Subcutaneous Morphine for Dyspnea in Cancer Patients

Methods

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

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.

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

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.