As-Needed Morphine: Yes, but at What Dose and at What Interval?

In response to a clinical case of a patient with severe pain requiring large doses of morphine, a question arose about the appropriate dose and schedule of as-needed (PRN) rescue morphine. After receiving varied local opinions, this question was investigated further by providing the following case scenario to several clinicians recognized for their expertise in pain management. Mrs Smith is an elderly woman with advanced, incurable cancer. She has recently been requiring large doses of morphine to control her pain. Her oral morphine dose for the last 2 weeks has been 1,000 mg of sustainedrelease morphine every 8 hours (a total of 3,000 mg/d). She has not had any undue toxicity from this dose. She is awake and alert and her constipation is controlled with appropriate laxatives. During the previous 2 weeks, she has developed exacerbated pain with an average daily pain score of 8 of 10. It is decided to admit her to the hospital and give her parenteral morphine to improve her pain control. For this exercise, assume that an appropriate evaluation was done, and no treatment other than narcotics is deemed necessary. After admitting her to the hospital, the attending physician calculates that she ought to have a 50% increase in her morphine equivalent dose. This equates to 4,500 mg/d of oral morphine. It is decided to translate this into an intravenous dose by dividing this by one third. This is calculated to be 1,500 mg/d of intravenous morphine. It is opted to administer this as a continuous intravenous morphine infusion of 60 mg/h. Because the physician is working with an experienced group of oncology nurses with hospice experience, and the physician plans to leave the hospital grounds (and will be available by pager for questions and emergencies, of course), she decides to order a PRN morphine dose for uncontrolled and/or breakthrough pain. She asks you for advice. The following two questions were asked of the experts: (1) What is the most appropriate intravenous bolus morphine PRN dose that should be given to this patient in the event that she still has severe pain (with a pain score of 7 to 8 of 10)? ___ mg. (2) At which intervals can this PRN morphine dose appropriately be repeated, assuming that the patient still has uncontrolled pain? ___ 10 minutes, ___ 15 minutes, ___ 30 minutes, ___ 60 minutes, ___ or other, please describe _____________________. The expert clinicians listed in Table 1 replied; their responses are listed in Table 2 Given the above-illustrated opinion conflicts, with a 10-fold variation in dose and a six-fold variation in timing interval, a search through published sources was conducted, mirroring a wide range of combinations regarding recommendations for both the PRN narcotic doses and the appropriate intervals at which they should be repeated in the event of continued pain. Data from 22 review articles and texts that review guidelines for the treatment of cancer pain, presented in Table 3, provided a 20-fold variation in recommended narcotic doses (1% to 20% of daily doses) along with scattered opinions, or no direction, regarding appropriate dose intervals for potential repeat doses. From the Department of Medicine and Department of Oncology, Mayo Clinic, Rochester, MN.