Meperidine‐associated myoclonus and seizures in long‐term hemodialysis patients

Abstract

Kaiko and colleagues [l] are to be congratulated on their clinical investigation of the neuroexcitatory effects of meperidine in cancer patients. Unfortunately, the neurotoxicity associated with this drug is not well appreciated in the medical community, as is illustrated by the following cases of neurotoxicity in two patients with chronic renal failure who were on hemodialysis. To my knowledge, only a single renal failure patient with such neurotoxiciry has been previously reported [2].A 61-year-old man had a history of recurring grand ma1 seizures for one year despite therapeutic blood levels of phenytoin sodium and phenobarbital; he also experienced light-sensitive, movement-precipitated multifocal myoclonus for several years, which was refractory to 2 mg of clonazepam. This patient had become addicted to oral meperidine, initially prescribed because of pain associated with Pager's disease. It became apparent that seizures and myoclonus would occur when the patient increased his dosage of meperidine to fifty to sixty, and sometimes as many as one hundred, 100-mg tablets per week. Meperidine was withdrawn and the anticonvulsants were stopped. In the two subsequent years, neither seizures nor myoclonus have recurred.A 58-year-old woman with severe abdominal pain was also seen in 1981. The patient had received a total of 1,875 mg of rneperidine within one week prior to the occurrence of a single grand ma1 seizure, which had been preceded by an increasing frequency of myoclonic jerks over several days. The electroencephalogram, computed tomographic scan of the brain, and magnesium level were normal. Meperidine was discontinued. No further seizures occurred, even after phenytoin sodium was stopped. Myoclonus gradually disappeared over several days.In patients with chronic renal failure, Kaiko and colleagues [l] point up the possible dilemma of distinguishing between multifocal myoclonus and seizures that are secondary to uremia and those that result from meperidine administration. In these two patients with chronic renal failure, differential diagnosis was not difficult. The myoclonus of both patients was painful, induced by movement of the extremities, and also (in the first case) stimulus-sensitive to bright light directed at the eyes. In contrast, the myoclonus in uremics, while also multifocal, occurs spontaneously at rest and is usually painless. Furthermore, both patients with chronic renal failure were alert and oriented during myoclonic periods, unlike patients with myoclonus secondary to uremia, who are usually obtunded or stuporous, and unlike the eight cancer patients with rnyoclonus, whose mental status was described by Kaiko and colleagues as "agitated delirium" 111.Grand ma1 seizures in both of the patients with chronic renal failure could not be distinguished from uremic convulsions. The association of the seizures with the distinctive myoclonus described here should suggest the correct diagnosis.Caution should be exercised in giving meperidine at frequent intervals for several days, because of the...

Long lasting respiratory depression induced by morphine‐6‐glucuronide?

“…A prerequisite is, however, that polar metabolites of such drugs are pharmacologically inactive since they will tend to accumulate in uraemia. An example is pethidine whose metabolite norpethidine is slowly eliminated in uraemic patients and which is probably responsible for convulsions sometimes seen in this group of patients (Szeto et al, 1977;Hochman, 1983).…”

Pro-and Anticonvulsant Effects of Anesthetics (Part I)

“…The risk of precipitating convulsions is theoretically greater with chronic oral administration because it produces lower meperidine and higher normeperidine blood levels due to extensive firstpass metabolism (102). However, seizures have occurred after both chronic oral (99,103) and intramuscular (100,104) administration. Myoclonus generally precedes the seizures, and both resolve over several days with discontinuation of meperidine administration (101,103).…”

“…However, seizures have occurred after both chronic oral (99,103) and intramuscular (100,104) administration. Myoclonus generally precedes the seizures, and both resolve over several days with discontinuation of meperidine administration (101,103).…”

Seizures and Meperidine: Overstated and Underutilized

“…Ten of the 50 reported patients (20%) had renal impairment, and 3/50 patients (6%) had liver impairment. Other confounding conditions included alcohol abuse (Danziger et al, 1994;Marinella, 1997), infection (Rodman and Maxwell, 1994;Knight et al, 2000;Hubbard and Wolfe, 2003;Eker et al, 2009), prior seizure history (Hochman, 1983;Stone et al, 1993), sickle cell disease (Pryle et al, 1992;Hagmeyer et al, 1993;Liu et al, 1994;Rodman and Maxwell, 1994;Nadvi et al, 1999;Dunwoody et al, 2006), and malignancy (Szeto et al, 1977;Kaiko et al, 1983;Armstrong and Bersten, 1986). One patient had Alzheimer's disease (Nagler et al, 2008), one had hereditary coproporphyria (Deeg and Rajamani, 1990), and one had severe burns and hyponatremia (Kyff and Rice, 1990).…”

“…Nevertheless, we found that clinical evidence relating meperidine use to seizures is scant overall, emphasizing the weakness of this association. Literature reports of seizures due to meperidine are confounded by use of other medications with potentially epileptogenic potential (Rodman and Maxwell, 1994), malignancy (Szeto et al, 1977;Kaiko et al, 1983;Armstrong and Bersten, 1986), renal impairment (Kaiko et al, 1983;Adair and Gilmore, 1994), prior seizures (Hochman, 1983), and sickling diseases (Pryle et al, 1992;Hagmeyer et al, 1993;Liu et al, 1994;Rodman and Maxwell, 1994;Nadvi et al, 1999;Dunwoody et al, 2006). The cases we reviewed included a significant number of pediatric patients (12/50 patients; age range 15 days to 17 years) in whom the metabolism and elimination of meperidine are lower (Pokela et al, 1992).…”