NSAlDs are effective in alleviating pain and inflammation in infants and children.
They are generally well tolerated when used for appropriate indications, in
recommended paediatric doses, and with consideration of relevant precautions.
NSAIDs have we1 known analgesic, antipyretic and anti-inflammatory effects.
This article discusses the main indications for their use in infants (excluding
neonates) and children, adverse effects that occur in this age group and the
principles guiding the choice of NSAID.
The main indication for NSAIDs in children is the treatment of inflammatory
pain. This includes a variety of chronic inflammatory conditions, most often
juvenile idiopathic arthritis (JIA), where NSAIDs are used for both their analgesic
and anti-inflammatory properties. One of the analgesic effect of NSAIDs is relatively
rapid but the anti-inflammatory effects may take longer (up to six to eight
weeks for optimal relief of chronic inflammation) and require higher doses than
those used for analgesia.
NSAIDs are analgesics for the treatment of mild to moderate acute pain where inflammation may be the principle underlying mechanism. In single doses they have analgesic &cacy comparable to that of paracetamol, which is the preferred first line agent because of its Dr Gazarian is Senior Lecturer, Schwl of Women's and
Children's Health, University of NSW, and Paediatric Clinical Pharmacologist and Rheumatologist, Sydney Children's Hospital, Randwick Ms Graudins is Quality Use of Medicines Pharmacist, Sydney Children's Hospital, Randwick, and Conjoint
Lecturer, School of Women's and Children's Health, University of NSW, Sydney, NSW.
superior tolerability profile. NSAIDs, such as ibuprofen, are used for analgesia in the postoperative period, either to decrease opioid requirements or to provide adjunctive analgesia with regular paracetamol.
NSAlDs for fever?
The role of NSAIDs in the treatment of febrile illness in children is more controversial. Most children tolerate low grade fever (less than 38.5"C) well and do not require pharmacological treatment for fever. Antipyretic therapy does not prevent febrile convulsions, and there is some evidence that such therapy may
prolong the course of some infections. If antipyretic therapy is needed (e.g.
for a symptomatic child with high fever), paracetamol is the preferred pharmacothe
rapy. Ibuprofen has equivalent antipyretic efficacy to paracetamol when used
at recommended doses, but it is unclear whether ibuprofen is equally effective in
relieving important clinical outcomes, such as the child's discomfort and symptoms
(a Cochrane review is currently investigating this question). It is also unclear whether ibuprofen has any safety advantage. Although short term use of
ibuprofen for fever control appears to be relatively safe, the comparative safety of
longer term and more widespread use for febrile illness in young children with typical underlying comorbidities (e.g. dehydration, mild renal impairment) has not
been clearly established. Known toxicities of NSAIDs include gastrointestinal and
renal adverse effects, with the latter more likely to manifest in those with recopxed
risk factors, such as volume depletion or borderline renal function. Most trials of
ibuprofen have not evaluated these outcomes systematically in febrile illness, but
there are case reports of such toxicities occur. The use of ibuprofen and paracetamol in combination or in an alternating regimen in the setting of febrile illness is discouraged.
The physiological effects of the combination may potentiate the risk of toxicity with each agent, and the efficacy and safety of this practice have not been well evaluated. The combined use of these antipyretics needs further investigation,
as there is evidence that it may also lead to an increased incidence of adverse
effects as a result of parental confusion about correct dosing.
Adverse effects and precautions: Serious toxicity associated with NSAIDs
appears to be rare in children. The spectrum of adverse effects that occur in adults
may also occur in children, although there are some differences.
Adverse gastrointestinal effect & related to the use of NSAIDs are a signilicant problem in adults. Although the magnitude of this problem in children is poorly documented, it is thought to be considerably less. Mild gastrointestinal symptoms (e.g. abdominal pain) are commonly reported in children receiving NSAIDs, but clinically significant gastroduodenal pathology is uncommon. In many children
who develop gastrointestinal symptoms, underlying disease, psychosocial factors
and concomitant medication may account for these effects.
To minimise gastrointestinal effects, NSAIDs should always be given with
food. Concurrent treatment with gastroprotective drugs is generally not necessary.
NSAIDs should be used with caution (and at the lowest effective dose) in children
who have underlymg gut pathology (e.g. inflammatory bowel disease).
If safety concerns exist and NSAIDs are definitely needed in a child
with asthma, the first dose should be administered under medical supervision.
Skin reactions A variety of skin reactions including pruritis,
urticaria, erythema multiforme and phototoxic reactions have been described.
Pseudoporphyria is a distinctive type of photodermatitis that occurs fairly com-
I monly in children with JIA receiving naproxen;individuals with fair skin are particularly susceptible.
All signs except scarring resolve with discontinuation of therapy, so early
recognition is important. CNS effects: A substantial proportion of children
receiving long term NSAID therapy may experience CNS effects, with headache
being the most common. Less common symptoms include fatigue, sleep disturbance and hyperactivity. Ibuprofen has been reported to cause aseptic meningitis, particularly in patients with systemic lupus erythematosus. Platelets
NSAIDs inhibit platelet aggregation and may prolong bleeding time for some
patients, especially with long term use.
Clinically significant bleeding has not been associated with NSAIDs in children
after tonsilletomy,'however, whether NSAIDs increase the risk of significant
bleeding in the postoperative period generally remains controversial. Risk may
vary with different procedures and so the management of an individual child. For an individual patient, the initial choice of NSAID should be based on which agent is likely to provide the most favourable bene£it to risk ratio for the condition being treated. Additional considerations include the availability of a palatable paediatric formulation, convenience of dosing schedule and afjfordability. NSAID combinations should be avoided because toxicity is likely to be increased without a proven increase in benefit. The NSAIDs currently available for use in children.
Only naproxen and ibuprofen are available in liquid form. Naproxen suspension
is the only liquid NSATD listed on the PBS (authority required, for chronic
inflammatory arthropathies where the patient is unable to take a solid dose
form). [This suspension was temporarily unavailable in Australia from mid-2002,
reinstated in the Australian market in late 2005, and relisted on the PBS in early
2006.1 Naproxen suspension is the most widely used NSAID for treating chronic
childhood arthropathies worldwide. It has a well established efficacy and safety
profile in children, has a convenient dosing schedule and is affordable. Ibuen
is somewhat less effective as an anti-inflammatory agent but has a more avourable toxicity profile. Aspirin is now used much less often in children
because of its association with a greater frequency of adverse effects (including
Reye's syndrome). Currently, the main role of aspirin is in the treatment of Kawasaki disease and rheumatic fever, and as an antiplatelet agent.
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