Risks, Diagnosis, and Management of Sepsis in Patients Undergoing Radiotherapy

Diagnosis and Management

Rapid detection and initiation of empiric systemic antibiotic therapy, oxygen support, and other supportive care are crucial for improved odds of patient survival. Supportive care should begin within 1 hour when sepsis is suspected.^1,10

Sepsis presents challenges because it is not always easily diagnosed. Bloodstream infection labs are negative in half of cases, and clinical signs have low specificity. However,  blood cultures and cultures of all suspected infection sites prior to antibiotic administration are still considered a mainstay of sepsis detection.^1,9-11 Medical imaging with radiography, ultrasonography, CT, and radioisotope-labeled infection imaging, including FDG-PET, starting prior to initiation of antibiotic therapy aid diagnosis and monitoring of antibiotic treatment response.¹⁰

Oncology nurses should know their facility’s sepsis management policies and guidelines, and each patient’s medical history, comorbidities, cancer treatment history, and sepsis risk factors, and must be on the lookout for signs of sepsis and septic shock following radiotherapy and other immunosuppressive cancer treatments. Any member of the patient’s cancer care team who suspects sepsis should immediately alert other team members to that suspicion to allow for the rapid initiation of supportive care and diagnostic workups.

Neutrophils are frequently involved in sepsis and organ dysfunction, and patients with neutropenic cancers have increased levels of interleukin-6 and -8, as well as granulocyte colony-stimulating factor (G-CSF).¹ The length and severity of neutropenia are risk factors for sepsis.^1,9

Although some patients with cancer and sepsis do not develop fever at all, fever is often the only sign of neutropenic sepsis.¹ Neutropenic patients are considered febrile if they have oral temperatures of 38.3°C (101°F) or fevers of at least 38.0°C (100.4°F) for 1 hour or more.¹ Patients who have sepsis without fever or with hypothermia are more likely to die than others.¹ Those who develop hypothermia without fever should be assessed for altered cognitive status, heart arrhythmias, and changes in urination.¹

Mucositis and mucous membrane ulcers also can indicate the presence of neutropenic sepsis.^1,9

Other signs and symptoms of sepsis include redness around a central line site; cough with or without sputum; difficulty breathing or shortness of breath; abnormal breathing sounds; diarrhea; abdominal or gastrointestinal tenderness; arterial hypotension; heart rate exceeding 90 bpm; tachypnea; fever; flushed and warm skin (early in sepsis); or cool, clammy, sweaty, mottled, or cyanotic skin (in cases of septic shock).^1,9,12 Patients may experience confusion, disorientation or restlessness, and painful urination or anuria (a halt in urination).¹ Physical examination of the respiratory, genitourinary, and gastrointestinal tracts including the mouth, should be undertaken for signs of infection.¹

For high-risk patients such as those undergoing chemoradiation for head and neck cancer, for example, monitoring for sepsis and systemic inflammation should be undertaken at least weekly if not more frequently.¹⁰ Monitoring should involve white blood cell count (WBC) labs and tracking of blood pressure, heart rate, respiratory rate, and blood oxygen levels.¹⁰

The quick Sequential sepsis related Organ Failure Assessment (qSOFA) is a tool used outside of ICU settings.^1,3,12 It involves 2 or more of the following and should prompt sepsis workup and treatment: Glasgow Coma Scale less than 13, systolic blood pressure of 100 mm Hg or less, and tachypnea (respiratory rate >22 breaths per minute).^1,3

As with clinical signs, lab test results are nonspecific and overlap with conditions other than sepsis.¹ Septic shock involves sepsis that requires blood pressure support.¹

Lactate, C reactive protein (CRP), and procalcitonin levels are sometimes included in suspected sepsis labwork.¹⁰ CRP levels higher than 17 mg/dL can differentiate sepsis from other causes of inflammation.¹⁰

Serum lactate is associated with impaired organ perfusion and lactate levels higher than 4 mmol/L.¹ Lactate levels above 2 mmol/L are indicative of organ dysfunction.^1,3 Leukopenia (WBC <4,000/mm³) and low platelet counts (<100,000/mm³) are associated with sepsis, as are increases in creatinine (>0.5 mg/dL) and bilirubin (>4 mg/dL).¹

Sepsis and septic shock are complex oncologic emergencies, and early detection and treatment improve a patient’s chances for survival.¹

References

1. Tavakoli A, Carannante A. Nursing care of oncology patients with sepsis. Semin Oncol Nurs. 2021;37(2):151130. doi:10.1016/j.soncn.2021.151130
2. Hensley MK, Donnelly JP, Carlton EF, Prescott HC. Epidemiology and outcomes of cancer-related and non-cancer-related sepsis hospitalizations. Crit Care Med. 2019;47(10):1310-1316. doi:10.1097/CCM.0000000000003896
3. Jairam V, Lee V, Park HS, et al. Treatment-related complications of systemic therapy and radiotherapy. JAMA Oncol. 2019;5(7):1028-1035. doi:10.1001/jamaoncol.2019.0086
4. Reinhart K, Daniels R, Kissoon N, et al. Recognizing sepsis as a global health priority — a WHO resolution. N Engl J Med. 2017;377(5):414-417. doi:10.1056/NEJMp1707170
5. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Sepsis Shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
6. Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2
7. Williams PT. Inadequate exercise as a risk factor for sepsis mortality. PLoS One. 2013;8(12):e79344. doi:10.1371/journal.pone.0079344
8. Moore JX, Donnelly JP, Griffin R, et al. Community characteristics and regional variations in sepsis. Int J Epidemiol. 2017;46(5):1607-1617. doi:10.1093/ije/dyx099
9. Gustinetti G, Mikulska M. Bloodstream infections in neutropenic cancer patients: a practical update. Virulence. 2016;7(3):280-297. doi:10.1080/21505594/2016.1156821
10. Mirabile A, Numico G, Russi EG, et al. Sepsis in head and neck cancer patients treated with chemotherapy and radiation: literature review and consensus. Crit Rev Oncol Hematol. 2015;95(2):191-213. doi:10.1016/j.critrevonc.2015.03.003
11. Kochanek M, Schalk E, von Bergwelt-Baildon M, et al. Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the Germany Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2019;98:1051-1069. doi:10.1007/s00277-019-03622-0
12. Centers for Disease Control and Prevention. Get Ahead of Sepsis. For patients and families: protect yourself and your family from sepsis. Accessed May 19, 2021. https://www.cdc.gov/sepsis/pdfs/Consumer_fact-sheet_protect-yourself-and-your-family-P.pdf