Bioavailability of rectal acetaminophen in children following anorectal surgery

Abstract

Background: Acetaminophen is widely used as an analgesic and antipyretic agent in pediatrics. Although bioavailability of rectal acetaminophen is unpredictable, rectal route is a usual and acceptable method of prescription. Major anorectal surgery may alter the normal structure of the surgical site, especially the vascular elements and the normal connections between port and systemic vessels. As a result the pharmacokinetics of rectal medications might also be altered. Based on this hypothesis, we decided to study acetaminophen plasma concentration among children who underwent these types of surgeries to determine the pharmacokinetic of absorption, plasma concentration, safety, and efficacy of rectal acetaminophen.

Materials and methods: The study included 20 cases with previous history of pull-through procedure owing to Hirschsprung's disease (HD), 20 cases with imperforate anus (IA) reconstructive surgeries who were admitted for colostomy closure, and 20 otherwise healthy cases of inguinal herniotomy. Venus blood sampling was done 4, 8 and 12 hrs after a single loading dose of rectal acetaminophen (40 mg/kg), and plasma acetaminophen concentration was compared between groups.

Results: Mean serum acetaminophen levels of the HD group were significantly higher than those of the herniotomy group (36.3 ± 6.79, 27.4 ± 8.42, 16.8 ± 7.62 versus 25.9 ± 9.12, 16.7 ± 6.74, 8.1 ± 5.79 (μg/ml) at 4, 8 and 12 hrs after drug administration and P < 0.05). The IA group had higher concentrations of plasma acetaminophen compared to the herniotomy group; however, the p values were not statistically significant. (31.4 ± 10.39, 21.5 ± 9.12, 13.3 ± 6.79 versus 25.9 ± 9.12, 16.7 ± 6.74, 8.1 ± 5.79 (μg/ml) at 4, 8 and 12 hrs after drug administration). Serum concentrations of acetaminophen in IA and HD patients were above the therapeutic range four hours after administering the loading dose (31.4 ± 10.39 and 36.3 ± 6.79 versus 5-20 μg/ml).

Conclusion: Bioavailability of rectal acetaminophen might get altered after major anorectal surgery in children. Rectal acetaminophen should be administered with special caution among infants with history of anorectal operations. Repeated dose of rectal acetaminophen may cause the drug blood concentration to reach toxic levels in these patients.

Type of study: Prospective comparative study.

Level of evidence: Level II.

Keywords: Acetaminophen; Anorectal malformation; Hirschsprung's disease; Pediatrics; Rectal.