to the intensive care unit (ICU) are at a higher risk to develop delirium, which predisposes them to longer lengths of ICU and hospital stay, increased in-patient mortality, and higher risk of new acquired cognitive impairment and dementia. Music listening is a non-pharmacological intervention that holds potential to decrease ICU delirium. The investigators propose a randomized controlled trial to evaluate the efficacy of a seven-day slow-tempo music intervention on the primary outcome of delirium/coma free days among mechanically ventilated, critically ill older adults.
Detailed description
One million adults in the United States receive mechanical ventilation for acute respiratory failure in the intensive care units (ICUs) annually and up to 80% of them develop delirium during their ICU stay. Presence of delirium predisposes older adults to immediate in-hospital complications including a longer length of ICU and hospital stay, increased risk of in-patient mortality and elevated costs of care. In addition, ICU delirium is associated with long-term post-discharge complications such as development of cognitive impairment and dementia. Recent research studies exploring pharmacological strategies to manage ICU delirium have not demonstrated efficacy; a limitation also acknowledged in the Society of Critical Care Medicine 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption guidelines. Music listening is a non-pharmacological intervention that has shown to decrease over-sedation, anxiety and stress in critically ill patients, factors that could predispose to ICU delirium. Our team is now proposing to conduct a large randomized clinical trial called Decreasing Delirium through Music (DDM) in Critically Ill Older Adults to evaluate the efficacy of a seven-day slow-tempo music intervention on the primary outcome of delirium/coma free days among mechanically-ventilated older adults admitted to the ICU.
Interventions
OTHERSlow Tempo Music
For up to seven days, enrolled subjects will receive one-hour slow tempo music listening sessions twice daily through noise-cancelling headphones.
OTHERAttention Control
Subjects will receive a noise cancellation headphone-applied condition identical to the music intervention experimental treatment in twice daily one hour-sessions for up to seven days.
Sponsors
National Institute on Aging (NIA)
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
Only the unblinded study coordinator is aware of randomization. Outcomes assessors are blinded
Intervention model description
Slow Tempo Music vs Attention Control
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 50 years or older. 2. English speaking. 3. Admitted to the intensive care unit (medical or surgical). 4. Expected mechanical ventilator support for ≥48 hours. 5. Consentable through a legally authorized representative. 6. Have access to a telephone.
Exclusion criteria
1. History of dementing illnesses and other neurodegenerative diseases such as Alzheimer's disease or vascular dementia. 2. Psychiatric illness which is not well controlled. 3. Alcohol withdrawal symptoms/concern for withdrawal. 4. Suspected or confirmed drug intoxication/overdose 5. Traumatic brain injury, ischemic or hemorrhagic cerebrovascular accident, or undergoing neurosurgery. 6. Uncorrected hearing or vision impairment including legal blindness. 7. Incarcerated at the time of study enrollment. 8. Enrolled in another clinical trial which does not permit co-enrollment. 9. Any medical condition precluding safe use of headphones such as: skin breakdown, burns, facial or skull fractures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days Free of Delirium and Coma | Seven day study intervention phase | Days free of delirium and coma will be the primary outcome for the trial. Days free of delirium and coma are the number of days after randomization patient is alive free of delirium and not in coma during the seven-day study intervention phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium Severity | Subjects will be followed up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan. | Delirium severity was assessed twice daily by trained research assistants by the CAM-ICU-7, a seven point rating scale (0-7) where higher scores reflect higher delirium severity (worse outcomes). The CAM-ICU-7 score are categorized as 0-2: no delirium, 3-5: mild to moderate delirium, and 6-7: severe delirium. For the twice daily assessments, the mean of the two assessments was used. |
| Pain Intensity | 4 times daily, before and after each intervention for up to 7 days while in the ICU and then twice daily up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan. | Pain will be assessed by trained research assistants utilizing the Critical Care Pain Observation Tool (CPOT), a valid and reliable instrument in critically ill patients with and without delirium.. Scale range 0-8, higher score indicates worse pain. For the 4 times daily assessments, the mean of the 2 post intervention assessments was used. |
| Anxiety | 4 times daily, before and after each intervention for up to 7 days while in the ICU and then twice daily up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan. | Anxiety intensity defined as a heightened state of apprehension, agitation, and arousal, will be measured four times daily before and after assigned intervention using a 100-mm Visual Analog Scale-Anxiety (VAS-A). Scale range 0-100, higher score indicates worse anxiety. For the 4 times daily assessments, the mean of the 2 post intervention assessments was used. |
| Cognition | 3 months post hospital discharge | Cognition will be measured by objective tests of memory, attention, information processing speed and executive cognitive function. The Auditory Verbal Learning Test \[AVLT\] will be administered using a phone-based format. During test administration there are 5 learning trials. After a 30-minute delay, the participants are asked to recall as many words as possible. The sum of learning trials are presented as scores ranging from 0-75, and for the 30-minute delay test scores range from 0-15. A lower score indicates a worse outcome. |
| Depression | 3 months post hospital discharge | We will use the Patient Health Questionnaire-9 (PHQ-9) to determine the impact of the music intervention on ICU survivor's mood. Scale range 0-27, higher score indicates worse depression. |
Countries
United States
Participant flow
Pre-assignment details
Per protocol subjects were considered to be enrolled in the study at the time of completion of the informed consent process. 160 subjects were enrolled. 159 subjects were randomized to one of the two study groups.
Participants by arm
| Arm | Count |
|---|---|
| Slow Tempo Music Slow-tempo 60-80 beats per minute relaxing music. The intervention includes two one-hour music listening sessions, once in the morning and once in the evening for up to seven days, delivered through noise-canceling headphones and iPad.
Slow Tempo Music: For up to seven days, enrolled subjects will receive one-hour slow tempo music listening sessions twice daily through noise-cancelling headphones. | 79 |
| Attention Control One-hour sessions consisting of a silence track twice daily delivered through noise-cancelling headphones for up to 7 days.
Attention Control: Subjects will receive a noise cancellation headphone-applied condition identical to the music intervention experimental treatment in twice daily one hour-sessions for up to seven days. | 80 |
| Total | 159 |
Baseline characteristics
| Characteristic | Attention Control | Total | Slow Tempo Music |
|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 9.3 | 67.9 years STANDARD_DEVIATION 9.2 | 67.6 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 30 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 63 Participants | 122 Participants | 59 Participants |
| Sex: Female, Male Female | 38 Participants | 72 Participants | 34 Participants |
| Sex: Female, Male Male | 42 Participants | 87 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 79 | 10 / 80 |
| other Total, other adverse events | 2 / 79 | 2 / 80 |
| serious Total, serious adverse events | 1 / 79 | 0 / 80 |
Outcome results
Primary
Days Free of Delirium and Coma
Days free of delirium and coma will be the primary outcome for the trial. Days free of delirium and coma are the number of days after randomization patient is alive free of delirium and not in coma during the seven-day study intervention phase.
Time frame: Seven day study intervention phase
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Slow Tempo Music | Days Free of Delirium and Coma | 2.5 Delirium/coma-free days by day 7 |
| Attention Control | Days Free of Delirium and Coma | 3 Delirium/coma-free days by day 7 |
p-value: 0.775Mixed Models Analysis
Secondary
Anxiety
We will use the Generalized Anxiety Disorder Scale (GAD-7) to determine the impact of the music intervention on ICU survivor's anxiety. Scale range 0-21, higher score indicates worse anxiety.
Time frame: 3 months post hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Tempo Music | Anxiety | 2.46 score on a scale | Standard Deviation 2.85 |
| Attention Control | Anxiety | 5.94 score on a scale | Standard Deviation 6.49 |
p-value: 0.196Wilcoxon (Mann-Whitney)
Secondary
Anxiety
Anxiety intensity defined as a heightened state of apprehension, agitation, and arousal, will be measured four times daily before and after assigned intervention using a 100-mm Visual Analog Scale-Anxiety (VAS-A). Scale range 0-100, higher score indicates worse anxiety. For the 4 times daily assessments, the mean of the 2 post intervention assessments was used.
Time frame: 4 times daily, before and after each intervention for up to 7 days while in the ICU and then twice daily up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan.
Population: maximum number of participants analyzed during day 1 through day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Slow Tempo Music | Anxiety | Day 4 | 37.86 score on a scale | Standard Deviation 36.36 |
| Slow Tempo Music | Anxiety | Day 5 | 25.72 score on a scale | Standard Deviation 30.23 |
| Slow Tempo Music | Anxiety | Day 1 | 40.56 score on a scale | Standard Deviation 34.41 |
| Slow Tempo Music | Anxiety | Day 6 | 34.36 score on a scale | Standard Deviation 35.4 |
| Slow Tempo Music | Anxiety | Day 3 | 39.38 score on a scale | Standard Deviation 37.45 |
| Slow Tempo Music | Anxiety | Day 7 | 43.63 score on a scale | Standard Deviation 24.67 |
| Slow Tempo Music | Anxiety | Day 2 | 38.40 score on a scale | Standard Deviation 33.49 |
| Attention Control | Anxiety | Day 7 | 28.83 score on a scale | Standard Deviation 38.4 |
| Attention Control | Anxiety | Day 1 | 43.13 score on a scale | Standard Deviation 33.77 |
| Attention Control | Anxiety | Day 2 | 38.82 score on a scale | Standard Deviation 34.81 |
| Attention Control | Anxiety | Day 3 | 35.39 score on a scale | Standard Deviation 38.28 |
| Attention Control | Anxiety | Day 5 | 53.50 score on a scale | Standard Deviation 38.97 |
| Attention Control | Anxiety | Day 6 | 37.80 score on a scale | Standard Deviation 44.57 |
| Attention Control | Anxiety | Day 4 | 39.50 score on a scale | Standard Deviation 33.31 |
p-value: 0.326Mixed Models Analysis
Secondary
Cognition
Cognition will be measured by objective tests of memory, attention, information processing speed and executive cognitive function. The Symbol Digit Modalities Test will be administered using a phone-based format. Score range 0-110, a lower score indicates a worse outcome.
Time frame: 3 months post hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Tempo Music | Cognition | 35.10 score on a scale | Standard Deviation 21.08 |
| Attention Control | Cognition | 30.13 score on a scale | Standard Deviation 12.44 |
p-value: 0.505Wilcoxon (Mann-Whitney)
Secondary
Cognition
Cognition will be measured by objective tests of memory, attention, information processing speed and executive cognitive function. The Auditory Verbal Learning Test \[AVLT\] will be administered using a phone-based format. During test administration there are 5 learning trials. After a 30-minute delay, the participants are asked to recall as many words as possible. The sum of learning trials are presented as scores ranging from 0-75, and for the 30-minute delay test scores range from 0-15. A lower score indicates a worse outcome.
Time frame: 3 months post hospital discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Slow Tempo Music | Cognition | AVTL Total Learning | 32.23 score on a scale | Standard Deviation 13.14 |
| Slow Tempo Music | Cognition | AVTL Delayed Recall | 5.3 score on a scale | Standard Deviation 3.6 |
| Attention Control | Cognition | AVTL Total Learning | 35.76 score on a scale | Standard Deviation 12.1 |
| Attention Control | Cognition | AVTL Delayed Recall | 5.9 score on a scale | Standard Deviation 3.4 |
p-value: 0.463Wilcoxon (Mann-Whitney)
Secondary
Cognition
Cognition will be measured by objective tests of memory, attention, information processing speed and executive cognitive function. The Wechsler Adult Intelligence Scale- III Digit Span test will be administered using a phone-based format. Score range 0-30, a lower score indicates a worse outcome.
Time frame: 3 months post hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Tempo Music | Cognition | 15.85 score on a scale | Standard Deviation 6.08 |
| Attention Control | Cognition | 13.88 score on a scale | Standard Deviation 4.48 |
p-value: 0.449Wilcoxon (Mann-Whitney)
Secondary
Cognition
Cognition will be measured by objective tests of memory, attention, information processing speed and executive cognitive function. The Multilingual Aphasia Examination Controlled Oral Word Association test will be administered using a phone-based format. Score range 0-no max score, a lower score indicates a worse outcome.
Time frame: 3 months post hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Tempo Music | Cognition | 32.31 score on a scale | Standard Deviation 14.46 |
| Attention Control | Cognition | 34.13 score on a scale | Standard Deviation 10.22 |
p-value: 0.612Wilcoxon (Mann-Whitney)
Secondary
Delirium Severity
Delirium severity was assessed twice daily by trained research assistants by the CAM-ICU-7, a seven point rating scale (0-7) where higher scores reflect higher delirium severity (worse outcomes). The CAM-ICU-7 score are categorized as 0-2: no delirium, 3-5: mild to moderate delirium, and 6-7: severe delirium. For the twice daily assessments, the mean of the two assessments was used.
Time frame: Subjects will be followed up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan.
Population: maximum number of participants analyzed during day 1 through day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Slow Tempo Music | Delirium Severity | Day 1 | 5.43 score on a scale | Standard Deviation 2.35 |
| Slow Tempo Music | Delirium Severity | Day 5 | 2.78 score on a scale | Standard Deviation 2.7 |
| Slow Tempo Music | Delirium Severity | Day 4 | 3.54 score on a scale | Standard Deviation 2.75 |
| Slow Tempo Music | Delirium Severity | Day 6 | 2.73 score on a scale | Standard Deviation 2.73 |
| Slow Tempo Music | Delirium Severity | Day 2 | 4.77 score on a scale | Standard Deviation 2.35 |
| Slow Tempo Music | Delirium Severity | Day 7 | 2.72 score on a scale | Standard Deviation 2.8 |
| Slow Tempo Music | Delirium Severity | Day 3 | 4.10 score on a scale | Standard Deviation 2.55 |
| Attention Control | Delirium Severity | Day 7 | 2.56 score on a scale | Standard Deviation 2.72 |
| Attention Control | Delirium Severity | Day 3 | 4.45 score on a scale | Standard Deviation 2.61 |
| Attention Control | Delirium Severity | Day 4 | 3.95 score on a scale | Standard Deviation 2.72 |
| Attention Control | Delirium Severity | Day 1 | 5.79 score on a scale | Standard Deviation 2.16 |
| Attention Control | Delirium Severity | Day 2 | 5.51 score on a scale | Standard Deviation 2.18 |
| Attention Control | Delirium Severity | Day 5 | 3.27 score on a scale | Standard Deviation 2.83 |
| Attention Control | Delirium Severity | Day 6 | 3.49 score on a scale | Standard Deviation 2.94 |
p-value: 0.995Mixed Models Analysis
Secondary
Depression
We will use the Patient Health Questionnaire-9 (PHQ-9) to determine the impact of the music intervention on ICU survivor's mood. Scale range 0-27, higher score indicates worse depression.
Time frame: 3 months post hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Tempo Music | Depression | 3.38 score on a scale | Standard Deviation 3.62 |
| Attention Control | Depression | 7.50 score on a scale | Standard Deviation 6.39 |
p-value: 0.058Wilcoxon (Mann-Whitney)
Secondary
Pain Intensity
Pain will be assessed by trained research assistants utilizing the Critical Care Pain Observation Tool (CPOT), a valid and reliable instrument in critically ill patients with and without delirium.. Scale range 0-8, higher score indicates worse pain. For the 4 times daily assessments, the mean of the 2 post intervention assessments was used.
Time frame: 4 times daily, before and after each intervention for up to 7 days while in the ICU and then twice daily up to 28 days post randomization. The first 7 days were used for analysis per the protocol statistical plan.
Population: maximum number of participants analyzed during day 1 through day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Slow Tempo Music | Pain Intensity | Day 6 | 0.17 score on a scale | Standard Deviation 0.48 |
| Slow Tempo Music | Pain Intensity | Day 7 | 0.20 score on a scale | Standard Deviation 0.55 |
| Slow Tempo Music | Pain Intensity | Day 1 | 0.42 score on a scale | Standard Deviation 0.94 |
| Slow Tempo Music | Pain Intensity | Day 2 | 0.34 score on a scale | Standard Deviation 0.85 |
| Slow Tempo Music | Pain Intensity | Day 3 | 0.32 score on a scale | Standard Deviation 0.82 |
| Slow Tempo Music | Pain Intensity | Day 4 | 0.51 score on a scale | Standard Deviation 0.87 |
| Slow Tempo Music | Pain Intensity | Day 5 | 0.44 score on a scale | Standard Deviation 0.91 |
| Attention Control | Pain Intensity | Day 1 | 0.30 score on a scale | Standard Deviation 0.72 |
| Attention Control | Pain Intensity | Day 6 | 0.25 score on a scale | Standard Deviation 0.47 |
| Attention Control | Pain Intensity | Day 3 | 0.21 score on a scale | Standard Deviation 0.47 |
| Attention Control | Pain Intensity | Day 7 | 0.61 score on a scale | Standard Deviation 1.29 |
| Attention Control | Pain Intensity | Day 5 | 0.31 score on a scale | Standard Deviation 0.64 |
| Attention Control | Pain Intensity | Day 4 | 0.31 score on a scale | Standard Deviation 0.65 |
| Attention Control | Pain Intensity | Day 2 | 0.34 score on a scale | Standard Deviation 0.83 |
p-value: 0.674Mixed Models Analysis