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Managing Neutropenic Sepsis in the Emergency Department

Introduction

Neutropenic sepsis constitutes a major life-threatening complication in patients undergoing cancer treatment particularly with chemotherapy, and a recent study reported mortality rates of between 2% to 21% in adult patients (Herbst et al., 2009). Neutropenic sepsis is considered a medical emergency that requires immediate investigation and treatment and has been defined as an absolute neutrophil of less than 0.5 × 109 /litre, or less than 1.0 × 109 /litre (NICE CG151, 2012). This case study will provide critical analysis of a patient’s management in ED and will evaluate how this patient management compares with clinical guidelines from the National Institute for Health and Care Excellence (NICE) and other available evidence for the management of the patient's presenting condition. In order to maintain patient confidentiality, any identifying features have been removed in keeping with the requirement of the Data Protection Act of 2018; hence, the patient will be referred to as “Mr TP”.

Case

Mr TP is a 79-year-old white male who presented to ED with complaint of 1/7 history of three episodes of vomiting that morning with associated symptoms of diarrhoea, sweating, reduced appetite, nausea and weight loss. He reported waking up around 4 am with urgency to open bowel but was unable to reach the toilet in time before his bowel opened. The patient managed to clean himself up but then when he tried to stand, he fell. Patient's son was unable to get him up from the toilet floor and hence called 999 for an ambulance. This was on a background of a 10-month history of multiple myeloma, as well as chemotherapy-induced pancytopenia.The patient described stool as watery and yellowish but no report of blood in the stool. He denies any fever but his tympanic temperature in ED was 39.7°C, no shortness of breath (SOB) and no constipation. Relevant past medical history includes multiple myeloma which he has been undergoing chemotherapy for, heart failure, type 2 diabetes, hypertension, transient ischemic attack (TIA) and end-stage renal failure which he has also been undergoing dialysis three times a week. The patient has no known drug or food allergy.

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Mr TP had no relevant family history of illness. In his social history, he is a non-smoker, drinks approximately 4 units of alcohol in a fortnight and denies recreational drug use. He lives with his wife and 1 of his 2 children at his house and no recent history of overseas travel. In his review of systems, he denies any headache, constipation, chest pain and shortness of breath. On examination, the patient was alert but appears lethargic and febrile. There were no visible bruising, scar, mass or other abnormalities on general inspection. Pulse was palpable bilaterally and of normal rate and rhythm, jugular venous pressure (JVP) was not raised, no sign of peripheral oedema or central cyanosis and his capillary refill time was less than 2 second. The chest was clear on auscultation; the abdomen was soft and non-tender, there were no involuntary guarding and bowel sounds were present. His vital signs revealed a respiratory rate of 25 breaths per minute, heart rate of 105 beats/minute, the tympanic temperature of 39.7°C, oxygen saturation of 97% in room air, BP 147/95 mmHg, and weight was 68 kilograms, height of 1.70 metres and body mass index was 23.5.

My clinical impression at initial assessment was neutropenic sepsis while differential diagnosis includes gastroenteritis, drug cytotoxic and myocardial infarction (MI). This was based on Mr TP initial symptoms at presentation, and considering his background history of multiple myeloma, as well as the likelihood of chemotherapy-induced pancytopenia. This agrees with studies which suggest that chemotherapy-induced neutropenia is a major complication of cytotoxic cancer therapy and is often associated with infections (Hashiguchi, et al. 2015; Leleu et al. 2018). I presented the patient’s history and examination to my supervisor(ED Consultant) who subsequently reviewed the patient.

The study by Warnock et al. (2018) mentions that diagnostic features of neutropenic sepsis mainly include the presence of temperature above 38ºC along with the presence of neutrophil count of 0.5X109 per litre of blood or lower. Moreover, the partial pressure of arterial oxygen (PaO2) less than 4.3kPa and a white cell count less than 4x 109/L or greater than 12 x 109/L are found among patients (Alison & Norma, 2017; Hayakawa, et al. 2016). In addition, the symptoms related to sepsis such as shaking, confusion, rapid heart rate that above 90 beats each minute and rapid breathing that is more than 20 breaths per minute are also present in patients with neutropenic sepsis (Jones, 2016). Although Mr TP having the spike in temperature of 39.7°C indicates a serious infection and was considered to have neutropenic sepsis, however, the NICE guidance accentuates that initial assessment of patients with suspected infection should involve identification of the cause of infection and any risk factors that would make the patient more predisposed to sepsis (NICE NG51, 2016). The neutrophil count in patients suffering from neutropenic sepsis is determined as in this disease it is seen that the neutrophils levels are lowered as a result of which the individuals become unable to fight the infection and develop sepsis (Wilson et al. 2018). Thus, blood samples from Mr TP are collected to determine the neutrophil count of the patient through full blood count to determine the severity of the illness along with blood culture is also suggested. This is because blood culture is the diagnostic test that helps in determining the nature of foreign invaders present in the blood (Wilson et al. 2018). Thus, blood culture report is required to determine the nature of medication to be effective for Mr TP for controlling his neutropenic sepsis.

The diagnostic test for Mr TP also included Kidney and Liver Test (albumin, urea and electrolytes (U+Es), C-reactive protein, blood gas including glucose and lactate, stool culture, chest x-ray, CT head and echocardiogram (ECG). The C-reactive protein test is regarded to be better marker for conforming presence of sepsis compared to temperature. The C-reactive protein level of 15.2 ± 8.2 mg/dL indicates the presence of mild sepsis, 20.3 ± 10.9 mg/dL indicates severe sepsis and 23.3 ± 8.7 mg/dL indicates patient experiencing septic shock (Wilson et al. 2018). The study by Herd et al. (2016) mentions that increased level of lactate in a patient indicates the person is suffering from severe sepsis. Thus, the lactate test is required to be performed for determining the urgency of care for the mentioned patient. The blood gas test is executed to determine the amount of oxygen and carbon dioxide in the blood for determining if oxygen supplementation is required for avoiding septic shock (Jones, 2016). The stool culture is executed in neutropenic sepsis to determine the nature of bacteria and viruses that are causing the infection (Jones, 2016).

The 500ml Intravenous rapid infusion of 0.9% normal saline at 20mg/kg was initiated and antibiotic treatment was commenced immediately following the collection of blood culture specimens. The benefit of delivering saline in neutropenic sepsis is that it controls the body pressure from dropping thus preventing patient to experience shock. However, the use of normal saline in the case of sepsis is that it may lead to cause metabolic acidosis in the patient and increase risk for kidney injury (Rosenzweig et al. 2019). As infectious organisms including antibiotic-resistant infection strains and septicaemia were not yet ruled out before treatment; empirical broad-spectrum antibiotics Tazocin (Piperacillin with Tazobactam) 4.5 g and vancomycin 1g were administered intravenously according to hospital protocol. This is in concurrence with NICE management guidelines which recommend immediate commencement of empiric antibiotic in patient with suspected neutropenic sepsis while waiting for laboratory result (Heinz, et al. 2017; NICE CG151, 2012; Szwajcer, Czaykowski, & Turner, 2011). The benefit of the use of Tazocin and Vancomycin is that they are able to act against bacteria causing serious infection but leads to side-effects such as allergic reaction, nausea, vomiting and others among patients (Heinz, et al. 2017). When the results of the laboratory investigation arrived, it revealed among other findings an absolute neutrophil count of 0.1×109 per litre. Hence, the assenting evidence for diagnosis of neutropenic sepsis, in this case, relies on a combination of low neutrophil count (0.1×109 per litre), the temperature of 39.7°C, and a heart rate of 105 beats per minute. The patient's CXR, CT head, ECG and bedside glucose results were unremarkable. Mr TP was subsequently reviewed by the medical team and admitted to the medical ward for further management of his condition.

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In conclusion, although the patient presented with symptoms consistent with clinical manifestation of sepsis, the diagnosis of neutropenic sepsis, in this case, was based on a combination of patient's initial presentation, vital signs, judicious physical examination, laboratory findings and signs of sepsis. This case displayed the signs and symptoms consistent with neutropenic sepsis. The choice of drug therapy and management were in concordance with NICE guidelines.

References:

Alison, T. & Norma, O. (2017). Recognition, diagnosis, and early management of sepsis: NICE guideline. British Journal of General Practice, 67 (657), 185-186.

Hashiguchi, Y., Kasai, M., Fukuda, T., Ichimura, T., Yasui, T., & Sumi, T. (2015).Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy.Anti-cancer drugs, 26(10), 1054–1060.

Hayakawa, M., Saito, S., Uchino, S., Yamakawa, K., Kudo, D., Iizuka, Y. et al. (2016).Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.Journal of intensive care, 4, 44.

Heinz, W. J., Buchheidt, D., Christopeit, M., von Lilienfeld-Toal, M., Cornely, O. A., Einsele, et al. (2017). Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Annals of hematology, 96(11), 1775–1792.

Herbst, C., Naumann, F., Kruse, E. B., Monsef, I., Bohlius, J., Schulz, H., et al. (2009).Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy.Cochrane Database Syst Rev. 21(1), CD007107.

Herd, F., Bate, J., Chisholm, J., Johnson, E. & Phillips, B., (2016). Variation in practice remains in the UK management of paediatric febrile neutropenia. Archives of disease in childhood, 101(4), 410-411.

Jones, T., (2016). Neutropenic sepsis. Nursing Standard (2014+), 31(5), 64.

Leleu, X., Gay, F., Flament, A., Allcott, K., &Delforge, M. (2018). Incidence of neutropenia and use of granulocyte colony-stimulating factors in multiple myeloma: is current clinical practice adequate? Annals of hematology, 97(3), 387–400.

Nasa, P., Juneja, D., & Singh, O. (2012). Severe sepsis and septic shock in the elderly: An overview. World journal of critical care medicine, 1(1), 23–30.

Rosenzweig, M.Q., Nugent, B., Belcher, S.M., Welsh, A. & Aitken, L., (2019). When the Patient Has Cancer: Effective Nurse Communication in the Non-Oncology Setting About Neutropenic Fever. Medsurg Nursing, 28(3), 57-162.

Spangler, R., Van Pham, T., Khoujah, D., & Martinez, J. P. (2014).Abdominal emergencies in the geriatric patient.International journal of emergency medicine, 7, 43.

Szwajcer, D., Czaykowski, P., & Turner, D. (2011).Assessment and management of febrile neutropenia in emergency departments within a regional health authority-a benchmark analysis.Current oncology (Toronto, Ont.), 18(6), 280–284.

Warnock, C., Totterdell, P., Tod, A.M., Mead, R., Gynn, J.L. & Hancock, B., (2018). The role of temperature in the detection and diagnosis of neutropenic sepsis in adult solid tumour cancer patients receiving chemotherapy. European Journal of Oncology Nursing, 37, 12-18.

Wilson, T., Cooksley, T., Churchill, S., Radford, J. & Dark, P., (2018). Retrospective analysis of cancer patients admitted to a tertiary centre with suspected neutropenic sepsis: Are C-reactive protein and neutrophil count useful prognostic biomarkers?. Journal of the Intensive Care Society, 19(2), 132-137.


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