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.
Key Words: Inflammation; Obstetrics; Sepsis; Septic shock.

Sepsis in Obstetrics
PATHOPHYSIOLOGY and
DIAGNOSTIC DEFINITIONS
Sheryl E. Parfitt, MSN, RNC-OB, Mary L. Bogat, MSN, RNC-OB, Sandra L. Hering, MSN, RNC-OB, CPHIMS,
and Cheryl Roth, PhD, WHNP-BC, RNC-OB, RNFA

epsis is not a new concept in healthcare. The term sepsis originated from the

S
Greek word sepo, which means “I rot.” In 400 BC, Hippocrates noted that
sepsis caused decay in the body. He was one of the first individuals to experi-
ment using wine and vinegar to treat the condition (Funk, Parrillo, & Kumar,
2009).
At the beginning of the 19th century, it was not unusual for women to die
after developing a fever during the postpartum period. Inaz Semmel-
weis, a practicing obstetrician in Vienna, Austria, realized there was a
Sepsis is a correlation between hygiene and infection when a friend died from a
wound obtained during an autopsy. He observed medical students com-
complex disease ing directly from performing autopsies on postmortem mothers to clin-
process that is ics where they examined pregnant women without washing their hands
or wearing surgical gloves. This breakthrough observation led to the
not completely introduction of handwashing before each examination and a decrease in
understood. 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), approxi-
mately 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

194 volume 42 | number 4 July/August 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

 leading cause of maternal mortality in the United States
and results in approximately 5% of all maternal admis-
sions 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 defini-
tions 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, al-
though individuals with chronic illnesses,
weakened immune systems, young chil-
ary
ibr
dren, and the elderly appear to be more
oL
ot
susceptible (National Institute of General
Ph
e
nc
Medicine, 2014). Pregnancy is thought to be
an immune-compromised state, potentially in-
Inaz Semmelweis
creasing vulnerability to infections that can cause
sepsis (Chebbo, Tan, Kassis, Tamura, & Carlson, 2016).
Most infections do not cause sepsis. In a normal in-
flammatory response to an invasive microbe or injury,
the body builds a wall around the affected area and pre-
vents it from spreading systemically (Figure 1). Vasodila-
tion occurs allowing increased circulation of immune
cells, which congregate together to fight the infection.
The complement system is triggered and sends out pro-
iStock / Wavebreakmedia
July/August 2017
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
teins 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).
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 im-
mune system overproduces inflammatory
cytokines, nitric oxide, and other media-
tors leading to further vasodilation and
severe hypotension. These factors also
play a role in the destruction of the endothe-
e
lial walls of the vessels, which in turn increases
i
Sc
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
In spite of many medical breakthroughs,
sepsis continues to present challenges in
the clinical setting.
MCN 195
FIGURE 1. Normal Inflammatory Process
Invasive • Vasodilation occurs/inflammatory
organism/ cascade activated
injury • Cytokines and complement
system activated
• Blood coagulation system
activated
Deactivators produced + healthy
anti-inflammatory response
system = inhibition of immune
reaction from occurring through-
out the body
FIGURE 2. Abnormal Inflammatory Process
Invasive • Vasodilation occurs/inflammatory
organism/ cascade activated
injury
• Cytokines and complement
system activated
• Blood coagulation system
activated
• Overproduction of inflammatory
cytokines
• Further vasodilation
• Destruction of vessel walls/fluid
leak into extravascular spaces
• Decreased intravascular
volume/hypotension
• Low level of activated protein C
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).
Many patients with sepsis display alterations in cardi-
ac 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 abnor-
mally activated leading to clotting disorders and potential
end-organ damage and death. Under normal circum-
stances, Protein C assists in inhibiting some of the clot-
ting factors while promoting the breakdown of clots. It
also displays anti-inflammatory mechanisms that assist in
196 volume 42 | number 4
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
keeping the inflammatory response in check. When sepsis
occurs, the exaggerated inflammatory response decreases
activation of Protein C leading to inflammation and clot-
ting abnormalities. The extrinsic pathway of the clotting
cascade is also activated leading to development of dis-
seminated intravascular coagulation, which causes further
organ damage. Finally, sepsis causes a change in mito-
chondria function so that cells are unable to extract
oxygen and use it for cellular metabolism, even with nor-
mal hemoglobin saturation levels (Pacheco et al., 2014).
Unless the destructive process of sepsis is stopped, it
eventually leads to end-organ damage and death.
Definitions
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 mea-
surements of temperature, heart rate, respiratory rate, and
white blood cell count only, and did not take into consid-
eration 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 ade-
quate 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 (Del-
linger 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:
Temperature: >38º Celsius (C) or <36º C
(100.4º Fahrenheit (F) or 96.8º F)
Heart rate >90 beats per minute (bpm)
Respiratory rate >90 breaths per minute
White blood cell count >12,000/millimeters to the third
power (mm³) or <4,000/mm³ or
>10% bands
Hyperglycemia Blood glucose >140 milligrams
per deciliter (mg/dL) in the
absence of diabetes
Altered mental status Confusion, agitation, combative-
ness (Dellinger et al., 2013).
The 2012 definitions for severe sepsis and septic shock
remained the same as that presented in 1992 (Dellinger
et al., 2013).
In 2015, a task force of 19 leading sepsis experts was
recruited by the SCCM and the European Society of In-
tensive Care Medicine to update sepsis definitions. They
July/August 2017
 defined sepsis as an infection with life-threatening organ
dysfunction. The term severe sepsis was discarded be-
cause 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 milli-
moles 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 Or-
gan 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).
In 2016, a panel of 55 interna-
tional experts representing 25 in-
Toxins ternational organizations joined
Microbe Three Ways Microbes to develop updated guidelines for
Damaged
Cause Damage the SSC (Rhodes et al., 2017).
tissue
They defined sepsis as “life-
1 Tissue Damage threatening organ dysfunction
Some microbes may adhere to and invade caused by a dysregulated host
tissue cells. Other microbes may produce
toxins that alter the chemical reactions in response to infection” (Rhodes
Microbe
cells. This results in a disruption in the cells' et al., p. 3). The panel also defined
normal function or causes the cell to die. septic shock as a “subset of sepsis
Redblood cell
Toxins
with circulatory and cellular/
Fibrin
metabolic dysfunction associated
(involved with clotting) with a higher risk of mortality”
Blood vessel (Rhodes et al., p. 4). They recom-
mend that hospitals and hospital
2 Blood Clots (intravascular coagulation) systems have in place a perfor-
Some microbial toxins may cause blood to mance improvement program for
coagulate (clot) in small vessels, forming
blockages. The tissue cells normally sepsis that includes sepsis screen-
supplied by these vessels are deprived of ing for acutely ill, high-risk pa-
blood, resulting in tissue damage. tients. Further recommendations
for treatment are included in the
2016 guidelines (Rhodes et al.).
These recommendations are for
the general population and do not
3 Fluid Leakage from Vessel address pregnancy or the post-
The walls of small blood vessels may be partum period.
damaged by microbial toxins. This leads to
fluid leakage from the vessel into the
Currently there are no nation-
surrounding tissue. The fluid loss results in ally agreed-upon criteria for SIRS
decreases blood pressure, and the heart is or sepsis in pregnant or peripar-
unable to pump an adequate amount of
blood to the vital organs.
tum patients, as the physiologic
changes of pregnancy have not
Damaged vessel wall been taken into consideration (Al-
Microbe bright et al., 2014). Furthermore,
Toxin there are no published studies
comparing the incidence of sepsis
in the obstetric population to sep-
sis in the general population. But
progress is being made in the development of several
Anatomical Chart Company

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
Fluid leakage
(Albright et al.; Edwards et al., 2015; Shields, Wiesner,
Klein, Pelletreau, & Hedriana, 2016).

July/August 2017 MCN 197

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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.
Conclusion
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 consid-
eration 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 out-
comes. ✜
Sheryl E. Parfitt is a Clinical Educator, HonorHealth
Scottsdale Shea Medical Center, Scottsdale, AZ. The
author can be reached via e-mail at sheryl.parfitt@
honorhealth.com
Mary L. Bogat is a Staff Nurse, HonorHealth Scotts-
dale Shea Medical Center, Scottsdale, and Clinical
Instructor, Scottsdale Community College, Scottsdale,
Arizona State University, Tempe, AZ.
Sandra L. Hering is a Informatics Support Specialist,
HonorHealth Scottsdale Shea Medical Center, Scottsdale,
AZ.
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 abnor-
malities, high or low temperatures (>38º C or <36º 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).
198 volume 42 | number 4
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Cheryl Roth is a Nurse Practitioner, HonorHealth
Scottsdale Shea Medical Center, Scottsdale, AZ.
The authors declare no conflicts of interest.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/NMC.0000000000000339
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