Fighting Sepsis: The Critical Value of the Lab
Sepsis, an often fatal condition in which the immune system's response turns against the body itself, is a leading cause of in-patient deaths in hospitals today. Automated diagnostic tests, however, can help save lives and reduce treatment costs by aiding physicians in diagnosing the life-threatening complication.
Sepsis typically progresses from tissue damage to organ failure and—in patients diagnosed with septic shock, its final and most severe manifestation—to death. Each year, the condition kills more people1 than HIV/AIDS, stroke, and breast and prostate cancer combined.
Some physicians believe that the condition has become more prevalent2 in response to the overuse of antibiotics. The number of patients hospitalized for sepsis in the U.S. doubled between 2000 and 20083, and now exceeds 1.6 million each year4. With early diagnoses and optimal treatment, however, 80% of sepsis deaths5 could be prevented.
Additionally, Sepsis is the single most expensive condition6 facing U.S. hospitals, which spent nearly $27 billion in 2014 to address the complication. While the public may hear less about this condition compared to stroke, cancer, or heart disease, reducing mortality and alleviating the impact that sepsis has on hospital workflow and budgets remains a top healthcare priority.
Unfocused prescription of antibiotics and misdiagnoses of sepsis cost the U.S. thousands of lives and $27 billion each year..
Learn how PCT-screening testing is making a difference..
PCT Screening: A Race Against Time
The CMS SEP-1 core measure, which prescribes the tests and interventions required when sepsis is suspected in an adult, has led to changes in care. However, diagnosing sepsis can be very difficult, especially in light of the unspecific signs and symptoms of the condition.
Today, a number of different biomarkers7 can be used to aid diagnosis and treatment. One of the most strategically important biomarkers is proving to be procalcitonin (PCT), a precursor to calcitonin, the hormone that regulates calcium levels in the blood.
When exposed to bacterial toxins, cells release PCT along with inflammatory cytokines8, so the biomarker can be used to gauge levels of inflammation and assess the degree of bacterial infection9 within the body. During viral infections, PCT production is lessened10 by Interferon gamma (IFN-γ) that is released during the host response to the virus. Thus, PCT concentration will not rise in viral infections as it does in the presence of a bacterial infection.
The first low-volume, manual PCT assays11 were developed and used in Europe in the late 1990s and approved for use in the U.S. a decade later. Designed for single-point evaluations, the systems could only handle a limited number of tests at one time. A number of vendors licensed the original patented assay technology and used it to develop their own platforms. In 2014, a groundbreaking clinical trial12, the MOSES PCT Monitoring Sepsis Study, showed that the odds of patients with sepsis surviving double if their measured PCT levels decrease by more than 80% between the first and fourth day of their treatment. Every hour that proper treatment is delayed can reduce those chances by 7.6%.13
This finding was incorporated into the indications of use for the first fully automated PCT assay cleared by the FDA. The system provides results in 18 minutes and does not require manual reagent preparation or hands-on testing, reducing the overall time required and allowing serial testing to be performed with numerous patients in healthcare settings.
From Screening to Antibiotic Stewardship
Laboratory professionals are in the position to move an automated PCT solution into their hospitals and healthcare networks, where the tests are being used to evaluate patients that present with a suspected infection, to monitor their progress, help guide their treatment, and prevent overprescription of antibiotics. Results are already being quantified: In one study, researchers found that using PCT to screen patients on the first day of their ICU hospitalization reduced stays14 by an average of 1.2 days and saved an average of $2,759 in total hospitalization and pharmacy costs per patient.
At Five Rivers Medical Center in Arkansas, Michael Broyles, head of clinical pharmacy and lab services, led a study15 comparing the effectiveness of sepsis treatment before and after PCT was introduced to guide antibiotic decision-making. Focusing on key benchmarks, this study found that length of hospitalization decreased by 47%, inhospital mortality went down by 62%, and 30-day readmission levels were halved.
At the University of California San Diego, a cross-disciplinary team that included lab professionals, cardiologists, and clinicians, led the move to implement use of PCT assays within the hospital, and a formal program was recently introduced.
Media reports show that other hospitals and healthcare systems are also achieving dramatic improvements in patient outcome using PCT, citing programs16 at hospitals that include Bronson Methodist Hospital in Michigan and New York Presbyterian. One unexpected benefit that the automated platforms have brought is the potential for a hospital to be able to invest in and use the same instrumentation to run PCT testing as well as other tests, such as high-sensitivity troponin assays, which are helping a growing number of physicians pinpoint patients suffering a heart attack with greater precision.
Whether helping to guide antibiotic decision making or staving off over-perscription of antibiotics, PCT promises to play a growing role in saving lives and reducing the cost and time devoted to managing this deadly condition.
1. “Using procalcitonin (PCT) to improve the odds in sepsis managementz.” labmedica.com, March 12, 2019, https://www.labmedica.com/whitepapers/sepsis_pct-brochure_en_low.pdf
2. Roger C. Bone, MD. “The Pathogenesis of Sepsis." Penn Sate University, March 12, 2019, http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.824.7787&rep=rep1&type=pdf
3. J Orthop Traumatol. “Incidence and predictive risk factors of postoperative sepsis in orthopedic trauma patients.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429254/
4. “Roche receives FDA clearance for its Procalcitonin (PCT) assay to help clinicians effectively assess sepsis risk and manage sepsis patients.” CISION PR Newswire, March 12, 2019, https://prnewswire.com/news-releases/roche-receives-fda-clearance-for-its-procalcitonin-pct-assay-to-help-clinicians-effectively-assess-sepsis-risk-and-manage-sepsis-patients-300289386.html
5. “Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pubmed/16625125
6. John Tozzi. “America Has a $27 Billion Sepsis Crisis.” Bloomberg, March 12, 2019, https://www.bloomberg.com/news/articles/2017-07-14/america-has-a-27-billion-sepsis-crisis
7. James D. Faix. “Biomarkers of sepsis.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613962/
8. “Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pubmed/11232031
9. “Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pubmed/15070906
10. “Role of biomarkers in sepsis care.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pubmed/24088989
11. MM Lloyd FCPath(SA), JM Kuyl FCPath(SA). “Comparison of three methods for procalcitonin analysis.” Medical Technology SA, March 12, 2019, http://www.mtsaj.co.za/index.php/mtsaj/article/viewFile/30/46
12. “Multi-Center Clinical Study Confirms Decreased Levels of Procalcitonin as an Independent Predictor of Mortality in Patients with Severe Sepsis and Septic Shock.” ThermoFicher Scientific, March 12, 2019, https://ir.thermofisher.com/investors/news-and-events/news-releases/news-release-details/2017/Multi-Center-Clinical-Study-Confirms-Decreased-Levels-of-Procalcitonin-as-an-Independent-Predictor-of-Mortality-in-Patients-with-Severe-Sepsis-and-Septic-Shock/d
13. “The golden hour of sepsis: initial therapy should start in the prehospital setting.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pubmed/24589883
14. “Routine Procalcitonin Screening Reduces Hospital Stays and Costs for Patients With Sepsis.” CHEST American College of Chest Physicians, March 12, 2019, http://www.chestnet.org/News/Press-Releases/2017/01/Routine-Procalcitonin-Screening-Reduces-Hospital-Stays-and-Costs-for-Patients-With-Sepsis
15. Micahel R. Broyles. “Impact of Procalcitonin-Guided Antibiotic Management on Antibiotic Exposure and Outcomes: Real-world Evidence.” National Center for Biotechnology Information, March 12, 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695623/
16. Anne Paxton. “Procalcitonin passes automation hurdle.” CAP Today, March 12, 2019, https://captodayonline.com/procalcitonin-passes-automation-hurdle/
Routine Procalcitonin Screening Reduces Hospital Stays and Costs for Patients With Sepsis
New retrospective study in CHEST found procalcitonin testing at admission reduced the length of stay and total cost of care
Procalcitonin passes automation hurdle
by Anne Paxton
Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study
Early diagnosis and initiation of resuscitation measures, antibiotic treatment and/or source control remains the cornerstone of sepsis care.