Defining Sepsis

"Severe sepsis is a modern-day pestilence, a leading cause of death worldwide. In the United States alone it kills 215,000 annually, making it the leading cause of death, after cardiovascular disease and cancer. More people die every day from sepsis (589 deaths per day) than from acute heart attack. Typical conditions that predispose patients to develop severe sepsis include cancer, multiple traumas from a motor vehicle accident, and pneumonia or other infections. Severe sepsis can even develop spontaneously in previously healthy patients, especially at the extremes of life – the very young or the elderly."

Kevin J. Tracey, MD
Fatal Sequence; The Killer Within

Sepsis is a serious medical condition caused by the body's systemic response to either a local or systemic infection.^1,2 Sepsis is a leading cause of death worldwide.^3-5

Pathogens associated with sepsis include:⁴

• Bacteria (typically the most common agent)
• Fungi
• Parasites
• Viruses

An early diagnosis of sepsis can significantly improve outcomes through clinical interventions such as antibiotic administration and hemodynamic and organ support.^6-8 Early identification of at-risk patients, early diagnosis, and appropriate therapy are daily challenges for clinicians based in the emergency department and other hospital departments because the signs and symptoms of sepsis are nonspecific, and thus it may be missed or confused with other medical conditions. The often rapid onset of sepsis can impede early diagnosis, reducing the critical window for implementation of effective therapeutic measures.⁶

a. First most common site of infection¹¹
b. Second most common site of infection¹¹
c. Third most common site of infection¹¹

Clinical Definition of Sepsis
The American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) have defined sepsis as confirmed or suspected infection in the presence of the systemic inflammatory response syndrome (SIRS).^1,2

SIRS is primarily characterized by the presence of at least two of the following signs:^1,2,7,9

• Temperature > 38.6ºC or < 36ºC
• Heart rate > 90 beats/minute
• Respiratory rate > 30 breaths/minute
• Leukocyte count > 12,000 cells/mm³ or < 4,000 cells/mm³.

Sepsis can progress to severe sepsis and/or septic shock. Progression is associated with a significant increase in morbidity and mortality.

Severe sepsis is defined as sepsis and single or multiple organ dysfunction.^1,2

Septic shock is defined as severe sepsis and hypotension that does not respond to adequate fluid replacement.^1,2

Need for Earlier Diagnosis
Early detection and specific clinical intervention have been shown to be crucial for the improved outcome of patients with sepsis.⁸ However, sepsis can be difficult to distinguish from other, non-infectious conditions in patients with clinical signs of inflammation, delaying therapeutic decision making.

Once a patient is in septic shock, survival rates can drop 7.6% for every hour that antibiotic therapy is delayed.⁶ Up to 72 hours may elapse before microbiological culture results are available, and false negatives are common. In addition, an infectious agent may never be identified in a large percentage of patients.^10,11

The Impact of Sepsis

Sepsis: A leading killer

Sepsis exacts a high toll.

• U.S. estimated cost exceeds $17 billion annually³
• Approximately 18 million cases estimated yearly worldwide¹⁰
• Sepsis affects over 35% of ICU patients, and manifests in approximately 2/3 of these patients as severe sepsis or septic shock^9,10
• Approximately 28.6% average overall mortality for sepsis, severe sepsis and septic shock¹²
• Up to 82% mortality for patients with septic shock¹²
• Delayed diagnosis leads to progression of disease and the need for more invasive and costly treatment⁶

Patients may suffer significant morbidities including:

• amputation (single or multiple)
• irreversible organ damage
• reduced quality of life
• reduced life expectancy¹³

Sepsis biomarker testing has been shown to significantly improve clinical decision making.^14,15

Who Is at Risk of Developing Sepsis?

• Sepsis can occur at any age
• The greatest risk occurs among the elderly and the newborn^3,4
• Sepsis is more likely to occur if the patient already has an underlying disease
• Sepsis can develop rapidly in previously healthy people¹⁵
• The incidence of sepsis is increasing by approximately 1.5% per year, and is expected to continue growing as the population ages.³

Neonatal Sepsis¹⁷

Sepsis in newborns can be particularly difficult to recognize and diagnose. Signs and symptoms are less specific than in adults, and interpretation may be highly subjective. Symptoms can include:

• Diminished activity
• Less vigorous sucking
• Apnea
• Bradycardia
• Temperature instability

Unlike older children and adults, only 10–50% of newborns may be consistently febrile for over 1 hour.

• Early-onset sepsis occurs within 7 days of birth, but onset most commonly occurs within 6 hours of birth
• Early-onset sepsis can occur in infants infected by pathogenic organisms infecting the mother’s birth canal or genitalia
• Pneumonia is a danger for infants who aspirate meconium as a complication of labor
• Late-onset sepsis (developing between 7 and 28 days after birth) is usually acquired from the environment
• Preterm infants, especially very low birth-weight babies, are at particular risk from infections acquired through invasive procedures and devices (e.g., venous or urinary catheters, ventilators, etc.)

References:
1. Bone RC. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644.
2. Levy M, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31(4):1250-56.
3. Angus DC, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29(7)1303-10.
4. Martin GS, et al. The epidemiology of sepsis in the United States from 1979 through 2000. NEJM. 2003;348:1546-54.
5. Linde-Zwirble WT, et al. Severe Sepsis epidemiology: sampling, selection, and society. Crit Care. 2004;8(4):222-6.
6. Kumar, A et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1593
7. Dellinger RP, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296 –327.
8. Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM. 2001; 345(19):1368-77.
9. Alberti C, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Int Care Med. 2002;28:108-21.
10. Vincent JL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb; 34(2):344-53.
11. Brun-Buisson C. The epidemiology of the systemic inflammatory response. Int Care Med. 2000; 26:s64-74.
12. Salvo I, et al. Intensive Care Med. 1995;21 Suppl 2:S244-9.
13. Quartin AA, et al. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997; 277(13):1058-63.
14. Harbarth et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001; 164:396.
15. Mokart D, et al. Procalcitonin, interleuking 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery. Brit J Anaesth. 2005;94(6)767-73.
16. Laurila JJ, et al. Cardiac tamponade and septic shock caused by viral infection in a previously healthy woman. Acta Anaesthesiol Scand 2005; 49:1384-6.
17. Infections in neonates. Beers MH, et al. editors. The Merck Manual, 18th edition. © 2006