Reply to the letter to the editor ‘Small repeated boluses are unreliable to provide rapid analgesia with intravenous morphine titration and mislead conversion ratio to oral morphine’ by Mercadante S.
Authors: M. Fallon, C.I. Ripamonti
Journal: Annals of Oncology (2018)

Dear Editor, We would like to thank Dr Sebastiano Mercadante [1.Mercadante S. Small repeated boluses are unreliable to provide rapid analgesia with intravenous morphine titration and mislead conversion ratio to oral morphine.Ann Oncol. 2018; 29: 2147-2148Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar] for his thoughtful comments regarding our recent Annals of Oncology article about the latest ESMO recommendations on the management of cancer pain [2.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 (310) Google Scholar]. We also recognize the best expertise on the management of rapid i.v. opioid titration as reported in several published papers. In the latest ESMO guidelines, we suggested i.v. morphine administration for rapid opioid titration in cases of severe pain according to previous reported randomized controlled study from Harris et al. [3.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] in which patients with moderate or severe pain (NRS ≥ 5) were randomized to 1.5 mg i.v. bolus doses of morphine every 10 min versus oral morphine 5 mg doses (if opioid-naive) or 10 mg (if already on weak opioid) four-hourly. In the same study, the ratio of initial i.v. morphine dose to the regular four-hourly oral morphine dose after 2 days varied between 1 : 0.5 and 1 : 3.3, and the median ratio was 1 : 0.95 (mean/1 : 1.16). These results can explain the suggested conversion ratio from i.v. to oral route. To our knowledge, this study represents the only randomized controlled trial on this topic with good level of evidence (II—small randomized trial) and grade of recommendation (B—moderate evidence for efficacy but with a limited clinical benefit, generally recommended) according to the ESMO Guidelines Committee. Clinical experience reported by Mercadante et al. [4.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] demonstrates a better knowledge of morphine pharmacokinetics and clinical approach for rapid morphine titration in several cancer pain emergencies reported as NRS ≥ 7. According to the author, several differences in the definition of cancer pain emergency have been reported in the literature and data are not clear [5.Kumar K.S. Rajagopal M.R. Naseema AM. Intravenous morphine for emergency treatment of cancer pain.Palliat Med. 2000; 14: 183-188Crossref PubMed Scopus (29) Google Scholar]. Despite the low level of evidence for this recommendation (a single center prospective observational study, without control group), we agree that the practice of i.v. morphine titration with 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. This also represents an important clinical research question to empower nonpain and palliative care specialists to practice this approach with confidence. None declared.