Please read an overview of the management of sepsis before reading this article.

Neutropenic sepsis is defined as a temperature of greater than 38°C or any symptoms and/or signs of sepsis, in a person with an absolute neutrophil count of 0.5 x 10⁹/L or lower. It is a common and potentially life-threatening complication of neutropenia.

It is important to note that patients with neutropenic sepsis may not always have a raised temperature due to an inability to mount an inflammatory response. This is more common in patients who are on steroids as these can mask symptoms such as pyrexia. It is vital that we have a high degree of suspicion in neutropenic patients/ patients with risk factors for neutropenia and assess these patients urgently.

High-risk patients

• Cancer patients
• HIV
• Those who have had recent courses of chemotherapy
• Patients on immunosuppressive therapy
• Patients on steroids
• Patients with pathology affecting the bone marrow e.g. myelodysplastic syndromes

It is also important to assess patients with suspected neutropenic sepsis for possible sources of infection, things to look out for include;

• Central lines
• Urinary catheter
• Recent blood products
• Any recent infections

Signs and symptoms

• Symptoms of signs of infection (these can be subtle in a patient with neutropenic sepsis). A systems-based approach is helpful here
  • Urinary 
  • Respiratory
  • Cardiovascular 
  • Skin
  • Neurological 
  • Gastrointestinal
• Feeling generally unwell
• Change in behaviour noticed by relatives/ carers 

Investigations and Management

• If the patient is being seen in the community, they will need urgent emergency transfer to secondary care. 
• NICE guidelines suggest starting empirical antibiotics immediately before any investigations. This usually Tazocin unless local guidelines state otherwise
  • This must be given ideally within 30 minutes of presentation (international guidelines recommend 1 hour)
• Consider giving oxygen if saturations are low. 
• IV fluids
• If they are a chemotherapy patient, they should have a card with a contact number for their home team. Contact them as they know the patient best & can advise
  • Consider whether G-CSF (filgrastim) may be required to boost the neutrophil count. Seek advice on this from the chemotherapy team

Confirming the diagnosis

• Full history and examination
• Bloods
  • FBC
  • Renal function and LFTs
  • CRP
  • Blood gas (assess glucose and lactate)
  • Blood cultures
    • Peripheral blood cultures as well as culture taken from any lines in situ
• Monitor urine output and fluid balance
• Have a low threshold to send a urine sample if clinically relevant
• Have a low threshold to perform a chest x-ray/sputum culture if clinically indicated
• Consider other imaging or investigations if clinically indicated

Scoring systems

The Multinational Association for Supportive Care in Cancer (MASCC) is a scoring system suggested in the NICE guidelines for assessing those patients who are at high risk for developing septic complications.

• Burden of illness:
  • No, or mild symptoms – 5 points.
  • Moderate symptoms – 3 points.
  • Severe symptoms – 0 points.
• Absence of hypotension (systolic blood pressure ≥90 mm Hg) – 5 points.
• Absence of chronic obstructive pulmonary disease – 4 points.
• Presence of solid tumour/lymphoma with no previous fungal infection – 4 points.
• No dehydration – 3 points.
• Outpatient status (at onset of fever) – 3 points.
• Age ≤60 years – 2 points.

Low-risk cases are those scoring ≥21.

Patients who are assessed as high risk should be monitored closely for complications relating to sepsis. Support from ITU/ HDU may be required for these patients. Empiric antibiotics should be continued in patients with an unresponsive fever unless otherwise directed by microbiology or if there is clinical deterioration. Antibiotic choice should be reviewed by senior colleagues with microbiology results to ensure the most appropriate antibiotic is prescribed for any organisms detected on culture.

Follow up

Patients with neutropenic sepsis should be reviewed regularly to ensure they are clinically improving. Their bloods including neutrophil count and renal function should be monitored closely. Senior colleagues may consider switching to oral antibiotics when the patient has remained apyrexial for at least 48 hours. The duration of antibiotic therapy and when the patient is discharged from hospital will depend on;

• Type of infection
• Other co-morbidities
• Neutrophil count
• Social situation
• Frailty

It is important to give these patients good safety net advice to return to hospital should they have any problems.

References

• UpToDate – Overview of Febrile Neutropenia
• NICE CKS – Neutropenic Sepsis
• Patient.info – Neutropenic Sepsis
• NICE Pathways – Neutropenic Sepsis

Written by Dr Shamilah Rahman (GP trainee)