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Art & science | The synthesis of art and science is lived by the nurse in the nursing act JOSEPHINE G PATERSON MANAGEMENT OF PATIENTS WITH LOW-RISK FEBRILE NEUTROPENIA Matt Fowler looks at how new tools to assess the possibility of septic complications can guide future care options Correspondence [email protected] Matt Fowler is advanced nurse practitioner for oncology, South Warwickshire NHS Foundation Trust Date of submission April 28 2015 Date of acceptance May 15 2015 Peer review This article has been subject to double-blind review and checked using antiplagiarism software Author guidelines journals.rcni.com/r/ cnp-author-guidelines Abstract The National Institute for Health and Care Excellence in the UK advocates that patients with neutropenia who are at low risk of developing septic complications should be considered for management in the community rather than in hospital. The Multinational Association of Supportive Care in Cancer (MASCC) risk index is widely used to identify patients who are deemed to be at low risk of developing septic complications as a result of febrile neutropenia (FN), but it has limitations. A newer tool, the Clinical Index of Stable Febrile Neutropenia (CISNE), CHEMOTHERAPY IS well documented to cause a plethora of toxicities, however, febrile neutropenia (FN) is one of the most serious complications (Innes et al 2003), with a mortality rate of 5% (de Naurois et al 2010). FN is defined by de Naurois et al (2010) as ‘an oral temperature >38.5°C or two consecutive readings of >38.0°C for two hours and an absolute neutrophil count <0.5 × 109/L, or expected to fall below 0.5 × 109/L’. In the nurse-led chemotherapy unit where I work as an advanced nurse practitioner (ANP) many of the decisions traditionally made by oncologists and haematologists are made by the nurse consultant and me. All patients who present as emergency admissions with suspected FN are initially managed by the senior nursing team during office hours. As an autonomous ANP, it is crucial that my decisions about patient management are backed up by robust evidence to safeguard the patient and 16 June 2015 | Volume 14 | Number 5 further stratifies patients who may be suitable for management in the community. This article uses a case study to explore the management of a patient who presented with suspected FN. It examines the use of the MASCC risk index and the CISNE to make recommendations for the future management of patients with low-risk FN in the community. Keywords Chemotherapy, low-risk febrile neutropenia, management, risk, treatment complications the practitioner. Greenhalgh et al (2014) advocated the use of evidence-based clinical guidelines, however, they stressed that care should still remain individualised. Glasziou et al (2013) cautioned against over-reliance on pathways/templates for managing patients as this can result in ‘overtreatment’ because of fear of litigation. Management of patients with FN is a classic example of protocol/ pathway-driven care. However, the variations in practice identified in the National Institute for Health and Care Excellence (NICE) (2012) guideline on managing patients with neutropenic sepsis suggest there is justification for examination of the initial diagnostic and management plan. Case study Julie (pseudonym) was a 38-year-old woman receiving adjuvant chemotherapy post-mastectomy for breast cancer who presented to the ambulatory CANCER NURSING PRACTICE Getty Art & science | adverse events chemotherapy unit ten days post-chemotherapy with a pyrexia of 38.0°C. Julie was at the nadir point in her chemotherapy cycle. She was cannulated on arrival, bloods taken for full blood count, urea and electrolytes, C-reactive protein (CRP), liver function tests as well as lactate and blood cultures. In accordance with local guidelines she received an immediate dose of intravenous (IV) tazocin and gentamicin empirically while blood results were processed. This practice was in accordance with local policy and the NICE (2012) guideline (Figure 1), as well as the surviving sepsis campaign (Dellinger et al 2013). Table 1 outlines the initial examination findings and investigations requested. As can be seen from Table 1, Julie had a temperature of 38.0°C and a neutrophil count of 0.2, which confirmed a diagnosis of neutropenic sepsis Figure 1 NICE pathway for suspected neutropenic sepsis in secondary and tertiary care Person with suspected neutropenic sepsis Emergency treatment and assessment Start antibiotic therapy Confirm diagnosis of neutropenic sepsis Assess the patient’s risk of septic complications Patients at low risk of septic complications Patients at high risk of septic complications Duration of antibiotic treatment Discharge (National Institute for Health and Care Excellence 2012) 18 June 2015 | Volume 14 | Number 5 Patients whose risk of septic complications is reassessed as low (NICE 2012). The National Cancer Institute (1999) classified neutropenia as follows: ■ Grade 1 ≥1.5-<2.0. ■ Grade 2 >1.0-<1.5. ■ Grade 3 >0.5-<1.0. ■ Grade 4 <0.5. Although FN carries a mortality rate of 5% (de Naurois et al 2010), Julie had grade 4 neutropenia, which can carry a mortality rate as high as 9% (Lalami et al 2006). Alternative options I have worked in haemato-oncology for more than 15 years and cared for many neutropenic patients. Julie’s care appeared to represent the ‘gold standard’: safe care in accordance with best available evidence. She received antibiotics within 30 minutes of arrival at hospital, had an uneventful stay with successful neutrophil recovery and a fiveday stay that is in accordance with national averages (Parish et al 2013). On deeper reflection, however, I considered whether her care could have been delivered differently. The NICE (2012) guideline advocated that patients with low-risk FN should be considered for management in the community, which has potential benefits for patients and healthcare economies. Worth et al (2011) identified savings of up to 30% for patients with low-risk FN managed as outpatients compared with the traditional method of receiving antibiotics as inpatients. Nonetheless, 25% of all deaths within 30 days of receiving chemotherapy have been attributed to FN (Yoong et al 2012). A literature search revealed a large amount of research on the subject of low-risk FN. Table 2 identifies the databases searched and the number of hits broken down into adult and paediatric settings. Search terms used were ‘low risk’, ‘febrile’ and ‘neutropenia’. Although there appeared to be a large amount of research available on the adult population with low-risk FN, there did not appear to be any published evidence of centres in the UK implementing the NICE (2012) recommendations for managing patients with low-risk FN. This notion was supported by Slavin and Thursky (2013) who, in a survey of oncologists in Australia and the UK, found an overwhelming reluctance by clinicians to manage patients with low-risk FN in the community. This was not the case in the paediatric setting as there was clear evidence of children with lowrisk FN being managed at home (Manji et al 2012, Orme et al 2014). Of further significance is that children are often at greater risk of developing CANCER NURSING PRACTICE Table 1 Initial examination findings and investigations requested Patient complaint: History of patient complaint Pyrexia Patient received third cycle of adjuvant FEC (fluorouracil/epirubicin/cyclophosphamide) with prophylactic GCSF (granulocyte-colony stimulating factor) injections ten days previously. Patient began experiencing shivers on waking this morning. Checked temperature and it was 38.5°C. Contacted acute oncology helpline and advised to attend unit immediately Temperature 38 Respiratory rate 15 Heart rate 78 Oxygen saturation 99% on room air Past medical history Mastectomy for breast cancer Caesarean section Blood pressure 120/76 Urine No abnormalities detected Systemic inflammatory response syndrome 1 Blood glucose level 5.2 Glasgow Coma Scale 15 Modified Early Warning Score 1 Medications Omeprazole 20mg daily No known drug allergies On examination A: Airway patent B: Chest clear, no cough/dyspnoea. Chest examination unremarkable; bilateral air entry on auscultation C: Capillary refill 2 seconds, haemodynamically stable and patient reports good urine output. Pulse strong and regular. Nil evidence of dehydration. No conjunctival pallor. Calves soft and non-tender with no oedema. No central venous access device in situ D: Blood glucose 5.2, GCS 15 E: Abdomen soft and non-tender, bowel sounds auscultated. Patient had bowels opened soft formed stool this morning. Nil evidence of petechiae and no lymphadenopathy. Nil epistaxis/reports of any bleeding. Oral cavity: nil evidence of mucositis Diagnosis Probable neutropenic sepsis Plan Full blood count (including differential) Urea and electrolytes Liver function tests C-reactive protein (CRP) Lactate Blood cultures Urine dipstick Cannulate 4.5g intravenous (IV) tazocin immediately and 320mg IV gentamicin 1,000ml 0.9% sodium chloride over eight hours Blood results Haemoglobin 118 White cell count 0.8 Neutrophils 0.2 Platelets 148 Sodium 136 Potassium 4.2 Urea 5.6 Creatinine 58 Bilirubin 12 Alkaline phosphatase 48 Alanine transaminase 40 CRP 5 Lactate 0.8 Blood cultures negative after five days complications as a result of FN than adults because their immune systems are not as well developed, they often receive intensive chemotherapy regimens and often have central venous access devices in situ (Sung et al 2011). Vidal et al (2013) conducted a systematic review comparing oral versus IV antibiotics for the management of patients with FN and found no significant difference in mortality or morbidity for CANCER NURSING PRACTICE those who were identified as low risk. However, they recommended that further research was required to stratify low-risk FN patients. MASCC risk index The Multinational Association of Supportive Care in Cancer (MASCC) risk index is the tool most widely used to identify low-risk FN patients (Klastersky et al 2000) (Table 3). June 2015 | Volume 14 | Number 5 19 Art & science | adverse events Table 2 Result of literature search for low-risk febrile neutropenia Database Number of hits Number for paediatrics Number for adults >18 years CINAHL 9 6 3 Cochrane 2 1 1 Embase 64 39 25 Medline 32 16 16 PubMed 399 205 194 Total 506 267 239 Table 3 Multinational Association of Supportive Care in Cancer scoring system for stratification of risk in febrile neutropenia Characteristic Weight Burden of illness: No or mild symptoms Moderate symptoms 5 3 No hypotension 4 No chronic obstructive pulmonary disease 4 Solid tumour or no previous fungal infection 4 No dehydration 3 Outpatient status 3 Age <60 years 2 Risk score >21 identified low-risk patients (Klastersky et al 2000) Table 4 Clinical Index of Stable Febrile Neutropenia tool and comparison with Julie’s score Score Julie Performance status >2 2 0 Stress-induced hyperglycaemia 2 0 Chronic obstructive pulmonary disease 1 0 Chronic cardiovascular disease 1 0 Mucositis grade >2 1 0 Monocytes <0.2 1 0 Characteristic (Adapted from Carmona-Bayonas et al 2011) 20 June 2015 | Volume 14 | Number 5 Using the MASCC risk index, Julie would have scored 25 as follows: burden of illness 5; no hypotension 4; no chronic obstructive pulmonary disease 4; solid tumour 4; no dehydration 3; outpatient status 3; and age <60 2. Julie’s score classified her as having low-risk FN. Although Klastersky et al (2000) suggested that low-risk FN patients can be managed in the community thus avoiding hospital admission, Talcott et al (2011) advocated the admission of low-risk FN patients for a period of 24 hours observation before discharge into the community. In view of the current perceived reluctance of clinicians to manage low-risk FN patients in the community, this option would appear to be feasible. Teuffel et al (2010) also identified a cohort of low-risk FN patients who go on to develop complications necessitating hospital admission; this further substantiates the case for initial admission to hospital for observation. In response to some of the concerns raised about the MASCC risk index including that it is not specific to solid tumours, Carmona-Bayonas et al (2011) devised the Clinical Index of Stable Febrile Neutropenia (CISNE) tool to identify patients who are at low risk of developing complications of FN and can be discharged home after 24 hours if their CISNE score is 0. Table 4 demonstrates the CISNE score as well as how Julie’s FN would have been classified. The fact that Julie had a MASCC risk index score of 25 and a CISNE score of 0 further supports the notion that she could have been managed in the community after an initial 24-hour inpatient admission. Although monocytes are recorded on the differential full blood count they are not routinely checked, hence I had to examine the results retrospectively and discovered that Julie had a monocyte count of 0.42. A new way of scoring There is evidence to support early discharge of low-risk FN patients as long as they fulfil criteria in accordance with a locally agreed tool. Although widely used in practice in the US, the MASCC risk index has limitations and in light of this the CISNE tool can be used to further stratify patients identified as low risk by the MASCC risk index (Carmona-Bayonas et al 2011). I propose that a combination of Systemic Inflammatory Response Syndrome (SIRS) score and CISNE score should be adopted in routine practice to identify low-risk FN patients who could be discharged home on oral antibiotics after a 24-hour hospital admission. NICE (2012) CANCER NURSING PRACTICE advocated that low-risk FN patients could be managed in the community, which also supports this recommended change in practice from a clinical governance perspective. More robust trials are advocated for management of low-risk FN patients in the UK (Phillips et al 2012), although this should not be seen as a barrier to implementing changes in practice. I intend to conduct a retrospective audit of notes of patients who have been admitted with FN over the past six months, an average of six patients a month, to identify how many would have been classified as low risk. As with any change in practice, the management of change process is important. Liaising with interested parties in the acute trust as well as primary care is fundamental, especially considering how such a change in practice could have far-reaching implications for both settings. Conclusion Although most chemotherapy can be administered in outpatient settings, it is time to start evaluating which further elements of the cancer patient pathway can be delivered in the ambulatory/home setting. Use of diagnostic tools including SIRS and the Modified Early Warning Score as well as the CISNE tool has the potential to revolutionise the care of patients with low-risk FN. In the case of Julie their use would have meant she could have been discharged home after 24 hours with oral antibiotics and robust education. This has fundamental and far-reaching implications for the healthcare economy and most importantly for patients. Online archive For related information, visit our online archive and search using the keywords Conflict of interest None declared References Carmona-Bayonas A, Gómez J, González-Billalabeitia E et al (2011) Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients. British Journal of Cancer. 105, 5, 612-617. de Naurois J, Novitzky-Basso I, Gill M et al (2010) Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Annals of Oncology. 21, Suppl 5, v252-v256. Dellinger R, Levy M, Rhodes A et al (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine. 41, 2, 580-637. Glasziou P, Moynihan R, Richards T et al (2013) Too much medicine; too little care. BMJ. 347:f4247. Greenhalgh T, Howick J, Maskrey N (2014) Evidence based medicine: a movement in crisis? BMJ. 348:g3725. Innes H, Smith D, O’Reilly S et al (2003) Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study. British Journal of Cancer. 89, 1, 43-49. CANCER NURSING PRACTICE Klastersky J, Paesmans M, Rubenstein E et al (2000) The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. Journal of Clinical Oncology. 18, 16, 3038-3051. Lalami Y, Paesmans M, Muanza F et al (2006) Can we predict the duration of chemotherapyinduced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis. Annals of Oncology. 17, 3, 507-514. Manji A, Beyene J, Dupuis L et al (2012) Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children – a systematic review of prospective trials. Supportive Care in Cancer. 20, 6, 1135-1145. National Cancer Institute (1999) Common Toxicity Criteria, Version 2.0. The National Cancer Institute, Bethesda MD. National Institute for Health and Care Excellence (2012) Neutropenic Sepsis: Prevention and Management of Neutropenic Sepsis in Cancer Patients. Clinical guideline 51. NICE, London. Orme L, Babl F, Barnes C et al (2014) Outpatient versus inpatient IV antibiotic management for pediatric oncology patients with low risk febrile neutropenia: a randomised trial. Pediatric Blood and Cancer. 61, 8, 1427-1433. Teuffel O, Amir E, Sung L et al (2010) Treatment strategies for low-risk febrile neutropenia in adult cancer patients: a cost-utility analysis. Journal of Clinical Oncology. 28, 15 Suppl, abstract 6102. Parish B, Cooksley T, Haji-Michael P (2013) Effectiveness of early antibiotic administration in septic patients with cancer. Acute Medicine. 12, 4, 196-200. Vidal L, Ben Dor I, Paul M et al (2013) Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database of Systematic Reviews. Issue 10. Phillips R, Hancock B, Graham J et al (2012) Prevention and management of neutropenic sepsis in patients with cancer: summary of NICE guidance. BMJ. 345:e5368. Slavin M, Thursky K (2013) Outpatient therapy for fever and neutropenia is safe but implementation is the key. Journal of Clinical Oncology. 31, 9, 1128-1129. Sung L, Phillips R, Lehrnbecher T (2011) Time for pediatric febrile neutropenia guidelines – children are not little adults. European Journal of Cancer. 47, 6, 811-813. Worth L, Lingaratnam S, Taylor A et al (2011) Use of risk stratification to guide ambulatory management of neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee. Internal Medicine Journal. 41, 1b, 82-89. Yoong J, Seah J, Hamilton K et al (2012) Mortality within 30 days of receiving systemic anti-cancer therapy at a regional oncology unit: what have we learned? Asia-Pacific Journal of Clinical Oncology. 8, 4, 325-329. Talcott J, Yeap B, Clark J et al (2011) Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. Journal of Clinical Oncology. 29, 30, 3977-3983. June 2015 | Volume 14 | Number 5 21