Sepsis: Causes, Complications, Risk Factors, Symptoms, Diagnosis, Prognosis and Treatment

It is a systemic inflammatory condition that occurs as a complication of an infection and, in severe cases, can be associated with acute and life-threatening organ dysfunction.

Around the world, sepsis has long been a common cause of illness and mortality in hospitals, intensive care units, and emergency departments.

At the beginning of the 21st century, however, its incidence increased, in part due to the growth of the elderly populations, which are the most susceptible to infection.

But factors such as increased life expectancy for people with immunodeficiency disorders such as AIDS, higher incidence of resistance to antibiotics, and greater use of anti-cancer chemotherapy and immunosuppressants used for organ transplantation.

Sepsis is a severe, whole-body response to bacteremia or other infection plus the malfunction or failure of an essential system in the body.

Septic shock is low blood pressure that endangers life and causes organ failure due to sepsis. Generally, the body’s response to infection is limited to the specific infected area.

But in sepsis, the response to infection occurs throughout the body, called the systemic response.

 

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

  • Fast heart rate
  • Rapid respiratory rate.
  • An abnormal white blood cell count.

Although many infections cause such symptoms throughout the body, in sepsis, the organs begin to malfunction, and blood flow becomes inadequate to parts of the body.

When a septic shock is diagnosed, blood pressure remains very low despite the administration of intensive intravenous fluids.

Causes

Anyone can get sepsis, although some people are more likely to get it, such as people with severe burns or injuries, weakened immune systems, infants, very young children, the elderly, or chronic illnesses.

When the body acquires an infection, chemicals are released through the bloodstream to fight the disease.

Sometimes, however, the body creates an overwhelming response to an infection, and chemicals released into the bloodstream can cause inflammation throughout the body.

This reaction is called sepsis. The inflammation can cause blood clots and leaky blood vessels.

Poor blood flow can cause damage to multiple organ systems and can even cause them to fail.

Any infection, such as bacterial, viral, or fungal, can cause sepsis; the most common varieties include pneumonia, an abdominal condition such as diverticulitis, appendicitis or gallbladder infections, urinary tract and kidney infections, and primary infections from the bloodstream (bacteremia).

Sepsis can progress to septic shock. Septic shock occurs when blood pressure drops dangerously low, weakening the heart.

The very old, the very young, and people with weakened immune systems are more susceptible to septic shock.

Sepsis occurs when toxins produced by certain bacteria cause cells in the body to release substances that trigger inflammation.

Although cytokines help the immune system fight infection, they can have harmful effects:

  1. They can cause blood vessels to widen (dilate), lowering blood pressure.
  2. They can cause blood to clot in small blood vessels within organs.

Often, sepsis is due to nosocomial infections, although it is an environment from which almost absolute asepsis is expected.

Fungi, like Candida, rarely cause sepsis.

The lungs, abdomen, or urinary tract are where infections leading to sepsis usually start.

However, sometimes the bacteria spread into the bloodstream (bacteremia).

Sepsis usually develops when the initial infestation involves an abscess; this situation increases the risk of bacteremia and sepsis.

Sometimes sepsis, like toxic shock syndrome, is caused by toxins made by bacteria and released into the bloodstream.

Complications of sepsis

Sepsis causes a drop in blood pressure and the formation of small clots that lead to several dangerous complications:

  • There is a decrease in blood flow to vital organs such as the brain, heart, lungs, and kidneys.
  • The heart, to compensate for this deficiency, increases the heart rate and, therefore, the amount of blood it pumps. And the bacterial toxins, together with the increased pumping work, can weaken the heart. As a result, the vital organs receive less blood.
  • If the tissues do not receive enough blood, they release excess lactic acid (a waste product), which passes into the bloodstream, causing an increase in the blood’s acidity level.

All of these effects result in a vicious cycle of organ malfunction that worsens:

  • The kidneys excrete little or no urine, and metabolic waste products (such as urea nitrogen) accumulate in the blood.
  • Blood vessel walls can leak, causing fluid to leak from the bloodstream into the tissues and causing swelling.
  • Lung function worsens because the blood vessels in the lungs leak fluid, which builds up, making it difficult to breathe.

As microscopic blood clots form, the proteins present in the blood that form the clots (called clotting factors) are consumed.

So afterward, excessive bleeding can occur.

Risk factors for sepsis

The risk of developing sepsis increases in those with conditions that reduce their ability to fight severe infections. These conditions include the following:

  • You are a newborn.
  • You are being a geriatric patient.
  • Be pregnant.
  • I have certain chronic conditions, such as diabetes or liver cirrhosis.
  • I have a weakened immune system due to medications that suppress the immune system, such as chemotherapy drugs or corticosteroids, or due to certain disorders such as cancer, AIDS, and immune diseases.

In addition to these risk factors, people affected by chronic diseases such as diabetes mellitus are also highly susceptible to sepsis.

Other risk factors include hospitalization and the introduction of medical devices such as surgical instruments into the body.

Symptoms

The first symptoms of sepsis include increased heart rate, increased respiratory rate, suspected or confirmed infection, and increased or decreased body temperature, that is, more than 38.5 ° C or less than 35 ° C.

The diagnosis of sepsis is based on the concurrence of at least two of the symptoms.

However, in many cases, the condition is not diagnosed until it has progressed to severe sepsis, characterized by symptoms of organ dysfunction, including irregular heartbeat, shortness of breath, confusion, dizziness, decreased urinary output, and skin discoloration.

The condition can then progress to septic shock when the above symptoms are accompanied by a marked drop in blood pressure.

Severe sepsis and septic shock can also involve the failure of two or more organ systems, at which point the condition can be described as multiple organ dysfunction syndromes.

The condition can progress through these stages in hours, days, or weeks, depending on treatment and other factors.

The risk also increases in people who are more likely to have bacteria entering the bloodstream.

These people include those who have a medical device inserted into the body, such as a catheter inserted into a vein or urinary tract, drainage tubes, or breathing tubes.

When medical devices are inserted, they can be contaminated with bacteria and enter the body, causing an infection.

Bacteria can also accumulate on the surface of these 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 needles used to administer medications are rarely sterile. An injection can cause varying degrees of bacteremia. People who use these drugs are also at risk for disorders that can weaken the immune system with diseases such as AIDS.
  • Possessing an artificial joint such as a prosthesis or a heart valve: certain anomalies cause bacteria to proliferate, manage to lodge, and accumulate in these structures. Bacteria can periodically release toxins into the bloodstream.
  • Present a resistant infection even when treated with drugs such as antibiotics: certain bacteria that cause infections are resistant to antibiotics. Antibiotics cannot eradicate them. Therefore, the disease remains despite the administration of these drugs and can cause sepsis.

As sepsis worsens, people become confused and less alert.

The body increases in temperature, and the skin becomes red. The pulse is faster, and the patient breathes rapidly.

People urinate less often and in smaller amounts, and blood pressure drops. Subsequently, the body temperature drops below normal levels, and breathing becomes difficult.

Blood flow is reduced, and the skin may turn cold and pale and turn bluish.

This reduction in blood flow can cause tissues, including the tissue that makes up vital organs (such as the tissues of the intestine), to die, leading to gangrene.

Diagnosis

Doctors diagnose sepsis using various physical findings and do laboratory tests that check for signs of infection and organ damage.

Many of the symptoms of sepsis, such as fever and shortness of breath, are the same as in other conditions, making sepsis difficult to diagnose in its early stages.

Laboratory blood sample studies

To confirm the diagnosis, blood samples are searched for bacteria (bacteremia), evidence that an infection could be causing sepsis, and abnormal levels of white blood cells.

Blood samples are taken to grow the bacteria in the laboratory, which takes 1 to 3 days.

However, if people have been taking antibiotics for their initial infection, bacteria may be present but may not grow in the culture.

Sometimes the catheters are removed from the body, and the tips are cut off and sent for culture.

When bacteria are found on the catheter, the bacteria are possibly spread through the bloodstream.

Blood tests evaluate lactic acid levels, the different metabolic waste products present, and the number of platelets.

When it is necessary to know the presence of other infections that can cause sepsis, samples of fluids or tissues are usually taken, such as urine, cerebrospinal fluid, tissue from wounds, or sputum.

These samples are cultured and checked for bacteria.

Imaging tests to find sources of infection

Your doctor may recommend chest x-rays and other imaging tests, such as ultrasounds, CT scans, and MRIs, to find out what the source of the infection is.

Other tests to look for signs of organ malfunction and complications of sepsis are also recommended, including the following:

  • Tests to evaluate the levels of oxygen present in the blood (oximetry) and thus evaluate the functioning of the lungs and blood vessels.
  • Electrocardiography to examine the existence of abnormalities in the heart rhythm and therefore establish if the blood supply to the heart is the most adequate.
  • Other tests to determine if the shock results from sepsis or another problem.

Sepsis prognosis

Without proper treatment, about 30 to 40% of patients who experience septic shock die.

Even with treatment, there is a significant risk of death.

But, the risk of death will vary depending on factors such as the urgency with which the treatment is carried out, the type of bacteria involved (especially in the case of bacteria resistant to antibiotics), and the state of health that present the patient.

Treatment

Doctors immediately treat sepsis and septic shock with antibiotics.

Usually, it is not expected until the results of the bacteriological tests confirm the diagnosis since a delay in the treatment reduces the chances of survival of the patient.

Treatment for sepsis is usually done in a hospital. Patients with septic shock are admitted to an intensive care unit for appropriate treatment.

Antibiotics

When choosing initial antibiotics, doctors consider which bacteria are most likely present, depending on where the infection started.

Generally, two or three antibiotics are given together to increase the chances of fighting bacteria, especially when the bacteria causing the infection is unknown.

Later, when the test results are available, doctors can substitute the most effective antibiotic against the specific bacteria causing the infection.

Intravenous solutions

Patients with septic shock receive large amounts of intravenous fluid to increase the amount of fluid in the bloodstream and thus raise blood pressure.

Oxygen

Oxygen is given through a mask, nasal prongs, or a breathing tube (endotracheal).

If necessary, a mechanical respirator (a machine that helps air in and out of the lungs) is used to aid breathing.

Elimination of the source of infection

If present, the abscesses are drained.

Catheters, tubes, or another medical device that may have caused the infection is ruled out.

Surgery may be done to remove infected tissue or dead tissue.

Other treatments

If intravenous solutions fail to raise blood pressure, doctors may administer medications, such as vasopressin or norepinephrine (which cause blood vessels to constrict), increase blood pressure, and increase blood flow in organs such as the brain—the heart, among others.

However, these drugs can constrict blood vessels even within organs and decrease blood flow through organs.

People with septic shock can develop high blood sugar (glucose) levels.

Because high blood sugar affects how the immune system responds to an infection, doctors give people insulin through a vein to lower the level of glucose in the blood.

Corticosteroids, such as hydrocortisone, can be given intravenously to people whose blood pressure remains low despite having received adequate fluids and medications to increase blood pressure and the source of the infection being treated.

Pathophysiology

At the cellular level, sepsis is characterized by changes in the function of endothelial tissue; the endothelium forms the inner surface of blood vessels in the coagulation process and blood flow.

These changes appear to be initiated by the cellular release of pro-inflammatory substances in response to the presence of infectious microorganisms.

The substances, which include short-lived regulatory proteins known as cytokines, interact with endothelial cells and thus cause endothelial damage and possibly endothelial cell death (apoptosis).

These interactions can cause the activation of clotting factors.

In tiny blood vessels (microvessels), the clotting response, combined with endothelial damage, can impede blood flow and cause the ship to leak.

As fluids and microorganisms escape into the surrounding tissues, the tissues begin to swell (edema); in the lungs, this leads to pulmonary edema, which manifests as shortness of breath.

If the supply of clotting proteins is depleted, bleeding can occur.

Cytokines also cause blood vessels to dilate (widen), causing a decrease in blood pressure.

The damage caused by the inflammatory response is widespread and has been described as a “pan-endothelial” effect due to the distribution of endothelial tissue in blood vessels throughout the body; this effect seems to explain the systemic nature of sepsis.

Related conditions

The existence of multiple conditions characterized by similar symptoms complicates the clinical picture of sepsis.

For example, sepsis is closely related to bacteremia, which is an infection of the blood with bacteria, and sepsis, which is a systemic inflammatory condition explicitly caused by bacteria and typically associated with bacteremia.

Sepsis differs from these conditions in that it can arise in response to infection with various microorganisms, including bacteria, viruses, protozoa, and fungi.

However, the occasional progression of sepsis to more advanced stages of sepsis and the frequent involvement of bacterial infection in sepsis prevent a clear clinical distinction between these conditions.

Sepsis is also distinguished from systemic inflammatory response syndrome, which can arise independently of infection from factors such as burns or trauma.

Sepsis through history

The Greek word sepsis means “putrefaction.” One of the earliest medical descriptions of putrefaction and a septicemic condition was provided in the 5th and 4th centuries BC in works attributed to the ancient Greek physician Hippocrates.

Unaware of infectious microorganisms, the ancient Greeks and the physicians who came after them variably associated disease with digestive disease, miasma, nasty air infection, and spontaneous generation.

These apocryphal associations persisted until the 19th century, when infection was finally the underlying cause of sepsis. This finding grew out of the work of British surgeon and medical scientist Sir Joseph Lister and French chemist and microbiologist Louis Pasteur.