Sirs and sepsis

SIRS and sepsis

Image: “Sepsis Steps” by Hadroncastle. License: CC BY-SA 4.0


Activation of cell systems and release of cellular mediators in sepsis

Sepsis is the term used to describe all life-threatening clinical signs of illness that arise in response to pathogenic germs and their products that enter the bloodstream from the point of infection. They activate cascade systems and special cell systems and trigger the formation and release of cellular mediators.

In order to provide a basis for clinical and epidemiological studies, the clinical pictures SIRS, sepsis, severe sepsis and septic shock are uniformly defined.

Systematic Inflammtory Response Syndrome

As systemic inflammatory response syndrome, short SIRS, refers to the first stage, which is independent of the triggering agent. At least 2 of the following criteria must be present for the SIRS diagnosis:

  • fever > 38 ° C or hypothermia 90 / min
  • Tachypnoe with a frequency > 20 / min or hyperventilation with a PCO2 12,000 / mm³ or leukopenia 10% immature neutrophil granulocytes in the blood

For the diagnosis sepsis also has one more infectiological genesis available. This means that an infection must be present via microbiological evidence or clinical criteria.

Acute organ dysfunction in severe sepsis

As severe sepsis every sepsis is valid for at least one acute organ dysfunction consists. The acute organ dysfunctions include:

  • Acute encephalopathy with impaired vigilance, restlessness and disorientation
  • Arterial hypotension with systolic blood pressure > 90 mmHg or MAP 1.5 times above the local standard reference range

The septic shock

Of the septic shock is defined as sepsis with a for At least 2 hours of sustained systolic blood pressure from Hadroncastle. License: CC BY-SA 4.0

The PIRO concept

The PIRO concept is an attempt to further develop the above-mentioned consensus criteria for sepsis. Thus, in analogy to the TNM classification of malignant tumors, a classification of sepsis has been proposed.

P stands for predisposition, I For infection, R For inflammatory reaction and O For organ dysfunction. Based on this classification, a risk stratification of sepsis can occur.

Other important terms are:

  • bacteremia is the presence of facultatively pathogenic bacteria in the bloodstream without circulatory involvement and other signs of intoxication.
  • endotoxemia is defined as the presence of endotoxins in the blood even without concomitant bacteremia. The endotoxin is lipopolysaccharide >Epidemiology

Increasing incidence of sepsis

The incidence of sepsis is on average in the European area 5 diseases in 1,000 hospital patients indicated and rising steadily. The reasons for the increasing incidence are more invasive examination techniques, which are a portal of entry for pathogenic germs, as well as the increase in the survival rate of patients with chronic diseases such as malignancies, liver diseases and HIV.

The cost of treating a patient with sepsis is around € 23,000, accounting for almost 40% of the total cost of intensive care in Germany.


Cause of sepsis syndrome

The sepsis syndrome arises on the basis of a predisposing immunity deficiency in diseases such as general infection, trauma and prolonged surgery, intoxication, chemotherapy, after splenectomy (OPSI = overwhelming postsplenectomy infection) and amicrobial inflammation.

Before antibiotics were used, streptococci were the most important pathogens in septic processes. Today one finds increased Gram-negative bacteria and staphylococci, which is due to the years of use of antibiotics effective in intensive care against Gram-negative bacteria and the resulting development of resistance.

With 25% is Escherichia coli today the bacterium most commonly isolated from blood cultures of septic patients. Also common are Staphylococcus aureus with 20%, Staphylococcus epidermidis (8%), Enterococci, Klebsiella and Pseudomonas. The most common sources of infection are the Peritonitis, pneumonia, meningitis and operation areas. In intensive care patients, bacteria can also enter the body through other ports such as intravenous and intraarterial catheters, peritoneal dialysis, and ventilation tubes.


Hypodynames stage of sepsis

In the outer membrane of Gram-negative bacteria is the lipopolysaccharide, short LPS, embedded. After bactericidal antibiosis or massive proliferation of bacteria, the LPS and thus proinflammatory potential is released into the circulation.

In the untreated early phase of sepsis is often a hypodyne stage in front. This phase is defined by Hypotension, low cardiac output and increased systemic resistance and will too cold shock called. In this phase, adequate volume replacement is most important, as circulatory shock accounts for around 40% of sepsis deaths.

Hypodynames initial stage of sepsis

Mediators are then used to induce arterial and venous vasodilation, which results in systemic hypotension with relative intravascular volume depletion through decreased systemic vascular resistance and venous pooling. One speaks of the hyperdynamic initial stage.

If a capillary leak syndrome with increased vascular permeability occurs, it is an absolute volume deficit. Typical for this phase is a increased cardiac output, whereby the hypovolemia can be temporarily compensated. Due to this hypocirculation, the blood is only slightly depleted of O2 and the mixed venous O2 saturation is high (SvO2 > 80%).

Even at this stage, there is also a reduced myocardial contactility, recognizable by the fact that the measured cardiac output does not correspond to the extent of the decreased systemic vascular resistance. This is due to various mediators such as TNF-α and endotoxins. The permanently elevated plasma catecholamine levels and the impaired myocardial microcirculation also cause a reduced sensitivity of the cardiac β-receptors. The relative heart failure in the septic syndrome is also called acute septic cardiomyopathy designated.

Hypodyne shock phase of sepsis

In some patients hypercirculation later suggests a mechanism of decompensation of the body’s homeostasis regulating mechanisms hypodyne shock phase around. The cardiac output decreases again, the resistance increases again. However, with sufficient volume replacement, the hyperdynamic circulatory constellation, often even to the final phase, is maintained in most patients.

Even in the hyperdynamic phase, however, it can lead to functional limitations of vital organs to organ failure. The blood gets into the organs through a failure of arteriolar vasomotion, that is, the rhythmic contraction and dilatation of the arterioles. This opens arteriovenous shunts, which are then increasingly flowed through. That’s what it’s all about tissue hypoxia and nutritional disorders.

Clinical studies have shown that systemic oxygen consumption is reduced while oxygen supply is generally increased as a result of septic hypermetabolism. But even with low avDO2 values, one must not assume sufficient cellular oxygenation, because the septic syndrome is an oxygen utilization disorder at the mitochondrial level. The affinity of hemoglobin for oxygen is also increased, so that the oxygen can be released to the tissue more difficult.

The Core problem of sepsis syndrome is thus the microcirculation disorder, which persists despite the counterregulation of the circulation. Left untreated, tissue hypoxia results in single or multiple organ failure, which is associated with a lethality of 50-80%. In the chronological sequence of the MOF (Multi Organ Failure) stands here the lung first of all, followed by kidney and liver.


Clinical parameters and sepsis markers

The image of sepsis is characterized at the beginning by a Keiminvasion. It comes to acute deterioration of the general condition With fever and in about one third of patients with chills. In the blood picture one finds leukocytosis, where primarily a leukopenia is possible. The distinction from the SIRS succeeds only by the proof of a sepsis or a source of infection.

pathogenesis symptom
germ invasion Fever, chills, bacteremia, red, warm, dry skin or pale, cold, moist skin, petechial hemorrhages
hemodynamics Tachycardia, blood pressure drop (especially the diastolic value)
coagulation Platelet fall, coagulation factors decrease
Organ dysfunction Tachypnoea (PO2 and PCO2 decrease), agitation, confusion, renal / hepatic insufficiency, encephalopathy, respiratory failure, myocardial insufficiency

The usual clinical parameters such as body temperature, leukocyte count and thrombocyte count and parameters of the coagulation system (Quick, PTT) usually can not properly reflect the extent of the complexity of the inflammatory process. For this reason further laboratory parameters have to be determined. Count among them IL-6 and IL-8 as proinflammatory mediators.

That too Lipopolysaccharin binding protein (LBP) and C-reactive protein (CRP) can be used for evaluation. In which procalcitonin is preferred over CRP, as it becomes highly positive only in a bacterial infection, while CRP also increases in other causes of SIRS, such as pancreatitis, burns, and major traumas. In addition, procalcitonin allows a more significant prediction of the severity of the infection.

Also the neurohumoral markers ANP (atrial natriuretic peptide) and the BNP / NT per BNB (Brain natriuretic peptide) may be elevated in patients with septic shock, wherein the BNB increase is an expression of cardiac dysfunction.

The lactic acidosis is a sign of tissue hypoxia.

Microbiological diagnostics

Even though blood cultures only in about 12 – 20% of the bacteremia are positive, they are essential for the detection of germs in suspected sepsis. They should be taken in case of fever (usually with fever above 38.5 ° C) before the start of antibiotic treatment under sterile conditions.

The minimum is to fill an aerobic and an anaerobic culture flask with about 10 ml of blood, but by default usually 3 pairs of blood culture bottles from different veins (or, for example, from a CVC or port and peripheral veins) are removed. In unfavorable vessel conditions or centralization, the femoral vein or femoral artery can also be punctured. If the patient is already under antibiotic therapy, cultures should be taken during the therapeutic trough mirror. For this purpose, there are also extra blood culture bottles containing exchange resins that bind the antibiotics and thus render them ineffective.

Image: “Blood culture tubes: orange label for anarobes, blue label for aerobic, and yellow label for pediatrics” by James Heilman. License: CC BY-SA 3.0

Depending on the clinical picture, of course, should more Samples such as urine, cerebrospinal fluid or bronchial secretions be obtained and examined microbiologically.

The focus search always includes the physical examination, medical history and diagnostic imaging.

Clinical findings Possible cause of sepsis
Cardiogenic auscultation typical of the ventricular sound endocarditis
Pulmonary rales / attenuated auscultation findings in lung examination Pneumonia, pleural empyema
Abdominal pressure pain / flank pain Pancreatitis, cholecystitis, pyelonephritis
Abdominal defense tension Peritonitis, pancreatitis
meningism Meningitis, encephalitis
Redness, overheating, pain of the skin Phlegmon, abscess


For the monitoring of septic patients in the intensive care unit, basic monitoring and extended monitoring are recommended, especially for hemodynamically difficult to control patients. The extended hemodynamic monitoring includes the transthoracic or transesophageal echocardiography for recording the left ventricular pump function.

Image: “Sepsis monitoring” by Patricia Pineda Vidal. License: CC BY-SA 4.0

Also a pulmonary artery catheter should be used to determine cardiac output and systemic vascular resistance. Especially suitable are PiCCO systems. They allow the measurement of cardiac output, extravascular lung water, intrathoracic blood volume and systemic vascular resistance using a combination of arterial pulse contour analysis and transpulmonary indicator dilution techniques. The sepsis guidelines of Dellinger et al. 2008 after (Survival Sepsis Campaign) owns especially the oxygen saturation as a monitoring parameter a high priority.


Detection and removal of sepsis

The basis of the successful therapy of sepsis is the detection of sepsis and its removal. Abscesses must be drained and infected foreign bodies removed. Assuming that a central venous catheter or port is populated and is the focus, the Time to positivity used. If the blood culture from the central catheter becomes positive before culture from a peripheral vein, it can be assumed that the CVC is infected. In the case of infections of endoprostheses, they must be removed in a new operation and, if necessary, replaced by antibiotic-containing spacers.

The antibiotic therapy must be adapted to the focus and the expected germ spectrum. If Sepsisherd is unknown, the antibiotic must cover all Gram-negative and positive bacteria, including anaerobes. Often there is one Combination of broad-spectrum penicillins such as piperacillin or cephalosporins of the 3rd generation (such as cefotaxime with an aminoglycoside such as gentamycin). Therapy should be started within the first hour after detection of severe sepsis with intravenous antibiotics and continued for 7-10 days.

If the septic disease progression persists when antibiotics are given, a secondary infection, an infected foreign body, an infected thrombosis and abscesses must be excluded. Also, it can be a so-called drug fever to act under medication.

In addition to the causal therapy measures, the rapid initiation of cardiovascular and organ-assisting supportive therapy is the decisive prognostic factor. In the early-goal-directed therapy he follows in case of suspected sepsis immediate volume therapy. In one study, the mortality rate was lowered by 16% compared to conventional intensive therapy.

Picture: “Looking into an intensive care unit. “By Norbert Kaiser. License: CC BY-SA 2.5

To fill the intravascular volume Colloids or crystalloids used. Volume delivery may result in a steady-state phase with hypercirculatory warm shock. In addition, one should Catecholamine therapy with norepinephrine respectively.

In spite of high doses of norepinephrine therapy-resistant circulatory failure, vasopressors such as terlipressin be used. The administration of dobutamine is indicated in patients with myocardial dysfunction.

Supportive respiratory insufficiency may require endotracheal intubation and ventilation. As up to 40% of patients with severe sepsis acute respiratory distress syndrome (ARDS) occurs, should be a respiration Lung protection with low tidal volumes hypercapnia can be tolerated. To prevent pulmonary collapse, a minimum of positive end-expiratory pressure (PEEP) should be used. To avoid ventilator-induced pneumonia, patients should be stored with the head of the bed raised 45 °.

Picture: “Samir” by Norbert Kaiser. License: CC BY-SA 3.0

Due to tissue hypoxia are erythrocyte preparations even at hemoglobin levels below 7 g / dl to transfuse. Also, the correction of the coagulation factors is advisable in the case of deficiency.

The intensive insulin therapy for the achievement of normoglycemia in the sense of sepsis prophylaxis delivers astonishingly favorable results in postoperatively ventilated intensive care patients. In septic patients, however, the benefits are controversial.

The general administration of immunoglobulins is not recommended, since reliable prospective studies are not available. Also, the administration of high-dose glucocorticoids does not improve the survival rate in patients with sepsis. In contrast, low-dose hydrocortisone in combination with catecholamines can buffer a hypothalamic-pituitary-adrenocortical-axis disorder that often occurs as part of sepsis.


Significant influence on the course and prognosis of sepsis have the time interval of the beginning of the disease and the time of initiation of the therapy or the acute treatment within the first 24 hours. One speaks of the so-called golden hours. Similar to other emergency medical conditions e.g. Myocardial infarction or apoplexy, even in sepsis only the immediate diagnosis and consecutive therapy initiation can prevent the often lethal course.

One of the main reasons for the persistently high mortality rate of severe sepsis and septic shock in both hospitalized and emergency department patients is late diagnosis and the resulting delay in therapy.

Of the MEDS score (mortality-in-emergency-department-sepsis-score) was developed for patients in the emergency room with suspected systemic infection. He has the goal Predictors of increased lethality already in the initial phase of hospital treatment. It is also important, for example, to select patients who are clinically still largely unremarkable, but have a creeping septic history with already global tissue hypoxia.

MEDS score based on Shapiro et al. 2003:

1. Terminal disease (life expectancy 65 years 3 points
6. Infection of the lower respiratory tract 2 points
7. residents 2 points
8th. reduced mental status 2 points

While mortality at 5 – 7 points is 3.3%, at 31.6% at 13 and more points, it is 10 times higher.

In addition to the lethality predictors of the MEDS score are a increased lactate serum concentration and a increased mixed venous oxygen saturation as an expression of a lack of tissue extraction, groundbreaking parameters of an early disrupted tissue oxygenation.

The lethality the sepsis is total around 28%. It depends mainly on the age of the patient and is around 10% for children and 38% for over 85s..

Popular exam questions about sepsis

The solutions are below the sources.

1. What does not belong to the diagnostic criteria of the SIRS?

  1. fever > 38.5 ° C or hypothermia 90 / min
  2. tachypnea > 20 min
  3. leukocytosis > 12,000 / mm³ or leukopenia 10% immature neutrophil granulocytes in the blood
  4. Proven infection as a cause

2. A 66-year-old patient received a total hip replacement 5 days ago due to a coxarthrosis on the left side. Now the patient is feverish with temperatures up to 39.2 ° C and becomes unstable. The surgical wound is very red and overheated. They assume an infection and take several aerobic and anaerobic blood cultures and wound smears. What is subsequently decisive for a successful therapy of sepsis?

  1. Circulatory stabilization using volume replacement therapy and norepinephrine
  2. Antibiosis with broad-spectrum antibiotics such as piperacillin in combination with gentamycin
  3. Operative restoration with wound debridement, jet lavage and removal of the colonized endoprosthesis
  4. Intensified insulin therapy
  5. Administration of immunoglobulins, activated protein C and hydrocortisone

3. What counts in the MEDS score is not one of the predictors associated with increased lethality in sepsis?

  1. Older > 65 years
  2. platelets

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