Management of Acute Pain in Children: Pharmacologic

Acetaminophen

Due to its excellent safety profile and lack of significant side effects, acetaminophen is the most commonly used analgesic agent in pediatric practice. It is a mainstay for mild to moderate pain, and is often combined with opioid analgesics for patients with more severe pain (i.e., acetaminophen with codeine). In fact, infants and children have generally demonstrated less toxicity with this drug even in the presence of overdose.²² Toxicity can result when the toxic metabolite of acetaminophen, acetyl-p-benzoquinone-imine (NAPQI), is produced in such high quantities that there is not enough glutathione peroxidase (GSH) to bind to it. Infants and children produce high levels of GSH as a part of hepatic growth and this seems to provide a protective effect. In a recent study comparing weanling to adult rats after a toxic dose of acetaminophen was administered, the weanling rats demonstrated a 24-fold increase in GSH/NAPQI conjugate production and significantly less histopathologic damage.²³

View Initial Dosage Guidelines for Nonopioid Analgesics in Infants and Children

Acetaminophen is available orally in several tablet and liquid formulations. Oral dosing of 10 to 15 mg/kg is commonly recommended, though single oral doses of 20 mg/kg appear quite safe in children. Neonates have a slower elimination half-life so the drug must be given less frequently. Daily maximum oral dosing is recommended not to exceed 90 mg/kg for children, 60 mg/kg for term neonates <10 days of age, and 45 mg/kg for premature infants >34 weeks gestational age.²⁴

Rectal preparations of acetaminophen are available for infants and toddlers who are unable or unwilling to take this medication orally. A series of studies has confirmed that rectal absorption is slow, somewhat variable, and comparatively inefficient. Single rectal doses of 30 to 45 mg/kg produced plasma concentrations that were generally in the effective range, and never in a range associated with hepatotoxicity.^25,26 Following these large rectal doses, there is a comparatively slow decline in plasma concentrations. Based on a 24-hour kinetic study, it was recommended that initial doses of 35 to 40 mg/kg be followed by subsequent doses of 20 mg/kg, with the dosing interval extended to at least 6 hours.²⁶ If a large rectal dose is to be followed by oral dosing, it is also recommended that a first oral dose be given no sooner than 6 hours after the initial dose. Dosage guidelines for acetaminophen and the most commonly used NSAIDs in children can be found in the table.²⁷