Small repeated boluses are unreliable to provide rapid analgesia with intravenous morphine titration and mislead conversion ratio to oral morphine
Authors: S. Mercadente
Journal: Annals of Oncology (2018)

Dear Editor, In a comprehensive ESMO recommendations on the management of cancer pain [1.Fallon M. Giusti R. Aielli F. et al.Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines.Ann Oncol. 2018; 29: iv166-iv191Abstract Full Text Full Text PDF PubMed Scopus (311) Google Scholar], authors suggest the use of an intravenous (i.v.) opioid titration for patients with severe pain. They quoted a paper in which increments of i.v. morphine were given as 1.5 mg boluses every 10 min [2.Harris J.T. Suresh Kumar K. Rajagopal MR. Intravenous morphine for rapid control of severe cancer pain.Palliat Med. 2003; 17: 248-256Crossref PubMed Scopus (63) Google Scholar], without reporting the level of initial pain intensity and considering a generic satisfactory pain relief as the main outcome. Indeed, patients who had a poor response to opioids and those who were already on strong opioids were excluded. Thus, only patients with minor opioid requirements were included. This approach was proportional to the magnitude of the problem, taking into account that patients were included with even moderate levels of pain intensity (≥5), that is not exactly what a patient experiences with severe pain, commonly considered ≥7. It is also surprising that a ratio of 1:1 was used for converting morphine to the oral route. In these recommendations, authors correctly recommend that the relative potency ratio of oral to i.v. morphine in patients receiving chronic treatment of cancer pain should be 3:1, contradicting the findings reported with such a modality of titration. A better knowledge of morphine pharmacokinetics and clinical experience may be useful in addressing the most appropriate strategy. The use of small repeated boluses at intervals may confuse the real needs, in relation to the calculation of the i.v.–oral conversion ratio, producing a series of overlapping curves providing poor effective drug concentration (Figure 1). For example, while a morphine dose of 20 mg administered within 10 min, produces a rapid effect from which clinical judgment can be derived, the same dose administered to spaced small boluses is unable to achieve an effective blood concentration. From the previously reported series, the maximum dose of 34.5 mg corresponds to 23 boluses of 1.5 mg repeated every 10 min, i.e. 215 min. During this phase, most of the morphine administered with the first boluses will have been eliminated, and the effective dose will be difficult to calculate. This observation explains the subsequent misleading conversion ratio of 1:1. Intravenous titration is indicated only for patients experiencing excruciating pain, receiving opioids at different doses, unsuccessfully, as this group of patients requires a more intensive approach, commensurate with the circumstances of severe distress. Boluses proportional to the previous level of tolerance, administered in a short time, are safe and effective, and allow a better calculation of the subsequent needs [3.Mercadante S. Villari P. Ferrera P. et al.Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion.Cancer. 2002; 95: 203-208Crossref PubMed Scopus (67) Google Scholar]. None declared.