Pethidine-related neurotoxicity in pediatric sickle cell disease: a systematic review

Abstract

Sickle cell disease describes a set of related blood disorders that result from defective production of hemoglobin that causes rigid fibers to form in the red blood cells, bending them into a characteristic sickle shape. These misshapen blood cells are then prone to becoming lodged in smaller blood vessels, resulting in a vaso-occlusive crisis, which can be very painful. Rapid and potent analgesia is crucial in the care of patients presenting with sickle cell crisis, and opioid analgesics, such as pethidine and morphine, have been the mainstay of treatment for decades. However, there are reports in the literature of seizures associated with pethidine use, particularly if used for more than a few days or in patients with kidney disease. A systematic review of the literature was conducted to identify any case reports or studies of the use of pethidine in children presenting with painful sickle cell crisis with a specific focus on the prevalence of seizures in this patient group. The pharmacology and pharmacokinetics of pethidine and its active metabolite norpethidine are briefly explored, along with alternative analgesic approaches, both pharmacological and nonpharmacological.