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Pharmacokinetics of paracetamol after cardiac surgery
C S Hopkins1, S Underhill, P D Booker
1Department of Anaesthesia, Royal Liverpool Children's Hospital.
Insights
Rectal paracetamol in neonates and children post-cardiac surgery may not reach therapeutic levels. Nasogastric administration showed higher plasma concentrations, with less variance in neonates.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
- Critical Care Medicine
Background:
- Post-cardiac surgery febrile children require effective antipyretic management.
- Paracetamol (acetaminophen) is commonly used, but its pharmacokinetics in this population are not fully understood.
- Route of administration (rectal vs. nasogastric) may influence drug bioavailability.
Purpose of the Study:
- To compare plasma concentrations of paracetamol following rectal and nasogastric administration in febrile children after cardiac surgery.
- To evaluate the impact of age (neonates vs. older children) on paracetamol pharmacokinetics.
- To assess the antipyretic efficacy of different administration routes.
Main Methods:
- A pharmacokinetic study involving 28 febrile children (9 days to 7 years) post-cardiac surgery.
- Paracetamol (15 mg/kg) administered via rectal suppository and nasogastric tube.
- Plasma paracetamol concentrations, elimination half-life, and area under the concentration-time curve (AUC) were measured.
- Antipyretic effect was assessed for both routes.
Main Results:
- Rectal paracetamol yielded sub-therapeutic plasma concentrations in neonates and children on postoperative day 1.
- Nasogastric administration resulted in higher plasma concentrations, particularly on postoperative day 2.
- Neonates exhibited less variance in plasma paracetamol concentrations.
- Plasma elimination half-life and AUC were significantly prolonged in neonates receiving suppositories.
- No significant difference in antipyretic effect between routes, but overall efficacy was lower than expected.
Conclusions:
- Rectal paracetamol administration may be suboptimal for achieving therapeutic concentrations in febrile neonates and children post-cardiac surgery.
- Nasogastric administration appears more reliable for achieving adequate paracetamol levels in this patient group.
- Age-related pharmacokinetic differences, especially in neonates, necessitate careful dosing considerations.
- Further research is needed to optimize paracetamol dosing strategies in pediatric cardiac surgical patients.
Abstract:
Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children.