IT ’S

A BO UT
TIME
TM

Recognizing the
Signs of Sepsis

Steven Q. Simpson, MD
Chief Medical Officer, Sepsis Alliance
Jim O’Brien, MD, MS
Board of Directors, Sepsis Alliance
Sepsis is a life-threatening condition caused by the body’s
response to infection. This complex response can lead to
tissue damage, organ failure, and death. The most common
source of infection is bacterial, but infection can also arise
from fungi, viruses, or parasites.1,2 According to the Centers for
Disease Control and Prevention, sepsis is the 11th leading cause
of death in the United States.3 However, deaths from sepsis
are frequently reported as other comorbidities, suggesting
that both incidence and cost estimates may be low.4 Older
studies likely underestimated mortality rates for sepsis; recent,
more accurate epidemiology indicates that sepsis accounts
for upwards of 270,000 deaths per year, placing sepsis as
the third leading cause of death in the U.S.5 In addition, Prompt treatment can have the best chance of
sepsis creates a significant financial burden on healthcare success.10 Treatment for sepsis
systems in the U.S., where there were over 1.5 million cases provides the should be initiated as early
of sepsis in 2014.6 At an average cost of over $18,000 per best chance for as possible; for many sepsis
sepsis hospital stay, this amounts to more than $27 billion reducing deaths and patients, this occurs when
annually.7 Pediatric sepsis effects more than 75,000 children they enter the emergency
in the United States per year, with healthcare costs in excess improving recovery department.11,12 Two important
of $4.8 billion.8 from sepsis. time-sensitive interventions
Among experts in the for patients are early antibiotic
healthcare community, administration and early
sepsis accounts for upwards of sepsis is considered a delivery of intravenous (IV)

270,000 deaths
time-sensitive condition and fluids.9 Early recognition
treatment protocols have and treatment have been
been developed to promote shown to decrease morbidity
per year rapid care.9 From the disease and mortality.13,14 Delays in
onset, the transition to serious antibiotic administration are
illness occurs during the critical associated with an increase
“golden hours,” the time in
which appropriate treatments

1 2
 In order to raise public awareness and promote recognition of

42% of this condition, Sepsis Alliance has developed the It’s About TIME™
campaign, an easily remembered acronym that can aid in the

Americans
recognition of the signs of sepsis and that imparts the importance
of receiving treatment quickly. It’s About TIME™ breaks down these
signs as:
have not heard of sepsis.20

in mortality.11,15,16 Survivors of sepsis are at an increased risk Temperature

for rehospitalization, particularly due to infection, and may higher or lower than normal
experience both acute and chronic health problems, known
as post-sepsis syndrome.17,18 Effects can include, but are
not limited to, decreased cognitive and physical function,
anxiety, depression, and symptoms of post-traumatic
stress.18,19
Infection
may have signs and symptoms of
Despite the prevalence and healthcare costs of sepsis, public
awareness around the condition is low. According to the
an infection
2017 Sepsis Alliance Awareness Survey, 42% of Americans
have not heard of sepsis.20 In addition to low awareness
of the disease, the signs and symptoms of sepsis are not
well known outside of healthcare settings. Less than 1%
Mental decline
of Americans can correctly identify the most common confused, sleepy, difficult to rouse
symptoms of sepsis.20 Even among healthcare providers,
sepsis is difficult to recognize and may be missed.21,22 Since
most sepsis cases start in the community, patients may need
to ask providers about sepsis and emergency care.5
Extremely ill
“I feel like I might die,” severe pain
or discomfort
© Sepsis Alliance 2018

3 4
 Temperature - Infection - May pulmonary disease, congestive
heart failure, cancer, and
Higher or lower have signs of an diabetes. The most common
infections leading to sepsis are
than normal infection pneumonia and urinary tract
Changes in body temperature In addition to changes in infections.
are one of the hallmarks of temperature, there are other
sepsis. Patients with sepsis can bodily signs that may indicate Pain is also associated with
present with fever, defined as a that an infection is present. For many types of infections.
temperature above 101 °F (38.3 people with diabetes, one of Intense pain may be localized
°C). Patients may instead present the signs of infection can be to an abscess related to
with hypothermia, defined as a a sudden elevation in blood infection. This can occur in
temperature below 98.6 °F (36.0 sugar, for example. Additionally, the gastrointestinal system (as
°C).23 However, some patients, sepsis can be the result of an in appendicitis), in a joint (as in
such as those taking certain infected cut or abrasion. If a cut septic arthritis) or related to an
types of medications, may not or abrasion develops redness organ (such as near the lungs
experience any changes in and tenderness, and continues in pneumonia or in a kidney
temperature.2 Temperature may to get larger, this may also be infection). Sepsis can also
be one of the first signs of illness a sign of infection. Certain produce generalized pain, like
that could potentially be sepsis, populations are more prone to the achiness associated with
so it is important to observe if infection, including those who flu. Pain should not be ignored,
any other signs of sepsis are also are immunocompromised or especially acute, intense pain;
present. If so, it is critical to seek suffer from liver disease. Other it is an indication that medical
medical treatment. risk factors include chronic evaluation is necessary.

5 6
Mental decline - Confused, sleepy, Extremely ill - “I feel like I might
difficult to rouse die,” severe pain or discomfort
Another symptom of sepsis can be altered mental state.24 Patients with sepsis often report that their symptoms are above
Many patients experience feelings of excessive confusion and and beyond previously experienced sickness. The severity of the
disorientation. This is often reported by family members, as the symptoms can make patients feel like they are on the verge of
person with sepsis is unable to communicate these feelings death. Faces of Sepsis, an online resource for sepsis survivors
because of their confusion. Recent advances in the management and those who have loved ones affected by sepsis, reports the
of sepsis have demonstrated the importance of recognizing experiences of sepsis patients.25 In describing their illness, quotes
altered levels of consciousness in patients suspected of being include "I was delirious from the fever and could barely breathe,"
septic.2 Symptoms can manifest themselves in a variety of "My initial memories are a jumble of breathing very fast, struggling
behaviors. Excessive sleeping can be a sign of sepsis. People with to bring in air, confusion, time distortion and feeling like I was
sepsis can sleep for extended periods of time and are difficult to dying," and "I told him ‘I’m dying.’" Additionally, some patients
wake up. Confusion can manifest itself in a variety of behaviors as report severe pain or discomfort, often located in the abdominal
well, with people acting strangely, speaking without making sense, region. As noted earlier, this acute, intense pain may be related to
or not acting like themselves. In some cases, people who are the infection that is triggering sepsis.
septic won’t be able to answer simple questions like “What is your
address?” If it takes someone more than 20 seconds to answer In some instances, friends and family are the ones to recognize
this question, it may indicate that something is wrong and it is the severe symptoms of sepsis. In one story, a survivor says, "My
time to help them get medical care. parents were in town and noticed how sick I was… my mom
brought me back (to the doctor)." Recognizing that a loved one is
experiencing significant illness is critical in directing them towards
proper medical care.

7 8
The goal of the It’s About TIME™ campaign is to raise awareness Awareness campaigns for other
around the symptoms of sepsis so that proper medical care can conditions have had a positive
begin as soon as possible. A delay in first antibiotic administration impact on the identification of the
is associated with an increase in the risk of mortality for each hour signs of disease that indicate the
delay.15,16 If sepsis is caught early, there are significant short- and need for prompt medical treatment.
long-term benefits for the patient.10 Treatment and triage protocols Public awareness campaigns about
have been shown to be effective in reducing the amount of time stroke are an example, as stroke is
another disease that benefits from
to IV fluids and antibiotics for patients with sepsis.11,26,27 Even the
rapid hospital treatment. Multimedia
timing of established treatment protocols has been revised to take
campaigns have been effective in
place in a shortened amount of time: down to 1 hour from 3- and increasing knowledge, awareness,
6-hour bundles.9 The recognition of sepsis as a medical emergency and the intention to respond
dictates that delays in treatment be minimized. to a stroke as an emergency.
Retrospective analysis of these
Though sepsis is treated in the medical setting, most cases of campaigns has shown positive
sepsis originate in the community. As many as 80% of sepsis effects on reducing patient delay
cases are present on admission to the hospital.5,28 Therefore, to hospital presentation and other
there is a need for recognizing the signs of sepsis by the general behavioral indicants.29
public, so appropriate steps will be taken to obtain emergency
treatment. Furthermore, awareness in the healthcare community Current treatments for sepsis can
may be limited to those with expert knowledge of sepsis; it may be effective if sepsis is caught in
be necessary for a patient to know and ask about emergency care time. By aiming to reduce the time
for sepsis, or risk not getting appropriate care. A public awareness to treatment of septic patients, it is
campaign like It’s About TIME™ is crucial to address sepsis feasible that this campaign can serve
in everyday life where sepsis strikes, as it can serve to inform its goal of reducing the incidence
people outside of the medical profession about what to look for of largely preventable deaths. The
when sepsis develops. Surviving Sepsis Campaign, aimed
at medical professionals, has been
successful in promoting timely and
Though sepsis is treated in the medical setting, effective treatment of sepsis.9,30 The
most cases of sepsis originate It’s About TIME™ campaign aims to
educate patients and the public at
in the community. large, so that the signs of sepsis are
well known to all.

9 10
References
1. Delaloye, J., & Calandra, T. (2014). Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence, 5(1),
161–169. https://doi.org/10.4161/viru.26187
2. Rello, J., Valenzuela-Sánchez, F., Ruiz-Rodriguez, M., & Moyano, S. (2017). Sepsis: A Review of Advances in Management.
Advances in Therapy, 34(11), 2393–2411. https://doi.org/10.1007/s12325-017-0622-8
3. CDC Wonder Query for 2016. Accessed from: https://wonder.cdc.gov/ucd-icd10.html
4. Epstein L, Dantes R, Magill S, Fiore A. Varying Estimates of Sepsis Mortality Using Death Certificates and Administrative
Codes — United States, 1999–2014. MMWR Morb Mortal Wkly Rep 2016;65:342–345. DOI: http://dx.doi.org/10.15585/
mmwr.mm6513a2
5. Rhee, C., Dantes, R., Epstein, L., Murphy, D. J., Seymour, C. W., Iwashyna, T. J., … for the CDC Prevention Epicenter
Program. (2017). Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014. JAMA, 318(13),
1241. https://doi.org/10.1001/jama.2017.13836
6. McDermott, K.W.; Elixhauser, A.; Sun, R.Trends in Hospital Inpatient Stays in the United States, 2005-2014. Healthcare
Cost and Utilization Project.
7. Pfuntner, A, Wier, LM, Steiner, C . Costs for Hospital Stays in the United States, 2010. HCUP Statistical Brief #146. January
2013. Agency for Healthcare Research and Quality, Rockville, MD. Available at http://www.hcup-us.ahrq.gov/reports/
statbriefs/sb146.pdf
8. Hartman ME, Linde-Zwirble WT, Angus DC, et al. Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care
Med 2013;14(7):686-693.
9. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med 2018.
10. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl
J Med 2001;345(19):1368-1377.
11. Seymour, C. W., Kahn, J. M., Martin-Gill, C., Callaway, C. W., Yealy, D. M., Scales, D., & Angus, D. C. (2017). Delays From
First Medical Contact to Antibiotic Administration for Sepsis*: Critical Care Medicine, 45(5), 759–765. https://doi.
org/10.1097/CCM.0000000000002264
12. Alam, N., Oskam, E., Stassen, P. M., Exter, P. van, van de Ven, P. M., Haak, H. R., … Stoffers, J. (2018). Prehospital antibiotics
in the ambulance for sepsis: a multicentre, open label, randomised trial. The Lancet Respiratory Medicine, 6(1), 40–50.
https://doi.org/10.1016/S2213-2600(17)30469-
13. Liu, V. X., Fielding-Singh, V., Greene, J. D., Baker, J. M., Iwashyna, T. J., Bhattacharya, J., & Escobar, G. J. (2017). The Timing
of Early Antibiotics and Hospital Mortality in Sepsis. American Journal of Respiratory and Critical Care Medicine, 196(7),
856–863. https://doi.org/10.1164/rccm.201609-1848OC
14. Seymour CW, Gesten F, Prescott HC, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.
N Engl J Med 2017;376(23):2235-2244.
15. Ferrer, R., Martin-Loeches, I., Phillips, G., Osborn, T. M., Townsend, S., Dellinger, R. P., … Levy, M. M. (2014). Empiric
Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour: Results From a Guideline-
Based Performance Improvement Program*. Critical Care Medicine, 42(8), 1749–1755. https://doi.org/10.1097/
CCM.0000000000000330
16. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the
critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96.
17. Granja, C., Dias, C., Costa-Pereira, A., & Sarmento, A. (2004). Quality of life of survivors from severe sepsis and septic
shock may be similar to that of others who survive critical illness. Critical Care, 8(2), R91.
18. Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA 2018;319(1):62-75.
19. Iwashyna TJ, Ely EW, Smith DM. Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe
Sepsis. Jama Network 2010;304(16):8.
20. Sepsis: A Word to Know, a Meaning to Learn. Accessed from: https://www.sepsis.org/sepsis-alliance-news/sepsis-word-
know-meaning-learn/
21. Poeze M, Ramsay G, Gerlach H, et al. An international sepsis survey: a study of doctors’ knowledge and perception about
sepsis. Crit Care 2004;8(6):R409-413.
22. Vincent JL. The Clinical Challenge of Sepsis Identification and Monitoring. PLoS Med 2016;13(5):e1002022.
23. Levy, M. M., Fink, M. P., Marshall, J. C., Abraham, E., Angus, D., Cook, D., … Ramsay, G. (2003). 2001 SCCM/ESICM/ACCP/
ATS/SIS International Sepsis Definitions Conference: Critical Care Medicine, 31(4), 1250–1256. https://doi.org/10.1097/01.
CCM.0000050454.01978.3B
24. Seymour, C. W., & Rosengart, M. R. (2015). Septic Shock: Advances in Diagnosis and Treatment. JAMA, 314(7), 708. https://
doi.org/10.1001/jama.2015.7885
25. Faces of Sepsis. Accessed from: https://www.sepsis.org/faces/
26. Leisman DE, Doerfler ME, Ward MF, et al. Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour
Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts. Crit Care Med 2017;45(3):395-406.
27. Hayden, G. E., Tuuri, R. E., Scott, R., Losek, J. D., Blackshaw, A. M., Schoenling, A. J., … Hall, G. A. (2016). Triage sepsis alert
and sepsis protocol lower times to fluids and antibiotics in the ED. The American Journal of Emergency Medicine, 34(1),
1–9. https://doi.org/10.1016/j.ajem.2015.08.039
28. Novosad, S. A. (2016). Vital signs: epidemiology of sepsis: prevalence of health care factors and opportunities for
prevention. MMWR. Morbidity and Mortality Weekly Report, 65.
29. Mellon, L., Doyle, F., Rohde, D., Williams, D., & Hickey, A. (2015). Stroke warning campaigns: delivering better patient
outcomes? A systematic review. Patient Related Outcome Measures, 61. https://doi.org/10.2147/PROM.S54087
30. 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. Intensive Care Medicine, 43(3),
304–377. https://doi.org/10.1007/s00134-017-4683-6