During the series of events called the

Sepsis has become the tenth leading cause of death in the United States. It is the No.1 cause of death in hospital noncardiac ICUs, where mortality ranges from 20% in patients with sepsis to 40% to 60% in patients with severe sepsis and septic shock.^2,3 Each year in the United States, the incidence of sepsis increases about 9%.² In 2006, more than 750,000 cases of sepsis with 225,000 deaths were reported — more deaths than from breast, colon/rectal, pancreatic, and prostate cancer combined.² By 2010, more than 1 million cases are expected.^1-6

Why is sepsis increasing?

Various factors have led to the increase in sepsis. First, the population is aging, and older patients are more likely to develop sepsis because of general reduced cell-mediated immunity. After age 60, the risk for developing sepsis increases exponentially.³ Secondly, the number of immunosuppressed patients is growing as a result of organ and bone marrow transplantation, more aggressive chemo- and radiation therapy for cancer, corticosteroid therapy, and HIV infection. Invasive diagnostic and therapeutic procedures (including arterial lines, pulmonary artery catheters, central venous lines, ventricular shunts, and Foley catheters) allow pathogenic organisms to bypass the body’s natural defenses and therefore also contribute to the increasing incidence of sepsis In addition, the emergence of resistant organisms is making infections more difficult to treat.³

Terminology confusion

For many years, the terminology describing the body’s inflammatory response to infection was confusing. Terms included sepsis, blood poisoning, bacteremia, and septicemia. Then, in 1991, the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference developed precise definitions for the stages of sepsis:

1. Infection — an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms.

2. Systemic inflammatory response syndrome (SIRS) — the systemic inflammatory response to a variety of severe clinical insults, including infection, pancreatitis, trauma, and burns. This response is manifested by two or more of the following conditions:

• Core temperature higher than 38 C (100.4 F) or less than 36 C (96.8 F)
• Heart rate higher than 90 beats/min.
• Respiratory rate higher than 20 breaths/min. or PaCO2 of less than 32 mmHg
• White blood cell count higher than 12,000/mm³, less than 4,000/mm³, or the presence of more than 10% immature neutrophils

3. Sepsis — a documented infection with at least two of the four systemic inflammatory response criteria. Sepsis is, by definition, caused by infection.

4. Severe sepsis — sepsis associated with dysfunction of one or more organ systems, hypoperfusion, or hypotension. Hypoperfusion and perfusion abnormalities can include lactic acidosis, and oliguria (scant urination).

5. Septic shock — sepsis with hypotension (systolic BP less than 90 Hg or a reduction of 40 mm Hg from baseline) despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include lactic acidosis, oliguria, or an acute alteration in mental status. Patients who are receiving inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured.

6. Multiple organ dysfunction syndrome — altered organ function due to altered perfusion in an acutely ill patient such that homeostasis cannot be maintained without intervention.⁴

Why things go wrong

Normally, the body’s immune system initiates a rapid protective inflammatory response to a microbial invasion. However, when this response exceeds the counterbalancing effect of anti-inflammatory regulation, the result can be catastrophic, often leading to multiorgan failure and death.³

The body’s innate immune system protects against infection by recognizing foreign antigens (proteins) unique to microorganisms. These antigens include material from the cell walls of bacteria and yeast, bacterial DNA, and the RNA from viruses. Receptors on the body’s T-cells can recognize these microbial antigens and bind to them. This binding leads to the activation of white blood cells (macrophages and neutrophils) and the release of special proteins called cytokines (interleukins, interferons, and tumor necrosis factor) that initiate the inflammatory response. This leads to microvascular permeability (leaky capillary walls) and vasodilation. Damage to blood vessel linings from inflammation triggers a coagulation cascade that causes blood (fibrin) clots to form and localize the infection. Normally, the formation of blood clots is controlled by a process called fibrinolysis or “clot busting.” But during sepsis, fibrinolysis is suppressed, and blood flow to vital organs and extremities becomes blocked with microscopic blood clots.

If the inflammatory process continues, severe sepsis can occur, leading to decreased blood flow to vital organs and sometimes death.⁷ When the body counteracts and tries to control the inflammatory response by producing anti-inflammatory cytokines, a period of immunosuppression occurs that, if prolonged, can increase the patient’s susceptibility to other infections.

On the alert for sepsis

Sepsis should be considered whenever a patient presents with a known or suspected infection and with two or more of the following symptoms of SIRS: fever or hypothermia, unexplained tachycardia and tachypnea, or altered white blood cell count. Other findings include peripheral vasodilation; cool, clammy skin; unexplained shock; and reduced mental alertness.⁷ If, in addition, any organ failure is confirmed, the diagnosis is considered severe sepsis.⁷ Under these conditions, airway, breathing, and circulation should be immediately assessed, and a thorough history and physical examination focused on identifying the source/site of infection should be conducted. Appropriate cultures and hemodynamic measurements need to be included.

System by system

Airway and breathing. Pulmonary signs of sepsis include an increased respiratory rate with hyperventilation, hypoxemia, and respiratory alkalosis. Increased permeability of the alveolocapillary membrane causes pulmonary edema. As respiratory muscles become fatigued, serum lactate accumulates. Nearly 85% of sepsis patients require ventilator support for one to two weeks during the course of the disease.^3,5 Tissue hypoxia can lead to acute respiratory distress syndrome, a common complication in up to 60% of cases of septic shock. ARDS mortality ranges from 35% to 65%. The extent of respiratory dysfunction can be confirmed by pulse oximetry, arterial blood gas analysis to assess oxygenation, and chest X-ray. A respiratory rate greater than 30 with hypoxemia and a pH less than 7.2 usually is a sign of approaching respiratory collapse.^3,7

Cardiovascular. During sepsis, adequate blood and oxygen are not circulated to the vital organs of the body even with increased cardiac output. The overproduction of vasoactive mediators such as nitric oxide and an impaired secretion of vasopressin lead to both arterial and venous vasodilation with leakage of plasma into the extravascular space. The results are decreased blood pressure, decreased venous return to the heart, and, ultimately, decreased cardiac output. The result is less oxygen to the tissues, leading to cellular dysfunction, lactic acidosis, and finally multiorgan failure. The adequacy of circulation can often be judged by looking at surrogate measures of perfusion (mentation, urinary output, skin perfusion, and blood pressure).^3,7

Hematology. Leukocytosis (an increase in white blood cells) with a shift to the left is commonly seen in sepsis, as is thrombocytopenia (a decreased number of  platelets) .

Fortunately, disseminated intravascular coagulation (depletion of clotting factors in the blood) is rare. A mild to moderate elevation in thrombin or activated partial thromboplastin time (aPTT) is common, as is decreased fibrinogen.⁹ Almost all patients with severe sepsis exhibit elevated plasma levels of D-dimer (marker of fibrinolytic events) even though they may have normal levels of other coagulation parameters, such as PT, PTT, and platelet count.³

Renal. Inadequate renal perfusion leads to oliguria, with urine output measuring less than 0.5 mL/kg per hour.¹⁰ Glomerular filtration decreases, and the kidneys no longer excrete sodium and water. The ability to regulate acid base and electrolyte balances is altered. Blood urea nitrogen and serum creatinine concentrations can increase. Serum creatinine levels of higher than 20 mg/dl can indicate renal failure that occurs in 50% of patients diagnosed with septic shock.^3,7

GI system. The GI tract quickly becomes hypoxic as blood is shifted to more vital organs. Gastrointestinal motility is impaired, and patients are at risk for a paralytic ileus. Stress ulcers are common. The liver loses its ability to detoxify the blood, and increases in hepatic transaminases and hyperbilirubinemia are seen.³

Central nervous system. Fever is caused by inflammatory mediators, and nearly 60% of patients with sepsis present with a fever higher than 38 C (100.4 F).¹¹ Many patients exhibit altered mental status, which usually is one of the earliest and most consistent clinical signs of sepsis.³

What to watch for

Overwhelming sepsis progresses to shock in about 40% of patients.^3,5 As a patient goes into shock, the body attempts to compensate. At first, the patient exhibits signs of restlessness and tachycardia with a widening pulse pressure, tachypnea, and oliguria. The elevated heart rate compensates for decreased venous return, and there is an increased rate and force of each cardiac contraction in an attempt to improve tissue perfusion. During this period, the patient’s skin appears warm, dry, and flushed because of increased cardiac output and vasodilation. The most important sign during the compensatory phase is the widening pulse pressure (the difference between systolic and diastolic pressure, with diastolic pressure representing peripheral vascular resistance). As vasodilatation increases and peripheral vascular resistance decreases, diastolic pressure drops with little change in systolic pressure.³

An increased respiratory rate ensues in an attempt to compensate for the metabolic acidosis caused by the release of lactic acid from hypoxic tissues. This expels carbon dioxide from the body and causes the pH of the bloodstream to increase.³ As the body attempts to keep the central nervous system and the cardiac system perfused, blood is shunted away from the renal system, and urinary output decreases.

If cardiac output continues to deteriorate, systolic blood pressure will drop, and the patient will enter the progressive phase of the shock syndrome, i.e., several organs are failing and the patient will present with changes in level of consciousness, hypotension, a rapid thready pulse, decreased urinary output, hypoactive bowel sounds, and rapid shallow breathing. The skin will become cold, clammy, and mottled. At this point, sepsis is far advanced, and at least half of the patients will die of multiple organ system failure.³

Multiple organ dysfunction syndrome

Multiple organ dysfunction syndrome is the sequential loss of normal functioning of vital organ systems. Mortality is high, up to 90%, when more than one organ system is involved. For those who do survive an episode of sepsis, the increased risk of death continues for up to five years after recovery.³

Sources of infection

Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae used to be the major cause of sepsis. But since the mid-1980s, gram-positive bacteria have become the predominant cause, accounting for 56% of cases.^1,2 The most common gram-positive bacteria causing sepsis today are Staphylococcus aureus, coagulase-negative staphylococcus, Streptococcus pneumoniae, and enterococci. As an example of the predominance of gram-positive bacteria infections in hospitals, more than 60% of bacteremias are caused by three gram-positive bacteria: coagulase-negative staphylococci (37%), S. aureus (13%), and enterococci (13%). The most common cause of community-acquired pneumonia is another gram-positive organism, S. pneumoniae. (50% of sepsis cases can be attributed to pneumonia.)

But while gram-negative bacteria are not the major cause of sepsis, they are the most deadly. Nearly 60% of gram-negative bacteremias lead to septic shock, while only 5% to 10% of patients with gram-positive or fungal bloodstream infections develop sepsis.^1,2,5,6 E. coli, K. pneumonia, Pseudomonas aeruginosa, Proteus species, Serratia species, and Neisseria meningitidis are the gram-negative bacteria of greatest concern.

The incidence of fungal sepsis has increased threefold since 1979, accounting for 5% of all cases of sepsis, severe sepsis, and septic shock.^5,6 Most cases are caused by Candida species. Candida is currently the fourth most frequent cause of nosocomial bloodstream infections in the United States and has the highest mortality rate (40%) of all bloodstream pathogens.^1,2

How to treat sepsis

Early recognition of sepsis and prompt treatment are essential for patient survival. Initially, a septic patient needs to be stabilized with supplemental respiratory and circulatory support through the administration of oxygen and volume infusion with crystalloid and/or colloid fluids. The goal is to restore the patient’s mean arterial pressure to 60-65 mmHg.^3,4 This improves tissue perfusion, cellular oxygenation, and cellular metabolism. With the patient stabilized, the underlying infection can be identified (location and organism) and a treatment plan developed.^3,4

Volume resuscitation is one of the most important treatments for patients with septic shock.⁴ Hypovolemia, due to vasodilation and capillary leak, is nearly universal and requires aggressive fluid infusions to restore blood pressure and tissue perfusion. Crystalloid (lactated Ringer’s) and colloid (albumin) fluid resuscitation are equally effective, with most patients requiring 1 to 2 liters of colloid or 4 to 8 liters of crystalloid to restore circulating volume. When the administration of fluids and oxygen to the patient is sufficient to reverse hypotension and restore organ perfusion, heart rate and capillary refill time will decrease, blood pressure will increase, and organ function will improve. However, when volume resuscitation is inadequate to restore blood pressure, vasoactive drugs is recommended. The most common agents are dobutamine (Dobutrex), norepinephrine bitartrate (Levophed), and vasopressin (Pitressin). During volume resuscitation, patients should be observed for signs of volume overload, which can appear as dyspnea from pulmonary edema.^5,6,7 In addition, pulmonary support (mechanical ventilation), renal support (dialysis), nutritional support (enteral feeding), glucose control, and hematological support (transfusions) may be needed.^6,7

Along with volume replacement, early administration of antimicrobials, preferably within two hours of recognizing sepsis, is essential. Since the causative microorganism usually has not been identified this early in treatment, broad spectrum and/or multiple antibiotics are used to provide the necessary coverage.

The Surviving Sepsis Campaign Guidelines outline evidence-based recommendations for targeting treatment of patients at risk of developing severe sepsis and septic shock based on existing research evidence.^8,9 The Surviving Sepsis Campaign Guidelines are aimed at providing resuscitation for sepsis-induced hypoperfusion and enhancing perfusion, antibiotic administration to combat infection, and cultures to identify the source of infection. Other aspects of treatment depend on the patient’s clinical changes and include mechanical ventilation to optimize oxygenation and use of evidence-based treatment practices for critically ill patients, including glucose control, steroid use for adrenal insufficiency, prophylaxis measures for deep vein thrombosis and stress ulcer prevention, renal replacement therapies, recombinant human activated protein C (rhAPC), blood product administration, sedation and analgesia, and consideration for limitation of support in critically ill patients.^8,9  

Patients with severe sepsis must be monitored continuously by experienced nurses able to assess subtle changes in their condition. Blood pressure, heart rate, pulse, respiratory rate, body temperature, urine output, mental status, central venous pressure, and arterial pressure should be carefully monitored and documented according to protocol. Recovery is possible with prompt and aggressive treatment using antibiotics, organ-system support, and meticulous care — and if complications are prevented.

Patients also need protection from nosocomial infections. Septic patients are extremely vulnerable to infections as the result of immune function depression and procedures that breach the body’s natural defenses. Since handwashing is the most effective measure to prevent transmission of infections, nurses must ensure that all staff and visitors wash their hands before and after contact with patients.

With knowledge of prevention and detection measures, nurses can guard their patients against the often life-threatening effects of sepsis and participate in the efforts to slow the growth in the incidence of sepsis.¹⁰