Meperidine (Demerol) was the first phenylpiperidine analgesic to come onto the market in the United States. Through the years it has been used extensively as a narcotic analgesic as well as a favored drug for sickle-cell crises, shaking chills, and various surgical uses. However, in more recent years, a growing number of clinicians are recognizing that the benefits of meperidine probably do not justify the risks.

Meperidine has disadvantages compared to other narcotics, even when given as monotherapy. It will provide adequate analgesia for the surgical patient on initial dosing, but the risk-benefit ratio then shifts somewhat. Meperidine has a half-life of only 3 to 5 hours. The primary metabolite, normeperidine, has a half-life of 15 to 20 hours, but it is only half as effective an analgesic as meperidine. A significant problem is that normeperidine has neuroexcitatory properties. So, when meperidine is given in repeated doses, which is often required given the relatively short-lived nature of its analgesic effect (for postoperative pain), there is a tendency for patients to experience irritability, tremors, muscle twitching, and new-onset seizures. Normeperidine toxicity can even prove fatal, especially in individuals with hepatic and/or renal impairment, because of their greater susceptibility to normeperidine accumulation.

Other problematic issues with the use of meperidine involve the likelihood of troublesome drug-drug interactions (DDIs). The first set of DDI concerns that must be considered by the anesthesia provider are pharmacodynamic in nature. As a serotonergically active agent, meperidine can act synergistically with other serotonergic drugs (such as fluoxetine, paroxetine, sertraline, and other selective serotonin reuptake inhibitors) or with monoamine oxidase inhibitors (phenelzine, tranylcypromine, selegiline, and linezolid) to produce a potentially lethal central serotonin syndrome (Table 61.1). This was the primary cause of the death of Libby Zion in the 1984 case that generated national attention for a number of years. She visited a New York emergency department and received meperidine for her shaking chills, even though she was known to be taking phenelzine. She developed a fever of 107.6°F in the course of her serotonin syndrome and eventually expired. Her death then became a rallying point around the issue of house staff work hours, as it was suspected that the resident who ordered the meperidine would have known better had he been better rested.