Author:
Daniel J.Tonellato
David A.Peak
Description
- Fever is defined as a temperature of 38°C (100.4°F) rectally:
- Oral and tympanic temperatures are generally 0.6-1°C lower
- Tympanic temperatures are not accurate in children younger than 6 mo. When measuring pull posteriorly and superiorly on the external ear at the midpoint between the apex of the helix and inferior border of the lobule
- Axillary temperatures are unreliable
- Children who are afebrile but have a reliable history of measured fever should be considered to be febrile to the degree reported
- Accounts for up to 20% of children presenting to the ED. Challenge is to identify those with significant underlying infections
Etiology
- General:
- Bacteremia
- Infants ≤90 d: E. coli and group B streptococcus
- Older infants: Streptococcus pneumoniae. Haemophilus influenzae type B less common with widespread immunizations
- Viral illness, often accompanied by exanthem (varicella, roseola, rubella), coxsackievirus (hand -foot-and -mouth disease)
- H. influenzae type B and S. pneumoniae vaccines have reduced incidence of Haemophilus and pneumococcal disease
- CNS: Meningitis, encephalitis
- Head, eyes, ears, neck, and throat (HEENT): Otitis media, facial cellulitis, orbital/periorbital cellulitis, pharyngitis (group A β-hemolytic streptococcus, herpangina, adenovirus pharyngoconjunctival fever), viral gingivostomatitis (herpes and coxsackievirus), cervical adenitis, sinusitis, mastoiditis, conjunctivitis, peritonsillar/retropharyngeal abscess
- Respiratory: Croup (paramyxovirus), epiglottitis, bronchiolitis (respiratory syncytial virus [RSV]), pneumonia, empyema, influenza
- Cardiovascular: Purulent pericarditis, endocarditis, myocarditis
- Genitourinary (GU): Cystitis, pyelonephritis
- GI: Bacterial/viral gastroenteritis, intussusception, appendicitis, hepatitis
- Extremity: Osteomyelitis, septic arthritis, abscess, cellulitis
- Miscellaneous: Herpes simplex virus infection in the neonate, Kawasaki disease, vaccine (DPT) reaction, heat exhaustion/stroke, factitious, familial dysautonomia, thyrotoxicosis, collagen vascular disease, vasculitis, rheumatic fever, malignancy, drug induced, overbundling (uncommon, recheck 15 min after unbundling)
- Occult bacteremia occurs in association with a host of clinical entities. The group at highest risk are those ≤24 mo with a fever of ≥39.4°C and a WBC of 15,000 cell/mm3
- Hyperpyrexia (temp >41°C (105.8°F) commonly associated with serious infection. Temperatures >42°C often have a noninfectious cause such as hyperthermia, head injury, drug ingestion, malignant hyperthermia
Signs and Symptoms
- Clinical appearance must be evaluated. Airway, breathing, and circulation (especially dehydration with impaired perfusion/color) need specific evaluation
- Early administration of antipyretics may facilitate assessment
- Toxicity associated with lethargy, delayed capillary refill, hypoventilation/hyperventilation, weak cry, decreased PO intake; purpuric or petechial rash, and /or hypotonia. Initial observation is crucial in this evaluation
- Tachycardia or tachypnea may be the only finding in children with serious underlying condition
- Fever with a temperature >38°C can raise a child's heart rate by 10 bpm for each degree Fahrenheit
- Temperature >40°C have been associated with an elevated bacteremia rate in children <24 mo
- Altered mental status:
- Lethargy presenting with decreased level of consciousness
- Irritability
- Impaired interaction with environment, parents, physician, toys
- Behavioral observation may be helpful in those >60 d:
- Child looks at and focuses on the clinician and spontaneously explores the room
- Child spontaneously makes sounds or talks in in a playful manner
- Child plays and reaches for objects
- Child smiles and interacts with parents or clinician
- Child quiets easily and interacts with parents or clinician
- Physical exam (PE) to search for underlying condition
- Tachypnea and hypoxia are the most sensitive signs for pneumonia. Also useful are rales, hypoxemia, cough >10 d, and fever >5 d
- Risk factors for occult UTI include female sex, uncircumcised boys, fever without source, and fever >39°C
- Fever and petechiae may be related to viral illness, Rocky Mountain spotted fever, or invasive bacterial infection, most commonly due to N. meningitidis
- Fever of unknown origin (FUO) is referred to as a febrile illness without identified cause that lasts 14 d or more. Causes may be infectious, collagen vascular, malignancy, etc.
- Seizure (simple vs. complex)
- Temperatures >42°C often have a noninfectious cause
- Serious infection may occur with normothermia or hypothermia
- Patients with underlying malignancy, central venous catheters, or ventricular peritoneal shunts may have few findings other than fever
- Antipyretics may change findings without impacting underlying disease. This may be useful in evaluation of patient, esp with respect to mental status
- ∼20% of children will have fever without definable source after history and PE
- Serious bacterial infections are unusual in infants presenting with ALTE
Essential Workup
- Oxygen saturation as mand atory fifth vital sign
- Resuscitate as appropriate
- Determine duration of illness, degree, pattern and height of fever, use of antipyretics, past medical history, drug allergies, immunization status and history, recent medications/antibiotics, birth history if <6 mo of age, exposures, feeding, activity, urine/bowel habits, travel history, and relevant review of systems
- Search for underlying condition
- Initiate antipyretic therapy
Diagnostic Tests & Interpretation
Lab
- CBC with differential
- Urinalysis (UA) and culture in all male infants younger than 6 mo, uncircumcised male infants <12 mo, and females <2 yr. Urines for culture should be obtained by catheterization or suprapubic techniques
- Blood culture:
- The development of automated blood culture systems has led to more rapid detection of bacterial pathogens
- CSF for cell count, Gram stain, culture, protein, and glucose for toxic children and those 0-28/30 d of age; consider for nontoxic-appearing children 28-90 d of age as well as older ones in whom meningitis must be excluded
- Stool for WBCs and culture when diarrhea present and suggestive of bacterial process
- C-reactive protein (CRP) elevation commonly provides confirmatory data related to the presence of infection. The sedimentation rate (ESR) is an adjunctive measure but takes longer to perform
- Procalcitonin is used in some settings as additional confirmatory information. A serum concentration ≤0.3 ng/mL may be helpful as an add-on test for identifying los risk, febrile infants <91 d of age
- Neonates with suspected HSV should have HSV PCR testing of blood and CSF and testing of skin lesions
- Viral testing (PCR) may help risk stratify for serious bacterial infection
Imaging
- CXR to exclude pneumonia if patient tachypneic or hypoxic
- Other studies as indicated to evaluate for specific underlying infection
Differential Diagnosis
See “Etiology”
Prehospital
- Resuscitate as appropriate:
- Begin cooling with antipyretics
Initial Stabilization/Therapy
- Treat any life-threatening conditions
- Antipyretic therapy
- Evaporative cooling techniques, such as sponge bath are not generally used
ED Treatment/Procedures
- Focal infections require evaluation and treatment
- Toxic children require prompt septic workup and appropriate antibiotics
- All potential life-threatening conditions must be excluded before treating a minor acute illness, which is more common
- Infants 0-28 d old need a full sepsis workup: CBC, UA, lumbar puncture, cultures (blood, urine, CSF). A CXR should be obtained if there is suspicion for pneumonia:
- Antibiotics: Ampicillin and either gentamicin or cefotaxime
- Consider empiric acyclovir for neonates at risk for HSV should be strongly considered in neonates (esp <42 d) with symptom including seizure, lethargy, toxic appearance, vesicular lesions, CSF pleocytosis or abnormal liver enzymes
- Admit
- Well appearing infants 29-90 d old need workup, selective antibiotics use (ceftriaxone) and reevaluation within 24 hr:
- H. influenzae type B and S. pneumoniae incidence has declined significantly with widespread vaccination
- It is currently reasonable to perform CBC, UA, blood culture, and urine culture with selective lumbar puncture, and defer antibiotics in low-risk patients (see definition under “Discharge Criteria”) if re-evaluation in 24 hr is ensured
- While lumbar puncture is optional in this setting, treatment with empiric antibiotics (ceftriaxone) without lumbar puncture may compromise subsequent re-evaluation
- Presence of bronchiolitis, influenza, or other virus on PCR in this age group decreases but does not eliminate the risk of bacteremia and meningitis, but the rate of UTI is still appreciable
- Children 3 mo-3 yr of age are evaluated selectively; those with recognizable viral syndrome (croup, stomatitis, varicella, bronchiolitis) generally do not require a specific workup beyond that appropriate for the illness unless there is toxicity; antibiotic use is individualized for specific identifiable infections and pending appropriate cultures:
- Well-appearing children with a temperature >39°C and no identifiable infection should prompt a UA and culture in all male infants <6 mo, uncircumcised male infants <12 mo, and females <2 yr. Urine for culture should be obtained by catheterization or suprapubic techniques
- Obtaining blood work or performing a lumbar puncture on a child 6 mo-3 yr of age is a clinical decision. Mand atory lumbar puncture in this age group based solely on the presence of fever has not been shown to be cost-effective and is not routinely recommended
- Children 3-6 mo of age who are incompletely immunized and have WBC >15,000/mm3 and no identifiable infection may benefit from empiric antibiotics until preliminary blood cultures are available because of the risk of bacteremia
- Children >3 yr need a carefully focused evaluation on specific findings. Although viral illness predominates, such organisms as group A streptococcus, Mycoplasma, and Epstein-Barr virus are common
- Immunocompromised children need aggressive evaluation, as do children with fever and petechiae/purpura, or sickle cell disease
- If methicillin-resistant S. aureus is considered, clindamycin or trimethoprim-sulfamethoxazole may be useful
- Future algorithms may allow for fewer lumbar punctures in low-risk children >7 d
Medication
First Line
- Acyclovir: 60 mg/kg/d IV divided q8h for 14-21 d depending upon cultures
- Ampicillin: 150 mg/kg/d IV divided q4-6h
- Cefotaxime: 100-150 mg/kg/d IV divided q8h
- Ceftriaxone: 50-100 mg/kg/d IV/IM divided q12h
- Vancomycin: 40-60 mg/kg/d IV divided q6-8h if S. pneumoniae suspected until sensitivities defined
- Gentamicin: 5 mg/kg/d IV divided q8-12h
Second Line
- Acetaminophen: 15 mg/kg per dose PO/PR (per rectum) q4-6h; do not exceed 5 doses/24 hr or 4 g/24 hr
- Ibuprofen: 10 mg/kg per dose PO q6-8h
- Specific antibiotics for identified or specific conditions
Disposition
Admission Criteria
- All toxic patients
- Infants 0-28 d of age with temperature >38°C
- Nontoxic infants 29-90 d of age with temperature >38°C who do not meet low-risk criteria (see definition under “Discharge Criteria”)
- Patients with fever and petechiae/purpura are generally admitted unless there is a specific non-life-threatening cause
- Immunocompromised children
- Poor compliance or follow-up
- Children requiring admission should generally have antibiotics administered before transfer to the ward
Discharge Criteria
- Infants 29-90 d of age meeting low-risk criteria:
- No prior hospitalizations, chronic illness, antibiotic therapy, prematurity
- Reliable, mature parents with working phone, available transport, thermometer, and living in relative proximity to ED
- No evidence of focal infection (except otitis media); nontoxic appearing; normal activity, perfusion, and hydration with age-appropriate vital signs
- Normal WBC (5-15,000/mm3), urine (negative Gram stain of unspun urine, leukocyte esterase or <5 WBC/high power field [HPF]), stool (<5 WBC/HPF) if performed, and CSF (<8 WBC/mm3 and negative Gram stain) if performed
- Infants 3-36 mo of age who are nontoxic and previously healthy with good follow-up:
- Follow-up by phone in 12-24 hr and re-evaluate in 24-48 hr with parental instructions to return if concerns develop or patient worsens
Issues for Referral
- Infectious disease for complex infection
- Hematology/oncology for immunocompromised patient or presence of fever and neutropenia
Follow-up Recommendations
- Patients discharged with fever require close follow-up, usually by their primary care provider and guidelines of when to return with any change or worsening of signs or symptoms
- Fever control should be reviewed with acetaminophen or ibuprofen
- American Academy of Pediatrics. Red Book 2018-2021: Report of the Committee on Infectious Diseases. 31st ed.Itasca, IL: AAP; 2018.
- American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever; MaceSE, GemmeSR, et al. Clinical policy for well-appearing infants and children younger than 2 years of age presenting to the emergency department with fever . Ann Emerg Med. 2016;67(5):625-639.e13.
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