Intervening in Sepsis: Can Nurses Do More?

Updated guidelines may help nurses identify sepsis quicker and treat it more efficiently

Consider a scenario that is all too familiar: You arrive for your regular shift in the medical intensive care unit (MICU). One of your patients is a previously healthy, 45-year-old female who is a mother of two. She came to the hospital via the emergency room the previous morning, with a high fever, low blood pressure, low urine output and back pain. The patient was found to have a kidney stone on a CT scan and was started on antibiotics and given intravenous fluids.

Unfortunately, her condition has deteriorated and she now requires intubation, placement on a ventilator and transfer to the MICU. You begin to suspect that she may have sepsis or even more devastating, septic shock. Characteristics of patients with sepsis vary and may include a fever, increased heart rate, rapid breathing, altered mental status, as well as other metabolic abnormalities and organ dysfunctions. Unless quickly identified and treated, her condition will continue to deteriorate.

Avoiding the Sepsis Cascade
Sepsis can have several causes, such as bacterial, viral or fungal infection, and may be an important complication of major trauma, burns, cancer or major surgical procedures. More recently, it has been reported that in some patients, elevated levels of endotoxin in the blood (a condition known as endotoxemia) may act as an initiator of the “sepsis cascade”-the physiological chain of events that can eventually lead to organ failure and death in a septic patient. It is estimated that as many as 50% of patients in septic shock have high levels of endotoxin.2

The mortality for septic shock with organ failure can be 50% or higher.3 In fact, each year approximately 350,000 patients develop septic shock and subsequent multi-organ dysfunction, leading to about 200,000 deaths. That classifies sepsis and its most severe form, septic shock, as the leading killer of patients in U.S. hospitals.

In an ideal scenario, sepsis should be diagnosed and treated as early as possible; but unfortunately, treatment and support options may or may not be effective. Patients presenting with sepsis or septic shock vary in many ways, including age, underlying disease, microbial etiology, and genetic makeup. Thus, devising new therapies for sepsis and septic shock has been difficult.4

2012 Guidelines Were Disappointing
In 2012, a consensus committee of 68 international experts representing 30 international organizations was convened to provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock.” Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting the general care of critically ill patients (who are considered high priority in severe sepsis); and 3) pediatric considerations.

Each of the 23 recommendations was based on a comprehensive literature review and grading of the quality of evidence. They included management details and treatment targets for the initial resuscitation, antimicrobial and vasopressor choices, fluid therapy, nutrition and others. However, even with the guidelines, current management of septic patients is non-specific and relies on a range of interventions. Early, aggressive treatment boosts the odds of surviving sepsis, as patients can deteriorate quickly in a matter of hours.

A study published in Critical Care Medicine, titled “The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis,” reported a mortality decrease of only 5.4% after two years’ of implementation of the “Surviving Sepsis Campaign Guidelines.”5

Thus, outcomes for patients with sepsis remain unacceptably poor, especially when compared to outcomes such as mortality for patients with heart disease and even many forms of cancer. Whereas the 2012 guidelines focus on early recognition and early intervention with intravenous fluids, vasopressors, oxygen, ventilation, nutritional support and corticosteroid therapy, there remains a significant gap in care for patients that do not respond to these interventions. There is no therapy approved by the FDA that is targeted to specifically treat sepsis.

Improved, targeted therapies for sepsis and septic shock are clearly needed. The incidence of sepsis has increased during the past 3 decades, as has its economic burden.6 In addition, the essential elements of treatment for sepsis have not changed in over 50 years.6

Clinical development of treatments for sepsis and septic shock are complicated by the condition’s various causes. Novel therapies, which have made it into clinical trials over the past 40 years but have failed to improve outcomes, include various anti-inflammatory strategies (such as anti-TNF immunoglobulins and anti-endotoxin strategies), organ support and recovery strategies (such as blood pressure control with vasopressors), and other therapies such as corticosteroids and anticoagulants.

Enter Sepsis-3 & The EAA
In March 2016, the Society for Critical Care Medicine unveiled a new definition for sepsis and septic shock aimed at helping practitioners identify the condition.1 The Sepsis-3 definition is this: “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” Septic shock is a subset of sepsis, in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.

The idea of targeting endotoxemia in sepsis has been around for over 30 years. Prior clinical research has demonstrated that higher endotoxin levels correlate with an increased risk for developing sepsis and a higher risk of mortality as well as.2 However, several promising drugs that were designed to reduce endotoxin in the blood failed to show efficacy. A new and exciting approach, using the concept of cleansing the blood of dangerous pathogens (called “blood purification”), is gaining ground.

Another novel treatment is comprised of an in-vitro diagnostic test followed by a targeted therapy (delivered via a medical device) to remove endotoxin from the blood. This might be poised to enter the marketplace as early as 2017.7 This therapy is specifically targeted at patients in septic shock with elevated levels of endotoxin in the blood.8 The diagnostic, called the Endotoxin Activity Assay (EAA), is FDA-cleared and CE marked (the European “proof-of-safety” mark) for the detection of endotoxemia. The EAA is highly sensitive and specific, providing results within 30 minutes.

Once septic shock patients are identified as being endotoxemic, they are treated with Toraymyxin, an adsorption column that functions in a veno-venous hemoperfusion mode similar to traditional dialysis. The active ingredient is the antibiotic Polymyxin B, which binds endotoxin and removes it from the bloodstream. The polymyxin B is chemically bonded to fibers in the cartridge; and, as blood passes through it, any endotoxin present is highly attracted to binding sites of polymyxin B, which effectively pulls the endotoxin out of the bloodstream and keeps it tightly bound to the cartridge.

This device is currently approved in 18 countries, including many in Europe and Asia, and has been tested in more than 90 published studies involving more than 7,000 patients.

Other New Developments on the Horizon
There are other products in development that follow a similar approach of blood purification, which may be applicable in the treatment of sepsis.

One such system, which is in the early stages of clinical testing, is designed to reduce excessive levels of inflammatory mediators (such as cytokines) from the blood. The goal for this type of treatment is to reduce the systemic inflammatory response syndrome (SIRS) that is seen in life-threatening inflammatory conditions. Use of this therapy may help to mitigate or even avoid deadly complications such as organ failure and avoid cell-mediated injury to otherwise healthy organs.  However, no major studies have evaluated the impact of this treatment on risk of death.

Returning to our patient in the MICU, we now know that despite great strides being made with respect to early intervention in sepsis, her odds of survival are not optimal. Therefore, to address the question in this article’s headline: yes, we can do more!

In your role as a nurse, being proactive on behalf of your patients may include helping your institution stay up-to-date on the new protocols and treatment options that may hold promise for septic patients. An application to the FDA to allow use of Toraymyxin is expected to be filed before the end of 2017.

Until then, the FDA has accepted a protocol for expanded access to the device; it is available for use on eligible patients at 15 U.S. hospitals that participated in a Phase III clinical trial. A similar program is planned for Canada, where there are 12 hospitals engaged in the clinical trial. If available, you can prompt your team to order an EAA test to evaluate whether or not your patient has endotoxemia. All nurses must “stay tuned” if they want to make a difference in the lives of their septic patients. 


  1. Singer M, Deutchman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810.
  2. Marshall JC, Foster DM, et al. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis. 2004;190(3):527-534.
  3. Martin GS. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther. 2012;10(6):701-706.
  4. Marshall JC. Sepsis: rethinking the approach to clinical research. J Leukoc Biol. 2008;83(3):471-482.
  5. Levy MM, Dellinger RPD, et al. Surviving sepsis campaign: the results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Medicine. 2010;36:222-231.
  6. Munford RS. Novel therapies for septic shock over the past 4 decades. JAMA. 2011;306(2):194-199.
  7. Klein DJ, Foster DM. The EUPHRATES trial. Trials. 2014;15:218.
  8. Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Septic Shock (EUPHRATES). Identifier NCT01046669.

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