Neutropenic Sepsis Management in Adult Patients

Febrile (temp <36 ͦC or >38 ͦC) or (37.5 ͦC-38 ͦC & generally unwell)

Neutropenia (with a neutrophil count <1x10⁹/L)

Assume neutrophil count is low if recent treatment with chemotherapy agents (i.e within preceding 3-4 weeks)

If afebrile, consider if other signs of sepsis are present, and recent use of antipyretics or steroid therapy.

If Neutrophils >1, consider whether immunocompromised – such as recent stem cell transplant, high dose steroids, immunosuppression drugs or a haematology malignancy

Initial Management (within 1 hour to meet Sepsis 6)

• Observations– Temp,BP,HR,RR,SpO₂& NEWS Score – Within 15 mins. Check for any new confusion
• Cannulate (if no central access) and take bloods – FBC, U+E, LFTs, Calcium, Magnesium, lactate, Albumin, Glucose, CRP, Coag and Blood cultures (peripheral and central (if have a line or portacath)). This can be done before medical review.
• Give oxygen to target O2 saturation > 94% (NB COPD 88-92%)
• Administer stat IV antibiotics within 1 hour First doses can be given on basis of last known eGFR . Do not give gentamicin to patients who have been given cisplatin. Discuss with on call Haematologist /Oncologist
• Do not wait for blood results to assess neutropenia before starting antibiotics.
• Give IV fluid (Give 250-500ml Plasmalyte PL148 over 5-15 minutes and reassess)
• Ensure passing urine – consider catheterisation to monitor output and commence accurate fluid charting.

Patients can deteriorate rapidly – If NEWS ≥5 or 3 in one parameter: Medical review (FY2 or above and Outreach Team) required within 20 mins. If initial management cannot be completed within 1 hour, it is the responsibility of the FY1/2 contacted to seek support.  Nursing staff should escalate above FY1/2 if no medic available within timelines or unhappy with medical management planned.

Escalate to the On Call SpR (Ask for on-call registrar via switch) or On Call Consultant if required.

ASSESSMENT:

• Take thorough history, including systemic enquiry, looking for potential infection source.
• Perform a meticulous and well documented physical examination, including mouth, sacrum and perineum as well as examining any peripheral or central lines.

INVESTIGATIONS:

• Imaging: CXR  (Don’t delay antibiotic therapy for trips to radiology. Unwell patients must be escorted).
• MSU - Take urine culture but don’t delay antibiotic therapy if micturition is not immediately possible.
• If diarrhoea, take stool sample for culture and difficile toxin
• If productive cough, send sputum for bacterial culture
• Viral throat swab
• Swab of line site, and any areas of broken skin
• If atypical pneumonia suspected, sputum for bacterial culture, Legionella PCR, fungal culture and PCR for viruses and Mycoplasma. When Pneumocystis jirovecii is suspected please send induced sputum or BAL and telephone the laboratory. 

Further management:

• Chase FBC result.
• Choose ongoing antibiotic regimen (see page 3)
• Consider G-CSF. If febrile and any of the following applies, give daily GCSF until neuts >1
  • Neutrophil count < 0.1x10⁹/L
  • Hypotension (>20mmHg below normal systolic BP, not responding to fluid challenge)
  • Multi-organ dysfunction (sepsis syndrome)
  • Pneumonia or invasive fungal infection
  • Predicted neutropenia >10days (usually haem regimens)

G-CSF dosing:  Filgrastim 300micrograms once daily if < 80kg, 480micrograms once daily if > 80kg.

Not indicated if neutropenia not caused by SACT (ie. leukaemia): contact on call Haematologist

• If patient does not pass urine for 3 hours perform bladder scan and consider catheterisation
• Withhold ACE-i, ARBs, NSAIDs, diuretics, metformin as per Sick Day Rules
• Consider adrenal insufficiency. If ≥3 high-dose oral glucocorticoids in last 12 months, (incl post-SACT antiemetic dexamethasone of 4mg BD for 3 days), or prolonged (>10 days) course of dexamethasone (≥6mg daily) or non-cancer related use of high dose inhaled or topical glucocorticoids – consider giving 100mg Hydrocortisone IV.  Consider following with either infusion of Hydrocortisone 200mg IV over 24 hours, or 50mg Hydrocortisone IM/IV four times daily. 
• If blood glucose abnormal on admission, ongoing monitoring of Blood sugars (BMs)

ONGOING MANAGEMENT:

• Daily bloods: FBC, U&Es, LFTs, Albumin and CRP
• Whilst febrile, daily blood cultures (peripheral and central)

1. Prompt antibiotic therapy is essential in neutropenic sepsis. The first dose of gentamicin can be given without knowledge of current renal function (see guidance on front of gentamicin chart). Doses should be calculated on the online calculator, which should be printed off and kept in the patient’s notes. NHS Borders gentamicin prescribing, administration and monitoring chart should be used.  After the first dose gentamicin levels should be monitored, entered onto the gentamicin chart, and doses adjusted as specified in the guidelines.
   
   
2. Duration of treatment with gentamicin should be limited to minimise toxicity. All prescriptions should be reviewed daily in conjunction with microbiology results. Renal toxicity is more likely in those who are septic, hypotensive or who are also on other potentially nephrotoxic drugs such as NSAIDs, ACE inhibitors or diuretics, regardless of initial eGFR. If possible these drugs should be withheld when septic.
   
   
3. The first dose of piperacillin / tazobactam 5g IV is safe whatever the renal function. Thereafter, if the creatinine clearance (CrCl) is less than 40ml/min, dosing frequency should be adjusted according to renal function as specified below:
   
   

   CrCl (ml/min)	Dosing frequency of piperacillin / tazobactam
   >40ml/min	6 hourly
   20-40ml/min	8 hourly
   <20ml/min	12 hourly

   
   
   
4. Use of vancomycin requires assessment of renal function and monitoring of drug levels, as per NHS Borders Antibiotic Prescribing Guidelines in Adults.
   
   Doses should be calculated on the online calculator, which should be printed off and kept in the patient's notes.
   
   NHS Borders Vancomycin, consider stopping the drug if no relevant culture isolates obtained (discuss with microbiology)
   
   
5. If there is a clear cut history of severe reaction to any β-lactam drugs (e.g. anaphylaxis, angioedema, bronchospasm) then all β -lactam drugs carry risk, including the penicillins co-amoxiclav and piperacillin-tazobactam, and all the cephalosporins

6. Avoid ciprofloxacin if previous cipro resistant Gram negative cultures, recent exposure to cipro as prophylaxis, C. difficile carriage or infection  in the past 12 weeks (equivocal or toxin positive stool), suspected MRSA or VRE, and only use with extreme caution in the frail elderly.

7. Document indication for antibiotics and length of treatment in patient notes wherever possible.

8. Patients will have a handheld SACT record – ask to see this as part of initial assessment

9. Refer all patients to Acute Oncology/Haematology inbox.

10. Contact details:
    
    
    Acute Oncology
    
    Mon-Fri 9am-4:30pm Bleep 3041
    
    Out of hours: On-Call Oncology Reg, 07798 774842 or via NHS Lothian switchboard 0131 537 1000
    Haematology On Call
    
    BGH: bleep 6246
    
    Out of hours: via NHS Borders switchboard
11. For further guidance on SACT toxicities/cancer complications, see NHS Borders Cancer Intranet site