Low Frequency of Meperidine-Associated Seizures in Sickle Cell Disease

Abstract

Pain control measures in sickle cell diseases are not uniform. Most clinicians use parenteral morphine or meperidine for severe pain. Reports of seizures associated with meperidine have led to a growing reliance on intravenous morphine, usually with patient-controlled devices. Acceptance of morphine has been poor among patients, and many prefer meperidine. The aim of this retrospective study was to determine the incidence of meperidine-associated seizures in a large, mostly pediatric population with sickling disorders. The results suggest that the incidence of seizures with meperidine is extremely small (0.4% of patients; 0.06% of admissions). The risk of seizures should not dissuade clinicians from using this drug.

Current Issues in Sickle Cell Pain and Its Management

“…Meperidine is associated with seizures in 1% to 12% of patients with SCD. 34,35 A recent retrospective study of hospitalized children reported a very low rate of seizures in sickle cell patients receiving meperidine, which was comparable with that observed in patients receiving morphine. 36 There is a subset of adult patients with SCD for whom meperidine is the only opioid that gives them relief without serious side effects.…”

Seizures and Meperidine: Overstated and Underutilized

“…Of these, 12 patients were below the age of 18. The majority of these seizures were published in case report form; one study was a prospective study of meperidine and normeperidine levels in 14 sickle cell crisis patients (Pryle et al, 1992), one was a cohort study of 14 patients with either renal failure or cancer comparing meperidine and normeperidine levels in those groups (Szeto et al, 1977), one was a chart review of patients at a single institution at high risk for drug toxicity (Seifert and Kennedy, 2004), one a retrospective study of 67 cancer patients examining excitatory effects of meperidine and their association between meperidine/normeperidine levels (Kaiko et al, 1983), and one a retrospective review of meperidineassociated seizures in a large population of pediatric sickle cell patients (Nadvi et al, 1999).…”

“…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).…”

“…In a study of 550 pediatric patients with sickle cell disease [which itself has been shown to predispose to seizure activity (Ali et al, 2010)], the incidence of seizures with meperidine was only 0.4% (Nadvi et al, 1999). Commonly cited predisposing factors to meperidineassociated seizures include impaired renal function, receiving meperidine through patient-controlled analgesia, and high doses of meperidine (Seifert and Kennedy, 2004).…”

“…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).…”