Effect of a musical intervention on tolerance and efficacy of non-invasive ventilation in the ICU: study protocol for a randomized controlled trial (MUSique pour l’Insuffisance Respiratoire Aigue - Mus-IRA)

Acute respiratory failure (ARF) is the most frequent organ failure in patients in the intensive care unit (ICU) [1]. Among the various respiratory supports, non-invasive ventilation (NIV) allows the administration of a positive pressure of air and oxygen, at a set inspiratory flow and FiO₂, which unloads respiratory muscles and enables alveolar recruitment. NIV has shown its efficacy in acute or chronic respiratory failure [2] and cardiac pulmonary edema [3] in terms of intubation rates [4, 5], mortality [5], and nosocomial infections [6]. These positive findings have not been so clearly found in de novo ARF, where NIV benefits may be outweighed by the risks of delaying intubation [7, 8], which has been associated with increased mortality [8]. Although NIV offers many undisputable advantages over invasive ventilation, its intolerance is one of its major drawbacks. Also, premature cessation of NIV because of intolerance may lead to intubation in some cases [7‐9]. Hence, investigators have searched for means of improving tolerance of the technique by increasing patient comfort. Light sedation has been shown to decrease NIV-induced discomfort [10‐13] and appears to be safe and effective, but this alternative remains a pharmacologic intervention requiring the administration of potentially dangerous anesthetic drugs, such as propofol, remifentanil, or dexmedetomidine. Among non-pharmacologic interventions, sophrology, which aims at increasing well-being through differential relaxation, has been assessed with interesting results [14]. However, only a limited number of patients have been evaluated, and the major drawback is the need for patient adherence, a specific caregiver’s training, and the presence of a single person with the patient for an entire 30-minute session, which makes it very dependent on the availability of the team.

Music therapy in health care settings has recently been investigated. In the perioperative setting, it has shown beneficial effects on anxiety, pain, analgesia use, and patient satisfaction [15]. In the ICU, several studies [16‐19] and a recent meta-analysis [20] described its effects in terms of anxiety and physiological changes (heart rate, respiratory rate, and blood pressure) in patients on invasive mechanical ventilation. These studies showed that music therapy is feasible in the ICU, with beneficial effects on physiological parameters, anxiety, and agitation.

Collected data at each time are summarized in the SPIRIT schedule of events shown in Table 1.

In the current study there are no anticipated risks or inconveniences. For this reason, neither safety interim analysis nor stopping rules are planned. Any unexpected medical event after inclusion (adverse events, AEs) will be recorded on the individual CRFs. Unexpected serious adverse events (SAEs) will be reported to the sponsor immediately, and all participating centers will be informed by the sponsor (Department de la Recherche Clinique - Assistance Publique - Hôpitaux de Paris).

In this randomized controlled trial, we expect an improvement of NIV tolerance and efficacy thanks to a simple, easily implemented, non-pharmacological intervention.

In everyday life, medical teams strive to improve patients’ care, and patient centeredness is crucial to quality of care [35]. Intolerance is one of NIV’s major drawbacks and has been associated with a higher risk of intubation [7‐9]. In the study of Delclaux et al. of NIV patients with hypoxemic ARF [8], intolerance was responsible for 14 % of NIV failures, leading to intubation in a third of them, a finding shared by others [9]. In order to improve NIV tolerance, ventilators have been bench-marked, and their performances rated [36‐38]. Likewise, physicians have focused their efforts on assessing appropriate humidification devices [39] and ventilator-patient interface types [40], and on reducing associated leaks [41]. Beyond these technical aspects, however, patient-centered outcomes may have been overlooked and must be taken into account.

This trial involves patient-centered care at two different levels. First, the patient is active in choosing the desired music type, which may maximize his/her adherence to the music intervention, as suggested by Chlan et al. with the use of a music preference assessment questionnaire [17]. Second, to evaluate music intervention efficacy, we defined a patient-reported measure as the primary outcome (variation of dyspnea discomfort) and as secondary outcomes (anxiety/depression and health-related quality of life at baseline and at day 90; post-trauma stress induced by NIV, at discontinuation of NIV session, and at day 90; the assessment of NIV discomfort, satisfaction, and trauma).

We have chosen to run this trial in three units that already provided patient-centered care, in particular regarding relatives’ visitation hours, patients’ comfort needs, and involvement of patients and their relatives in the decision-making process.

Music therapy has shown its beneficial effects on patient anxiety, pain [24], and physiological events (heart rate, blood pressure) either outside [15, 42‐44] or inside the ICU [16‐20]. These studies showed that music therapy is feasible in the ICU, although only a small proportion of invasively ventilated patients (5.3 %) might benefit from such an intervention [17]. As such, music effects have never been assessed during NIV, a ventilator mode increasingly used in the ICU [45]. Therefore, one may surmise that many more patients will be affected by this intervention. Given that anxiety is one of NIV’s major drawbacks, our aim is to decrease potential stressful feelings that might be induced by NIV with the music therapy. This has been shown in the ICU: Han et al. [18] showed that a single music session significantly decreased anxiety (measured by the Spielberger State/Trait Anxiety Inventory) in patients invasively ventilated, compared to those who did not receive music. Likewise, Chlan et al. showed a significant effect of patient-directed music therapy on reducing anxiety (measured by a visual analog scale) compared with usual care during ICU stays in patients being ventilated [17].

It has been shown that post-ICU symptoms of anxiety, depression, or post-traumatic stress disorder (PTSD), especially in NIV patients [46], might occur up to 90 days after an ICU stay. Unfortunately, these symptoms were not assessed after this time in previous studies of music intervention, and never in NIV patients. In our trial, we plan to evaluate these symptoms and to find if a punctual intervention (i.e., 30 minutes of music intervention during NIV sessions) can diminish such post-ICU symptoms. Short- and long-term assessment of NIV-related PTSD seems necessary to determine the length of action of the interventions being tested.

Chlan et al. evidenced that music administration led to significantly less anxiety and sedation intensity compared to usual care in ventilated patients. But this was not evidenced when comparing usual care to noise-canceling headphones. We therefore decided to build a three-arm trial in order to distinguish the effects of the music and of the isolation of the noise and the light of the ICU. As ICU patients report noise as the main source of discomfort [47], we naturally question in our trial the role of noise isolation and of music in NIV (and ICU) tolerance, and therefore tested the “sensory deprivation” strategy.

To conclude, our trial tests an original non-pharmacologic, simple, and toxin-free therapy to improve one of the most stressful situations in the ICU. We deliberately choose patient-centered outcomes to assess this patient-centered intervention.

Enrollment is ongoing. Inclusions started on May 2015 and are expected to be completed in May 2016.