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

Sara Campagna,Simona Sannuto,Fabio Acquafredda,Antonella Milo,Silvia Gonella,Marco Tampellini,Riccardo Sperlinga,Andrea Saini,Giorgio Scagliotti,Alfredo Berruti

doi:10.3390/cancers11010018

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.

Highlights

IntroductionAs “a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain” [2]
Breakthrough pain (BTP) is defined as “transitory exacerbations of pain that occur on a background of stable pain otherwise adequately controlled by around-the-clock opioid therapy” [1]or as “a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain” [2]
A recent review of the most relevant national and international guidelines identified some differences in terms of the definition, diagnostic criteria, and treatment of breakthrough pain (BTP): generic cancer pain guidelines continue to support the use of oral opioids as an analgesic rescue therapy, while specific BTP guidelines promote transmucosal opioids for this purpose [7]

Summary

Introduction

As “a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain” [2]. The clinical characteristics of BTP may change significantly among patients, typically BTP has a rapid onset (median interval to peak pain of 3 min), short duration (average of 30 to 60 min), high frequency A recent review of the most relevant national and international guidelines identified some differences in terms of the definition, diagnostic criteria, and treatment of BTP: generic cancer pain guidelines continue to support the use of oral opioids as an analgesic rescue therapy, while specific BTP guidelines promote transmucosal opioids for this purpose [7]. BTP highly impacts healthcare system expenditure, leading to more frequent medical visits and hospital admissions, and longer hospitalizations [9]

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