Symptoms, Diagnosis & Treatment > Fact Sheets > Yale Medicine

As with adults, when babies and children develop an infection, their immune systems fight the invading culprit, whether it’s bacteria, a virus, or a fungus. But sometimes the immune system’s response to an infection can spin out of control, leading to a life-threatening condition called sepsis. Sepsis occurs when the body’s response to an already-present infection gets out of hand, leading to severe inflammation throughout the body that, in turn, can cause tissue damage and organ failure. When organs begin to stop functioning, the body can enter a stage of sepsis called “septic shock,” and the threat of death is imminent. 

While sepsis is a serious condition at any age, it is particularly dangerous for children because their symptoms can be more difficult to detect. “The biggest difference between adult and pediatric sepsis is recognition,” says Yale Medicine pediatric intensive care doctor Sarah Kandil, MD. “A lot of symptoms we look for in sepsis, like a fever, are similar to other illnesses in children.”  

Though pediatric sepsis is unusual, it’s not all that rare either. Studies estimate that more than 75,000 children are treated for severe sepsis each year in the U.S. 

Sepsis can develop from an injury as simple as an infected scrape on the arm, or it can emerge on top of an already life-threatening condition, such as acute appendicitis. “Those who have a weakened immune system, like kids undergoing chemotherapy, can be especially susceptible,” Dr. Kandil says.  

Besides being more difficult to detect in children, parents, caregivers, and even medical staff may not have enough knowledge about the signs of sepsis. “We have an ongoing campaign in at Yale New Haven Children’s Hospital that encourages medical providers and families to be aware of sepsis,” Dr. Kandil says. 

All Yale Medicine’s pediatric care providers are trained to recognize the early signs of sepsis in children, in order to provide quick and accurate care to interrupt the condition’s progress.  

Septic Shock: Causes, Treatment, Complications

Although septic shock is a complication of sepsis, septic shock has its own set of possible complications. This is because a dangerously low blood pressure affects oxygen levels and blood flow.

While severe sepsis can limit organ function, septic shock leads to complete organ failure when inflammation and low blood pressure aren’t controlled. Between severe inflammation triggering blood clots and low blood pressure causing inadequate blood flow, your organs may not receive sufficient oxygen or blood to function properly. (2)

Kidney failure, heart dysfunction, respiratory failure, and multiple organ failure are all complications of sepsis and septic shock, notes Brown. “Patients may need dialysis temporarily or long-term if their kidneys are shutting down, and death can occur if multiple organ systems become dysfunctional and shut down.”

She further relates the dangerous effect of low blood pressure on the brain, stating the increased likelihood of stroke when blood can’t circulate to all areas of the brain.

In addition to possible organ failure, septic shock can lead to amputation of a limb. The risk for amputation increases when blood clots form in the body. Blood clots prevent the passage of blood. And when parts of the body are deprived of blood and oxygen long term, body tissue starts to die. (2)

Sometimes, the damage is reparable. When too much of your body tissue dies, the only option is to remove the dead tissue. This may involve removal of a finger, toe, foot, arm, or leg. (4)

Even if you recover from septic shock, you may live with post-sepsis symptoms for weeks or months. (9)

“Recently, we are starting to recognize how sepsis can cause patients to be debilitated for long periods of time, and very weak after they leave the hospital,” explains Brown. “The combination of being hospitalized, fighting off an infection, and being immobile can cause significant wear and tear on the body.”

Post-sepsis symptoms can include insomnia, fatigue, depression, and cognitive decline. (9)

One Last Thing on Preventing Sepsis and Avoiding Septic Shock

If you suspect sepsis, it’s important that you go to the hospital immediately. The longer you wait, the greater the risk of the infection progressing into a life-threatening emergency.

Unfortunately many people diagnosed with septic shock don’t survive. And because this condition strains the immune system, there’s also the risk of recurrent infections after leaving the hospital. (2) Therefore, learning how to recognize symptoms and thus get early treatment is your best chance of survival.

What Happens When Your Body Is in Septic Shock?

What do Muppet creator Jim Henson, singer Chuck Brown, and boxer Muhammad Ali have in common? They all died of the same thing: septic shock, triggered by an infection. Sadly, conditions like septic shock can bring the most diverse of people together. Before penicillin was discovered in the early 1900s, dying from an infection and septic shock was common place, no matter who you were. And while penicillin and other antibiotics have saved millions of lives over the years, infections still cause deaths around the world, including over 258,000 people in the United States every year.

Most people know of someone or have heard of someone who died of a common infection, such as pneumonia, influenza or a urinary tract infection. In reality, it’s not the infection that caused the death. It was septic shock, triggered by the infection. Septic shock is a medical emergency. It is a dangerous and life-threatening condition that occurs when your blood pressure drops and stays too low after you have developed an infection.

How does septic shock develop?

When you get an infection, your immune system tries to protect you by producing extra white blood cells that are programmed to seek out and destroy invading organisms. When all goes well, your immune system fights off the infection, although you may need help from some medications such as antibiotics or antivirals. If the organism enters the bloodstream it can quickly multiply and spread throughout the body. As this happens the germ releases toxic substances that poison the blood vessels and aggravate the immune system. Sometimes your immune system may go awry, and instead of fighting the infection, it turns on itself, attacking the healthy cells. When this happens, you develop sepsis. It is your body’s toxic response to the infection.

The first signs of sepsis may be quite vague, but they include low blood pressure, fast heartbeat, or a higher or lower than usual body temperature. Blood tests may show a higher than normal number of white blood cells in your blood. If the infection isn’t treated or controlled at this point, sepsis can progress to severe sepsis. One or more organs, like your kidneys or lungs, start to fail, and tiny blood clots may form in your blood, restricting blood flow to your limbs.

Severe sepsis, if not treated quickly, can lead to septic shock.

How is septic shock treated?

People who are in septic shock need urgent intensive care. The medical team has to approach treatment from different angles for it to be successful:

• Raise your blood pressure: IV fluids usually help raise blood pressure, but you may need medications called vasopressors. These narrow the blood vessels, which then in turn increases your blood pressure and sends blood to your vital organs.

• Treat the infection: Your doctors must find out what caused the infection that triggered the sepsis and give the appropriate antibiotics.

• Provide oxygen: You may have an oxygen mask over your nose and mouth, or a tube just under your nose, to deliver oxygen for you to breathe. If your lungs are failing, you may be intubated, which means a tube will be inserted through your mouth into your trachea, which leads to your lungs. This tube will be attached to a ventilator, which will help you breathe.

• Surgery: Surgery may be done for two reasons, to clear out infection or to remove dead tissue. Some people with septic shock develop gangrene in their hands, arms, feet, legs, or even their nose and ears. The tiny blood clots that formed in the blood vessels can prevent blood flow to the limbs. Also when the body is in shock, it tries to concentrate the blood flow to the most important parts, such as the brain. If other parts of the body, such as fingers and toes, don’t get good enough blood flow, the tissue can die, causing gangrene. Amputation is the only option once gangrene is present.

Septic shock can almost always be prevented. If you have an infection, it’s important to watch for signs of sepsis. If you suspect that you may have sepsis, go to your local emergency room or urgent care clinic right away. Early treatment can and does save lives.

Recovering from Sepsis

Sepsis is an extreme immune reaction of the human body toward serious bacterial infection circulating in the bloodstream. It becomes life-threatening or lethal when it manifests in the extreme stages of severe sepsis and septic shock.

The time it takes for full recovery from sepsis for each individual differs. Recovery depends on several factors such as the severity of infection, the patient’s overall health condition, and the type of treatment provided.

Effects of sepsis. Presence of numerous bacteria in the blood, causes the body to respond in organ dysfunction. Image Credit: Designua / Shutterstock

Mild Sepsis Recovery

In mild sepsis, complete recovery is possible at a quicker rate. On average, the recovery period from this condition takes about three to ten days, depending on the appropriate treatment response, including medication.

Severe Sepsis Recovery

Severe sepsis requires immediate treatment in the critical care area for a period of one month or more. Recovery is achievable, but it takes a longer time. Many individuals are known to have regained normal health after severe sepsis without residual dysfunctions. In severe sepsis, the recovery period duration varies from patient to patient, as it depends on the number of organs impacted by the infection and the extent of organ dysfunction.

Post-Sepsis Syndrome (PSS)

About 50% of severe sepsis survivors experience either short- or long-term cognitive and physical problems, collectively termed as post-sepsis syndrome, during their recovery period. The difficulties may include physical (excessive fatigue, weaker muscle strength, bloated limbs, and chest pain), psychological (anxiety, memory loss), and mental (inability to do simple arithmetical calculations) issues.

Recovery from Post-Sepsis Syndrome:

It is necessary to provide rehabilitation facilities to the patient so that they can return to normal life. The duration of recovery from PSS is about two years or more.

Recovery at hospital: Recovery from post-sepsis syndrome is initiated in the hospital by the physiotherapist, who helps the patients to carry out simple everyday activities on their own, such as:

• bathing, getting dressed, and walking
• doing physical exercises, as advised by the physiotherapist, in order to regain muscle strength

Recovery at home: After discharge from hospital, the sepsis survivor needs detailed care at home along with regular reviews with the healthcare provider.

• They need to have complete rest and build up their strength with slowly increasing activities, as they are likely to feel weak and tired.
• A balanced diet is essential. Small meals and supplemental nutrition drinks are suggested for those with a lack of appetite.
• To avoid depression and anxiety, interaction with family and friends is necessary.
• Small targets are fixed to achieve daily tasks.

Recovery After a Hospitalization for SepsisPlay

Septic Shock Recovery

Septic shock is a life-threatening stage of generalized infection, where the chance of patient survival is only about 50%, owing to multiple organ dysfunction associated with low blood pressure. Complete recovery from septic shock would imply the termination of any auxiliary therapies, which is not usually possible. In most cases, a patient with pre-existing chronic disease who survives septic shock is likely to need lifelong supportive treatment because of permanent organ dysfunction.

Rehabilitation for Patients with Amputated Limbs

Amputation of a part of the body, such as one or more fingers or toes, or of a limb, either in part or completely, is sometimes done to increase the rate of survival in patients who develop gangrene during septic shock. Amputation leads to scarring and changes in the structure of normal tissue, which is termed contractures, as a result of the normal wound healing process. To prevent contracture, the physiotherapist will recommend

• exercises to make the joint muscles mobile
• scar massage once it is healed;
• application of appropriate splints to hold the scar area in a stretched position
• appropriate medication to avoid pain
• in case of amputation of lower limbs, the use of prosthetic (artificial) limbs is helpful for the independent movement of young patients, while crutches or wheelchairs may be useful for elders

Rehabilitation of Patients with Kidney Damage

Even after surviving septic shock, some patients require lifelong dialysis due to kidney failure.

• The patient should perform physical activities like walking and moderate exercises
• Perform small tasks with a goal-oriented approach to achieve eventual independence to as large an extent as possible
• Go for dialysis therapy as scheduled by the doctor
• Since dialysis is not a cure, the patients may be registered for renal transplantation to ensure partial or complete recovery

New Findings in Recovery of Sepsis

Patients with late stages of sepsis need more time to recover when there is post-sepsis or sepsis-induced organ dysfunction. More research or studies are needed to find the best way of overcoming these complications.

Neutralization of HMGB1 Protein

A recent report by the Journal of Leukocyte Biology states that if a protein called high mobility group box 1(HMGB1), which is elevated in the late stages of sepsis, is increased or neutralized, white blood cell (neutrophil) dysfunction can be corrected. This promotes the ability of the body to destroy bacteria during the recovery period.

Mesenchymal Stem Cell Therapy

The world’s first trial of stem cell therapy for sepsis was performed in Ottawa. A septic shock patient in Ottawa hospital was administered 30 million mesenchymal cells along with the specific treatment for sepsis, which resulted in complete recovery.

References

Further Reading

The Relationship Between Sepsis and COVID-19: What We Know

By the bioMérieux Connection Editors

The Global Sepsis Alliance has stated that COVID-19 can cause sepsis, the body’s overwhelming and life-threatening response to an infection that can lead to organ damage and death. In the U.S., one in three patients who die in a hospital die of sepsis. Many different types of infections can cause sepsis, but the most common cause is pneumonia. Pneumonia is severe lung inflammation that occurs in response to an infection in which the air sacs fill with pus, making it difficult to breathe. Bacterial, viral and fungal infections can cause pneumonia and therefore sepsis.

Research suggests that COVID-19 may lead to sepsis due to several variables, including direct viral invasion, the presence of a bacterial or viral co-infection, and/or the age of the patient.

Two published case series about patients with severe COVID-19 from the Seattle, WA, area reported septic shock severe enough to require drugs to support the heart and circulation in almost 70% of patients. The overall organ damage among these patients was also substantial. More than 30% of patients in one series had evidence of liver injury and 75% had evidence of a depressed immune response. The other series reported acute kidney failure in almost 20% of affected patients requiring ICU care. In these studies, the great majority of patients tested negative for co-infection of bacteria and viruses. The lack of bacterial or viral co-infection suggests that the observed septic shock and/or organ damage may have been directly related to SARS-CoV-2.

While viral sepsis is a possible complication of SARS-CoV-2, viral infections alone generally do not cause sepsis as frequently as bacterial infections do. For example, seasonal influenza is commonly associated with bacterial co-infection that leads to severe illness. It is typically this kind of severe illness that requires admission to the ICU and causes ventilator-associated pneumonia. Often times, flu-associated bacterial co-infection is caused by pathogens that colonize in the nasopharynx—the upper part of the throat that sits behind the nose. Common bacterial pathogens that lead to pneumonia and sepsis include staphylococcus and streptococcus. From the case series previously discussed, COVID-19 may differ from seasonal influenza, causing sepsis more often by itself, rather than from a bacterial co-infection.

However, other data suggest that co-infection with COVID-19 may be more common. A study published in April 2020 investigated the co-infection rates between SARS-CoV-2 and other respiratory pathogens and found that more than 20% of positive SARS-CoV-2 specimens also tested positive for one or more non-SARS-CoV-2 pathogens. These specimens came from symptomatic patients, with symptoms ranging in severity. A retrospective study of hospitalized COVID-19 patients found an even greater likelihood of co-infection. The study showed that, of patients who did not survive, half had experienced a secondary infection. Of the non-survivors, 100% of patients had sepsis and 70% were noted to have septic shock.

In the case of COVID-19, the virus’s effect on the body as a whole and its relationship to sepsis are not yet well understood. This may be due to inconsistent testing for secondary pathogens and because researchers are still trying to determine what the best care and treatments are for COVID-19. While certain treatments seem promising, such as convalescent plasma, dexamethasone, or the antiviral treatment, remdesivir, they are still experimental. The current health of the patient, age, and presence of co-morbidities can also play a role in patient outcomes. Overall, COVID-19 can have a vast impact on virtually all organ systems, and the severity of its impact on the organs is directly associated with survival. Even though researchers are still investigating the relationship between COVID-19 and sepsis, proper care for sepsis in patients with severe COVID-19 remains very important.

Opinions in this article are not necessarily those of bioMérieux, Inc.

Research gives clear target for drug development and further study into memory loss — ScienceDaily

The loss of memory and cognitive function known to afflict survivors of septic shock is the result of a sugar that is released into the blood stream and enters the brain during the life-threatening condition. This finding, published today in the Proceedings of the National Academy of Sciences, explains the premature mental aging that follows septic shock and may shed light on memory loss in other diseases.

“This sugar is getting into the hippocampus, and it shouldn’t be in there,” said Robert Linhardt, professor of biocatalysis and metabolic engineering at Rensselaer Polytechnic Institute, and lead author of the study. “We actually think this is rewiring memory in the hippocampus, and it’s causing memory loss. Neural circuits are being disrupted or broken or connected in the wrong way.”

The study is the latest outcome of a six-year partnership between Linhardt and Dr. Eric Schmidt, an expert on sepsis and assistant professor in the Department of Medicine at University of Colorado Denver.

Sepsis is a systemic infection of the body. One-third of patients admitted to hospitals with sepsis go into septic shock. Of those, half will die. In a 2016 study published in the American Journal of Respiratory and Critical Care Medicine, a team that included Schmidt and Linhardt developed a simple but accurate test for determining whether patients in septic shock would recover or die.

The test uses a urine sample to check concentrations of a type of sugar — glycosaminoglycans — that ordinarily coat cells lining blood vessels and other surfaces inside the body. In septic shock, the body sheds fragments of these sugars, and the team found that higher concentrations portend death. The test is used in clinical settings, and the insight has helped doctors search for more effective therapies.

Their next step tested whether a link exists between the sugars and mental aging associated with septic shock. Research published in the February edition of the Journal of Clinical Investigations showed that, during septic shock, fragments of the sugar heparan sulfate crossed the blood-brain barrier and entered the hippocampus, a region of the brain critical to memory and cognitive function. Evidence indicated that the heparan sulfate might be binding with brain-derived neurotrophic factor (BDNF), which is critical to hippocampal long-term potentiation, a process responsible for spatial memory formation. The researchers also found that presence of an enriched heparan sulfate in the blood plasma of septic patients upon admission to an intensive care unit predicted cognitive impairment detected 14 days after discharge.

To be sure, the researchers wanted to see the heparan sulfate enter the hippocampus and bind with BDNF. The new study in PNAS shows exactly that. To follow heparan sulfate into the brain in a sea of other sugars moving through the bloodstream Linhardt’s team had to synthesize heparan sulfate tagged with a stable carbon isotope, which unlike many other labeling methods, is completely safe and was identical to the natural sugar. It took them two years to figure out how to do it.

Then they put their hypothesis to the test. In healthy mice, 100 percent of the tagged heparan sulfated was excreted through the urine within 20 minutes, and none ever entered the brain. But in septic mice, researchers found a small amount of tagged heparan sulfate in the hippocampus region of the brain.

“Now that we know the cause of cognitive damage in septic shock, it gives us a clear target for a drug therapy: something that binds to the sugar and clears it, or an enzyme that converts it to something that won’t impair cognitive function,” Linhardt said. “This is an important advance, and we’re excited about the story that’s unfolding. “

Story Source:

Materials provided by Rensselaer Polytechnic Institute. Original written by Mary L. Martialay. Note: Content may be edited for style and length.

FAQs – Australian Sepsis Network

These are the answers to some of the most common questions we receive about sepsis, both from individuals and healthcare providers.

Sepsis is an illness that can happen in response to an infection and can quickly become life-threatening. It can affect all parts of the body.

In severe cases of sepsis, one or more organs fail. In the worst cases (known as septic shock), sepsis causes the blood pressure to decrease to dangerous levels and the heart to become weaker. Once this happens, multiple organs may fail quickly and, if not corrected, the patient will die.

Sepsis is a medical emergency that can be difficult to diagnose, and to treat.

What are the symptoms of sepsis?

Common symptoms of sepsis are fever, chills, rapid breathing, rapid heart rate, rashes, drowsiness, confusion, and disorientation, and not passing urine.

Many of these symptoms, such as fever and difficulty with breathing, are similar to symptoms of other conditions, like the flu. This makes it difficult to diagnose sepsis in its early stages, especially in hospitalised patients who will have other causes of those symptoms.

What causes sepsis?

Sepsis occurs when the body’s response to an infection becomes harmful. Infection causes your immune system releases chemicals into your blood to fight the infection.

These chemicals can cause generalised inflammation in the body making blood vessels leak and causing blood clots. These changes can damage all the body’s organs.

Almost any type of infections can lead to sepsis, this includes infections of the lungs, abdomen (such as appendicitis), urinary tract, skin, or other part of the body.

Infections acquired in hospitals or other healthcare settings (healthcare-associated infections), can also lead to sepsis.

Who gets sepsis?

Anyone can get sepsis, but the risk is higher in:

• People with weak immune systems
• Infants and young children
• Elderly people
• People with pre-existing illnesses, such as diabetes, AIDS, cancer, and kidney or liver disease
• People suffering from a severe burn or physical trauma

How many people get sepsis?

Each year around 18,000 people are treated in an Intensive Care Unit (ICU) in Australia and New Zealand for severe sepsis. The number of people treated for sepsis is increasing because:

• The population is aging
• More people have chronic illnesses
• More people are getting being treated with immunosuppressive drugs, chemotherapy, and organ transplants
• Bacteria are becoming more resistant to antibiotics

How is sepsis diagnosed?

Doctors will suspect sepsis from a number of physical symptoms like fever, increased heart rate, increased breathing, mental confusion or drowsiness. They will also do laboratory tests to confirm the diagnosis. These tests include a blood test to reveal if the number of white blood cells is abnormal (a common sign of sepsis), or tests to detect bacteria in the bloodstream or in urine.  X-ray and scans may be performed to identify or confirm the source of the infection.

How is sepsis treated?

People with sepsis are treated in hospital and those with severe sepsis are usually treated in the intensive care unit. Treatment targets the infection, while supporting vital organs and giving intravenous fluids and drugs to maintain blood pressure.

In severe cases when organs fail, life-support treatments such as artificial ventilation (breathing machine) or kidney dialysis, may be necessary. Surgery may be needed to control a local site of infection such as in appendicitis or following a perforated bowel.

Are there any long-term effects of sepsis?

Many people who survive severe sepsis recover completely and return to normal lives.

Some people, especially those who have required prolonged treatment in an ICU may experience longer term problems including permanent organ damage.

Other longer term effects include difficulty sleeping, concentrating or returning to work, reduced energy and musculoskeletal problems.

What is being done to improve outcomes from sepsis?

Many government agencies, doctors, nurses and other healthcare providers are working to prevent sepsis and to improve the recognition and treatment of sepsis.

Examples are:

• Australian Commission on Safety and Quality in Health Care
  • Healthcare Associated Infection (HAI) Prevention Program
  • National Antimicrobial Stewardship Initiative
  • National Hand Hygiene Initiatives
• National Infection Control Guidelines
• NSW Clinical Excellence Commission’s “Sepsis Kills” Program
• Better Care Victoria’s ‘Sepsis Improvement Project’

Blood test for sepsis in an adult

Sepsis: types, procedures, how to determine

About sepsis

Infectious blood poisoning, or, more precisely, sepsis, is a condition that really threatens a person’s life. In oncology, sepsis is the result of the penetration of pathogenic microorganisms into the human body. It is they that provoke the beginning of the production of biologically active substances, the so-called inflammatory mediators.

Our tissues and organs react very actively to this process, which is why inflammatory foci appear in different parts of the body. They also cause an imbalance in vital functions. As already noted, in such a situation, a lethal outcome is very possible.

It is important for an oncologist to pay special attention to diagnostic procedures and the treatment of sepsis, because it is he who quite often occurs in cancer patients. The risk group consists of operated patients who are in the therapy ward. It is even theoretically impossible to create ideal sterile conditions. And here the task of doctors is to apply the latest diagnostics of the disease and the ability to take the necessary measures to solve this problem.

Why there is

Sepsis is caused by microorganisms. These are parasites, fungi, bacteria, and viruses, which in most cases penetrate into the body from the external environment.

Sometimes sepsis develops from the natural flora of the body, this usually happens with an extremely reduced immunity.

Do not think that the very fact of infection penetration into our body initiates sepsis. There are additional factors leading to the generalization of this process.

Here we are talking primarily about the risk group:

• Age 75+;
• Injury;
• Burns;
• Alcoholism;
• Addiction;
• Diseases of a chronic nature;
• Operations performed;
• Availability of invasive devices;
• Long-term treatment in the clinic;
• Failure of the immune system due to illness or chemotherapy;
• Pregnancy, childbirth.

Types of sepsis

The classification of the disease is based on the localization of the primary focus:

• Primary sepsis;
• Secondary sepsis.

If in the primary it is impossible to establish the localization of the focus, then in the case of secondary sepsis, depending on its location, it is classified:

• Percutaneous. The focus is on the skin;
• Odontogenic. The cause of the occurrence is diseases of the dentoalveolar system;
• Otogenic. Inflammation in the ear;
• Gynecological sepsis. The focus is in the female genital organs;
• Surgical. Infection during surgery or invasive procedures.

When the test is ordered

It happens that the symptoms of sepsis are mild and resemble the manifestations of other diseases.

Symptoms that should alert the doctor and prescribe tests:

• Increased body temperature;
• Rapid breathing and contractions of the heart muscle;
• Profuse sweating;
• Signs of dysfunction of various organs.

In severe situations, the patient is observed:

• Lethargy;
• Confusion of consciousness;
• Decrease in blood pressure;
• Coldness in limbs, cyanosis;
• The appearance of spots on the skin.

An important reason to prescribe tests to detect sepsis is that previously conducted studies suggest blood poisoning.

As a rule, the quick SOFA (qSOFA) scale criteria are used for the study, where it is important to identify 3 criteria that summarize the presence of sepsis:

• Upper blood pressure below 100 mm Hg. Art .;
• Respiration rate up to 22 per minute;
• Change of thinking.

For a more accurate diagnosis, the criteria of the SOFA scale are used, which take into account the results of laboratory tests.

Test procedure

An international method for the quantitative diagnosis of bacterial toxins is the analysis of endotoxin activity (EAA). It is the only FDA approved method to date.

Endotoxin is a lipopolysaccharide by its chemical nature. It is a strong inflammatory mediator. And even at the initial stages of the development of sepsis, its level rises sharply.

An endotoxin level analysis is a blood sampling followed by the addition of unique antibodies to it, which, by binding to a bacterial lipopolysaccharide, absorb neutrophils.

Due to this, biochemical reactions begin in the cells and there is a rapid absorption and consumption of oxygen.

The intensity of the resulting luminescence, which is recorded by means of a luminometer, makes it possible to judge the level of endotoxin in the blood.

The result obtained during the study is evaluated from 0 to 1:

0 – no endotoxin;

less than 0.4 – the level is low;

0.4–0.59 – intermediate level;

0.6 and more – high level;

1 – critical level.

This analysis is straightforward.

Pros of the test:

• Fast results;
• Simplicity;
• Informative value;
• Identification of the risk of developing sepsis;
• Diagnosis of sepsis in its early stages.

Clinic Onco.Rehab has everything you need to carry out this test for sepsis.

Erythrocytes with sepsis

Red blood cells are blood cells that contain hemoglobin and are responsible for transporting oxygen and carbon dioxide.

With the development of sepsis in the later stages, they are destroyed. First of all, what happens:

• Anemia, i.e. hemoglobin decreases;
• Decrease in the number of erythrocytes;
• There is free hemoglobin, which activates the production of substances associated with inflammation;
• Reducing their deformation, and hence their main functions.

ESR with sepsis

ESR, or erythrocyte sedimentation rate (male rate 2-15 mm / hour, female 1-10 mm / hour.) increases with blood poisoning. This is a clear indicator that an inflammatory process is taking place in the body.

Leukocytes with sepsis

An increase in the number of leukocytes in the blood causes leukocytosis. The reason for the increase in these white blood cells is the development of the process of inflammation.

In some cases, a special type of leukocytes decreases, neutrophils leads to neutropenia. This is a deplorable symptom.

Platelets for sepsis

Thrombocytopenia caused by a decrease in the number of platelets in the blood is a clear symptom of the presence of sepsis.

The risk of death depends directly on:

• How much the patient’s platelet count is reduced;
• The timing of this state.

How to define sepsis?

With sepsis, mortality can reach 10 to 40%. It depends on several important factors:

• Type of pathogen;
• General health of the patient;
• Time of diagnosis and treatment initiation.

It happens that the inflammatory process proceeds in the form of septic shock, in which there is a violation of blood circulation, metabolic processes in cells, a significant drop in blood pressure. In this state, mortality reaches its maximum threshold.

Onco.Rehab integrative oncology clinic practices all types of sepsis treatment:

• Antibiotics;
• Medicines capable of supporting vital functions;
• Infusion therapy;
• The latest devices for plasmapheresis, etc.d.

Clinic of integrative oncology Onco.Rehab: our partners do everything necessary for the early diagnosis of sepsis, we provide immediate assistance, we carry out resuscitation measures.

Sepsis-associated encephalopathy (review) | Beloborodova

1. Ziaja M. Septic encephalopathy. Curr. Neurol. Neurosci. Rep. 2013; 13 (10): 383.DOI: 10.1007 / s11910-013-0383-y. PMID: 23954971

2. Chaudhry N., Duggal A.K. Sepsis associated encephalopathy. Adv. Med. 2014; 2014: 762320. DOI: 10.1155 / 2014/762320. PMID: 26556425

3. Pinheiro da Silva F., Machado M.C., Velasco I.T. Neuropeptides in sepsis: from brain pathology to systemic inflammation. Peptides. 2013; 44: 135-138.DOI: 10.1016 / j.peptides.2013.03.029. PMID: 23583479

4. Annane D, Sharshar T. Cognitive decline after sepsis. Lancet Respir. Med. 2015; 3 (1): 61-69. DOI: 10.1016 / S2213-2600 (14) 70246-2. PMID: 25434614

5. Kaur J., Singhi P., Singhi S., Malhi P., Saini A. G. Neurodevelopmental and behavioral outcomes in children with sepsis-associated encephalopathy admitted to pediatric intensive care unit: a prospective case control study.J. Child Neurol. 2015; 31 (6): 683-690. DOI: 10.1177 / 0883073815610431. PMID: 26500243

6. Vincent J.L., Abraham E. The last 100 years of sepsis. Am. J. Respir. Crit. Care Med. 2006; 173 (3): 256-263. Doi: 10.1164 / rccm.200510-1604OE. PMID: 16239619

7. Dellinger R.P., Levy M.M., Rhodes A., Annane D., Gerlach H., Opal S.M., Sevransky J.E., Sprung CL, Douglas IS, Jaeschke R., Osborn TM, Nunnally ME, Townsend SR, Reinhart K., Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R .; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Crit. Care Med. 2013; 41 (2): 580-637. DOI: 10.1097 / CCM.0b013e31827e83af. PMID: 23352941

8.Angus D.C., Linde-Zwirble W.T., Lidicker J., Clermont G., Carcillo J., Pinsky M.R. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit. Care Med. 2001; 29 (7): 1303-1310. DOI: 10.1097 / 00003246-200107000-00002. PMID: 11445675

9. Jacob A., Brorson J. R., Alexander J. J. Septic encephalopathy: Inflammation in man and mouse. Neurochem. Int. 2011; 58 (4): 472–476.DOI: 10.1016 / j.neuint.2011.01.004. PMID: 21219956

10. Piva S., McCreadie V. A., Latronico N. Neuroinflammation in sepsis: sepsis associated delirium. Cardiovasc. Hematol. Disord. Drug Targets. 2015; 15 (1): 10-18. DOI: 10.2174 / 1871529X15666150108112452. PMID: 25567339

11. Wilson J. X., Young G.B. Progress in clinical neurosciences: sepsis-associated encephalopathy: evolving concepts.Can. J. Neurol. Sci. 2003; 30 (2): 98-105. DOI: 10.1017 / S031716710005335X. PMID: 12774948

12. Singer M., Deutschman CS, Seymour CW, Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal S., Rubenfeld GD, van der Poll T., Vincent JL, Angus DC The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).JAMA. 2016; 315 (8): 801-810. DOI: 10.1001 / jama.2016.0287. PMID: 26

8

13. Zampieri F.G., Park M., Machado F.S., Azevedo L.C. Sepsis-associated encephalopathy: not just delirium. Clinics (Sao Paulo). 2011; 66 (10): 1825-1831. DOI: 10.1590 / S1807-59322011001000024. PMID: 22012058

14. Ebersoldt M., Sharshar T., Annane D. Sepsis-associated delirium.Intensive Care Med. 2007; 33 (6): 941-950. DOI: 10.1007 / s00134-007-0622-2. PMID: 17410344

15. Gofton T.E., Young G.B. Sepsis-associated encephalopathy. Nat. Rev. Neurol. 2012; 8 (10): 557-566. DOI: 10.1038 / nrneurol.2012.183. PMID: 22986430

16. Maltseva L.A., Bazilenko D.V. The role of sepsis-associated encephalopathy in the formation of multiple organ failure syndrome in patients with severe sepsis and septic shock.Vestn. intensity. therapy. 2015; 3: 11-15.

17. Young G.B. Encephalopathy of infection and systemic inflammation. J. Clin. Neurophysiol. 2013; 30 (5): 454-461. DOI: 10.1097 / WNP.0b013e 3182a73d83. PMID: 24084178

18. Hosokawa K., Gaspard N., Su F., Oddo M., Vincent J.-L., Taccone F.S. Clinical neurophysiological assessment of sepsis associated brain dysfunction: a systematic review.Crit. Care. 2014; 18 (6): 674. DOI: 10.1186 / s13054-014-0674-y. PMID: 25482125

19. Piazza O., Cotena S., De Robertis E., Caranci F., Tufano R. Sepsis associated encephalopathy studied by MRI and cerebral spinal fluid S100B measurement. Neurochem. Res. 2009; 34 (7): 1289-1292. DOI: 10.1007 / s11064-008-9907-2. PMID: 19132530

20.Sharshar T., Carlier R., Bernard F., Guidoux C., Brouland JP, Nardi O., de la Grandmaison GL, Aboab J., Gray F., Menon D., Annane D. Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med. 2007; 33 (5): 798-806. DOI: 10.1007 / s00134-007-0598-y. PMID: 17377766

21. Oddo M., Taccone F.S. How to monitor the brain in septic patients? Minerva Anestesiologica. 2015; 81 (7): 776-788. PMID: 25812488

22.Stubbs D.J., Yamamoto A.K., Menon D.K. Imaging in sepsis-associated encephalopathy-insights and opportunities. Nat. Rev. Neurol. 2013; 9 (10): 551-561. DOI: 10.1038 / nrneurol.2013.177. PMID: 23999468

23. Pfister D., Siegemund M., Dell-Kuster S., Smielewski P., Rüegg S., Strebel S.P., Marsch S.C., Pargger H., Steiner L.A. Cerebral perfusion in sepsis-associated delirium. Crit. Care. 2008; 12 (3): R63. Doi: 10.1186 / cc6891.PMID: 18457586

24. Szatmári S., Végh T., Csomós A., Hallay J., Takács I., Molnár C., Fülesdi B. Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit. Care. 2010; 14 (2): R50. Doi: 10.1186 / cc8939. PMID: 20356365

25.Busygin S.N., Klink Yu.P., Bubnova I.D. Hemodynamic regulation and whey protein S100 in various clinical forms of septic encephalopathy.Ural honey. magazine. 2013; 3 (108): 53-57.

26. Zenaide P. V., Gusmao-Flores D. Biomarkers in septic encephalopathy: a systematic review of clinical studies. Rev. Bras. Ter. Intensiva. 2013; 25 (1): 56-62. PMID: 23887761

27. Yao B., Zhang L.N., Ai Y.H., Liu Z.Y., Huang L. Serum S100b is a better biomarker than neuron-specific enolase for sepsis-associated encephalopathy and determining its prognosis: a prospective and observational study. Neurochem. Res. 2014; 39 (7): 1263-1269. DOI: 10.1007 / s11064-014-1308-0. PMID: 24760429

28. Gashilova F.F., Zhukova N.G. Neuron-specific enolase in blood serum as a diagnostic marker of parkinsonism. Bul. Siberian medicine. 2005; 4 (3): 28-33.

29. Nguyen D.N., Spapen H., Su F., Schiettecatte J., Shi L., Hachimi-Idrissi S., Huyghens L. Elevated serum levels of S-100 protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock. Crit. Care Med. 2006; 34 (7): 1967-1974. DOI: 10.1097 / 01.CCM.0000217218.51381.49. PMID: 16607230

30. Hsu A.A., Fenton K., Weinstein S., Carpenter J., Dalton H., Bell M.J. Neurological injury markers in children with septic shock. Pediatr. Crit. Care Med.2008; 9 (3): 245-251. DOI: 10.1097 / PCC.0b013e3181727b22. PMID: 18446104

31. Tomasi CD, Vuolo F., Generoso J., Soares M., Barichello T., Quevedo J., Ritter C., Dal-Pizzol F. Biomarkers of delirium in a low-risk community-acquired pneumonia-induced sepsis … Mol. Neurobiol. 2017; 54 (1): 722-726. DOI: 10.1007 / s12035-016-9708-6. PMID: 26768428

32.Comim C.M., Cassol-Jr O.J., Constantino L.C., Petronilho F., Constantino L.S., Stertz L., Kapczinski F., Barichello T., Quevedo J., Dal-Pizzol F. Depressive-like parameters in sepsis survivor rats. Neurotox. Res. 2010; 17 (3): 279-286. DOI: 10.1007 / s12640-009-9101-6. PMID: 19705213

33. Comim C.M., Silva N.C., Mina F., Dominguini D., Scaini G., Morais M.O., Rosa D.V., Magno L.A., Streck E.L., Romano-Silva M.A., Quevedo J. , DalPizzol F. Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis. Synapse. 2014; 68 (10): 474-479. DOI: 10.1002 / syn.21760. PMID: 24978930

34. Vasconcelos A.R., Yshii L.M., Viel T.A., Buck H.S., Mattson M.P., Scavone C., Kawamoto E.M. Intermittent fasting attenuates lipopolysaccharideinduced neuroinflammation and memory impairment. J. Neuroinflammation.2014; 11: 85. DOI: 10.1186 / 1742-2094-11-85. PMID: 24886399

35. Ritter C., Miranda AS, Giombelli VR, Tomasi CD, Comim CM, Teixeira AL, Quevedo J., Dal-Pizzol F. Brain-derived neurotrophic factor plasma levels are associated with mortality in critically ill patients even in the absence of brain injury. Crit. Care. 2012; 16 (6): R234. Doi: 10.1186 / cc11902. PMID: 23245494

36. Girard T.D., Jackson J.C., Pandharipande P.P., Pun B.T., Thompson J.L., Shintani A.K., Gordon S.M., Canonico A.E., Dittus R.S., Bernard G.R., Ely E.W. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit. Care Med. 2010; 38 (7): 1513-1520. DOI: 10.1097 / CCM.0b013e3181e47be1. PMID: 20473145

37. Sweis R., Ortiz J., Biller J. Neurology of sepsis. Curr. Neurol. Neurosci. Rep.2016; 16 (3): 21. DOI: 10.1007 / s11910-016-0623-z. PMID: 26820754

38. Tanaka T., Sunden Y., Sakoda Y., Kida H., Ochiai K., Umemura T. Lipopolysaccharide treatment and inoculation of influenza A virus results in influenza virus-associated encephalopathy-like changes in neonatal mice. J. Neurovirol. 2010; 16 (2): 125-132. DOI: 10.3109 / 13550281003682521. PMID: 20345319

39. Flierl MA, Stahel PF, Rittirsch D., Huber-Lang M., Niederbichler AD, Hoesel LM, Touban BM, Morgan SJ, Smith WR, Ward PA, Ipaktchi K. Inhibition of complement C5a prevents breakdown of the blood– brain barrier and pituitary dysfunction in experimental sepsis. Crit. Care. 2009; 13 (1): R12. Doi: 10.1186 / cc7710. PMID: 19196477

40. Barichello T., Machado R.A., Constantino L., Valvassori S.S., Réus G.Z., Martins M.R., Petronilho F., Ritter C., Quevedo J., Dal-Pizzol F. Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Crit. Care Med. 2007; 35 (9): 2186-2190. DOI: 10.1097 / 01.CCM.0000281452.60683.96. PMID: 17855835

41. Calsavara A.C., Rodrigues D.H., Miranda A.S., Costa P.A., Lima C.X., Vilela M.C., Rachid M.A., Teixeira A.L. Late anxiety-like behavior and neuroinflammation in mice subjected to sublethal polymicrobial sepsis. Neurotox. Res. 2013; 24 (2): 103-108. DOI: 10.1007 / s12640-012-9364-1. PMID: 23224747

42. Gao R., Kan M.Q., Wang S.G., Yang R.H., Zhang S.G .. Disrupted tryptophan metabolism induced cognitive impairment in a mouse model of sepsis-associated encephalopathy. Inflammation. 2016; 39 (2): 550-560. DOI: 10.1007 / s10753-015-0279-x. PMID: 26508338

43.Wu J., Zhang M., Hao S., Jia M., Ji M., Qiu L., Sun X., Yang J., Li K. Mitochondria-targeted peptide reverses mitochondrial dysfunction and cognitive deficits in sepsis-associated tncephalopathy … Mol. Neurobiol. 2015; 52 (1): 783-791. DOI: 10.1007 / s12035-014-8918-z. PMID: 25288156

44. Venturi L., Miranda M., Selmi V., Vitali L., Tani A., Margheri M., De Gaudio A.R., Adembri C. Systemic sepsis exacerbates mild post-traumatic brain injury in the rat. J. Neurotrauma. 2009; 26 (9): 1547-1556. DOI: 10.1089 / neu.2008-0723. PMID: 19257801

45. Semmler A., ​​Frisch C., Debeir T., Ramanathan M., Okulla T., Klockgether T., Heneka M.T. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp. Neurol. 2007; 204 (2): 733-740. DOI: 10.1016 / j.expneurol.2007.01.003. PMID: 17306796

46.Janz D.R., Abel T.W., Jackson J.C., Gunther M., Heckers S., Ely E.W. Brain autopsy findings in intensive care unit patients previously suffering from delirium: a pilot study. J. Crit. Care. 2010; 25 (3): 538.e7-538.e12. DOI: 10.1016 / j.jcrc.2010.05.004. PMID: 20580199

47. Semmler A., ​​Hermann S., Mormann F., Weberpals M., Paxian S.A., Okulla T. , Schäfers M., Kummer M.P., Klockgether T., Heneka M.T. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism.J. Neuroinflammation. 2008; 5: 38. DOI: 10.1186 / 1742-2094-5-38. PMID: 18793399

48. Yokoo H., Chiba S., Tomita K., Takashina M., Sagara H., Yagisita S., Takano Y., Hattori Y. Neurodegenerative evidence in mice brains with cecal ligation and puncture-induced sepsis: preventive effect of the free radical scavenger edaravone. PLoS One. 2012; 7 (12): e51539. DOI: 10.1371 / journal.pone.0051539. PMID: 23236515

49.Papadopoulos M.C., Lamb F.J., Moss R.F., Davies D.C., Tighe D., Bennett E.D. Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex. Clin. Sci. (Lond.). 1999; 96 (5): 461-466. DOI: 10.1042 / CS19980327. PMID: 10209077

50. Sharshar T., Gray F., Poron F., Raphael J. C., Gajdos P., Annane D. Multifocal necrotizing leukoencephalopathy in septic shock. Crit. Care Med. 2002; 30 (10): 2371-2375. DOI: 10.1097 / 00003246-200210000-00031. PMID: 12394971

51. Messaris E., Memos N., Chatzigianni E., Konstadoulakis M.M., Menenakos E., Katsaragakis S., Voumvourakis C., Androulakis G. Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis. Crit. Care Med. 2004; 32 (8): 1764-1770. DOI: 10.1097 / 01.CCM.0000135744.30137.B4. PMID: 15286556

52.Liu L., Xie K., Chen H., Dong X., Li Y., Yu Y., Wang G., Yu Y. Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Res. 2014; 1589: 78-92. DOI: 10.1016 / j.brainres.2014.09.030. PMID: 25251596

53. Bozza F.A., D’Avila J.C., Ritter C., Sonneville R., Sharshar T., Dal-Pizzol F. Bioenergetics, mitochondrial dysfunction, and oxidative stress in the pathophysiology of septic encephalopathy.Shock. 2013; 39 (Suppl 1): 10-16. DOI: 10.1097 / SHK.0b013e31828fade1. PMID: 23481496

54. Green R., Scott L. K., Minagar A., ​​Conrad S. Sepsis associated encephalopathy (SAE): a review. Front. Biosci. 2004; 9: 1637-1641. DOI: 10.2741 / 1250. PMID: 14977574

55. Basler T., Meier-Hellmann A., Bredle D., Reinhart K. Amino acid imbalance early in septic encephalopathy.Intensive Care Med. 2002; 28 (3): 293-298. DOI: 10.1007 / s00134-002-1217-6. PMID: 11

8

56. Azevedo L.C. Mitochondrial dysfunction during sepsis. Endocr. Metab. Immune Disord. Drug Targets. 2010; 10 (3): 214-223. PMID: 20509844

57. N.V. Beloborodova, V.V. Teplova, N.I. Fedotcheva. The role of microbial metabolites in mitochondrial dysfunction in sepsis.Saarbrücken: Lambert Academic Publishing; 2013: 96.

58. Nico B., Ribatti D. Morphofunctional aspects of the blood – brain barrier. Curr. Drug Metab. 2012; 13 (1): 50-60. PMID: 22292807

59. Taccone F.S., Castanares-Zapatero D., Peres-Bota D., Vincent J.L., Berre J., Melot C. Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock.Neurocrit. Care. 2010; 12 (1): 35–42. DOI: 10.1007 / s12028-009-9289-6. PMID: 19806473

60. Taccone F.S., Scolletta S., Franchi F., Donadello K., Oddo M. Brain perfusion in sepsis. Curr. Vasc. Pharmacol. 2013; 11 (2): 170-186. PMID: 23506496

61. Soejima Y., Fujii Y., Ishikawa T., Takeshita H., Maekawa T. Local cerebral glucose utilization in septic rats.Crit. Care Med. 1990; 18 (4): 423-427. DOI: 10.1097 / 00003246-19