Effect of Non-Invasive Vagus Nerve Stimulation in Burn Patients

This study is a randomized controlled experimental study designed to investigate the effects of non-invasive vagus nerve stimulation (nVNS) on anxiety, sleep quality, pain, itching, and autonomic nervous system function in adults with burn injuries.

The study population will consist of patients followed at the Burn Outpatient Clinic of Kartal Dr. Lütfi Kırdar City Hospital in Istanbul, Türkiye. Eligible participants will be adults aged 18 to 65 years who have completed the acute phase of burn injury, whose burn injury occurred between 1 month and 1 year before enrollment, and who have second- or third-degree burns involving 5% to 30% of total body surface area. Participants must also report at least one complaint related to anxiety, sleep quality, pain, or itching and provide written informed consent.

A total of 60 participants are planned to be included. Participants will be randomly assigned in equal numbers to an intervention group or a control group. The intervention group will receive conventional physiotherapy and nVNS. The control group will receive conventional physiotherapy only. Both groups will receive treatment 5 days per week for a total of 10 sessions. Conventional physiotherapy will be planned according to each participant's needs and may include strengthening exercises, stretching exercises, balance exercises, active and passive range-of-motion exercises, and interventions for edema. Each conventional physiotherapy session will last approximately 45 minutes.

In the intervention group, nVNS will be applied using electrodes positioned on the tragus and the anterior and posterior surfaces of the concha of the right and left external ear. Stimulation will be delivered continuously for 20 minutes with a biphasic asymmetric waveform, a pulse duration of 300 microseconds, and a frequency of 25 Hz. The stimulation intensity will be increased in 0.1 mA steps until the sensory threshold is reached. If a participant feels unwell during stimulation, the procedure will be stopped.

Outcome assessments will be performed before treatment and after completion of the 10th session. Anxiety will be assessed using the Beck Anxiety Inventory. Sleep quality will be assessed using the Pittsburgh Sleep Quality Index. Pain will be assessed using a visual analog scale. Itching severity will be assessed using the 12-Item Pruritus Severity Scale. Autonomic nervous system function will be evaluated using heart rate variability measurements recorded with a Polar H10 heart rate sensor and analyzed with Kubios HRV software.

The study aims to determine whether adding nVNS to conventional physiotherapy provides additional benefits for psychological symptoms, sleep quality, pain, itching, and autonomic function in burn rehabilitation.

• Non-Invasive Vagus Nerve Stimulation (Device): Non-invasive vagus nerve stimulation will be applied using a Vagustim device. Electrodes will be placed on the tragus and the anterior and posterior surfaces of the concha of both ears. Stimulation will be applied continuously for 20 minutes per session with a biphasic asymmetric waveform, a pulse duration of 300 microseconds, and a frequency of 25 Hz. Stimulation intensity will be increased in 0.1 mA steps until the sensory threshold is reached. The procedure will be stopped if the participant feels unwell.
• Conventional Physiotherapy (Other): Conventional physiotherapy will be planned according to each participant's needs and will be provided by a physiotherapist. The program may include strengthening exercises, stretching exercises, balance exercises, active and passive range-of-motion exercises, and interventions for edema. Sessions will be performed 5 days per week for a total of 10 sessions, with each session lasting approximately 45 minutes.

Primary outcomes

• Change in Anxiety Level [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Anxiety level will be assessed using the Beck Anxiety Inventory. The scale includes 21 items scored from 0 to 3, with a total score ranging from 0 to 63. Higher scores indicate greater anxiety severity.
• Change in Sleep Quality [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Sleep quality will be assessed using the Pittsburgh Sleep Quality Index. The scale evaluates sleep quality and sleep disturbances over the previous month. The total score ranges from 0 to 21, and higher scores indicate poorer sleep quality.
• Change in Pain Intensity [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Pain intensity will be assessed using a visual analog scale. Participants will mark their pain level on a 100-mm line, where higher scores indicate greater pain intensity.
• Change in Pruritus Severity [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Pruritus severity will be assessed using the 12-Item Pruritus Severity Scale. The scale evaluates multiple aspects of itching, including location, duration, frequency, intensity, scratching behavior, emotional effects, sleep disturbance, daily activity effects, and quality-of-life impact. Higher scores indicate more severe itching.
• Change in Root Mean Square of Successive Differences [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Autonomic nervous system function will be assessed using the root mean square of successive differences between normal RR intervals derived from heart rate variability analysis. RR interval data will be recorded with a Polar H10 heart rate sensor during a 5-minute resting measurement and analyzed using Kubios HRV software. The root mean square of successive differences will be reported in milliseconds.
• Change in Standard Deviation of Normal-to-Normal Intervals [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Autonomic nervous system function will be assessed using the standard deviation of normal-to-normal intervals derived from heart rate variability analysis. RR interval data will be recorded with a Polar H10 heart rate sensor during a 5-minute resting measurement and analyzed using Kubios HRV software. The standard deviation of normal-to-normal intervals will be reported in milliseconds.
• Change in Low-Frequency/High-Frequency Ratio [Baseline and after completion of 10 treatment sessions, up to 2 weeks]: Autonomic nervous system function will be assessed using the low-frequency/high-frequency ratio derived from heart rate variability analysis. RR interval data will be recorded with a Polar H10 heart rate sensor during a 5-minute resting measurement and analyzed using Kubios HRV software. The low-frequency/high-frequency ratio will be reported as a ratio.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Adults aged 18 to 65 years
* Patients who have completed the acute phase of burn injury
* Burn injury occurred at least 1 month and no more than 1 year before enrollment
* Second- or third-degree burn involving 5% to 30% of total body surface area
* Presence of at least one complaint related to anxiety, sleep quality, pain, or itching
* Able to read and understand Turkish
* Willing to participate in the study
* Written informed consent provided

Exclusion Criteria:

* Infection, ulcer, or scar tissue on the auricle
* Burn injury in the head and neck region preventing application of the device over the auricular branch of the vagus nerve
* Metallic implant in the skull
* Excessive sensitivity, injury, or inflammation in the ear
* Chronic pulmonary disease and/or chronic cardiac disease
* Resting heart rate below 60 beats per minute
* Presence of a pacemaker, cochlear implant, or similar implanted device
* Uncontrolled hypertension
* Lack of cooperation or inability to comply with study procedures

• Sümeyye Akçay, Asst. Prof., Principal investigator, Fenerbahçe University