Approach to a patient with fever in Emergency Department

The commonest presenting complaint of infection is fever. The increase in body temperature regulatory set point causes the rise in temperature above the normal range (36.5 – 37.5 degree C). Conditions related to infectious and or noninfectious may cause fever as a response to pyrogenic substances forming due to specific triggers (Table 1). Certain mechanism in hypothalamus controls this. This is a very complicated process, so that it is not always that infection is invariably associated with fever or every febrile person is having an infection.

Definition of fever:

Although a fever technically is any body temperature above the normal of 98.6 F (37 C), in practice a person is usually not considered to have a significant fever until the temperature is above 100.4 F (38C) or feverish. (https://www.medicinenet.com/script/main/art.asp?articlekey=3425).

Table1 (from scholarena.com).

Infectious	Non Infectious
Sepsis,   Bacterial Infection, Cellulitis, Cholecystitis/Cholangitis, Pneumonia, Osteomyelitis, Urinary Tract Infection, Abscesses, Meningitis, Otitis/Sinusitis, Carditis/Endocarditis, Viral Infections, Parasitic Infections, Arthropod Infections, Fungal Infections	Seizures, Hyperthyroidism, Neuroleptic Malignant Syndrome, Serotonin Syndrome, Heat Stroke, Sympathomimetic Use, Anticholinergic Overdose, Malignant Hyperthermia, Intracranial Hemorrhage, Malignancies, Autoimmune, Pulmonary Embolism, Cerebrovascular Accidents, Thrombosis

Hyperpyrexia:

This is a condition when fever is more than 106.7 degree F. The usual differential in Emergency department is

1. Sepsis
2. Heat Exposure
3. Neuroleptic Malignant Syndrome
4. Medication Side effect (Drug fever)
5. Serotonin Syndrome
6. Thyroid storm

(Adapted from :McGugan EA. Hyperpyrexia in the emergency department. Emergency Medicine 2001;13(1):116).

In 1970 two historical studies reported fever in 50% (>37.5°C) and 57.1% (>38°C) of patients with pulmonary embolism respectively. The landmark Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study showed that a much lower rate of fever in their patients with Pulmonary embolism.  Their findings were that 14% of patients with fever (≥ 100.0°F) had no identifiable source of that  fever other than pulmonary embolus. The incidence of pulmonary hemorrhage or infarction was not statistically significant higher in those with fever. Calvo-Romero et.al performed a retrospective review of 154 patients with acute pulmonary embolism and found 18.2% had fever (>37°C) without any other known causes. So in the diagnostic approach of fever pulmonary embolism should always be suspected specially when other causes are not clear.

Some important Facts:

• Not all fever is from an infectious source. Keep a broad differential and narrow based on a detailed history, a thorough physical exam, and lab/imaging results.
• Blood cultures are not a routine part of the evaluation of fever and should be deployed in clinical scenarios which are evidence-based (e.g. septic shock) or when the results would affect patient care.
• CRP, PCT, and ESR can be helpful in certain patient care scenarios as adjunctive information when trying to establish the source of a fever as infectious in etiology. Lack of specificity for each of these makes the clinical pre-test probabilityparamount prior to ordering these tests.
• Not all septic patients have fever! Those without fever have been shown to have worse in-hospital outcomes.
• Oral temperatures can be used for clinical decision making if a fever is documented. However, the poor sensitivity of oral temperatures mandates that a core temperature be obtained if the result would change management.  Bottom line: if you suspect sepsis and the patient is afebrile orally, get a core temperature.
• Use your clinical judgment when deciding whether to treat a fever—not all fevers need to be treated with anti-pyretics.
• Do not dismiss the diagnosis of pulmonary embolus because the patient is febrile. (http://www.emdocs.net/evaluation-fever-emergency-department/)

Clinicians should also consider whether Candida species are likely pathogens when choosing initial therapy. Risk factors for invasive Candida infections include immunocompromised status (neutropenia, chemotherapy, transplant, diabetes mellitus, chronic liver failure, chronic renal failure), prolonged invasive vascular devices (hemodialysis catheters, central venous catheters), total parenteral nutrition, necrotizing pancreatitis, recent major surgery (particularly abdominal), prolonged administration of broad-spectrum antibiotics, prolonged hospital/ICU admission, recent fungal infection, and multisite colonization (^3,4). If the risk of Candida sepsis is sufficient to justify empiric antifungal therapy, the selection of the specific agent should be tailored to the severity of illness, the local pattern of the most prevalent Candida species, and any recent exposure to antifungal drugs. Empiric use of an echinocandin (anidulafungin, micafungin, or caspofungin) is preferred in most patients with severe illness, especially in those patients with septic shock, who have recently been treated with other antifungal agents, or if Candida glabrata or Candida krusei infection is suspected from earlier culture data (^1,2). Triazoles are acceptable in hemodynamically stable, less ill patients who have not had previous triazole exposure and are not known to be colonized with azole-resistant species. Liposomal formulations of amphotericin B are a reasonable alternative to echinocandins in patients with echinocandin intolerance or toxicity (^1, 2). Knowledge of local resistance patterns to antifungal agents should guide drug selection until fungal susceptibility test results, if available, are received. Rapid diagnostic testing using β-D-glucan or rapid polymerase chain reaction assays to minimize inappropriate anti-Candida therapy may have an evolving supportive role. However, the negative predictive value of such tests is not high enough to justify dependence on these tests for primary decision-making.

Surviving Sepsis Campaign 2018:

Definition:

• Sepsis: Life-threatening organ dysfunction caused by dysregulated host response to infection
• Septic Shock: Subset of sepsis with circulatory and cellular/metabolic dysfunction associated with higher risk of mortality

qSOFA (Quick SOFA) Criteria:

• Respiratory rate ≥22/min
• Altered mentation
• Systolic blood pressure <&=100 mm Hg
• Any clinical evidence of infection and any 2 or more of this is sepsis (SSC 2016)

Hour-1 Surviving Sepsis Campaign Bundle of Care  (2018)

• Measure lactate level*
• Obtain blood cultures before administering antibiotics.
• Administer broad-spectrum antibiotics.
• Begin rapid administration of 30mL/kg crystalloid for hypotension or lactate level ≥ 4 ​mmol/L.
• Apply vasopressors if hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mm Hg.

* “Time zero” or “time of presentation” is defined as the time of triage in the Emergency Department or, if presenting from another care venue, from the earliest chart annotation consistent with all elements of sepsis (formerly severe sepsis) or septic shock ascertained through chart review.

References:

1. Bow EJ, Evans G, Fuller J, et al. Canadian clinical practice guidelinesfor invasive candidiasis in adults. Can J Infect Dis Med Microbiol. 2010;21:e122–e150.
2. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–50.
3. Pittet D, Monod M, Suter PM, et al. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–758.
4. Blumberg HM, Jarvis WR, Soucie JM, et al; National Epidemiology of Mycoses Survey(NEMIS) Study Group. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis. 2001;33:177–186.

Author:

Dr. Apurba Kumar Borah
Head of the Department
Critical Care and Emergency Medicine
Narayana Superspeciality Hospital, Guwahati, Assam.