Musical Intervention and Physiological Stress and Inflammatory Biomarkers in Mechanically Ventilated ICU Patients

Effects of a Musical Intervention on Hormonal and Inflammatory Biomarkers in Mechanically Ventilated Critically Ill Patients

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

Study Overview

• Status: Completed
• Conditions: Inflammation; Critical Illness; Stress, Physiological; Sedation; Respiration, Artificial
• Intervention / Treatment: Other: Music Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Music Intervention; Participants assigned to this arm receive a structured music therapy session delivered through headphones in addition to usual ICU care.	Other: Music 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.
No Intervention: Standard Care (Control); Participants assigned to this arm receive usual ICU care without any additional auditory intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Serum Cortisol	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.	Only one intervention per person will be performed. Serum levels will be measured before and after the intervention (minute 0 and 60).
Levels of Prolactin	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.	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.
Levels of Interleukin 6	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bispectral Index (BIS)	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.	BIS values will be measured immediately before and after the intervention (minute 0 and 60).
Systolic Blood Pressure	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.	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	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.	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.
Heart Rate	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.	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.
Respiratory Rate	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.	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.
Oxygen Saturation	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.	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.
Intracranial Pressure	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.	Intracranial pressure was measured before (minute 0) and after (minute 60) the intervention in patients with an invasive ICP monitor.
Sedation Medication Use	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.	Sedative medication infusion rates were measured at baseline (minute 0) and after the intervention (minute 60).

Collaborators and Investigators

• Sponsor: University of Oviedo
• Collaborators: Sociedad Española de Enfermería Intensiva y Unidades Coronarias
• Investigators: Principal Investigator: Alba Maestro-González, Ph.D., University of Oviedo

Publications and helpful links

General Publications

• Erdogan Z, Atik D. Complementary Health Approaches Used in the Intensive Care Unit. Holist Nurs Pract. 2017 Sep/Oct;31(5):325-342. doi: 10.1097/HNP.0000000000000227.
• Umbrello M, Sorrenti T, Mistraletti G, Formenti P, Chiumello D, Terzoni S. Music therapy reduces stress and anxiety in critically ill patients: a systematic review of randomized clinical trials. Minerva Anestesiol. 2019 Aug;85(8):886-898. doi: 10.23736/S0375-9393.19.13526-2. Epub 2019 Apr 3.
• Thaut MH. Music as therapy in early history. Prog Brain Res. 2015;217:143-58. doi: 10.1016/bs.pbr.2014.11.025. Epub 2015 Jan 31.
• Seyffert S, Moiz S, Coghlan M, Balozian P, Nasser J, Rached EA, Jamil Y, Naqvi K, Rawlings L, Perkins AJ, Gao S, Hunter JD 3rd, Khan S, Heiderscheit A, Chlan LL, Khan B. Decreasing delirium through music listening (DDM) in critically ill, mechanically ventilated older adults in the intensive care unit: a two-arm, parallel-group, randomized clinical trial. Trials. 2022 Jul 19;23(1):576. doi: 10.1186/s13063-022-06448-w.
• Kakar E, Billar RJ, van Rosmalen J, Klimek M, Takkenberg JJM, Jeekel J. Music intervention to relieve anxiety and pain in adults undergoing cardiac surgery: a systematic review and meta-analysis. Open Heart. 2021 Jan;8(1):e001474. doi: 10.1136/openhrt-2020-001474.
• Khan SH, Wang S, Harrawood A, Martinez S, Heiderscheit A, Chlan L, Perkins AJ, Tu W, Boustani M, Khan B. Decreasing Delirium through Music (DDM) in critically ill, mechanically ventilated patients in the intensive care unit: study protocol for a pilot randomized controlled trial. Trials. 2017 Nov 29;18(1):574. doi: 10.1186/s13063-017-2324-6.
• Khan SH, Kitsis M, Golovyan D, Wang S, Chlan LL, Boustani M, Khan BA. Effects of music intervention on inflammatory markers in critically ill and post-operative patients: A systematic review of the literature. Heart Lung. 2018 Sep-Oct;47(5):489-496. doi: 10.1016/j.hrtlng.2018.05.015. Epub 2018 Jul 9.
• Taets GGC, Jomar RT, Abreu AMM, Capella MAM. Effect of music therapy on stress in chemically dependent people: a quasi-experimental study. Rev Lat Am Enfermagem. 2019 Jan 17;27:e3115. doi: 10.1590/1518-8345.2456.3115.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2023
• Primary Completion (Actual): June 28, 2025
• Study Completion (Actual): January 27, 2026

Study Registration Dates

• First Submitted: October 14, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: critical care; music therapy; inflammation; sedation; stress, psychological; respiration, artificial
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Behavioral Symptoms; Respiratory Tract Diseases; Respiration Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Critical Illness; Inflammation; Respiratory Aspiration; Stress, Psychological; Therapeutics; Complementary Therapies; Patient Care; Psychotherapy; Behavioral Disciplines and Activities; Rehabilitation; Aftercare; Continuity of Patient Care; Sensory Art Therapies; Music Therapy
• Other Study ID Numbers: 2022.537; Investiga SEEIUC 2023 (Other Identifier: SEEIUC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared because the dataset contains sensitive clinical and biological information from critically ill patients that cannot be completely de-identified.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No