AGING
July 1, 2001

Sepsis

Older hospitalized patients are often given too little food.

Sepsis, also known as the sepsis syndrome or SIRS, is the combination of inflammation throughout the body; problems with the blood's clotting mechanism (coagulopathy); and low blood pressure (hypotension). All three are part of the body's immune response to infection. In its most severe form, sepsis can drastically reduce blood flow to the major organs, leading eventually to septic shock, widespread organ failure and death.

Sepsis caused by infection occurs in approximately one in five of all hospital admissions. Though surprisingly common — over 700,000 cases of severe sepsis occur in the United States each year — most people know very little about sepsis.

While death rates from severe sepsis are highly variable, the overall rate is approximately one-third of all cases. The death rate varies considerably, however, by age...

Bacteria and infections are not the only cause of sepsis. In 1991, the American College of Chest Physicians and the Society of Critical Care Medicine put forward a new term, Systemic Inflammatory Response Syndrome (or SIRS), in recognition of the fact that the sepsis syndrome frequently occurs in persons who have suffered insults other than infection.

SIRS is defined as a widespread inflammatory response that occurs following a one of many bodily insults, including infection, trauma, pancreatitis or burns.1 SIRS is considerably more common than sepsis caused by infection alone, occurring in over half of all hospitalized patients and in up to 90% of those in intensive care units.

Medicare statistics from 1991 through 1997 show a marked increase in sepsis in hospitalized older Americans.2 Much of the increase has occurred in older African American men. Sepsis is now the tenth leading cause of death among older adults in the United States. Over the last decade, not only has sepsis become more common but it has also become more deadly. Researchers3 trying to account for this increase have identified a number of factors that are associated with death from sepsis in the elderly. These include old age, being male, diabetes, hospitalization for cancer, disability and cognitive problems such as dementia and Alzheimer's disease.

While death rates from severe sepsis are highly variable, the overall rate is approximately one-third of all cases. The death rate varies considerably, however, by age, ranging from 5% to 35% of young people to 37% to 50% of older people.4 On average, fewer than one third of those who suffer an episode of severe sepsis are still alive one year later. By one estimate, sepsis is responsible for $5 to $10 billion of the annual United States health care budget.

The History of Sepsis
As long ago as 2735 B.C., the Chinese Emperor, Sheng Nung, wrote about the use of herbal medicines to treat fever brought on by sepsis. In more recent history, many infections that cause sepsis have changed the course of history. There is the "Black Death" of the bubonic plague epidemic in medieval Europe, the deaths of New World natives exposed to Old World contagions imported by European colonists and the uncountable deaths of wounded war veterans in the American Civil War and many other armed conflicts.

The concept of anti-sepsis (an organized, rational effort to prevent and treat sepsis) was originated by John Pringle, Surgeon General of the British army in the 18th century. A century later, Ignaz Semmelweis introduced antiseptic techniques for the care of women during childbirth. Semmelweis's advances brought the death rate from puerperal fever down from 13.6% of all women who were giving birth to 1.5%. In 1879, the French physician Louis Pasteur identified the streptococcus bacteria as the cause of puerperal sepsis. Thirteen years later, Richard Pfeiffer discovered that bacteria released poisonous endotoxins in the body of a person afflicted with sepsis. The recognition by Sir Alexander Fleming that a certain mold could be toxic to bacteria resulted in the discovery of penicillin and ushered in the modern era of antibiotic treatments.

Toward the end of the twentieth century, it became clear that sepsis causes the release of what are known as inflammatory mediators, (for example, tumor necrosis factor-alpha and interleukin-1). These and other mediators can cause hypotension (low blood pressure), damage to the cardiovascular system, and, ultimately, fatal damage to bodily organs and stroke.

Warning Signs of Sepsis
Doctors diagnosing sepsis and SIRS look for two or more of the following conditions:
  1. Abnormal body temperature
  2. Tachycardia, or racing of the heart
  3. Breathing difficulties
  4. Abnormal white blood cell count

Other symptoms and signs associated with sepsis include hypotension and mental deterioration, ranging from lack of attention and confusion to agitation, lethargy and coma. Before they develop low blood pressure, sepsis sufferers may experience tachycardia (very rapid heart beat).

Prolonged sepsis can also lead to neuromuscular and respiratory weakness and severe muscle wasting, leaving victims vulnerable to pneumonia and other problems.

Gastrointestinal effects of sepsis include jaundice, gastrointestinal bleeding, constipation, decreased urine production and kidney failure. In the blood, sepsis can cause both high and low blood sugar, electrolyte abnormalities, and coagulation problems that lead to profuse bleeding. While sepsis normally causes fever, older victims sometimes have no fever; and in some cases they may actually have abnormally low body temperature.

In the early stages of sepsis, older persons are much more likely to be delirious. This delirium may take the form of lack of attention or non-responsiveness. For instance, a demented patient who screams frequently may suddenly stop screaming. In some cases, a series of falls may be the only evidence of sepsis-induced delirium.

Older persons with sepsis are also more likely to suffer from kidney, breathing and heart problems, and are more likely to develop septic shock and a condition known as multiple organ dysfunction syndrome (MODS). Finally, older persons typically take longer and have more difficulty bouncing back from severe sepsis. A bout of sepsis is often the event that causes them to be admitted to a nursing home.

Risk Factors For the Development of Sepsis
While we do not know exactly why and how sepsis and septic shock are becoming more common, the answer may well lie in the increasing prevalence of certain risk factors. The first is old age. The average age of most residents of Western nations is increasing and changes in the immune system of older persons puts them at increased risk for developing infections.

In addition, we know that older persons are particularly prone to weight loss and malnutrition, both of which strain the immune system. Another factor is the rise of diseases that increase the risk of sepsis. These include diabetes, cancer and AIDS. Diabetes occurs in almost one in five older persons. Half of the persons with diabetes are over 60 years. Alcoholics are also at increased risk for sepsis.

Another risk factor for sepsis is medical treatment itself; and older people tend to receive more medical attention than other groups. In particular, urinary catheters carry a high infection risk and are associated with increased death rates in the elderly. The same is true for the use of intravenous catheters, particularly in the jugular vein. Older persons are more likely to have surgery and other invasive procedures that put them at increased risk of sepsis. Because they take more antibiotics, older persons are more likely to develop antibiotic-resistant microorganisms within their bodies.

Treatments for Sepsis
The primary treatment in a person with sepsis is immediate administration of the proper antibiotics.10 Timely antibiotic therapy has been shown to reduce a person's risk of dying from sepsis by 50%.

Another important consideration is food. Studies have shown that older persons often fail to get adequate nutrition while they are in the hospital. This is a problem because malnutrition stresses the immune system and can worsen the effects of sepsis.

As for drug treatment, the evidence suggests that treating sepsis with corticosteroids and other anti-inflammatories is ineffective and may actually be harmful. However, there have been some encouraging results from recent trials using a new drug called recombinant human activated protein-C (drotrecogin alfa). This drug appears to be able to reverse the inflammation and coagulation problems that accompany sepsis. Other, similar drugs that target specific components of the body's response to infection are now being developed and studied.

Summary
Sepsis remains an extremely serious condition that is particularly dangerous for older persons. Early recognition of infection and treatment with antibiotics remain the safest and most effective treatment. It is also important to recognize, especially with older sufferers, that maintaining adequate nutrition is vital. A drug called activated protein-C has also shown encouraging results in recent studies.

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