29th December 2024

Neutropenic sepsis

Overview of neutropenic sepsis

Chemotherapeutic drugs generally work by interrupting cell replication pathways. This can be highly effective as an anti-cancer therapy, however can lead to side effects in normal tissues with high replication rates. Bone marrow suppression is one such side effect.

Any cell line within the marrow may be suppressed; typically bone marrow failure secondary to cytotoxic drugs results in pancytopenia. Typically, neutropenic nadir occurs first, 7 to 14 days post chemotherapy (Table 6).

Neutropenia leads to significant risk of infection and sepsis and can be life threatening. It is essential to consider febrile neutropenia and initiate antibiotic therapy readily in patients receiving chemotherapy who present with fever.

Definitions in neutropenic sepsis

Risk factors for neutropenic sepsis

There is an increased risk of neutropenic sepsis in:

• Haematological malignancies
• High-dose/intensive chemotherapy regimes
• Receiving first cycle of chemotherapy or low first-cycle neutrophil nadir < 0.5 x 10⁹/L
• Previous neutropenic fever
• Long duration of, or severe neutropenia
• Performance status > 1
• Older age (> 65 years old )
• Comorbidities including diabetes mellitus, liver disease and renal disease
• Hypoalbuminaemia with (albumin < 35 g/dL)
• Pre-treatment anaemia (pre-treatment haemoglobin < 120 g/L)

Investigations and management of neutropenic sepsis

Investigation and management of patients with febrile neutropenia and neutropenic sepsis is broadly the same. Septic patients will require earlier close monitoring and early escalation to critical care or high dependency units.

Investigations in neutropenic sepsis

Admission investigations include:

• Blood gas for lactate
• Blood tests including FBC and differential, renal and liver function
• Septic screen, comprising blood cultures (peripheral and from lines), urine/sputum/stool/wound samples as appropriate, and chest X-ray

Emergency management of neutropenic sepsis

• Empirical broad-spectrum antibiotics (e.g. piperacillin-tazobactam) should be initiated in febrile patients receiving chemotherapy within 60 minutes of presentation to hospital, i.e. prior to results of FBC. Taking cultures should not delay delivery of antibiotics
• IV fluids are given if clinically hypovolaemic
• Granulocyte colony stimulating factor (G-CSF) can be started to support neutrophil count if neutropenia is confirmed. This should be discontinued after neutrophil count improves to > 1.0.
• Close monitoring and early escalation is essential, including sepsis management and early discussion with critical care teams

Ongoing management of neutropenic sepsis

• Monitor cell counts and support as necessary. Generally, platelet transfusions may be considered in discussion with the haematology team if platelet count is either < 10 x 10⁹/L, or < 20 x 10⁹/L and bleeding or septic. Alternative causes that may contribute to pancytopenia in septic patients should be considered, including disseminated intravascular coagulation.
• Consider escalation or rationalisation at 48 hours:
  • With ongoing temperature spikes or deterioration, antibiotic therapy may be escalated.
  • If cultures identify a culprit organism, antibiotics should be rationalised in discussion with microbiology. If line cultures are positive, line removal may be required.
  • Of note, causative organisms are not identified in 2/3 cases, in which case a course of empirical antibiotics can be completed, depending on suspected source.
• Consider opportunistic infections at 4-6 days:
  • Failure of fever to resolve after 5 days should prompt repeat cultures and consideration of an opportunistic infection caused by fungal or parasitic organisms, e.g. Pneumocystis carinii.
  • These patients may require further imaging with CT scans and escalation of antimicrobial therapy.
• The patient’s oncology team should be informed, and further chemotherapy is generally delayed until the patient has recovered from the infection. Future chemotherapy can be managed with dose reductions, changing chemotherapy agent or regime, or prophylactic administration of G-CSF during treatment cycles.

References

• Cassidy J, Bissett D, Spence RAJ, Payne M, Morris-Stiff GJ. Oxford Handbook of Oncology. 4th ed. Oxford: Oxford University Press; 2015
• Rolston KVI, Nesher L. Febrile neutropenia [Internet]. BMJ Best Practice. 2019 [cited 2022 Apr 17]. Available from: https://bestpractice.bmj.com/topics/en-gb/950
• National Institute for Health and Care Excellence. Neutropenic sepsis [Internet]. NICE. 2022 [cited 2022 Apr 17]. Available from: https://cks.nice.org.uk/topics/neutropenic-sepsis/