Pediatric use of intravenous and intramuscular phenytoin: lessons learned

Abstract

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin.