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  • Writer's pictureP.K. Peterson

Sepsis in Children: Recent Developments

“Never Again: Those two words sum up our overwhelming feelings following Rory’s death. We had not heard of sepsis before his death. . . If the public had been educated about sepsis our son would be alive.”

Ciaran and Orlath Staunton, founders of The Rory Staunton END SEPSIS Foundation


“Improvements in care should thus be judged not only by improved outcomes among patients with sepsis but also by decreased progression to sepsis among patients with infection.”

Erin F. Carlton, MD, MSc, Associate Professor, Pediatric Critical Care Medicine, University of Michigan

 



Sepsis is a life-threatening condition caused by an over-reactive immune response to an infection. According to the Centers for Disease Control and Prevention (CDC), sepsis is the third most common cause of death in U.S. hospitals. But it is the leading cause of death among children worldwide.

At the time of my first Germ Gems post on sepsis on November 3, 2019: “Sepsis: What Everyone Needs to Know,” children and adolescents with sepsis weren’t on the radar screen of the CDC. That has changed dramatically. In recent years, the CDC has spearheaded a number of programs aimed at improving the early recognition and treatment of sepsis in children. My focus in this week’s post is on the new emphasis in diagnosing and treating sepsis in this young age group.


Recap of sepsis. Sepsis itself is not an infection; instead it is an overreactive response of the immune system to an infection. As I’ve discussed in several previous Germ Gems posts, the immune system is a “double-edged sword.” We can’t live without its contributions to host defense against invasive pathogens. But mediators produced by an over-activated, dysregulated immune system are what make you feel sick, and they are to blame for sepsis. Of these mediators, proteins produced by immune cells called cytokines are the bad actors. (Reference to these mediators can be found in several earlier Germ Gems posts, for example, a “cytokine storm” triggered by SARS-CoV-2 kills many people with severe COVID-19.)


The CDC defines sepsis as: “[T]he body’s extreme response to an infection. It is a life-threatening medical emergency. Sepsis happens when an infection you already have triggers a chain reaction throughout your body.”


While many kinds of pathogens can trigger sepsis, bacteria, like Staphylococcus aureus, species of the genus Streptococcus, and gram-negative bacteria, as well as viruses, such as influenza virus and SARS-CoV-2, are the most notorious. Infections by these microbes at different body sites (most commonly, lungs, skin, gastrointestinal tract, or kidneys) can be the inciting event.


What are the signs and symptoms of sepsis? Clinical evidence of sepsis is characterized by the signs and symptoms you would associate with having an infection, e.g., fever and chills, tachycardia (rapid heart rate), pain, shortness of breath, and confusion or disorientation. The latter two symptoms—shortness of breath and confusion/disorientation— are the most worrisome; they suggest decreased blood flow to vital organs such as the heart and lungs, respectively. Reduced blood flow to these organs may also be the consequence of very low blood pressure, which is the hallmark of septic shock, a grave consequence of sepsis (mortality is greater than 50%).


Epidemiology of sepsis. According to the CDC, at least 1.7 million adults in America develop sepsis every year, 350,000 of whom die during hospitalization or are discharged to hospice care. The CDC has identified risk factors for sepsis which include: adults 65 or older; people with a weakened immune system; people with chronic medical conditions (diabetes, lung disease, kidney disease, and cancer); and infants (children younger than one). But children that are older than one and adolescents (between 10 and 19 years old) are also at risk.


The tragic story of Rory Staunton. On its website, the Society to Improve Diagnosis in Medicine posted “From a Small Scrape to Sepsis,”—the heart-wrenching story of Rory Staunton, a 12-year-old boy from Queens, N. Y., who died from sepsis in 2012.  Rory’s sepsis was precipitated by a relatively unremarkable skin infection; he scraped his arm when diving for a ball in his school gym on a Wednesday afternoon.

The next morning he had a high fever and was vomiting. His parents contacted his pediatrician who thought Rory had a gastrointestinal virus and sent him to the emergency department of a hospital in Queens where he was treated for dehydration from the vomiting and sent home. Rory continued to get worse. His parents took him back to the emergency room on Friday, and he was admitted. But by then it was too late. “Bacteria [group A Streptococcus] had entered his blood, through the cut on his arm. Rory was in septic shock.” He “died within 48 hours of streptococcal sepsis, a complication of the simple scrape on his arm, from a bacterial skin infection that went undetected.”


In April 2012, Rory’s parents established “The Rory Staunton END SEPSIS Foundation” the goal of which is to “ensure that no other child or young adult dies from undetected sepsis.” Rory’s parents and their foundation played a pivotal role in several major initiatives led by the CDC in developing new guidelines for hospitals to intervene earlier in the management of sepsis. (See, “CDC Sets New Standards for Hospitals to Combat Sepsis,” New York Times, August 24, 2023; “New Criteria Identify Sepsis in Children With Infection,” MDedge, Pediatric News, January 31, 2024.”)


The CDC’s new guidelines for hospitals caring for patients with sepsis stress seven core elements: leadership, accountability, action, tracking, reporting, education, and multi-professional expertise (including experts from the hospital’s antimicrobial stewardship program, infectious diseases department, and pharmacy).


Managing sepsis in children and adolescents: what’s new? The CDC’s new guidelines for management of sepsis in young Americans quickly evolved into a global collaboration, the results of which are reported in a January 23, 2024 publication in the Journal of the American Medical Association, “International Consensus Criteria for Pediatric Sepsis and Septic Shock.”


Using an international survey and systematic analysis of 172,984 children with suspected infection, a novel 4-organ-system model called the “Phoenix Sepsis Score” emerged in the past two years.  The Phoenix Sepsis Score criteria rely on 4 systems—cardiovascular, respiratory, neurological, and coagulation—for identifying children with infections at higher risk of poor outcomes. The Society of Critical Care Medicine task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection.

 

New focus on communicable diseases in children—birth to adolescence. According to a study by Peter Azzopardi and colleagues published in the July 2023 issue of The Lancet,  “[T]here were 3×0 million deaths from communicable disease among children and adolescents globally in 2019, equivalent to one death every 10 seconds.” But a commentary in the same issue of The Lancet, “Communicable diseases across the entire developmental window of childhood and adolescence: an outstanding agenda,” reported that because of improved public health measures, over the past three decades infectious disease-related mortality plummeted in children younger than 5 years.


These achievements did not extend to older children. As the commentary article concluded: “[A]ttention must be given to the entire period of development from birth to adolescence if children are to survive and thrive and realise their full potential.” Indeed, the findings in Azzopardi’s study and in studies of sepsis-related mortality make a compelling case for sustained investment in communicable diseases in childhood and adolescene.

 

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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