Neutropenic sepsis Flashcards
Define sepsis
Sepsis - life threatening organ dysfunction due to a dysregulated response to infection.
Year 1 revision: Definitions
1) infection
2) sepsis
3) SIRS
4) Severe sepsis
- Infection = invasion and multiplication of pathogenic microbes in an area of the body where they are not normally found
- sepsis = life threatening organ dysfunction due to a dysregulated response to infection (From Year 1 sepsis could also be defined as SIRS + confirmed / suspected infection, when the body’s own response to infection causes injury to its own tissues and organs).
- SIRS = systemic inflammtory response syndrome –> inflammatory response to infection that affects the whole body
- Severe sepsis = Sepsis PLUS severe organ dysfunction (includes septic shock)
Define septic shock
Septic shock = is sepsis with persistent hypotension for which you require vasopressors to maintain a mean ABP of > or = to 65mmHg and having a serum lactate of greater than 2 mmol/L despite adequate volume rescucitation.
What is neutropenic sepsis?
- Neutropenic sepsis/ febrile neutropenia = common complication of chemotherapy
- can occur in all types of cancer but often more common in patients w haematological malignancies than in solid tumours
- Risk greatest in first treatment but is cumulative with ongoing cycle of therapy
- risk of life threatening infection is related to the degree of immunosppression - assessed by the ANC (absolute neutrophil count) –> risk rises with falling ANC
- Neutropenic sepsis level = neutrophil count of less than 0.5x 109 / L or less than 1 x 109/L and is expected to fall 500cells/microlitre within next 48 hrs. Temperature of > 38 for an hour or single oral temperature of > 38.3.
Define neutropenic sepsis
Definition: Neutropenic sepsis
is a life threatening complication of anticancer treatment, describes the significant inflammatory response ot a presumed bacterial infection in an individual w or w/out fever.
A temperature of greater than 38OC or any symptoms and/ or signs of sepsis, in a person with absolute neutrophil count of 0.5x109 /L or lower.
What are the risk factors for the development of neutropenic sepsis?
- Age > 65 years
- low albumin level (below normal of 35 g/L)
- pre-existing organ dysfunction
- pre treatment haemoglobin lower than 120g/L
- full dose intensity chemotherapy
- low first cycle nadir (nadir = lowest reading) absolute neutrophil count < 500cells/ microlitre
- haematological malignancies
- concurrent radiotherapy (alongside chemotherapy)
- previous episoders of neutropenia following chemotherapy
LO: Pathophysiology of neutropenic sepsis
Pathophysiology of neutropenic sepsis:
- Occurs when a patient with neutropenia develops a life threatening infection –> pathogen only identified in 1/3 patients; host endogenous flora is primary source of pathogen
- Chemotherapy suppresses both the production of WBC’s and damages the mucosa in the gut, which increases the translocation of bacteria (gut flora). ( chemoT basically inhibits any rapidly dividing cell within the body).
- Due to disruption of mucosa in gut and pharynx (oro and nasal pharynx) –> translocation of gram negative (E.coli/ Klebsiella, Pseudomonas) and gram positive bacteria (staphylococci, staph aureus)
- Inhibition of WBC production –> inhibit production of neutrophils –> phagocytes w central role in fighting off bacterial infections
- deficit in neutrophils and damaged mucosa –> set up for bacterial infection without the ability to fight it off (immunosuppression) = sepsis
Understand neutropenic sepsis is an acute medical emergency - why?
- Neutropenic sepsis - medical emergency as patient may go into septic shock
What are some common causes of neutropenia?
Neutropenia causes broadly divided into hereditary and acquired.
Hereditary causes - often inherited disorder in neutrophil elastase ELA2
Acquired: Split into infection, drugs, autoimmune and intrinsic bone disease
- Intrinsic bone disease
- haematological malignancy
- leukaemia/ lymphoma
- myeloma
- myelodysplasia
- Aplastic anaemia
- Tumor infiltration or ionising radiation
-
Drug mediated/ iatrogenic :
- Cytotoxic chemotherapy
- DMARDS
- stem cell transplant
- Anti-thyroid - carbimazole
- Anti-psychotic - clozapine, olanzapine
- Abx’s –> penicillins
-
Autoimmune:
- autoimmune neutropenic anaemia –> Crohns/ RA/ Sjogrens/SLE
-
Infection:
- bacterial sepsis
- viral - EBV/CMV/ viral hepatitis /HIV
- TB/malaria/ dengue fever/ typhoid/ toxoplasmosis
History in neutropenic sepsis?
- Presenting complaint:
- incidental fever at home?
- Generally unwell? Fevers/ rigors/ malaise
- any focal symptoms - e.g. productive cough, rash, dysuria, diarrhoea, jaundice, abdominal pain
- HPC:
- Cancer diagnosis - e.g. acute leukaemia particularly high risk, chronic bone marrow failure e.g. myelodysplastic syndrome/ aplastic anaemia also high risk
- Last chemotherapy - when and what? (HSC transplant recipients at particularly high risk until engraftment)
- duration of symptoms
- other chemotherapy SE’s –> mucositis/ diarrhoae/ hepatitis/ confusion
- PMH:
- other causes of neutropenia or organ failure
- Drug Hx
- Clozapine/ sulfasalazine, antithyroid drugs (carbimazole)
- Allergies - penicillin allergy severely restrict tx options for neutropenic sepsis
Examination features in neutropenic sepsis?
- Fever- temp of 38 or above for more than 1 hour - evaluate fast w cultures for emp Abx
- Features of septic shock:
- tachycardia
- Tachypnoea
- hypotension - septic shock if fails to repsond to fluid bolus of 500 ml 0.9% saline or similar
- hypoxia
- Hydration status - mucuous membranes, skin turgor, cap refill
- Signs of infection:
- Mucositis/ oral ulcers –> provide port of entry for host flora to enter bloodstream
- Cough and abnormal breath sounds (pneumonia)
- SOB (pneumonia)
- Abdo pain (GI infection)
- N & V (GI infection)
- Diarrhoea (GI infection)
- dysuria and pyuria (UTI)
- skin erythema/ warmth/ rash - soft tissue infection
- inflammation or ulceration of genital/anal area - again source of normal flora into bloodstream
- infected indwelling catheter
What are the updated SIRS criteria?
Temperature above 38 or below 36
Heart rate > 90 bpm
Respiratory rate > 20/min or pCO2 < 32mmHg
White blood cells : WCC> 12,000/ uL or WCC< 4000/uL or 10% immature WCC
Blood Glucose > 7.7 mol /L WITHOUT DIABETES
Decreased conscious level
What are the appropriate investigations for neutropenic sepsis?
Initial investigations:
-
Cultures:
- Blood cultures –> from periphery/ central venous catheter
- Consider urine culture/ stool culture/ fungal cultures
- May need to do LP on patient with evidence of CNS infection - headache/ neck stiffness/ photophobia/ altered mental status –> could show elevated WBC/blood/ increased protein.
- viral molecular assay
- Bloods:
- FBC –> ANC - absolute neutrophil count < 500 cells/ microlitre or < 1000 w projected ANC becoming less than 500
- CRP
- ESR
- clotting
- U&E’s –> evidence of renal dysfunction –> w chemotherapy toxicity/ drug fever (Normal or elevated)
-
LFT –>
- elevated LFT –> could indicate hepatic infection/ elevated also in chemoT and drug fever
- low albumin – >risk factor for neutropenic S
- Blood film
- Group and save
Other bedside:
- ABG/VBG –> for glucose and immediate lactate results
- ECG for baseline
Imaging:
- CXR –> evidence of pneumonia
What are the management steps in neutropenic sepsis?
-
ABCDE approach
- Good venous access and fluid challenges
- Oxygen if sats < 94%
- Vital priorty = blood cultures from peripheral vein or indwelling lines, then broad spectrum Abx.
- Sepsis six p/w: Within 1 hour of presentation
-
Take:
- blood cultures
- serum lactate
- urine output
-
Give:
- High flow O2
- Empirical Abx
- IV fluid resucitation
-
Take:
- Which Abx -
-
Tazocin 4.5 mg IV every 6 hrs
- piperacillin/ tazobactam
- If penicillin hypersensitive –> give ciprofloxacin PLUS clindamycin or aztreonam plus vancomycin
- Continue Abx till afebrile or neutropenia > 0.5
- If persists (which is persistent fever longer than 3-5 days): look for CMV, fungi, central line infection
- for viral CMV –> ganciclovir
- microbiologist + haematologist
- full barrier nursing room (handwashing)
-
Tazocin 4.5 mg IV every 6 hrs
What prevention is there for neutropenic sepsis?
- Recomb human granulocyte colony stimulating factor - rHG-CSF –> subcutaneously + production of neutrophils in BM
- Neutropenic diet –> cooked, canned, bottle/boiled water
- Prophylactic Abx -> fluoroquinolone
Severe sepsis red flags?
Even if lacking any other sign of sepsis:
1) HR> 130 bpm
2) RR > 25/ min
3) BP < 90 mmHg or MABP < 65mmHg
4) purpuric rash with negative glass test
5) oxygen saturation < 91%
6) serum lactate > 2 mmol/L
7) decreased conciousness on GCS
Amber sepsis criteria?
