Could Music be an Alternative to Sedation in Patients Treated Total Knee Arthroplasty With Regional Anesthesia?
Condition: Anxiety; Surgery; Drug Toxicity; Anesthesia; Pain
MeSH terms: Drug-Related Side Effects and Adverse Reactions
Study type: Interventional

Summary: 
      Background: Anxiety is a common phenomenon in hospitalized patients. In order to reduce it
      during the surgical procedure, sedatives and anxiolytics are used, which can cause
      undesirable side effects for patients. Music is described as an effective tool to reduce this
      anxiety suffered by the patient in the perioperative process.

      Objectives: To evaluate the effect of music in patients anxiety and pain during perioperative
      process in surgical intervention with regional anaesthesia without sedatives or anxiolytics.

      Design: A randomized parallel clinical trial study with single-blinded and three harms.

      Setting: Operating theater of a public district hospital (serving around 111.000 people)
      Participants: All patients operated of Total Knee Arthroplasty (TKA) with regional
      anaesthesia with age between 50 and 85 years old within level I or II of the classification
      of the American Society of Anaesthesiologists (ASA).

      Methods: A total of 81 patients for TKA were randomly assigned to: a control group
      (headphones without music, without sedation), a sedative group (headphones without music,
      with sedation) and a experimental group (headphones with music, without sedation). 27
      participants for each group. All the participants were using headphones so that it was a
      single-blinded study. The experimental group were provided with the same music, Piano Guys
      group. The variables of study were: the pain was measured by vale numerical scale (VNS), the
      anxiety was measured by the use of State-Trait Anxiety Inventory (STAI), heart rate (HR)
      variability, blood pressure (BP) variability, saturation of oxygen (Sat02).

      Relevance to Clinical Practice: sedation that can causes unwanted side effects by surgical
      patients can be replaced by music. The music decrease anxiety and pain values in orthopaedic
      surgery patients.

      Keywords: Anxiety, Drugs, Music therapy, Pain, Perioperative, Surgery.
    

Detailed description: 
      1. Introduction Patients generally experience high levels of anxiety when are hospitalized
           to undergo surgery and other invasive procedures. Anxiety is an emotional state or
           condition characterized by stress and unpleasant feelings. Awake patients in the
           operating theatre are afraid of they will feel pain during the surgical and/or regional
           anaesthetic procedures, which contributes to increased anxiety. Patients operated under
           regional anaesthesia are in particular need of sedation during the perioperative period.
           The purpose of the sedation is to ensure comfort, full cooperation and cardiovascular
           stability of patients who can maintain a patent airway. However, because of the adverse
           effects (respiratory depression, nausea, vomiting), optimal patient satisfaction is hard
           to achieve. Additionally, intraoperative anxiety is often associated with a greater
           incidence of pain after surgery.

           On the other hand, toxicity of general anaesthetics has been recently studied from its
           neurotoxic effect to neuroapoptosis. In some cases, they may cause postoperative
           cognitive dysfunction, and other side effects known as hypoxemia, respiratory depression
           and increased morbidity and mortality.

           Music has been suggested as a potential intervention to reduce anxiety and pain in the
           operating room environment. Systematic meta-analysis conducted by Nilsson revealed that
           50% of studies (12 of 24) published between January 1995-January 2007 found significant
           reductions in anxiety scores as measured by STAI. and then more studies have been
           carried out on the benefits of music, which have continued to show that music reduces
           preoperative and postoperative anxiety and also reduces postoperative pain.

           There are also studies that conclude that patients to listening music require less
           midazolam to achieve a similar degree of relaxation as controls in ambulatory surgery
           patients and that the relaxing music a useful alternative to midazolam for
           pre-medication before surgery.

           Music holds considerable promise as an adjuvant pain management therapy and in mild
           cases may be used to supplement, perhaps even replace, pharmaceutical interventions
           before, during, and after painful procedures. The maximal reduction in pain intensity
           levels is 0.9 units on a zero to ten scale; although this difference reaches statistical
           significance, its clinical importance is unclear.

           The aim of this study was to evaluate the effect of the use of music in the
           perioperative process of patients undergoing surgery of total knee arthroplasty with
           regional anaesthesia without sedatives and compare anxiety and pain of these patients
           operated with regional anaesthesia, listening to or not music through headphones in
           patients without sedation.

        2. Material and methods 2.1 Research design and setting This study was a randomized
           clinical trial study with single-blind, three harms and parallel, that took place in the
           operating theatre conducted from January 2017 to January 2018.

      The participants who had the signed informed consent, once they reached the surgical area,
      were divided into the three groups according to the randomization list, control group
      (headphones without music, without sedation), sedation group (headphones without music, with
      sedation), intervention group (headphones with music, without sedation).

      Ninety-five patients were eligible for the purpose of this study and ten were refused to
      participate in the study. From the 85 remaining subjects, 29 were allocated to the control
      group, 27 to the sedation group, while 29 were allocated to the intervention group. The
      CONSORT flow diagram of the progress through the phases of a parallel randomised trial of the
      three groups is shown on Figure 1.

      There were not changes to methods after trial commencement.

      2.2 Participants and Sample size The study was performed on participants scheduled for a
      Total Knee Arthroplasty procedure in a Public Hospital from January 2017 to January 2018. The
      inclusion criteria were: (1) age with a range from 50 to 85 years old, (2) had regional
      anaesthesia, (3) duration of surgery not exceeding two hours (4) was willing to participate
      in the study and signed an informed consent form. The exclusion criteria were: (1) those
      patients with classification system of American Society of Anaesthesiologists (ASA) 3 or 4,
      (2) allergic drugs used, (3) psychiatric patients or cognitive issues, (4) patients with whom
      we have communication problems, (5) patients who for any reason need another type of
      anaesthesia.

      Sample size was determinate regarding the possible differences in the value of numerical pain
      among the 3 groups studied. Thus, in an analysis of the variance of a three-level factor
      (ANOVA), assuming a common standard deviation of 1.5 and a minimum difference to detect of 1
      point (or equivalent, to detect a difference in any quantitative variable of 0,66 standard
      deviations), with a statistical power of 80% and an alpha error of 0.05, 53 patients were
      needed in each of the three groups to detect the difference as statistically significant. A
      maximum 10% follow-up loss was considered. The result of the sample was 159 participants. An
      interim analysis was carried out that according to the statistical calculation had to be
      carried out when arriving at 81 participants (27 for each group). If the result was
      significant beneficial or harmful compared to the concurrent placebo group the study could be
      stopped.

      2.3 Randomization Randomization lists were generated based on pseudorandom numbers with the
      SPSS program. For the study, 3 blocks of 81 patients each were performed, corresponding to 27
      patients for each group.

      All randomization was independent of the researches. Randomization was done by a statistician
      who was not part of the data analysis.

      When a participant was a candidate to participate in the study, the random allocation table
      was consulted when the group was assigned, the researchers elaborated a closed envelope with
      information on the intervention received (with or without sedation and with or without music)
      by the participant in case it was It is necessary to break the simple blind. They were also
      told to the participants that they would not say whether or not they would listen to music.

      The staff, personnel and the assistants to the investigation were blinded to the participants
      group assignment.

      2.4 Intervention Once the participants were included in the study, they were assigned a group
      according to the randomization table. The participants of the control group were placed with
      headphones that no produced music and were administered 2 ml of serum, participants in the
      sedation group were placed with headphones without music and were administered the
      corresponding dose of midazolam (0.025 mg / kg in patients under 65 years of age. In patients
      over 65 years of age and / or with hepatic insufficiency or renal insufficiency with
      glomerular filtration <30 ml / h, the dose of midazolam was 0.015 mg / Kg.) and the
      participants of the intervention group were placed with headphones that produced music and
      were administered 2 ml of serum. All the participants were administered the same anaesthetic
      (levobupivacaine) for regional anaesthesia and the same analgesics in the postoperative
      period (ropivacaine, dexketeroprofen, paracetamol). A standardization of anaesthesia and
      analgesia was performed by the anaesthesiology and resuscitation service of the hospital.

      The music that the group's patients listened to during their stay in the operating theatre
      was a collection of songs from the music group Piano Guys, played a volume of 50-55 db. The
      headphone used were Audio-Technica ATH-M40X and the mp3 was iPod Nano (Apple).

      According to some studies, it is recommended that therapeutic music should have a slow tempo,
      low pitch, regular rhythm, and pleasing harmonics, and should consist of string, flute, and
      piano selections (Nilsson, 2008; Pelletier, 2004). In a Cochrane review, the genre and the
      duration of the soothing music did not seem to influence the effectiveness of music
      intervention.

      There were not any changes to trial outcomes after the trial commenced.

      2.5 Instruments and Measurements We employed both subjective and objective measures for
      anxiety and pain in our study.

      2.5.1 State-Trait Anxiety Inventory (STAI) The State-Trait Anxiety Inventory (STAI) consists
      of two different parts, termed STAI-Trait Anxiety Inventory (STAI-TA) and STAI-State Anxiety
      Inventory (STAI-SA). This test requires patients to complete a 40-item, 20 items measuring
      state anxiety and 20 items measuring trait anxiety (Spielberger et al.,1970) adding each one
      of the items of each subscale. The score can range between 0 and 60, representing the highest
      and lowest levels of anxiety, respectively. In our study, STAI-TA test results were evaluated
      preoperatively. The STAI-SA was performed during the waiting room (Orthopaedic unit, 30
      minutes before surgery) and postoperative period in Post anaesthesia care unit (PACU)
      (recovery period, 30 minutes after surgery). There are no cut points, but direct scores are
      transformed into centiles based on sex and age.

      2.5.2 Vale Numerical Scale (VNS) Pain intensity is frequently measured for visual analogue
      scale (VAS) or numerical ranting scale (NRS). We used the NRS, pain was assessed on a
      10-point pain intensity numerical rating scale, where 0=no pain and 10=worst possible pain
      (Lee et al.2015). The researcher gave oral instruction of ''Please said the point at the
      number to show how much pain do you have right now''. The pain was measured in preoperative,
      intraoperative and postoperative phase.

      2.5.3 Hemodynamic constants: To measure HR and BP, the researchers placed the sensor on the
      radial area of the patient's forearm for 15 minutes. Monitoring of the electrocardiogram
      (ECG) and capillary oxygen saturation (SatO2) was continuous. The participants were asked not
      to move around to ensure the quality of the readings. In our study, HR, BP and SatO2 was
      measured by a Datex Ohmeda TYPE D-LCC15..03.

      2.6 Data collection process This research was approved by the Ethical Committee for Clinical
      Research, (approved code: PR218/16).

      The researchers (SR, MR) checked the operating schedule and met potential participants in the
      room of orthopaedic unit where we take the signed consent and we gave them the STAI
      questionnaire.

      When the participants reached preoperative area, the researchers looked the group that
      belonged to each participant according to randomization list and they were monitored
      hemodynamic constants (HR, BP, SatO2), the headphones were placed with or without music and
      the dose of sedation or physiological serum (placebo) was administrated according to the
      study group to which they belonged. The dose of sedation or serum was repeated every 45
      minutes until surgery was finished. All the data (STAI preoperative and postoperative, VNS
      preoperative and postoperative, hemodynamic constants every 15 minutes, dose anaesthetics and
      analgesics, sociodemographic variables) were registered in a graph created by researchers.

      The data collection in each phase, preoperative, intraoperative and postoperative, was
      carried out by nurses who did not belong to the research team, who were educated before
      starting the study so that there were no biases in the collection.

      2.7 Statistical analysis Categorical variables were described by means of the number of
      cases, the percentage with respect to the total by category and the number of available data.
      Continuous variables were described by means of the number of cases, the mean and the
      standard deviation or the median and the inter-quartile range (IQR). Continuous variables
      were compared using Student's t-test or Mann-Whitney U-test as appropriate. Fisher's exact
      test or Pearson's χ2 test were applied to assess the relationship between categorical
      variables. In order to evaluate the main objective, a covariance analysis was performed to
      evaluate the role of the intervention in the change in the value of the final pain compared
      to initial pain. The effects of each intervention were compared by pairs with the adjustment
      for multiple comparisons of Tukey. The rest of the study variables (STAI questionnaire and
      hemodynamic constants (BP, HR, SatO2)) were analysed similarly. Models were replicated
      adjusted by age and gender. Analyses were performed with R software 3.4.0. The statistical
      significance was set at a probability level <0.05.

      2.8 Ethical considerations The participants who met the inclusion criteria were informed by
      the researchers and they were also given an informative document of the study. The
      participants who wanted to participate in the study signed an informed consent.

      4.1 Limitations When we performed the post-STAI test in the Post Anesthesia Care Unit (PACU),
      some patients could not read the questionnaire because they did not have the glasses, so the
      nurse had to ask the questions. In future studies, a better research design or a more
      suitable testing location can provide a better understanding on this subject. Additional
      research could examine the effectiveness of listening to preferred music, the use of music as
      an alternative to another type of sedative drug such as propofol, for other surgical
      patients, as well as their satisfaction.

      Conflict of interest and Funding None Acknowledgements The authors thanks all professionals
      who have collaborated in the study: surgery nurses, nursing traumatology department and
      nursing supervision.

      Thanks especially Dr Xavier Pelfort and Dr Joan Miquel, for assistance with study design,
      statistical analysis, manuscript review and anaesthetist Dr Josep Mª Bausili for assistance
      with anaesthesia standardization.
    

Intervention name(s): Music therapy; Sedation with midazolam
Intervention type(s): Other; Drug
Intervention description(s): To evaluate the effect of music in patients anxiety and pain during perioperative process in surgical intervention with regional anaesthesia without sedatives or anxiolytics.; To evaluate the effect of sedation (in comparation with music group) in patients anxiety and pain durin perioperative process in surgical intervention with regional anesthesia without music
Intervention MeSH terms: Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Other
Keywords: Anxiety; Pain; perioperative; Surgery; Music Therapy; Drugs