Postoperative analgesia using diclofenac and acetaminophen in children
Summary
Background
Diclofenac dosing in children for analgesia is currently extrapolated from adult data. Oral diclofenac 1.0 mg·kg−1 is recommended for children aged 1–12 years. Analgesic effect from combination diclofenac/acetaminophen is unknown.
Methods
Children (n = 151) undergoing tonsillectomy (c. 1995) were randomized to receive acetaminophen elixir 40 mg·kg−1 before surgery and 20 mg·kg−1 rectally at the end of surgery with diclofenac suspension 0.1 mg·kg−1, 0.5 mg·kg−1, or 2.0 mg·kg−1 before surgery or placebo. A further 93 children were randomized to receive diclofenac 0.1 mg·kg−1, 0.5 mg·kg−1, or 2.0 mg·kg−1 only. Postoperative pain was assessed (visual analogue score, VAS 0–10) at half-hourly intervals from waking until discharge. Data were pooled with those from a further 222 children and 30 adults. One-compartment models with first-order absorption and elimination described the pharmacokinetics of both medicines. Combined drug effects were described using a modified EMAX model with an interaction term. An interval-censored model described the hazard of study dropout.
Results
Analgesia onset had an equilibration half-time of 0.496 h for acetaminophen and 0.23 h for diclofenac. The maximum effect (EMAX) was 4.9. The concentration resulting in 50% of EMAX (C50) was 1.23 mg·l−1 for diclofenac and 13.3 mg·l−1 for acetaminophen. A peak placebo effect of 6.8 occurred at 4 h. Drug effects were additive. The hazard of dropping out was related to pain (hazard ratio of 1.35 per unit change in pain). Diclofenac 1.0 mg·kg−1 with acetaminophen 15 mg·kg−1 achieves equivalent analgesia to acetaminophen 30 mg·kg−1.
Conclusions
Combination therapy can be used to achieve similar analgesia with lower doses of both drugs.
