Sepsis is the body’s extreme response to an infection. It is a life-threatening medical emergency that requires early recognition and intervention. Sepsis is a condition caused by an over-reactive immune response to an infection and is a major cause of death globally. Normally, when bacteria or other microbes enter the human body, the immune system efficiently destroys the invaders. In sepsis, the immune system goes into overdrive, and the chemicals it releases into the blood to combat the infection trigger widespread inflammation that can ravage the entire body (Recknagel et al., 2012).
Severe sepsis is unfortunately common, expensive, and frequently fatal. More than 1.5 million cases of sepsis occur annually in the United States, and its incidence continues to rise. It has been estimated that between 15% and 30% of these people die (NIGMS, 2018). This means about 250,000 people die from sepsis each year in the United State (CDC, 2018a). Most sepsis cases are community-acquired: 7 in 10 patients with sepsis had recently used healthcare services or had chronic conditions requiring frequent medical care.
In New York State, severe sepsis and septic shock impacts approximately 50,000 patients each year, and on average almost 30% of patients will die from this syndrome. In addition, many more may experience lifelong impairments as a result of the broad impact that sepsis can have on organ and tissue function (NYSDOH, 2017).
In 2017 New York State Governor Andrew Cuomo signed into law amendments to Public Health Law § 239 and Education Law § 6505, directing approved infection control continuing education providers to add sepsis education and identification material to their mandated NYS Infection Control courses.
The purpose of these changes to education and health law is to establish a sepsis awareness, prevention, and education program within the Department of Education that will educate students, parents, and school personnel about sepsis awareness. In addition, the new guidelines are intended to help healthcare providers recognize early signs of sepsis in children and adults and initiate rapid treatment protocols.
In May 2013, New York State became the first state to issue sepsis regulations, collectively known as “Rory’s Regulations,” mandating that all New York hospitals adopt, develop, and implement best practices for the early detection and timely treatment of sepsis (ASTHO, 2017). These regulations (10 NYCRR 405.2 and 405.4) were enacted after the death of Rory Staunton, a 12-year-old boy whose sepsis stemmed from an infected scrape, which was initially treated as a virus. Rory's parents set up a foundation to push for standard sepsis care in all states. The regulations require hospitals in New York State to adopt evidence-based protocols to ensure early diagnosis and treatment of sepsis.
Beginning in 2014 each acute care hospital in New York State that provides care to patients with sepsis is required by amendment of Title 10 of the New York State Codes, Rules and Regulations (Sections 405.2 and 405.4) to develop and implement evidence-informed sepsis protocols that describe their approach to both early recognition and treatment of sepsis patients (NYSDOH, 2017).
This law requires hospitals to:
Hospitals are required to report data to the New York State Department of Health, which is used to calculate each hospital’s performance on key measures of early treatment and protocol use. Hospitals are also required to submit sufficient clinical information on each patient with sepsis to allow the DOH to develop a methodology to evaluate “risk adjusted” mortality rates for each hospital. Risk adjustment permits comparison of hospital performance and takes into consideration the different mix of demographic and comorbidity attributes, including sepsis severity, of patients cared for within each hospital (NYSDOH, 2017).
Although these regulations are new, the New York State DOH reports that between 2014 and 2016 the use of protocols for sepsis care in adults increased from approximately 74% to nearly 85%. Mortality decreased during this period from 30% to 25% (Hershey & Kahn, 2017).
Sepsis does not arise on its own. It stems from another medical condition, such as an infection in the lungs, urinary tract, skin, abdomen, or other part of the body. Invasive medical procedures like the insertion of a vascular catheter can introduce bacteria into the bloodstream and bring on the condition (NIGMS, 2018).
Many different types of microbes can cause sepsis, including bacteria, fungi, and viruses, but bacteria are the most common culprits. Severe cases often result from a body-wide infection that spreads through the bloodstream, but sepsis can also stem from a localized infection (NIGMS, 2018). Once a septic reaction is triggered, the resulting damage is widespread, extensive, and life-threatening.
Originally sepsis was described as a disease specifically related to Gram-negative bacteria. This is because sepsis was thought to be a response to endotoxin—a molecule felt to be relatively specific for Gram-negative bacteria. In fact, some of the original studies of sepsis showed that Gram-negative bacteria were among the most common causes of sepsis. This resulted in a number of trials that focused on Gram-negative therapies, and even highly specific therapies for endotoxin, which were felt to be potentially useful treatments for sepsis. It is now recognized that sepsis can be caused by any bacteria, as well as from fungal and viral organisms.
While bacterial causes of sepsis have increased, fungal causes of sepsis have grown at an even more rapid pace. This may represent a general increase in hospital-acquired cases of sepsis, or it may reflect effective treatment of bacterial infections, which then allowed fungal infections to grow without competition (Martin, 2012).
In a classic systemic infection, the body’s immune response is self-limiting: the immune forces are called into action, the battle is fought, and the army retires. Sepsis begins like a typical infection and often presents with the signs of a classic systemic infection—fever, tachycardia, tachypnea, and an elevated white blood cell count. However, in sepsis the natural checks and balances fail. Instead of tapering off and disappearing, the inflammatory forces spread beyond the infected region.
The immune response begins as pro-inflammatory signal molecules enter the bloodstream in large numbers. As they travel through the vascular system, these molecules cause dilation and leaking of the endothelium that lines the blood vessels. The usual orderly movement of oxygen, nutrients, and fluids through the capillary walls is disrupted and organs become hypoxic (starved of oxygen).
If the sepsis continues, organ hypoxia and damage becomes organ failure, and at this point the condition is called severe sepsis. Severe sepsis increases the likelihood that the patient will die. When the organ system that fails is the circulatory system, the arterial wall muscles can no longer contract sufficiently to maintain adequate blood pressure. Now the patient is in septic shock, and the chance of surviving declines further (Shapiro et al., 2010).
The systemic collapse that occurs in sepsis is called systemic inflammatory response syndrome (SIRS). SIRS can be triggered by a variety of causes, including noninfectious causes such as pancreatitis, trauma, or burns. When it is triggered by an infection, SIRS is called sepsis and, unlike other types of SIRS, sepsis must be treated with antibiotics to remove or control the primary source of the infection.
Although any infection can trigger sepsis, to develop sepsis, a microbial infection is necessary but not sufficient: it appears that a patient also needs a pre-existing susceptibility. Support for this idea can be seen in large surveys of ICU patients. These surveys found that “approximately 70% to 80% of the cases of severe sepsis in adults occurred in individuals who were already hospitalized for other reasons” (Munford & Suffredini, 2009).
The likelihood that a local infection will progress to sepsis varies according to its source and location. For example, pulmonary or abdominal infections are 8 times more likely to develop into sepsis than are urinary tract infections (Munford, 2008). The most common sites of infection that lead to sepsis are:
Anyone at any age can get sepsis, but it is more common in infants, older adults, and those who are chronically ill or immune-suppressed. About 2 of every 3 patients who develop sepsis already have another significant illness. People with chronic health conditions such as diabetes, cancer, kidney and liver disease, suppressed immune systems, and patients with implanted devices or endotracheal tubes are at increased risk of developing sepsis (Neviere, 2013).
The increasing number of sepsis cases in the United States may be due to:
Early recognition of sepsis is the responsibility of all healthcare providers. The challenge is to pick out the signs of sepsis from among the other abnormalities plaguing a patient. To make sepsis easier to identify, there has been an effort to standardize its definition despite its wide range of presentations.
In 1991 the American College of Chest Physicians and the Society of Critical Care Medicine issued the first consensus definition of sepsis in an effort to standardize its terminology. It characterized sepsis as an abnormal response to infection called “systemic inflammatory response syndrome” (SIRS) (Cortés-Puch & Hartog, 2016).
From mild to severe, sepsis was defined as:
This intentionally broad definition described the common early clinical manifestations seen in septic patients: fever, mental status changes, tachypnea, tachycardia, hypotension, leukocytosis, thrombocytopenia, and coagulation abnormalities were considered for inclusion in the definition (Balk, 2014). In 2001 the definition was expanded to include a number of additional general, inflammatory, hemodynamic, and organ dysfunction variables.
In 2016 an international task force revised the definition of sepsis as a “dysregulated” host response causing life-threatening organ dysfunction that is associated with the acute change of at least 2 points in the sequential organ failure assessment (SOFA) score (Cortés-Puch & Hartog, 2016).
New sepsis criteria were advocated as “Sepsis-3” in 2017, which redefined sepsis as infection complicated by one or more organ dysfunctions. Organ system dysfunctions are assessed with an increase in the Sequential Organ Failure Assessment (SOFA) score by 2 or more points. This definition of sepsis is only applied to adult population (Kawasaki, 2017).
Classic signs and symptoms of a systemic infection that may be associated with sepsis in persons with confirmed or suspected infection can include:
The severity of the septic reaction should also produce other warning signs, such as:
* Pulse pressure is the difference between the systolic and the diastolic blood pressure values.
People who are elderly, immunocompromised, or neutropenic (have an abnormally low levels of white blood cells) are the most likely to develop a septic response to an infection. Because of our aging population and because medical care is increasing the longevity of immunocompromised patients, the cases of sepsis are increasing in the United States (CDC, 2018b).
The incidence of sepsis increases with age due to increasing comorbidity, exposure to instrumentation, institutionalization, immune-senescence, and malnutrition. The outcome of older patients with sepsis is worse compared to younger patients and is associated with higher healthcare costs (Warmerdam et al., 2017).
Septic patients often have a fever, sometimes with chills and sometimes with an abrupt onset. However, the majority of septic patients are elderly, and this demographic brings with it a caution about using fever to recognize sepsis. Older adults develop fevers less readily than younger patients, and sepsis in older adults can present without fever, with only a modest fever, or with hypothermia (Jui, 2010).
To improve early sepsis recognition and outcomes in older patients, the quality of emergency department (ED) sepsis care is critically important. Atypical symptom presentation, including delirium, malaise, and functional decline, and the absence of classical symptoms such as fever, tachycardia, and hypoxemia may result in poor sepsis recognition, thus delaying treatment. As a result, older patients may present to the ED with more acute potentially reversible sepsis-related organ dysfunction, especially because older patients have a higher risk for deterioration due to less physiological reserve (Warmerdam et al., 2017).
Poor sepsis recognition may also affect the quality of care of older patients in the ED, which has a large impact on mortality. In a recent study, implementing a Surviving Sepsis Campaign–based quality improvement program, in patients who were hospitalized with a suspected infection, full compliance with recommended quality performance measures was associated with a large reduction of in-hospital mortality. Unfortunately, full bundle compliance* was achieved in only approximately 40% of the patients. Previous studies suggest that this may be even worse in older patients, due to the aforementioned poor sepsis recognition (Warmerdam et al., 2017).
*Bundle: A bundle is a selected set of elements of care that, when implemented as a group, have an effect on outcomes beyond implementing the individual elements alone. Each hospital's sepsis protocol may be customized, but it must meet the standards created by the hour-1 bundle. Enhancing reliability of the hour-1 bundle allows teams to focus on aspects of the changes they are implementing. The aim is to create a reliable system that reduces the odds for both death and morbidity from sepsis (Surviving Sepsis Campaign, 2018).
Sepsis is one of the leading causes of mortality among children worldwide. It is a life-threatening condition that affects many children regardless of underlying healthcare issues. Although demographic data does not clearly show it, many children who are reported to die from other underlying conditions actually die directly from sepsis (Kawasaki, 2017).
The management of pediatric sepsis was comprehensively advocated through systematic review process in the Surviving Sepsis Campaign guidelines (SSCG) 2008 and 2012. Unfortunately, many recommendations and suggestions were still based on low-quality evidence and expert consensus, and sometimes only on evidence in adult sepsis. Furthermore, the latest version of SSCG did not include a specific description of the management of pediatric sepsis (Kawasaki, 2017).
Consensus guidelines emphasize basic principles of goal-directed resuscitation, prompt antimicrobial administration, and supportive care of organ dysfunction in pediatric sepsis. However, few large clinical trials have addressed the management of critically ill children with severe sepsis. Consequently, debate remains about the optimal approach to both basic and adjuvant therapies. For example, vasoactive strategies, immune stimulation, and plasma exchange would all benefit from further evaluation in rigorous pediatric trials (Weiss et al., 2015).
Signs and symptoms of neonatal sepsis include:
Signs of sepsis in children include:
Severe sepsis can develop if sepsis continues, leading to organ hypoxia and organ failure. Severe sepsis increases the likelihood that the patient will die. When the organ system that fails is the circulatory system, the arterial wall muscles can no longer contract sufficiently to maintain adequate blood pressure. Now the patient is in septic shock, and the chance of surviving declines further (Shapiro et al., 2010).
Severe sepsis and septic shock are unfortunately common, complicated and deadly conditions within the same pathophysiologic spectrum. If a clinician believes that a patient is exhibiting SIRS secondary to infection, that patient has sepsis. If that same patient has signs or symptoms of organ dysfunction, then that patient has severe sepsis. Septic shock is then characterized by overall tissue hypoperfusion, tissue hypoxia, or general hypotension that fails to respond to fluid resuscitation (Tannehill, 2012).
Severe Sepsis (Sepsis Syndrome)
Severe sepsis, or sepsis syndrome, is present when the patient has progressed to a stage in which one or more organs or organ systems begin to fail. The Surviving Sepsis Campaign no longer uses the term severe sepsis but simply sepsis.
Sepsis is considered severe when a patient has one of the following clinical problems:
Septic shock is acute circulatory failure with refractory (difficult to reverse) hypotension that is unexplainable by other causes. The term shock describes a condition in which many tissues throughout the body become hypoxic due to poor perfusion. In shock, normal homeostatic mechanisms are either not functioning or not adequate to deliver enough oxygen to tissues. If it is not reversed, shock leads to organ failure and death. Septic shock is a form of distributive shock. In septic shock, there is hypotension and vasodilation that cannot be reversed by giving adequate fluids. When the hypotension of septic shock does not respond to vasopressors, the condition is called refractory septic shock (Munford & Suffredini, 2009).
Septic shock presents with hypotension, oliguria, abnormal mental status (restlessness, confusion, lethargy, or coma), and metabolic acidosis due to an increased concentration of lactate in the blood. When the shock is septic, it can also present with tachycardia, tachypnea, fever, and a high white blood cell count (Gaieski, 2013). A key sign in sepsis is hypotension that cannot be reversed with fluids alone.
The hypotension of shock may be absolute, with a systolic blood pressure <90 mm Hg. Alternately, the hypotension of shock may be relative and take the form of a drop in systolic blood pressure >40 mm Hg; in this situation, hypertensive people can be in shock although their presenting blood pressures are within the normal range. When a person is in shock, vasopressors are frequently needed to maintain adequate perfusion of tissues.
For a patient in shock, diagnostic tests, a physical examination, and a medical history should not delay procedures that will stabilize the patient’s circulation and respiration. Instead, data should be collected while the patient is being resuscitated. It is important to know the patient’s blood and serum chemistry values, so resuscitators need to draw blood samples.
Initial tests include a complete blood count with a differential, basic blood chemistries, liver function tests, coagulation studies, cardiac enzymes, blood gases, lactate levels, blood type with cross match, and toxicology screening (Shapiro et al., 2010). Two sets of blood cultures should be drawn with the initial labs and prior to administration of antibiotics.
Did You Know . . .
To optimize a patient’s chance of survival, sepsis must be treated rapidly and efficiently. Every hour of delay in treatment reduces the average patient’s survival by 8%.
The initial step in the treatment of sepsis is to stop the infection, protect the vital organs, and prevent a drop in blood pressure. International clinical practice guidelines and the Centers for Medicare and Medicaid Services (CMS) recommend the prompt identification of sepsis and treatment with broad-spectrum antibiotic agents and intravenous fluids (Seymour et al., 2017).
More seriously affected patients might need a breathing tube, kidney dialysis, or surgery to remove an infection. Despite years of research, scientists have not yet developed a medicine that specifically targets the aggressive immune response seen with sepsis (NIGMS, 2018). Prompt diagnosis and treatment are critical for optimal outcomes; there is increased morbidity/mortality with delayed recognition and response.
New York Codes, Rules, and Regulations parts 405.2 and 405.4 require all sepsis protocols to include receipt of the following care within 3 hours:
Protocols also require a 6-hour bundle, consisting of:
Diagnostic modalities include blood cultures and other testing to identify source and site or infection and organ dysfunction. Treatment includes administration of appropriate IV antimicrobial therapy, with source identification and de-escalation of antibiotics as soon as feasible. These recommendations are supported by preclinical and observational studies suggesting that early treatment with antibiotics and intravenous fluids could reduce the number of avoidable deaths (Seymour et al., 2017).
Healthcare providers can help patients and family members protect themselves against sepsis by teaching the signs and symptoms of sepsis and the importance of prompt and early treatment.
Sepsis is a medical emergency. A person with sepsis should look ill and should seek immediate care for worsening infection and signs and symptoms. Time matters. Call your doctor or go to the emergency department immediately if you suspect sepsis.
Infection prevention is a critical part of preventing sepsis. This includes proper hand hygiene, wound care, and vaccination. Be aware that children and older adults, as well as immunocompromised people and those with chronic illnesses, are at higher risk for contracting sepsis than the general population.
Warning signs and symptoms of sepsis include:
Talk to your doctor or nurse about steps you can take to prevent infections. Some steps include taking good care of chronic conditions and getting recommended vaccines.
Always remember, sepsis is a medical emergency. Time matters. Giving relevant history and information to healthcare providers can help with early identification and treatment of sepsis, leading to improved outcomes.
The Need for Sepsis Awareness: Dana’s Story
In December 2011, a lack of awareness of sepsis—a disease responsible for more American deaths each year than breast cancer, prostate cancer, and AIDS combined—nearly cost me my life. It began with a little bump on my shoulder one afternoon. I did not know that within 24 hours that small bump would develop into life-threatening septic shock and soon I would find myself in the ICU.
The seemingly insignificant little bump became swollen and I developed symptoms that felt like the worst flu of my life. When my husband discovered my temperature was over 104 degrees, he rushed me to the emergency room, just on a hunch that this was not an ordinary flu.
He had never heard of sepsis, and I had heard the word, but thought it was a rare, largely obsolete disease. I had no idea of the symptoms and certainly no idea it could be happening to me. When I arrived at the hospital, I was the sickest I had ever been in my life. My temperature was soaring, my blood pressure was falling, and my arm was in excruciating pain. I soon learned the bump on my arm actually was a skin infection, which had led to cellulitis.
The doctors acted quickly and I was soon admitted to the ICU, where I vacillated between life and death. I was cognizant enough to worry whether I would make it out of the hospital and home again to my two small children, and if so, whether all my limbs would be coming home with me.
After several terrifying, agonizing days, I began to recover, transitioning first out of the ICU and then out of the hospital. I went home to begin what would be a deceptively arduous recovery. Having survived and avoided severe complications like amputations, I expected my recovery would be swift, but it was not. Weeks turned to months, even years, before I began to feel like “myself” again. I did not know then that post-sepsis or post-ICU syndrome exists and can affect many sepsis and ICU patients. Today, nearly three years later, I have much of my strength back, although some of the physical and (of course) the emotional impacts still linger.
As difficult as my recovery was, I am lucky to be alive. I am lucky that the doctors and nurses at my hospital were aware of sepsis. They saved my life. Others—who either do not make the fortunate decision to seek emergency medical care, or whose symptoms are overlooked or misdiagnosed—are not as lucky.
But surviving sepsis should not be a matter of luck. The public and medical professionals alike must be aware of sepsis. We must know the name of this deadly disease, and we must know the symptoms. By being aware and suspecting sepsis, we will be able to save more lives—which just might be our own, or those of our loved ones. The CDC’s efforts to increase sepsis awareness and improve treatment will result in fewer lives lost to this sudden, swift and often-fatal disease.
Source: CDC Safe Healthcare Blog September 11, 2014.