US Pharm. 2024;49(2):27-29.

Sepsis is a potentially life-threatening condition. It is a serious infection resulting from the presence of harmful bacteria in the blood or other tissues. The body’s reaction to this condition can lead to the malfunctioning of various organs, shock, and death.1

Bacterial infections cause most cases of sepsis. However, sepsis can also be a result of other infections, including viral infections, such as COVID-19 or influenza, or fungal infections during which the body will show a severe inflammatory response.1

Sepsis manifests in three stages: sepsis, severe sepsis, and septic shock. Currently, sepsis is a substantial global health burden and is the leading cause of death among adults in the ICU. It affects more than 900,000 people annually in the United States.1

Medical technology advances over the past decade, standardized protocols, and physician awareness have significantly improved survival, but mortality rates remain from 20% to 36%, with approximately 270,000 deaths annually in the U.S.2

Of patients with sepsis, 80% are initially treated in an emergency department, and the remainder develop sepsis during hospitalization for other conditions.3 Major risk factors for developing sepsis are age 65 years or older, chronic illness, malnutrition, immunosuppression, recent surgery or hospitalization, and indwelling devices.4 Approximately one-third of sepsis cases occur in the postoperative period.5

Although an increasing number of patients admitted for sepsis improve enough to be discharged from the hospital, these patients have higher rates of return and readmission, significantly reduced physical and cognitive functions, and death within 12 months in some cases.6


Pneumonia is the most common cause of sepsis. Respiratory, gastrointestinal, genitourinary, and skin or soft-tissue infections are also among the most common sources of sepsis. These account for more than 80% of all sepsis cases.7 Indwelling medical devices, endocarditis, and meningitis or encephalitis each account for 1% of sepsis cases.8

Bacterial microbes (gram-negative [62%] or gram-positive [47%]) are the most common causative organisms for sepsis.8 Some patients with sepsis are infected with multiple microbial organisms. A small number of patients with sepsis have fungal, viral, or parasitic infections. It is reported that in approximately 50% of patients, the source for sepsis is undetermined.


Fever is the most common manifestation of sepsis.9 The absence of fever, however, does not exclude sepsis. Sepsis-induced hypothermia and the absence of fever are more likely in older adults and in people with chronic alcohol abuse or immunosuppression.10 Hypotension is the presenting abnormality in approximately 40% of patients with sepsis.11 In older adults, generalized weakness, agitation or irritation, or altered mental status may be the only manifestation.


Sepsis has a variable presentation depending on the source of the initial infection and may not be apparent until late in the course of illness, when signs and symptoms are obvious. There are several medical conditions that mimic sepsis and should be considered in the differential diagnosis (e.g., acute pulmonary embolus, acute myocardial infarction, acute pancreatitis, acute transfusion reaction, adrenal crisis, acute alcohol withdrawal, thyrotoxicosis).12 To improve the diagnosis of sepsis, clinicians must obtain historical, clinical, laboratory, and radiographic data supportive of infection and organ dysfunction.

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.12

Laboratory Testing

Laboratory testing should include a complete blood count with differential; basic metabolic panel; lactate, procalcitonin, and liver enzyme measurements; coagulation studies; and urinalysis. Arterial or venous blood sampling can determine the degree of acid-base abnormalities, which are common in sepsis and are likely secondary to tissue hypoperfusion (lactic acidosis) and renal dysfunction.13

Clinicians should obtain two sets of peripheral blood cultures (including a set from a central venous catheter, if present), as well as cultures of urine, stool (for diarrhea or recent antibiotic use), sputum (for respiratory symptoms), and skin and soft tissue (for skin abscess, ulceration, or drainage). Cerebrospinal, joint, pleural, and peritoneal fluid cultures are obtained as clinically indicated.2,14


Imaging studies should include chest radiography, with additional studies as indicated, such as echocardiography for suspected endocarditis, CT of the chest for empyema or parapneumonic effusion, and CT of the abdomen/pelvis for renal or abdominal abscess.14


Early and thorough treatment raises the likelihood of recovery. People who have sepsis need close monitoring and treatment in an ICU. This is because people with sepsis may need lifesaving measures to stabilize breathing and heart action.

IV Fluid Therapy

The first step in sepsis management is establishing vascular access and initiating balanced solutions (e.g., Ringer lactate, Ringer acetate, or Plasma-Lyte). Patients with sepsis should receive an IV crystalloid at 30 mL per kg within the first 3 hours.15 Infusing an initial 1-L bolus over the first 30 minutes is an accepted approach. The remainder of fluid resuscitation should be given by repeat bolus infusions.16 Infusion of IV fluids in this manner enhances preload and cardiac output, thereby improving oxygen delivery. However, the hemodynamic effects of fluid boluses in sepsis lasts only 60 minutes.17

Frequent reassessment of fluid balance beyond initial resuscitation is recommended to avoid under- or overhydration. Dynamic blood pressure response, tissue perfusion (lactate clearance), and most importantly urine output (should be 0.5 mL/kg/hour or greater) can be used to help avoid volume overload, particularly in patients with chronic renal disease, heart failure, or acute lung injury.17

Antimicrobial Therapy

In sepsis, treatment with antibiotics begins as soon as possible. Broad-spectrum antibiotics, which are effective against a variety of bacteria, are often used first. When blood test results show which bacterium is causing the infection, the first antibiotic may get switched out for a second one.18

Initial antibiotic therapy should be broad and started empirically based on the suspected infection site, likely pathogen, clinical context (community- vs. hospital-acquired), and local resistance patterns.18 The use of inappropriate antibiotics is associated with up to a 34% increase in mortality.19 Antibiotic therapy should be narrowed or redirected once culture results are available and the causative organism has been identified. This approach reduces the risk of antimicrobial resistance, drug toxicity, and overall treatment cost.20

Antibiotic therapy for 7 to 10 days is sufficient for most infections associated with sepsis, including culture-negative sepsis.15 Specific infections (e.g., endocarditis, osteomyelitis) or colonized endovascular devices or orthopedic hardware that cannot be removed require a longer duration of antibiotic therapy.

Currently, there is no consensus on deescalation of combination antibiotic therapy, particularly in culture-negative sepsis. Factors to consider include clinical progress during treatment, use of biomarkers (e.g., decreasing procalcitonin levels) to monitor antibiotic response, and fixed duration of combination therapy.20

Vasopressor Therapy

Norepinephrine is the first-line vasopressor agent for patients with septic shock if initial fluid resuscitation fails to restore mean arterial pressure (MAP) to 65 mmHg or greater.15 Vasopressor therapy clearly improves survival in these patients and should be started within the first hour following initial fluid resuscitation.21 Failure to initiate early vasopressor therapy in patients with septic shock increases mortality rates by 5% per hour of delay.22

Norepinephrine should be initiated at 2 mcg to 5 mcg per minute and titrated up to 35 mcg to 90 mcg per minute to achieve a MAP of 65 mmHg or greater.20 If norepinephrine fails to restore the MAP to this level, vasopressin (up to 0.03 units per minute) can be added as a second-line agent, followed by the addition of epinephrine (20 mcg to 50 mcg per minute), if needed.23

Vasopressor therapy should be titrated to maintain adequate hemodynamic status and should be used for the shortest duration possible.23


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