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Causes of Sepsis

Sepsis does not arise on its own. It stems from another medical condition, such as an infection in the lungs, urinary tract, skin, abdomen, or other part of the body. Invasive medical procedures like the insertion of a vascular catheter can introduce bacteria into the bloodstream and bring on the condition (NIGMS, 2018).

Many different types of microbes can cause sepsis, including bacteria, fungi, and viruses, but bacteria are the most common culprits. Severe cases often result from a body-wide infection that spreads through the bloodstream, but sepsis can also stem from a localized infection (NIGMS, 2018). Once a septic reaction is triggered, the resulting damage is widespread, extensive, and life-threatening.

Originally sepsis was described as a disease specifically related to Gram-negative bacteria. This is because sepsis was thought to be a response to endotoxin—a molecule felt to be relatively specific for Gram-negative bacteria. In fact, some of the original studies of sepsis showed that Gram-negative bacteria were among the most common causes of sepsis. This resulted in a number of trials that focused on Gram-negative therapies, and even highly specific therapies for endotoxin, which were felt to be potentially useful treatments for sepsis. It is now recognized that sepsis can be caused by any bacteria, as well as from fungal and viral organisms.

While bacterial causes of sepsis have increased, fungal causes of sepsis have grown at an even more rapid pace. This may represent a general increase in hospital-acquired cases of sepsis, or it may reflect effective treatment of bacterial infections, which then allowed fungal infections to grow without competition (Martin, 2012).

Development of Sepsis Following Infection

In a classic systemic infection, the body’s immune response is self-limiting: the immune forces are called into action, the battle is fought, and the army retires. Sepsis begins like a typical infection and often presents with the signs of a classic systemic infection—fever, tachycardia, tachypnea, and an elevated white blood cell count. However, in sepsis the natural checks and balances fail. Instead of tapering off and disappearing, the inflammatory forces spread beyond the infected region.

The immune response begins as pro-inflammatory signal molecules enter the bloodstream in large numbers. As they travel through the vascular system, these molecules cause dilation and leaking of the endothelium that lines the blood vessels. The usual orderly movement of oxygen, nutrients, and fluids through the capillary walls is disrupted and organs become hypoxic (starved of oxygen).

If the sepsis continues, organ hypoxia and damage become organ failure, and at this point the condition is called severe sepsis. Severe sepsis increases the likelihood that the patient will die. When the organ system that fails is the circulatory system, the arterial wall muscles can no longer contract sufficiently to maintain adequate blood pressure. Now the patient is in septic shock, and the chance of surviving declines further (Shapiro et al., 2010).

The systemic collapse that occurs in sepsis is called systemic inflammatory response syndrome (SIRS). SIRS can be triggered by a variety of causes, including noninfectious causes such as pancreatitis, trauma, or burns. When it is triggered by an infection, SIRS is called sepsis and, unlike other types of SIRS, sepsis must be treated with antibiotics to remove or control the primary source of the infection.

Although any infection can trigger sepsis, to develop sepsis, a microbial infection is necessary but not sufficient: it appears that a patient also needs a pre-existing susceptibility. Support for this idea can be seen in large surveys of ICU patients. These surveys found that “approximately 70% to 80% of the cases of severe sepsis in adults occurred in individuals who were already hospitalized for other reasons” (Munford & Suffredini, 2009).

Early Recognition of Sepsis

Early recognition of sepsis is the responsibility of all healthcare providers. The challenge is to pick out the signs of sepsis from among the other abnormalities plaguing a patient. To make sepsis easier to identify, there has been an effort to standardize its definition despite its wide range of presentations.

Classic signs and symptoms of a systemic infection that may be associated with sepsis in persons with confirmed or suspected infection can include:

• Fever
• Tachypnea
• Tachycardia
• High white blood cell count

The severity of the septic reaction should also produce other warning signs, such as:

• Hot, flushed skin
• Newly altered mental status
• Hypotension
• Widened pulse pressure*
• Elevated blood lactate level
• Thrombocytopenia

* Pulse pressure is the difference between the systolic and the diastolic blood pressure values.

People who are elderly, immunocompromised, or neutropenic (have an abnormally low levels of white blood cells) are the most likely to develop a septic response to an infection. Because of our aging population and because medical care is increasing the longevity of immunocompromised patients, the cases of sepsis are increasing in the United States (CDC, 2018).

Severe Sepsis and Septic Shock

Severe sepsis can develop if sepsis continues, leading to organ hypoxia and organ failure. Severe sepsis increases the likelihood that the patient will die. When the organ system that fails is the circulatory system, the arterial wall muscles can no longer contract sufficiently to maintain adequate blood pressure. Now the patient is in septic shock, and the chance of surviving declines further (Shapiro et al., 2010).

Severe sepsis and septic shock are unfortunately common, complicated and deadly conditions within the same pathophysiologic spectrum. If a clinician believes that a patient is exhibiting SIRS secondary to infection, that patient has sepsis. If that same patient has signs or symptoms of organ dysfunction, then that patient has severe sepsis. Septic shock is then characterized by overall tissue hypoperfusion, tissue hypoxia, or general hypotension that fails to respond to fluid resuscitation (Tannehill, 2012).

Severe sepsis, or sepsis syndrome, is present when the patient has progressed to a stage in which one or more organs or organ systems begin to fail. The Surviving Sepsis Campaign no longer uses the term severe sepsis but simply sepsis.

Sepsis is considered severe when a patient has one of the following clinical problems:

• Cardiovascular system dysfunction
• Acute respiratory distress syndrome (ARDS)
• Dysfunction of two or more other organs or systems

Septic shock is acute circulatory failure with refractory (difficult to reverse) hypotension that is unexplainable by other causes. The term shock describes a condition in which many tissues throughout the body become hypoxic due to poor perfusion. In shock, normal homeostatic mechanisms are either not functioning or not adequate to deliver enough oxygen to tissues. If it is not reversed, shock leads to organ failure and death. Septic shock is a form of distributive shock. In septic shock, there is hypotension and vasodilation that cannot be reversed by giving adequate fluids. When the hypotension of septic shock does not respond to vasopressors, the condition is called refractory septic shock (Munford & Suffredini, 2009).

Septic shock presents with hypotension, oliguria, abnormal mental status (restlessness, confusion, lethargy, or coma), and metabolic acidosis due to an increased concentration of lactate in the blood. When the shock is septic, it can also present with tachycardia, tachypnea, fever, and a high white blood cell count (Gaieski, 2013). A key sign in sepsis is hypotension that cannot be reversed with fluids alone.

The hypotension of shock may be absolute, with a systolic blood pressure <90 mm Hg. Alternately, the hypotension of shock may be relative and take the form of a drop in systolic blood pressure >40 mm Hg; in this situation, hypertensive people can be in shock although their presenting blood pressures are within the normal range. When a person is in shock, vasopressors are frequently needed to maintain adequate perfusion of tissues.

For a patient in shock, diagnostic tests, a physical examination, and a medical history should not delay procedures that will stabilize the patient’s circulation and respiration. Instead, data should be collected while the patient is being resuscitated. It is important to know the patient’s blood and serum chemistry values, so resuscitators need to draw blood samples.

Principles of Sepsis Treatment

The initial step in the treatment of sepsis is to stop the infection, protect the vital organs, and prevent a drop in blood pressure. International clinical practice guidelines and the Centers for Medicare and Medicaid Services (CMS) recommend the prompt identification of sepsis and treatment with broad-spectrum antibiotic agents and intravenous fluids (Seymour et al., 2017).

More seriously affected patients might need a breathing tube, kidney dialysis, or surgery to remove an infection. Despite years of research, scientists have not yet developed a medicine that specifically targets the aggressive immune response seen with sepsis (NIGMS, 2018). Prompt diagnosis and treatment are critical for optimal outcomes; there is increased morbidity/mortality with delayed recognition and response.

New York Codes, Rules, and Regulations parts 405.2 and 405.4 require all sepsis protocols to include receipt of the following care within 3 hours:

• Obtaining of a blood culture before the administration of antibiotics
• Measurement of the serum lactate level
• Administration of broad-spectrum antibiotics (Seymour et al., 2017)
• Protocols also require a 6-hour bundle, consisting of:
• Administration of a bolus of 30 ml of intravenous fluids per kilogram of body weight in patients with hypotension or a serum lactate level of 4.0 mmol or more per liter
• Initiation of vasopressors for refractory hypotension
• Re-measurement of the serum lactate level within 6 hours after the initiation of the protocol (Seymour et al., 2017)

Diagnostic modalities include blood cultures and other testing to identify source and site or infection and organ dysfunction. Treatment includes administration of appropriate IV antimicrobial therapy, with source identification and de-escalation of antibiotics as soon as feasible. These recommendations are supported by preclinical and observational studies suggesting that early treatment with antibiotics and intravenous fluids could reduce the number of avoidable deaths (Seymour et al., 2017).