Written by: Nick Wleklinski, MD (PGY-2) Edited by: Steve Chukwuelebe, MD (NUEM ‘19) Expert commentary by: Sean Fox, MD, FACEP, FAAP
Febrile Neutropenia: Is Admission Always Necessary?
Febrile Neutropenia:
• Defined as an ANC <500 cells/μL with a temperature of >101F (38.8C) or >100.4F sustained for 1 hour
• Most common in hematologic malignancies, however those with solid tumors are also at risk, especially after first round of chemotherapy (1)
• Systemic dysfunction (i.e. hypotension, respiratory failure, renal insufficiency, etc.) seen in 25- 30% of cases and infection/severe sepsis carries a high mortality rate (2)
Yet, not all “hot” neutropenics must be admitted and given IV antibiotics. Local practice patterns may vary, but there are guidelines defining those who are appropriate for outpatient management.
How do you define a “low risk” Febrile Neutropenic?
• Do they look sick, have signs of end organ dysfunction, and/or have a myriad of comorbidities? Then admission is the right call.
• Do they have a knack for getting infected with resistant bugs? Are they already taking a fluoroquinolone to keep the bad bacteria at bay? Sorry, you’ll be coming into the hospital.
• Do they live far away, alone, and/or have a history of not following up? ADMIT (1, 2)
• For those who were able to answer “NO” to the above questions, then it’s time to use the MASCC (Multinational Association for Supportive Care in Cancer) and CISNE (Clinical Index of Stable Febrile Neutropenia) scores to further risk stratify.
More reasons to Use MDCalc:
MASCC Score: Utilizes subjective clinical data and non-laboratory objective data to help risk stratify patients. The study was validated in all cancer types (solid, hematologic, and bone marrow transplant). The higher the score, the better; a score >21 is considered low-risk. While this score has a decent sensitivity (60-95%) for identifying low risk patients, those classified as low risk still have ~10% risk of developing serious complications (i.e. hypotension, organ dysfunction) (1, 3). That is where the CISNE score comes in.
CISNE score: Strictly uses objective data to help stratify patients. A CISNE of 0 indicates low risk; 1-2, intermediate; and ≥ 3, high risk. This score is applied to seemingly stable patients to better stratify their risk. In the validation study, the complication rate was significantly lower in the low risk group compared to the high risk, 1.1% vs. 32.5%, respectively, yielding a specificity of 96.6% when identifying low risk patients (4, 5).
Using both: These scores can be used similarly to the Wells and PERC criteria, with MASSC ~ Wells and CISNE ~ PERC. This combination works well as the MASCC has a higher sensitivity but poor specificity when predicting poor outcomes for low risk patients while the CISNE is completely opposite (5, 6). The CISNE was not validated on patients with hematologic malignancies but can still help stratify the risk of discharging these patients (7).
Using the dynamic duo:
Antibiotics:
Discharge: The goal- provide Pseudomonas coverage. It is still recommended these patients be observed for 4 hours prior to discharge (1).
Admission: Start with monotherapy, unless the patient is severely ill or has focal infection (pneumonia, cellulitis, etc.); then provide additional coverage (i.e. Vancomycin). Make sure to consider previous infection history and local resistance patterns.
Duration of antibiotics: Currently, it is recommended to continue antibiotics until the neutropenia has resolved. There has been some debate on earlier discontinuation prior to neutrophil recovery, but there is no solid evidence supporting this yet (8).
To Summarize:
• Some febrile neutropenics can be sent home, but require scrutiny and coordination with the patient’s oncologist for close follow up
• MASCC and CISNE are a good tool to help risk stratify, but clinical judgement is still your best friend
• Consider that discharging low-risk patients prevents exposure to nosocomial infections and the burden of a hospital stay, which tends to average about 4 days (9).
Expert Commentary
NUEM team,
Thank you for this concise review and reminder of the challenges inherent in managing patients who are neutropenic and febrile. Febrile neutropenia, deserves our vigilance as it is associated with substantial mortality! Unquestionably, these can be some of the most critically ill patients in your department but who may also be deceptively “well appearing.”
Similar to other conditions that have the high potential for severe M&M, febrile neutropenia nearly mandates an ultra-cautious approach: resuscitate, get lots of cultures, give antibiotics, and admit. That being noted, the management is continuing to evolve, and it is incumbent upon all of us to endeavor to stay abreast of the most current recommendations. Your post is a useful tool toward that end.
Similar to other high-risk conditions, we are learning how to better define a low-risk population that does not benefit from aggressive management strategies. I appreciate the summary flow diagram for the management suggestions for the febrile neutropenic patient. In my experience, physicians who often manage these patients would likely concur with it. The one key point that cannot be overstated is the importance of including the patient’s oncologist in the decision process early. The scoring systems include clinical estimations that are best made in concert with the oncologist.
While we may be improving our ability to define the low-risk febrile neutropenic patient, I still assume the worst regardless of how well the patient appears. I actively search for any subtle sign of sickness. I anticipate the patient’s occult illness if they are well-appearing. If all of the stars align (and the moon and sun eclipse while a rainbow is overhead), then perhaps the oncologist and I will be able to define the patient as being low enough risk to go home after antibiotics.
I appreciate this post as a means to help us all to continue to refine our knowledge base; as part of our career’s quest is to learn every day.
Sean M. Fox, MD, FACEP, FAAP
Professor of Emergency Medicine & Professor of Pediatrics
Program Director, Emergency Medicine Residency Program
Department of Emergency Medicine
Carolinas Medical Center
References:
1. Taplitz, R. A., Kennedy, E. B., Bow, E. J., Crews, J., Gleason, C., Hawley, D. K., . . . Flowers, C. R. (2018). Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: Amercian Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. Journal of Clinical Oncology, 1443-1453. doi:10.1200/JCO.2017.77.6211
2. Zimmer, A. J., & Freifeld, A. G. (2019). Optimal Management of Neutropenic Fever in Patients with Cancer. Journal of Oncology Practice, 15(1), 19-24. doi:10.1200/JOP.18.00269
3. Klasktersky, J., Paesmans, M., Rubenstein, E., Boyer, M., Elting, L., Feld, R., . . . Talcott, J. (2000). The Multinational Association for Supportive Care in in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cacner patients. Journal of Clinical Oncology, 18(16), 3038-3051. doi:10.1200/JCO.2000.18.16.3038
4. Carmona-Bayonas, A., Jiménez-Fonseca, P., Echaburu, J. V., Antonio, M., Font, C., Biosca, M., Ayala de la Peña, F. (2015). Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study. Journal of Clinical Oncology, 33(5), 465- 471. doi:10.1200/JCO.2014.57.2347
5. Ahn, S., Rice, T., Yeung, S.-c., & Cooksley, T. (2018). Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents. Supportive Care in Cancer, 26(5), 1465-1470. doi:10.1007/s00520-017-3985-0
6. Moon, H., Choi, Y. J., & Sim, S. H. (2018). Validation of the Clinical Index of Stable Febrile Neutropenia (CISNE) model in febrile neutropenia patients visiting the emergency department. Can it guid emergency physicians to a reasonable decision on outpatient vs. inpatient treatment? PLoS ONE. doi:https://doi.org/10.1371/journal.pone.0210019
7. Coyne, C., Le, V., Brennan, J., Castillo, E., Shatsky, R., Ferran, K., . . . Vilke, G. (2017). Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Annals of Emergency Medicine, 69(6), 755-764. doi:10.1016/j.annemergmed.2016.11.007
8. Stern, A., Carrara, E., Bitterman, R., Yahav, D., Leibovici, L., & Paul, M. (2019). Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD012184.pub
9. Baugh, C. W., Wang, T. J., Caterino, J. M., Baker, O. N., Brooks, G. A., Reust, A. C., & Pallin, D. J. (2016). Emergency Department Management of Patients with Febrile Neutropenia: Guideline Concordant or Overly Aggressive? Academic Emergency Medicine, 24(1), 83-91. doi:10.1111/acem.13079
How to Cite This Post
[Peer-Reviewed, Web Publication] Wleklinski, N., Chukwuelebe, S. (2020, Jan 27). Febrile Neutropenia. [NUEM Blog. Expert Commentary by Fox, S]. Retrieved from http://www.nuemblog.com/blog/febrile-neutropenia
