Treating A Fever

I threw it out to the facebook page for people to vote on what I should write on next, and the topic of most interest was the use of Panadol in treating fever.

My poor little munchkin has had 2 fevers in the last three weeks, and a snotty nose cold in between. I feel like a walking zombie from all the night-wakings, and I imagine she doesn't feel too crash hot either. In the process of dealing with these fevers, I learned that the taste of Panadol makes my baby gag and throw up. (Amazingly, we got to 9 months without really having a situation arise where we thought Panadol might be necessary.) Panadol can, however, be successfully administered to her by an over-the-counter suppository.

Having to administer Panadol by suppository does make you think fairly hard about whether you really need to give it. So I started to do some research.  As a result of this research, I have come to the conclusion that in most cases I will not give Panadol (or Neurofen for that matter) to my baby in order to bring down her temperature.

Fancy Word Alert

Just so there's no confusion, here's a quick rundown on some of the fancy words used in this post.

The active ingredient in Panadol is paracetamol which is also known as acetaminophen and occasionally APAP. One of the uses of paracetamol is to reduce fever. A substance which reduces fever is called an antipyretic. Other well-known antipyretics are aspirin (acetylsalicylic acid), and ibuprofen which is the active ingredient in Nurofen. A child with a fever is sometimes referred to as being 'febrile' and fever is sometimes called 'pyrexia'.

What is a Fever?

Fevers are different from hyperthermia. A fever is when your body deliberately raises its core temperature, usually in response to a virus or bacteria. Hyperthermia is when your temperature rises from other sources, such as heat stroke or taking a drug stimulant like cocaine (just in case, you know, your baby decides to smoke crack). Babies who are hot because they bundled up in too much clothing and bedding do not have a fever. They have hyperthermia. Unwrap them and they cool down. Babies with fever may develop cooler skin if they are stripped down, but if you... ahem... stick a thermometre up their bum, it will still read hot.

On one view, any temperature above 37.8 degrees Celcius is considered to be a fever in a baby (Carson, Walsh 2007). However, it should be noted that infant body temperature can vary quickly by about a degree just from excessive clothing, hot weather, digestion, and bathing (Walsh 2007). Body temperature may also be hottest in the early afternoon and lowest in the middle of the night (Walsh 2007).

Over 37.8 but under 40 degrees Celcius is considered a 'low grade' fever. Only fevers over 41.5 degrees Celcius are considered a 'high grade' fever (sometimes called 'hyperpyrexia').

What is the Best Way To Take a Temperature?

A recent Italian review of the literature of fevers found that the best way to take a baby's temperature is a digital thermometre under the arm (axillary temperature). A thermometre in the mouth (oral temperature) is unreliable. A thermometre in the anus (rectal temperature) is very reliable but quite invasive so shouldn't be used unless necessary. An ear thermometre (tympanic temperature) can be very reliable if you know how to use it, but if you don't can be difficult, and in newborns the ear canal is too curved to get a reliable reading.

I actually find that I can tell whether my baby has a temperature by feeling the top of her head and her tummy, or in any 'folds' like under her arms. Once I was used to her usual temperature, an elevated temperature felt like the skin was 'burning'. Even a fever of 38.2 has been quite obvious to the touch. The temperature of her skin other than in these places seems to reflect the room temperature and not necessarily whether she has a fever.

We have an ear thermometre and an underarm thermometre. The ear thermometre is great because it takes about 1 second to do a reading, whereas with the underarm thermometre we have to persuade our unhappy, squirmy baby to stay still for about 90 seconds. So far, our ear thermometre readings have been confirmed by underarm readings, so I prefer it because it is less distressing / invasive for our baby.

Fever Helps Your Baby

When a baby is a newborn, fever can often be an indication of some serious problem, so parents are instilled with a terror of fevers in their babies. This is not helped by health practitioners following out of date information. But the overwhelming opinion of leading health organisations based on current medical evidence is that in most cases, you are better not to treat your baby's fever.

You should worry about a fever if:

• your baby is under 3 months;
• your baby has some significant complication to their immune system like cancer or HIV;
• your baby's temperature is over 41 degrees Celcius (and even then it might be ok if it's just a fever and not hyperthermia);
• your baby has other symptoms that indicate they are not coping with an illness, such as dehydration, significant distress, vomiting or diarrhoea, or becoming limp.

Otherwise, no. The fever is not a problem, it is actually helping your baby!

Fever is your body's equivalent of a 'scorched earth' strategy in the fight against the virus. The body raises its core temperature in order to make it a hostile environment to invading bacteria / viruses, and the fever also triggers the production of large numbers of cells to fight the illness.

The most recent statement by the American Academy of Pediatrics in February 2011 states:

“fever is not an illness but is, in fact, a physiological mechanism that has beneficial effects in fighting infection. Fever retards the growth and reproduction of bacteria and viruses, enhances neutrophil production and T-lymphocyte proliferation, and aids in the body's acute-phase reaction. The degree of fever does not always correlate with the severity of illness. Most fevers are of short duration, are benign, and may actually protect the host. Data show beneficial effects on certain components of the immune system in fever, and limited data have revealed that fever actually helps the body recover more quickly from viral infections, although the fever may result in discomfort in children.” (Sullivan)

This statement also says:

• “There is no evidence that children with fever, as opposed to hyperthemia, are at increased risk of adverse outcomes such as brain damage.”
• “There is no evidence that reducing fever reduces morbidity or mortality from a febrile illness.”
• “There is no evidence that antipyretic therapy decreases the recurrence of febrile seizures.”
• “Studies of health care workers, including physicians, have revealed that most believe that the risk of heat-related adverse outcomes is increased with temperatures above 40 degrees Celcius, although this belief is not justified.”

In various animals, the positive effects of a moderate fever have been well documented. In a study of iguanas injected with a deadly bacteria, 50% of those whose fevers were kept down died, whereas of those who were untreated and ran a temperature 2 degrees above normal, only 15% died. Similar results have been found in tests on goldfish, grasshoppers, crickets, and rabbits. In studies of lizards and rabbits given aspirin to lower a fever, most of those that were not given the aspirin survived, but all those given the aspirin died, except a few who managed to produce a fever despite the aspirin. A number of studies in humans also show a link between fever and survival in serious bacterial illnesses (Moltz).

But I was Told To Give Panadol and/or Ibuprofen by a Health Professional

The evidence about the beneficial properties of fevers has only emerged recently (particularly in the last five years), so many health professionals have not caught up. It is well documented that inaccurate advice on treating fevers is still given by large numbers of health professionals (see Sullivan, Scrase and Tranter, Carson, Walsh 2006, Edwards et al). The practice of paediatric nurses in this respect have been described as 'inconsistent, ritualistic antipyretic use in fever management' (Edwards et al). The same study observed that nurses often administer antipyretics following insistence from an anxious parent, not because they believe it is necessary (Edwards et al). A recent study showed that almost a third of paediatric nurses believed that fever itself was dangerous and that paracetamol should be administered (Warwick).

I am not a health professional, and I'm not telling you to ignore the advice of your health professional.  But the American Academy of Pediatrics are undeniably health professionals who have looked at the most up to date research on this topic and their view is that low-grade fever is usually a beneficial response.  So I would encourage you to challenge your health professional (perhaps with the AAP statement) or seek a second opinion if they insist you must bring down a low-grade fever with an antipyretic.

Fever and Immunisations

In the 1980s, scientists began to look at ways to make immunisations less stressful for babies and parents, and so studied whether paracetamol could help deal with or prevent fever in babies who were immunised. It was found that paracetamol was pretty effective at lowering or preventing fever, and so it became common to recommend to parents to give Panadol before vaccines and then again every 4 hours for a couple of days (Pedulla).

It was not until 2007 that scientists noted that the original studies dealt with vaccines that were no longer used and some up-to-date studies were conducted. A 2008 study of 270 babies found that paracetamol had no noticeable effect with respect to reducing comfort or fever.

In 2009, a study monitored the extent to which children who were immunised produced antibodies. It found that children given paracetamol (as opposed to a placebo) produced significantly less antibodies in response to the vaccine (Prymula). Whether children produced enough antibodies seemed to vary dramatically depending upon the vaccine. There were vaccines (eg. polio) where the children given paracetamol still produced protective levels of antibodies, but others where many did not reach that protective level (eg. some strains of pneumococcal). (Prymula) This study also found that fevers greater than 39.5 degrees Celcius were uncommon regardless of whether paracetamol was given. Interestingly, this study had not aimed to look at paracetamol's effect on antibodies, but rather children's antibody responses to various vaccines, and separately what effect paracetamol had on fever (Prymula).

It should be noted that these are only preliminary studies, and further studies would be necessary to confirm the effect, and also to establish whether it is dependent upon the timing and dosage of paracetamol. However, the initial results are concerning enough for most health care providers to recommend that paracetamol not be routinely before or following immunisation (see, for example, Sullivan). Whether paracetamol should be given in cases where an adverse reaction does occur is a subject of debate, and it is likely we will soon see further research on this topic.

Effect of Antipyretics on Fever

Paracetamol and ibuprofen have both been shown to be fairly effective in lowering the core body temperature of babies with fevers, although there is some evidence that ibuprofen is a bit more effective with high grade fevers and has a longer-lasting effect (Perrott, Sullivan). There was a review of 12 studies that found paracetamol was no more effective than a placebo, but the studies included in this review had only small numbers of patients (Chiappini et al).

Aspirin is also effective, however, it is widely accepted that aspirin should not be used to treat fever in children. It is believed to be linked to a condition called 'Reye syndrome', which involves nausia, vomiting, delirium, and coma. Reye syndrome appears to be a severe, though not necessarily common side-effect of aspirin. Only 555 cases were reported in its peak year in 1980. Reye's syndrome is almost unknown since the introduction of warnings not to give aspirin to children (Beutler and Jamieson).

Possible Issues With Antipyretics

There are concerns that antipyretics like Panadol and Neurofen:

• interfere with the body's natural immune response;
• mask the symptoms of the illness, making it harder to diagnose (Scrase and Tranter).

There are some incidents where it appears that paracetamol and ibuprofen led to such a drop in temperature as to cause hypothermia (a temperature that is too low), but studies have not been conducted to confirm how often this occurs (Richardson).

Antipyretics Do Not Prevent Febrile Convulsions

Studies indicate that use of antipyretics do not prevent febrile seizures (Fetveit, Sullivan). Febrile seizures are usually benign and resolve themselves, and the only treatment necessary is to protect the child from hurting themselves during the seizure (Fetveit). However, you should probably seek medical advice if your child has a seizure, since they can have additional issues. Particularly seek help if seizures are recurrent during the same illness, go on for longer than 15 minutes, or start on one side of the body (Fetveit).

While febrile seizures can be very scary, children with febrile seizures have no risk of increased mortality (Leung and Robson).

Side Effects of Paracetamol (Panadol)

In a large International New Zealand-based study of 205 487 children, use of paracetamol to treat fevers in the first year of life was linked to a significant increase in the risk of asthma by age 6-7. It was also also associated with increased risk of rhinoconjunctivis and eczema in the first year of life and at age 6-7 years (Beasley et al). This study controlled for maternal education, antibiotic use, breasftfeeding, parental smoking, diet, and siblings. The study interviewed parents of 6-7 year olds about their child's current asthma, and their paracetamol usage recently and in the first year of the child's life.

It found that developing severe asthma by age 6-7 was about 1.5 times more likely if paracetamol was used for fever in the first year of life. Further, rhinoconjunctivis and eczema were also almost 1.5 times more likely with paracetamol usage in the first year of life.

An additional independent risk existed for paracetamol use in school-aged children. If paracetamol had been used a few times in the 12 months prior to the study, the child was 1.5 times more likely to have severe asthma symptoms, and if used once or more per months was over 3 times more likely to have severe asthma symptoms.

There are two likely explanations for these results. The first is that use of paracetamol increases susceptibility to asthma. The second is that paracetamol is frequently used to treat an illness that increases susceptibility to asthma (and so the two become associated, though it is in fact the illness, rather than the paracetamol that is the problem). An Editorial in the American Journal of Respiratory and Critical Care Medicine suggested that as lower respiratory tract rhinoviruses is associated with development of asthma, perhaps treating such viruses with paracetamol actually prolongs and worsens the illness by inhibiting antibodies, and this results in the higher rate of asthma (Holgate). A smaller Australian study of 620 children found that when the incident of early lower respiratory tract infections was controlled for, the link between asthma and paracetamol disappeared. However, one of the weaknesses of this study (apart from its size) is that nearly all the children in the study had taken at least some paracetamol, and that all the children in the study were those with a family history of symptoms for asthma or allergic diseases (Lowe).

The idea that paracetamol itself is a problem is also supported by a study which found that children whose mothers used paracetamol during pregnancy were at increased risk of asthma at 5 years of age (Holgate).

Side Effects of Ibuprofen (Neurofen)

Ibuprofen is a 'nonsteroidal anti-inflammatory drug' (a NSAID). NSAIDs can cause gastritis, bleeding, and ulcers of the stomach, duodenum and esophagus. Such symptoms are rare with ibuprofen, but have occurred even with the typical 'safe' doses used to reduce fever (Sullivan). By rare, the rate has been estimated as 7.2-17 children per 100,000 treated with ibuprofen (Chiappini).

NSAIDs also make extra work for the kidneys, and so seek medical advice before using in children with dehydration, cardiovascular disease, and preexisting renal disease. However, in two large studies of infants over 6 months who were given paracetamol or ibuprofen, the total rate of hospitalisation was 1-1.6%, and none were hospitalised for acute renal failure (Chiappini). The safety of ibuprofen for children under 6 months has not been established (Sullivan).

Alternating Paracetamol and Ibuprofen

It is a common practice among many mums I know to alternate Panadol and Neurofen. Because they work in different ways, they using them together does not cause an overdose, and so it has become a popular way to provide relief to a baby when the soothing effect of one of the drugs has worn off but it is too soon to give another dose. It is apparently a common treatment in the US (Carson).

In terms of its effect in reducing fever, it does not significantly bring down fever any more quickly (Erlewyn-Lajeunesse et al). However, over time paracetamol and ibuprofen together do have more of an effect at lowering fever and keeping down the temperature (Nabulsi et al).

There is no scientific research into whether this is a safe practice. The rate of short term and long term side effects is unknown. The American Academy of Paediatricians urge health care providers to 'exercise discretion' when recommending alternating paracetamol and ibuprofen because of the lack of research (Carson).

One possible problem is that paracetamol and ibuprofen tax the kidneys. The kidneys produce a chemical called glutathione in order to process some of the otherwise toxic chemicals in paracetamol. However, ibuprofen reduces the amountof glutathione the kidneys produce and blocks blood flow in the kidneys generally. This means that if the two drugs are taken together this could in theory lead to a build up of a toxic substance that the kidneys are unable to process (Carson).

The AAP position is: “there is insufficient evidence to support or refute the routine use of combination treatment.” However, they express concerns that it is more difficult to keep track of dosing and so is associated with overdosing, and that most of the time it is used to help the parents feel better about their 'fever phobia' rather than because it helps the child (Sullivan).

Overdosing on Panadol

According to Panadol's website, 15mg of paracetamol for every 1kg of body weight up to 4 times a day is the recommended dosage for children under 12 years. The liquid Baby Panadol has 100mg/1ml. So, a 6kg baby could have 1ml up to four times in a 24 hour period. The suppositories have 125mg, which is more than the recommended dose for a baby under 8kg, which is presumably why this product is suggested for 6mths+.

Overdosing on panadol can cause liver damage and death (Vale). A substance called N-acetylcysteine can help combat an overdose of panadol is given within 8-10 hours of the panadol overdose. If left untreated mortality is about 5% (Vale). In a baby under 12 months, over 100 mg/kg/day is likely to be toxic, particularly if continued over several days, and over 300mg/kg/day is likely to be fatal (Shann). A one-off dose of 150mg/kg can also be toxic (Aripin and Choonara).

Children with diabetes, obese children, dyhydrated or malnutritioned children or those who are not eating are at particular risk of paracetamol toxicity (Chiappini, Shivbalan) In an Indian study of paracetamol poisoning, all poisoned children were given more than 90mg/kg/day and had one of the risk factors (Shivbalan). Children under 1 month should not be given paracetamol except under medical advice and with monitoring.

To avoid overdosing:

• use only 'Baby Panadol' (or other brand equivalent) suitable for children under 12 months;
• measure the amount carefully according to the instructions, and using a proper measuring syringe (not, for example, a teaspoon); and
• write down when each dose is given and make sure to communicate with other persons who may also be looking after your baby.

Physical Treatments for Fever

Physical treatments include the cool baths, stripping off clothing, cool compresses, air-conditioning etc.

Physical methods for treating fever remain controversial. Lukewarm sponge baths do not seem to cause adverse effects, but more abrupt or significant methods (eg. cold baths, ice bags, rubbing the body with alcohol) have been shown to cause adverse effects including increasing the fever and depleting the patient's energy (Chiappini et al). Physical methods do not effectively lower a fever, although they are very effective for heat stroke.

Tepid (lukewarm – water about 30 degrees Celcius) sponging has been studied in various studies, some of which showed no or very little result, and one which showed a lowering of up to 0.8 degrees Celcius after about 15 minutes of sponging (Purssell). When combined with an antipyretic, sponging does not seem to have any additional effect on lowering body temperature (Newman). Sponging causes only a short-term fall in temperature, but it appears to have no negative side-effects, such as a rebound temperature when sponging is dicontinued (Purssell).

Removing clothing and turning on fans have been shown to have little to no effect on reducing the core body temperature of a fever (Purssell).

It should be noted that during the initial phase of a fever, a patient feels cold and will not appreciate being further cooled, and excess cooling may trick the body into thinking it needs to heat up more to reach the temperature it is aiming for with the fever. It is therefore important not just to 'cool' the patient because they seem hot to you, but to look at whether cooling measures seem to actually make them more comfortable (Scrase and Tranter).

Treating the Child's Discomfort

If fever itself is not a problem, then it is not the fever itself we must treat but the underlying illness. Parents nevertheless need support to feel that they are 'doing something' to look after their sick child, and need to look at ways to relieve their child's discomfort. The latest medical opinion supports the use of paracetamol or neurofen, not to reduce fever, but in those situations where it could provide pain relief to the child (Sullivan).

For quick discomfort, such as injection, giving the child something sweet to suck on (eg a dummy dipped in a sweet substance) has been shown to reduce pain for 2-5 minutes in infants (Harrison et al). This isn't very feasible or effective for something ongoing like a fever, though is worth bearing in mind if blood tests or catheters become necessary. If trying this at home also remember that honey and corn syrup are not suitable for babies because of the risk of botulism.

Other proven pain management techniques in infants include kangaroo care (holding the baby with your skin touching their skin), and breastfeeding (Harrison et al). Kangaroo care has been shown to have greater pain reduction for the pain of immunisation (Harrison et al).

With the second fever my baby had recently, I found that kangaroo care really helped. We usually sleep near each other on separate mattresses, but during the fever she wanted to sleep on my exposed stomach and chest, and this really did seem to help her relax and sleep.

Psychological Issues In Treating a Fever

It is important to recognise that many parents and health practitioners have an abiding fear of fever to the extent that the medical literature now speaks of 'fever phobia' (Chiappini et al, Clinch et al, Walsh 2006). Febrile convulsions are particularly scary and almost certainly create a situation of parental anxiety. Parental anxiety can lead to unnecessary drug use or other interventions (eg. unnecessary invasive tests).

For my part, I remember being so worried with my baby's first fever above 39 degrees Celcius that I took her to hospital and had a sample of urine taken by catheter (necessary for a girl to get an uncontaminated sample). I was advised that the catheter was a little uncomfortable but not painful. What I didn't realise is that it would take 3 goes to get the catheter in, while my baby was held down screaming, and that the later test results revealed the scratching around drew blood (presence of red blood cells in sample). Afterwards Bethany cried and cried in my arms, more distressed than after her immunisations. It was at that point that I realised that my need to be reassured and feel like I was 'doing something' had led me to request my baby go through an unnecessarily stressful and painful procedure.

“In 1980 48% to 53% of parents woke sleeping febrile children. Today [2006], this has increased ot between 66% and 92%. Parents need reassurance that they are managing their febrile child appropriately. They often contact medical practitioners for low fevers or fevers of short duration. Although this creates guilt in some parents, they feel they have little choice; their concern for their child needed a shared responsibility.”

Apart from creating stressful experiences for the child, a child may actually find a parent's anxiety stressful, and that this stress taxes their body and makes it harder for them to fight the illness:

“The sense of loss of control when faced with a febrile child contributes to parental anxiety. Parents' control refers to the adequate control of the observed effects of an illness and protecting their child from potential harm. … Similarly to childhood fever, pain in children is also a significant source of anxiety for the parent and adequate pain management helps reduce parental anxiety, which may reduce the child's anxiety and aid recovery” (Clinch)

It is therefore important that parents support each other in order to make an informed choice about whether to administer antipyretics or have tests conducted looking at all the circumstances.

Now when I decide not to administer paracetamol for a fever, I tell myself I am doing something - I am helping my baby's body have the best shot at fighting the infection itself.

References:

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Carson 'Alternating Acetaminophen and Ibuprofen in the Febrile Child: Examination of the Evidence Regarding Efficacy and Safety' (2003) Volume 29(5) Pediatric Nursing 379.

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