Critical Illness, Inflammation, Respiration, Artificial, Sedation, Stress, Physiological
Conditions
Keywords
music therapy, critical care, stress, psychological, respiration, artificial, sedation, inflammation
Brief summary
This randomized clinical trial evaluates the effects of a musical intervention on hormonal and inflammatory biomarkers in sedated adult patients undergoing invasive mechanical ventilation in an intensive care unit. Serum cortisol, prolactin, and interleukin-6 levels are measured before and after the intervention, together with hemodynamic parameters. The aim is to assess whether music modulates physiological stress and inflammatory responses in critically ill patients
Detailed description
This randomized controlled clinical trial evaluates the effects of a musical intervention on hormonal and inflammatory biomarkers in critically ill adults receiving invasive mechanical ventilation. The study is conducted in the intensive care unit of a tertiary hospital in Spain. Participants: Eligible patients are adults who are intubated, mechanically ventilated, equipped with an arterial catheter, adequately sedated, and not experiencing pain during the intervention period. Patients are enrolled consecutively and randomly assigned to one of two groups. Interventions: The intervention group receives a structured music session delivered through headphones in addition to usual ICU care. The control group receives usual ICU care and remains undisturbed for the same duration. The intervention does not interfere with routine clinical procedures. Outcomes and Variables: Primary outcomes include serum cortisol, prolactin, and interleukin-6 levels as indicators of hormonal and inflammatory responses. Secondary outcomes include physiological parameters related to hemodynamic status. All variables are measured at three time points: before the intervention, during the intervention period, and immediately after the intervention. Data Collection and Analysis: Biological samples and physiological measurements are collected by trained ICU staff following standardized procedures. Descriptive statistics are calculated for all variables. Normality and homoscedasticity are assessed prior to comparative analyses. When required, post-hoc tests are applied. Statistical significance is defined as p ≤ 0.05. No inferential statistical analyses were performed for ClinicalTrials.gov; results are presented descriptively according to PRS requirements.
Interventions
OTHERMusic Therapy
A 60-minute session of relaxing, slow-tempo recorded music (60-80 bpm) delivered through over-ear headphones. The intervention is administered once, while the patient remains sedated and mechanically ventilated. Volume and audio equipment are adjusted according to ICU safety protocols.
Sponsors
University of Oviedo
Sociedad Española de Enfermería Intensiva y Unidades Coronarias
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Patients were blinded due to continuous sedation throughout the intervention period. Bedside healthcare professionals responsible for routine care, sedation, and hemodynamic monitoring were also unaware of group allocation. Laboratory personnel analyzing biomarker samples were blinded to treatment assignment. The investigator placing the headphones was not blinded due to the nature of the intervention.
Intervention model description
Two-arm parallel design comparing a musical intervention plus usual care versus usual care alone in mechanically ventilated ICU patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults aged ≥18 years. Admitted to the intensive care unit (ICU) for at least 24 hours. Intubated and undergoing invasive mechanical ventilation. Presence of an arterial catheter and/or central venous catheter. Sedation level corresponding to BIS 40-60. Absence of pain at baseline and during the intervention, defined as a CPOT score = 0 (Critical-Care Pain Observation Tool). No previous exposure to music therapy or other musical interventions during the current hospital stay.
Exclusion criteria
Severe neurological disease or injury, including encephalitis, diffuse axonal injury, or other central nervous system pathologies. Severe psychiatric illness. Suspected or confirmed drug or alcohol intoxication, overdose, withdrawal, or abstinence syndrome. Hearing impairment that would limit perception of the music intervention. Cranial or skull lesions preventing safe placement of headphones. Limitation of therapeutic effort or expected death within the next 24 hours. Diagnosis of brain death. Inability to obtain informed consent from the legal representative within 72 hours of ICU admission. Refusal by the responsible attending physician.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Serum Cortisol | Only one intervention per person will be performed. Serum levels will be measured before and after the intervention (minute 0 and 60). | Serum cortisol levels were measured from venous blood samples collected immediately before (minute 0) and after (minute 60) the music intervention or standard care using standard laboratory assays. This measure reflects the acute physiological stress response. |
| Levels of Prolactin | Only one intervention per person will be performed. Serum levels will be measured before and after the intervention. That is, at minute 0 and 60. | Serum prolactin levels were measured from venous blood samples obtained immediately before (minute 0) and after (minute 60) the intervention using standard laboratory immunoassays. This biomarker reflects neuroendocrine stress response and can indicate changes related to the music intervention. |
| Levels of Interleukin 6 | Only one intervention per person will be performed. Serum levels will be measured before and after the intervention. That is, at minute 0 and 60. | Serum interleukin-6 (IL-6) levels were measured from venous blood samples collected immediately before (minute 0) and after (minute 60) the intervention using standard laboratory immunoassays. IL-6 is a pro-inflammatory cytokine and its serum concentration reflects acute systemic inflammatory activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bispectral Index (BIS) | BIS values will be measured immediately before and after the intervention (minute 0 and 60). | The Bispectral Index (BIS) is a processed electroencephalographic scale used to quantify the depth of sedation or anesthesia. BIS values range from 0 to 100, where 100 represents a fully awake state and 0 represents EEG silence. Lower scores indicate deeper sedation, while higher scores indicate lighter sedation. BIS values were obtained using standard BIS monitoring immediately before (minute 0) and after the intervention (minute 60). No subscales exist; the BIS value is a single composite index. |
| Systolic Blood Pressure | Blood pressure was measured before (minute 0) and after (minute 60) the intervention. Although values were recorded every 10 minutes, only baseline and final measurements are reported. | Systolic blood pressure was obtained using standard ICU monitoring before (minute 0) and after (minute 60) the intervention. This measure reflects hemodynamic response to the music intervention or standard care. |
| Diastolic Blood Pressure | Blood pressure was measured before (minute 0) and after (minute 60) the intervention. Although values were recorded every 10 minutes, only baseline and final measurements are reported. | Diastolic blood pressure was obtained using standard ICU monitoring before (minute 0) and after (minute 60) the intervention. This measure reflects autonomic and vascular response to the music intervention or standard care. |
| Heart Rate | Heart rate was measured before (minute 0) and after (minute 60) the intervention. Although values were recorded every 10 minutes, only baseline and final measurements are reported. | Heart rate was obtained using standard ICU monitoring before (minute 0) and after (minute 60) the intervention. Heart rate reflects autonomic and physiological stress response to the music intervention or standard care. |
| Respiratory Rate | Respiratory rate was measured before (minute 0) and after (minute 60) the intervention. Although values were recorded every 10 minutes, only baseline and final measurements are reported. | Respiratory rate was obtained using standard ICU respiratory monitoring before (minute 0) and after (minute 60) the intervention. Respiratory rate reflects ventilatory response to the music intervention or standard care. |
| Oxygen Saturation | Oxygen saturation was measured before (minute 0) and after (minute 60) the intervention. Although values were recorded every 10 minutes, only baseline and final measurements are reported. | Oxygen saturation (SpO₂) was obtained using standard ICU pulse oximetry before (minute 0) and after (minute 60) the intervention. This measure reflects oxygenation status and respiratory response to the music intervention or standard care. |
| Intracranial Pressure | Intracranial pressure was measured before (minute 0) and after (minute 60) the intervention in patients with an invasive ICP monitor. | Intracranial pressure (ICP) was obtained from invasive intraparenchymal or ventricular monitoring devices in patients who had such monitors in place. Measurements were taken at baseline (minute 0) and post-intervention (minute 60). ICP reflects cerebral compliance and intracranial dynamics. |
| Sedation Medication Use | Sedative medication infusion rates were measured at baseline (minute 0) and after the intervention (minute 60). | This outcome includes multiple sedative, analgesic, and neuromuscular-blocking agents used in the ICU. Each drug is reported using its appropriate clinical unit (e.g., mg/kg/h for intravenous medications and ml/h for inhaled anesthetics such as sevoflurane). Mean and standard deviation are presented separately for the music intervention group and the control group at baseline and post-intervention. Each drug appears as an independent row, and units do not mix within rows. |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORAlba Maestro-González, Ph.D.
University of Oviedo
Participant flow
Recruitment details
Patients were consecutively recruited between October 1, 2023, and June 28, 2025, in the intensive care unit of a tertiary-level public university hospital in Spain. Eligible participants were identified daily by the research team through review of ICU admissions and clinical records. Legal representatives were approached for informed consent once eligibility criteria were confirmed.
Pre-assignment details
No significant events occurred between enrollment and randomization. All enrolled participants met eligibility criteria at the time of enrollment and were randomly assigned to the intervention or control group without exclusions or withdrawals prior to group assignment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.05 Years STANDARD_DEVIATION 10.38 |
| APACHE II Score | 20.7 Points on a scale STANDARD_DEVIATION 6.29 |
| Days on IMV | 4.18 Days STANDARD_DEVIATION 4.8 |
| Race and Ethnicity Not Collected | 0 Participants |
| Reason for ICU Admission Neurological | 45 Participants |
| Reason for ICU Admission Other | 7 Participants |
| Reason for ICU Admission Respiratory | 14 Participants |
| Reason for ICU Admission Trauma | 9 Participants |
| Region of Enrollment Spain | 55 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 74 Participants |
| Ventilatory Mode Pressure assist-control | 1 Participants |
| Ventilatory Mode Pressure support | 25 Participants |
| Ventilatory Mode Volume assist-control | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 0 / 55 | 0 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
None listed