Treating fever significantly increases comfort, activity, feeding, and fluid intake and decreases the patient's temperature compared with placebo (strength of recommendation (SOR): A, multiple randomized controlled trials [RCTs]). It doesn't shorten or prolong the overall duration of illness or reduce the recurrence of febrile seizures (SOR: A, multiple RCTs). In patients with varicella, reducing fever prolongs the time it takes for lesions to crust, but doesn't appear to cause group A streptococcal necrotizing fasciitis (SOR: B, multiple prospective cohorts)

Bailey, Justin

Miller, Robert J.

Sullivan, Kerry

University of Missouri: MOspace

Evidence-based answers from the Family Physicians Inquiries Network353JFPONLINE.COM VOL 59, NO 6  |  JUNE 2010  |  THE JOURNAL OF FAMILY PRACTICEEVIDENCE-BASED ANSWERA  Robert J. Miller, MDFamily Medicine Residency, Travis Air Force Base, CalifJustin Bailey, MD Uniformed Services University of the Health Sciences, Travis AFB, CalifKerry Sullivan, MLIS  Walden University, Minneapolis, MinnTreating fever signifi cantly increases comfort, activity, feeding, and fl uid intake, but doesn’t reduce recurrence of febrile seizures.  Does lowering a fever >101°F in children improve clinical outcomes?  it depends on which outcomes you look at. Treating fever sig-nifi cantly increases comfort, activity, feed-ing, and fl uid intake and decreases the patient’s temperature compared with pla-cebo (strength of recommendation (SOR): A, multiple randomized controlled tri-als [RCTs]). It doesn’t shorten or prolong the overall duration of illness or reduce the recurrence of febrile seizures (SOR: A, multiple RCTs). In patients with varicella, reducing fever prolongs the time it takes for lesions to crust, but doesn’t appear to cause group A streptococcal necrotizing fasciitis (SOR: B, multiple prospective cohorts).Ibuprofen and acetaminophen reduce fever eff ectively and safely; their side eff ect levels are similar to placebo (SOR: A, mul-tiple RCTs). Physical methods of cooling also are eff ective for lowering fever (SOR: A, high-quality meta-analysis).Evidence summaryTh e possible risks and benefi ts of lowering fever with antipyretics have prompted much discussion in the medical literature. Most evidence supporting the useful eff ects of fe-ver comes from animal models. A few human studies in special populations (patients with brain trauma) suggest that antipyretics may worsen certain aspects of disease processes.1However, many studies show that antipyretics do clinically benefi t, and don’t harm, the typi-cal child with an upper respiratory illness.2-4Acetaminophen improves some symptoms, but doesn’t shorten feverA double-blind, randomized, placebo-controlled trial of 210 children with upper respiratory illness showed that giving acet-aminophen signifi cantly increased short-term temperature reduction compared with placebo (0.36°F vs 0.09°F/hr; P<.001). Acet-aminophen also improved subjective symp-toms at 6 hours over placebo: activity (60% vs 16%;  P<.001), alertness (58% vs 21%; P<.001), comfort (37% vs 7%; P<.001), mood (36% vs 12%; P<.001), appetite (20% vs 1%; P<0.001), and fl uid intake (22% vs 2%; P<.001).2 Total time until complete resolution of fever (de-fi ned as no fever with or without medication) didn’t diff er between treatment and placebo groups (32 hr for acetaminophen vs 36 hr for placebo; P=.23).2A similar study failed to show a statisti-cally signifi cant diff erence between acet-aminophen and placebo in fever clearance time (34.7 vs 36.1 hr), mood, comfort, or ap-petite. However, the study did fi nd signifi cant improvement in activity (38% vs 11%; P=.005) and alertness (33% vs 12%; P=.036) based on parents’ reports.3 Ibuprofen is a better antipyretic than acetaminophenA meta-analysis (N=84,192) comparing ac-etaminophen with ibuprofen found both drugs to be equally effi  cacious analgesics; ibuprofen was a more eff ective antipyretic. Both drugs had the same level of adverse out-comes when compared with each other and placebo.5  CONTINUED ON PAGE 360360 THE JOURNAL OF FAMILY PRACTICE  |   JUNE 2010  |   VOL 59, NO 6An RCT involving children with varicella  found that acetaminophen increased the time for lesions to crust compared with placebo. ReferencesLowering fever doesn’t reduce recurrence of febrile seizuresAntipyretics don’t appear to aff ect the recur-rence of febrile seizures. In a well-designed, randomized, double-blind, placebo-controlled trial, 230 patients 1 to 4 years of age with 1 or more risk factors for febrile seizures were ran-domized to fever reduction with ibuprofen or placebo. Th e estimated 2-year probability for recurrent febrile seizure was 32% in the ibupro-fen group and 39% for the placebo group. Th e diff erence between the groups was not signifi -cant (relative risk=0.9; 95% confi dence interval [CI], 0.6-1.5).6  Varicella lesions crust more slowly with acetaminophenAn RCT involving 68 children with varicella found that acetaminophen increased the time for lesions to crust compared with placebo (6.7 days for acetaminophen vs 5.6 days for place-bo) and that acetaminophen didn’t alleviate itch-ing or improve appetite. However, patients taking acetaminophen were more active by day 2.7 NSAIDs don’t cause necrotizing fasciitisA case-control study of 48 children with vari-cella suggested an association between ibu-profen and increased incidence of necrotizing soft tissue infections (odds ratio [OR]=11.5; 95% CI, 1.4-96.9),8 but larger reviews haven’t borne out this fi nding. A review of 5 prospec-tive studies of nonsteroidal anti-infl amma-tory drugs and invasive soft-tissue infections (N=912; 114 cases of necrotizing fasciitis) failed to show any connection. Th e largest study (474 cases) suggested a trend that was not statistically signifi cant (OR=3.5; 95% CI, 0.8-16).9 Nonpharmacologic measures also lower feverA Cochrane review showed that cool water sponging caused fever reduction similar to an-tipyretics at 1 hour; sponging combined with ibuprofen reduced the proportion of patients still febrile at 1 hour. Common side eff ects of spong-ing included goose pimples and shivering. Th e antipyretic eff ect didn’t last beyond a few hours.10RecommendationsConcerning treatment of fever, Nelson’s Pediatrics states, “Fever with temperatures less than 39°C (102.2°F) in healthy children generally does not require treatment. As tem-peratures become higher, patients tend to become more uncomfortable and adminis-tration of antipyretics often makes patients feel better. Other than providing symptom-atic relief, antipyretic therapy does not change the course of infectious diseases. Antipyretic therapy is benefi cial in high-risk patients who have chronic cardiopulmonary diseases, met-abolic disorders, or neurologic diseases and in those who are at risk for febrile seizures. Hy-perpyrexia (>41°C [105.8°F]) indicates greater risk for severe infection and should always be treated with antipyretics.”11                          JFPACKNOWLEDGEMENTSThe opinions and assertions contained herein are the private views of the authors and not to be construed as offi cial, or as refl ecting the views of the United States Air Force Medical Service or the US Air Force at large. 1.   Mackowiak PA, Plaisance KI. Benefi ts and risks of antipyretic therapy. Ann NY Acad Sci. 1998;856:214-223. 2.   Gupta H, Shah D, Gupta P, et al. Role of paracetamol in treatment of childhood fever: a double-blind randomized placebo con-trolled trial. Indian Pediatr. 2007;44:903-911.  3.   Kramer MS, Naimark LE, Roberts-Brauer R, et al. Risks and ben-efi ts of paracetamol antipyresis in young children with fever of presumed viral origin. Lancet. 1991;337:591-594.  4.   Bernard GR, Wheeler AP, Russell JA, et al. Th e eff ects of ibu-prophen on the physiology and survival of patients with sepsis. Th e Ibuprofen in Sepsis Study Group. N Engl J Med. 1997;336:912-918. 5.   Perrott DA, Pirra T, Goodenough B, et al. Effi  cacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis. Arch Pediatr Adolesc Med. 2004;158:521-526.  6.   Van Stuijvenberg M, Derksen-Lubsen G, Steyerberg EW, et al. Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrence. Pediatrics. 1998;102:E51.  7.   Doran TF, DeAngelis C, Baumgardner RA, et al. Acetamino-phen: more harm than good for chickenpox? J Pediatr. 1989;114:1045-1048.  8.   Zerr DM, Alexander ER, Duchin JS, et al. A case control study of necrotizing fasciitis during primary varicella. Pediatrics. 1999;103:783-790.  9.   Aronoff  DM, Bloch KC. Assessing the relationship between the use of nonsteroidal antiinfl ammatory drugs and necro-tizing fasciitis caused by group A streptococcus. Medicine (Baltimore). 2003;82:225-235.  10.   Meremikwu M, Oyo-Ita A. Physical methods for treating fever in children. Cochrane Database Syst Rev. 2003;(2):CD004264.   11.   Powell K. Fever. In: Kliegman RM, Behrman RE, Jenson HB, et al., eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saun-ders Elsevier; 2007:1084-1086.CONTINUED FROM PAGE 353

Does lowering a fever >101F in children improve clinical outcomes?

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