Doctor123.org

Fever, Adult, Emergency Medicine

Basics

Description

- Infectious processes: - CNS, chest and lung, gastrointestinal, genitourinary, skin, soft tissue and bone, vascular and endocardial - Iatrogenic: Catheters, implants, hardware, recent surgical sites.

- 1 ° CNS processes such as CVA, trauma, seizures - Neoplastic fevers - Drug fever: - Most drugs can cause elevated temperatures by a wide variety of mechanisms - Toxidromes (e.g., adrenergic, anticholinergic, dopaminergic, salicylate overdose, serotonin toxicity) - Hypersensitivity: - Allergic reaction - Serum sickness

- Jarisch-Herxheimer reaction - Local phlebitis from irritant drugs

- Miscellaneous: - Alcoholic cirrhosis - Acute inhalation exposures (e.g., metal fume fever) - Cotton fever: - Febrile reaction from an injected contaminant when IV drug abusers strain drug through cotton

- Sickle cell disease - Hemolytic anemia - Pulmonary embolus

- Common causes of FUO: - Infectious: - Abdominal and pelvic abscesses - Cardiac (endocarditis, pericarditis) - Cat scratch disease - Cytomegalovirus - Epstein-Barr virus - TB (miliary, renal, or meningitic) - Typhoid enteric fevers - Visceral leishmaniasis

- CBC: - Important in determining neutropenia in patients with risk factors - Neutrophilia and bandemia suggestive of bacterial infection - Lymphocytosis suggestive of typhoid, TB, brucellosis, and viral disease - Atypical lymphocytosis seen in mononucleosis, cytomegalovirus, HIV, rubella, varicella, measles, and viral hepatitis - Monocytosis suggestive of TB, brucellosis, viral illness, and lymphoma

- Antipyretics: - Generally either acetaminophen or NSAIDs - Inhibit the cyclooxygenase enzyme, thereby blocking synthesis of prostaglandins.

- Monotherapy: - Cefepime - Ceftazidime - Imipenem

- Antipyretics: - Acetaminophen: 650-1,000 mg PO/PR q4-6h; do not exceed 4 g/24h - Aspirin: 650 mg PO q4h; do not exceed 4 g/24h - Ibuprofen: 800 mg PO q6h

- Antibiotics: - Cefepime: 2 g IV q12 - Ceftazidime: 2 g IV q8 - Gentamicin or tobramycin (D): 2 mg/kg IV load then 1.7 mg/kg q8h + piperacillin/tazobactam (B) 3.375 g IV q4h or ticarcillin/clavulanate (B) 3.1 g IV q4h - Imipenem/cilastatin: 500-1,000 mg IV q8h - Meropenem (B): 1 g IV q8h - Ciprofloxacin: 750 mg PO BID + amoxicillin/clavulanate (B) 875 mg PO BID

  • Fever is an elevation of core body temperature caused by an increase in the bodys thermoregulatory set point.
  • Prostaglandin E2 (PGE2) synthesis in the anterior hypothalamus controls the thermostat, and is the target of antipyretics.
  • Core temperature is regulated to 37 °C ± 2 °C.
  • Autonomic discharge from hypothalamus can raise core temperature through shivering and dermal vasoconstriction.
  • Normal circadian variation in core temperature occurs with nadir in early morning and peaks in late afternoon.
  • Fever is not synonymous with hyperthermia or hyperpyrexia.
  • Hyperthermia is an elevated temperature with normal thermostat set point; caused by excessive endogenous heat production or endogenous production (e.g., malignant hyperthermia or heat stroke).
  • Hyperpyrexia is extreme fever >41.5 °C usually from CNS hemorrhages.
  • Both exogenous and endogenous factors can raise the body's set thermoregulatory point:Endogenous pyrogens include PGE2, IL-1, IL-6, TNF, IFN-γ.Exogenous pyrogens include lipopolysaccharide (LPS) endotoxin and other TLR ligands, and toxic shock syndrome toxin (TSST-1) and other MHC II ligands.
  • Patients on anticytokine medications or glucocorticoids have impaired fever response.
  • Fever of unknown origin (FUO):Fever >38.3 °C for at least 3 wk as an outpatient and 3 days of inpatient evaluation or 3 outpatient visits without determining etiology.

Etiology

  • Infectious processes:CNS, chest and lung, gastrointestinal, genitourinary, skin, soft tissue and bone, vascular and endocardialIatrogenic: Catheters, implants, hardware, recent surgical sites.
  • 1 ° CNS processes such as CVA, trauma, seizures
  • Neoplastic fevers
  • Drug fever:Most drugs can cause elevated temperatures by a wide variety of mechanismsToxidromes (e.g., adrenergic, anticholinergic, dopaminergic, salicylate overdose, serotonin toxicity)Hypersensitivity:Allergic reactionSerum sicknessJarisch-Herxheimer reactionLocal phlebitis from irritant drugs
  • Severe withdrawal:
  • Systemic rheumatologic and inflammatory diseases (e.g., familial Mediterranean fever, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, temporal arteritis)
  • Endocrine:Hyperthyroidism, pheochromocytoma
  • Miscellaneous:Alcoholic cirrhosisAcute inhalation exposures (e.g., metal fume fever)Cotton fever:Febrile reaction from an injected contaminant when IV drug abusers strain drug through cottonSickle cell diseaseHemolytic anemiaPulmonary embolus
  • Common causes of FUO:Infectious:Abdominal and pelvic abscessesCardiac (endocarditis, pericarditis)Cat scratch diseaseCytomegalovirusEpstein-Barr virusTB (miliary, renal, or meningitic)Typhoid enteric feversVisceral leishmaniasisNeoplastic:Colon adenocarcinomaHepatocellular carcinoma and metastasesMyeloproliferative disordersLeukemia and lymphomaRenal cell carcinoma

Diagnosis

Signs and Symptoms

History

  • Chills, shivering, and rigors:Rigors may suggest bacteremia
  • Weight loss:Suggestive of neoplastic, chronic infectious, or endocrine disorders
  • Night sweats:Suggestive of neoplastic, chronic inflammatory disease, or TB
  • Specific fever patterns:Daily morning temperature spikes:Miliary TB, typhoid fever, polyarteritis nodosaRelapsing fevers: Febrile episode with alternating afebrile intervals:Seen in malaria, Borrelia infections, rat-bite fever, and lymphomaRemittent fever: Temperature falls daily but does not return to normal:Seen in TB and viral diseasesIntermittent fevers: Exaggerated circadian rhythm:Seen in systemic infections, malignancy, and drug feverDouble quotidian fever:Common pattern of 2 temperature spikes in 24 hrIn FUO, consider miliary TB, visceral leishmaniasis, and malarial infections
  • High-risk features:Anticytokine therapy (e.g., TNF-α monoclonal antibodies, calcineurin inhibitors)Glucocorticoid useImmunosuppressed statesIncomplete vaccination statusIV drug usePregnancy and peripartum patientsRashRecent chemotherapyRecent travelSplenectomy

Physical Exam

  • Elevated core temperature:Temperature >38 °C (100.4 °F) rectally or 37.5 °C (99.5 °F) orallyLower thresholds in patients older than 65 yr, as the febrile response is not as strong
  • Diaphoresis:Absence of diaphoresis with severe hyperthermia suggests anticholinergic poisoning or heat stroke.
  • Tachycardia:For each degree of elevation in temperature in Fahrenheit, there should be a 10 bpm increase in pulse.Relative bradycardia (Faget sign):Associated with malaria, typhoid fever, CNS disorders, lymphoma, drug fever, brucellosis, ornithosis, Legionnaire disease, Lyme disease, and factitious fevers
  • Muscle rigidity, clonus, and hyper-reflexia:Associated with specific toxidromes and medical conditions
  • Changes in mental status:Toxic-metabolic encephalopathy vs. primary CNS disorder
  • Rash:Lesion type, distribution, and progression can offer important clues to diagnosis.Petechia, purpura, vesicles, mucosal, or palm and sole involvement require special note
  • Signs of hyperthyroidism:

Essential Workup

  • Core temperature is most acutely measured rectally.
  • Careful history and physical exam (PE) necessary to determine need for further diagnostic testing:History should elicit any sick contacts, previous infections, occupational exposures, recent travel, medications, animal or tick exposure, and immunization status.

Diagnosis Tests & Interpretation

Lab

  • CBC:Important in determining neutropenia in patients with risk factorsNeutrophilia and bandemia suggestive of bacterial infectionLymphocytosis suggestive of typhoid, TB, brucellosis, and viral diseaseAtypical lymphocytosis seen in mononucleosis, cytomegalovirus, HIV, rubella, varicella, measles, and viral hepatitisMonocytosis suggestive of TB, brucellosis, viral illness, and lymphoma
  • Lactate:Initial and repeat measurements useful for screening for sepsis, risk stratification, and management decisions
  • Urinalysis and urine culture
  • Blood cultures:Obtain for all systemically ill patients, and patients at risk for bacteremia
  • Thick and thin blood smears and malaria antigen testing in at-risk individuals for parasitic and intraerythrocytic infections
  • Stool culture and Clostridium difficile assay for suspected individuals.
  • Heterophile antibody testing in select patients.
  • Erythrocyte sedimentation rate and C-reactive protein generally not useful:Very high values suggestive of endocarditis, osteomyelitis, TB, and rheumatologic conditions.
  • Decreased immunocompetence, increased risk of systemic spread, increased exposure to health care settings, may have comorbid conditions.
  • If institutionalized consider the infectious implications of multiple potential sick contacts.

Imaging

  • CXR:In patients with PE finding of cardiopulmonary disease and patients with unclear fever source
  • CT or MRI may be indicated if lumbar puncture or osteomyelitis is considered, respectively.

Differential Diagnosis

  • The differential diagnosis is very broad as listed above, but is generally categorized as infectious vs. noninfectious, and by immunocompetency.

Treatment

Pre-Hospital

  • No specific field interventions required
  • Monitoring and IV access should be obtained in the field for unstable patients or patients with altered mental status.

Initial Stabilization/Therapy

  • ABCs for unstable patients.
  • Initiate early broad-spectrum antibiotics for patients with suspected sepsis or unstable vital signs, particularly those who are at high risk for serious bacterial infection.

Ed Treatment/Procedures

  • Antipyretics:Generally either acetaminophen or NSAIDsInhibit the cyclooxygenase enzyme, thereby blocking synthesis of prostaglandins.
  • Empiric antibiotics for neutropenic patients:Combination therapy:Extended spectrum β-lactam (ceftazidime, piperacillin) with an aminoglycosideMonotherapy:CefepimeCeftazidimeImipenem
  • Empiric antibiotics for asplenic patients for encapsulated bacteria
  • Empiric antiviral therapy for patients with encephalitis and potential disseminated viral infections (e.g., recent organ or bone marrow transplant patients, AIDS patients)
  • External cooling mechanism rarely indicated

Medication

  • Antipyretics:Acetaminophen: 650-1,000 mg PO/PR q4-6h; do not exceed 4 g/24hAspirin: 650 mg PO q4h; do not exceed 4 g/24hIbuprofen: 800 mg PO q6h
  • Antibiotics:Cefepime: 2 g IV q12Ceftazidime: 2 g IV q8Gentamicin or tobramycin (D): 2 mg/kg IV load then 1.7 mg/kg q8h + piperacillin/tazobactam (B) 3.375 g IV q4h or ticarcillin/clavulanate (B) 3.1 g IV q4hImipenem/cilastatin: 500-1,000 mg IV q8hMeropenem (B): 1 g IV q8hCiprofloxacin: 750 mg PO BID + amoxicillin/clavulanate (B) 875 mg PO BID
  • Antivirals:Herpes simplex virus and varicella-zoster virus (VZV):Acyclovir 10-15 mg/kg IV q8hInfluenza A and B:Oseltamivir 75 mg PO q12h

Follow-Up

Disposition

Admission Criteria

  • Patients with unstable vital signs require ICU admission.
  • When identified, the underlying source of the fever usually determines the disposition.
  • Certain high-risk groups who have fever without an identifiable source:Neutropenic patientsImmunosuppressed or immunocompromised patientsAsplenic patientsIV drug abusers
  • Lower thresholds for admission in patients older than 60 yr and diabetics

Discharge Criteria

Immunocompetent patients with stable vital signs and an identified source of fever or a high suspicion of a nonthreatening viral infection may be safely discharged.

Issues for Referral

The suspected etiology of the fever determines the referral to a primary care physician or a specialist.

Followup Recommendations

Appropriate outpatient treatment and follow-up for further outpatient assessment of the suspected etiology.

Pearls and Pitfalls

  • Screening lactates for sepsis.
  • Early, empiric, and broad-spectrum antibiotic coverage for all septic patients.
  • Consider all potential sources of infection.
  • Careful consideration for the immunosuppressed, elderly, and IV drug users.

Additional Reading

  • Cunha BA. Fever of unknown origin: Focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin North Am. 2007;21:1137-1187.
  • Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56-e93.
  • Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA. 1992;268(12):1578-1580.

Codes

ICD9

  • 780.60 Fever, unspecified
  • 780.61 Fever presenting with conditions classified elsewhere

ICD10

  • R50.2 Drug induced fever
  • R50.9 Fever, unspecified
  • R50.81 Fever presenting with conditions classified elsewhere

SNOMED

  • 386661006 fever (finding)
  • 7520000 Pyrexia of unknown origin (finding)
  • 95908009 Drug fever (finding)