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Sepsis, Severe Sepsis, and Septic Shock

By Paul M. Maggio, MD, MBA, Stanford University Hospital ; Carla Carvalho, MD, MPH, Stanford University Hospital

Sepsis is a serious bodywide response to bacteremia or another infection. Severe sepsis is sepsis plus either failure of an essential system in the body or inadequate blood flow to parts of the body due to an infection. Septic shock is life-threatening low blood pressure (shock) due to sepsis.

  • Usually, sepsis results from certain bacterial infections, often acquired in a hospital.

  • Having certain conditions, such as a weakened immune system, certain chronic disorders, an artificial joint or heart valve, and certain heart valve abnormalities, increases the risk.

  • At first, people have a high (or sometimes low) body temperature, sometimes with shaking chills and weakness.

  • As sepsis worsens, the heart beats rapidly, breathing becomes rapid, people become confused, and blood pressure drops.

  • Doctors suspect the diagnosis based on symptoms and confirm it by detecting bacteria in a sample of blood, urine, or other material.

  • Antibiotics are given immediately, and people with septic shock are given oxygen and fluids by vein and sometimes drugs to increase blood pressure.

Usually, the body’s response to infection is limited to the specific area infected. But in sepsis, the response to infection occurs throughout the body—called a systemic response.

This response includes an abnormally high temperature (fever) or low temperature (hypothermia) plus one or more of the following:

Severe sepsis is sepsis that causes organs to malfunction and blood flow to become inadequate to parts of the body.

Septic shock is diagnosed when blood pressure remains low despite intensive treatment with fluids by vein.

Causes

Sepsis occurs when toxins produced by certain bacteria cause cells in the body to release substances that trigger inflammation ( cytokines). Although cytokines help the immune system fight infection, they can have harmful effects:

  • They can cause the blood vessels to widen (dilate), decreasing blood pressure.

  • They can cause blood to clot in tiny blood vessels inside organs.

Most often, sepsis is caused by infection with certain kinds of bacteria that are usually acquired in a hospital. Rarely, fungi, such as Candida, cause sepsis. Infections that can lead to sepsis begin most commonly in the lungs, abdomen, or urinary tract. In most people, these infections do not lead to sepsis. However, sometimes bacteria spread into the bloodstream (a condition called bacteremia). Sepsis may then develop. If the initial infection involves an abscess, the risk of bacteremia and sepsis is increased. Occasionally, such as in toxic shock syndrome, sepsis is triggered by toxins released by bacteria that have not spread into the bloodstream.

Complications

The decreased blood pressure and small clots lead to a series of harmful complications:

  • Blood flow decreases to vital organs (such as the kidneys, lungs, heart, and brain).

  • The heart attempts to compensate by working harder, increasing the heart rate and the amount of blood pumped. Eventually, the bacterial toxins and the increased work of pumping weaken the heart. As a result, the heart pumps less blood, and vital organs receive even less blood.

  • When tissues do not receive enough blood, they release excess lactic acid (a waste product) into the bloodstream, making the blood more acidic.

All of these effects result in a vicious circle of worsening organ malfunction:

  • The kidneys excrete little or no urine, and metabolic waste products (such as urea nitrogen) accumulate in the blood.

  • The walls of blood vessels may leak, allowing fluid to escape from the bloodstream into tissues and cause swelling.

  • Lung function worsens because blood vessels in the lungs leak fluid, which accumulates, making breathing difficult.

Blood clots continue to form, using up the proteins in blood that make up clots (clotting factors). Then, excessive bleeding may occur (see also Disseminated Intravascular Coagulation (DIC)).

Risk Factors

The risk of sepsis is increased in people with conditions that reduce their ability to fight serious infections. These conditions include the following:

  • Being a newborn (see Sepsis in the Newborn)

  • Being elderly

  • Being pregnant

  • Having certain chronic disorders such as diabetes or cirrhosis

  • Having a weakened immune system due to use of drugs that suppress the immune system (such as chemotherapy drugs or corticosteroids) or due to certain disorders (such as cancer, AIDS, and immune disorders)

The risk is also increased in people who are more likely to have bacteria enter their bloodstream. Such people include those who have a medical device inserted into the body (such as a catheter inserted into a vein or the urinary tract, drainage tubes, or breathing tubes). When medical devices are inserted, they can move bacteria into the body. Bacteria may also collect on the surface of such devices, making infection and sepsis more likely. The longer the device is left in place, the greater the risk.

Other conditions also increase the risk of sepsis:

  • Injecting recreational drugs: The drugs and needles used are rarely sterile. Each injection may cause bacteremia to varying degrees. People who use these drugs are also at risk of disorders that can weaken the immune system (such as AIDS).

  • Having an artificial (prosthetic) joint or heart valve or certain heart valve abnormalities: Bacteria tend to lodge and collect on these structures. The bacteria may continuously or periodically be released into the bloodstream.

  • Having an infection that persists despite treatment with antibiotics: Some bacteria that cause infections and sepsis are resistant to antibiotics. Antibiotics do not eradicate the resistant bacteria. Thus, if an infection persists in people who are taking antibiotics, it is more likely to be caused by bacteria that are resistant to antibiotics and that can cause sepsis.

Symptoms

Most people have a fever, but some have a low body temperature. People may have shaking chills and feel weak. Other symptoms may also be present depending on the type and location of the initial infection. Breathing, heart rate, or both may be rapid.

As sepsis worsens, people become confused and less alert. The skin becomes warm and flushed. The pulse is rapid and pounding, and people breathe rapidly. People urinate less often and in smaller amounts, and blood pressure decreases. Later, body temperature often falls below normal, and breathing becomes very difficult. The skin may become cool and pale and mottled or blue because blood flow is reduced. Reduced blood flow may cause tissue, including tissue in vital organs (such as the intestine), to die, resulting in gangrene.

When septic shock develops, blood pressure is low despite treatment. Some people die.

Diagnosis

  • Culture of a blood sample

  • Tests to find the source of infection (tests usually include chest x-rays and other imaging tests and cultures of fluid or tissue samples)

Doctors usually suspect sepsis when a person who has an infection suddenly develops a very high or low temperature, a rapid heart rate or breathing rate, or low blood pressure.

To confirm the diagnosis, doctors look for bacteria in the bloodstream ( bacteremia), evidence of another infection that could be causing sepsis, and an abnormal number of white blood cells in a blood sample.

Samples of blood are taken to try to grow (culture) the bacteria in the laboratory (a 1- to 3-day process). However, if people have been taking antibiotics for their initial infection, bacteria may be present but may not grow in the culture. Sometimes catheters are removed from the body, and the tips are cut off and sent for culture. Finding bacteria in a catheter that had contact with the blood indicates that bacteria are probably in the bloodstream.

To check for other infections that may cause sepsis, doctors take samples of fluids or tissue, such as urine, cerebrospinal fluid, tissue from wounds, or sputum coughed up from the lungs. These samples are cultured and checked for bacteria.

Chest x-rays and other imaging tests, such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), may also be done.

Other tests are done to look for signs of organ malfunction and other complications of sepsis. They may include the following:

  • Blood tests to measure levels of lactic acid and other metabolic waste products, which may be high, and the number of platelets (cells that help the blood clot), which may be low

  • Blood tests or a sensor placed on a finger (pulse oximetry) to measure oxygen levels in the blood and thus evaluate how well the lungs and blood vessels are functioning

  • Electrocardiography (ECG) to look for abnormalities in heart rhythm and thus determine whether the blood supply to the heart is adequate

  • Other tests to determine whether shock results from sepsis or another problem

Prognosis

Without treatment, most people with septic shock die. Even with treatment, there is a significant risk of death. On average, about 30 to 40% of people with septic shock die. However, the risk of death varies greatly depending on many factors, including how quickly people are treated, the type of bacteria involved (particularly whether the bacteria are resistant to antibiotics) and the patient's underlying health status.

Treatment

  • Antibiotics

  • Intravenous fluids

  • Oxygen

  • Removal of the source of infection

Doctors immediately treat sepsis, severe sepsis, and septic shock with antibiotics. Doctors do not wait until test results confirm the diagnosis because a delay in antibiotic treatment greatly decreases the chances of survival. Treatment occurs in a hospital.

People with symptoms of severe sepsis or septic shock are immediately admitted to an intensive care unit for treatment.

Antibiotics

When choosing the initial antibiotics, doctors consider which bacteria are most likely to be present, which depends on where the infection started. Often, two or three antibiotics are given together to increase the chances of killing the bacteria, particularly when the source of the bacteria is unknown. Later, when the test results are available, doctors can substitute the antibiotic that is most effective against the specific bacteria causing the infection.

Intravenous fluids

People with septic shock are also given large amounts of fluid by vein (intravenously) to increase the amount of fluid in the bloodstream and thus increase blood pressure. Giving too little fluid is not effective but giving too much fluid can cause severe lung congestion.

Oxygen

Oxygen is given through a mask, through nasal prongs, or through a breathing (endotracheal) tube if one has been inserted. If needed, a mechanical ventilator (a machine that helps air get in and out of the lungs) is used to help with breathing.

Removal of the source of infection

If present, abscesses are drained. Catheters, tubes, or other medical devices that may have started the infection are removed or changed. Surgery may be done to remove infected or dead tissue.

Other treatments

If intravenous fluids do not increase blood pressure, doctors sometimes give drugs, such as vasopressin or norepinephrine (which cause blood vessels to narrow), to raise blood pressure and increase blood flow to the brain, heart, and other organs. However, because these drugs may narrow blood vessels within organs, they sometimes decrease the amount of blood flow through the organs.

Sometimes people who have septic shock develop a high blood sugar (glucose) level. Because high blood sugar impairs how the immune system responds to an infection, doctors give insulin by vein to people to lower the level of glucose in the blood.

Corticosteroids (such as hydrocortisone) may be given by vein to people whose blood pressure remains low despite being given adequate fluids, drugs to increase blood pressure, and having the source of their infection treated.

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • LEVOPHED
  • VASOSTRICT
  • CORTEF, SOLU-CORTEF

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