Perioperative Acetaminophen Dosing in Obese Children

Abstract

Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1–10). Postoperative maintenance dosing is used to keep this effect at a steady-state concentration. The loading dose in children is commonly prescribed per kilogram. That dose is consistent with the linear relationship between the volume of distribution and total body weight. Total body weight is made up of both fat and fat-free mass. The fat mass has little influence on the volume of distribution of acetaminophen but fat mass should be considered for maintenance dosing that is determined by clearance. The relationship between the pharmacokinetic parameter, clearance, and size is not linear. A number of size metrics (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale clearance and all consequent dosing schedules recognize curvilinear relationships between clearance and size. This relationship can be described using allometric theory. Fat mass also has an indirect influence on clearance that is independent of its effects due to increased body mass. Normal fat mass, used in conjunction with allometry, has proven a useful size metric for acetaminophen; it is calculated using fat-free mass and a fraction (Ffat) of the additional mass contributing to total body weight. However, the Ffat for acetaminophen is large (Ffat = 0.82), pharmacokinetic and pharmacodynamic parameter variability high, and the concentration–response slope gentle at the target concentration. Consequently, total body weight with allometry is acceptable for the calculation of maintenance dose. The dose of acetaminophen is tempered by concerns about adverse effects, notably hepatotoxicity associated with use after 2–3 days at doses greater than 90 mg/kg/day.

Child and Adolescent Bariatric Surgery in an Urban Tertiary Center: Special Anesthetic Considerations for Obesity

“…Normal therapeutic doses of acetaminophen should yield plasma concentrations in the same range as patients without obesity reaching a target concentration of 10 mg/L, which is associated with a score of 2.6 pain units on the visual analogue scale. 31 Acetaminophen is eliminated by glucuronidation and sulfation, with hepatotoxic adducts formed by CYP2E1 metabolism. A study investigating the PK of oral acetaminophen in children aged 10-17 years with nonalcoholic fatty liver disease illustrated no difference in PK parameters as compared to age-matched controls, but the excretion of acetaminophen-glucuronide was higher in children with nonalcoholic fatty liver disease.…”