Neutropenic sepsis

Question 1

Define neutropenic sepsis.

Answer 1

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.

Question 2

What is sepsis? What is septic shock?

Answer 2

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

Question 3

What is febrile neutropenia?

Answer 3

Febrile neutropenia is the most common complication of anticancer treatment, and describes the presence of fever in a person with neutropenia. Definitions vary.

Question 4

How common is neutropenic sepsis?

Answer 4

Incidence increasing probably with use of anticancer drugs and immunosuppressive therapy - febrile neutropenia occurs in about 8 of 1000 chemo patients

Question 5

What are the causes of neutropenia?

Answer 5

• 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

Question 6

Which bacterial and fungal organisms are likely to cause sepsis in a neutropenic patient?

Answer 6

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

Question 7

What are the risk factors for neutropenic sepsis?

Answer 7

• Chemotherapy
• Age - infants and over 60s
• Corticosteroids
• Antibiotics
• Advanced malignancy
• Central venous access device
• TPN
• Co-morbidities
• Previous surgery

Question 8

What are the signs and symptoms of neutropenic sepsis?

Answer 8

• 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

Question 9

What investigations would you do for a patient with suspected neutropenic sepsis?

Answer 9

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