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ORIGINAL RESEARCH

Effect of the Combination of Music and Nature

Sounds on Pain and Anxiety in Cardiac Surgical

Patients: A Randomized Study

Susanne M. Cutshall, MS, RN, ACNS-BC; Patricia G. Anderson, MS, RN, ACNS-BC; Sharon K. Prinsen, MS, RN; Laura J. Wentworth, MS, RN, ACNS-BC; Tammy L. Olney, BSN, RN; Penny K. Messner, DNP, RN, ACNS-BC; Karen M. Brekke; 2huo Li; Thoralf M. Sundt III, MD;

Ryan F. Kelly; Brent A. Bauer, MD

Background • Postoperative pain and anxiety are common in cardiac surgery patients. Studies have suggested that music can decrease anxiety in hospitalized patients.

Primary Study Objective • This study focused on the efficacy and feasibility of special music, which included nature sounds, for pain and anxiety.

Methods/Design • In this randomized controlled trial, postop-erative cardiovascular surgery patients were randomly assigned to a music group to receive 20 minutes of standard postoperative care and music twice daily on postoperative days 2 through 4 or to a control group to receive 20 minutes of standard care with a quiet resting period twice daily on postoperative days 2 through 4. Setting • Cardiovascular surgical unit of Saint Marys Hospital, Rochester, Minnesota.

Participants • One hundred patients completed the study (music group, n=49; control group, n = 51).

Intervention • The music was delivered through CD players in the patients' rooms.

Primary Outcome Measures • Pain, anxiety, satisfaction, and relaxation were evaluated from visual analog scales.

Results • Data showed a significant decrease in mean (SD) pain scores after the second session of day 2 for the music group (change, -1.4 [1.4]) compared with the control group (change, -0.4 [1.4]) (P^.OOl). Mean relaxation scores improved more at the first session of day 2 for the music group (change, 1.9 [2.7]) compared with the control group (change, 0.3 [2.9[) (P = .03). The music group also showed lower anxiety and increased satisfaction overall, but these differences were not statistically significant. No major barriers to using the therapy were identified.

Conclusion • Recorded music and nature sounds can be inte-grated into the postoperative care of cardiovascular surgery patients. The recordings may provide an additional means for addressing common symptoms of pain and anxiety while pro-viding a means of relaxation for these patients. (Altern Thcr Health Met!. 2011;17(4);16-23.)

Susanne M. Cutshall, MS, RN, ACNS-BC, is an integrative health

specialist in the Department of Surgery, Mayo Clinic, Rochester, Minnesota. Patricia G. Anderson, MS, RN, ACNS-BC, is a certified clinical nursing specialist; Sharon K. Prinsen, MS, RN, is an administrator; Laura J. Wentworth, MS, RN, ACNS-BC, is

a certified clinical nursing specialist; Tammy L. Olney, BSN, RN,

is a manager; and Penny K. Messner, DNP, RN, ACNS-BC, is a cer-tified clinical nursing specialist, all in the Department of Nursing, Mayo Clinic. Karen M. Brekke is a research study coordinator at the Neuroimmunology Laboratory, Mayo Clinic.

Zhuo Li is a statistician in the Division of Biomédical Statistics

and Informatics, Mayo Clinic. Thoralf M. Sundt III, MD, is a consultant and Ryan F. Kelly is an administrator in the Division of Cardiovascular Surgery, Mayo Clinic. Brent A.

Bauer, MD, is a consultant in the Division of General Internal

Medicine, Mayo Clinic.

Corresponding author: Brent A. Bauer, MD E-mail address: bauer.hrent@mayo.edu

Authors' notes: Mayo Clinic does not endorse the product mentioned in this article. The authors have no conflict of interest to disclose.

C

oronary artery bypass graft (CABG) and cardiac valve

surgery are performed more than 700 000 times each year in medical facilities throughout the United States.' Even though technology has improved dramatically and the outcomes of these operations are generally suc-cessful, open heart surgery is a major surgical procedure. Patients experience pain and anxiety, and they usually stay in the hospital for a week after heart surgery.-'

Frequently, patients who undergo cardiac surgery experience anxiety as they anticipate unfamiliar or uncomfortable events

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before and after surgery.*'^ During recovery after surgery, patients may feel helpless and be concerned about loss of control, physical discomfort, and doubts about their progress.^' In addition, unfa-miliar environments and sounds can create physiologic complica-tions and delay recovery.'*

Along with having anxiety, patients experience pain after cardi-ac surgery. This type of postoperative pain has no fiinctional value beyond signaling the presence of tissue damage fi'om surgery, and it may actually have harmfijl psychologic and physiologic consequenc-es. As the stress response increases, wound healing may be impaired."-' Pain also interferes with the patient's sleep and appetite and can create anxiety, compounding complications with other com-ponents of the cardiovascular system and gastrointestinal tract, thereby prolonging recovery.'""

The Agency for Healthcare Research and Quality recom-mendations for pain management include the use of cognitive-behavioral interventions such as relaxation, music, distraction, and imagery.''' These interventions have been shown to reduce the amount of pain medication used and to improve the manage-ment of pain and anxiety.'"^

Music is well known as a positive integrative therapy with its therapeutic qualities of enhancing well-being, reducing anxi-ety and stress, and distracting people from unpleasant painful stimuli.'""'' Ambient Therapy (Ambience Medical, Omaha, Nebraska) uses specifically designed music that combines natu-ral sounds recorded in a 200 x 200-foot time-delay algorithm with musical parts created to enhance emotions. These specifi-cally recorded sounds of nature are thought to minimize the patient's perception of spikes or startle sounds in his or her envi-ronment. Thi:-; effect is hypothesized to provide patients with a new perceptual reality so that the hospital environment is sooth-ing and comfortsooth-ing, helpsooth-ing the patient counteract feelsooth-ings of pain and anxiety.™ Evidence shows that a convergence occurs between sensory input (such as ambient music) and neural out-put (through I he central nervous system) that regulates pain and stress responses.-'

The purpose of this study was to test the effects of structured music with nature sounds on the level of pain and anxiety in cardiac surgical patien is.

METHODS Research Design

A stratified randomized experimental design was used to assign patients to standard postoperative care in combination with ambi-ent music sessions (the music group) or to standard postoperative care in combination with matched quiet resting sessions (the control group) (Figure 1). This protocol was reviewed and approved by the Mayo Clinic Institutional Review Board.

Research Setting

The participants were cardiac surgical patients at Saint Marys Hospital in Rochester, Minnesota. Data were collected while the patients were in the cardiovascular surgical intensive care and pro-gressive care units of the hospital.

g

Enro l Allocatio n

g

•B

ô

349 Patients assessed for eligibility

176 Excluded

55 Did not meet inclusion criteria 89 Refused to participate 32 Excluded for other reasons

173 Randomized

87 Allocated to standard care and quiet resting sessions

51 Completed the sessions

51 Included in analysis

86 Allocated to standard care and ambient music sessions

49 Completed the sessions

49 Included in analysis

FIGURE 1 Patient Flowchart. In this randomized controlled trial, cardi-ac surgical patients were randomly assigned to receive standard

pstop-erative care with sessions of either quiet rest or ambient music. Inclusion Criteria

Participants were cardiac surgical patients, aged 18 years or older, who had undergone first-time CABG surgery or cardiac valve surgery (or both) and had consented to participate in the study. Exclusion Criteria

Patients were excluded fi-om the study if they were non-English speaking, if they were intubated on postoperative day 2, or if they had a diagnosis of chronic pain, a chronic psychiatric disorder, or a hearing impairment that would interfere with hearing the music. Randomization

At the start of postoperative day 2, patient pain levels were assessed on a scale fi-om 0 (no pain) to 10 (the most intense pain), and stratification for randomization was based on a pain level of 4 or less (the institutional pain level goal) or greater than 4. The random-ization was blocked to ensure balanced allocation throughout the course of the study. There were 25 randomized blocks of 4 patients and 25 randomized blocks of 2 patients. Each set of 50 blocks was changed into a random order as well. To account for potentially non-random dropouts, the non-randomization scheme was determined in advance for 150 patients per stratum, and enrollment was continued until at least 100 patients in total had completed day 4 of the study. The use of cards in sealed envelopes prevented the study coordinator

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who was enrolling patients from knowing to which group each patient was randomly assigned.

Interventions

Music Group. On postoperative day 2, the study coordinator met with each patient in the music group, confirmed consent, and explained the process of randomization based on pain level. Patients were encouraged to assume a comfortable position in bed during the intervention. The study coordinator read to the patient a printed script and obtained measurements of pain, anxiety, satisfaction, and relaxation orally with a visual analog scale (VAS). The coordinator then measured the patient's blood pressure and heart rate. The patient was given a choice of four compact discs (CDs); Summer Song, Autumn Song, Bird Song, or Night Song. Each private room was equipped with a CD player on the nightstand next to the bed. The selected CD was played for 20 minutes twice daily on postoperative days 2 through 4, in the morning (between 8 AM and noon) and in the afternoon (between 1 PM and 6 PM). During the intervention, the patient's room door was closed, and a sign was posted stating, "Do Not Disturb/Patient Resting." After the 20 minutes of music therapy, measurements were repeated for pain, anxiety, relaxation, satisfaction, blood pressure, and heart rate. Data were collected on age, sex, surgical procedure, and total daily dosage of opioids admin-istered over the 3-day period for both groups.

Control Group. On postoperative day 2, the study coordina-tor met with each patient in the control group, confirmed informed consent, and explained the process of randomization based on pain level. Patients assigned to the control group were encouraged to rest for 20 minutes in bed. Pain, anxiety, relax-ation, satisfaction, blood pressure, and heart rate data were col-lected before and after the rest period. A "Do Not Disturb/Patient Resting" sign identical to that for patients in the music group was posted at the patient's door.

Evaluation

Patients reported measures of pain, anxiety, relaxation, and overall satisfaction before and after interventions on postoperative days 2,3, and 4. A VAS was used to evaluate pain, anxiety, relaxation, and overall satisfaction before and after the intervention (ambient music or quiet rest). For pain and anxiety, negative changes Indicated improvement, whereas for relaxation and satisfaction, positive changes indicated improvement. Heart rate and blood pressure mea-surements were collected by the study coordinator before and after each 20-minute session.

Sample Justification

It was estimated that a sample size of approximately 50 patients per group (100 total) completing the study on day 4 would be need-ed to detect an effect size of 0.60 at 80% power for a 2-tailneed-ed Wilcoxon rank sum test with an a level of .05.

Statistical Analysis

Data were analyzed with descriptive statistics. Continuous vari-ables were summarized as mean (standard deviation) and median.

Categorical variables are presented as frequency and percentage of group totals. The changes in measurements of pain, anxiety, relaxation, satisfaction, blood pressure, and heart rate from before the intervention to after the intervention were compared between music and control groups. The analysis also compared the difference in the amount of opi-oid medications used during days 1 through 5 between groups.

Comparisons of continuous variables between groups, such as pain and anxiety levels, were evaluated with the two-sample / test or Wilcoxon rank sum test. Between-group comparisons of categorical variables, such as sex, were assessed using the x^ test or Fisher exact test. Since age was significantly different between the tv\'o groups, the difference in change of anxiety and pain between groups was also tested with age-adjusted linear models. P values of less than .05 were considered statistically significant.

RESULTS

The characteristics of the two groups were similar for sex, type of surgery, and baseline pain score. Most participants were male (76% in the music group and 78% in the control group). The majority of patients had a baseline pain score of 4 or less. All patients were extu-bated on the day of surgery or early the next morning. Chest tubes were placed in all patients and were removed according to standard practice (ie, in approximately 2-3 days). In both groups, more patients had either a CABG or a heart valve procedure than a combination of both. Patients in the music group were older than patients in the con-trol group (mean age, 66 [13] years vs 60 [12] years; P-.O3) (Table 1).

TABLE 1 Demographic and Clinical Features of Patients in the

Ambient Music Group and Patients in the Control Group Feature Age, y Mean (SD) Median Length of stay, d Mean (SD) Median Gender, no. (%) Female Male

Baseline pain score, no. (% ¿4

>4

Surgical procedure, no. (% CABG CABG-H valve Valve Music (n=49) 65.6(12.9) 67 5.9 (3.6) 5 12(24.5) 37(75.5) ) 35 (71.4) 14(28.6) ) 17(34.7) 7(14.3) 25(51.0) Control (n=51) 60.2 (12.4) 60 7.9(12.8) 5 11 (21.6) 40(78.4) 37(72.6) 14(27.5) 15(29.4) 5(9.8) 31(60.8) Abbreviation: CABG, coronary artery bypass graft.

*P values are based on comparisons of mean values for the 2 group

Pvalue* .03 .48 .73 .90 .59

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Data showed a significant decrease in mean pain scores after the second session of day 2 for the music group (change, -1.4 [1.4]) compared with the control group (change, -0.4 [1.4]) (P = .001) (Figure 2). Mean relaxation scores improved more at the first session of day 2 for the music group (change, 1.9 [2.7]) compared with the control group (change, 0.3 [2.9]) {P = .03). Besides the difference mentioned above, the mu.sic group had lower anxiety and increased satisfaction overall, although these differences were not statistically significant (Figures 3-5).

Diastolic blood pressure decreased significantly on day 4 after session 2 in the music group compared with the control group (Table 2). The differences in the various outcomes between groups remained after age difference was adjusted in models. There was a trend of decreasing opioid use on day 3 in the music group that was not statis-tically significant (Table 3).

Several qtialitative observations were noted. The study coordina-tor found that patients and families were very receptive to being in the study and listening to music selections or having quiet time. There were individual preferences for certain selections; some patients pre-ferred specific combinations of music and nature sounds. In both groups, some patients brought their own music to listen to outside of the study sessions, and some patients listened to music in the operat-ing room, too. The coordinator found that it was difficult for patients

to not be interrupted during the session in the busy cardiac surgical unit and that it was a little easier to locate patients in their rooms in the afternoon. Nurses were receptive to the study interventions and made comments about the positive effect on the environment for the patients and for themselves.

DISCUSSION

In this study, patients in the music group had a significant reduction in pain soon after surgery and an overall trend of increases in reported relaxation scores. They also had an overall trend of lower reported anxiety scores and a trend of increased levels of satisfaction with care overall. The.se results are consis-tent with those of other studies that examined the effects of music listening in hospitalized patients."" Assisting patients with any amount of reduction in pain and anxiety after cardiac surgery is valuable for healing and improving the overall experi-ence for the patients."^' Research on pain management suggests that early treatment to relieve pain may help prevent long-term pain.^^ Interventions such as ambient music should be consid-ered as an adjuvant for more complete relief of postoperative pain for cardiac surgery patients. This recommendation is con-firmed by a similar study with cardiac surgery patients at another medical facility with similar patient populations."

3.02 . 5

1

•i 2 0 -4eanl ^^ 1.5- 1.0- 0.5-0.0

VA.,

/

9 9 Music - - • - - Control i 1 I 1

\ / \•

1 1 1 1—1—1—

Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post

Session 1 Session 2 Session 1 Session 2 Session 1 Session 2

Day 2 Day 3 Day 4

FIGURE 2 Ml an Pain Scores. Patients rated their pain on a scale fhim 0 (no pain) to 10 (the most intense pain) before (Pre) and after (Post) each session

of ambient music (for patients in the music group) or quiet rest (for patients in the control group).

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TABLE 2 Variable Measurements Before and After Intervention Sessions for Patients in the Ambient Music Group and Patients in the Control Group

Variable*

Change after session 1 Pain

Anxiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care Change after session 2

Pain Anxiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care Change after session 1

Pain Anxiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care Change after session 2

Pain Atixiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care Change after session 1

Pain Anxiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care Change after session 2

Pain Anxiety Relaxation

Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Satisfaction with care

n 49 49 49 49 49 49 49 48 48 48 48 48 48 48 49 49 49 49 49 49 49 47 47 47 47 47 47 46 48 48 48 47 47 47 47 47 47 47 47 47 47 47 Mean -0.9 -0.7 1.9 -3.8 -0.4 -0.3 0.3 -1.4 -0.3 1.4 -5.6 -1.1 0 -0.3 -1.1 -0.4 0.5 1.5 1.9 1.5 -0.04 -0.7 -0.3 1.3 1.1 1.8 -1.1 0.1 -0.8 -0.6 0.6 -3.4 -1.3 -0.8 0.2 -0.7 -0.5 0.8 -4.6 -3.5 -2.7 0.1 Music SD Day 2 1.6 1.3 2.7 15.5 71 5.1 1.5 1.4 1.3 2.5 20.2 70 4.4 2.1 Day 3 1.9 1.5 2.7 13.0 10.6 6.9 1.3 2.2 1.4 1.9 12.3 9.3 8.0 1.4 Day 4 1.4 1.9 2.5 12.6 15.8 11.6 1.0 1.8 1.1 1.7 11.8 9.0 6.8 0.4 Median - 1 0 1 - 1 - 1 0 0 - 1 0 1 -2.5 -0.5 0 0 - 1 0 0 0 0 1 0 0 0 1 0 0 - 1 0 0 0 0 - 3 -3 - 1 0 0 0 0 - 3 - 4 0 0 n 51 51 51 51 51 51 50 50 50 49 49 47 50 49 51 51 51 47 47 48 50 50 50 50 48 48 49 49 51 51 51 49 49 51 51 51 51 51 50 50 48 51 Control Mean -0.7 -0.3 0.3 -1.6 -0.9 1.7 -0.3 -0.4 -0.4 1.3 -1.9 -2.9 -0.6 -0.1 -0.8 -0.2 1.0 -2.0 -1.4 -0.4 -0.04 -0.3 -0.6 0.7 -0.6 -0.6 1.4 -0.02 -0.6 -0.5 0.4 -2.6 -1.0 -0.5 0.2 1.4 -0.1 1.0 -2.6 -0.6 -1.2 0.1 SD 1.7 1.8 2.9 n.2 72 9.5 1.9 1.4 1.3 3.1 9.8 6.4 4.4 2.1 2.0 2.3 2.6 9.4 6.5 8.1 0.8 1.7 1.4 3.3 8.3 11.6 6.1 0.4 1.4 1.3 2.0 16.5 9.1 8.6 1.5 10.9 1.6 2.0 10.9 6.4 in 0.9 *Pain. anxiety, relaxation, and satisfaction were evaluated with a visual analog scale from 0 (least amount) to 10 (greatest amount). f P values are based on comparisons of mean values for the 2 groups

Median 0 0 0 - 1 0 0 0 - 1 0 1 -1 -2 0 0 - 1 0 0 0 0 -0.5 0 0 0 0 0.5 0 1 0 0 0 0 -2 - 2 - 1 0 0 0 0 - 1 0 0 0 Pvaluef .67 .50 .03 .76 .88 .30 .17 .001 .55 .47 .56 .10 .88 .86 .58 .97 .67 .18 .10 .04 .97 .15 .09 .33 .86 .23 .15 .33

.n

.77 .36 .61 .34 .65 .20 .11 .37 .94 .38 .047 .69 .42

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3 . 0 - , 1.0 ^ 0 . 5 - 0.0-— Music • - Control T I I I 1 1 \ 1 1 1 1 1

Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post

Session 1 Session 2 Session 1 Session 2 Session 1 Session 2 Day 2 Day 3 Day 4

FIGURE 3 ^'Iean Anxiety Scores. Patients rated their anxiety on a scale from 0 (least) to 10 (most) before (Pre) and after (Post) each session of ambient

music (for patients in the music group) or quiet rest (for patients in the control group).

9.5-1 9 . 0 8 . 5

-I 8-0

M

OS S 7.5 7.0 6.5 -6.0 — Music — Control '~\ I I I ! i 1 1 i 1 1 —

Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Session 1 Session 2 Session 1 Session 2 Session 1 Session 2

Day 2 Day 3 Day 4

FIGURE 4 Mean Relaxation Scores. Patients rated their relaxation on a scale from 0 (least) to 10 (most) before (Pre) and after (Post) each session of

ambient music (for patients in the music group) or quiet rest (for patients in the control group).

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8.6

Session 1 Session 2 Session 1 Session 2 Session 1 Session 2 Day 2 Day 3 Day 4

FIGURE 5 Mean Satisfaction Scores. Patients rated their satisfaction on a scale from 0 (least) to 10 (most) before (Pre) and after (Post) each session of ambient music (for patients in the music group) or quiet rest (for patients in the control group).

TABLE 3 Dosages of Fentanyl and Oxycodone in the Ambient Music Group and the Control Group

Drug

Dayl

Fentanyl, pg daily Oxycodone, mg twice daily Day 2

Fentanyl, pg daily Oxycodone, mg twice daily Day 3

Fentanyl, pg daily Oxycodone, mg twice daily Day 4

Fentanyl, pg daily Oxycodone, mg twice daily Day 5

Fentanyl, pg daily Oxycodone, mg twice daily

n 43 6 46 25 40 33 14 26 3 15 Music Patients Mean(SD) 1975 (113.6) 75 (4.2) 594.5(426.1) 16.2 (15.7) 349.1 (3270) 16.8(11.3) 1877 (218.6) 16.2 (10.8) 300.3(2171) 24.0(17.3)

*P values are based on comparison of mean values for the groups.

Median 176 5 488 10 240 10 80 13 180 20 n 44 7 51 29 45 35 18 27 3 18 Control Patients Mean (SD) 283.6 (211.7) 9.3 (3.5) 6574 (473.2) 16.7(9.5) 344.3 (292.7) 22.0 (13.1) 219.2 (240.0) 20.9(12.3) 174.3 (96.3) 20.6(13.4) Median 258 10 490 15 260 20 130 20 160 18 Pvalue* .13 .42 .55 .28 .75 .07 .89 .14 .41 .65

This study has a number of limitations. The intervention was limited to a particular type of music with nature sounds. Allowing patients to choose their own music might strengthen the impact of the intervention. We did not restrict patients in either group from

using their own music. Thus, some of the controls may have been exposed to the intervention (or to music of a similar nature). This could have weakened the effect seen in the present study. Finally, all subjects were patients undergoing cardiovascular surgery, so the

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results cannot necessarily be generalized to other populations. An understanding of the role of treatment modalities, such as music and nature sounds, in managing anxiety and pain is needed to help achieve a balance between pain medications and the assorted side effects.'"" Patients are increasingly seeking integrative therapies, and numerous facilities are incorporating them into the care provided. One study suggested that approximately 50% of patients have incorporated the use of integrative therapies for pain management because conven-tional pain medications were not effective in relieving pain."^

Music is considered a simple, cost-effective way to improve a person's mood and decrease anxiety and pain associated with surgery or other medical procedures.^'^' Hospitalization and illne.ss are stress-fiil and are ofti.'n associated with fear of pain. Stress and pain during hospitalization may interfere with sleep quality, appetite, digestion, behavior, and wound healing, resulting in longer hospital stays.'"'^'

Future studies would be beneficial to confirm the results of the present study and to explore the effect of natural sounds in producing outcomes. The frequency and timing of music listening needs to be explored, especially in a busy ho.spital with many possible interrup-tions. Although this music study had structured music times during the day, patients may prefer music at other times during the day. Another consideration is the preoperative and intraoperative role of ambient music. Patient preferences aLso may be a key component of the effectiveness of such therapies and could be addressed in nature studies that offered a wider range of music and nature sounds.

In conclusion, this study showed that recorded music and nature .sounds can be integrated into the postoperative care of cardio-vascular .surgery patients. For cardiocardio-vascular surgery patients, ambi-ent music ma) provide an additional means for addressing common symptom.s of pain and anxiety while providing a means of relaxation. The use of any complementary modalities that can provide some symptomatic relief and increase patient satisfaction is a welcome addition to patient care and provides patients with options to consid-er to improve the hospital or surgical expconsid-erience.

Acknowledgments

We gratefully acknowledge the participation of the Healing Enhancement team members in assisting and supporting this study. The CDs used in this study were donated by Ambience Medical, We also acknowledge the Saint Marys Hospital Auxiliary for its ongoing support in providing the gift olmusic and other healing resources for our patients. Finally, this work was further supported by a generous gift from Richard J, and Sharon M. Mrocek.

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