Circadian variation of pain as a measure of the analgesia requirements during the first 24-postoperative hours in patients using an opioid Patient Controlled Analgesia delivery system

Abstract

Circadian rhythms have governed the everyday life of every single organism that has lived on Earth. The present study addresses the rhythms of cortisol and melatonin, their analgesic properties and the potential circadian rhythm of pain as a driver of the frequency of self-administered analgesia in postoperative patients with an opioid Patient Controlled Analgesia (PCA) delivery system. It aims to determine if acute 24-hour post-operative pain displays a circadian variation by analysing the number of times that patients self-administered morphine for pain relief and incidentally to determine if gender has any association with the frequency of self-administered analgesia. For that purpose, the frequencies of self-administered analgesia were divided into four periods of six hours each (three of them approximately corresponded to the day, and 1 to the night). A Multi-level Poisson regression analysis compared frequencies during period 4 (night) to all others (1, 2 and 3). The results show that there was a statistically significant difference between the frequencies of self-administered opioids in the night period compared to any other day period (p-value of <0.001, for periods 1, 2 and 3 respectively compared to period 4). Differences in terms of gender were also statistically significant (p < 0.001) with men’s opioid consumption almost double that of women’s but with much steeper rate of decline (p<0.001). These results may be partly explained by the rhythms of melatonin, cortisol and ß-endorphine, morphine’s chronopharmacology and possibly by oestrogen and progesterone.