PAIN CONSULT: PROBLEMS WITH MEPERIDINE

Abstract

w, Few nurses would be surprised to hear that injectable meperidine (IM Demerol) is the most frequently prescribed and administered analgesic for the short-term relief of moderate to severe pain. Like other narcotics', its side effects are respiratory depression, sedation, and hypotension. It is also well known that prolonged use of IM meperidine almost invariably results in severe fibrosis of muscle tissue that may cause permanent damage to muscles and nerves. Now, however, there is increasing evidence that there is another problem with meperidine-central nervous system excitatory effects. One study reported last year that one of the drug's metabolites-normeperidine-may cause nervous system effects ranging from shakiness to grand mal seizures(1). Another study indicated a relationship between meperidine and mood change. The first study investigated the relationship between plasma levels of meperidine and normeperidine and signs and symptoms of CNS excitation. Sixtyseven patients (42 men, 23 women, 2 children, age range 6-78) who were receiving meperidine either for acute postoperative pain (48 patients) or for the chronic pain of advanced cancer (19 patients) were studied. The number of days on meperidine ranged from 1 to 30, and the total daily doses ranged from 75 mg to 1,100 mg. Responses were categorized as followed: 1. asymptomatic-19 patients 2. shaky feelings-20 patients 3. tremors or twitches-18 patients 4. multifocal myoclonus or grand mal seizures-10 patients Patients with symptoms of CNS excitation had received meperidine for a longer period and at a higher dose than those who were asymptomatic. Symptomatic patients also had higher normeperidine plasma levels and a higher ratio of normeperidine to meperidine in plasma than the asymptomatic patients. The levels of meperidine in plasma did not differ among the four groups. It was concluded that the intensity of CNS excitation was associated with the accumulation of normeperidine in plasma. Although renal dysfunction was identified as one cause of normeperidine accumulation, five of the patients with the more severe toxic effects of multifocal myoclonus or seizures showed no dysfunction. Suggested treatment of normeperidine toxicity: 1. Stop meperidine immediately. 2. Substitute another narcotic, specifically morphine, for analgesia. 3. Use diazepam or another anticonvulsant if seizures occur. 4. Do not try to treat normeperidine toxicity with naloxone (Narcan). Naloxone antagonizes meperidine, but not normeperidine. In fact, naloxone may further excite the CNS, possibly precipitating a seizure(2). The second study used a sample of postoperative patients, 47 of whom received meperidine as their routine analgesic and 29 of whom received other narcotic analgesics(1). These patients were assessed for changes in mood from Day One to Day Two of the study. Patients were asked to estimate their moods using 15 contrast phrase pairs such as "cheerful/ got the blues" or "very uneasy/very much at ease." Among the 47 patients receiving meperidine, significant changes in mood occurred from Day One to Day Two. In particular, the meperidine patients tended to describe themselves as angry, "blue," sad, pessimistic, apprehensive, restless, and shaky. On the other hand, among the 29 patients receiving other narcotic analgesics, there were no statistically significant changes in mood scores, and there was some tendency toward a more positive mood. Thus routine postoperative use of meperidine appears to be associated with mild negative mood changes. The implications of these two studies are fairly clear. We should reevaluate the routine use of meperidine. While the use of meperidine for a few days to relieve moderate to severe postoperative pain may pose only mild problems of negative mood change and toxicity, the prolonged administration of increasing doses of meperidine is more likely to pose a real threat to patient safety in terms of toxic effects from the accumulation of the CNS stimulant normeperidine. Use of meperidine in patients with renal dysfunction is probably very unwise, since these patients seem especially likely to accumulate normeperidine.