Urgent considerations

See Differentials for more details

Fever and neutropenia

Fever in a neutropenic patient is an emergency and should be addressed immediately. Fever may be the only symptom of infection in neutropenic patients.[42] See Febrile neutropenia.

Sepsis

Patients with febrile neutropenia are at risk of sepsis and septic shock.[43][44]​​​​ Sepsis is a spectrum of disease, where there is a systemic and dysregulated host response to an infection.[45]​ Presentation ranges from subtle, non-specific symptoms (e.g., feeling unwell with a normal temperature) to severe symptoms with evidence of multi-organ dysfunction and septic shock. Patients may have signs of tachycardia, tachypnoea, hypotension, fever or hypothermia, poor capillary refill, mottled or ashen skin, cyanosis, newly altered mental state, or reduced urine output.[46]​ Sepsis and septic shock are medical emergencies.

Risk factors for sepsis include: age under 1 year, age over 75 years, frailty, impaired immunity (due to illness or drugs), recent surgery or other invasive procedures, any breach of skin integrity (e.g., cuts, burns), intravenous drug misuse, indwelling lines or catheters, and pregnancy or recent pregnancy.[46]

Early recognition of sepsis is essential because early treatment improves outcomes.[46][47][Evidence C][Evidence C]​​​​​​ However, detection can be challenging because the clinical presentation of sepsis can be subtle and non-specific. A low threshold for suspecting sepsis is therefore important. The key to early recognition is the systematic identification of any patient who has signs or symptoms suggestive of infection and is at risk of deterioration due to organ dysfunction. Several risk stratification approaches have been proposed. All rely on a structured clinical assessment and recording of the patient’s vital signs.[46][48][49]​​​[50][51]​ It is important to check local guidance for information on which approach your institution recommends. The timeline of ensuing investigations and treatment should be guided by this early assessment.[50]

Treatment guidelines have been produced by the Surviving Sepsis Campaign and remain the most widely accepted standards.[47][52]​ Recommended treatment of patients with suspected sepsis is:

  • Measure lactate level, and remeasure lactate if initial lactate is elevated (>2 mmol/L [>18 mg/dL])

  • Obtain blood cultures before administering antibiotics

  • Administer broad-spectrum antibiotics (with methicillin-resistant Staphylococcus aureus [MRSA] coverage if there is high risk of MRSA) for adults with possible septic shock or a high likelihood for sepsis

  • For adults with sepsis or septic shock at high risk of fungal infection, empirical antifungal therapy should be administered

  • Begin rapid administration of crystalloid fluids for hypotension or lactate level ≥4 ​mmol/L (≥36 mg/dL). Consult local protocols

  • Administer vasopressors peripherally if hypotensive during or after fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mmHg, rather than delaying initiation until central venous access is secured. Noradrenaline is the vasopressor of choice

  • For adults with sepsis-induced hypoxaemic respiratory failure, high-flow nasal oxygen should be given.

Ideally these interventions should all begin in the first hour after sepsis recognition.[52]

For adults with possible sepsis without shock, if concern for infection persists, antibiotics should be given within 3 hours from the time when sepsis was first recognised.[47]​ For adults with a low likelihood of infection and without shock, antibiotics can be deferred while continuing to closely monitor the patient.[47]

For more information on sepsis, please see our topics Sepsis in adults and  Sepsis in children.

Agranulocytosis (absolute neutrophil count <0.1 x10⁹/L or <100 neutrophils/mm³)

Severe agranulocytosis requires urgent management. If a drug is suspected as the cause, it must be discontinued immediately. The most common drug causes are clozapine, antithyroid drugs (thionamides), and sulfasalazine.[17][18][19][20]

Severe agranulocytosis is also seen in the congenital neutropenias, of which the most common are severe congenital neutropenia and cyclic neutropenia.

Antibiotic prophylaxis, including coverage of gram-negative species, should be administered. The recombinant neutrophil cytokine granulocyte colony-stimulating factor is also used, particularly in the management of congenital neutropenias.

Speciality consultation should be sought if the practitioner is not familiar with treating agranulocytosis.

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