Inflammation, Obstetrics, Sepsis, Septic shock



  1. Parfitt, Sheryl E. MSN, RNC-OB
  2. Bogat, Mary L. MSN, RNC-OB
  3. Hering, Sandra L. MSN, RNC-OB, CPHIMS
  4. Roth, Cheryl PhD, WHNP-BC, RNC-OB, RNFA


Abstract: In spite of many medical breakthroughs, sepsis continues to be challenging to identify, treat, and successfully resolve, including among the obstetric population. Sepsis is the result of an overactive, complex inflammatory response that is not completely understood. Currently there are no nationally agreed-upon criteria for systemic inflammatory response syndrome or sepsis in pregnant or peripartum women, as the physiologic changes of pregnancy have not been taken into consideration.


This article is the first in a series of three that discuss the importance of sepsis and septic shock in pregnancy. The focus of this article is to understand the proposed pathophysiology of sepsis and new definitions associated with sepsis and septic shock. Knowledge of these conditions can assist in better identification of sepsis in the obstetric population.


Article Content

Sepsis is not a new concept in healthcare. The term sepsis originated from the Greek word , which means "I rot." In 400 BC, Hippocrates noted that sepsis caused decay in the body. He was one of the first individuals to experiment using wine and vinegar to treat the condition (Funk, Parrillo, & Kumar, 2009).

Figure. Inaz Semmelw... - Click to enlarge in new windowFigure. Inaz Semmelweis

At the beginning of the 19th century, it was not unusual for women to die after developing a fever during the postpartum period. Inaz Semmelweis, a practicing obstetrician in Vienna, Austria, realized there was a correlation between hygiene and infection when a friend died from a wound obtained during an autopsy. He observed medical students coming directly from performing autopsies on postmortem mothers to clinics where they examined pregnant women without washing their hands or wearing surgical gloves. This breakthrough observation led to the introduction of handwashing before each examination and a decrease in maternal mortality to less than 3% in the maternity ward where he worked. In spite of this knowledge, Semmelweis was met with resistance from the medical community and was fired from his position, eventually dying from sepsis, a disease he had spent his lifetime studying (Funk et al., 2009).


In spite of many breakthroughs, sepsis continues to challenge the medical community. According to the Centers for Disease Control and Prevention (CDC, 2014), approximately 258,000 Americans die from sepsis each year, and thousands who survive are left with life-altering effects. Between 2011 and 2012, 12.7% of pregnancy-related deaths were attributed to some type of infection or sepsis (CDC, 2016). Sepsis is the fourth leading cause of maternal mortality in the United States and results in approximately 5% of all maternal admissions to the intensive care unit (ICU) (Albright, Ali, Lopes, Rouse, & Anderson, 2014). The purpose of this article is to promote understanding of the pathophysiology of sepsis and updated definitions associated with sepsis and septic shock.


Pathophysiology of Sepsis

Sepsis is a complex disease process that is not completely understood. It does not develop on its own but stems from some type of infectious process that goes awry. It can be caused by bacteria, fungi, or viruses. No one is immune to sepsis, although individuals with chronic illnesses, weakened immune systems, young children, and the elderly appear to be more susceptible (National Institute of General Medicine, 2014). Pregnancy is thought to be an immune-compromised state, potentially increasing vulnerability to infections that can cause sepsis (Chebbo, Tan, Kassis, Tamura, & Carlson, 2016).


Most infections do not cause sepsis. In a normal inflammatory response to an invasive microbe or injury, the body builds a wall around the affected area and prevents it from spreading systemically (Figure 1). Vasodilation occurs allowing increased circulation of immune cells, which congregate together to fight the infection. The complement system is triggered and sends out proteins that act like a corral around the foreign pathogen. Local activation of the blood coagulation system results, causing fibrin clots to be created and deposited in the area blocking further spread of the bacteria or toxin. Deactivators are produced which together with a healthy anti-inflammatory response system, inhibit the immune reaction from occurring throughout the body (Hall, 2015).

Figure 1 - Click to enlarge in new windowFIGURE 1. Normal Inflammatory Process

Sepsis is the result of an overactive, complex inflammatory reaction. Instead of remaining localized, products of the inflammatory response get swept into the circulation and cause major problems throughout the body (Figure 2). The immune system overproduces inflammatory cytokines, nitric oxide, and other mediators leading to further vasodilation and severe hypotension. These factors also play a role in the destruction of the endothelial walls of the vessels, which in turn increases capillary permeability. Capillaries, where much of the exchange of oxygen and carbon dioxide occurs, contain only one thin layer of endothelial cells and occasional connective tissue. With destruction of the endothelial lining, fluid leaks into the extravascular spaces in the lungs, brain, abdomen, heart, and skin. Shifts of fluid from inside the vessel to outside lead to decreased intravascular volume. Patients who are septic may appear edematous, even though they are actually intravascularly dry. This leads to hypotension, hemoconcentration, and edema, which profoundly affect oxygenation of the tissues and organs (Hall, 2015; Pacheco, Saade, & Hankins, 2014).

Figure 2 - Click to enlarge in new windowFIGURE 2. Abnormal Inflammatory Process

Many patients with sepsis display alterations in cardiac function. Both systolic and diastolic changes can occur with a drop in the mean arterial pressure (MAP). It has been reported that an ejection fraction of less than 45% (normal >55%) may be present in 60% of patients with a diagnosis of sepsis during the first 7 to 10 days of the disease process (Funk et al., 2009; Pacheco et al., 2014).


In severe cases of sepsis, the clotting cascade is abnormally activated leading to clotting disorders and potential end-organ damage and death. Under normal circumstances, Protein C assists in inhibiting some of the clotting factors while promoting the breakdown of clots. It also displays anti-inflammatory mechanisms that assist in keeping the inflammatory response in check. When sepsis occurs, the exaggerated inflammatory response decreases activation of Protein C leading to inflammation and clotting abnormalities. The extrinsic pathway of the clotting cascade is also activated leading to development of disseminated intravascular coagulation, which causes further organ damage. Finally, sepsis causes a change in mitochondria function so that cells are unable to extract oxygen and use it for cellular metabolism, even with normal hemoglobin saturation levels (Pacheco et al., 2014). Unless the destructive process of sepsis is stopped, it eventually leads to end-organ damage and death.



A search of the literature presented evolving criteria when defining sepsis. The concept of Systemic Inflammatory Response Syndrome (SIRS) was first introduced by The American College of Chest Physicians and the Society of Critical Care Medicine (SCCM) in 1992 (Pacheco et al., 2014). Criteria for this diagnosis included abnormal measurements of temperature, heart rate, respiratory rate, and white blood cell count only, and did not take into consideration physiologic changes that occur in pregnant women. Sepsis was characteristically defined as presence of an infection with at least two SIRS criteria present, becoming life-threatening in the presence of end-organ dysfunction. Patients experiencing severe hypotension in spite of adequate fluid resuscitation and requiring use of vasopressors were diagnosed with septic shock (Pacheco et al.).


The Surviving Sepsis Campaign (SSC) is a consensus committee of international experts from 30 international organizations. They first met in 2004 to set definitions and guidelines for practitioners treating sepsis (Dellinger et al., 2004). Their criteria for diagnosis and treatment of sepsis were revised in 2008, 2012, and then again in 2016 (Dellinger et al., 2008; 2013; Howell & Davis, 2017; Rhodes et al., 2017). In 2012, sepsis was defined as the presence of an infection with signs of systemic involvement, adding hyperglycemia and altered mental status to the original set:


The 2012 definitions for severe sepsis and septic shock remained the same as that presented in 1992 (Dellinger et al., 2013).

Table No caption ava... - Click to enlarge in new windowTable No caption available.

In 2015, a task force of 19 leading sepsis experts was recruited by the SCCM and the European Society of Intensive Care Medicine to update sepsis definitions. They defined sepsis as an infection with life-threatening organ dysfunction. The term severe sepsis was discarded because sepsis itself is a potentially severe condition leading to a death rate of approximately 10% or higher (SCCM, 2016). Septic shock was defined as a subcategory of sepsis with hypotension that does not respond to fluid boluses, requirement for vasopressors to sustain a MAP of at least 65 mmHg, and a serum lactate level greater than 2 millimoles per liter (mmol/L) (Abraham, 2016). This new standard eliminates the use of SIRS criteria in exchange for a new diagnostic tool called the quick Sequential Organ Failure Assessment (qSOFA), a tool used in ICU units to assess mortality predictions. The tool consists of three criteria seen in patients diagnosed with an infection:


* An alteration in mental status


* A decrease in systolic blood pressure of less than 100 mmHg


* Respiration rate greater than 22 breaths per minute



Patients displaying two or more of these conditions have a significantly higher risk of a prolonged stay in the ICU or to die in the hospital (Antonelli et al., 2016; SCCM, 2016).

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

In 2016, a panel of 55 international experts representing 25 international organizations joined to develop updated guidelines for the SSC (Rhodes et al., 2017). They defined sepsis as "life-threatening organ dysfunction caused by a dysregulated host response to infection" (Rhodes et al., p. 3). The panel also defined septic shock as a "subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality" (Rhodes et al., p. 4). They recommend that hospitals and hospital systems have in place a performance improvement program for sepsis that includes sepsis screening for acutely ill, high-risk patients. Further recommendations for treatment are included in the 2016 guidelines (Rhodes et al.). These recommendations are for the general population and do not address pregnancy or the postpartum period.


Currently there are no nationally agreed-upon criteria for SIRS or sepsis in pregnant or peripartum patients, as the physiologic changes of pregnancy have not been taken into consideration (Albright et al., 2014). Furthermore, there are no published studies comparing the incidence of sepsis in the obstetric population to sepsis in the general population. But progress is being made in the development of several modified obstetric early warning scoring systems that will assist obstetric personnel in early identification of patients with suspected clinical deterioration in the most common areas of maternal mortality, including sepsis (Albright et al.; Edwards et al., 2015; Shields, Wiesner, Klein, Pelletreau, & Hedriana, 2016).



Sepsis is a complex disease process that remains a major cause of maternal mortality in the United States (Albright et al., 2014). The SSC has recommended use of the qSOFA tool to assist in screening and management of sepsis. Unfortunately, this tool does not take into consideration the physiologic changes of pregnancy, making diagnosis challenging for obstetric patients. Continued study of the physiologic process of sepsis and its impact in pregnancy, as well as development of obstetric-related sepsis identification tools may lead to better patient outcomes.


Suggested Clinical Nursing Implications


* Perinatal infections have the potential to lead to sepsis and septic shock.


* Patients with sepsis may display alterations in major organ systems, such as the heart, kidneys, brain, and clotting system (Pacheco et al., 2014).


* Common findings of patients with sepsis include decreased MAP, ejection fraction <45%, clotting abnormalities, high or low temperatures (>38[degrees] C or <36[degrees] C), tachycardia, tachypnea, and mental status changes (Funk et al., 2009; Pacheco et al., 2014).


* Consider that hypotension, hemoconcentration, and edema may mean that the woman with sepsis is intravascularly dry and needs immediate hydration therapy (Hall, 2015; Pacheco et al., 2014).


* Currently there are no nationally agreed-upon criteria for diagnosis of sepsis in pregnancy or peripartum patients. Attention to vital sign trends and abnormalities can assist nurses in prompt recognition and treatment of this condition (Albright et al., 2014).




Abraham E. (2016). New definitions for sepsis and septic shock: Continuing evolution but with much still to be done. Journal of the American Medical Association, 315(8), 757-759. doi:10.1001/jama.2016.0290 [Context Link]


Albright C. M., Ali T. N., Lopes V., Rouse D. J., Anderson B. L. (2014). The Sepsis in Obstetrics Score: A model to identify risk of morbidity from sepsis in pregnancy. American Journal of Obstetrics & Gynecology, 211(1), 39.e1-39.e8. [Context Link]


Antonelli M., DeBacker D., Dorman T., Kleinpell R., Levy M., Rhodes A. (2016). Surviving sepsis campaign responds to Sepsis-3. Retrieved from [Context Link]


Centers for Disease Control and Prevention. (2014, May 22). Sepsis-Data Reports. Retrieved from[Context Link]


Centers for Disease Control and Prevention. (2016, January 21). Pregnancy Mortality Surveillance System. Retrieved from [Context Link]


Chebbo A., Tan S., Kassis C., Tamura L., Carlson R. W. (2016). Maternal sepsis and septic shock. Critical Care Clinics, 32(1), 119-135. [Context Link]


Dellinger R. P., Carlet J. M., Masur H., Gerlach H., Calandra T., Cohen J., ..., Levy M. M. (2004). Surviving Sepsis Campaign Management Guidelines Committee. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Critical Care Medicine, 32(3), 858-873. [Context Link]


Dellinger R. P., Levy M. M., Carlet J. M., Bion J., Parker M. M., Jaeschke R., ..., Vincent J. L. (2008). International Surviving Sepsis Campaign Guidelines Committee. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Critical Care Medicine, 36(1), 296-327. doi:10.1097/01.CCM.0000298158.12101.41 [Context Link]


Dellinger R. P., Levy M. M., Rhodes A., Annane D., Gerlach H., Opal S. M., ..., Moreno R. (2013). Surviving Sepsis Campaign Guidelines Committee. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine, 41(2), 580-637. doi:10.1097/CCM.0b013e31827e83af [Context Link]


Edwards S. E., Grobman W. A., Lappen J. R., Winter C., Fox R., Lenguerrand E., Draycott T. (2015). Modified obstetric early warning scoring systems (MOEWS): Validating the diagnostic performance for severe sepsis in women with chorioamnionitis. American Journal of Obstetrics and Gynecology, 212(4), 536.e1-536.e8. doi: [Context Link]


Funk D. J., Parrillo J. E., Kumar A. (2009). Sepsis and septic shock: A history. Critical Care Clinics, 25(1), 83-101. doi:10.1016/j.ccc.2008.12.003 [Context Link]


Hall J. (2015). Guyton and Hall textbook of medical physiology (13th ed.). Philadelphia, PA: Elsevier. [Context Link]


Howell M. D., Davis A. M. (2017). Management of sepsis and septic shock. Journal of the American Medical Association, 317(8), 847-848. doi:10.1001/jama.2017.0131 [Context Link]


National Institute of General Medicine. (2014). Sepsis fact sheet. Retrieved from [Context Link]


Pacheco L. D., Saade G. R., Hankins G. D. (2014). Severe sepsis during pregnancy. Clinical Obstetrics and Gynecology, 57(4), 827-834. doi:10.1097/GRF.0000000000000066 [Context Link]


Rhodes A., Evans L. E, Alhazzani W., Levy M. M., Antonelli M., Ferrer R., ..., Dellinger R. P. (2017). Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Critical Care Medicine, 45(3), e1-67. doi:10.1097/CCM.0000000000002255 [Context Link]


Shields L. E., Wiesner S., Klein C., Pelletreau B., Hedriana H. L. (2016). Use of maternal early warning trigger tool reduces maternal morbidity. American Journal of Obstetrics and Gynecology, 214(4), 527.e1-527.e6. doi:10.1016/j.ajog.2016.01.154 [Context Link]


Society of Critical Care Medicine. (2016). Sepsis definitions. Retrieved from [Context Link]