Sepsis: Diagnosis and Management


Am Fam Physician. 2020 Apr 1;101(7):409-418.

Author disclosure: No relevant financial affiliations.

Guidelines published in 2016 provide a revised definition of sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality. The measurement of serum lactate has been incorporated into the latest septic shock definition. The guidelines recommend the Sequential Organ Failure Assessment (original and quick versions) as an important tool for early diagnosis. Respiratory, gastrointestinal, genitourinary, and skin and soft tissue infections are the most common sources of sepsis. Pneumonia is the most common cause of sepsis. Although many patients with sepsis have fever, the clinical manifestation can be subtle, particularly in older patients and those who are immunocompromised. Initial evaluation of patients with suspected sepsis includes basic laboratory tests, cultures, imaging studies as indicated, and sepsis biomarkers such as procalcitonin and lactate levels. Fluid resuscitation is the priority in early management, including administering an intravenous crystalloid at 30 mL per kg within the first three hours. Antimicrobial therapy should also be initiated early. Most research indicates that antimicrobial therapy should be started within three hours of presentation. The latest guidelines recommend starting antimicrobials within one hour, but this is controversial. Vasopressor therapy is indicated if hypotension persists despite fluid administration. Future trials of sepsis management are focusing on improving long-term rates of readmission and death, physical disability, cognitive impairment, and quality of life.

Sepsis is a substantial global health burden and is the leading cause of death among adults in intensive care units (ICUs).1 It affects more than 900,000 people annually in the United States, with an incidence of 535 cases per 100,000 person-years.2 Medical advances over the past decade, standardized protocols, and physician awareness have significantly improved survival, but mortality rates remain between 20% and 36%, with approximately 270,000 deaths annually in the United States.35



2016 guidelines provide a new definition for sepsis: a life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality; the presence of hypotension is no longer required.*

Medical advances over the past decade, standardized protocols, and physician awareness have significantly improved survival in patients with sepsis, but mortality rates remain between 20% and 36%, with approximately 270,000 deaths annually in the United States.

Lactate-guided resuscitation (i.e., measuring lactate every four to six hours until levels have normalized) reduces overall mortality compared with no lactate monitoring.

SIRS = systemic inflammatory response syndrome; SOFA = Sequential Organ Failure Assessment.

*—The 2016 guidelines include the SOFA and quick SOFA to aid in diagnosis. Online calculators are available at and Although the SIRS criteria ( are no longer endorsed in the guidelines, they still have a role in the identification of acute infection.

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Clinical recommendationEvidence ratingComments

In settings other than the intensive care unit, the quick Sequential Organ Failure Assessment ( can help clinicians recognize possible sepsis early in the evaluation.9,1214


Validation studies and retrospective analysis of observational studies

Sepsis care protocols decrease sepsis-related mortality and should be implemented in all medical facilities.2124


Multiple prospective cohort trials

Patients with sepsis should complete the sepsis bundle (fluid resuscitation, antibiotics, lactate measurement, and cultures) within three hours of presentation.2427


Systematic reviews and retrospective trials

As part of fluid resuscitation, patients with sepsis should receive an intravenous crystalloid at 30 mL per kg.21


Expert consensus guideline

Norepinephrine is the first-line vasopressor agent for patients with septic shock if initial fluid resuscitation fails to restore mean arterial pressure to 65 mm Hg or greater.21,28,29


Multiple studies with head-to-head comparisons of norepinephrine and other vasopressors and a meta-analysis showing that norepinephrine reduces sepsis-related mortality

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented

The Authors

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ROBERT GAUER, MD, is a hospitalist in the Department of Internal Medicine at Womack Army Medical Center, Fort Bragg, N.C....

DAMON FORBES, MD, is medical director of critical care service in the Department of Medicine and associate program director for critical care, hospitalist fellowship, in the Department of Family Medicine at Womack Army Medical Center. He is also a pulmonary/critical care staff physician at Womack Army Medical Center.

NATHAN BOYER, MD, is chief of pulmonary medicine in the Department of Internal Medicine at Landstuhl Regional Medical Center, Germany. At the time this article was written, he was chief of pulmonary medicine in the Department of Internal Medicine at Womack Army Medical Center.

Address correspondence to Robert Gauer, MD, Womack Army Medical Center, Family Medicine Residency Clinic, Bldg. 4-2817, Riley Rd., Fort Bragg, NC 28310 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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