Evidence-based recommendations for symptomatic fever management in children

Parents and carers should identify danger symptoms and assess conditions beyond fever, prioritize social and physical environment enhancement over fever reduction, and use antipyretic medicine as first-line treatment for healthy children with acute febrile illness.

Fever is a physiologically controlled temperature increase with a strong upper limit, regulated by protective endogenous antipyretics and thermosensitive neuron inactivity at temperatures above 42˚C. It’s a common health concern, rarely reaches 41˚C and is not as dangerous as feared by parents and health professionals. The growth of "fever-phobia" is attributed to worries held by parents, tutors, and caregivers about potentially dangerous causes of fever, such as severe bacterial infections, and false beliefs that fever is a sufficient trigger for brain damage.

Numerous research studies have reported a significant proportion of parents, instructors, and caregivers administering antipyretics when there is little to no fever with incorrect dosage, or inadequate time between doses. Fever is a physiological response that helps fight illness and has no long-term negative consequences on the nervous system. Relieving the child's suffering rather than lowering their body temperature should be the main objective of treating fever in children.

Improper fever control can impede diagnosis and raise the possibility of overdosing on antipyretics. Additionally, using rectal formulations, administering these medications in the presence of underlying illnesses for which they are contraindicated, and switching between or combining the use of two antipyretics are other variables may exacerbate drug toxicity. Lastly, excessive therapy could have a big financial effect in high- and low-income nations.

The diverse attitudes towards fever have resulted in inconsistencies in managing it. Despite evidence suggesting fever as an evolutionary resource aiding in overcoming acute infections, many healthcare providers and parents view it as a dangerous condition. In the USA, an accidental overdose of paracetamol resulted in 100 fatalities in 2006. Since antipyretic medication can be detrimental, organizations have produced clinical practice guidelines (CPGs) to manage fever in children.

CPGs guide treatment, eliminate evidence-based disparities, and lessen irrational fear and excessive suppression attempts. A review of seven CPGs found that even high-quality guidelines are not comprehensive or consistent in their recommendations. The entire range of recommendations for treating childhood fever is still unknown. Therefore, it is necessary to summarize all recommendations and assess the evidence level for each recommendation offered by the CPGs currently in use for fever treatment.

RATIONALE BEHIND RESEARCH

Even with the most recent recommendations, there is no consensus advice that is supported by the data, and many of them contradict it. The threshold question remains unanswered despite its basic relevance. Guidelines remain problematic for the most common intervention (antipyresis). So far, no comprehensive evaluation of the evidence supporting the CPG recommendations for fever has been conducted.

OBJECTIVE

To perform a comprehensive evidence-based assessment of CPGs for the symptomatic management of pediatric fever.

Literature search

The study used various databases viz., PubMed, Google Scholar, pediatric society websites and guideline databases to locate CPGs (documents on symptomatic fever management in children, issued by governmental organizations, pediatric associations, or other healthcare groups) from each of the 195 countries, covering the period from 1995 to 2020. The International Pediatric Association's website was used to scrutinize relevant documents related to fever among national pediatric associations.

The Oxford Centre for Evidence-Based Medicine, or OCEBM, evaluated the quality of the evidence pertaining to each recommendation. To examine the body of evidence pertaining to the threshold for starting antipyresis, a GRADE evaluation was carried out. The systematic review adhered to the PRISMA statement to structure all methods. Suitable medical guideline databases were found via a Google search for "medical guideline databases" and then searched using specific terms.

Inclusion criteria

• All CPGs published between 1995 and September 1, 2020, in the 57 languages that were accessible on PubMed, were included, regardless of whether they were meant for parents or healthcare professionals.
• The latest CPGs of each series were included.

Exclusion criteria

Articles that were identical to other guidelines or the ones that did not focus on symptomatic management of fever were excluded.

Study selection and data extraction

One reviewer extracted data from all sources into an excel table.
 

Data and statistical analysis

N/A

Risk of bias and quality assessment

Two investigators analyzed the highest level of supporting evidence using a modified version of the OCEBM Criteria for each recommendation. The best quality evidence was produced by systematic reviews of randomized trials (level 1). This was followed by systematic reviews of observational and single randomized control trials (level 2), individual prospective observational studies, systematic reviews of case reports, and individual case reports (level 3), individual case reports (level 4), and mechanistic explanations (level 5).

The OCEBM was modified to assign systematic reviews of prospective observational studies to level 2, case reports to level 3, and suitable non-human studies to level 5. The rigor of systematic reviews was assessed using AMSTAR criteria, with a rating of one level lowered if the review met fewer than 7 out of 11 criteria. For instance, a systematic review of randomized trials was classified as level 2 instead of level 1. Two researchers independently assessed the evidence quality. They resolved any kind of disagreements via discussion.

Study outcomes

N/A

Outcomes

Study and participant characteristics:

• After the identification of 586 documents, 441 were disregarded because they were duplicates or not relevant. The remaining records (145) were retrieved in full text, and 71 were eliminated since they weren't CPGs.
• The study incorporated 74 fever management guidelines from 49 countries, including three international and national guidelines, and 6 from other national or international guidelines, ensuring that the recommendations represent at least 55 countries' fever management strategies.
• The inventory of recommendations revealed conflicting advice across all categories, and only a few CPGs provided references to support their recommendations.
• Several papers discussing the effect of fever control on the course of illness in intensive care unit patients were found through the search. Upon closer inspection, these studies excluded minors expressly or included a threshold value for rescue treatment.
• The research discovered that the antipyretic RCTs' placebo arms used a threshold rescue value to function, and neither trial provided data on temperature-related morbidity or death. Permissive fever management probably didn't have any bad effects, but the studies weren't included since the outcomes weren't measured.

Study quality:

N/A

Effect of intervention on the outcome:

• Recommendations varied widely regarding antipyretic thresholds, type and dose; ambient temperature; clothing; activity; fluids; nutrition; proctoclysis; external applications; complementary/herbal treatments; media; and age-specific approaches.
• Most recommendations had low or indeterminable OCEBM evidence levels (Level 3–4).
• The GRADE assessment showed a very low level of evidence for antipyresis thresholds (Table 1).

Since CPGs present low evidence levels for recommendations and a very low threshold for antipyresis, they need to be improved in terms of methodology, applicability and editorial independence. Thus, it becomes imperative to summarize and evaluate the existing information to produce a consensual and evidence-based fever guideline.

Antipyresis Temperature Threshold: Evidence vs Clinical Practice

• In general, CPGs advocate avoiding treating fever, regardless of the temperature. There is little consensus about the ideal temperature for the antipyresis threshold; estimates range from 37.5°C to 40.5°C without any discernible pattern.
• According to the GRADE evaluation, the highest threshold for antipyresis utilized in research shows that a threshold below 39.5 ˚C is unnecessary; nonetheless, the necessity of such a threshold remains uncertain due to inadequate data.
• There is a paucity of research to assess if a body temperature-based antipyretic threshold is necessary. Studies reveal that heat-related unfavorable outcomes rise with temperatures over 40°C, and over 90% of physicians prescribe antipyretic medication at higher temperatures, despite guidelines against the utilization of temperature-based antipyretics.
• A UK study reveals that despite guidelines recommending treating distress, pediatric ICUs still set a fever threshold of 38˚C, with 58% of caregivers deeming a 39˚C fever unacceptable.

Pharmacologic Treatment: Medication Selection, Dosage, Side Effects

• All recommendations prescribe paracetamol as the only medicine, and 17 guidelines recommend it above ibuprofen. While they both work well to reduce body temperature, there is weaker evidence that they are also valuable in reducing distress.
• Ibuprofen was shown to have a superior impact in 15 out of 30 RCTs, with no  pivotal difference detected in either the effect or safety profiles in the remaining studies.
• The question arises whether paracetamol should be relegated to second-line treatment owing to its faster toxic level and higher death rate as opposed to ibuprofen, despite both drugs having equivalent safety profiles at therapeutic doses.
• The side effects of ibuprofen normally go away, but long-term problems from toxic epidermal and soft tissue necrolysis, as well as fatalities from asthma triggers, have been reported.
• About 67% of patients in medical practice use alternating antipyretics, despite research suggesting they may not improve temperature management and magnify the risk of supratherapeutic doses, or reduce pain. Parents often misdose antipyretics, suggesting a consensus on medication choice and communication methods.

Preventing Febrile Seizures with Antipyretics:

• Antipyretics are ineffective in evading febrile seizures (Level 1), as several RCTs and systematic reviews have shown.
• A trial revealed that antipyretics are ineffective in lowering temperature during febrile episodes linked to febrile seizures.
• According to a recent study, giving paracetamol via the rectal route considerably decreased the risk of having more febrile seizures during the same fever episode.

Nonpharmacologic Interventions: Bathing, Compressing, Rubbing, and Consuming Fluids

• Guidelines suggest increasing fluid intake to prevent dehydration, but not in excess. There is a dearth of data on the type of fluid and optimal intake during fever.
• Proctoclysis, while not mentioned in a single guideline, has been found to aid in maintaining hydration status thereby enhancing well-being and reducing hospitalizations.
• 25% of guidelines mention nutrition, with the majority agreeing that children should not be forced to eat during fever, but no studies have been identified on this topic.
• Different physical treatments must be utilized depending on the fever's stage. To minimize the energy required for the fever and pain to grow, the kid should be kept warm.
• Despite high-level evidence suggesting tepid sponging increases discomfort, 61% of guidelines still support its use, while 63% support compresses.
• Majority of guidelines don’t recommend cool/ice bath. External cooling causes a short-term temperature decrease, leading to peripheral vasoconstriction and metabolic heat production. This causes shivering and increased discomfort in children. The initial reduction may not be worth the discomfort, suggesting a focus on temperature reduction rather than distress management.

Complementary Recommendations:

• Although complementary therapies like homeopathic recommendations; Aconitum, Belladona, Ferrum phosphoricum and Chamomile are widely used by parents and medical professionals, three guidelines recommend them. The poor level of evidence supporting these therapies may be attributed to alternative medicine not favoring fever suppression.
• Based on scientific research, well-being therapies are more or equally effective and satisfying when compared to traditional procedures, and they are also highly safe and tolerable.

Other Potential Issues Not Yet Incorporated In the Issued Guidelines:

• The majority of nations are creating policies for children's screen time, but advice about screen use during illness is also fundamental.
• The quality of parental care via friendship, empathy, and interaction during sickness is an important factor for both short-term and long-term health, but it is not well addressed in the guidelines. Distress can be curtailed by fostering relational and sympathetic fever control by lowering fever fear through education or counselling.