Factors influencing the prescribed dose of opioid analgesics in cancer patients

The dose of opioids prescribed for cancer pain does not always correlate with the actual pain severity. However, there is little evidence to explain this observation. In the present study, we sought to determine factors that influence the dose of opioid analgesics. A total of 227 patients who were administered opioids between August 2012 and May 2016 and later expired within the Department of Palliative Care at Ashiya Municipal Hospital were included, and the following variables were examined: age, sex, type of cancer, Verbal Rating Scale before and after the administration of the maximum prescribed dose of opioids, type of opioids and route of administration, blood test results, pain severity, and use of adjuvants. Data were analyzed using step-wise multiple linear regression. Median of the maximum prescribed dose of opioids, expressed in oral morphine equivalent, was 68.6, 60.0, and 39.2 mg for patients aged <65, 65-74, and ≥75 years, respectively. Step-wise multiple linear regression analysis further demonstrated that an increase in age by 1 year decreased the maximum prescribed dose of opioids by 0.98-fold (p = 0.006). Other factors that influenced the maximum prescribed dose of opioids included the use of analgesic adjuvants (1.91-fold, p = 0.001), oral administration (0.54-fold, p = 0.016), and elevated level of bilirubin (0.95-fold by 0.1 mg/dL increase, p = 0.013). Opioids examined in the study are metabolized in the liver by cytochromes P450 or by glucuronidation. Thus, if reduced drug metabolism causes the reduction in the maximum prescribed dose of opioids, liver function may contribute to this effect. Based on our findings that old age is associated with a lower prescribed dose of opioids, future studies should examine additional variables included in laboratory tests in more detail and measure hepatic blood flow to determine the cause of this association.