Innovations in Sepsis Therapy

By Anne Dabrow Woods, DNP, RN, CRNP, ANP-BC, AGACNP-BC, FAAN, Chief Nurse of Health, Learning, Research and Practice, Wolters Kluwer
Twitter: @wkhealth

Sepsis is one of the leading causes of hospital mortality, present in more than half of the hospital deaths in the U.S. It is also one of the costliest diagnoses in the U.S. with a healthcare spend of over $20 billion dollars annually (Rhee, et al., 2017).

Because of these staggering facts, its not at all unthinkable that researchers are searching for innovative ways to fight this diagnosis and prevent deaths to improve patient outcomes and decrease the cost burden to the American healthcare system. Several therapies have the potential to assist healthcare professionals with fighting sepsis: Extracorporeal Membrane Oxygenation (ECMO).

In patients with sepsis, who also have comorbid left ventricular failure or cardiomyopathy, inotropic agents such as dobutamine and dopamine have been used to improve myocardial function. In some cases, these standard therapies have been proven insufficient and resulting in the deaths of patients due to them having septic shock with LV failure.

Falk, Hultman and Broman studied the use of extracorporeal membrane oxygenation in sepsis patients. In their study of 37 patients, 27 of them were placed on venoarterial ECMO and 10 were placed on veno-venous ECMO. The patients were then divided into two groups, patients with septic shock plus left ventricular failure, and patients with just septic shock. Ninety percent of the septic shock plus LV failure patients survived after receiving veno-arterial ECMO. However, the group who just had septic shock and were placed on veno-venous ECMO, 64.7% survived (Falk, Hultman, & Broman, 2019).

Although this study had a small sample size, the results indicate the growing evidence for using veno-arterial ECMO for those with septic shock cardiomyopathy as a way to improve outcomes. Further research in this area would be beneficial.

Elevating the pressure with synthetic angiotensin II
Angiotensin II is one of the most powerful vasoconstrictors in the body. When a patient is in distributive shock, treatment has been centered around catecholamine-based vasopressors such as norepinephrine, epinephrine, and phenylephrine to cause vasoconstriction and increase blood pressure. In 2017, the Food and Drug Administration approved Giapreza, a synthetic angiotensin II agent as an adjuvant treatment for distributive shock.

In the angiotensin for the Treatment of High Output Shock Study, also called ATHOS, 344 patients were reviewed. One hundred sixty-three patients received synthetic angiotensin II, in addition to their catecholamine-based vasopressors, and 158 patients received placebo, in addition to catecholamine-based vasopressors. The patients who received synthetic angiotensin II as an adjuvant to standard catecholamine vasopressor therapy achieved a higher target mean arterial pressure over the control group. In addition, the intervention group was also able to lower their catecholamine vasopressor requirement faster than the control group. There were several safety issues that were associated with the study; increased risk of thromboembolic events, infection and delirium (Khanna, et al., 2017).

This study demonstrates the efficacy of synthetic angiotensin II as an adjuvant agent to standard therapy. And in distributive shock, having another agent to utilize is encouraging. As with any medication however, the healthcare provider must consider the risk/benefit ratio of initiating treatment with this new medication.

HAT therapy: an opportunity to use low cost interventions to make a big impact
Sepsis is one of the most expensive diagnoses healthcare professionals see in the acute care setting. Researchers have looked closely to determine if there is a low-cost alternative to managing the current process. In 2016, Marik, Khangoora, Rivera, Hooper, and Catravas published a retrospective study on the use of hydrocortisone, ascorbic acid and thiamine (HAT) for the treatment of sepsis. The study consisted of 47 patients in the control group and 47 patients in the intervention group. The control group had a 40.4% in hospital mortality rate while the intervention group only had an 8.5% in hospital mortality rate (Marik, et al., 2016).

Today the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) clinical trial is taking place to determine if the use of 3 low-cost agents, used together, can demonstrate a notable benefit in a larger investigative group. The Universities and health systems currently involved in this study include: Johns Hopkins, Emory, Vanderbilt, Virginia Commonwealth University, Eastern Virginia Medical School, Grady Memorial, Sentara Health and Thomas Jefferson University and Hospital.

If the use of HAT therapy is proven to be effective in decreasing hospital mortality, the results will be far reaching since hospitals in developing nations will also be able to take advantage of these results.

The impact of sepsis and septic shock on the nation and around the globe are staggering. Innovation from researchers and healthcare professionals looking at alternative ways to treat sepsis and septic shock will lead to a better understanding of these conditions and improve practice and patient outcomes. The use of ECMO in the right patient population, adjuvant use of synthetic angiotensin II with standard therapy, and HAT therapy are just a few of the leading innovations in distributive shock research.