Emergency Department Management of the Febrile Child
Emergency Department Management of the Febrile Child
Author: Robert A. Felter, MD, FAAP, Medical Director, Pediatric Emergency and Inpatient Services, Commonwealth Emergency Physicians, Inova Loudon Hospital, Leesburg, Virginia
Peer Reviewer: John P. Santamaria, MD, FAAP, FACEP, Affiliate Professor of Pediatrics, University of South Florida School of Medicine, Tampa, Florida
The infant or child with a fever is a common occurrence in an emergency department (ED). Unfortunately, the ED physician or pediatrician is then faced with the challenge of identifying the individual risk of each child for a serious bacterial illness (SBI). Advances in vaccinations add to the rapidly evolving diagnostic evaluation of an infant or child with a fever. Fears regarding the emergence of resistant bacteria fuel the desire of the physician to perform the minimum number of tests to accurately identify the child at risk for an SBI and to only initiate antibiotic therapy when there is clearly a benefit to the patient. The ED physician must maintain vigilance in this rapidly evolving area of research and must understand the controversies and risks associated with the various suggested strategies for evaluation of an infant or child with fever.
— The Editor
Introduction
The febrile infant or child poses one of the most challenging clinical situations for an ED physician. Because fever is a frequent reason for ED visits—up to 20% of visits—it is a dilemma confronted every day.1 Most parents have a 'fever phobia', which is exacerbated by the medical community and the media. Many parents and some health care providers believe fever by itself can be harmful2 and that all fever must be treated. This belief may be due to the association of fever with seizures, although it is widely known that febrile seizures are usually benign and cannot be prevented by antipyretic agents. A recent study showed that parents seek evaluation of a child with a fever because they are unable to control the fever, they fear that the disease is progressing, or they fear the child has an underlying SBI. In addition, response to antipyretic medicine, while reassuring to parents, has no predictive value that the child does not have an SBI.3 Studies have shown that as many as 1 in 5 children with fever will have no obvious source of infection after a comprehensive history and physical examination.4 SBIs include bacteremia, meningitis, urinary tract infection (UTI), pneumonia, septic arthritis, and osteomyelitis. While the vast majority of children presenting with fever will have self-limited viral illnesses, a few will have an SBI. Differentiating the child with a viral illness from an SBI may be difficult, especially early in the course of the disease.
The significance of the fever must be addressed when advising parents, especially if the child is to be discharged home with observation.2 Fever may have some beneficial aspects (including regulation of the immune response), and fever treatment may have some undesirable effects, but no conclusive data exist to support either point.5 While the beneficial effects of fever are debatable, fever from infectious disease in children is not harmful. Neither parents nor the ED physician want to send a febrile child home with a possible SBI; no approach has shown 100% accuracy in identifying the child with an SBI from children without. Even 99% accuracy means that a child may be discharged home at risk for significant morbidity and mortality.
From the ED physician's perspective, several important issues must be addressed. Soaring medical costs, patient safety, and a desire to avoid unnecessary testing has resulted in an effort to selectively test patients. Not all children with fever can be admitted to the hospital; this action would be overly expensive and possibly increase morbidity. Likewise, not all children should be started on empiric antibiotics. This would contribute to the problem of resistant bacteria, already a major health concern. Also, in the current litigious milieu, ED physicians are aware that any missed diagnosis will most likely result in legal action.
More than 300 articles have been written about the evaluation and management of the febrile child. The busy ED physician will be unable to read and analyze all of the articles, but recent articles by the American College of Emergency Physician (ACEP)3 and Avner and Baker6 provide excellent summaries of the current state of practice. Various protocols and guidelines have been suggested. These guidelines and protocols have changed over the years as more research has been completed and new vaccines have been widely used. The changing etiologies of SBI in children continue the controversies over ideal management. A variety of approaches have been suggested by different studies including observation scores, laboratory studies, and use of outpatient antibiotic agents.
This article has several objectives. First is to review the approaches that are the most frequently recommended for evaluation of the child with fever without source (FWS) and clarify frequent misunderstandings from review of the literature. It is important to note the word current because the recommendations are evolving as more research has been performed over the last decade and will continue to evolve as the effect of widespread vaccination is realized. Second is to summarize the management strategies that 1) identify children at risk for an SBI, 2) provide a management plan for children not admitted to the hospital or started on empiric antibiotic medications, and 3) provide risk management suggestions for the ED physician. Third is to discuss the effect of vaccinations on management strategies of children with FWS.
Determination of Fever
The definition of what constitutes a fever in a child has been debated, but for the purposes of evaluating infants a rectal temperature of 100.4° F is considered a fever. The temperature should be taken rectally especially in infants younger than 6 months,6 or in any child when an accurate oral temperature cannot be obtained. A true fever in children younger than 2 months will guide the diagnostic evaluation. Although temperatures in children older than 6 months may be taken by otic thermometers, the results are very user dependent, and, therefore, not reliable for determining the true presence of a fever.7 Axillary temperatures are unreliable,8 but an elevated axillary temperature is indicative of a fever, while a low or normal temperature is not useful. Tactile fevers are very unreliable. Temple thermometers also have been shown to be unreliable for infants.9 An infant determined to be febrile at home by a reliable method must be presumed to have been febrile even if the temperature later in the ED is normal. Also, a child believed to be febrile and given antipyretic agents at home must be considered to have been febrile even if the temperature later is normal in the ED. Response to antipyretic agents is not useful in determining if the child has an SBI.10 A child believed to be febrile at home, given no antipyretic medication, and who is afebrile in the ED may be presumed to be afebrile. Infants are susceptible to environmental conditions that may influence their body temperature, but overbundling should not be considered the reason for an elevation of temperature in an infant.
Studies have shown that the higher the temperature, the more likely the child has a bacterial infection.1 However, especially for the child who is to be managed as an outpatient, the height of the fever should only be one aspect for the parents to monitor. The overall condition of the child should be stressed as a reason to call or seek medical attention. The child with a temperature of 38.5°C who is lethargic is more worrisome than the child with a temperature of 39.0°C who is active and playful. Especially in infants, a temperature below normal with a concerning clinical history is very disturbing and requires immediate attention. ED personnel as well as parents often overlook this situation.
Infants and children with FWS originally were divided into three major categories: those younger than 1 month, children 1 to 3 months, and children 3 to 36 six months of age. A recent publication by the ACEP Clinical Policies Committee continues recommending these age category divisions for fever management guidelines.3
Clarifications and Controversies
Some physicians have misinterpreted the recommendations for children with FWS. This misunderstanding has led to some physicians treating all young children with fever with intramuscular ceftriaxone.11 FWS is limited to children who have no historical or physical evidence to explain the presence of an elevated temperature and have no significant past medical history that puts them in a higher risk category.
Examples:
• A 12-month-old child with an upper respiratory infection or otitis media has a fever with source. A child with a history of vomiting and diarrhea and fever has a fever with source. These children should be managed as their clinical presentation and diagnosis requires.
• A child with a history of prematurity, sickle cell disease, or VP shunt has a significant past medical history that puts the child at higher risk for an SBI. A child with tachycardia or tachypnea does not have a normal physical examination. None of these children should be included in the recommended evaluation for FWS, although some of the laboratory studies may be recommended for both.
The ED physician also should seriously consider parental observations and concerns regarding their child not behaving normally although on presentation the child may appear normal. An unusual amount of crying, sleepiness, or poor feeding may be subtle clues to an underlying SBI.
The age divisions also are debated. Some authors—in contrast to the categories of 0-30 days, 30-90 days, and 3 to 36 months—use 0 to 1 month, 1 to 2 months, and 2 to 24 months as the age groups.12
A sepsis evaluation (See Table 1.) is the evaluation for a child with known or suspected sepsis. As will be mentioned several times, any child who appears septic (e.g., lethargic, hypotensive, purpuric rash) requires immediate stabilization, evaluation, and antibiotic therapy. These children should have a complete sepsis workup as their clinical condition allows.
| Table 1. Laboratory Evaluation of the Child with Sepsis |
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The child with FWS who appears nontoxic may have a laboratory evaluation to determine if he/she is at higher risk for an SBI (See Table 2.). Several studies have suggested low-risk criteria for an SBI. Various studies have used the following criteria to determine if a child is at low risk for an SBI:
- No clinical evidence of infection of the ear, skin, bone, or joints.
- White blood cell (WBC) count between 5,000 and 15,000.
- Fewer than 1500 bands.
- Normal urinalysis.
- If diarrhea is present, fewer than 5 WBC per high power field, and no blood in stool.
- No infiltrate on chest radiograph.
| Table 2. Laboratory Evaluation of the Child with Fever without Source (FWS) |
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• Complete blood count with differential • Urinalysis and culture (boys younger than 6 months and girls younger than 2 years) • Stool for fecal leukocytes if diarrhea is present • Chest radiograph if respiratory symptoms are present |
The usefulness of the complete blood count (CBC) recently has been questioned, especially for determining the child at low risk for an SBI.13 Other tests have been evaluated with FWS including pneumococcal antigen assay14,15 and CRP,16,17 with variable results. The latter study suggested that the CRP measurement has a better predictive value than the WBC count.
The Infant Younger Than One Month
There is consensus that any child younger than 1 month (30 days) presenting with fever as defined above, with or without source should 1) have a complete sepsis evaluation (Table 1), 2) be started on appropriate antibiotic therapy (Table 3), and 3) be admitted to the hospital regardless of his/her clinical presentation. Children in this age range exhibit few if any of the classic signs of sepsis, and because they have immature immune systems they may deteriorate rapidly. Children younger than 1 month—especially if born prematurely—are at greater risk for bacterial infection.18 Although this recommendation is fairly clear, a few important points must be made. If the infant is hemodynamically unstable, the infant should be aggressively stabilized and begun on antibiotic therapy even if the sepsis evaluation is not completed. Performing a lumbar puncture on an unstable child can be perilous. Likewise, if intravenous access is not obtained, antibiotic agents can be given intramuscularly, although caution should be used with this strategy in the patient with shock. If the child will be transferred to a tertiary care center, stabilization and antibiotic therapy should be started before transport.
| Table 3. Empiric Antibiotic Therapy |
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As noted above, virtually everyone would agree that the febrile infant who is 30 days of age or younger should have a sepsis evaluation and be hospitalized for parenteral antimicrobial therapy pending the results of the assessment. In the context of treatment, the sepsis evaluation would include cultures of cerebrospinal fluid, blood, and urine; a complete blood cell count with differential; a cerebrospinal fluid examination that includes gram stain, cell count, glucose and protein levels measurement; and urinalysis. The reasons that these infants are at higher risk include exposure to potential pathogens in the birth canal without the benefit of passively transferred maternal antibodies and the previously mentioned immature immune system, specifically, the ability of neonatal neutrophils to migrate from the blood into sites of infection and inflammation is reduced. As a consequence, there is a greater risk that these infants will not be able to localize and eradiate a pathogen leading to an increased risk of an SBI.
Group B streptococcus (GBS), Escherichia coli, and Listeria monocytogenes are the typical pathogens in the first few weeks of life; GBS and Listeria monocytogenes can cause late-onset sepsis. Infants in the community are exposed to Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, each of which can cause sepsis as maternally derived immunity wanes. Staphylococcus aureus and Salmonella species occasionally may also cause invasive disease in this age group. Herpes simplex virus can manifest as sepsis in this age group; however, the older the infant the more likely it is that there will be concomitant skin or mucous membrane involvement. Rarely, respiratory syncytial virus, enterovirus, and adenovirus can present with clinical manifestations that are indistinguishable from an SBI.
Empiric antimicrobial therapy for the febrile infant younger than 1 month is aimed at the most common pathogens (Table 3). Ampicillin intravenously is used to cover for Listeria monocytogenes. Although gentamicin is used in the context of the neonatal intensive care unit for coverage of gram-negative bacteria, once the infant has been discharged home, community pathogens (e.g., Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) can predominate; consequently, a third-generation cephalosporin is used intravenously to complete empiric coverage. Cefotaxime is preferred in this age group because ceftriaxone can displace bilirubin from its albumin binding site, and it should be used with caution in this age group if the infant is jaundiced. Acyclovir should be considered if herpes simplex virus is suspected on clinical or epidemiological grounds.
The increasing number of premature infants surviving the neonatal period has resulted in a greater number being seen in the ED. A premature infant cannot be managed in the same manner as a term newborn. It is prudent to consider the child's age starting from his/her predicted birth date for this evaluation.
The Child from One to Three Months
This is the clinical population for which a significant amount of research has been generated to identify patients who do not require an extensive diagnostic evaluation and empiric antibiotic therapy. While children in this age range may give more clinical cues to their degree of wellness (e.g., interaction with environment, social smile), they still present significant challenges to ED physicians. Clinical criteria alone will not provide adequate accuracy to determine if a child with fever has an SBI similar to the infant younger than 30 days. The ill-appearing child requires the same immediate and aggressive treatment in this age range. Several guidelines and criteria have been used to attempt to identify a child at low risk for an SBI.
When the patient who has FWS is between 30 and 90 days of age, the key to treatment involves the identification of the patient as low risk for an SBI.19 This determination involves the use of clinical and laboratory criteria. Clinical evaluation includes history, physical examination, and assessment of social situation. Laboratory evaluation involves complete blood count with differential, urinalysis, microscopic evaluation of stool when diarrhea is present, and chest radiograph if respiratory signs or symptoms are discovered. A recommendation to include pulse oximetry as part of routine vital signs on all febrile children will help in deciding if a child should receive a chest radiograph as part of the initial workup.20
The low-risk infant can be managed in one of two ways: 1) a single dose of intramuscular ceftriaxone after blood, urine, and cerebrospinal fluid cultures have been obtained and re-evaluation within 24 hours has been arranged, or 2) urine culture obtained but no antibiotic therapy started, along with careful observation. Some authors do not recommend use of parenteral antibiotic agents unless a lumbar puncture and CSF examination have been performed.20 This approach eliminates the problem faced if the child worsens and there is the possibility of a partially treated meningitis. More recent studies21 have verified that the risk of an SBI is very low (0.4%) in a similar population of infants cared for by experienced physicians using clinical judgment. The authors suggest that well-appearing infants, aged 25 days or older with a temperature less than 38.6°C can be managed as low risk without antibiotic therapy but with close observation. The children in the study underwent fewer invasive tests, received fewer antibiotic medications, and were less likely to be hospitalized. The suggestion was that experienced clinicians using their clinical skills are just as accurate as clinical guidelines while reducing costs and preventing iatrogenic morbidity. High-risk infants are admitted, cultures are obtained, and the patient treated with intravenous antibiotic agents as indicated by the clinical situation and the suspected pathogens (including late onset GBS and Listeria monocytogenes); empiric therapy with ampicillin plus a third-generation cephalosporin is standard. If the gram stain of the CSF suggests a pneumococcal infection, then vancomycin should be substituted for ampicillin (Table 3).
The importance of follow-up for any child sent home, regardless of the management, cannot be overemphasized. A call back in 12 hours and a follow-up visit in 24 hours are prudent. If the ED physician is planning to have the patient seen by the patient's primary care physician, that person should be called before discharge and should agree to the plan. This discussion should be documented in the ED chart. The parents should be advised of clinical signs and symptoms of a worsening condition. Monitoring the temperature is important but should not be the only symptom followed. A temperature more than 41°C requires immediate attention.5 A below-normal temperature or any abnormal behavior also requires prompt evaluation.
The Child from Three to Thirty-Six Months
Children in the age range of 3 to 36 months have been considered at risk for occult bacteremia. It is in this age range that widespread vaccinations for Hemophilus influenza and Streptococcus pneumoniae have had a great effect, and the effect will continue to be tracked and monitored. Historically, the majority of cases of occult bacteremia were due to Streptococcus (50%-90%).22 A smaller amount were due to H. influenza and even less due to Salmonella and Neisseria meningitidis. Most of the cases due to Streptococcus were self-limited. Although bacteremia caused by Hemophilus was less frequent, it was more frequently associated with meningitis. Widespread use of the HiB vaccine has drastically reduced the incidence of occult bacteremia due to this bacterium.
For children with FWS between 3 months and 36 months of age, substantial controversy exists. Any child in this age group without a focus who appears toxic should receive appropriate cultures and diagnostic tests, hospitalization, and parenteral antibiotic therapy.23 If the child is well-appearing and has no readily identified focus, diagnostic tests other than urinalysis are not routinely indicated and no antibiotic treatment should be given. Others argue that such a strategy for the well-appearing child with FWS will fail to identify occult Streptococcus pneumoniae bacteremia, resulting in some of these individuals developing Streptococcus pneumoniae meningitis.24 This latter group promotes the use of a complete blood count for patients with FWS and a temperature of 39.0°C or higher. If the white blood cell count is 15,000 or higher, they recommend a blood culture and empiric ceftriaxone therapy.25 When pneumococcal meningitis is considered, vancomycin should be added to cover for the possibility of penicillin-resistant Streptococcus pneumoniae (Table 2). Some suggest that such controversy will fade with the advent of the heptavalent pneumococcal conjugate vaccine (PCV7).22 However, we cannot be certain that PCV7 will have the same dramatic effect as the conjugate Haemophilus influenzae type b vaccine, largely because of the many non-vaccine pneumococcal serotypes; only time will tell.
Any child discharged to home from the ED as noted above should have follow-up arranged before discharge. General statements (e.g., Follow up with your primary care physician if the patient worsens.) are unwise.
Management of Fever
While debate remains regarding the need to treat fever in children, parents and professionals usually recommend some form of therapy. Parents should be advised that treating their child's fever as outpatient management is for comfort and not for therapeutic reasons. Insistence on maintaining an afebrile state causes unnecessary anxiety for parents and promotes fever phobia. The two medications most commonly used are acetaminophen and ibuprofen. Their mechanisms of action are different, and acetaminophen has no anti-inflammatory activity. While there is no consensus favoring one for fever management, a recent meta-analysis of the existing literature reported that single doses of ibuprofen (e.g., 5 to 10 mg/kg) were superior to acetaminophen (10 to 15 mg/kg) in fever reduction.26 The use of both medications at the same time is confusing and may lead to inappropriate dosing.5 Because of the association with Reye's syndrome, aspirin is not recommended for use in children.
Management of FWS in the Age of Vaccines
The advent of widespread use of vaccines for Haemophilus influenzae type b has virtually eliminated disease from this pathogen. PCV7 has led to dramatic reductions in invasive pneumococcal disease. However, not all children have been immunized, especially those of lower socioeconomic position;27 a group served by inner-city EDs. Consequently, it is imperative that an accurate immunization history be included in the management of the febrile child. Table 4 summarizes the relationship between age at onset of immunization and the minimum number of doses required to confer protection. All four Haemophilus influenzae type b vaccines conjugate polyribosylribotol phosphate (PRP) to various carrier proteins: tetanus toxoid (PRP-T), mutant diphtheria toxin protein conjugate (HbOC), outer-membrane protein (OMP) of Neisseria meningitidis (PRP-OMP), and diphtheria toxoid (PRP-D). PRP-OMP induces substantial immunity after a single dose, while PRP-T and HbOC require one to three doses for an optimal response28 depending upon the age at which immunization is started. A recent case-controlled study of PCV7 revealed 88% vaccine effectiveness after one dose.29 Another study described a low rate of occult bacteremia due to Streptococcus pneumoniae despite the fact that few infants in the community had received three doses of PCV7.22 At this time, it appears that a single dose of PCV7 significantly lowers the incidence of pneumococcal bacteremia. A history of immunization to Haemophilus influenzae type b and Streptococcus pneumoniae, even partial completion of an immunization schedule, may reduce the risk of SBI from these pathogens and should be incorporated into management strategies. The practice of obtaining complete blood counts and blood cultures may diminish if studies continue to show the reduced likelihood of occult bacteremia from S. pneumonia.22
| Table 4. Minimum Number of Vaccine Doses Necessary to Confer Protection |
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Neisseria meningitidis is now the most frequent cause of bacterial meningitis in children and adolescents 2 to 18 years old in the United States. A quadrivalent meningococcal conjugate vaccine (MCV4, Menactra) was approved by the FDA in 2004 for use in those individuals from 11 to 55 years old. The vaccine confers protection against meningococcal A, C, Y and W-135 sero-groups. Similar vaccines in the United Kingdom have successfully reduced endemic meningococcal disease30 and have been used safely in infants.31 Trials are currently underway in infants with conjugate meningococcal vaccines in the United States.
Conclusion
The ED physician currently faces significant clinical challenges. First is not to miss any child who might have a serious disease. The second is to avoid contributing to the prevalence of resistant Pneumococcus by treating every febrile child with antibiotic agents. The problem will be more difficult as occult bacteremia lessens, but the number of febrile children remains virtually unchanged. In a cost-effective analysis, the empiric use of antibiotic agents may be difficult to justify,32 but this fact will be a small comfort to the parents of child who develops an SBI after an ED visit. Parental education, the involvement of the primary care physician, and close observation remain key in management of the febrile child.33
Acknowledgment: The author wishes to acknowledge the assistance of John Venglarcik, MD.
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