What causes an out of control anesthesia that leads to death

Catastrophic chain reaction

sepsisby Elke Wolf, Weimar

Paul Ehrlich called sepsis "horror autotoxicus" because he knew how powerless doctors often face the disease. The sepsis, however, has not lost any of its horror. It is still the number one cause of death in Germany's non-cardiological intensive care units.

Professor Dr. Konrad Reinhart at the press conference on the occasion of the 1st International Sepsis Congress last week in Weimar. Sepsis is as common as myocardial infarction, but is much more likely to be fatal. Of around 150,000 people who develop sepsis every year in Germany, 80,000 die, said Reinhart, chairman of the German Sepsis Society and chief physician at the clinic for anesthesiology and intensive therapy at the University of Jena. Patients die because internal organs fail. A comparison with other diseases shows that sepsis is by no means a rare infection. On the contrary: 300 out of 100,000 citizens in the US will develop sepsis, 110 out of 100,000 will develop breast cancer, 50 out of 100,000 will develop colon cancer and 17 out of 100,000 will develop AIDS.

Sepsis is rarely the "red stripe on the arm that draws to the heart." Rather, it is the most aggressive form of infection, caused by microorganisms and their toxins, which can lead to internal organs failing within a few hours. "Sepsis can occur as a complication of any infectious disease," emphasized Reinhart, including pneumonia, tonsillitis and malaria. Nevertheless, it is not present in the consciousness of patients or doctors, according to Reinhart.

If the body fails to limit the actual infection to the place of origin, pathogenic microorganisms and their toxins continuously enter the bloodstream and trigger inflammation in all organs of the body, comparable to a "chain reaction that got out of hand in a nuclear reactor disaster." The immune system is disrupted - it simultaneously releases pro- and anti-inflammatory mediators. As a result, homeostasis and blood coagulation are out of balance. The organism fights against blood loss and stimulates the production of tissue thromboplastin (tissue factor). Fibrinogen plasma levels rise. At the same time, fibrinolysis is inhibited by increased activation of PAI-1 (plasminogen activator inhibitor 1).

The massive influx of various factors leads to an imbalance between substances that promote and inhibit coagulation. In acute sepsis, both bleeding and thrombotic vascular occlusion therefore occur. Within a few hours all vital organs are inflamed and threaten to fail due to insufficient blood flow. After all, the defense mechanisms of the immune system are directed against the own body.

Symptoms not very specific

In this situation there is no chance of survival without immediate intensive care treatment. The mortality rate increases rapidly with the number of failed organs. Reinhart: "The first thing it often hits is the brain." Around 20 to 40 percent of these patients die despite antibiotic therapy and treatment in the intensive care unit - up to 80 percent if more than three organs fail. Diagnosis and therapy as early as possible are therefore crucial for the patient's survival. But this is where the problem lies: Symptoms of sepsis, which can be traced back to a reduced supply of oxygen to the organs, such as confusion, fever, chills, accelerated breathing and heartbeat as well as low blood pressure, are not very specific. Fever due to bacteremia is also not very informative.

The diagnosis is made up of a whole series of laboratory values ​​like a puzzle, although not all values ​​have to be conspicuous in every patient. Reinhart hopes that immunological markers will soon become established in everyday ward life, which are currently being tested in studies and which enable an earlier diagnosis than according to clinical criteria. The risk of sepsis can be minimized through various immediate measures, but it cannot be prevented in principle: If possible, the infectious focus such as an infected gallbladder should be removed. The pathogen can be identified quickly and appropriate antibiotics must be administered early on. The increased blood sugar level should be reduced with intensified insulin therapy, explained Reinhart.

Tremendous expenses

Given the complex effects of sepsis, it is hardly surprising that the treatment is extremely costly. In Germany, the direct therapy costs alone are estimated at up to 2.45 billion euros, which makes up around 45 percent of the total costs for intensive therapy. In Germany, sepsis patients spend an average of 16 days in intensive care and are treated in hospital for around 32 days, Reinhart presented the current data. According to a study by the university clinics in Jena and Göttingen, the hospital costs of patients with sepsis were around 25,695 euros - 1,454 euros per day.

The number of sepsis cases will increase in the future as there are more and more older people with age-related previous illnesses who, according to Reinhart, are particularly prone to blood poisoning. In the USA, for example, the incidence of sepsis has increased fivefold in the past 20 years. But many young and hitherto healthy people can also develop sepsis and die. The most common cause of this is pneumonia (44 percent), bacteria in the blood (17.3 percent) or infections of the urinary tract and genital organs (9.1 percent). Modern medical technologies and operations, without which survival with certain diseases was impossible until a few years ago, also increase the general risk of sepsis. Antibiotic resistance, on the other hand, currently only plays a subordinate role - at least in Germany.

The chairman of the Sepsis Society regrets that if the sepsis is not sufficiently noticed by the medical community, then it is as good as non-existent in the public consciousness. In media such as Spiegel, Focus or FAZ, diseases such as cancer, heart attacks or AIDS are cited by a factor of a hundred more often than sepsis, our own studies have shown. “There's another lobby behind that. The research-based pharmaceutical industry also tends to invest its money in other areas. «The term sepsis is hardly used at all, both colloquially and in the media. It is more like "died of pneumonia"; the correct choice of words would, however, be "died of sepsis as a result of pneumonia". Reinhart: "You generally don't die of pneumonia."

Not always optimally treated

The German Sepsis Society has set itself the goal of reducing the number of sepsis deaths by 25 percent over the next five years. Reinhart considers this requirement to be realistic, "if we conduct intensive education and manage to consistently put the current state of research into practice." Lately there has been a lot of progress in sepsis therapy. However, the findings from the studies have not yet been adequately implemented in everyday clinical practice because some of the new therapies are not suitable for every patient and are often associated with additional costs. If the financial possibilities are already limited, the situation will be exacerbated by the planned health modernization law, says Professor Dr. Hilmar Burchardi from the University of Göttingen. He sees significant treatment deficits for the patients.

Modern intensive therapy for sepsis consists, among other things, of artificial ventilation and shock treatment at an early stage, kidney replacement procedures, artificial nutrition and the substitution of the body's own blood cells and substances. However, after years of stagnation, drug therapy itself has recently started to move. For example, low-dose hydrocortisone lowers the mortality rate from 65 to 50 percent in patients with a proven sepsis-related deficiency in this hormone.

A new active ingredient for the treatment of sepsis is drotrecogin alfa (for example Xigris®). With this recombinant human activated protein C, a targeted drug for the treatment of sepsis is available for the first time. In adult patients with severe sepsis and multiple organ failure, the active ingredient is indicated in addition to standard therapy. The body's own protein impresses with its three-fold mechanism of action. It has an antithrombotic effect by blocking factors Va and VIIIa. By inhibiting PAI-1, it promotes fibrinolysis. It also suppresses the release of the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor-a. According to Reinhart, activated protein C has proven its effectiveness in studies. The mortality rate fell from almost 31 percent to 24.7 percent. The active ingredient is suitable for around 20 percent of patients.

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