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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Is Open Access

      Heart rate variability during treatment of breakthrough pain in patients with advanced cancer: a pilot study

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          Abstract

          Background

          Decisions on the intensity of analgesic therapy and judgments regarding its efficacy are difficult at the end of life, when many patients are not fully conscious and pain is a very common symptom. In healthy individuals and in postoperative settings, nociception and subsequent pain relief have been shown to induce changes in the autonomic nervous system (ANS), which can be detected by measuring heart rate variability (HRV).

          Objectives

          The changes in the ANS were studied by measuring HRV during opioid therapy for cancer breakthrough pain (CBTP) in palliative-care patients with cancer and compared these changes with patient-reported pain levels on a numeric rating scale (NRS).

          Patients and methods

          The study included ten patients with advanced cancer and baseline opioid therapy. In each patient, a 24-hour peak-to-peak HRV measurement with a sampling rate of 4,000 Hz was performed. High frequency (HF), low frequency (LF), total power, pNN50 (indicating parasympathetic activity), and log LF/HF were obtained in two intervals prior to therapy and in four intervals thereafter. Intensity of CBTP was recorded using a patient-reported NRS prior to therapy and 30 minutes afterward.

          Results

          CBTP occurred in seven patients (three males and four females; mean age: 62 ± 5.2 years) and was treated with opioids. A highly significant positive correlation was found between opioid-induced reduction in patient-reported pain intensity based on NRS and changes in log LF/HF ( r > 0.700; p < 0.05). Log LF/HF decreased in patients who had a reduction in pain of >2 points on the NRS but remained unchanged in the other patients.

          Conclusion

          Our data suggest that log LF/HF may be a useful surrogate marker for alleviation of CBTP in patients with advanced cancer and might allow detection of pain without active contribution from patients.

          Most cited references22

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          Graphic representation of pain.

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            A comparison of pain rating scales by sampling from clinical trial data.

            The goals of this study were to examine agreement and estimate differences in sensitivity between pain assessment scales. Multiple simultaneous pain assessments by patients in acute pain after oral surgery were used to compare a four-category verbal rating scale (VRS-4) and an 11-point numeric rating scale (NRS-11) with a 100-mm visual analog scale (VAS). The sensitivity of the scales (i.e., their ability [power] to detect differences between treatments) was compared in a simulation model by sampling from true pairs of observations using varying treatment differences of predetermined size. There was considerable variability in VAS scores within each VRS-4 or NRS-11 category both between patients and for repeated measures from the same patient. Simulation experiments showed that the VAS was systematically more powerful than the VRS-4 in all simulations performed. The sensitivity of the VAS and NRS-11 was approximately equal. In this acute pain model, the VRS-4 was less sensitive than the VAS. The simulation results demonstrated similar sensitivity of the NRS-11 and VAS when comparing acute postoperative pain intensity. The choice between the VAS and NRS-11 can thus be based on subjective preferences.
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              Breakthrough pain: characteristics and impact in patients with cancer pain.

              Few surveys have been performed to define the characteristics and impact of breakthrough pain in the cancer population. In this cross-sectional survey of inpatients with cancer, patients responded to a structured interview (the Breakthrough Pain Questionnaire) designed to characterize breakthrough pain, and also completed measures of pain and mood (Memorial Pain Assessment Card (MPAC)), pain-related interference in function (Brief Pain Inventory (BPI)), depressed mood (Beck Depression Inventory (BDI)), and anxiety (Beck Anxiety Inventory (BAI)). Of 178 eligible patients, 164 (92.2%) met the criteria for controlled background pain. The median age was 50.6 years (range 26 to 77 years), 52% were men, and 80.6% were Caucasian. Tumor diagnoses were mixed, 75% had metastatic disease, 65% had pain caused directly by the neoplasm, and a majority had mixed nociceptive-neuropathic pain. The median Karnofsky Performance Status score was 60 (range 40 to 90). Eighty-four (51.2%) patients had experienced breakthrough pain during the previous day. The median number of episodes was six (range 1 to 60) and the median interval from onset to peak was 3 min (range 1 s to 30 min). Although almost two-thirds (61.7%) could identify precipitants (movement 20.4%; end-of-dose failure 13.2%), pain was unpredictable in a large majority (78.2%). Patients with breakthrough pain had more intense (P < 0.001) and more frequent (P < 0.01) background pain than patients without breakthrough pain. Breakthrough pain was also associated with greater pain-related functional impairment (difference in mean BPI. P < 0.001), worse mood (mood VAS, P < 0.05; BDI, P < 0.001), and more anxiety (BAI, P < 0.001). Multivariate analysis confirmed that breakthrough pain independently contributed to impaired functioning and psychological distress. These data confirm that cancer-related breakthrough pain is a prevalent and heterogeneous phenomenon. The presence of breakthrough pain is a marker of a generally more severe pain syndrome, and is associated with both pain-related functional impairment and psychological distress. The findings suggest the need for further studies of breakthrough pain and more effective therapeutic strategies.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2016
                12 December 2016
                : 9
                : 1215-1220
                Affiliations
                Clinical Division of Palliative Care, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
                Author notes
                Correspondence: Herbert Hans Watzke, Clinical Division of Palliative Care, Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Tel +43 1 40400 44550, Fax +43 1 40400 78600, Email herbert.watzke@ 123456meduniwien.ac.at
                Article
                jpr-9-1215
                10.2147/JPR.S120343
                5161332
                28003771
                b17d143e-5cdd-49ef-a30c-f4e3779825fd
                © 2016 Masel et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Anesthesiology & Pain management
                heart rate variability,cancer breakthrough pain,advanced cancer,palliative care

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