Febrile Neutropenia (Or Suspected) in Adults - Patient Management Procedure Cairns and Hinterland Hospital and Health Service.

Transcription

1 Procedure Document Number CHHSD-CoC-Proc-Clin-307-V4-02/20 Febrile Neutropenia (Or Suspected) in Adults - Patient Management Procedure Cairns and Hinterland Hospital and Health Service Custodian/Review Officer: Advanced Pharmacist Cancer Care Version no: 4.0 Applicable To: All Clinical Staff Approval Date: 27/05/2017 Effective Date: 27/05/2017 Next Review Date: February 2020 Authority: EDMS Approving Officer Dr Don Martin, A/Executive Director of Medical Services Supersedes: Version 3.0 Key Words: Neutropenia, Oncology, Chemotherapy Accreditation References: National Standards and EQuIPNational Standard 3,9 Purpose Febrile neutropenia is a common and potentially life threatening complication of chemotherapy treatment or of a known haematological malignancy/disorder. Patients may rapidly develop septicaemia and shock over the course of hours. Patients receiving anti-cancer therapy should be educated on this risk and advised to seek prompt medical advice if febrile or are feeling unwell. Patients should be advised to contact the Cancer Care Services or present to the Emergency Department if this occurs. Febrile neutropenic (or suspected febrile neutropenic) patients are a medical priority. Patients who are receiving cytotoxic chemotherapy or have a haematological malignancy may present with fever or appear unwell. They should be presumed to be neutropenic and managed as below until blood results are available Key Points Triage Category 2 and commence management pathway Presume all patients to be neutropenic until proven otherwise Fever is only one diagnostic criterion; patients can be very unwell but not be febrile Commence antibiotics as PRIORITY (within 30mins if clinically unstable; within 60mins if clinically stable) **do NOT wait for return of blood results before commencing antibiotics** Advise Oncology/Haematology team of admission Version No.: 4.0 ; Effective From: 27/05/2017 Page 1 of 16

2 Scope This procedure relates to all clinical staff in the Cairns and Hinterland Hospital and Health Service. Supporting documents The Neutropenic Patient Indications for Protective Isolation. PA Hospital Cancer Services - Oncology Haematology Unit Handbook - Neutropenic Fever Forms MR277 Febrile Neutropenia (or suspected) Patient Management Procedure for the Management of Patients with Febrile Neutropenia Patients for whom the guideline is applicable: All adult patients who have received chemotherapy or have a known haematological malignancy/disorder and present with: Or Temperature >38.3 C orally (or equivalent) or >38 C orally (or equivalent) on at least two occasions within one hour. 1,2 Signs of sepsis or is unwell (sepsis criteria: 2 or more of the following: systolic BP 100mmHg, respiratory rate 22 per minute, altered mental status) ie. Patients don t have to be febrile (that is only one criterion); they can be afebrile but still very unwell. ALL patients should be presumed to be neutropenic until proven otherwise, and treated as below (do not wait for blood count results before starting antibiotic treatment). Neutropenia definition: Absolute Neutrophil Count (ANC) < 0.5x10 9 /L or Absolute Neutrophil Count (ANC) <1.0x10 9 /L and predicted fall to below 0.5x10 9 1,2 /L. Version No.: 4.0 ; Effective From: 27/05/2017 Page 2 of 16

3 Day 1 (Admission) Triage Category 2 Patients presenting at triage window may appear well however clinical deterioration may be rapid and occult Ensure patient is isolated and neutropenic precautions applied (as per procedure Start Febrile Neutropenia Care Pathway (see Standing Order in Appendix 1) Assessment and Investigations (see below) Patient history (type of cancer, details of recent or current chemotherapy, or nonmalignant disease being treated with cytotoxic therapy etc) Contact treating team: During business hours contact Oncology or Haematology Advanced Trainee, after hours contact on call Oncologist or Haematologist to discuss management via Cairns Hospital switchboard Unless patient is clinically unstable, please endeavour to complete the initial workup (complete assessment and investigations, patient history and commence febrile neutropenia pathway) prior to contacting the treating team so that a comprehensive clinical picture can be described to the treating team. For patients in regional sites determine plan for transfer to Cairns Hospital in case of deterioration (and ensure plan is documented). NB. All regional patients not responding to antibiotic treatment by Day 3 should be transferred to Cairns Hospital, on discussion with treating team or on call Oncologist/Haematologist. Ensure appropriate fluid resuscitation (if sepsis-induced hypotension: 30mL/kg of IV crystalloid fluid to be given within the first 3 hours) - contact ICU if IV fluid resuscitation not achieving haemodynamic stability Empirical IV antibiotics (see Table 1) must be commenced within 30 minutes of presentation if clinically unstable (hypotension, hypoxia, confusion, major organ dysfunction); or within 60 minutes if clinically stable. DO NOT WAIT for neutrophil count or blood culture results before starting antibiotic therapy Blood cultures should be taken before starting antibiotics wherever possible, but should NOT delay antibiotic therapy. Version No.: No 4.0 ; Effective From: 27/05/2017 Page 3 of 16

4 Assessments: Observations: Temperature, blood pressure (including postural drop), pulse rate, respiratory rate and oxygen saturation. Physical examination: focusing on potential sites of infection (including mouth, skin, vascular access devices, chest, abdomen, peri-anal). In the absence of neutrophils, signs of infection may be subtle. NB. Avoid invasive procedures. Investigations: 1 set (aerobic and anaerobic bottles) from each lumen of central venous access device (CVAD) if present. N.B do not flush line before withdrawal of blood from CVAD (label clearly with site and lumen) 1 set peripheral blood cultures (label clearly with site) Full blood count (+ consider PT/APTT and Fibrinogen if DIC is suspected) Electrolytes/ Urea / Creatinine / LFTs / CRP ECG if hypotensive or otherwise indicated Mid stream urine / indwelling catheter urine specimen Swab of CVAD exit sites Swab of any other suspicious or focal lesions Chest X-ray Sputum ( if clinically indicated ) Faeces ( if clinically indicated ) Consider arterial blood gases Lumbar puncture indicated if change in neurological status Patients who have a high risk of complications include: Haematological malignancy Recent myelosuppressive chemotherapy (within 8 weeks) Concurrent chemotherapy and radiotherapy Age >60 Co-morbidities e.g. diabetes, poor nutritional status. Bone marrow involvement of cancer Delayed surgical healing or open wounds Haematological malignancy Significant mucositis Recent myelosuppressive chemotherapy (within 8 weeks) Clinically unstable (e.g. hypotensive, oliguric) Concurrent On corticosteroid chemotherapy >25mg and prednisolone radiotherapy (or equivalent) daily Age Rapidly >60 falling neutrophil count over successive days Previous history of neutropenia Recent hospitalisation for infection Version No.: No 4.0 ; Effective From: 27/05/2017 Page 4 of 16

5 Table 1: Initial antibiotic therapy (for patients with normal renal function) 1,2 Patient Group Recommendation (grading and level of evidence) INITIAL therapy only: subsequent therapy should be directed by clinical findings Clinically unstable patients (i.e. sepsis) Administer within 30 minutes of presentation No penicillin allergy: Piperacillin-tazobactam 4.5 g IV 6 hourly (grade A) Non-life threatening penicillin allergy (rash): Ceftazidime 2 g IV 8 hourly (grade C) (The combination of a betalactam antibiotic with an aminoglycoside is the regimen of choice) Clinically stable patients Administer within 60 minutes of presentation (Beta-lactam monotherapy is recommended unless allergy to the recommended agent/s) Life threatening (immediate) penicillin/beta-lactam allergy: seek advice from Infectious Diseases team Ciprofloxacin 400mg IV 8-hourly + Gentamicin 7mg/kg ideal body weight IV once daily for maximum 3 days, then for review by Infectious Diseases team. Monitor renal function and adjust dose if necessary + Vancomycin 25mg/kg stat, then 1.5 g IV 12 hourly (if CrCl >90 ml/min, otherwise refer to etg dosing guidelines) No penicillin allergy: Piperacillin-tazobactam 4.5g IV 6 hourly Non-life threatening penicillin allergy (rash): Ceftazidime 2g IV 8 hourly Life threatening (immediate) penicillin/beta-lactam allergy: seek advice from Infectious Diseases team Oral or IV Ciprofloxacin (oral Ciprofloxacin dose: mg BD; dose reduce in renal impairment). N.B. IV Ciprofloxacin is restricted to critically ill patients or those unable to swallow. + For patients known to be colonised with MRSA or who have clinical evidence of a suspected line infection add: Vancomycin 1.5g IV 12 hourly (if CrCl >90 ml/min, otherwise refer to etg dosing guidelines) Version No.: No 4.0 ; Effective From: 27/05/2017 Page 5 of 16

6 Patient Group Recommendation (grading and level of evidence) Patients with cellulitis, obviously infected vascular devices, or MRSA carriers with extensive skin breaks/desquamation Piperacillin-tazobactam 4.5 g IV 6 hourly (grade A) (Ceftazidime or Ciprofloxacin if penicillin/beta-lactam allergic). + Vancomycin 1.5g IV 12 hourly (if CrCl >90 ml/min, otherwise refer to etg dosing guidelines) Patients with features of abdominal or perineal infection Piperacillin-tazobactam 4.5 g IV 6 hourly (grade A) NB. Piperacillin/tazobactam will provide adequate anaerobic cover, other than for suspected or proven C.difficile infection in this situation Metronidazole therapy is required. if penicillin/beta-lactam allergic seek advice from Infectious Diseases team If clinical suspicion of C.difficile infection, add Metronidazole 500mg IV 8-hourly Day 2 and 3: Patients not responding to initial therapy ***if patient is at a regional hospital and not responding to antibiotic treatment by Day 3 they should be transferred to Cairns Hospital, on discussion with treating team or on call Oncologist/Haematologist*** Although it is common practice to add vancomycin to the initial regimen after 48 hours if fever persists, no significant benefit has been demonstrated in controlled trials. Vancomycin is indicated if a Gram-positive organism resistant to other drugs is isolated from blood culture or if the patient has progression of a clinical infection. If indicated, add: Vancomycin 1.5g IV, 12 hourly if CrCl >90 ml/min; dose adjustment required in setting of renal impairment, refer to etg for monitoring and subsequent doseadjustment guidelines. Version No.: No 4.0 ; Effective From: 27/05/2017 Page 6 of 16

7 Day 4 and 5: Patients not responding to antibacterial therapy In patients, particularly high risk patients (see Table 2 for risk stratification), who have persistent fevers of unknown origin for 96 hours despite broad-spectrum antibiotics, a chest x-ray and CT of the chest and sinuses should be done as a matter of priority to investigate for fungal infection. Antifungal therapy is then initiated as indicated according to Figures 1 and 2 on the following pages and in consultation with the Infectious Diseases team. Also, on consultation with the Infectious Diseases team, consider changing Piperacillin/Tazobactam (or Ceftazidime) to Meropenem +/- addition of Vancomycin if not on Vancomycin therapy already. Table 2: Estimating the risk of fungal complications in cancer patients 1 Infection Risk Low Intermediate High Disease/Therapy examples Standard chemotherapy regimens for most solid tumours Anticipated neutropenia <7 days Autologous haematopoietic stem cell transplant (HSCT) Lymphoma Multiple myeloma Chronic lymphocytic leukaemia Purine analogue therapy: fludarabine, clofarabine, nelarabine, cladribine Anticipated neutropenia 7-10 days Anticipated neutropenia >10 days Allogenic HSCT Acute leukaemia induction, consolidation Alemtuzumab therapy Graft versus host disease treated with high dose steroids Low Fungal Infection Risk Usually high, but some experts suggest modifications depending on patient status Purine analogues: intermediate risk when used as sole therapy, high risk when used in an intensive chemotherapy regimen Usually high, but significant variability exists related to duration of neutropenia, immunosuppressive agents, and status of underlying malignancy Version No.: No 4.0 ; Effective From: 27/05/2017 Page 7 of 16

8 Figure 1: Antifungal management guidelines for low/intermediate risk patients 1,2 Persistent fevers of unknown origin for 96 hours despite broad-spectrum antibiotics in a LOW / INTERMEDIATE RISK (refer to Table 2) neutropenic patient URGENT CXR, CT chest and sinuses On prophylactic fluconazole? No Yes Evidence of Invasive Aspergillosis? Evidence of Invasive Aspergillosis? No Yes No Yes Monitor patient and continue investigations as clinically indicated. Consider Oral or IV Fluconazole Oral or IV Voriconazole, depending on patient s clinical state (consider addition of Caspofungin if severe, microbiologicallyconfirmed Invasive Aspergillosis) *alternative to Voriconazole = liposomal Amphotericin Monitor patient and continue investigations as clinically indicated. Consider IV Caspofungin Oral or IV Voriconazole, depending on patient s clinical state (consider addition of Caspofungin if severe, microbiologicallyconfirmed Invasive Aspergillosis) *alternative to Voriconazole = liposomal Amphotericin Version No.: No 4.0 ; Effective From: 27/05/2017 Page 8 of 16

9 Figure 2: Antifungal management guidelines for high riskpatients 1 Persistent fevers of unknown origin for 96 hours despite broad-spectrum antibiotics in a HIGH RISK (refer to Table 2) neutropenic patient URGENT CXR, CT chest and sinuses On prophylactic posaconazole? No Evidence of Invasive Aspergillosis? No Yes Yes Continue posaconazole prophylactic therapy. Consider sending away posaconazole level. NB. IV posaconazole is available for patients with suspected or confirmed oral absorption issues IV Caspofungin Oral or IV Voriconazole * depending on patient s clinical state (consider addition of Caspofungin if severe, microbiologicallyconfirmed Invasive Aspergillosis) *alternative to Voriconazole = liposomal Amphotericin Consider alternative source of infection Consult with Infectious Disease Unit Version No.: No 4.0 ; Effective From: 27/05/2017 Page 9 of 16

10 Table 3: Recommended doses of IV antifungal agents 1,3 Fluconazole IV 400 mg once daily (an 800 mg loading dose can be given). Higher doses have been used. Voriconazole IV 6mg/kg Q12H for 2 doses, then 4mg/kg Q12H (to nearest 50mg). Caspofungin IV 70 mg on the first day, then 50 mg once daily (70 mg once daily if >80 kg). Posaconazole IV 300 mg twice daily on day 1, then 300 mg once daily. Liposomal Amphotericin IV 3mg/kg once daily, increase up to 5mg/kg once daily if necessary. Table 4: Additional precautions/contraindications to antifungal agents 3,4 Renal impairment: Liposomal Amphotericin, Voriconazole, Fluconazole and Posaconazole. Hepatic impairment: Voriconazole and Caspofungin. Drug interactions: All agents, but particularly azole antifungals. Table 5: Notable administration requirements of antifungal agents 4 Voriconazole: Take tablets on an empty stomach 1 hour before or 2 hours after food. Liposomal Amphotericin Ensure filter is used when adding reconstituted vials to glucose infusion bag; pre-check that the intended infusion volume will produce final concentration of 0.2-2mg/L before adding the contents of vials to the infusion bag. Posaconazole: Take tablets with or without food. Food does not influence absorption. Version Administer No.: No IV 4.0 via ; Effective central From: line 27/05/2017 (can do once-off peripherally if needed) with 0.5micron in-line filter. Page 10 of 16

11 Ongoing Management Granulocyte Colony Stimulating Factor (G-CSF) may be considered in selected patients at high risk for infection-associated complications or who have prognostic factors that are predictive of poor clinical outcomes. Patients who received pegfilgrastim prophylactic therapy as part of their chemotherapy treatment do not require further G-CSF. For patients who have not received any pegfilgrastim, the addition of filgrastim 5micrograms/kg daily should be discussed with the covering consultant. Medication history should be recorded and cessation of any oral anti-cancer therapy including targeted agents e.g. sunitinib, lenalidomide and capecitabine. Patient should be admitted to a single room on the ward and cared for as per The Neutropenic Patient Indications for Protective Isolation. Ref No. CHHSD-CoC- Proc-Onc-236-V1-3/11 Patients in regional hospitals who are high risk or not responding to antibiotic therapy should be transferred as soon as is practical to Cairns Hospital for further management. Version No.: No 4.0 ; Effective From: 27/05/2017 Page 11 of 16

12 Definition of Terms Term Definition / Explanation / Details Source Fever A single temperature equivalent to Prevention and Treatment of 38.3ºC orally or equivalent to 38ºC Cancer-related Infections. orally over one hour period National Comprehensive Cancer Network Guidelines, version 1, Temperature of at least 38.3 C (or at least 38 C on two occasions) Neutropenia <500 neutrophils/mcl or <1000 neutrophils/mcl and a predicted decline to <500/mcL over the next 48 hours Immediate Management of Neutropenic Fever. Cancer Institute NSW. eviq Cancer Treatments Online, version 2 (last modified 21 Jan 2014) Prevention and Treatment of Cancer-related Infections. National Comprehensive Cancer Network Guidelines, version 1, Immediate Management of Neutropenic Fever. Cancer Institute NSW. eviq Cancer Treatments Online, version 2 (last modified 21 Jan 2014) Mosby s Medical, Nursing & Allied Health Dictionary. (2002) 6th ed. Version No.: No 4.0 ; Effective From: 27/05/2017 Page 12 of 16

13 References and Suggested Reading 1. Prevention and Treatment of Cancer-related Infections. National Comprehensive Cancer Network Guidelines, version 1, Immediate Management of Neutropenic Fever. Cancer Institute NSW. eviq Cancer Treatments Online, version 2 (last modified 21 Jan 2014) 3. Moulds, R. et al. etg Complete Therapeutic Guidelines (2014). Antibiotic therapy. Therapeutic Guidelines Ltd. (access etg via Clinician s Knowledge Network (CKN) on QHEPS) 4. Rossi S. Australian Medicines Handbook. (2014) Australian Medicines Handbook Pty Ltd. (access AMH via Clinician s Knowledge Network (CKN) on QHEPS) Dellinger RP et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. Crit. Care. Med. 2008; 36: [published correction appears in Crit Care Med 2008; 36: Australian and New Zealand Consensus Guidelines for the Use of Antifungal Agents in the Haematology/Oncology Setting Internal Medicine Journal 2008; 38: De Naurois J, Novitzky-Basso I, Gill M.J. et al. Management of Febrile Neutropenia: ESMO Clinical Practice Guidelines. Annals of Oncology 2010; 21; 5: Kumar A et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006, Jun; 34(6): Robbins, G. K. (2010). Fever in the neutropenic adult with cancer. Prentice A.G, Glasmacher A, Hobson R.P et al. Guidelines on the Management of Invasive Fungal Infection During Therapy for Haematological Malignancy. British Committee for Standards in Haematology; British Society for Haematology. Cameron, D. Management of Chemotherapy-associated febrile neutropenia. British Journal of Cancer 2009; 101, S18-S22 Jorgensen K.J, Gotzsche P.C, Johansen H.K. Voriconazole Versus Amphotericin B in Cancer Patients with Neutropenia (Review), 2009; The Cochrane Collaboration. Walsh T.J, Pappas P, Winston D.J et al. Voriconazole Compared with Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Neutropenia and Persistent Fever. The New England Journal of Medicine 2002; 346; 4: Version No.: No 4.0 ; Effective From: 27/05/2017 Page 13 of 16

14 Walsh T.J, Teppler H, Donowitz G.R. et al. Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Persistent Fever and Neutropenia. The New England Journal of Medicine 2004; 351; 14: Herbrecht R, Denning D.W, Patterson T.F. et al.voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis. The New England Journal of Medicine 2002; 347; 6: Myeloid Growth Factors. National Comprehensive Cancer Network Guidelines, Consultation Consultant Haematologist (x 3) Consultant Oncologist (x 3) Consultant Infectious Diseases (x2) Cancer Care Pharmacist Infectious Diseases Pharmacist Oncology Clinical Educator (x3) Nurse Educator, Emergency Department Director of Oncology Clinical Services Medical Director, Emergency Department Director of Pharmacy Nurse Unit Manager, Day Oncology Unit Medicines Management Committee Procedure Revision and Approval History Version No. Created/Modified by Amendments authorised by Approved by 1.0 Jason Black, Advanced Pharmacist Cancer Care 2.0 Belinda Aspinall, Senior Pharmacist Cancer Care Jason Black, Advance Pharmacist Cancer Care Medicines Management Committee Trinity Hub 2.1 Jason Black Additional recommendations from RCA added 3.0 Jason Black Advanced Pharmacist Cancer Care 4.0 Belinda Aspinall, Senior Pharmacist Cancer Care Standing Order added Executive Director of Medical Services Executive Director of Medical Services Version No.: No 4.0 ; Effective From: 27/05/2017 Page 14 of 16

15 Audit Strategy Level of risk Audit strategy Audit tool attached Audit date Audit responsibility High risk Review of all Primes related to Febrile Neutropenia at the monthly Medication Safety Committee meeting and monthly Cancer Services Team Tier 4 meeting. Prime Ongoing monthly review at Medication Safety Committee meeting. Ongoing monthly review at Cancer Services Team Tier 4 meeting. Clinical Director of Cancer Services. Key elements / indicators / outcomes Compliance with the procedure. Document Communication and Implementation Plan Action Identify the target group: All clinical staff involved in the management of Febrile Neutropenia Provide a time line for communication and implementation milestones: 3 months Identify method of communication: Training / Written/ Verbal List education and training available to support implementation: QHEPS Identify frequency of communication: Ongoing Responsible Position Oncology CNC Oncology CNC Oncology CNC Oncology CNC Oncology CNC Appendices: 1. CHHHS Triage Category: Febrile Neutropenia Form Version No.: No 4.0 ; Effective From: 27/05/2017 Page 15 of 16

16 Cairns and Hinterland Health Service District (Affix patient identification label here) URN: Family Name: Given Names: Address: APPENDIX 1 Date of Birth: Sex: M F For patients who: TRIAGE: CATEGORY 2 Are receiving chemotherapy or have suspected/confirmed neutropenia (Neutrophil count<1.0) Have a temperature 38 C (including reported pre-hospital) or > 37.5 C if on steroid therapy CONTACT TREATING ONCOLOGIST/ HAEMATOLOGIST ASSESSMENT Attended Time Staff Initial Date Establish non-invasive monitoring immediately BP, HR, RR, Sp0 2 Physical examination, focusing on potential sites of infection Obtain IV access either peripherally or use CVAD (Central Venous Access Device). If unable gain IV access seek medical assistance Collect blood including BLOOD CULTURES (minimum 2 sets) via peripheral AND CVAD access. FBC/ ELFTs/ CRP/ CMP/ Xmatch/ PT/APTT and Fibrinogen if DIC suspected DO NOT DELAY ANTIBIOTICS WHILST AWAITING BLOOD RESULTS See standing order below : Must give within 30 mins of presentation if septic or 60 minutes if clinically stable Urinalysis ( + sputum culture / faeces if indicated ) Chest X-Ray ECG if hypotensive or indicated (e.g. chest pain) Swab any venous access devices if redness/pus around exit site Swab any wounds/focal lesions (if present) Repeat physical assessment frequently and assess response to treatment by constant clinical observation and uninterrupted monitoring Allergies and Contraindications checked & documented MEDICATIONS Instructions for standing orders: Record on the medication chart in the once only section. The responsible Medical Officer must check this record and confirm by signing within 2 hours. If patient is allergic to any of the antibiotics below, consult medical staff. Do not administer. (NB. Alternative antibiotic options are listed in Table 1 on page 5 of this protocol). STAT Antibiotics can be NURSE INITIATED Dose Route Frequency Rate Piperacillin 4g/Tazobactam 0.5g in NaCl 0.9% mL 4.5g IV stat Then Q6H 20 min If in septic shock or severely unwell add Gentamicin 7mg/kg (use ideal body wt.) in NaCl 0.9% mL IV Stat Then Daily 20 min Stat Vancomycin 25mg/kg (use actual body weight) in NaCl 0.9% 500mL IV Then 1.5g 10mg/ BD (unless min renally impaired) Regular appropriate antibiotics MUST be charted before a patient is admitted to the ward Name Signature Designation Initials Date Clinical Indicators: 1. Patient triaged as minimum Category 2 2. Patient appropriately isolated 3. Evidence of continuous monitoring 4. Antibiotics commenced within 1 hour of triage Version No.: No 4.0 ; Effective From: 27/05/2017 Page 16 of 16