Abstract: Objectives. Opiates and benzodiazepines are commonly used during invasive coronary angiography (ICA) to address pain and anxiety. In the United States (US), these medications are used in more than 90% of such cases. The utility of these medications during ICA has not been addressed by the scientific societies. The goals of this study were to evaluate the impact of music on the use of opiates and benzodiazepines and levels of pain and anxiety in patients undergoing ICA. Methods. In this prospective pilot study, a total of 72 subjects undergoing elective ICA were randomized to receive planned pharmacologic standard conscious sedation (SCS), including opiates and/or benzodiazepines pre-ICA vs music plus opiates and/or benzodiazepines as needed. Pain and anxiety levels, as well as use of SCS medications, were monitored during the periprocedural period. Results. Baseline characteristics, including rates of anxiety, depression, and other psychiatric disorders, were similar between the SCS and music groups. The levels of pain and anxiety were relatively low and similar between the two cohorts during the peri-ICA period. There was a trend toward less frequent use of SCS medications in the music group (62.2% in the SCS group vs 40.0% in the music group; P=.06) and significantly less use of midazolam per case in the music group (0.68 mg in the SCS group vs 0.37 mg in the music group; P=.048). SCS medication use also differed significantly between the two operators. Conclusions. Listening to patient-selected music during the peri-ICA period may reduce the need for pharmacologic conscious sedation without adversely affecting pain and anxiety levels.
J INVASIVE CARDIOL 2020;32(11):440-444. Epub 2020 October 22.
Key words: music, opiates, sedation
Opiates and benzodiazepines are commonly used preprocedurally to address pain and anxiety for patients undergoing invasive coronary angiography (ICA) in the United States (US); use of these medications exceeds 90% in US cases.1 These drugs have many deleterious side effects, including confusion, memory loss, hypoxemia, respiratory suppression or arrest, and drug-drug interactions that could result in adverse outcomes, such as delayed healing, increased healthcare utilization, and cost.2-10
Over the past 2 decades, increasing attention has been paid to non-pharmacologic interventions that may ameliorate pain or anxiety associated with a variety of medical conditions. Music has been used as a mechanism to achieve these goals.11-16 However, the advantages and disadvantages of music vs pharmacologic standard conscious sedation (SCS) have not been studied. The goals of this pilot study were to evaluate the impact of music on pain and anxiety levels, as well as the use of SCS medications during ICA.
In this prospective pilot study, which was conducted collaboratively between the medical and nursing departments, subjects undergoing ICA were randomized to either: (1) planned SCS with pre-ICA midazolam and/or fentanyl without any background music (SCS arm); or (2) patient self-selected music without preplanned SCS during the periprocedural period (Music arm). Patients were screened for eligibility during their routine precardiac catheterization clinic visit or on the morning of their scheduled ICA procedure, and were approached by study staff for enrollment into the study. Inclusion criteria included: (1) age >18 years old; (2) non-emergent ICA; and (3) ability and willingness to participate in the study and sign the informed consent form. Exclusion criteria included: (1) acute myocardial infarction requiring emergency ICA; (2) documented history of major hearing problems or deafness; (3) contraindication to SCS medications; and (4) unwillingness to comply with study procedures and requirements.
For those randomized to the Music group, music was started approximately 20 minutes prior to arrival in the cardiac catheterization laboratory (CCL), and continued throughout the procedure and during the recovery period up to 1 hour. Choice of music was based on each subject’s stated preferences (specific genre, artists, or songs were searched in one of the mainstream digital music libraries). Music was delivered through a portable media player with single-use, disposable ear buds. The appropriate volume was adjusted by CCL nursing staff per patient request. Ear buds were used in only 1 ear of each subject to ensure adequate communication between the subject and the attending provider and CCL staff. After “timeout” (the process of identifying the patient and the intended procedure) and prior to administration of local anesthesia with 2% lidocaine subcutaneously (defined as the start time for the procedure), all subjects were assessed for their levels of pain and anxiety by the nursing staff, and were asked whether they wanted to receive pharmacologic conscious sedation. Midazolam (0.5-1.0 mg intravenously) and/or fentanyl (25-50 µg intravenously) were administered to all subjects who requested pharmacologic sedation, including those in the Music arm. The administered dose of these medications depended on age, weight, renal function, and other clinical criteria, and was chosen at the discretion of the operator. In addition, SCS was not administered to those in the SCS arm if they requested to not receive SCS.
Subjects were assessed for their levels of anxiety (according to a 0-10 anxiety severity analog scale) and pain (according to the Wong-Baker Faces analog pain rating scale)17 prior to entering the CCL, as well as just before the official start of the procedure (defined as the time of administration of lidocaine), during ICA (at least once every 15-20 minutes into the ICA, and as needed based on the assessment of the circulating registered nurse or the operator), and after ICA (prior to leaving the CCL) by CCL nurses not involved in the study. If clinically appropriate, additional midazolam and/or fentanyl was administered during the ICA when requested by the subject or at the operator’s discretion. All procedures were performed at a single teaching facility under the supervision of 2 experienced interventional cardiologists. ICAs through all access sites were included. This study was approved by the institutional review board of the Veterans Affairs Greater Los Angeles Healthcare System. All subjects provided written consent to participate in the study. Enrollment of the study lasted between November 2017 and May 2018.
Statistical analysis. Treatment effects were examined by comparing the 2 treatment arms. For pain, anxiety, and amount of medications used, independent t-tests were utilized. Dichotomous variables, such as use of any sedation, were compared through contingency-table Chi-squared analysis. The t-tests were two tailed, and an alpha level of significance of P=.05 was used for all analyses. SAS software, version 9.4 (SAS) was used for all statistical analyses.
Between November 2017 and May 2018, a total of 77 patients consented to participate in the study. Five subjects did not have ICA and were excluded from the analysis (1 patient left against medical advice, ICA was canceled in 2 patients, and 2 patients did not undergo scheduled ICA). Seventy-two patients were randomized and enrolled in the study, with 37 randomized to the SCS arm and 35 randomized to the Music arm. Baseline characteristics are shown in Table 1. The overall population included 68 men (94.4%), with average age of 69.03 years. Diabetes (38 patients; 52.8%) and hypertension (68 patients; 94.4%) were very prevalent in the entire cohort. Twenty-eight patients (39.1%) had current or history of illicit drug use and 16 patients (22.2%) had posttraumatic stress disorder (PTSD).
Table 2 presents the anxiety and pain levels in the periprocedural period. Neither pain nor anxiety were significantly different between the SCS and Music groups during the overall periprocedural period. Additionally, there were no significant differences in the pre-, intra-, or postprocedural periods between the 2 groups.
Table 3 presents the use of midazolam and fentanyl in the SCS and Music groups. Overall, 23 patients (62%) in the SCS group and 14 patients (40%) in the Music group received any sedation (P=.06). Average dose of midazolam administered was lower in the Music group vs the SCS group (0.37 mg vs 0.67 mg, respectively; P=.048). Average fentanyl dose administered was similar in the Music group vs the SCS group (15.7 µg vs 20.9 µg, respectively; P=.36). Frequency of sedation used in high-risk subjects (defined as those with depression, anxiety, PTSD, or other psychiatric disorders) was significantly higher than in those without such disorders (22 of the 32 patients with disorders [69%] vs 15 of the 40 patients without disorders [38%]; P<.01).
As a post hoc analysis, patterns of pain and anxiety as well as SCS medication use were compared between the 2 operators. While the patients’ levels of pain and anxiety did not differ significantly based on the different operators, there was a significant difference in the frequency of any SCS medications used between the 2 operators (69.7% in operator 1 vs 35.9% in operator 2; P<.01). In addition, there was a significant difference in the per-case dose of midazolam (0.82 mg administered by operator 1 vs 0.28 mg administered by operator 2; P<.01) and nominally reduced dose of fentanyl used per case (22.73 µg administered by operator 1 vs 14.74 µg administered by operator 2; P=.15).
Use of preplanned pharmacologic conscious sedation during ICA is the standard of care in North America. However, a search of the literature fails to objectively justify this practice. In the late 1980s and 1990s, increased attention was focused on pain management. The Joint Commission for the Accreditation of Healthcare Organizations mandate for improved recognition and treatment of pain led to a shift in practice toward more aggressive pain management strategies. Concepts such as “titrate to effect,” the “fifth vital sign,” and “no tolerance” were promoted to more effectively treat pain.18 Without much scholarly investigation, this movement gained significant adoption over the ensuing years, with detailed and comprehensive protocols placed into practice in the majority of healthcare centers throughout the US. The current standard of care in most US CCLs is preplanned routine administration of opiates and/or sedatives without asking patients their preferences.
Recent studies reveal that opiate-related deaths have quadrupled since the 1990s.19-21 A study evaluating donor and recipient characteristics for adult cardiac transplants revealed a 9-fold increase in overdose-death donors from 2000 to 2016.22 With the rise of the current opiate and sedative epidemic in the US and increased mortality related to these drugs, more attention is being paid to the healthcare providers’ practice patterns in prescribing such medications, and the soundness of such practices. In an emergency department study, physicians’ prescribing habits for opioids varied significantly within the same clinical setting. As a major public health policy concern, even an acute and brief exposure to opiates has been associated with higher rates of their long-term use.23 The authors of that study concluded that the rate of use of such medications differs among healthcare providers and might be influenced by culture, training, and geography. They also commented that there was a lack of adequate formal training in the use of pharmacologic sedation and analgesia for non-anesthesia healthcare providers.23 Supporting the above findings, a recently published study found that opiates and benzodiazepines were used in 92% of ICAs in North America, but in only 38% of such cases in other parts of the world.1 Consistent with the above, our study revealed a significant difference in the use of SCS medications between the 2 operators included in the present study, who are of different cultural backgrounds.
Our previous retrospective study revealed that playing patient-selected music significantly reduced rates and amounts of opiates and sedatives used during invasive cardiac catheterization.24 The current prospective, randomized study investigated the impact of music on pain and anxiety levels, as well as the use of pharmacologic conscious sedation during ICA. To our knowledge, this is the first study of its kind to investigate such a question. Our study had several important findings. First, there were no significant differences in the levels of pain and anxiety in the peri-ICA period between the SCS and Music groups. Second, the levels of the patients’ self-reported pain and anxiety during the peri-ICA period were very low in both the SCS and Music groups. Third, the use of SCS medication (midazolam) was significantly lower in the Music group vs the SCS group. Fourth, playing patient-selected music resulted in a trend toward decreased rates of SCS medication use (P=.06). Fifth, there was a significant difference in the usage of SCS medications between the 2 study ICA operators. Sixth, given the choice, many subjects in the SCS group elected not to receive opiates and sedatives before ICA.
The finding that music was as effective as SCS for pain and anxiety management may have multiple explanations. First, music can potentially mask or alleviate perception of pain and anxiety; multiple mechanistic hypotheses have been speculated for these potential beneficial effects. One common theory is that playing music detracts attention from the stressful event (in this case, ICA) and redirects it to a pleasant event (in this case, listening to patient-selected music).25,26 Multiple physiologic explanations have also been speculated, including potential effects of music on the autonomic and central nervous systems, leading to decreased adrenergic activity and increased levels of endorphins.27-29 Another possible reason for our study findings is that local anesthesia is not always administered appropriately; many operators do not allow adequate time for lidocaine or SCS medications to exert their effect. In addition, baseline pain and anxiety levels in general were low in our study subjects. It can also be argued that SCS patients in the current study did not receive enough SCS medications. However, consistent with our findings, 2 small, prospective studies investigating the role of opiates in reducing pain and anxiety during ICA or aortofemoral angiography failed to show any benefit.30,31
ICA is a high-volume procedure in the US (>1,000,000 cases/year)32 and around the world, and while the use of SCS medications is common during ICA, the need for SCS and safety or efficacy of such medications during ICA has not yet been addressed by the US, Canadian, or European cardiovascular societies.33,34
Study limitations. First, while randomized, this was a small study. Second, blinding was not performed and is difficult to accomplish because of the nature of the intervention. Third, no SCS placebo medications were administered. Fourth, vascular spasm is a well-known complication of ICA performed through radial approach. Our current project had a limited number of radial cases (10; 14%). While half of these subjects received no SCS medications and none experienced vascular spasm, our results may not be applicable to radial cases. Fifth, while 14 patients (19.4%) underwent ad hoc percutaneous interventional procedures, most had ICA only, and our conclusions cannot be generalized to other cardiac procedures. Sixth, our study involved only veterans and mostly men, and these results may not be generalizable to non-veterans or women. In addition, we did not observe any acute in-CCL complications attributable to music, but our study was not powered to evaluate such outcomes. Finally, as pain and anxiety are somewhat subjective, we felt having subjects involved in the assessment of their need for SCS medications was important. This postrandomization flexibility in the protocol led to significant crossover rates in both study arms and significantly reduced the difference in exposure rates between the 2 arms. However, this also allowed us to honor each patient’s wish for such medications regardless of music.
Significant obstacles exist to support the current standard practice of routine, planned, pre-ICA SCS strategy. These include: (1) lack of evidence for the need for such medications or desire from patients to routinely receive such medications before ICA; (2) lack of data-driven evidence for the safety and efficacy of opiates and benzodiazepines during ICA to reduce pain and anxiety; (3) the potential for acute and long-term harm from such medications; (4) lack of guidance from the national and international cardiovascular societies regarding the use of such medications during ICA; and (5) lack of this practice outside the US and North America.1
The above gaps and limitations, along with the potential utility of music and other non-pharmacologic interventions, represent potential opportunities to improve the future quality of ICA care, including the exploration of opportunities to minimize or eliminate unnecessary opiate and sedative use.
Acknowledgments. We would like to acknowledge Miss Michelle Treadwell for her help in submitting this manuscript.
From the 1Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California; 2University of California, Los Angeles, Los Angeles, California; 3Stony Brook University, Stony Brook, New York; 4Veteran Affairs Durham Healthcare System, Durham, North Carolina; 5Duke University, Durham, North Carolina; 6Yale University, New Haven, Connecticut.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript accepted April 1, 2020.
Address for correspondence: Ramin Ebrahimi, MD, Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, mail code 111E, Los Angeles, CA 90073. Email: Ebrahimi@ucla.edu
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