Define neutropenic sepsis.
Neutropenic sepsis is a potentially life-threatening complication of neutropenia (low neutrophil count).
It 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.
What is sepsis? What is septic shock?
Sepsis is a syndrome defined as life-threatening organ dysfunction due to a dysregulated host response to infection
Shock - subset of sepsis involving circulatory, cellular and metabolic abnormalities –> higher risk of mortality than sepsis alone
Diagnosis of septic shock:
- hypotension despite fluid correction and ionotropes AND
- hyperlactataemia >2mmol/L
What is febrile neutropenia?
Febrile neutropenia is the most common complication of anticancer treatment, and describes the presence of fever in a person with neutropenia. Definitions vary.
How common is neutropenic sepsis?
Incidence increasing probably with use of anticancer drugs and immunosuppressive therapy - febrile neutropenia occurs in about 8 of 1000 chemo patients
What are the causes of neutropenia?
- Drugs and treatments:
- cytotoxic chemotherapy
- haematopoietic stem cell transplantation
- immunosuppressive drugs like azathioprine, methotrexate
- penicillin, carbimazole, phenytoin etc
- Infections:
- Viral - HIV, influenza, hep B, CMV, RSV, EBV cause transient BM suppression
- BM failure -
- aplastic anaemia,
- myelodysplastic syndromes,
- acute leukaemia
- Nutritional deficiencies
- B12 and folate
- Rare
- Genetic conditions e.g. Kostmann’s syndrome
Which bacterial and fungal organisms are likely to cause sepsis in a neutropenic patient?
Gram +ve pathogens (commonly):
- Staph aureus
- Enterococcus sp
- Strep pneumoniae
- S. pyogenes
Gram -ve pathogens (less commonly):
- E coli
- Klebsiella
- Enterobacter sp
- Pseudomonas aeruginosa
Fungal:
- Candida sp
- Aspergillus sp
What are the risk factors for neutropenic sepsis?
- Chemotherapy
- Age - infants and over 60s
- Corticosteroids
- Antibiotics
- Advanced malignancy
- Central venous access device
- TPN
- Co-morbidities
- Previous surgery
What are the signs and symptoms of neutropenic sepsis?
- Suspect if known neutropenia. Unexpected deterioration
- Features of infection - dysuria, diarrhoea, productive cough
- General - malaise, agitation, fever (>38oC), chills, shivers, rigors. NB some may not have fever but hypothermia instead.
- Cardio - Tachycardia, hypotension, slow cap refill - mottled/ashen skin, pallor/cyanosis, cold peripheries
- Rash - non-blanching in meningococcal disease
What investigations would you do for a patient with suspected neutropenic sepsis?
Give 3 - oxygen, antibiotics, fluids (bolus)
Take 3 - blood culture (before abx), serial lactate, urine output hourly
Investigations:
- Blood culture
- ABG - lactate, glucose
- FBC - WCC may be high/low, ?DIC, neutropenia
- CRP - high
- Creatinine, urea, electrolytes - dehydration/AKI
- LFTs - high bil or ALT may show cholestasis
- Clotting screen - may be abnormal
- Urinalysis
- Sputum microscopy and culture
- CXR, CT
- Bronchoalveolar lavage - if severe or prolonged
