Quality Corner – The Bleeding Fistula and Neutropenic Fever

Author: Christine Kulstad, MD (EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Welcome to Quality Corner, a new emDocs series evaluating tough cases and potential areas for improvement. The cases described below are based on ED bouncebacks, with all identifying details removed, and are limited to what was documented in the medical record.

Case 1 – The Bleeding Fistula

A 52-year-old man was sent from his hemodialysis (HD) center for an AV fistula problem. He had completed his dialysis session, but the center was unable to stop the bleeding afterwards. He arrived with normal vital signs and no other complaints. Of note, he was taking warfarin and had an INR of 6. The initial provider documented that the bleeding was controlled with one stitch, the patient was briefly observed, and he was discharged. He returned to the ED 2 days later with a complaint of non-functional fistula and was admitted for an angioplasty of his fistula. Could this have been avoided?

Bleeding from AV fistulas can be life threatening due to the poor function of platelets in renal failure, the use of anticoagulation during HD, and the frequent presence of aneurysms at the fistula site. This patient had the additional bleeding risk factor of a supra-therapeutic INR. For life or limb threatening bleeding, application of a suture or even a tourniquet at the bleeding site is clearly appropriate. For less severe bleeding, start simple and add therapies as needed. First apply direct pressure, which has probably been tried at the dialysis center, so add topical agents to promote clotting like Gelfoam, thrombin powder, or whichever combat dressing your hospital uses. If the bleeding has not stopped, give IV DDAVP to improve platelet function. The dose is ten-fold higher than when used for DI, and it has an onset of action within one hour (Hedges SJ, 2007). Estrogens can be used for bleeding in renal failure but take up to 6 hours for maximal effect (Hedges SJ, 2007). Literature review found no studies evaluating topical TXA for this specific indication, but there is evidence of its effectiveness for stopping bleeding in operative settings and epistaxis. In this patient, reversal of INR should be considered, depending on his reason for anti-coagulation and the difficulty of controlling the bleeding. PCC would be preferred, as it would reverse his anticoagulation in about 30 minutes (Leissinger CA, 2008) and not require as much volume as FFP for this HD patient.

Take Home Points:

  • Avoid sutures or tourniquets for AV fistulas (or grafts) unless life or limb threatening bleeding is occurring.
  • Many topical agents – from thrombin powder to combat dressings to TXA – exist to help stop the bleeding.
  • IV DDAVP improves the platelet dysfunction in renal failure patients.

Case 2 – Neutropenic Fever

A 24-year-old male with a PMH of ALL currently undergoing chemotherapy, came to the ED for fever. His initial vital signs were HR 102, Temp 37.2, RR 16, BP 128/70.  He had no symptoms to suggest a source of infection. His evaluation included a normal UA and CXR, unremarkable BMP, and a CBC that showed an absolute neutrophil count of 150. He was given IVF and pain control in the ED, and felt improved. He was then discharged with instructions to follow-up with his oncologist.

He returned 24 hours later with a complaint of persistent fevers and pus draining from his PICC line. His heart rate on this visit was 128, with a normal temperature. He was given broad spectrum antibiotics and admitted for neutropenia and PICC line infection. At both visits, he reported a Tmax at home of 102 F, although he was never febrile in the ED. Although it may have been examined, no mention was made of his PICC line in the chart for his first visit, only the ubiquitous “Skin: warm and dry”.

The IDSA defines fever in neutropenic patients as either a single oral temp of greater than 38.3 C or a temperature greater than 38.0 C for more than 1 hour (Freifeld AG & America.). Our patient, with his single oral temp of 102 F (38.9 C), easily qualifies. As a reminder, neutropenia is technically defined by an ANC of less than 1500 cells µL, although a patient with “neutropenic fever” is usually one with severe neutropenia defined by an ANC < 500 cells/µL (Freifeld AG & America., 2011). Our patient was severely neutropenic but did not have a fever in the ED, which likely falsely reassured his provider. Patients with documented fever at home should be treated as if febrile in the ED. Patients, and even providers, are not as accurate in determining fever by symptoms or touch (Singh M, 2003).

The potential sources of fever in the neutropenic patient are considerable, but the most common identified cause is bacteremia (Freifeld AG & America., 2011). All patients should have blood cultures and a CBC with differential ordered, and a UA and CXR should be strongly considered. A good physical exam must be performed, including careful examination of the skin, especially indwelling lines. Digital rectal exam or rectal temp should be avoided, as it may allow GI flora to cross the mucosa. Additional findings, like abdominal tenderness or neck stiffness, guide further testing.

Broad spectrum antibiotics should be given within 60 minutes of patient presentation. Monotherapy with an anti-pseudomonal beta-lactam like cefepime, imipenem, or piperacillin-tazobactam is appropriate for most patients. If patients have pneumonia, skin or soft tissue infections, suspected catheter infection, or are septic, add vancomycin – Vanc/Zosyn for all your sepsis needs (Freifeld AG & America., 2011).

Most of these patients will be admitted, however, carefully selected patients can be discharged. They must look and feel well, display normal vitals, and have excellent follow-up. The decision to discharge should be made in conjunction with their oncologist. The CISNE (Clinical Index of Stable Febrile Neutropenia) score can also help support that decision (Carmona-Bayonas A, 2011) (Coyne CJ, 2017).  Like all clinical decision rules, it’s important to apply to patients it was designed for, namely well-appearing patients. It uses a 7-day outcome of complications: hypotension, arrhythmia, heart or renal failure, major bleeding, respiratory failure, DIC, acute abdomen, or delirium, which seem reasonable as serious patient-oriented outcomes. Most of the score components are easy to determine, except the ECOG score– a marker of the effect of illness on patients. It ranges from Asymptomatic to Dead, with the middle ground being symptomatic with greater or less than 50% of your day spent in bed. Both can be found on MDCalc.

Importantly, discharged patients should receive a dose of antibiotics in the ED and continue oral antibiotics at home. ASCO guidelines recommend a fluoroquinolone + amoxicillin/clavulanate or fluoroquinolone+ clindamycin (Flowers CR S. J., 2013) in the PCN allergic patient.

Take Home Points:

  • Neutropenic patients with a measured temperature greater than 38 C, even at home, need rapid, thorough evaluation.
  • Patients with neutropenic fever should have blood cultures and broad spectrum IV antibiotics within 60 minutes of arrival to the ED.
  • Carefully selected patients with excellent follow up can be managed as outpatients, with oral antibiotics.

References/Further Reading:

Carmona-Bayonas A, G. J.-B. (2011). Prognostic evaluation of febrile. Br J Cancer., 105(5), 612-7.

Coyne CJ, L. V. (2017). Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med, 69(6), 755-64.

Flowers CR, S. J. (2013). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 31(6), 794-810.

Flowers CR, S. J. (n.d.). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of C.

Freifeld AG, B. E., & America., I. D. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis, 52(4), e56-93.

Hedges SJ, D. S. (2007). Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol, 3(3), 138-53.

Leissinger CA, B. P. (2008). Role of prothrombin complex concentrates in reversing warfarin anticoagulation: A review of the literature. Am J Hematol., 83, 137-43.

Singh M, P. M. (2003). Accuracy of perception and touch for detecting fever in adults: a hospital-based study from a rural, tertiary hospital in Central India. Trop Med Int Health., 8(5), 408-14.


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