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(Allegaert et al, 2008). A review of 20 studies (Level II to Level III‐3) indicated efficacy following
oral, rectal, and IV administration, but dose sparing and safety have not been demonstrated
with spinal administration (Bozkurt, 2005). Many studies for post‐tonsillectomy pain have low
sensitivity (Hamunen & Kontinen, 2005) and tramadol has been variably reported to be more
effective than low‐dose paracetamol (Pendeville et al, 2000 Level II), have similar efficacy to
morphine (Engelhardt et al, 2003 Level II), and be less effective than pure agonist opioids (Ozer et
al, 2003 Level II; Ozalevli et al, 2005 Level III‐1) or ketoprofen (Antila et al, 2006 Level II). Further
controlled trials are required to determine the role and optimum dose of tramadol in children.
The side effects of tramadol are similar to opioids, with similar or reduced rates of nausea and
vomiting (10% to 40%), sedation and fatigue, but less constipation and pruritus and no reports
of respiratory depression in children (Bozkurt, 2005).
Pharmacokinetics
Oral administration is subject to extensive first‐pass hepatic metabolism. Rectal bioavailability
is good with low interindividual variability (Zwaveling et al, 2004). Maximum plasma
concentrations post IV, oral and rectal dosing are achieved between 0.3 and 2.4 hours
postadministration (Bozkurt, 2005). Analgesic efficacy is associated with a plasma concentration
of tramadol of 100 ng/mL in adults and children and O‐desmethyl tramadol (M1) of 15 ng/mL
(Garrido et al, 2006).
The primary metabolite is 0‐desmethyl tramadol (M1), formed by the enzyme CYP2D6. In
addition to inter‐individual variability in functional allele expression (resulting in poor, normal,
extensive or ultra metabolisers), there are age‐related changes in maturation of CYP2D6
(Allegaert, Van den Anker et al, 2005; Allegaert et al, 2008). Tramadol clearance is linked to weight
and postmenstrual age (PMA): increasing rapidly from 25 weeks PMA to 80% of the adult
value by 45 weeks PMA (Garrido et al, 2006; Allegaert et al, 2008).

10.5.5 Corticosteroids
Dexamethasone reduced vomiting and resulted in an earlier return to soft diet following
tonsillectomy (Steward et al, 2003 Level I). A single dose of intraoperative dexamethasone
(0.4 to 1 mg/kg; maximum 8 to 50 mg) reduced pain (by 1 on VAS scale 0 to 10 cm) on the
first postoperative day (Afman et al, 2006 Level I). A reduction in postoperative analgesic
requirements following tonsillectomy, and a dose‐dependent reduction in postoperative
CHAPTER 10 (maximum 20 mg) has recently been confirmed. However, the study was terminated after
nausea and vomiting following dexamethasone 0.05 mg/kg, 0.15 mg/kg or 0.5 mg/kg

randomisation of 215 children as dexamethasone, but not postoperative use of ibuprofen, was
associated with an increased risk of bleeding, which was highest after the largest dose (RR 6.8;
95% CI 1.8 to 16.5) (Czarnetzki et al, 2008 Level II).
10.5.6 Other pharmacological therapies

Acute otitis media is common in children. Analysis of four RCTs investigating topical local
anaesthetic drops for pain associated with acute otitis media, found insufficient evidence to
evaluate efficacy or adverse effects (Foxlee et al, 2006 Level I). Administration of lignocaine 2%
as ear drops reduced pain at 10, but not 20 or 30 minutes (Bolt et al, 2008 Level II).
In children with acute migraine, ibuprofen and sumatriptan reduced headache (NNT 2.4 and
7.4 respectively) or completely relieved pain (NNT 4.9 and 6.9 respectively) (Silver et al, 2008
Level I). Paracetamol, zolmitriptan, rizatriptan and dihydroergotamine were not significantly
better than placebo, but the number of RCTs in children was small.

352 Acute Pain Management: Scientific Evidence