Sepsis is a life-threatening condition that occurs when the body’s immune system has an extreme response to an infection. Once a body goes into sepsis, organ dysfunction can occur and the body’s reaction to this often leads to organ and tissue damage. If not diagnosed and treated promptly, the progression of sepsis can lead to multiple organ failure and in some cases, death.
Explaining further, Dr Jared Ross, a board-certified emergency medicine physician and assistant professor at the University of Missouri Medical School, tells us how easy it is for an infection to lead to sepsis: “Any type of infection can lead to sepsis. This includes urinary tract infections, pneumonia (lung infections), skin or wound infections, as well as infections resulting from surgical wounds.”
Sepsis can affect anyone, no matter how old or young, but tends to occur more in those who are vulnerable to infection. Therefore, it’s important for all healthcare providers and physicians to know the early warning signs and symptoms to look out for. These signs often tend to be similar to symptoms of a general infection, such as a fever, rapid breathing or an increased heart rate.
Prevention and control measures
According to the World Health Organization (WHO), sepsis acquired in healthcare settings is one of the most frequent adverse events during care delivery and affects hundreds of millions of patients worldwide every year. Since the Covid-19 pandemic, there has been an increased awareness on healthcare associated infections (HCAs). However, it seems that there still isn’t enough effort being put into preventing the spread of sepsis in healthcare settings. Simply implementing basic measures such as good hygiene practices and limiting inter-patient transfer has the potential to significantly reduce sepsis cases.
“Hospital-acquired infections can cause sepsis, and reducing hospital-acquired infections can make patients safer. This includes good hygiene practices, especially hand hygiene and removing urinary catheters and other medical devices as soon as possible,” explains Ross.
Dr Kenneth Remy, associate professor of medicine at Case Western Reserve University, agrees: “Sepsis is a syndrome that is challenging to prevent per se. For instance, key areas that lead to prevention include vaccinations against influenzas, pneumonia and other bacterial infection vaccinations. Rapid treatment of infections can mitigate sepsis through the administration of early antibiotics in the outpatient setting to effective hand hygiene and wound care.”
Good hygiene and sanitation practices are just a few of the fundamentals needed to prevent the spread of sepsis in healthcare settings. As well as this, evidence has shown that being vaccinated against common infectious agents, such as influenza and pneumococcus, can reduce the incidence of infections that may progress to sepsis. Prophylactic measures, including the use of antimicrobial agents in high-risk patients, also plays a role in prevention.
“There are several resources to help healthcare workers and caregivers identify early signs of sepsis and get help. This includes the TIME mnemonic from the Sepsis Alliance and educational material from the Surviving Sepsis Campaign and UK Sepsis Trust,” suggests Ross.
Standard therapeutic approaches
The timely and effective treatment of sepsis involves several key strategies, beginning with the cornerstone of sepsis treatment – the early administration of broadspectrum antibiotics. In an ideal situation, this should be given to patients within the first few hours of recognising sepsis, and as the causative organism is identified, antibiotic therapy should be narrowed down to target the specific pathogen. This practice is known as de-escalation. Alongside antibiotic therapy, fluid resuscitation is essential for stabilising patients with sepsis. Intravenous fluids help to maintain blood pressure and ensure adequate organ perfusion. Crystalloids, such as normal saline or lactated Ringer’s solution, are typically used. The amount and rate of fluid administration should be tailored to the patient’s needs and response. For patients who do not respond well to fluid resuscitation, vasopressors are administered to maintain adequate blood pressure and perfusion. Norepinephrine is the first-choice vasopressor, with other options such as dopamine used based on the patient’s response and specific needs.
And, lastly, supportive care measures play a vital role in managing sepsis, including mechanical ventilation in patients who may be dealing with respiratory failure, or renal replacement therapy for those patients with acute kidney injury. Administrating and combining these therapeutic approaches in a timely manner can significantly improve outcomes for sepsis patients.
Emerging treatments and innovations
While advancements in standard therapies have played an important role in reducing the spread of sepsis, there is still a need for ongoing research into novel treatments and innovations. Remy tells us more about recent research that has shown promise in improving sepsis outcomes: “Phenotyping patients based on immune function and evaluating against potential bacterial specificity are allowing for more personalised therapies. Our laboratory and others are leading a number of endeavours that are attempting to personalise sepsis care and understand the biology of the syndrome.”
Research has found that immunotherapy has been proven to modulate the body’s immune response to sepsis. This is done by monoclonal antibodies targeting specific components of the immune system. For example, antibodies against interleukin-6 (IL-6) and other cytokines are in various stages of clinical trial at the University of Osaka, showing promise in reducing the inflammatory response in sepsis.
As well as immunotherapy, some adjunctive therapies have generated interest in recent years, though their roles remain controversial. Corticosteroids, for example, are sometimes used to reduce inflammation, but their benefits must be weighed against potential risks. The combination of vitamin C, thiamine and hydrocortisone has also shown some promise in small studies, though larger trials are needed to confirm its efficacy.
However, advancements in this field aren’t being made as rapidly as the public health industry would like. “The greatest hindrance to our success in developing a treatment for sepsis is frankly funding,” says Remy. Statistics from the UK Sepsis Trust show that sepsis kills more than breast, bowel and prostate cancer combined. However, there is a lack of funding available for research on the disease.
And, of course, as with every other industry, advancements in technology are playing a role in improving healthcare services, including enhancing sepsis management. For example, novel diagnostic tools, such as biosensors and biomarkers are enabling earlier and more accurate detection of infections just as sepsis, allowing healthcare workers to treat sepsis rapidly.
Additionally, AI and machine learning are also now being used to predict the onset of sepsis and personalise treatment strategies according to each individual patient, which not only improves the patients outcome but also their overall experience. This innovation came after researchers of Lund University in Sweden were able to recently combine the unique molecular signature of sepsis with AI tools to predict patient risk of organ failure and death.
But reducing the spread of sepsis should not be solely left to emerging treatments and innovations. Hospitals also have a duty to play their role in the prevention of the disease. Ross puts it simply: “Hospitalacquired infections can cause sepsis, and reducing hospital-acquired infections can make patients safer.”
A need for interdisciplinary research
Despite an increase in research surrounding sepsis, there is still significant need for interdisciplinary collaboration to improve sepsis research and treatment practices, as well as integrate more diverse expertise and practices.
“Bringing together specialists from fields like immunology, microbiology, genetics and pharmacology can lead to a more thorough understanding of the pathophysiology of sepsis,” explains Remy. “This collaboration can help identify new biomarkers for early diagnosis and develop targeted therapies.”
As well as this, interdisciplinary research can allow for improvements in policy and guideline development, by allowing for collaboration between researchers, clinicians, public health experts and policy makers. This will lead to the development of evidence-based guidelines and policies that standardise sepsis care and prevention strategies.
There is a clear need for change in current policies and guidelines, Remy stresses. “Many policies are focused certainly at the population level, but it does not translate necessarily to a better understanding of epigenetic differences in patients or in individuals. With additional funding, we can really get to where we need to be…[as] one patient dies every three seconds [globally] from sepsis. We are poised to change that.”
Unfortunately, sepsis remains a significant challenge in public healthcare due to its high mortality rate and the complexity of its management. Early detection, prompt treatment and comprehensive care are crucial in improving outcomes for sepsis patients. Ongoing research into emerging treatments and technological advancements holds promise for the future, potentially revolutionising the way we are able to control and contain the spread of sepsis, in both society as well as in healthcare settings.
