g/ml
and with additional analgesia as serum acetaminophen concentration increased. It
thus appears that the target serum concentration for antipyresis will also
provide analgesiaAcetaminophen Dosing; Rectal and Subsequent Oral Dosing.
Initial recommended dosing for oral and rectal administration of acetaminophen ranged from 10-15 mg/kg until serum acetaminophen levels were studied and effective levels determined. Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target serum concentrations (10-20 micro gram/ml). Rectal acetaminophen is often administered during operations to provide supplemental analgesia or antipyresis in children. With doses of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia most patients did not achieve peak or sustained serum values in the 10-20 micro gram/ml serum concentration range associated with antipyresis.
Pain relief shows that 20-mg/kg liquid suspension of
rectal acetaminophen was equi-analgesic to 1 mg/kg intramuscular meperidine in
children undergoing tonsillectomy with or without adenoidectomy. In another
study of children having the same procedure, a suppository dose of 35 mg/kg was
equianalgesic to 1 mg/kg ketorolac. If acetaminophen's analgesic effect is
associated with the antipyretic effect then doses in the 40 mg/kg are needed.
Others have shown superior analgesia and an opioid-sparing effect in children
with a serum concentration more than 10.5 g/ml
and with additional analgesia as serum acetaminophen concentration increased. It
thus appears that the target serum concentration for antipyresis will also
provide analgesia
Dose-dependent and potentially fatal hepatotoxicity is the most serious acute side effect of acetaminophen administration. Toxicity after single-dose administration is generally not observed with concentrations less than 120 micro gram/ml 4 h after ingestion, and in the Birmingham study at doses of 30 mg/kg blood concentrations were 22.7 micro gram/ml at their highest which is 20% of the toxic concentration.
In summary, an acetaminophen regimen of 40 mg/kg as an
initial dose followed by 20 mg/kg every 6 h results in serum concentrations
centered at the target range of 10–20 g/ml.
This should be a dosing regimen of 24 hours duration only.
Reference:
1. Birmingham PK : Twenty-four-hour pharmacokinetics of rectal acetaminophen in children. ANESTHESIOLOGY 1997; 87: 244–52
2. Rusy LM : A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg 1995; 80:226-9.
3. Gaudreault P : Pharmacokinetics and clinical efficacy of intrarectal solution of acetaminophen. Can J Anaesth 1988; 35:149-52
4. Birmingham PK : Initial and subsequent dosing of rectal acetamenophen in children. Anesthesiology 2001;94:385-389