dextromethorphan and Pain--Intractable

Caring for patients with prolonged persistent pain remains one of nursing's greatest challenges. Increased knowledge and understanding of pain pathways, however, has enabled new treatments to be incorporated into pain management regimes. Of particular interest has been the association of the N-methyl-D-aspartate (NMDA) receptors with the development of hyperalgesia and 'wind-up'. This review will explore the physiological processes associated with these phenomena, and the use of NMDA receptor antagonists such as ketamine and dextromethorphan to prevent and treat persistent pain. The importance of nurses understanding the modes of action of these drugs will be illustrated through presentation of two case histories.

Topics: Anesthetics, Dissociative; Dextromethorphan; Drug Monitoring; Female; Humans; Ketamine; Male; Middle Aged; Pain, Intractable; Receptors, N-Methyl-D-Aspartate

This multicenter trial examined the efficacy and safety of dextromethorphan (DM) as an enhancer of analgesia and modulator of opioid tolerance in cancer patients with pain. Eligible patients were randomized to slow-release morphine plus DM or slow-release morphine plus placebo. The initial DM dose was 60 mg four times daily for seven days, with an increase to 120 mg four times daily, if tolerated, for another seven days. During the study, patients recorded medications and scores for pain, nausea, drowsiness, and insomnia. Sixty-five patients were randomized. Although average pain scores (12.6 vs. 15.8), number of breakthrough doses (9 vs. 11.3), and change in total morphine consumption (550.9 mg vs. 597.1mg) were less in the DM group than placebo group, the differences were not statistically significant (P=0.31-0.33). Side-effect scores were not statistically significantly different. Dizziness was greater in the DM (58%) than placebo (36%) group. This study showed a statistically nonsignificant enhancement of analgesia or modulation of opioid tolerance in cancer patients with pain when DM was added to morphine. Participants receiving the DM also had more toxicity, particularly dizziness. This toxicity and the limited evidence of effect do not support the use of DM to enhance opioid analgesia or to modulate opioid tolerance in cancer patients.

Topics: Aged; Analgesics, Opioid; Delayed-Action Preparations; Dextromethorphan; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain, Intractable; Terminal Care

Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation. Dextromethorphan (DM), a potent NMDA antagonist with a good safety profile, may be a promising agent for the treatment of persistent pain. An open-label randomized trial was designed to examine the effects of combining DM with NSAIDs, dextropropoxyphene, or morphine in cancer patients with pain. Patients who required a change in the step of the World Health Organization's (WHO) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were randomly allocated to receive DM 30 mg three times a day (30 patients) or conventional treatment (30 patients). There were 20 patients randomized for each step of the analgesic ladder. Pain mechanisms, pain intensity (numerical 0-10 scale), symptoms more frequently present in advanced cancer patients or associated with opioid therapy (graded on a 0-3 scale--not at all, slight, a lot, awful), opioid escalation index, days on opioid treatment, and adverse effects were recorded. After 2 days 75%, 80%, and 100% of patients treated with DM in steps 1, 2, and 3, respectively, required conventional treatment, because adequate pain relief had not been achieved (pain scale > 4). Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes. Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days, due to poor pain control. A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder. No significant analgesic effects could be found when DM at this dose was combined with NSAIDs, dextropropoxyphene, or morphine.

Topics: Analgesics, Opioid; Dextromethorphan; Dextropropoxyphene; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Female; Humans; Male; Middle Aged; Morphine; Neoplasms; Pain, Intractable; Palliative Care