Policy for the clinical management of patients with febrile neutropenia

 

FEBRILE NEUTROPENIA POLICY- including emergency management of cancer patients receiving chemotherapy and/or having Hickman/PICC lines. 

This document should be read in conjunction with the procedure for the admission of Oncology and Haematology patients and the policy for access to oncology patients medical notes out of hours.

 

Policy Background

Patients undergoing chemotherapy are advised to contact the hospital immediately if they develop any of the following symptoms:

1. A fever of 38° C or more

2. Shivers or shakes

3. Signs of bleeding

4. Feeling unwell accompanied with any of the following:

  • lots of vomiting (>6 times in 24 hours)

  • diarrhoea (>5 times per day or severe cramping)

  • cough

  • dysuria

  • an ulcerated sore mouth which makes drinking difficult

Patients with the above problems should contact the Oncology or Clinical Haematology Unit during normal working hours or present to the Accident & Emergency department.
 

Policy Objective

This policy outlines the assessment and initial clinical management of patients who have been diagnosed as having febrile neutropenia. It also covers emergency treatment of cancer patients who present with fever while receiving chemotherapy and/or with indwelling Hickman/PICC line.

Policy Statements

• Each patient undergoing chemotherapy contacting the hospital due to feeling unwell will have febrile neutropenia diagnosed or ruled out urgently. NOTE: Not all seriously ill, neutropenic patients with septicaemia will present with pyrexia, especially those who are dehydrated or taking steroids or NSAIDS.

• If the blood count is not available, but the patient is febrile and is receiving chemotherapy, he/she should be treated as having febrile neutropenia

• A patient with febrile neutropenia will receive urgent treatment and will commence IV antibiotics within 1 hour of their diagnosis (see guidelines for choice of antibiotics)

• Those patients who have febrile neutropenia will be admitted to hospital as as in-patient according to the Policy for the Emergency Admission of Unwell Oncology and Haematology patients.

Initial assessment

1. History of current condition to include the last date of chemotherapy and treatment intent (e.g. curative, adjuvant, palliative)

2. General examination, look for a focus of infection or evidence of inappropriate bruising or bleeding.

3. General observation including pulse, temperature, pulse oximetry and blood pressure.

4. Urgent full blood count (and differential) plus U&E’s, CRP, Clotting and Group & Save. If pyrexial or sepsis is suspected take blood cultures, both peripherally and from intravenous access devices. Ensure full aseptic technique if handling a central catheter.

5. CXR (if patient has respiratory symptoms or signs), MSU and swabs from IV sites and wounds and sputum if indicated.

6. Clotted blood sample (5-7 ml) should be sent for viral serology and convalescent sample after 10-14 days (if indicated).

A patient is considered neutropenic if the neutrophil count is <1.0 x 109/L

 

Initial management of patients who are febrile and neutropenic

(1) Intravenous antibiotics must be commenced within 1 hour of arrival

Monotherapy with Piperacillin-Tazobactam (Tazocin) 4.5g 8 hourly is recommended unless the patient is shocked when Meropenem 1g 8 hourly should be used. In patients who are allergic to Penicillin use Meropenem 1g infused over 15 minutes. The dose of Meropenem should be reduced in renal failure.

Commence IV hydration with 8 hourly 0.9% Normal Saline (3 litres in 24 hours).

Review after 12 hours in light of microbiology results and discuss with the Clinical  Haematologist. 

  
 Consider adding
  • Gentamicin 6mg/kg STAT (in 100ml 0.9% Sodium Chloride over 30 minutes) for antimicrobial synergy. If further doses are planned, serum level monitoring must be performed 6-14 hours after dose.
  • Metronidazole 500mg IV tds if the patient’s mouth is ulcerated or significant GI upset.
  •  Acyclovir 400mg PO 5 times per day x 5 days if viral lesions are present.
  •  Fluconazole  200mg PO once daily ( for 7-14 days) if oral candidiasis.
  • Teicoplanin 400mg IV every 12 hours for first 3 doses and then 600mg once daily - if a central line infection is suspected.
  •  Erythromycin 500mg PO four times a day – if the patient has pneumonia. If the patient cannot take oral medication give Clarithromycin 500mg IV every 12 hours.

 

(2). Patients receiving chemotherapy

Some patients may present while still receiving chemotherapy via an ambulatory pump or during a course of oral chemotherapy.

If Chemotherapy in situ via ambulatory pump:

i) Disconnect pump if appropriately trained staff available. Use a male/female luer lock bung to seal the end of the pump extension set and dispose of in cytotoxic sharps bin.

ii) If appropriately trained staff not available pump must be clamped off to stop the delivery of cytotoxic chemotherapy drugs.

iii) Inform chemotherapy unit the next working day.

 

(3). If patients are taking oral cytototoxic chemotherapy tablets e.g cyclophosphamide, capecitabine, vinorelbine. etoposide. These should be stopped.

Patients with indwelling Hickman lines or PICC lines may present with signs of bacteraemia (rigors after line is flushed or accessed) or infection. On occassions where the patient is not neutropenic they may still require admission for intravenous antibiotcs. Please discuss with the on-call Consultant Haematologist. 


Inform chemotherapy department of patients admission on Ext: 6024 (answer phone available out of hours).

 

Second Line Management

If fever persisits after 48hours and if no definate organism isolated in blood cultures:
  • Review signs and symptoms for any focus of infection
  • Repeat blood and urine cultures
  • Do a chest X-ray if not done on presentation

CHANGE ANTIBIOTICS TO:

Meropenem 1g IV three times daily – reconstitiute each 1g vial with 20ml 0.9% sodium chloride from the infusion bag and then add it back to the 100ml bag of 0.9% sodium chloride and give over 30 minutes.

PLUS

Vancomycin 1g IV twice a day ( if not already on Teicoplanin or Vancomycin) Reconstitute each 500mg vial with 10ml of water for injection or each 1g vial with 20ml of water for injection and then add the required dose to a 250ml bag of sodium chloride 0.9% infusion and give over at least 60 minutes. Vancomycin dose should be reduced in patients with renal impairment. Monitor Vancomycin levels after 48 hours.

If fever persists over 96 hours and no definate organism is isolated in blood cultures, consider adding in Amphotericin-B (1 mg/kg daily) or Abisome (3-5mg/kg daily) depending on patients clinical state, renal function and peripheral/central access.Amphotericin-B must be given centrally. Started at 1mg/kg once a day. NB. This must be given in glucose 5% infusion with a pH of >4.2. Pharmacy should be able to confirm that a batch of glucose 5% is of the correct pH. If necessary you add 1-2ml buffer solution.

 

USE OF G-CSF (FILGRASTIM):

Please discuss this with a consultant haematologist before starting treatment.
Adjunctive treatment of febrile and neutropenic patients with G-CSF is not recommended in uncomplicated patients. It should be considered in patients at high risk of infection-associated complications plus adverse prognostic factors such as:

• Profound neutropenia (<0.1 x 109/l)
• Pneumonia
• Hypotension
• Multi-organ dysfunction
• Invasive fungal infection
• Elderly patients 
• Uncontrolled primary disease

 

DURATION OF ANTIBIOTIC THERAPY:


1. If there is a focus of infection or if blood/urine culture is positive:

Treat with appropriate antibiotics for at least 5 afebrile days or 7 days, whichever is longer. A longer duration of treatment may be needed in a particular patient e.g. for gram negative bacteraemia. However, oral antibiotics according to sensitivity may be used once the patient is afebrile and no longer neutropenic. The decision should be based on clinical judgement.

2. If there is no focus of infection and if cultures negative:

Neutrophil recovery is the most important factor in deciding when to discontinue therapy. Stop antibiotics once the neutrophil count rises to and is >0.5 x 10 9/l for two consecutive days and the patient has been afebrile for 48hours.
If neutrophil count remains < 0.5 x 10 9/l, but the patient has been afebrile for 5-7 days. Continue antibiotics until there is early sign of haematological recovery.

 

Authors:

Julie Bliss Oncology Clinical Nurse Specialist
Jenny Durston  Haematology Clinical Nurse Specialist
Andrea Stevens Consultant Oncologist
Dr. Matthew Lumley Consultant Clinical Haematologist
Dr. Das Pillay  Consultant Microbiologist

REFERENCES

1. EORTC (1996) Monotherapy with Meropenem versus Combination Therapy with Ceftazidine plus Amikacin as Empriric Therapy for Fever in Granulocytopenic Patients with Cancer. Antimicrobial Agents and Chemotherapy. Vol. 40. Pp 1108-1115.
2. Freeman, C. D. (1997) Once-daily dosing of aminglycoside:review and recommendations for clinical practice. Journal of Antimicrobial Chemotherapy. Vol. 39. Pp 677-686.
3. Stockley, I. (1999) Drug Interactions. 5th Edtn.  Pharmacy Press. London.