Perioperative Use of High-Dose Rectal Acetaminophen

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2001;7(9) 

In This Article

Pharmacokinetic Considerations

Many standard pediatric dosing texts cite identical doses for oral and rectal acetaminophen administration, typically 10 to 15 mg/kg given up to every 4 hours.[1] It is well known, however, that absorption from the rectal route is slow and often erratic. Several factors may account for this variability, including the placement of the suppository, the degree of lipophilicity of the vehicle, and the pH within the rectum. This erratic absorption pattern frequently results in serum acetaminophen concentrations that fail to reach the target for antipyresis of 10 to 20 mcg/ml.[2] The ideal serum concentration for analgesia remains largely undefined.

Because of this delayed absorption, several investigators have suggested using higher doses when administering acetaminophen by the rectal route in children, as well as adults.[3,4,5,6,7,8,9,10,11,12] If the optimal dose for rectal administration could be determined, the use of this route might prove ideal for the perioperative setting. The slower rate of absorption could provide a prolonged analgesic effect during recovery.

In 1995, Montgomery and colleagues evaluated the pharmacokinetics of high-dose rectal acetaminophen in 10 children (average age 3.4±0.5 years).[3] A single 650 mg suppository, providing a dose of approximately 45 mg/kg, was administered immediately after induction of anesthesia. Serum samples were collected over a 4-hour period in the first five patients, but extended to 7 hours in the remaining patients after a prolonged absorption phase was identified. The average maximum serum concentration for the 10 children was 13.3±5.9 mcg/ml. The time to maximum concentration occurred at 198±70 minutes. Based on their results, the authors suggested that a 45 mg/kg rectal acetaminophen dose was roughly equivalent to a 10 to 15 mg/kg oral dose.

The results of Montgomery's group were subsequently reproduced in a larger dose-ranging study. Birmingham and colleagues at Children's Memorial Hospital in Chicago conducted a trial of rectal acetaminophen in 28 children (ages 2 to 12 years) undergoing orthopedic surgery.[4] Patients were randomized to receive a single 10, 20, or 30 mg/kg dose after induction of anesthesia. Serum sampling was performed over a 24-hour period and the results analyzed with nonparametric mixed-effects modeling (NONMEM). Pharmacokinetic analysis showed considerable patient variability and wide differences in dissolution rates. In the patients receiving the two larger (325 and 650 mg) suppositories, the average time to complete dissolution was 3 hours. Only the 30 mg/kg dose produced serum concentrations within the predetermined target range of 10-20 mcg/ml, with an average maximum serum concentration of 14.2±5.1 mcg/ml. While this study was not designed to evaluate analgesic efficacy, the authors concluded that a rectal acetaminophen dose of 40 mg/kg would likely be needed to provide adequate serum acetaminophen concentrations in the perioperative setting.

Similar results were observed by Hansen and coworkers in a study of 17 infants given rectal acetaminophen 25 mg/kg during induction of anesthesia.[5] The average maximum serum acetaminophen concentration (10.9±5.1 mcg/ml) was considered by the authors to be subtherapeutic. Average time to maximum concentration was 102.4±59.1 minutes.


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