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. 2018 Dec 24;11(1):18.
doi: 10.3390/cancers11010018.

The Circadian Rhythm of Breakthrough Pain Episodes in Terminally-ill Cancer Patients

Sara Campagna  1 , Riccardo Sperlinga  2 , Antonella Milo  3 , Simona Sannuto  4 , Fabio Acquafredda  5 , Andrea Saini  6 , Silvia Gonella  7 , Alfredo Berruti  8 , Giorgio Vittorio Scagliotti  9 , Marco Tampellini  10
Affiliations

The Circadian Rhythm of Breakthrough Pain Episodes in Terminally-ill Cancer Patients

Sara Campagna et al. Cancers (Basel). .

Abstract

Opioid therapy must be adjusted to the rhythm of a cancer patient's pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients. Consecutive adult cancer patients at their EOL treated with long-acting major opioids to control background pain (Numeric Rating Scale ≤ 3/10) were recruited from two Italian palliative care services. Using a personal diary, patients recorded the frequency and onset of BTP episodes and the analgesic rescue therapy taken for each episode over a 7-day period. Rhythms identified in BTP episodes were validated by Cosinor analysis. Overall, 101 patients were enrolled; nine died during the study period. A total of 665 BTP episodes were recorded (average of 7.2 episodes, mean square error 0.8) per patient, with 80.6% of episodes recorded between 8:00 a.m. and 12:00 a.m. At Cosinor analysis, a circadian rhythm of BTP episodes was observed, with a Midline Estimating Statistics of the Rhythm (MESOR) of 1.5, a double amplitude of 1.8, and an acrophase at 12:30 p.m. (p < 0.001). Oral morphine was the most frequent analgesic rescue therapy employed. In terminally-ill cancer patients, BTP episodes follow a circadian rhythm; thus, tailoring the timing of opioid administration to this rhythm may prevent such episodes. This circadian rhythm of BTP episodes in terminally-ill cancer patients should be confirmed in larger samples.

Keywords: analgesics; breakthrough pain; circadian rhythm; neoplasms; palliative care; quality of life.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total number of self-reported breakthrough pain episodes stratified by time frame.
Figure 2
Figure 2
Pattern of breakthrough pain episodes. Note. All patients, solid line (MESOR 1.5; amplitude 0.9; acrophase at 12:30 p.m.; p < 0.001); patients with bone metastases (dashed line; MESOR 1.5; amplitude 1.1; acrophase at 12:15 p.m.; p < 0.001); patients with ECOG ≥ 3 (dotted line; MESOR 1.4; amplitude 0.6; acrophase at 1:00 p.m.; p < 0.01). Abbreviations: MESOR, Midline Estimating Statistics of the Rhythm; ECOG, Eastern Cooperative Oncology Group.
Figure 3
Figure 3
Quality of life scores according to the total number of breakthrough pain episodes (p < 0.001); Note. The number of patients belonging to each subgroup is reported on the top of the respective column; Abbreviations. BTP, breakthrough pain; SEM, mean square error, POS, Palliative Outcome Scale.
See this image and copyright information in PMC

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