Online Medical Reference


Bethany Lehman, DO

Patricia Dandache, MD

Published: January 2020


Sepsis is a syndrome of the physiologic, pathologic, and biochemical abnormalities precipitated by infection. Sepsis is an important clinical entity because it can lead to organ dysfunction and death. Though the reported incidence of sepsis has risen over the last 10 years, attributable mortality has declined over this time period due to earlier identification and treatment of this syndrome.1 Yet even with these advances, sepsis continues to be a significant cause of mortality and morbidity worldwide.

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According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis -3), sepsis is defined as life-threatening organ dysfunction caused by a deregulation host response to infection.2

The systemic inflammatory response syndrome (SIRS) criteria are no longer used as the defining criteria for sepsis as these values may not necessarily indicate a life-threatening, deregulated host response.3,4 Instead, the Sequential Organ Failure Assessment (SOFA) score is now used to help identify organ failure and sepsis. Organ dysfunction is defined as an acute change in the total SOFA score of 2 points or greater due to underlying infection. The SOFA score accounts for multiple organ systems including respiratory, cardiovascular, hepatic, hematologic, nervous, and renal, as described in Table 1.5

Table 1: Sequential Organ Failure Assessment (SOFA) Score







PaO2/FiO2 mm Hg

≥ 400

< 400

< 300

< 200 with respiratory support

< 100 with respiratory support

Platelets x 103/µL

≥ 150

< 150

< 100

< 50

< 20

Bilirubin mg/dL

< 1.2

1.2 – 1.9

2.0 – 5.9

6.0 – 11.9

> 12.0

Blood pressure (catecholamine doses given as µg/kg/min for at least 1 hour)

MAP ≥ 70 mm Hg

MAP < 70 mm Hg

Dopamine < 5
dobutamine any dose

Dopamine 5.1 – 15
epinephrine ≤ 0.1
norepinephrine ≤ 0.1

Dopamine > 15
epinephrine > 0.1
norepinephrine > 0.1

Glasgow coma score


13 – 14

10 – 12

6 – 9

< 6

Creatinine mg/dL
Urine output mL/dL

< 1.2

1.2 – 1.9

2.0 – 3.4

3.5 – 4.9

> 5.0
< 200

CNS = central nervous system; MAP = mean arterial pressure.

Adapted by permission from Springer Nature (Vincent J.-L., Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996; 22:707-710) © 1996.

The baseline SOFA score is assumed to be zero in patients without known, preexisting organ dysfunction. Depending on a patient’s baseline level of risk, a SOFA score of 2 or greater identified a two- to 25-fold increase in mortality compared with patients with a SOFA score less than 2. Patients with a SOFA score of 2 or greater had an overall mortality risk of approximately 10% with presumed infection2. Even patients presenting with modest organ dysfunction can rapidly deteriorate, emphasizing the seriousness of this condition and the need for close monitoring and serial evaluation.

Because the SOFA score requires laboratory values to make an assessment, the quick Sequential Organ Failure Assessment (qSOFA) may be of use when evaluating patients with suspected infection at the bedside. A qSOFA score of 2 of the 3 criteria listed in Table 2 may be indicative of sepsis. The Sepsis-3 task force recommends the use of the qSOFA score to guide further investigation of organ dysfunction with initiation or escalation of therapy and referral to the intensive care unit for close monitoring as appropriate.2

Table 2: Quick Sequential Organ Failure Assessment (qSOFA) Score

qSOFA Criteria


Respiratory rate ≥ 22 breaths/min


Change in mental status


Systolic blood pressure ≤ 100 mm Hg


Data from Singer 20162.

A subset of sepsis, septic shock is defined as sepsis in which underlying circulatory, cellular, and metabolic derangements are profound enough to substantially increase patient mortality risk to 40% or greater.6 Patients with septic shock are those with clinical suspicion of sepsis and persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mm Hg and with serum lactate level > 2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

The term "severe sepsis" was removed from the 2016 "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock" definitions.7 For the purpose of evaluating historical studies, severe sepsis was defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion.8 However, the Center for Medicare and Medicaid Services continues to use the term “severe sepsis.”

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Prevalence and Incidence

The epidemiology of sepsis is difficult to determine due to differing and changing case definitions. In the United States, estimates of an average annual age-adjusted incidence of sepsis are between 300 to 1,000 cases per 100,000 persons. It appears that the incidence of sepsis has increased over the last 10 years but the mortality is decreasing in industrialized countries.1 Hospital mortality in patients with septic shock continues to remain around 40%.6 Evidence of the epidemiology of sepsis in developing countries is limited but mortality from sepsis-related infections appears to be three- to fourfold the rate of developed countries.1

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Inflammatory Cascade

Sepsis can occur as a result of infection at any body site, including the lungs, abdomen, urinary tract, skin, or soft tissue and as a result of a primary blood stream infection. Bacteria are the pathogens most commonly associated with the development of sepsis, although fungi, viruses, and parasites can cause sepsis.

The outer membrane component of gram-negative organisms (eg, lipopolysaccharide [LPS], lipid A, endotoxin) or gram-positive organisms (eg, lipoteichoic acid, peptidoglycan), as well as fungal, viral, and parasitic components trigger activation of the host immune system via a family of transmembrane receptors known as Toll-like receptors (Figure 1). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) within the monocyte subsequently leads to the production of proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin 1 (IL-1). These cytokines initiate the production of toxic downstream mediators, including prostaglandins, leukotrienes, platelet-activating factor, and phospholipase A2. Sepsis occurs when the release of these proinflammatory mediators exceed the response needed for control of local infection and creates a generalized, systemic response. These mediators damage the endothelial lining and promote increased capillary leakage.9 Furthermore, cytokines lead to the production of adhesion molecules on endothelial cells and neutrophils, which in turn promotes further endothelial injury. Activated neutrophils additionally release nitric oxide, a potent vasodilator that leads to hypotension and septic shock.

Inflammation and Coagulation Link

TNF-α and IL-1 have direct effects on the endothelial surface by promoting the expression of tissue factor, the first step in the extrinsic pathway of coagulation, on the surfaces of the endothelium and monocytes. This leads to the production of thrombin, a proinflammatory substance. Thrombin results in fibrin clots in the microvasculature, a complication of sepsis most easily recognized in meningococcal septic shock with purpura fulminans. Fibrinolysis is also impaired during the septic process, as TNF-α and IL-1 promote production of a potent inhibitor of fibrinolysis: plasminogen activator inhibitor-1.10

Proinflammatory cytokines disrupt the body's natural modulators of coagulation and inflammation, activated protein C (APC), and antithrombin. Protein C circulates as an inactive zymogen and is converted to APC in the presence of thrombin and the endothelial surface-bound protein thrombomodulin. Studies have shown that proinflammatory cytokines can shear thrombomodulin from the endothelial surface and lead to downregulation of this molecule, thus preventing the activation of protein C10,11

APC and its cofactor protein S turn off thrombin production by cleaving factors Va and VIIIa. APC also restores fibrinolytic potential by inhibiting plasminogen activator inhibitor-1.12

Antithrombin is the second naturally-occurring endothelial regulator affected during sepsis. Antithrombin inhibits thrombin production at multiple steps in the coagulation cascade and binds to and inhibits thrombin directly. When bound to endothelial cell surface glycosaminoglycans (GAGs), antithrombin leads to the production of the anti-inflammatory molecule prostacyclin (prostaglandin I2 [PGI2]).13 Neutrophil elastase cleaves GAGs off the surface of the endothelial lining, thus limiting the anti-inflammatory properties of antithrombin and leading to uncontrolled bleeding and microthrombi deposition.14


CD4 lymphocytes play a key role in the inflammatory response of sepsis. At first, these cells assume a T helper cell, type 1 (Th1) phenotype and produce large amounts of the proinflammatory mediators, including interferon gamma, TNF-α, and IL-2. Over time, however, CD4 lymphocytes evolve to a T helper cell, type 2 (Th2) phenotype associated with the production of anti-inflammatory cytokines such as IL-10, IL-4, and IL-13. This evolution is driven by the release of catecholamines and corticosteroids. The cytokines, in turn, dampen the immune response and can lead to the deactivation of monocytes. Additionally, TNF released during the early stages of sepsis can cause apoptosis of lymphocytes in the gut and further immunosuppression.15

Systemic Effects

Sepsis can affect every organ in the body, with cytopathic injury and cellular apoptosis caused by a deregulated immune response. The imbalances in the coagulation cascade and endothelial injury described above result in microcirculatory changes and diffuse tissue ischemia. Signs and symptoms of sepsis depend on the organ system affected. The major organs affected during sepsis are the lungs, heart, central nervous system (CNS), kidneys, and liver.


Dyspnea, tachypnea, and hypoxia may result from inflammatory mediator-induced endothelial injury occurring in the pulmonary vasculature with associated increase in microvascular permeability and noncardiogenic pulmonary edema16


Hypotension is a defining factor of septic shock and most reflective of cardiovascular dysfunction—either at the level of the myocardium, as a result of the myocardial depressant effects of TNF, or at the level of the vessel, caused by vasodilation and capillary leak.17 Myocardial depression affects both the right and left ventricles, which may help the clinician differentiate septic shock from cardiogenic shock caused by coronary atherosclerotic myocardial ischemia. Prostacyclin and nitric oxide are produced by endothelial cells as a response to sepsis and lead to vasodilation. The redistribution of intravascular fluid due to increased endothelial permeability and reduced vascular tone similarly contributes to hypotension.18


Altered mental status is a common finding in sepsis and included in the qSOFA criteria. Endothelial activation creates a disturbance in the blood brain barrier and allows for the passage of neurotoxic factors that cause a decrease in neurotransmitters and result in toxic metabolic encephalopathy. Inflammatory mediators, ischemia, and hypoxemia create oxidative stress and associated cellular dysfunction and apoptosis also contributing to encephalopathy.19


Acute kidney injury due to acute tubular necrosis results from hypoperfusion due the vasodilatory effects of nitric oxide. Other factors that play a role in acute kidney injury during sepsis are not fully understood. Acute kidney injury can occur in patients with sepsis without hypotension. It has been suggested that the surge of inflammatory markers and oxidative stress associated with sepsis may cause renal endothelial damage. Activation of the coagulation cascade may lead to microvascular thrombi formation and renal microcirculatory injury.20


The liver plays a large role in bacterial clearance, producing inflammatory cytokines (TNF, IL-6, IL-1ß) and chemokine (C-C motif chemokine ligand 2) as a response to danger-associated molecular patterns (DAMPs) from microbial invasion. This response results in downstream signaling of hepatocyte production of acute-phase proteins and other inflammatory mediators (IL-8 and C-X-C motif chemokine ligand 1). Neutrophils and monocytes then accumulate in the liver increasing antimicrobial detection. The overwhelming inflammatory response can lead to liver injury especially in those with preexisting cirrhosis. Sepsis related mechanisms of liver injury include hypoxic hepatitis (shock liver), occurring in patients with hypotension and hypoxemia, sepsis-induced cholestasis, and secondary sclerosing cholangitis.21

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Risk Factors

Recognition of patient risk factor for sepsis are of utmost important for this life-threatening condition. Identified risk factors for sepsis include

  • Age
    • Less than 2 years
    • 65 and older
  • Comorbidities
    • Diabetes
    • Obesity
    • Immunosuppression
    • Malignancy
    • Protein calorie malnutrition
    • Human immunodeficiency virus
  • Other
    • Community acquired pneumonia
    • Intensive care unit admission
    • Bacteremia
    • Previous hospitalization.22,23,24,25,26,27

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Signs and Symptoms 

The signs and symptoms of sepsis and septic shock are nonspecific and include tachycardia, fever, tachypnea, and organ dysfunction, characterized by cyanosis, decreased capillary refill, ileus, or altered mental status. Hemodynamic measurements that suggest septic shock includes increased cardiac output and low systemic vascular resistance. Abnormalities of the complete blood count, comprehensive metabolic panel, clotting factors, and acute-phase reactants may also indicate burgeoning sepsis (Table 3).

Table 3: Laboratory Indicators of Sepsis




White blood cell count

Leukocytosis or leukopenia

Endotoxemia may cause early leukopenia



In the absence of diabetes

Platelet count

Thrombocytosis or thrombocytopenia

High value early may be seen as acute-phase response; low platelet counts seen in overt DIC

Arterial hypoxemia

PaO2/FiO2 < 300 mm Hg

Measure of oxygen delivery to tissues

Coagulation cascade

INR > 1.5; elevated D-dimer level; prolonged PT and PTT

Abnormalities can be observed before onset of organ failure and without frank bleeding.

Creatinine level

Elevated from baseline

Doubling-indicates acute renal injury

Lactic acid level

Lactic acid > 2 mmol/L

May indicate tissue hypoxia

Liver enzyme levels

Elevated alkaline phosphatase, AST, ALT, bilirubin levels

Indicates acute hepatocellular injury caused by hypoperfusion

Serum phosphate level


Inversely correlated with proinflammatory cytokine levels

Acute oliguria

Urine output < 0.5 mL/kg/hour

Despite adequate fluid resuscitation

C-reactive protein level


Acute-phase response

Procalcitonin level


Associated with bacterial infections

ALT = alanine aminotransferase; AST = aspartate transaminase; DIC = disseminated intravascular coagulation; INR = International Normalized Ratio; PaO2/FiO2 = ratio of partial pressure of arterial oxygen to the faction of inspired oxygen; PT = prothrombin time; PTT = partial thromboplastin time.

Data from Vincent 19965.

Conditions other than sepsis can produce organ dysfunction. Noninfectious illnesses that should be considered in the differential diagnosis of a patient with organ dysfunction include tissue injury caused by trauma, hematoma, venous thrombosis, myocardial or pulmonary infarction, transplant rejection, acute pancreatitis, thyroid storm, Addisonian crisis, drug or blood product reaction, tumor lysis syndrome, and central nervous system hemorrhages.28 Microbiologic workup should be pursued in patients with features of sepsis to delineate an infection diagnosis.

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The diagnosis of sepsis requires clinician interpretation of clinical, laboratory, and microbiologic data to ascertain the presence of an infection with concomitant organ dysfunction. The SOFA and qSOFA described above assess organ dysfunction but do not diagnose sepsis. Microbiologic cultures specific to the suspected infection should be obtained prior to the initiation of antimicrobials to help with identifying a pathogen as sterilization of cultures can occur rapidly with antibiotic administration.29 Workup should include at least 2 sets of blood cultures, and may include cerebrospinal fluid, urine, wound, respiratory, and other body fluid cultures depending on the patient’s presenting symptoms.

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Practice Guidelines

Eleven societies involved in the care of the critically ill collaboratively produced guidelines for the care of patients with severe sepsis, published in 2004 and updated in 2008, 2012, 2016, and 2018.7,8,30,31,32 The 2018 update, “Surviving Sepsis Campaign Bundle,” emphasizes the urgent recognition and treatment of sepsis.32

Resuscitation and management should begin immediately on patient presentation. Within the first hour, a lactate level should be drawn. If the initial lactate is over 2 mmol/L , then the lactate should be repeated within the hour. Cultures should be obtained prior to the start of broad-spectrum antibiotics within the hour. If the patient is hypotensive or has a lactate greater than 4 mmol/L, rapid administration of 30 mL/kg of intravenous crystalloid fluid should be started. If the patient remains hypotensive during or after fluid resuscitation, vasopressors should be initiated to maintain MAP of 65 mm Hg or greater. “Time zero” refers to time of triage in the emergency room or from the earliest chart annotation consistent with all elements of sepsis or septic shock.32

Fluid Resuscitation

Fluid resuscitation at the recognition of sepsis is paramount for the treatment of hypoperfusion and associated organ dysfunction. Following initial fluid resuscitation, the administration of additional fluids should be guided by frequent reassessment of the patient’s hemodynamic status with clinical examination and physiologic variables. In patients with an elevated lactate, fluid resuscitation should be given until lactate has normalized. An elevated lactate may represent tissue hypoxia and is associated with poor outcomes.33

Appropriate Diagnosis and Antimicrobial Treatment

The latest Surviving Sepsis Campaign update recommends the administration of appropriate antimicrobial therapy within the first hour of sepsis or septic shock identification. Appropriate cultures should be obtained prior to antibiotic initiation, and these always include at least 2 sets of blood cultures. Furthermore, appropriate cultures from all suspected sites of infection, as long as this does not lead to prolonged delays in antimicrobial administration (such as could occur for lumbar puncture or sputum cultures).32 The site of infection and causative organism(s) are often unknown at first and thus merit antibiotic selection guided by the patient’s history, comorbidities, and previous infections, as well as local pathogen prevalence and hospital susceptibility patterns. Many clinical studies have demonstrated a twofold increase in mortality caused by sepsis when inappropriate antimicrobial therapy is given. Studies have demonstrated an incremental but statistically significant increase in mortality with each hour delay in the administration of appropriate antibiotic therapy from the onset of septic shock.34

Empiric coverage for the suspected pathogen is paramount as survival may decrease up to fivefold in patients with septic shock that received inadequate antimicrobial coverage.35

A clinical trial of patients with sepsis revealed that the lungs are the most common sites of infection, followed by the abdomen and urinary tract.36 Gram-positive, gram-negative, and mixed bacterial infections are the most common pathogens responsible for sepsis and septic shock. Fungal organisms accounted for 4.6% of sepsis cases in 2000.37 The most common gram-positive organisms are Staphylococcus aureus and Streptococcus pneumoniae, while the most common gram-negative organisms are Escherichia coli, Klebsiella spp., Pseudomonas spp., and Enterobacter spp.36 Samples for blood cultures should be taken from a percutaneous site and from any intravascular catheters. Samples for Gram stain and culture should be taken from suspected sites of infection. Empiric antifungal therapy should be given to patients at high risk for fungal infections, such as those with immunocompromised status, prolonged invasive vascular devices, total parenteral nutrition, necrotizing pancreatitis, recent major intra-abdominal surgery, prolonged administration of broad-spectrum antibiotics, prolonged hospital admission, and previous fungal infection.38 Patients specifically at risk of non-albicans Candida should be empirically treated with an echinocandin. Appropriate empiric coverage can be selected by means of institution-specific antibiograms or with an infection diseases consultation39,40,41

The infective pathogen is not identified in a third of patients with sepsis.35 When a pathogen is identified, antimicrobials should be deescalated to the most effective narrow-spectrum antibiotic. When no pathogen is identified, clinicians should deescalate antibiotics in accordance with the patient’s clinical improvement. If no infection is suspected, antimicrobials should be discontinued. Clinicians should preform daily assessments for appropriate deescalation of antimicrobial therapy. A procalcitonin may be used to discontinue antibiotics in patients who demonstrated clinical features of sepsis with limited evidence of infection. A meta-analysis of randomized controlled trials in patients with suspected sepsis noted that procalcitonin use led to earlier discontinuation of antibiotics with no change in patient mortality rates.42

Source Control of Infection

Adequate source control is as important as appropriate antimicrobial therapy in the treatment of a patient with sepsis. This requires rapid diagnosis of the underlying infection driving the life-threatening, deregulated immune response. Source control may include removal of infected foreign bodies, such as urinary catheters, intravascular catheters, peritoneal dialysis cannulas, prosthetic joints, vascular grafts, and mechanical valves. Incision and drainage of cutaneous abscesses as well as open or percutaneous drainage of intra-abdominal abscesses may also be merited to establish adequate source control.43 For patients with necrotizing fasciitis, mortality and extent of tissue loss are directly related to the rapidity of surgical intervention. Intra-abdominal infections including gastric perforation, ischemic bowel or volvulus, cholangitis, and cholecystisis may also warrant further surgical intervention. Identification and management should ideally occur within 6 to 12 hours of diagnosis.7, 44

Vasopressor Treatment

Norepinephrine is the first-line agent for the treatment of septic shock. Norepinephrine is a potent vasoconstrictor with few cardiac effects. Norepinephrine has the added advantage of causing fewer tachyarrhythmias than dopamine and does not suppress the hypothalamic-pituitary axis, thus resulting in less immunosuppressive effects. A clinical trial comparing dopamine and norepinephrine in fluid-resuscitated patients with septic shock demonstrated a greater reversal of hypotension and lower mortality with the use of norepinephrine.45 Vasopressin has become the agent of choice in cases of septic shock refractory to norepinephrine. Vasopressin increases blood pressure and allows norepinephrine drips to be weaned.46 Second-line agents for the treatment of septic shock include epinephrine, phenylephrine, and dopamine. Dopamine increases cardiac index and systemic vascular resistance. Low-dose dopamine compared with placebo for sepsis in a meta-analysis showed no difference between the groups; therefore dopamine is not recommended for use in septic shock.47 The use of epinephrine and phenylephrine is hampered by both drugs’ negative effects on splanchnic blood flow.48 For patients with low cardiac output but adequate left ventricular filling pressure, dobutamine is the first-line agent.

Low-Dose Corticosteroid Treatment for Septic Shock

Corticosteroids have long been considered for sepsis management because of their anti-inflammatory properties and beneficial effects on vascular tone. Clinical trials of high-dose, short-course corticosteroids have not demonstrated mortality benefits in patients with severe sepsis; however, trials of long-course, low-dose corticosteroids (< 200 mg/day of hydrocortisone for at least 5 days) have been associated with a shorter time to shock reversal and improved mortality compared with standard of care.49 The largest of these trials showed improved mortality in patients with refractory septic shock no longer than 8 hours in duration with the use of hydrocortisone 50 mg every 6 hours and with fludrocortisone 50 µg daily for 5 days. Notably, patients included in this study did not respond with a 9 µg/dL rise in cortisol level 1 hour following adrenocorticotropic hormone (ACTH) stimulation.50 This trial suggests a treatment benefit with corticosteroids only in patients with adrenal insufficiency or adrenal resistance caused by sepsis.

Yet, a separate, larger trial, Corticosteroid Therapy of Septic Shock (CORTICUS), in a less severely-ill patient population with septic shock did not reveal a mortality benefit with low-dose corticosteroids—though a shorter time to shock reversal was noted. A higher incidence of hyperglycemia and superinfections was observed in the corticosteroid-treated arm.51 A systematic review showed no significant effect on mortality for any dose of steroids versus standard of care and a more recent meta-analysis did not support the CORTICUS trial’s conclusion that corticosteroid treatment benefit is related to ACTH test results.52 Due to these conflicting conclusions, the Surviving Sepsis Campaign guidelines recommend against the use of corticosteroids to treat patients with septic shock if adequate fluid resuscitation and vasopressor therapy are able to maintain MAP goals. In patients for whom vasopressors and adequate fluid resuscitation are insufficient to restore hemodynamic stability, 200 mg per day of intravenous hydrocortisone is recommended.7 The results of an ACTH test are not necessary to determine which patients should be treated.51

Glycemic Control

While early studies suggested tight blood glucose control during sepsis may decrease the rate of infectious complications and improve outcomes in patients with sepsis,53,54 more recent randomized control trials and meta-analyses showed that intensive insulin control may be associated with increased mortality due to hypoglycemic episodes.53,54 Most notably, the Normoglycemic in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study titrated insulin to maintain blood glucose levels of 180 mg/dL in the conventional glucose control group compared to goal blood glucose levels of 81 to 108 mg/dL in the intensive control group. The intensive control group had an increased mortality rate and increased event rate of severe hypoglycemia.55 The goal blood glucose level in patients with septic shock should be less than or equal to 180 mg/dL and insulin should be administered when 2 consecutive blood glucose levels are greater than 180 mg/dL. Patient blood glucose levels should be monitored every 1 to 2 hours until stabilized while on insulin.

Ventilator Treatment for Acute Respiratory Distress

Thanks to the efforts of organized networks of acute respiratory distress syndrome (ARDS) investigators in the U.S. and abroad, much has been learned about the appropriate ventilator management of patients with ARDS caused by sepsis. A randomized control trial demonstrated lower mortality and an increase in the number of days off the ventilator when a lower (6 mL/kg) tidal volume strategy compared with a standard (12 mL/kg) tidal volume strategy was employed.56 The upper limit goal for plateau pressures should be 30 cm H2O. Higher positive end-expiratory pressures (PEEP) in ARDS leads to improved gas exchange with possibly increased lung compliance. A meta-analysis showed a benefit of higher PEEP and is therefore recommended in patients with sepsis or septic shock.57 Prone position ventilation has been shown to improve oxygenation and survival and decrease mortality in patients with ARDS.58,59

Further recommendations are made in the guidelines for ventilator management. High frequency oscillatory ventilation, beta2 receptor agonists, and pulmonary artery catheters are not recommended for patients with sepsis and resultant ARDS. Neuromuscular blocking agents are recommended for 48 hours in patients with sepsis-induced ARDS and a ratio of partial pressure of arterial oxygen to the faction of inspired oxygen (PaO2/FiO2) less than 150 mm Hg. For septic patients without evidence of tissue hypoperfusion and ARDS, conservative fluid management is recommended.7


Blood transfusions in the critically ill have the potential to increase oxygen-carrying capacity but also pose an increased risk of nosocomial infection. In the early goal directed therapy protocol, transfusing red blood cells to achieve a hematocrit of 30% was used as part of the strategy to reach a central venous oxygen saturation of 70% during the first 6 hours of hospital stay. A study by Hébert and colleagues in critically ill patients demonstrated that maintaining hemoglobin between 7 mg/dL and 9 mg/dL and transfusing only when the hemoglobin drops below 7 mg/dL is not associated with a worse outcome than maintaining the hemoglobin above 10 g/dL.60 Red blood cell transfusion should only be given when hemoglobin concentration decreases to less than 7 g/dL.

Current guidelines recommend against the use of erythropoietin for the treatment of anemia in the context of sepsis. Fresh frozen plasma is not recommended to correct clotting abnormalities attributable to sepsis in the absence of ongoing bleeding or planned invasive procedures. Platelet transfusions are recommended for platelets less than 10,000 mm3 in the absence of bleeding and for platelets less than 20,000 mm3 if the patient has significant bleeding risk. In patients with active bleeding or planned surgery or invasive procedures, platelets should be transfused to obtain counts greater than 50,000 mm3. The use of intravenous immunoglobulins in sepsis or septic shock is not recommended.7

Additional Treatment Components

Additional components in the management of patients with sepsis include adequate nutrition, deep venous thrombosis prophylaxis, and gastric ulcer prophylaxis.7 Adequate nutrition is best accomplished enterally to avoid catheter-related blood stream infections and to maintain the integrity of the gastrointestinal mucosa so as to prevent the possibility of translocation of bacteria across the intestinal wall. Enteral feeds containing omega-3 fatty acids was associated with reduced mortality as compared with standard enteral feeds in a small clinical trial of patients with sepsis.61 Deep venous thrombosis prevention can be accomplished with the use of intermittent subcutaneous heparin or the continuous use of pneumatic compression stockings. Gastric ulcer prophylaxis is accomplished with sucralfate, an H2 receptor antagonist, or a proton pump inhibitor in patients with risk factors.

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Prevention of sepsis and septic shock relies on the reduction of infectious risk factors. Every effort should be made to vaccinate susceptible patients against influenza, Hemophilus influenzae, and Streptococcus pneumoniae. Asplenic patients and patients living in close quarters should additionally receive vaccination against Neisseria meningitidis.The incidence of intravascular catheter-related blood stream infections can be diminished by strict procedures to ensure sterile insertion and maintenance of the catheter with chlorhexidine dressings at the exit site. Cases of ventilator-associated pneumonia can be decreased by maintaining aspiration precautions, with ventilated patients positioned at a 45-degree angle. Universal hand hygiene should be strongly encouraged. Surveillance and urgent intervention should be pursued for hospitalized patients with early clinical signs and symptoms of sepsis to prevent escalation to septic shock.

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  • Sepsis is defined as life-threatening organ dysfunction caused by a deregulation host response to infection.
  • The Sequential Organ Failure Assessment (SOFA) score is used to help determine organ failure and sepsis.
  • Organ dysfunction is defined as an acute change in total SOFA score of 2 or more points consequent to the infection.
  • Sepsis occurs when the host’s immune response becomes generalized, causing imbalances in the coagulation cascade, endothelial injury, tissue ischemia, cellular injury, and apoptosis.
  • The signs and symptoms of sepsis and septic shock are nonspecific but may include fever, tachycardia, hypotension, and an elevated lactate.
  • Expedited therapy is critical in sepsis due to the high mortality. Within the first hour, cultures should be obtained, lactate should be drawn, fluid resuscitation with rapid administration of 30 mL/kg of crystalloid should be started (if patient has an elevated lactate greater than 4 or is hypotensive), and appropriate antimicrobials should be given.
  • If the patient remains hypotensive during or after fluid resuscitation, vasopressors should be initiated to maintain a mean arterial pressure (MAP) greater than 65 mm Hg.

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