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A Basic Review of Sepsis

Megan Johnson, ACNP-BC

Sepsis is the clinical syndrome that results as a result of an inflammatory response to an infection. The inflammatory cascade causes a disruption in the homeostasis that leads to the clinical symptoms and over time can lead to vasodilation, capillary leak syndrome, and eventually organ dysfunction which can ultimately result in the possibility of death. In 1992, the American College of Chest Physicians/Society of Critical Care Medicine issued a consensus statement to establish the defining criteria for sepsis syndrome. For the first time, this allowed a common nomenclature for disease classification and systematic comparisons across studies of septic patients.

Systemic inflammatory response syndrome (SIRS) is defined as two or more of the following: tachycardia, tachypnea, hyperthermia or hypothermia, high or low white blood cell count, or bandemia; sepsis is the combination of infection plus SIRS; severe sepsis is sepsis plus organ dysfunction; and septic shock is severe sepsis plus hypotension, defined as a systolic blood pressure below 90 mm Hg, not responsive to a fluid challenge. In the SCCM guidelines published by Dellinger et al in 2013, sepsis is now defined as the presence of a probable or known infection in conjunction with one of the diagnostic criteria for sepsis. The diagnostic criterion for sepsis, severe sepsis and septic shock is as listed below.

Diagnostic Criteria for Sepsis, Severe Sepsis and Septic Shock3

Sepsis (documented or suspected infection plus ≥1 of the following)

  • General variables
    • Fever (core temperature, >38.3°C)
    • Hypothermia (core temperature, <36°C)
    • Elevated heart rate (>90 beats per min or >2 SD above the upper limit of the normal range for age)
    • Tachypnea
    • Altered mental status
    • Substantial edema or positive fluid balance (>20 ml/kg of body weight over a 24-hr period)
    • Hyperglycemia (plasma glucose, >120 mg/dl [6.7 mmol/liter]) in the absence of diabetes
  • Inflammatory variables
    • Leukocytosis (white-cell count, >12,000/mm3)
    • Leukopenia (white-cell count, <4000/mm3)
    • Normal white-cell count with >10% immature forms
    • Elevated plasma C-reactive protein (>2 SD above the upper limit of the normal range)
    • Elevated plasma procalcitonin (>2 SD above the upper limit of the normal range)
  • Hemodynamic variables
    • Arterial hypotension (systolic pressure, <90 mm Hg; mean arterial pressure, <70 mm Hg; or decrease in systolic pressure of >40 mm Hg in adults or to >2 SD below the lower limit of the normal range for age)
    • Elevated mixed venous oxygen saturation (>70%)
    • Elevated cardiac index (>3.5 liters/min/square meter of body-surface area)
  • Organ-dysfunction variables
    • Arterial hypoxemia (ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, <300)
    • Acute oliguria (urine output, <0.5 ml/kg/hr or 45 ml/hr for at least 2 hr)
    • Increase in creatinine level of >0.5 mg/dl (>44 μmol/liter)
    • Coagulation abnormalities (international normalized ratio, >1.5; or activated partial-thromboplastin time, >60 sec)
    • Paralytic ileus (absence of bowel sounds)
    • Thrombocytopenia (platelet count, <100,000/mm3)
    • Hyperbilirubinemia (plasma total bilirubin, >4 mg/dl [68 μmol/liter])
  • Tissue-perfusion variables
    • Hyperlactatemia (lactate, >1 mmol/liter)
    • Decreased capillary refill or mottling
  • Severe sepsis (sepsis plus organ dysfunction)
  • Septic shock (sepsis plus either hypotension [refractory to intravenous fluids] or hyperlactatemia).

Risk Factors for Sepsis

There are risk factors which may increase the odds in which someone develops sepsis. Risk factors include chronic diseases such as chronic obstructive pulmonary disease (COPD), AIDS, cancer, and the immunosupressed. Other less commonly known risk factors that predispose a person to sepsis include, age in which sepsis is highest in infants and elderly, sex which is more common in males than in females, and ethnic groups which is higher in African Americans and Hispanics than in caucasians.7

In addition, sepsis is more common in the winter months secondary to the rise in number of persons with pneumonia. Other persons that may be at in increased risk of developing sepsis include those patients that are bedridden, paralyzed, those with foley catheters, wounds, or venous access lines in place. Severe sepsis and septic shock, combined, are the tenth leading cause of death, resulting in 215,000 deaths annually and 50.37 deaths per 100,000 people in the United States.6

It is estimated that the mortality rates range between 20 and 50 percent.4 In addition, sepsis is the most common cause of death in a non-coronary ICU. According to the data that was published in 2008 by the National Center for Health Care Statistics the number and rate of hospitalizations between the years of 2000 and 2008 doubled (Figure 1), and patients who carried the diagnosis of sepsis or septic shock had a length of stay that was on average 75% longer than other hospitalized patients. The data from that time period as published by the National Center for Health Care Statistics also revealed the following:

  • Only 2% of hospitalizations in 2008 were for septicemia or sepsis, yet they made up 17% of in-hospital deaths.
  • In-hospital deaths were more than eight times as likely among patients hospitalized for septicemia or sepsis (17%) compared with other diagnoses (2%).
  • In addition, those hospitalized for septicemia or sepsis were one-half as likely to be discharged home, twice as likely to be transferred to another short-term care facility, and three times as likely to be discharged to long-term care institutions, as those with other diagnoses.
  • For those under age 65, 13% of those hospitalized for septicemia or sepsis died in the hospital, compared with 1% of those hospitalized for other conditions.
  • For those aged 65 and over, 20% of septicemia or sepsis hospitalizations ended in death compared with 3% for other hospitalizations.

Sepsis costs $16 billion dollars annually and approximately $22,100 per case.6 Sepsis can be caused by any pathogen and it is ever changing. In the United States the most common cause of sepsis is Gram-positive bacteria.4 Healthcare providers including those on the emergency medical service team have an opportunity to recognize sepsis and initiate treatment immediately, with the hopes of increasing the chance of survival.

Early Detection and Treatment

Now that we know the a little bit more about what sepsis is and who is at increased risk it is important to mention how pre-hospital medical personnel can assist with early detection and possibly intervention in the patient with sepsis. Currently there are two widely used screening tools internationally for patients with possible sepsis to be used by pre-hospital personnel. Those include the Robson screening tool and the BAS 90-30-90 scale. Both of these tools refer to the clinical signs in a patient suspected of having and active infection. The Robson screening tool consists of two parts to help identify and isolate those patients with septic shock so pre-hospital management can be initiated. With this tool, a patient is considered septic if any two of the following conditions are met5:

  • Temperature > 38.3°C (100.9°F) or < 36.0°C (96.8°F)
  • Heart rate > 90 beats per minute
  • Respiratory rate > 20 breaths per minute
  • Acutely altered mental status
  • Serum glucose < 120 mg/dL or 6.6 mmol/L

In addition, the BAS 90-30-90 scale is a Swedish model that utilizes an objective approach for evaluating potentially septic patients. With this method, a patient is considered to be septic if one or more of the criteria is met5:

  • Systolic blood pressure <90 mm/Hg
  • Respiratory rate > 30 breaths per minute
  • Oxygen saturation < 90%

Both scales are good screening tools to assess for the possibility of an infection as well as to evaluate for hypoperfusion. In many places there are pre-hospital protocols that are currently using these two screening methods or a combination of the two as a part of their sepsis alert protocols. Using tools similar to these may help to decrease the amount of time that early goal directed therapy is initiated.

Moreover, the surviving sepsis guidelines have instituted Sepsis bundles to assist with Early Goal Directed Therapy (EGDT). Treatments in the EGDT include initiation of fluid resuscitation with specific points for end resuscitation as well as the implementation of broad spectrum antibiotics (Figure 2). It is important to remember that patients that are at the point of severe sepsis or septic shock can require as much as 4 to 6 liters of fluid for initial resuscitation. Many places have sepsis protocols in place that can and will guide a clinician through the treatment process. For all patients early identification of sepsis and early initiation of goal directed therapy is the key to increasing their chance of survival and their overall prognosis.



  1. National Center for Health Statistics. (2011, June). Inpatient care for septicemia or sepsis: a challenge for patients and hospitals (Issue Brief No 62). Hyattsville, MD: Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A.
  2. National Institute of Health. (2014, August). Sepsis Fact Sheet. Retrieved August 26th, 2014 from http://www.nigms.nih.gov/Education/Pages/factsheet_sepsis.aspx.
  3. Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., et al. (2013). Guidelines for the management of severe sepsis and septic shock. Critical Care Medicine, 41(2), 580-637.
  4. Nevier, Remi. (2014) Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis. Retrieved from Up To Date August 12th, 2014.
  5. Wesley, Keith. (2014). Assessing and Managing Sepsis in the Pre-hospital Setting. [Electronic Version]. Journal of Emergency Medical Services, March 2014.
  6. Guerra, W., Mayfield, T., Meyers, M., Clouatre, A., and Riccio, J. (2013). Early Detection and treatment of patients with severe sepsis by pre-hospital personnel. The Journal of Emergency Medicine, 44(6), 1116-1125.
  7. Angus, D. and Van der Poll, T. (2013). Severe Sepsis and Septic Shock. [Electronic Versions]. New England Journal of Medicine, 369, 840-851.

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