1 Introduction
Fever is the primary presentation for a host of childhood illnesses, and its underlying cause is generally benign. Fever may have a beneficial effect in terms of fighting infection [
1], although its value in the recovery process is far from clear, since in vivo data are largely lacking. Fever can, however, be associated with distress and discomfort in children, leading to a high degree of parental concern. For febrile children without any indication of a serious underlying condition (‘low-risk’ fever), national guidelines recommend home management [
1‐
4]. However, despite the recognition over 30 years ago of parental misconceptions around childhood fever and calls for improved educational intervention, ‘fever phobia’ remains common, and parents and caregivers continue to show uncertainty, misjudgment and anxiety in managing their feverish child [
5‐
7].
Recently, the UK’s National Institute for Health and Care Excellence (NICE) issued guidelines for the assessment and initial treatment of the feverish child, an update of earlier guidelines produced in 2007 [
2]. NICE defines fever as an elevation of body temperature above the normal daily variation. For the assessment of children with fever, NICE has developed the ‘traffic light’ system for identifying the risk of a serious illness such as meningitis (Table
1). Children who have all the green (low-risk) features and no amber (intermediate-risk) or red (high-risk) features are most likely to have a self-limiting viral infection, and can be cared for at home with appropriate advice provided to parents and caregivers. Key among the updated recommendations is the advice to treat with an antipyretic only if the child appears distressed, with a focus on comforting the child, rather than on achieving normothermia (Table
2). In line with evidence showing increased discomfort and a lack of efficacy relative to antipyretics [
8‐
10], physical interventions such as tepid sponging are no longer recommended for the treatment of fever [
2].
Table 1
NICE guidelines for identifying low-risk, intermediate-risk and high-risk fever in children [
2]
Color (of skin, lips or tongue) | Normal color | Pallor reported by parent/carer | Pale/mottled/ashen/blue |
Activity | Responds normally to social cues Content/smiles Stays awake or awakens quickly Strong normal cry/not crying | Not responding normally to social cues No smile Wakes only with prolonged stimulation Decreased activity | No response to social cues Appears ill to a healthcare professional Does not wake or if roused does not stay awake Weak, high-pitched or continuous cry |
Respiratory | | Nasal flaring Tachypnea: respiratory rate >50 breaths/minute, age 6–12 months >40 breaths/minute, age >12 months Oxygen saturation ≤95% in air Crackles in the chest | Grunting Tachypnea: respiratory rate >60 breaths/minute Moderate or severe chest indrawing |
Circulation and hydration | Normal skin and eyes Moist mucous membranes | Tachycardia: >160 beats/minute, age <12 months >150 beats/minute, age 12–24 months >140 beats/minute, age 2–5 years Capillary refill time ≥3 seconds Dry mucous membranes Poor feeding in infants Reduced urine output | Reduced skin turgor |
Other | None of the amber or red symptoms or signs | Age 3–6 months and temperature ≥39 °C Fever for ≥5 days Rigors Swelling of a limb or joint Non-weight bearing limb/not using an extremity | Age <3 months and temperature ≥38 °C Non-blanching rash Bulging fontanelle Neck stiffness Status epilepticus Focal neurological signs Focal seizures |
Table 2
NICE guidelines for antipyretic interventions in children [
2]
Antipyretic agents do not prevent febrile convulsions and should not be used specifically for this purpose |
Tepid sponging is not recommended for the treatment of fever |
Children with fever should not be underdressed or over-wrapped |
Consider using either paracetamol or ibuprofen in children with fever who appear distressed |
Do not use antipyretic agents with the sole aim of reducing body temperature in children with fever |
When using paracetamol or ibuprofen in children with fever: |
Continue only as long as the child appears distressed |
Consider changing to the other agent if the child’s distress is not alleviated |
Do not give both agents simultaneously |
Only consider alternating these agents if the distress persists or recurs before the next dose is due |
Management of the distressed, feverish child therefore relies on the use of drug intervention and both ibuprofen and paracetamol (acetaminophen) are given equal status in the current guidelines. Parents and caregivers therefore need to choose between the two, the key aspects of which are compared in Table
3, and may seek guidance from healthcare professionals (HCPs) as to which is more appropriate for their child.
Table 3
Summary of over-the-counter (OTC) paracetamol and ibuprofen for the distressed, feverish child
Typical OTC dosing interval | 4 hours | 6 hours |
Route of OTC administrationa
| Oral, palatable suspension is available | Oral, palatable suspension is available |
Commercial availability | Brands such as Calpol and Tylenol are established and familiar to parents | Potentially less familiarity with brands such as Nurofen for Children |
Efficacy | | Effective [ 2]. Better than paracetamol at reducing fever-related discomfort [ 26, 27] |
Safety considerations relevant to specific patient groups | May be preferable for children with gastrointestinal infection | Risk of gastrointestinal irritation [ 35], true incidence uncertain due to under-reporting, short-term use may be asymptomatic |
May be preferable in patients at high risk of gastrointestinal bleeding | Risk of gastrointestinal bleeding—potentially serious, but rare. No significant difference in risk from paracetamol [ 1, 40, 41] |
Increased risk of asthma-related outpatient attendance in children with asthma [ 49] | May be preferable for children with asthma (but without aspirin-sensitive asthma) |
May be preferable for children with chicken pox | Risk of severe cutaneous complications in patients with varicella or herpes zoster [ 77] |
Risk of hepatotoxicity—potentially serious, but rare [ 1, 88] | May be preferable where there is a risk of dosing error or confusion |
May be preferable for children who are dehydrated or with pre-existing renal disease or multi-organ failure | Risk of renal toxicity—potentially serious, but rare [ 1] |
Interestingly, despite equal recommendation in guidelines, there is evidence to suggest that paracetamol is the ‘favored’ antipyretic medication for home management of pediatric fever [
11]. The reasons for this apparent discrepancy are unclear, although over-the-counter (OTC) paracetamol has been available for longer than ibuprofen, and brand names such as Calpol and Tylenol are consequently firmly established in the minds of parents. This familiarity can present advantages (rapid access when required) and disadvantages (resistance to change). There may also be perceptions, for both parents and HCPs, around relative safety and efficacy. This narrative literature review of recent data aims to determine whether there are any clinically relevant differences in efficacy and safety between ibuprofen and paracetamol that may recommend one agent over the other in the management of the distressed, feverish child. In addition, it also explores why there is a discrepancy between current guidelines and the real-world use of these treatments.
2 To Treat or Not to Treat
Before discussing treatment, it is important to consider what constitutes ‘distress’ and how parents interpret this term [
12]. Perception of distress is likely to vary markedly between parents, and may be linked to factors such as level of education, socioeconomic status and cultural background [
13‐
15]. This may impact on when a parent decides to start treating their child with an antipyretic, whether to change antipyretics, or indeed when to consult an HCP. The problem of defining distress is recognized in the NICE guidelines, and the Guideline Development Group has called for studies on home-based antipyretic use and parental perception of distress caused by fever in order to clarify issues such as triggers for antipyretic use and help-seeking behavior [
2].
The rationale for treating only the distressed, feverish child is based on the fact that absolute body temperature alone does not appear to be an indicator of serious infection [
16,
17]. In addition, there is no evidence that fever in itself increases the risk of parentally-feared adverse events such as febrile convulsions or brain damage [
18], and lowering temperature with antipyretics does not appear to be effective at preventing febrile convulsions [
19,
20]. Based on such data, recent guidelines emphasize the need to treat only the symptoms of fever in children who are either in discomfort or distressed, and not to focus on normothermia [
1‐
3]. Despite this, an elevated body temperature (whatever site or method of measurement is used), even below 38 °C, continues to be a cause of concern for many parents [
7]. Unfounded concerns contribute to reports that the vast majority of caregivers would give antipyretic medication to a feverish child, even if the child appeared otherwise comfortable [
7,
13,
21]. Overall, it seems that parental misconceptions around fever and ‘fever phobia’ have changed little since this problem was first recognized over 30 years ago [
6]. Overcoming such concerns and gaining parental acceptance of current recommendations not to give antipyretics simply to reduce fever in children, but only to alleviate distress [
2,
22], is clearly a major challenge.
4 Summary and Conclusions
The NICE guidelines give equal recommendation to the use of paracetamol or ibuprofen for the short-term treatment of distress in low-risk feverish children [
2]. Therefore, the caregiver or HCP has to make a choice between these readily available OTC agents.
The aim of this review has been to compile and compare the efficacy and safety data from available clinical studies that directly compare ibuprofen and paracetamol such that any clinically relevant differences can be considered and sensible conclusions drawn as to whether one agent has advantage over the other, and to enable the caregiver (or HCP) to make an informed choice.
The age of the child can be a factor in the decision of which antipyretic to use, since paracetamol can be given at 2 months of age whereas ibuprofen has an OTC license in infants aged over 3 months (weight > 5 kg) with a higher threshold of 6 months in some other countries, including the USA. However, from the age of 3 (or 6) months, both paracetamol and ibuprofen are suitable (Table
4).
Antipyretic efficacy data for ibuprofen and paracetamol are not relevant to the use of these agents in feverish children, considering the NICE guidance to focus on comforting the child, rather than on achieving normothermia. However, they do provide useful information. Antipyretic efficacy may indicate relevant pharmacologic onset and duration of effect, especially where distress is due to the mismatch in environmental and body temperatures. However, distress is likely multi-factorial so antipyretic efficacy cannot currently be used as a direct surrogate for efficacy against distress in feverish children; further research is required.
The evidence indicates that ibuprofen may provide greater relief of symptoms in the distressed, feverish child compared with paracetamol [
26,
27]. The longer duration of action of ibuprofen means the number of doses can be kept to a minimum, and a single dose may be all that is required in certain circumstances (e.g., post-immunization pyrexia). In addition, the faster onset of action and greater symptomatic relief with ibuprofen means that the NICE recommendation to relieve distress can be achieved more rapidly, with the concomitant advantage of a faster return to ‘normal’ family life.
Meta-analyses confirm that the safety and tolerability profiles of paracetamol and ibuprofen in pediatric fever are similar [
25,
33]. Both drugs are associated with specific rare adverse effects, which are difficult to detect and quantify in all but the largest clinical trials, and which may be relevant to specific patient populations. For example, ibuprofen may be preferable in the setting of asthma (without known aspirin sensitivity) or where there is a risk of the parent or caregiver experiencing confusion overdosing (and potentially overdosing the child), whilst paracetamol may be preferable when children have chicken pox, are dehydrated, have pre-existing renal disease or multi-organ failure, or are at increased risk of GI bleeding (Table
3). In reality, such children are likely to be under the care of a clinician, who is best placed to weigh up the risks and benefits of each drug for the individual patient.
Paracetamol is generally conceived by the public (or HCPs) as being a ‘safer agent’ with fewer adverse effects. Possible reasons to explain this misconception could include the earlier potential exposure to paracetamol (after the child’s first immunization at 2 months of age), perhaps leading to a general misconception around its safety and tolerability. Therefore, with earlier familiarity, in the absence of advice to the contrary, many parents are likely to remain loyal to a drug they are used to. In addition, the fact that paracetamol is licensed for use in younger children may mean that parents perceive it to be a ‘safer’ medication. Familiarity also introduces risks, and the consequences of too frequent and unnecessary use of paracetamol can be serious. A further reason may be the often-cited advice to give ibuprofen with food (or milk), which could be associated with a perception of GI intolerability, despite the lack of evidence relating to short-term OTC usage.
While alternating treatment with ibuprofen and paracetamol may offer some advantages over monotherapy, a lack of efficacy and safety data in children, together with concerns around dosing confusion and risk of overdose, are currently considered to outweigh any benefit except in patients where single-agent treatment is ineffective.
The NICE guidelines recommend that children should only be treated for as long as symptoms persist; avoiding overtreatment is an important consideration with antipyretics, as with any drug. Conversely, delaying treatment or underdosing may result in unnecessary discomfort to a distressed, feverish child, and may affect their desire to eat or drink. Ongoing distress in febrile children may also impact parents and the wider family. Fears that antipyretic use may prolong febrile illness have been shown to be unfounded and there is there is little evidence to suggest that antipyretics mask the symptoms and signs of serious illness [
87]. Encouraging the appropriate use of antipyretics in distressed, feverish children is therefore clearly important.
In conclusion, fever is a common symptom of childhood infection which in itself does not require treatment. However, fever in children can be distressing for all concerned and there is a need for improved education and healthcare advice so that parents and caregivers can confidently and effectively manage a child’s low-grade fever at home. This includes being aware of the choice of OTC antipyretics available to them, knowing when to treat with an antipyretic agent, and being well informed on which agent to choose. The long-term goal of childhood fever management is improved self-care/home-care plans, with the advice and help of local pharmacists. This approach will help to empower parents and caregivers, enabling them to make informed decisions about their child’s wellbeing rather than relying on general practitioners or emergency departments. NICE guidelines recommend treatment when dealing with a distressed, feverish child, with the focus on comforting the child rather than reducing the temperature. Whilst the guidelines do not recommend one agent over another, evidence presented in this paper suggests that ibuprofen may provide greater efficacy in terms of the relief of symptoms in the distressed, feverish child and that short-term OTC ibuprofen and paracetamol have similar safety and tolerability profiles, although each may be preferred in some specific patient populations.