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Neutropenic Sepsis: A Preventable Death?

Neutropenic Sepsis: A Preventable Death?

Yashvi Vijh

 

Neutropenic sepsis is unfortunately, a too often fatal complication of various anti-cancer treatments; the greatest risk of which arises from cytotoxic chemotherapy [1]. Its incidence is majorly concerning, due to the condition’s potentially life threatening nature [2]. The incidence of Neutropenic Sepsis after invasive myelosuppressive chemotherapy is between 70 and 100 per cent [3-5].

 

From the introduction of modern chemotherapy almost eighty years ago to the current day, there has been an exponential increase in the usage of this treatment, and consequentially its side effects [6]. Therefore, the basis of neutropenic sepsis is almost entirely iatrogenic, which may increase our responsibility as physicians, including the important responsibility to provide our patients with the correct information regarding neutropenic sepsis, both written and oral [7]. Recognising this condition can sometimes be difficult for patients and clinicians alike as patients may look well in the early stages, and symptoms are often vague [2].

 

A patient’s neutrophil count is depleted to 0.5 x10^9 neutrophils per litre or below in an attack of neutropenic sepsis. In addition to this, either a temperature greater than or equal to 38 degrees Celsius must be present for a diagnosis [7]. Neutropenic sepsis is a likely explanation of patients’ symptoms if they have had chemotherapy in the 7 to 10 days prior to displaying symptoms [8].

 

As chemotherapy is already a very stressful time for patients, it may be beneficial for the patients to always bring other family members, friends or carers to the consultations [9]. These personnel may be in a more proficient mental state at the time to retain and understand all the information regarding neutropenic sepsis [10]. This increases the likelihood that symptoms will be picked up in their initial stages. There is also a greater likelihood that the patient will be brought into hospital immediately despite possibly benign-seeming early stage symptoms, if pushed to do so by their loved ones [10].

 

The Sussex Cancer Network compiled the HEAT campaign to raise awareness of neutropenic sepsis for non-specialist staff that encounter it, for example, paramedics [2]. HEAT is an acronym that represents the four most important points to remember when screening a patient for neutropenic sepsis; History, Examine, Action and Treat. Fortunately, HEAT leaflets and posters with key signs and symptoms together with a flow chart with relevant interventions for the clinical response team have been successfully distributed to many ambulance services, GP surgeries and acute NHS Trusts across the UK [2].

 

The British National Formulary (BNF) states that for patients above the age of 12 years old, 4.5g of Piperacillin and Tazobactam must be infused intravenously into the patient every 6 hours [11]. Children between 2–12 years should be given 90 mg/kg every 6 hours instead, ranging to 4.5g if necessary [11]. Treatment must be continued in patients with an unresolving fever, but discontinued in those whose symptoms respond well to treatment even if the neutrophil count is still low [7].

 

Unfortunately, the truth remains that mortality rates for untreated patients ranges between 2 and 21 per cent [7]. A study at the Royal Marsden Hospital showed that following a course of chemotherapy there were a total of 161 chemotherapy related deaths in the 30 days that followed. Within this, 124 were due to the natural progression of cancer. Of the remaining 37 cases, 7 were due to neutropenic sepsis [12]. This shows that almost 1 in 5 of the deaths not due to disease progression were directly due to neutropenic sepsis, which highlights the severity of the situation. Guidelines state that the time for ‘door to needle’ for these neutropenic patients should be no more than one hour – ‘the Golden hour’. [13]. This refers to the time between which the patient presents to acute care services and the time taken for them to be given the life-saving antibiotic treatment that they need.

 

The fact that NICE has identified no major studies that will affect recommendations in the next 3–5 years may be the greatest hallmark of all for neutropenic sepsis being a ‘preventable death’ [14]. Timely hospital admission and administration of the highly efficacious antibiotic treatment, together with providing the patient and family with sound advice regarding the many diffuse presentations of neutropenic sepsis, can go a fair way in preventing this tragedy [2].  

 

References:

  1. Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients’, National Collaborating Centre for Cancer for NICE (September 2012). Available on: https://www.nice.org.uk/guidance/cg151/evidence/full-guideline-188303581. Accessed on 5/12/16
  2. Barrett K, Dikken C (2011) Neutropenic sepsis: preventing an avoidable tragedy. Journal of Paramedic Practice 3(3): 116–2
  3. DanaiPA, Moss M, Mannino DM, Martin The epidemiology of sepsis in patients with malignancy. Chest 2006; 129:1432-1440.
  4. MartinGS, Mannino DM, Eaton S, Moss  The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546-1554.
  5. MoererO, Quintel M. Sepsis in adult patients—definitions, epidemiology and economic aspects]. Internist (Berl) 2009; 50:788. 790–784, 796–788.
  6. Goldman B (2005) Multidrug resistance: Can new drugs help chemotherapy score against cancer. J Natl Cancer Inst 95(4): 255-7
  7. Neutropenic sepsis: prevention and management in people with cancer, NICE, Sept. 2012. Available on: https://www.nice.org.uk/guidance/cg151. Accessed on 25/9/16
  8. Signs and symptoms of neutropenic sepsis. Fast access to cancer treatment support group. (Date unknown) Available on: http://generalpracticemedicine.org/img%20NEUTSEP025.pdf. Accessed on 6/12/16
  9. Varani S, Stanzani M, Paolucci M, Melchionder F, Castellani G, Nardi L et al. Diagnosis of bloodstream infections in immunocompromised patients by real time PCR. J Infect 2009; 58: 346-51.
  10. Moore S (2007) Facilitating oral chemotherapy treatment and compliance through patient/family focused education. Cancer nursing. 2, 112-122.
  11. Piperacillin with Tazobactam, British National Formulary (BNF). November 2016. Available on: http://www.evidence.nhs.uk/formulary/bnf/current/5-infections/51-antibacterial-drugs/511-penicillins/5114-antipseudomonal-penicillins/piperacillin-with-tazobactam. Accessed on 7/12/16
  12. O’Brien, M E R et al. “Mortality within 30 Days of Chemotherapy: A Clinical Governance Benchmarking Issue for Oncology Patients.” British Journal of Cancer12 (2006): 1632–1636. PMC. Web. 6 Dec. 2016
  13. Chemotherapy Services in England: ensuring quality and safety. National Chemotherapy Advisory Group. Available on: http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_104501.pdf. Accessed on 6/12/16.
  14. NICE Guidelines for Neutropenic Sepsis overview: CG151 September 2012. Available on: https://www.nice.org.uk/guidance/cg151. Accessed on 11/03/17

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