Sie sind auf Seite 1von 10

Guidance for the Clinician in

Rendering Pediatric Care

Clinical ReportFever and Antipyretic Use in


Children
Janice E. Sullivan, MD, Henry C. Farrar, MD, and the
abstract SECTION ON CLINICAL PHARMACOLOGY AND THERAPEUTICS,
and COMMITTEE ON DRUGS
Fever in a child is one of the most common clinical symptoms managed
KEY WORDS
by pediatricians and other health care providers and a frequent cause fever, antipyretics, children
of parental concern. Many parents administer antipyretics even when
ABBREVIATIONS
there is minimal or no fever, because they are concerned that the child NSAIDnonsteroidal anti-inammatory drug
must maintain a normal temperature. Fever, however, is not the The guidance in this report does not indicate an exclusive
primary illness but is a physiologic mechanism that has benecial course of treatment or serve as a standard of medical care.
effects in ghting infection. There is no evidence that fever itself wors- Variations, taking into account individual circumstances, may be
appropriate.
ens the course of an illness or that it causes long-term neurologic
This document is copyrighted and is property of the American
complications. Thus, the primary goal of treating the febrile child Academy of Pediatrics and its Board of Directors. All authors
should be to improve the childs overall comfort rather than focus on have led conict of interest statements with the American
the normalization of body temperature. When counseling the parents Academy of Pediatrics. Any conicts have been resolved through
a process approved by the Board of Directors. The American
or caregivers of a febrile child, the general well-being of the child, the
Academy of Pediatrics has neither solicited nor accepted any
importance of monitoring activity, observing for signs of serious ill- commercial involvement in the development of the content of
ness, encouraging appropriate uid intake, and the safe storage of this publication.
antipyretics should be emphasized. Current evidence suggests that
there is no substantial difference in the safety and effectiveness of
acetaminophen and ibuprofen in the care of a generally healthy child
with fever. There is evidence that combining these 2 products is more
effective than the use of a single agent alone; however, there are con-
cerns that combined treatment may be more complicated and contrib-
ute to the unsafe use of these drugs. Pediatricians should also promote
patient safety by advocating for simplied formulations, dosing in-
structions, and dosing devices. Pediatrics 2011;127:580587
www.pediatrics.org/cgi/doi/10.1542/peds.2010-3852
INTRODUCTION doi:10.1542/peds.2010-3852
Fever is one of the most common clinical symptoms managed by pedi- All clinical reports from the American Academy of Pediatrics
atricians and other health care providers and accounts, by some esti- automatically expire 5 years after publication unless reafrmed,
revised, or retired at or before that time.
mates, for one-third of all presenting conditions in children.1 Fever in a
child commonly leads to unscheduled physician visits, telephone calls PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

by parents to their childs physician for advice on fever control, and the Copyright 2011 by the American Academy of Pediatrics

wide use of over-the-counter antipyretics.


Parents are frequently concerned with the need to maintain a normal
temperature in their ill child. Many parents administer antipyretics
even though there is either minimal or no fever.2 Approximately one-
half of parents consider a temperature of less than 38C (100.4F) to be
a fever, and 25% of caregivers would give antipyretics for tempera-
tures of less than 37.8C (100F).1,3 Furthermore, 85% of parents (n
340) reported awakening their child from sleep to give antipyretics.1
Unfortunately, as many as one-half of parents administer incorrect
doses of antipyretics; approximately 15% of parents give suprathera-
peutic doses of acetaminophen or ibuprofen.4 Caregivers who under-

580 FROM THE AMERICAN ACADEMY OF PEDIATRICS


Downloaded from by guest on June 2, 2017
FROM THE AMERICAN ACADEMY OF PEDIATRICS

stand that dosing should be based on more quickly from viral infections, al- tributable to heat stroke. Thus, extrap-
weight rather than age or height of fe- though the fever may result in discom- olating similar outcomes from these
ver are much less likely to give an in- fort in children.11,1618 Evidence is in- different illnesses is problematic.
correct dose.4 conclusive as to whether treating with
Physicians and nurses are the primary antipyretics, particularly ibuprofen TREATMENT GOALS
source of information on fever man- alone or in combination with acet- A discussion of the use of antipyretics
agement for parents and caregivers, aminophen, increases the risks of in febrile children must begin with
although there are some disparities complications with certain types of in- consideration of the therapeutic end
between the views of parents and phy- fections.19,20 Potential benets of fever points. When counseling families, phy-
sicians regarding antipyretic treat- reduction include relief of patient dis- sicians should emphasize the childs
ment.1 The most common indications comfort and reduction of insensible comfort and signs of serious illness
for initiating antipyretic therapy by pe- water loss, which may decrease the rather than emphasizing normother-
diatricians are a temperature higher occurrence of dehydration. Risks of mia. A primary goal of treating the fe-
than 38.3C (101F) and improving lowering fever include delayed identi- brile child should be to improve the
the childs overall comfort.5 Although cation of the underlying diagnosis and childs overall comfort. Most pediatri-
only 13% of pediatricians specically initiation of appropriate treatment cians observe, with some supporting
cite discomfort as the primary indi- and drug toxicity. data from research, that febrile chil-
cation for antipyretic use,6 this in- There is no evidence that children with dren have altered activity, sleep, and
tent is generally implied in their rec- fever, as opposed to hyperthermia, are behavior in addition to decreased oral
ommendations. Most pediatricians at increased risk of adverse outcomes intake.28 Unfortunately, there is a pau-
(80%) believe that a sleeping ill child such as brain damage.7,9,2123 Fever is a city of clinical research addressing the
should not be awakened solely to be common and normal physiologic re- extent to which antipyretics improve
given antipyretics.5 sponse that results in an increase in discomfort associated with fever or ill-
Antipyretic therapy will remain a com- the hypothalamic set point in re- ness. It is not clear whether comfort
mon practice by parents and is gener- sponse to endogenous and exogenous improves with a normalized tempera-
ally encouraged and supported by pe- pyrogens.9,23 In contrast, hyperthermia ture, because external cooling mea-
diatricians. Thus, pediatricians and is a rare and pathophysiologic re- sures, such as tepid sponge baths, can
health care providers are responsible sponse with failure of normal ho- lower the body temperature without
for the appropriate counseling of par- meostasis (no change in the hypotha- improving comfort.7,29 The use of alco-
ents and other caregivers about fever lamic set point) that results in heat hol baths is not an appropriate cooling
and the use of antipyretics.7 production that exceeds the capability method, because there have been re-
to dissipate heat.9,23 Characteristics ported adverse events associated with
PHYSIOLOGY OF FEVER of hyperthermia include hot, dry skin systemic absorption of alcohol.30 Fur-
It should be emphasized that fever is and central nervous system dysfunc- thermore, antipyretics have other clin-
not an illness but is, in fact, a physio- tion that results in delirium, convul- ical outcomes, including analgesia,
logic mechanism that has benecial ef- sions, or coma.23 Hyperthermia which may enhance their overall clini-
fects in ghting infection.810 Fever re- should be addressed promptly, be- cal effect. Regardless of the exact
tards the growth and reproduction of cause at temperatures above 41C to mechanism of action, many physicians
bacteria and viruses, enhances neu- 42C, adverse physiologic effects be- continue to encourage the use of anti-
trophil production and T-lymphocyte gin to occur.7,9,24 Studies of health pyretics with the belief that most of the
proliferation, and aids in the bodys care workers, including physicians, benets are the result of improved
acute-phase reaction.1114 The degree have revealed that most believe that comfort and the accompanying im-
of fever does not always correlate with the risk of heat-related adverse out- provements in activity and feeding,
the severity of illness. Most fevers are comes is increased with tempera- less irritability, and a more reliable
of short duration, are benign, and may tures above 40C (104F), although sense of the childs overall clinical con-
actually protect the host.15 Data show this belief is not justied.5,23,2527 A dition. Because these are the most im-
benecial effects on certain compo- child with a temperature of 40C portant benets of antipyretic therapy,
nents of the immune system in fever, (104F) attributable to a simple febrile it is of paramount importance that pa-
and limited data have revealed that fe- illness is quite different from a child rental counseling focus on monitoring
ver actually helps the body recover with a temperature of 40C (104F) at- of activity, observing for signs of seri-

PEDIATRICS Volume 127, Number 3, March 2011 581


Downloaded from by guest on June 2, 2017
ous illness, and appropriate uid in- ited on the actual risks of fever and the leading to hepatotoxicity; therefore,
take to maintain hydration. benets of antipyretic therapy, it is such doses are not recommended.
The desire to improve the overall com- recognized that improvement in pa- Although hepatotoxicity with acetamin-
fort of the febrile child must be bal- tient comfort is a reasonable thera- ophen at recommended doses has
anced against the desire to simply peutic objective. Furthermore, at this been reported rarely, hepatoxicity is
lower the body temperature. It is well time, there is no evidence that temper- most commonly seen in the setting of
documented that there are signicant ature reduction, in and of itself, should an acute overdose. In addition, there is
concerns on the part of parents, be the primary goal of antipyretic signicant concern over the possibility
nurses, and physicians about potential therapy. of acetaminophen-related hepatitis in
adverse effects of fever that have led to the setting of a chronic overdose. The
Acetaminophen
a description in the literature of fever most commonly reported scenarios
phobia.31 The most consistently iden- After sufcient evidence emerged of are those of children receiving multi-
an association between salicylates
tied serious concern of caregivers ple supratherapeutic doses (ie, 15
and health care providers is that high and Reye syndrome, acetaminophen
mg/kg per dose) or frequent adminis-
fevers, if left untreated, are associated essentially replaced aspirin as the pri-
tration of appropriate single doses at
with seizures, brain damage, and mary treatment of fever. Acetamino-
intervals of less than 4 hours, which
death.1,25,32,33 It is argued that by creat- phen doses of 10 to 15 mg/kg per dose
has resulted in doses of more than 90
ing undue concern over these pre- given every 4 to 6 hours orally are gen-
mg/kg per day for several days.46,47 Giv-
sumed risks of fever, for which there is erally regarded as safe and effective.
ing an adult preparation of acetamino-
no clearly established relationship, Typically, the onset of an antipyretic ef-
phen to a child may result in suprath-
physicians are promoting an exagger- fect is within 30 to 60 minutes; approx-
erapeutic dosing. In 1 case series,46
ated desire in parents to achieve nor- imately 80% of children will experience
half of the children with hepatotoxicity
mothermia by aggressively treating a decreased temperature within that
time (Table 1). had received adult preparations of
fever in their children. acetaminophen.
There is no evidence that reducing fe- Although alternative dosing regimens
One safety concern is the effect of
ver reduces morbidity or mortality have been suggested,41 43 no consis-
acetaminophen on asthma-related
from a febrile illness. Possible excep- tent evidence has indicated that the
use of an initial loading dose by either symptoms; although asthma has also
tions to this could be children with un-
the oral (30 mg/kg per dose) or rectal been associated with acetamino-
derlying chronic diseases that may re-
(40 mg/kg per dose) route improves phen use, causality has not been
sult in limited metabolic reserves or
antipyretic efcacy. The higher rectal demonstrated.4851
children who are critically ill, because
these children may not tolerate the in- dose is often used in intraoperative
conditions but cannot be recom- Ibuprofen
creased metabolic demands of fever.34
Finally, there is no evidence that anti- mended for use in routine clinical The use of ibuprofen to manage fever
pyretic therapy decreases the recur- care.44,45 The use of higher loading has been increasing, because it seems
rence of febrile seizures.22,35,36 doses in clinical practice would add to have a longer clinical effect related
potential risks for dosing confusion to lowering of the body temperature
Despite insufcient evidence, many pe-
diatricians recommend the routine
practice of pretreatment with acet-
aminophen or ibuprofen before a pa- TABLE 1 Antipyretic Information
tient receives immunizations to de- Variable Acetaminophen Ibuprofen
crease the discomfort associated with Decline in temperature, C 12 12
Time to onset, h 1 1
the injections and subsequently at the Time to peak effect, h 34 34
injection sites and to minimize the fe- Duration of effect, h 46 68
brile response.9,17,3739 In addition, re- Dose, mg/kg 1015 every 4 h 10 every 6 h
sults of 1 recent study suggested the Maximum daily dose, mg/kg 90 mg/kga 40 mg/kg
Maximum daily adult dose, g/d 4 2.4
possibility of decreased immune re- Lower age limit, mob 3 6
sponse to vaccines in patients treated Data represent approximate averages from referenced sources.42,43,52,54,71,82
early with antipyretics.40 a Label is for 75 mg/kg; 90 mg/kg per day should be limited to less than 3 consecutive days.83-85

b Unless specically recommended by a health care provider for the younger patient and, then, only after the infant has been

Although the available literature is lim- examined by a health care provider.

582 FROM THE AMERICAN ACADEMY OF PEDIATRICS


Downloaded from by guest on June 2, 2017
FROM THE AMERICAN ACADEMY OF PEDIATRICS

(Table 1). Studies in which the effec- dehydration or with complex medical alternating acetaminophen and ibu-
tiveness of ibuprofen and acetamino- illnesses.61 63 In children with dehydra- profen for fever control, 81% of whom
phen were compared have yielded tion, prostaglandin synthesis becomes stated that they had followed the ad-
variable results; the consensus is that an increasingly important mechanism vice of their health care provider or
both drugs are more effective than pla- for maintaining appropriate renal pediatrician.70 Although 4 hours was
cebo in reducing fever and that ibupro- blood ow. The use of ibuprofen or any the most frequent interval, parents re-
fen (10 mg/kg per dose) is at least as NSAID interferes with the renal effects ported alternating therapy every 2, 3,
effective as, and perhaps more effec- of prostaglandins, which reduces re- 4, and 6 hours, which suggests that
tive than, acetaminophen (15 mg/kg nal blood ow and potentially precipi- there is no consensus on dosing
per dose) in lowering body tempera- tates or worsens renal dysfunction.61,63 instructions.
ture when either drug is given as a sin- However, it is not possible to deter-
At the time of this report, 5 studies had
gle or repetitive dose.5257 Data also mine the actual incidence of
been identied that compared alter-
show that the height of the fever and ibuprofen-related renal insufciency
nating ibuprofen and acetaminophen
the age of the child (rather than the after short-term use, because it has
versus either acetaminophen or ibu-
specic medication used) may be the not been systematically investigated
profen as single agents.7175 Initially,
primary determinants of the efcacy or reported.64 Children who are at
changes in temperature were similar
of antipyretic therapy; those who have greatest risk of ibuprofen-related re-
for all groups in these studies, regard-
a higher fever and are older than 6 years nal toxicity are those with dehydration,
less of therapy. However, 4 or more
show decreased efcacy or response to cardiovascular disease, preexisting
hours after the initiation of treat-
antipyretic therapy.54 Studies that com- renal disease, or the concomitant use
ment, lower temperature was consis-
pare the effect of ibuprofen versus acet- of other nephrotoxic agents.62 Another
tently observed in the combination-
aminophen on childrens behavior and potential group at risk is infants
treatment groups. For example, 6 and
comfort are generally lacking. younger than 6 months because of the
8 hours after the initiation of the study,
possibility of differences in ibuprofen
There is no evidence to indicate that a greater percentage of children were
pharmacokinetics and developmental
there is a signicant difference in the afebrile in the combination group
differences in renal function.65 Data
safety of standard doses of ibuprofen (83% and 81%, respectively) compared
are inadequate to support a specic
versus acetaminophen in generally with those in the group that received
recommendation for the use of ibupro-
healthy children between 6 months ibuprofen alone (58% and 35%, respec-
fen for fever or pain in infants younger
and 12 years of age with febrile illness- tively).71 Only 1 study72 evaluated is-
than 6 months (there are dosing data
es.58 Similar to other nonsteroidal anti- sues related to stress and comfort and
for neonatal closure of patent ductus
inammatory drugs (NSAIDs), ibupro- found lower stress scores and less
arteriosus66,67), although the package
fen can potentially cause gastritis,59,60 insert states to ask a doctor for guid- time missed from child care in the
although no data suggest that this is a ance on its use in this population. An- combination-treatment group. An-
common occurrence when used on an other potential risk associated with other study73 showed a trend toward a
acute basis, such as during a febrile the use of ibuprofen is the possible as- normalization of fever-related symp-
illness.58 However, there have been sociation between ibuprofen and toms by 24 and 48 hours after institu-
case reports of bleeding, gastritis, varicella-related invasive group A tion of therapy, but these trends disap-
and ulcers of the stomach, duodenum, streptococcal infection.68,69 However, peared by day 5.
and esophagus associated with many at the time of this report, data were Although the aforementioned studies
NSAIDs, including ibuprofen, even when insufcient to support a causal rela- provide some evidence that combina-
used in typical antipyretic and analgesic tionship between ibuprofen and inva- tion therapy may be more effective at
doses.59,60 Ibuprofen does not seem to sive group A streptococcal disease. lowering temperature, questions re-
worsen asthma symptoms. main regarding the safety of this prac-
Concern has been raised over the Alternating or Combination tice as well as the effectiveness in im-
nephrotoxicity of ibuprofen. In numer- Therapy proving discomfort, which is the
ous case reports, children with febrile A practice frequently used to control primary treatment end point. The pos-
illnesses developed renal insufciency fever is the alternating or combined sibility that parents will either not re-
when treated with ibuprofen or other use of acetaminophen and ibuprofen. ceive or not understand dosing in-
NSAIDs. Thus, caution is encouraged In a convenience sample survey of 256 structions, combined with the wide
when using ibuprofen in children with parents or caregivers, 67% reported array of formulations that contain

PEDIATRICS Volume 127, Number 3, March 2011 583


Downloaded from by guest on June 2, 2017
these drugs, increases the potential tions, physicians should encourage cians should advocate for a limited
for inaccurate dosing or overdos- families to only use 1 formulation. number of formulations of acetamino-
ing.76,77 Finally, this practice may only Acetaminophen is the most common phen and ibuprofen and for clear label-
promote the fever phobia that already single ingredient implicated in emer- ing of dosing instructions and an in-
exists. gency department visits for medica- cluded dosing device for antipyretic
Although there is some evidence that tion overdoses among children, and products.
combination therapy may result in a more than 80% of these emergency
visits are a result of unsupervised LEAD AUTHORS
lower body temperature for a greater Janice E. Sullivan, MD
period of time, there is no evidence ingestions81; therefore, proper han- Henry C. Farrar, MD
that combination therapy results in dling and storage of antipyretics
COMMITTEE ON DRUGS, 2009 2010
overall improvement in other clinical should be encouraged. Daniel A. C. Frattarelli, MD, Chairperson
outcomes. Also, these studies have not Jeffrey L. Galinkin, MD
SUMMARY Thomas P. Green, MD
contained adequate numbers of sub- Mary A. Hegenbarth, MD
Appropriate counseling on the man-
jects to fully evaluate the safety of this Mark L. Hudak, MD
agement of fever begins by helping Matthew E. Knight, MD
practice. Therefore, there is insuf-
parents understand that fever, in and Robert E. Shaddy, MD
cient evidence to support or refute the
of itself, is not known to endanger a FORMER COMMITTEE ON DRUGS
routine use of combination treatment
generally healthy child. In contrast, fe- MEMBER
with both acetaminophen and ibupro-
ver may actually be of benet; thus, the Wayne R. Snodgrass, MD, PhD
fen. Practitioners who choose to follow
real goal of antipyretic therapy is not CONSULTANT
this practice should counsel parents
simply to normalize body temperature Robert M. Ward, MD
carefully regarding proper formula-
but to improve the overall comfort and LIAISONS
tion, dosing, and dosing intervals and
well-being of the child. Acetaminophen John J. Alexander, MD Food and Drug
emphasize the childs comfort instead
and ibuprofen, when used in appropri- Administration
of reduction of fever. Janet D. Cragan, MD Centers for Disease
ate doses, are generally regarded as
Control and Prevention
safe and effective agents in most clini- George P. Giacoia, MD National Institutes of
INSTRUCTIONS FOR CAREGIVERS
cal situations. However, as with all Health
It is critically important for pediatri- drugs, they should be used judiciously Michael J. Rieder, MD Canadian Paediatric
cians to clearly describe the appropri- Society
to minimize the risk of adverse drug Adelaide Robb, MD American Academy of
ate use (ie, formulation, dose, and dos- effects and toxicity. Combination ther- Child and Adolescent Psychiatry
ing interval) of acetaminophen and apy with acetaminophen and ibupro- Hari C. Sachs, MD Food and Drug
ibuprofen to caregivers (Table 1). Child fen may place infants and children at Administration
safety will be further enhanced by increased risk because of dosing er- STAFF
clear labeling and the development of rors and adverse outcomes, and these Raymond J. Koteras, MHA
rkoteras@aap.org
simplied dosing methods, standard- potential risks must be carefully con-
ized drug concentrations, and stan- sidered. When counseling a family on SECTION ON CLINICAL PHARMACOLOGY
dardized delivery devices.78 80 Cough- the management of fever in a child, pe- AND THERAPEUTICS, 2009 2010
Janice E. Sullivan, MD, Chairperson
and-cold products that contain diatricians and other health care pro- Glen S. Frick, MD
acetaminophen and ibuprofen should viders should minimize fever phobia Lynne G. Maxwell, MD
not be given to children because of the and emphasize that antipyretic use Ian M. Paul, MD
possibility that parents may uninten- John F. Pope, MD
does not prevent febrile seizures. Pedi- Thomas G. Wells, MD
tionally give their child simultaneous atricians should focus instead on mon-
doses of an antipyretic and a cough- FORMER EXECUTIVE COMMITTEE
itoring for signs/symptoms of serious
MEMBERS
and-cold medication that contains the illness, improving the childs comfort Charles J. Cote, MD
same antipyretic. In addition, there is a by maintaining hydration, and educat- Henry C. Farrar, MD
lack of proven efcacy for this class of ing parents on the appropriate use, Richard L. Gorman, MD
combination products for children. For dosing, and safe storage of antipyret- STAFF
children who require liquid prepara- ics. To promote child safety, pediatri- Raymond J. Koteras, MHA

584 FROM THE AMERICAN ACADEMY OF PEDIATRICS


Downloaded from by guest on June 2, 2017
FROM THE AMERICAN ACADEMY OF PEDIATRICS

REFERENCES
1. Crocetti M, Moghbeli N, Serwint J. Fever 18. Plaisance KI, Kudaravalli S, Wasserman SS, 33. Karwowska A, Nijssen-Jordan C, Johnson D,
phobia revisited: have parental misconcep- Levine MM, Mackowiak PA. Effect of antipy- Davies HD. Parental and health care provider
tions about fever changed in 20 years. Pedi- retic therapy on the duration of illness in understanding of childhood fever: a Canadian
atrics. 2001;107(6):12411246 experimental inuenza A, Shigella sonnei, perspective. CJEM. 2002;4(6):394 400
2. Bilenko N, Tessler H, Okbe R, Press J, Goro- and Rickettsia rickettsii infections. Phar- 34. Kayman H. Management of fever: making
discher R. Determinants of antipyretic mis- macotherapy. 2000;20(12):14171422 evidence-based decisions. Clin Pediatr
use in children up to 5 years of age: a cross- 19. Burnett AM, Domachowske JB. Therapeutic (Phila). 2003;42(5):383392
sectional study. Clin Ther. 2006;28(5): considerations for children with invasive 35. Duffner PK, Baumann RJ. A synopsis of the
783793 group A streptococcal infections: a case se- American Academy of Pediatrics practice
3. Kramer MS, Naimark L, Leduc DG. Parental ries report and review of the literature. Clin parameters on the evaluation and treat-
fever phobia and its correlates. Pediatrics. Pediatr (Phila). 2007;46(6):550 555 ment of children with febrile seizures. Pedi-
1985;75(6):1110 1113 20. Ospina CAC, Salcedo A. Ibuprofen increases atr Rev. 1999;20(8):285287
4. Li SF, Lacher B, Crain EF. Acetaminophen soft tissue infections in children. BMJ. 2008; 36. Sadleir LG, Scheffer IE. Febrile seizures.
and ibuprofen dosing by parents. Pediatr 337:a1767 BMJ. 2007;334(7588):307311
Emerg Care. 2000;16(6):394 397 21. Schmitt BD. Fever in childhood. Pediatrics. 37. Lewis K, Cherry JD, Sachs MH, Tarle JM, Over-
5. May A, Bauchner H. Fever phobia: the pedi- 1984;74(5 pt 2):929 936 turf GD. The effect of prophylactic acetamino-
atricians contribution. Pediatrics. 1992; 22. American Academy of Pediatrics, Steering phen administration on reactions to DTP vac-
90(6):851 854 Committee on Quality Improvement and cination. Am J Dis Child. 1988;142(1):62 65
6. Mayoral CE, Marino RV, Rosenfeld W, Green- Management, Subcommittee on Febrile Sei- 38. Ipp MM, Gold R, Greenberg S, et al. Acetamin-
sher J. Alternating antipyretics: is this an al- zures. Febrile seizures: clinical practice ophen prophylaxis of adverse reactions fol-
ternative? Pediatrics. 2000;105(5):1009 1012 guidelines for the long-term management lowing vaccination of infants with diphtheria-
7. El-Radhi AS. Why is the evidence not affect- of the child with simple febrile seizures. Pe- pertussis-tetanus toxoids-polio vaccine.
ing the practice of fever management? Arch diatrics. 2008;121(6):12811286 Pediatr Infect Dis J. 1987;6(8):721725
Dis Child. 2008;93(11):918 920 23. Bouchama A, Knochel JP. Heat Stroke. N Engl 39. Centers for Disease Control and Prevention.
8. Jaffe DM. Assessment of the child with fe- J Med. 2002;346(25):1978 1988 Pertussis vaccination: use of acellular per-
ver. In: Rudolph CD, Rudolph AM, Hostetter 24. Trautner BW, Caviness AC, Gerlacher GR, tussis vaccines among infants and
MK, Lister GE, Siegel NJ, eds. Rudolphs Pe- Demmler G, Macias CG. Prospective evalua- childrenrecommendations of the Advi-
diatrics. 21st ed. New York, NY: McGraw-Hill; tion of the risk of serious bacterial infection sory Committee on Immunization Practices
2002:302309 in children who present to the emergency (ACIP) [published correction appears in
department with hyperpyrexia (tempera- MMWR Morb Mortal Wkly Rep. 1997;46(30):
9. Kohl KS, Marcy SM, Blum M, et al; Brighton
ture of 106F or higher). Pediatrics. 2006; 706]. MMWR Recomm Rep. 1997;46(RR-7):
Collaboration Fever Working Group. Fever
118(1):34 40 125. Available at: www.cdc.gov/mmwr/
after immunization: current concepts and
preview/mmwrhtml/00048610.htm.
improved future scientic understanding. 25. Poirier MP, Davis PH, Gonzalez Del Ray JA,
Accessed October 13, 2009
Clin Infect Dis. 2004;39(3):389 394 Monroe KW. Pediatric emergency depart-
ment nurses perspective on fever in chil- 40. Prymular, Siegrist CA, Chlibeck R, et al. Ef-
10. Hasday JD, Garrison A. Antipyretic therapy
dren. Pediatr Emerg Care. 2000;16(1):9 12 fect of prophylactic paracetamol adminis-
in patients with sepsis. Clin Infect Dis. 2000;
tration at time of vaccination on febrile re-
31(suppl 5):S234 S241 26. Howe AS, Boden BP. Heat-related illness in
actions and antibody responses in children:
11. Adam HM. Fever and host responses. Pedi- athletes. Am J Sports Med. 2007;35(8):
two open-label, randomized controlled tri-
atr Rev. 1996;17(9):330 331 1384 1395
als. Lancet. 2009;374(9698):1339 1350
12. Kluger MJ. Fever revisited. Pediatrics. 1992; 27. Jardine DS. Heat illness and heat stroke. Pe-
41. Trluyer JM, Tonnelier S, dAnthis P, Leclerc
90(6):846 850 diatr Rev. 2007;28(7):249 258
B, Jolivet-Landreau I, Pons G. Antipyretic ef-
13. Kluger MJ. Fever: role of pyrogens and cryo- 28. Mistry RD, Stevens MW, Gorelick MH. Short- cacy of an initial 30 mg/kg loading dose of
gens. Physiol Rev. 1991;71(1):93127 term outcomes of pediatric emergency de- acetaminophen versus a 15 mg/kg mainte-
14. Roberts NJ. Impact of temperature eleva- partment febrile illnesses. Pediatr Emerg nance dose. Pediatrics. 2001;108(4). Avail-
tion on immunologic defenses. Rev Infect Care. 2007;23(9):617 623 able at: www.pediatrics.org/cgi/content/
Dis. 1991;13(3):462272 29. Greisman LA, Mackowiak PA. Fever: bene- full/108/4/e73
15. Nizet V, Vinci RJ, Lovejoy FH. Fever in chil- cial and detrimental effects of antipyretics. 42. Nabulsi M, Tamim H, Sabra R, et al. Equal
dren. Pediatr Rev. 1994;15(4):127135 Curr Opin Infect Dis. 2002;15(3):241245 antipyretic effectiveness of oral and rectal
16. Doran TF, De Angelis C, Baumgardner RA, 30. Meremikwu M, Oyo-Ita A. Physical methods acetaminophen: a randomized controlled
Mellits ED. Acetaminophen: more harm than versus drug placebo or no treatment for trial. BMC Pediatr. 2005;5:35 42
good for chickenpox? J Pediatr. 1989; managing fever in children. Cochrane Data- 43. Scolnik D, Kozer E, Jacobson S, Diamond S,
114(6):10451048 base Syst Rev. 2003;(2):CD004264 Young NL. Comparison of oral versus nor-
17. Michael Marcy S, Kohl KS, Dagan R, et al; 31. Schmitt BD. Fever phobia. Am J Dis Child. mal and high dose rectal acetaminophen in
Brighton Collaboration Fever Working 1980;134(2):176 181 the treatment of febrile children. Pediat-
Group. Fever as an adverse event following 32. Betz MG, Grunfeld AF. Fever phobia in the rics. 2002;110(3):553556
immunization: case denition and guide- emergency department: a survey of chil- 44. Birmingham PK, Tobin MJ, Fisher DM,
lines of data collection, analysis and pre- drens caregivers. Eur J Emerg Med. 2006; Henthorn TK, Hall SC, Cot CJ. Initial and
sentation. Vaccine. 2004;22(5 6):551556 13(3):129 133 subsequent dosing of rectal acetamino-

PEDIATRICS Volume 127, Number 3, March 2011 585


Downloaded from by guest on June 2, 2017
phen in children. Anesthesiology. 2001; Lubsen G. Antipyretic efcacy of ibuprofen 70. Wright AD, Liebelt EL. Alternating antipyret-
94(3):385389 and acetaminophen in children with febrile ics for fever reduction in children: an un-
45. Birmingham PK, Tobin MJ, Henthorn TK, et seizures. Arch Pediatr Adolesc Med. 1995; founded practice passed down to parents
al. Twenty-four-hour pharmacokinetics of 149(6):632 637 from pediatricians. Clin Pediatr (Phila).
rectal acetaminophen in children: an old 58. Lesko SM, Mitchell AA. The safety of acet- 2007;46(2):146 150
drug with new recommendations. Anesthe- aminophen and ibuprofen among children 71. Nabulsi MM, Tamim H, Mahfoud Z, et al. Al-
siology. 1997;87(2):244 252 younger than two years of age. Pediatrics. ternating ibuprofen and acetaminophen in
46. Heubi JE, Barbacci M, Zimmerman HJ. 1999;104(4). Available at: www.pediatrics. the treatment of febrile children: a pilot
Therapeutic misadventures with org/cgi/content/full/104/4/e39 study. BMC Med. 2006;4:4 12
acetaminophen: hepatotoxicity after multiple 59. Autret-Leca E, Bensouda-Grimaldi L, Maur- 72. Sarrell EM, Wielunsky E, Cohen HA. Antipy-
doses in children. J Pediatr. 1998;132(1): age C, Jonville-Bera AP. Upper gastrointes- retic treatment in young children with
2227 tinal complications associated with NSAIDs fever: acetaminophen, ibuprofen or both al-
47. Henretiz FM, Selbst SM, Forrest C, Kearney in children[in French]. Therapie. 2007;62(2): ternating in a randomized double-blind
TK, Orel H, Werner S, Williams TA. Repeated 173176 study. Arch Pediatr Adolesc Med. 2006;
acetaminophen overdosing: causing hepa- 60. Berezin SH, Bostwick HE, Halata MS, Feerick 160(2):197202
totoxicity in children clinical reports and J, Newman LJ, Medow MS. Gastrointestinal 73. Hay AD, Costelloe C, Redmond NM, et al.
literature review. Clin Pediatr (Phila). 1989; bleeding in children following ingestion of Paracetamol Plus Ibuprofen for the Treat-
28(11):525528 low dose ibuprofen. J Pediatr Gastroenterol ment of Fever in Children (PITCH): random-
48. Kanabar D, Dale S, Rawat M. A review of ibu- Nutr. 2007;44(4):506 508 ized controlled trial [published correction
profen and acetaminophen use in febrile 61. Ulinski T, Guigonis V, Dunan O. Acute renal appears in BMJ. 2009;339:b3295]. BMJ.
children and the occurrence of asthma- failure after treatment with non-steroidal 2008;337:a1302
related symptoms. Clin Ther. 2007;29(12): anti-inammatory drugs. Eur J Pediatr. 74. Erlewyn-Lajeunesse MDS, Coppens K, Hunt
2716 2723 2004;163(3):148 150 LP, et al. Randomised controlled trial of
49. Lesko SM, Louik C, Vezina RM, Mitchell AA. 62. John CM, Shukla R, Jones CA. Using NSAID in combined paracetamol and ibuprofen for
Asthma morbidity after short-term use of volume depleted children can precipitate fever. Arch Dis Child. 2006;91(5):414 416
ibuprofen in children. Pediatrics. 2002; acute renal failure. Arch Dis Child. 2007; 75. Kramer LC, Richards PA, Thompson AM,
109(2). Available at: www.pediatrics.org/ 92(6):524 526 Harper DP, Fairchok MP. Alternating
cgi/content/full/109/2/e20 63. Moghal NE, Hegde S, Eastham KM. Ibuprofen antipyretics: antipyretic efcacy of acet-
50. Etminan M, Sadasafavi M, Jafari S, Doyle- and acute renal failure in a toddler. Arch Dis aminophen versus acetaminophen alter-
Waters M, Aminzadeh K, Fitzgerald JM. Acet- Child. 2004;89(3):276 277 nated with ibuprofen in children. Clin Pedi-
aminophen use and the risk of asthma in chil- 64. Lesko SM, Mitchell AA. Renal function after atr (Phila). 2008;47(9):907911
dren and adults: a systematic review and short-term ibuprofen use in infants and 76. Schmitt BD. Concerns over alternating acet-
metaanalysis. Chest. 2009;136(5):1316 1323 children. Pediatrics. 1997;100(6):954 957 aminophen and ibuprofen for fever. Arch
51. Allmers H, Skudlik C, John SM. Acetamino- 65. Allegaert K, Cossey V, Debeer A, et al. The im- Pediatr Adolesc Med. 2006;160(7):757
phen use: a risk for asthma? Curr Allergy pact of ibuprofen on renal clearance in pre- 77. Saphyakhajon P, Greene G. Alternating
Asthma Rep. 2009;9(2):164 167 term infants is independent of the gestational acetaminophen and ibuprofen in children
52. Goldman RD, Ko K, Linett LJ, Scolnik D. Anti- age. Pediatr Nephrol. 2005;20(6):740 743 may cause parental confusion and is dan-
pyretic efcacy and safety of ibuprofen and 66. Hammerman C, Shchors I, Jacobson S, gerous. Arch Pediatr Adolesc Med. 2006;
acetaminophen in children. Ann Pharmaco- Schimmel MS, Bromiker R, Kaplan M, Nir A. 160(7):757
ther. 2004;38(1):146 150 Ibuprofen versus continuous indomethacin 78. Frush KS, Lao X Hutchinson P, Higgins JN.
53. Perrott DA, Piira T, Goodenough B, Cham- in premature neonates with patent ductus Evaluation of a method to reduce over-
pion D. Efcacy and safety of acetamino- arteriosus: is the difference in the mode of the-counter medication dosing error.
phen vs ibuprofen for treating childrens administration? Pediatr Res. 2008;64(3):291 Arch Pediatr Adolesc Med. 2004;158(7):
pain or fever: a meta-analysis. Arch Pediatr 67. Su BH, Lin HC, Chiu HY, Hsieh HY, Chen HH, Tsai 620 624
Adolesc Med. 2004;158(6):521526 YC. Comparison of ibuprofen and indometha- 79. Rand CM, Conn KM, Crittenden CN, Halter-
54. Wilson JT, Brown RD, Kearns GL, et al. Single- cin for early-targeted treatment of patent duc- man JS. Does a color-coded method for
dose, placebo-controlled comparative tus arteriosus in extremely premature measuring acetaminophen doses reduce
study of ibuprofen and acetaminophen an- infants: a randomized controlled trial. Arch the likelihood of dosing error? Arch Pediatr
tipyresis in children. J Pediatr. 1991;119(5): Dis Child Fetal Neonatal Ed. 2008;93(2): Adolesc Med. 2004;158(7):625 627
803 811 F94 F99 80. Food and Drug Administration, Center for
55. Walson PD, Galletta G, Chomilo F, Braden NJ, 68. Zerr DM, Alexander ER, Duchin JS, Koutsky Drug Evaluation and Research. Joint meet-
Sawyer LA, Scheinbaum ML. Comparison of LA, Rubens CE. A case-control study of ne- ing of the Drug Safety and Risk Management
multidose ibuprofen and acetaminophen crotizing fasciitis during primary varicella. Advisory Committee, Nonprescription
therapy in febrile children. Am J Dis Child. Pediatrics. 1999;103(4 pt 1):783790 Drugs Advisory Committee, and the Anes-
1992;146(5):626 632 69. Lesko SM, OBrien KL, Schwartz B, Vezina R, thetic and Life Support Drugs Advisory
56. Kauffman RE, Sawyer LA, Scheinbaum ML. An- Mitchell AA. Invasive group A streptococ- Committee; June 29 30, 2009: questions
tipyretic efcacy of ibuprofen vs acetamino- cal infection and nonsteroidal anti- to the committee. Available at: www.fda.
phen. Am J Dis Child. 1992;146(5):622 625 inammatory drug use among children gov/downloads/AdvisoryCommittees/
57. Van Esch A, Van Steensel-Moll HA, Steyer- with primary varicella. Pediatrics. 2001; CommitteesMeetingMaterials/Drugs/
berg EW, Offringa M, Habbema JD, Derksen- 107(5):1108 1115 DrugSafetyandRiskManagementAdvisory

586 FROM THE AMERICAN ACADEMY OF PEDIATRICS


Downloaded from by guest on June 2, 2017
FROM THE AMERICAN ACADEMY OF PEDIATRICS

Committee/UCM170188.pdf. Accessed May Handbook: Formulary. 17th ed. Philadel- Acetaminophen poisoning: an evidence-based
12, 2010 phia, PA: Elsevier/Mosby; 2005 consensus guideline for out-of-hospital man-
81. Schillie SF, Shehab N, Thomas KE, Budnitz 83. Temple AR. Pediatric dosing of acetamino- agement. Clin Toxicol (Phila). 2006;44(1):118
DS. Medication overdoses leading to emer- phen. Pediatr Pharmacol (New York). 1983; 85. Penna AC, Sawson KP, Penna CM. Is pre-
gency department visits among children. 3(3 4):321327 scribing paracetamol pro re nata accept-
Am J Prev Med. 2009;37(3):181187 84. Dart RC, Erdman AR, Olson KR, et al; Amer- able? J Paediatr Child Health. 1993;29(2):
82. Robertson J, Shilkofski N. The Harriet Lane ican Association of Poison Control Centers. 104 106

PEDIATRICS Volume 127, Number 3, March 2011 587


Downloaded from by guest on June 2, 2017
Fever and Antipyretic Use in Children
Janice E. Sullivan, Henry C. Farrar, the Section on Clinical Pharmacology and
Therapeutics and Committee on Drugs
Pediatrics 2011;127;580; originally published online February 28, 2011;
DOI: 10.1542/peds.2010-3852
Updated Information & including high resolution figures, can be found at:
Services /content/127/3/580.full.html

References This article cites 78 articles, 27 of which can be accessed free


at:
/content/127/3/580.full.html#ref-list-1
Citations This article has been cited by 29 HighWire-hosted articles:
/content/127/3/580.full.html#related-urls
Subspecialty Collections This article, along with others on similar topics, appears in
the following collection(s):
Committee on Drugs
/cgi/collection/committee_on_drugs
Section on Clinical Pharmacology and Therapeutics
/cgi/collection/section_on_clinical_pharmacology_and_thera
peutics
Pharmacology
/cgi/collection/pharmacology_sub
Toxicology
/cgi/collection/toxicology_sub
Permissions & Licensing Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
/site/misc/Permissions.xhtml
Reprints Information about ordering reprints can be found online:
/site/misc/reprints.xhtml

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2011 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on June 2, 2017


Fever and Antipyretic Use in Children
Janice E. Sullivan, Henry C. Farrar, the Section on Clinical Pharmacology and
Therapeutics and Committee on Drugs
Pediatrics 2011;127;580; originally published online February 28, 2011;
DOI: 10.1542/peds.2010-3852

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/127/3/580.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2011 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on June 2, 2017