Article of the Month

2012; Volume 13, No 9, September

Article of the Month

Efficacy of opioid rotation to continuous parenteral hydromorphone in advanced cancer patients failing on other opioids

Oldenmenger WH, Lieverse PJ, Janssen PJJM, Taal W, van der Rijt CCR, Jager A.
Supportive Care Cancer 2012; 20: 1639-47

The authors report a retrospective study on 104 consecutive advanced cancer patients who were extensively pre-treated with one or more opioids with inadequate nociceptive pain control (pain intensity > 4 on a 0-10 numerical scale) or intolerable (moderate to severe) side effects who were then rotated to parenteral hydromorphone. After starting parenteral administration of hydromorphone, the pain intensity at rest and upon movement, and any side effects were recorded twice each day. The moment that adequate pain control was reached was defined as the first day of at least 2 consecutive days with a reported mean pain score of 4 or less.

The main reasons for rotation to parenteral hydromorphone were inadequate pain control combined with/without expected delivery problems due to high opioid dosages and intolerable side effects with persistent pain.

Before starting parenteral hydromorphone, 18% of the patients used morphine, and 76% used fentanyl; 88% had been treated with two or more opioid rotations with various drugs. Before switching to intravenous (13 patients) or subcutaneous hydromorphone (91 patients), the median oral morphine equivalent daily dose was 600 mg/day (range 72 - 2,592 mg/day). The median oral dose of hydromorphone at start was 48 mg/day (range 5-216). Adequate pain control was achieved in 5 days in 83% of the patients and their mean pain intensity at rest decreased from 5.4 to 2.4 (p<0.001) whereas pain on movement decreased from 7.4 to 3.8 (p<0.001). Eight of 86 patients still had side effects. Among the 86 patients who achieved adequate pain control on parenteral hydromorphone, only 17% rotated to oral or transdermal opioids, 11 patients rotated to spinal analgesia and 1 received a nerve block.

Why I chose this article

Opioid rotation is the process of switching from one opioid to another opioid when side effects, and/or analgesic ineffectiveness or tolerance develops. By means of the sequential administration of different opioids, it is possible to act on different subtypes of opioid receptors, thus improving the symptoms and reducing tolerance. Patients who have poor analgesic efficacy or tolerability with one opioid can frequently tolerate another opioid well, although the mechanisms that underlie this variability to different opioids are not known. Different explanations on the role of opioid switching have been proposed, such as genetic makeup, tolerance to different opioid effects, the incomplete cross-tolerance among opioids selective for the same receptor subtype due to differential affinity for receptor subtypes, the differences in profile of active metabolites between various opioids and the pain mechanism. The ideal alternative opioid has not been characterized. However high potency parenteral opioids administered intravenously or subcutaneously are indicated for rapid titration in case of severe pain where oral route might not be indicated and/or for patients who need rapid dose escalation. Hydromorphone is an analogue of morphine with similar pharmacokinetic and pharmacodynamic properties, but about 5 times more potent. Parenteral hydromorphone may be a valid solution when a switch of the opioid is indicated.

Reviewed by Dr. Carla Ripamonti (Italy).
Dr. Ripamonti is a life time adviser to the IAHPC Board and her bio may be viewed here.

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