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In children, the time to reach steady‐state serum drug concentrations following transdermal
application is longer, and the elimination half‐life is shorter as clearance is enhanced, but
there have been no randomised trials of efficacy (Zernikow et al, 2007).
Codeine
Codeine is a weak opioid and conversion to morphine (by CYP2D6) is required for analgesia.
Intermediate or poor metabolisers — 46% of children undergoing tonsillectomy in a United
Kingdom population (Williams et al, 2002) — may have reduced or minimal effect from codeine;
while ultra metabolisers may attain high peak morphine levels and are at risk of sedation and
respiratory depression (Kirchheiner et al, 2007 Level III‐3; Voronov et al, 2007). Perceived
advantages of codeine include less respiratory depression in neonates and reduced nausea
and vomiting compared with morphine (Williams et al, 2002 Level II) but may relate to low levels
of active metabolites and be associated with reduced efficacy (Williams et al, 2001).
Oral codeine has a similar time to peak effect but decreased total absorption compared with
rectal and IM delivery (McEwan et al, 2000 Level II). IV administration should be avoided as
severe hypotension may result (Shanahan et al, 1983 Level IV).
There are conflicting reports of efficacy for postoperative pain. Addition of codeine to
paracetamol has been reported to improve analgesia (Pappas et al, 2003 Level II) or have no
effect (Moir et al, 2000 Level II). Comparison of codeine and morphine for tonsillectomy has
shown either no difference (Semple et al, 1999 Level II) or an increased requirement for rescue
analgesia following codeine (Williams et al, 2002 Level II). Codeine was less effective than
ibuprofen for acute musculoskeletal pain in children (Clark et al, 2007 Level II).
Oxycodone
Oxycodone is increasingly used in children, with efficacy shown in multiple settings: oral use
in the emergency department for children with orthopaedic injuries (Charney et al, 2008 Level II;
Koller et al, 2007 Level II); use of an oral controlled‐release (CR) preparation as a step‐down
following PCA in adolescents after spinal fusion (Czarnecki et al, 2004 Level IV); IV bolus dose
administration for postoperative rescue analgesia (Kokki, Laisalmi et al, 2006 Level IV); and IV PCA
(in adolescents and adults) (Silvasti et al, 1999 Level II).
In infants over 6 months of age, the pharmacokinetic profile of oxycodone is similar to adults
and dosing can be based on the weight of the child (El‐Tahtawy et al, 2006). Similar absorption is
seen following buccal and sublingual absorption (Kokki, Rasanen et al, 2006), but there is less
interindividual variability following IV administration (Kokki et al, 2004). In neonates and infants,
the half‐life is prolonged and interindividual variability in kinetics is increased even following
IV administration (Pokela et al, 2005). CHAPTER 10
Other opioids
A large number of opioid preparations have been utilised in children, but availability varies in
different countries, and many have not been investigated in controlled trials. See Howard et al
(Howard et al, 2008) for additional details. A review of paediatric and adult studies using
hydromorphone found no clear advantage over other opioids in terms of analgesic efficacy
or side‐effect profile (Quigley, 2002 Level I). Several opioids are used as spinal analgesics in
children, but the lack of comparative studies provide limited evidence for superiority of one
agent (Williams & Howard, 2003 Level IV).
Tramadol
Evidence for the use of tramadol in paediatric acute pain is currently limited by studies of
small sample size, difficulty determining comparative analgesic doses, and licensing only for
16 years and over. Dosing is the same in children as in adults (1 to 2 mg/kg 6 hourly), with
some reporting use of a 2 to 3 mg/kg IV loading dose then infusion of 5 to 8 mg/kg/24hours
Acute pain management: scientific evidence 351