Introduction   Opioid infusions, either intravenous (IV) or subcutaneous (SQ – see Fast Fact #28), can provide smooth and efficient control of distressing pain or dyspnea in the imminently dying patient. Opioids correctly titrated to provide symptom relief will not cause respiratory depression (see Fast Fact #8). It is common for clinicians to order an opioid infusion in the dying patient as follows: Start morphine infusion at 1 mg/hr, titrate to affect. This type of order is pharmacologically unsound and unsafe. Health care institutions (e.g., hospitals, hospice facilities) should adopt clinical practice guidelines that meet current national standards. The following is a step-by-step approach to rational opioid infusion prescribing in the dying patient and is most appropriate for morphine or hydromorphone infusions; a future Fast Fact will discuss the use of methadone.

First, before starting an opioid infusion, calculate a total daily dose of the currently use opioids. Then convert this to reasonable conversion dose of the new opioid. Then convert this to a basal or hourly infusion rate.

Example: a patient on oral extended-release morphine 60 mg q12, now unable to swallow. 60 mg q 12 = 120 mg/24 hours PO morphine = 48 mg IV morphine/24 hours (utilizing a 2.5:1 ratio as recommended in references #7&8) = approximately 2 mg/hr IV infusion basal rate).

Second, if the current opioid dose is not effective, dose escalate the basal dose by 25-100% (see Fast Fact #20).

Third, keep in mind, opioid infusions can take many hours to reach their steady state dose. So if the patient is very uncomfortable, give a loading as needed dose when starting the infusion.

Example: for a 1 mg/hr basal rate, give 2-5 mg loading dose (see reference 4).

Fourth, choose a bolus dose (i.e. ‘rescue’ or ‘PCA’ dose if a patient-controlled analgesia system is being used). This can be a nurse-initiated bolus dose when using a standard IV infuser, or a patient, nurse or family-initiative bolus using a PCA device. Even though the dying patient may be unable to press the button, the nurse or family members can use the PCA device, depending on local hospital policy. Based on patterns of breakthrough pain, a bolus dose of 50% – 150% of the hourly rate is a place to start. For example, for a morphine infusion of 2 mg/hr, choose a starting bolus dose of 1-3 mg.

Fifth, choose a dosing interval. The peak analgesic effect from an IV bolus dose is about 20 minutes. Thus, the dosing interval (i.e. ‘lockout interval’ for a PCA device) should be in the range of 20 minutes. In some cases, clinicians may choose a longer interval (e.g., 60 minutes) in a PCA system due to pre-programmed limits in the theoretical amount of volume that can be administered in an hour.

Sixth, reassess for desired effect vs. side effects every 10-15 minutes until stable. Adjust bolus dose size every 30-60 minutes until desired effect is achieved. The ‘right’ bolus dose is one which controls undesirable symptoms with acceptable toxicities.

Seventh, reassess the need for a change in the basal rate no more frequently than every 8 hours. Use the number of administered bolus doses as a rough guide when calculating a new basal rate; never, however, increase the basal rate by more than 100% at any one time. When increasing the basal rate, consider a loading dose to achieve steady-state blood levels more rapidly.

Common sense cautions   The above guidelines should be thought of as a rough guide; differences in age, renal and pulmonary function and past responses to opioids must be considered when developing an appropriate analgesic treatment plan. When patients become anuric close to death, continuous dosing may be discontinued in favor of bolus dosing to prevent metabolite accumulation, myoclonus, allodynia, and agitated delirium.

References

1. Caraceni A, Hanks G, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. The Lancet Oncology 2012; 13: e58-e68.
2. Report of a WHO Expert Committee. Cancer pain relief and palliative care. World Health Organ Tech Rep Ser. 1990; 804:1-75.
3. Levy M. Pharmacologic treatment of cancer pain. N Engl J Med. 1996; 335:1124-32.
4. Management of cancer pain: adults. Clin Pract Guideline Quick Ref Guide Clin. 1994:1-29. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7509686?dopt=Abstract.
5. Portenoy RK. Continuous Infusion of Opioid Drugs in the Treatment of Cancer: Guidelines for Use. J Pain Symptom Manage. 1986; 1:223-228.
6. Reddy A, Vidal M, Stephen S, et al. The conversion ratio from intravenous hydromorphone to oral opioids in cancer patients. J Pain Symptom Manage 2017; 54(3):280-288.
7. McPherson ML. Demystifying opioid conversion calculations: a guide for effective dosing. 2nd ed. Bethesda:ASHP; ©2018.

Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published September 2006; 3rd Edition May 2015; 4th Edition in September 2024.
Conflicts of Interest: None to report