Dose ratio between morphine and hydromorphone in patients with cancer pain: a retrospective study

Abstract

Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid rotation is often necessary in the event of toxicity and/or inadequate analgesia. Equianalgesic reference tables based on single dose comparisons are possibly inadequate for patients on chronic treatment and developing tolerance. This retrospective study of opioid rotation involving M and HM sought to determine the equianalgesic dose ratio for 91 rotations in 74 consecutively evaluable cancer pain patients. Only rotations involving subcutaneous (s.c.-s.c.) and oral (p.o.-p.o.) routes were evaluated. There were 44 rotations from M-HM (34: s.c.-s.c., 10: p.o.-p.o.) and 47 rotations from HM-M (35: s.c.-s.c., 12: p.o.-p.o.). Expressing all ratios as M/HM, the median dose ratios (lower-upper quartiles) for s.c. and p.o. rotations were 4.92 (4.1-5.9) vs. 5.76 (4.9-5.8) for M-HM (P = 0.28, NS) and 4.0 (3.1-4.8) vs. 3.45 (2.8-4.2) for HM-M (P = 0.4, NS), respectively. Pain intensity, as measured on a visual analogue scale (VASP), showed no significant difference between mean values pre- and post-rotation. A unified overall median dose ratio of 4.29 (3.3-5.3, lower-upper quartiles) was calculated by expressing all of the HM-M dose ratios as M/HM and combining them with the dose ratios for all of the M-HM rotations. This suggests a potency ratio of approximately 4.3:1 between M and HM. When expressed as M/HM for dose ratio comparison, the median dose ratio for all HM-M rotations was 3.7 (2.9-4.5, lower-upper quartiles) vs. 5 (4.2-5.9) for M-HM rotations (P = 0.0001), suggesting that the opioid to which rotation is taking place is more potent than our proposed unified overall median dose ratio of 4.29:1 would predict. Our data suggests that HM is 5 times more potent than M when given second (M-HM), but is only 3.7 times more potent when given first (HM-M). We therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of 3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids. There was no correlation observed between M-HM and HM-M dose ratios and the level of previous opioid dose, in contrast to HM to methadone rotation where the dose ratio was higher in patients receiving higher doses of HM.

Toxicity and/or insufficient analgesia by opioid therapy: risk factors and the impact of changing the opioid. A retrospective analysis of 273 patients observed at a single center

“…In all trials, differences between the supposed and the actual equi-analgesic doses were great. The comparison of patients who required an opioid change (OCH) with those who did not suggested that the incidence of AE was dose dependent [12,25]. In most of the studies the equi-analgesic doses before and after opioid rotation differed substantially from those expected on the basis of single-dose trials and were obviously influenced by the sequence of opioids administered [5,18,25,39,40].…”

Switching from Methadone to a Different Opioid: What Is the Equianalgesic Dose Ratio?

“…The use of opioid consumption rather than analgesic reporting has been established as an alternate viable method of establishing equianalgesic dose ratios. 3,7,8 Multiple studies support the validity of the MEDD conversion ratios used in the methods section this study and in clinical practice.…”

“…7,8,[10][11][12][13][14][15][16][17][18][19] For patients receiving methadone and a second opioid prior to the switch, the MEDD of the second opioid was subtracted from the MEDD calculated for the day when stable dose was reached. The remainder was used to calculate the equianalgesic dose ratio with the previous methadone dose (Fig.…”

“…2,6 Many studies have addressed the equianalgesic dose ratios for switching between morphine and hydromorphone, morphine and oxycodone, and when switching from morphine to methadone. [7][8][9][10] Only two small studies report on rotations involving methadone in the opposite direction, that is when switching from methadone to an alternate opioid. 1,8 The direction of opioid rotation is important, as the conversion factors that result are not necessarily equivalent when switching the opioid in the opposite direction.…”

Acute pain management for opioid dependent patients

“…Side-effects can prevent continuing dose escalation in some cases. Much of the work on opioid rotation comes from palliative care requiring large doses of opioid analgesics to achieve satisfactory pain control [36][37][38][39]. It has been hypothesised that incomplete cross-tolerance enables the substitute opioid to achieve improved pain control at lower dosage, with fewer adverse effects, as a result of reduced levels of both the parent compound and any accumulation of toxic metabolites [36].…”