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BRIEF REPORT

Subcutaneous Morphine for Dyspnea in Cancer Patients

Eduardo Bruera; Tara MacEachern; Carla Ripamonti; and John Hanson

1 November 1993 | Volume 119 Issue 9 | Pages 906-907

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Dyspnea has been defined as an uncomfortable awareness of breathing [1]. It occurs in approximately 29% to 74% of patients with terminal cancer [2, 3] and is perceived as one of the most devastating symptoms by the patient and the family. Controlled single-dose trials have suggested that opioids are effective in the management of dyspnea associated with chronic obstructive lung disease [4]. However, opioids were poorly tolerated in these patients during repeated administration, mostly because of sedation and nausea [5]. These side effects usually disappear with the development of tolerance and are rarely a cause for discontinuing treatment among the approximately 80% of terminal cancer patients who receive opioids for pain [6]. However, the effects of opioids on the dyspnea of cancer have not been the focus of prospective studies.

A previous uncontrolled study by our group suggested that subcutaneous morphine was able to decrease the intensity of dyspnea without statistically modifying oxygen saturation, respiratory rate, or the end tidal PaCO₂^[7].

Methods

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The purpose of this study was to conduct a crossover, placebo-controlled trial to assess the effects of morphine on the intensity of dyspnea in 10 consecutive patients with terminal cancer. The mechanism of dyspnea was progressive lung tumor in 3 patients, lung metastases in 4 patients, pleural effusion in 1 patient, and carcinomatous lymphangitis in 1 patient, respectively. All patients were fully conscious, had normal cognitive status (score of 24 in the mini-mental state questionnaire) [8], were complaining of shortness of breath while in bed, and were receiving continuous oxygen using nasal prongs at a rate of 2 to 6 L/min. All patients received intermittent subcutaneous injections of morphine every 4 hours for the management of cancer pain. The morphine dose had not changed for at least 5 days, and all patients had good pain control (defined as no or mild pain most of the day and 2 extra analgesic doses/day). At 10:00 a.m. (time of their regular morphine dose) after at least 1 hour of bed rest, patients were randomized to receive subcutaneous injections of morphine or placebo. On the following day at 10:00 a.m. a crossover was made, and patients received the alternate treatment. Patients received an average dose of 34 ± 12 mg of morphine. This dose was calculated to be 50% higher than the regularly scheduled dose in order to overcome potential development of tolerance. Dyspnea was assessed using a visual analog scale (0, no shortness of breath; 100, worst shortness of breath). Pain was assessed at baseline using a visual analog scale (0, no pain; 100, worst pain).

Results

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Table 1 shows the results 30, 45, and 60 minutes after the injection of morphine or placebo. Baseline results were not different between day 1 and day 2. Improvement (P < 0.02) was seen in the intensity of dyspnea without any change in respiratory rate or oxygen saturation level measured by pulse oximetry.

View this table: [in this window] [in a new window]   Table 1. Effect of Morphine and Placebo on Dyspnea, Oxygen Saturation, and Respiratory Rate*

 

After the completion of the study, the patient and the investigator each blindly chose morphine as more effective for the patient's dyspnea in 9 and 8 patients, chose placebo in 0 and 1 patient, and had no preference in 1 patient and 1 patient, respectively (P = 0.01 for patients, P = 0.044 for investigators, binomial distribution). After studying the effects of morphine in these initial controlled patients, we used morphine intermittently for dyspnea in 45 consecutive patients with terminal cancer. In all patients, morphine was prescribed on an "as needed" basis. All patients were already receiving regular morphine for cancer pain. The dose used for dyspnea was the same as the regular dose used for pain. Patients received a total of 312 subcutaneous doses. Good subjective response ("no dyspnea" or "mild dyspnea") was documented by the nurse 30 minutes after the injection in 281 patients (90%), poor response was documented in 12 patients (4%) ("moderate" or "severe" dyspnea), and the response was not documented in 17 patients (5%). No patients had respiratory depression.

Discussion

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Our results suggest that intermittent injections of morphine are safe and effective for the management of dyspnea in terminal cancer. Because our patients also had cancer pain, it is possible that some patients might have perceived less dyspnea after morphine, because it decreased the intensity of pain. An unpleasant sensation (dyspnea) could also be heightened by the presence of another unpleasant sensation (pain). However, this probably did not occur, because all patients had stable pain control (visual analog scale 21 ± 27 on a 0-100 scale and had no change in morphine dose for 5 days). Future studies should determine the ideal dosage and modality of administration (as needed compared with regular dosing) of morphine, the relation between morphine's effect on pain and the effect on dyspnea, and the safety on the approximately 20% of terminal cancer patients who are not receiving opioids.

3. Billings JA. Dyspnea, cough and other respiratory symptoms. In: Billings JA, ed. Outpatient Management of Advanced Cancer. Philadelphia: J.B. Lippincott; 1985:83.

7. Bruera E, Macmillan K, Pither J, MacDonald RN. Effects of morphine on the dyspnea of terminal cancer patients. J Pain Symptom Manage. 1990; 5(6):341-4.

Author and Article Information

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From Edmonton General Hospital, Edmonton, Alberta, Canada, Cross Cancer Institute, Edmonton, Alberta, Canada, and National Cancer Institute, Milano, Italy.
Requests for Reprints: Eduardo Bruera, MD, Edmonton General Hospital, Palliative Care Program, Room 9Y39, 11111 Jasper Avenue, Edmonton, Alberta, T5K 0L4, Canada.

References

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1. Wasserman K, Casaburi R. Dyspnea: physiological and pathophysiological mechanisms. Annu Rev Med. 1988; 39:503-15.

2. Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest. 1986; 89:234-6.

4. Woodcock AA, Gross ER, Gellert A, Shah S, Johnson M, Geddes DM. Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med. 1981; 305:1611-6.

5. Woodcock A, Gross E, Gellery A. A comparison of diazepam and promethazine in the treatment of breathlessness in patients with chronic obstructive lung disease. Br Med J. 1982; 1:96.

6. Foley KM. The treatment of cancer pain. N Engl J Med. 1985; 313: 84-95.

8. Folstein MF, Fetting JH, Lobo A, Niaz U, Capozzoli KD. Cognitive assessment of cancer patients. Cancer. 1984; 53(10 Suppl):2250-7.

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