What is sepsis and how does it develop. Who is at risk for sepsis. What are the signs and symptoms of sepsis. How is sepsis diagnosed and treated. Can sepsis be prevented. What are the long-term effects of sepsis. How does sepsis differ from other inflammatory conditions.

The Silent Killer: Unraveling the Complexity of Sepsis

Sepsis, often referred to as blood poisoning, is a life-threatening medical emergency that occurs when the body’s response to infection spirals out of control. This extreme reaction can rapidly lead to tissue damage, organ failure, and even death if not recognized and treated promptly. Despite its severity, sepsis remains a poorly understood condition among the general public.

To grasp the gravity of sepsis, consider these sobering statistics:

• At least 1.7 million adults in America develop sepsis annually
• Approximately 350,000 adults who develop sepsis die during hospitalization or are discharged to hospice
• One in three people who die in a hospital had sepsis during that hospitalization
• In nearly 87% of cases, sepsis or the infection causing it starts before a patient is admitted to the hospital

Sepsis Unveiled: Causes and Mechanisms

How does sepsis develop? Sepsis occurs when an existing infection triggers a chain reaction throughout the body. This overactive immune response can quickly escalate, causing widespread inflammation and potential organ dysfunction. While any infection can potentially lead to sepsis, those most commonly associated with the condition often originate in the lungs, urinary tract, skin, or gastrointestinal system.

Is sepsis caused by specific pathogens? While bacterial infections are the most common culprits, viral infections like COVID-19 and influenza, as well as fungal infections, can also result in sepsis. It’s crucial to understand that sepsis itself is not contagious, but the underlying infections that lead to it may be transmissible.

The Infectious Origins of Sepsis

What types of infections commonly lead to sepsis? Some of the most frequent sources include:

1. Pneumonia
2. Urinary tract infections (UTIs)
3. Skin infections, such as cellulitis
4. Abdominal infections, like appendicitis or diverticulitis
5. Bloodstream infections (bacteremia)

Identifying High-Risk Individuals: Who’s Most Vulnerable to Sepsis?

While sepsis can affect anyone, certain groups are at higher risk for developing this life-threatening condition. Understanding these risk factors is crucial for early detection and prevention.

Who is most susceptible to sepsis? The following groups are considered high-risk:

• Adults 65 years or older
• People with weakened immune systems
• Individuals with chronic medical conditions (e.g., diabetes, lung disease, cancer, kidney disease)
• Those who have recently experienced severe illness or hospitalization
• Survivors of previous sepsis episodes
• Children younger than one year old

The Impact of Comorbidities on Sepsis Risk

How do underlying health conditions increase sepsis risk? Chronic diseases can compromise the body’s ability to fight infections effectively, making it more susceptible to overwhelming immune responses. For instance, diabetes can impair circulation and wound healing, while cancer treatments may suppress the immune system, leaving individuals more vulnerable to infections that could potentially lead to sepsis.

Recognizing the Red Flags: Signs and Symptoms of Sepsis

Early detection of sepsis is crucial for improving outcomes. However, the symptoms can be subtle and easily mistaken for other conditions. Familiarizing yourself with the warning signs can potentially save lives.

What are the key indicators of sepsis? Look out for the following signs and symptoms:

• High heart rate or weak pulse
• Confusion or disorientation
• Extreme pain or discomfort
• Fever, shivering, or feeling very cold
• Shortness of breath
• Clammy or sweaty skin

It’s important to note that these symptoms may vary from person to person, and sepsis can present differently in children compared to adults. Additionally, symptoms may be influenced by the underlying infection causing sepsis.

The Sepsis Spectrum: From Early Stages to Septic Shock

How does sepsis progress? Sepsis can rapidly evolve through several stages:

1. Systemic Inflammatory Response Syndrome (SIRS): The initial stage characterized by widespread inflammation
2. Sepsis: SIRS combined with a confirmed or suspected infection
3. Severe Sepsis: Organ dysfunction begins to occur
4. Septic Shock: A dramatic drop in blood pressure that can lead to multiple organ failure

As sepsis advances to septic shock, additional symptoms may emerge, including the inability to stand, extreme drowsiness, and significant changes in mental status.

The Race Against Time: Diagnosing and Treating Sepsis

Sepsis is a medical emergency that requires immediate attention. Prompt diagnosis and treatment are critical for improving survival rates and minimizing long-term complications.

How is sepsis diagnosed? Diagnosing sepsis typically involves a combination of clinical assessment and laboratory tests, including:

• Physical examination to evaluate vital signs and symptoms
• Blood tests to check for signs of infection, organ dysfunction, and abnormal blood clotting
• Imaging studies (e.g., X-rays, CT scans) to identify the source of infection
• Urine tests to detect urinary tract infections
• Wound secretion analysis for skin infections

The Golden Hour: Time-Critical Treatment for Sepsis

What is the primary approach to treating sepsis? The cornerstone of sepsis treatment is the “Sepsis Six,” a set of interventions that should be initiated within the first hour of diagnosis:

1. Administer high-flow oxygen
2. Obtain blood cultures
3. Give broad-spectrum antibiotics
4. Start intravenous fluid resuscitation
5. Measure serum lactate and hemoglobin
6. Monitor urine output

Additional treatments may include vasopressors to support blood pressure, mechanical ventilation for respiratory failure, and in severe cases, dialysis for kidney support.

Beyond Survival: Long-Term Consequences of Sepsis

While immediate survival is the primary focus in sepsis treatment, the battle doesn’t end upon hospital discharge. Many sepsis survivors face long-term physical, cognitive, and emotional challenges.

What are the potential long-term effects of sepsis? Survivors may experience:

• Post-sepsis syndrome, characterized by physical and psychological symptoms
• Increased risk of recurrent infections
• Cognitive impairment, including memory problems and difficulty concentrating
• Chronic pain and fatigue
• Post-traumatic stress disorder (PTSD)
• Organ damage, potentially requiring ongoing medical care or rehabilitation

The Road to Recovery: Rehabilitation After Sepsis

How can sepsis survivors optimize their recovery? A comprehensive rehabilitation program may include:

1. Physical therapy to rebuild strength and mobility
2. Occupational therapy to regain independence in daily activities
3. Cognitive rehabilitation to address memory and concentration issues
4. Psychological support to manage emotional challenges and PTSD
5. Nutritional counseling to support overall health and immune function

Sepsis Prevention: Strategies for Reducing Risk

While it’s not always possible to prevent sepsis, there are steps individuals can take to reduce their risk of developing this life-threatening condition.

How can one lower the chances of developing sepsis? Consider the following preventive measures:

• Practice good hygiene, including regular handwashing
• Stay up-to-date on vaccinations, including flu shots and pneumococcal vaccines
• Manage chronic health conditions effectively
• Seek prompt medical attention for infections and wounds that aren’t healing
• Be aware of the signs and symptoms of sepsis
• Follow prescribed antibiotic regimens completely

The Role of Healthcare Providers in Sepsis Prevention

How can healthcare systems contribute to sepsis prevention? Hospitals and clinics can implement various strategies:

1. Develop and adhere to infection control protocols
2. Implement sepsis screening tools in emergency departments and inpatient units
3. Provide ongoing education for healthcare professionals on sepsis recognition and management
4. Establish rapid response teams for suspected sepsis cases
5. Monitor and improve antibiotic stewardship programs

Sepsis Across the Lifespan: Special Considerations for Different Age Groups

Sepsis can affect individuals of all ages, but its presentation, risk factors, and management may vary across different life stages.

How does sepsis differ in various age groups?

Neonatal Sepsis

Newborns, especially premature infants, are particularly vulnerable to sepsis. Signs may include:

• Temperature instability
• Feeding difficulties
• Lethargy or irritability
• Respiratory distress

Pediatric Sepsis

Children may exhibit different symptoms compared to adults, such as:

• High fever or hypothermia
• Rapid breathing
• Decreased urination
• Mottled skin

Sepsis in Older Adults

Elderly individuals may present with atypical symptoms, including:

• Sudden changes in mental status
• Loss of balance
• Decreased appetite
• Weakness

Understanding these age-specific considerations is crucial for early recognition and appropriate management of sepsis across all life stages.

Emerging Research and Future Directions in Sepsis Management

The field of sepsis research is continuously evolving, with new insights and potential treatments on the horizon.

What are some promising areas of sepsis research?

• Biomarker discovery for early sepsis detection
• Immunomodulatory therapies to balance the immune response
• Personalized treatment approaches based on genetic profiles
• Novel antimicrobial strategies to combat drug-resistant pathogens
• Artificial intelligence for predicting sepsis onset and guiding treatment

The Future of Sepsis Care: Precision Medicine and Beyond

How might sepsis treatment evolve in the coming years? Emerging trends include:

1. Tailored antibiotic regimens based on rapid pathogen identification
2. Targeted immunotherapies to modulate specific aspects of the sepsis response
3. Advanced organ support technologies, such as extracorporeal membrane oxygenation (ECMO)
4. Integration of wearable devices for continuous patient monitoring
5. Development of sepsis-specific rehabilitation programs

As research progresses, these innovations hold the potential to significantly improve sepsis outcomes and quality of life for survivors.

What is Sepsis? | Sepsis

• What is sepsis?
• Is sepsis contagious?
• What causes sepsis?
• Who is at risk?
• What are the signs & symptoms?
• What should I do if I think I might have sepsis?
• Fact Sheet, Brochure, and Conversation Starter

Anyone can get an infection, and almost any infection, including COVID-19, can lead to sepsis. In a typical year:

• At least 1.7 million adults in America develop sepsis.
• At least 350,000 adults who develop sepsis die during their hospitalization or are discharged to hospice.
• 1 in 3 people who dies in a hospital had sepsis during that hospitalization
• Sepsis, or the infection causing sepsis, starts before a patient goes to the hospital in nearly 87% of cases.

Sepsis is the body’s extreme response to an infection. It is a life-threatening medical emergency.   Sepsis happens when an infection you already have triggers a chain reaction throughout your body.  Infections that lead to sepsis most often start in the lung, urinary tract, skin, or gastrointestinal tract. Without timely treatment, sepsis can rapidly lead to tissue damage, organ failure, and death.

Is sepsis contagious?

You can’t spread sepsis to other people. However, an infection can lead to sepsis, and you can spread some infections to other people.

Sepsis happens when…

Transcript: Sepsis happens when [TXT 1 1 KB]

What causes sepsis?

Infections can put you or your loved one at risk for sepsis. When germs get into a person’s body, they can cause an infection. If you don’t stop that infection, it can cause sepsis. Bacterial infections cause most cases of sepsis. Sepsis can also be a result of other infections, including viral infections, such as COVID-19 or influenza, or fungal infections.

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Who is at risk?

Anyone can develop sepsis, but some people are at higher risk for sepsis:

Adults 65 or older

People with weakened immune systems

People with chronic medical conditions, such as diabetes, lung disease, cancer, and kidney disease

People with recent severe illness or hospitalization

People who survived sepsis

Children younger than one

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What are the signs & symptoms?

A person with sepsis might have one or more of the following signs or symptoms:

High heart rate or weak pulse

Confusion or disorientation

Extreme pain or discomfort

Fever, shivering, or feeling very cold

Shortness of breath

Clammy or sweaty skin

A medical assessment by a healthcare professional is needed to confirm sepsis.

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What should I do if I think I might have sepsis?

Sepsis is a medical emergency. If you or your loved one has an infection that’s not getting better or is getting worse, ACT FAST.

Get medical care IMMEDIATELY. Ask your healthcare professional, “Could this infection be leading to sepsis?” and if you should go to the emergency room.

If you have a medical emergency, call 911. If you have or think you have sepsis, tell the operator. If you have or think you have COVID-19, tell the operator this as well. If possible, put on a mask before medical help arrives.

With fast recognition and treatment, most people survive.  Treatment requires urgent medical care, usually in an intensive care unit in a hospital, and includes careful monitoring of vital signs and often antibiotics.

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Fact Sheet, Brochure, and Conversation Starter (Print Only)

Protect Yourself and Your Family from Sepsis [PDF – 2 pages]

It’s Time to Talk about Sepsis [PDF – 2 pages]

Start the Conversation Today [PDF – 2 Pages]

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Sepsis – Symptoms & causes

Overview

Sepsis is a serious condition in which the body responds improperly to an infection. The infection-fighting processes turn on the body, causing the organs to work poorly.

Sepsis may progress to septic shock. This is a dramatic drop in blood pressure that can damage the lungs, kidneys, liver and other organs. When the damage is severe, it can lead to death.

Early treatment of sepsis improves chances for survival.

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Symptoms

Symptoms of sepsis

Symptoms of sepsis may include:

• Change in mental status.
• Fast, shallow breathing.
• Sweating for no clear reason.
• Feeling lightheaded.
• Shivering.
• Symptoms specific to the type of infection, such as painful urination from a urinary tract infection or worsening cough from pneumonia.

Symptoms of sepsis are not specific. They can vary from person to person, and sepsis may appear differently in children than in adults.

Symptoms of septic shock

Sepsis may progress to septic shock. Septic shock is a severe drop in blood pressure. Progression to septic shock raises the risk of death. Symptoms of septic shock include:

• Not being able to stand up.
• Strong sleepiness or hard time staying awake.
• Major change in mental status, such as extreme confusion.

When to see a doctor

Any infection could lead to sepsis. Go to a health care provider if you have symptoms of sepsis or an infection or wound that isn’t getting better.

Symptoms such as confusion or fast breathing need emergency care.

Causes

Any type of infection can lead to sepsis. This includes bacterial, viral or fungal infections. Those that more commonly cause sepsis include infections of:

• Lungs, such as pneumonia.
• Kidney, bladder and other parts of the urinary system.
• Digestive system.
• Bloodstream.
• Catheter sites.
• Wounds or burns.

Risk factors

Some factors that increase the risk infection will lead to sepsis include:

• People over age 65.
• Infancy.
• People with lower immune response, such as those being treated for cancer or people with human immunodeficiency virus (HIV).
• People with chronic diseases, such as diabetes, kidney disease or chronic obstructive pulmonary disease (COPD).
• Admission to intensive care unit or longer hospital stays.
• Devices that go in the body, such as catheters in the vein, called intravenous, or breathing tubes.
• Treatment with antibiotics in the last 90 days.
• A condition that requires treatment with corticosteroids, which can lower immune response.

Complications

As sepsis worsens, vital organs, such as the brain, heart and kidneys, don’t get as much blood as they should. Sepsis may cause atypical blood clotting. The resulting small clots or burst blood vessels may damage or destroy tissues.

Most people recover from mild sepsis, but the mortality rate for septic shock is about 30% to 40%. Also, an episode of severe sepsis raises the risk for future infections.

Sepsis

Sepsis

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• Sepsis

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Key Facts

• Sepsis occurs when the body’s response to an infection causes damage to its own tissues and organs, and can lead to death or serious deterioration.
• The global epidemiological burden of sepsis cannot be accurately estimated. It is estimated that it develops in more than 30 million people each year and possibly kills 6 million people(1). The problem of sepsis is likely to be most prevalent in low- and middle-income countries.
• An estimated 3 million newborns and 1.2 million children suffer from sepsis each year (2). Three out of ten deaths due to neonatal sepsis are suspected to be due to drug-resistant pathogens.
• One in ten deaths due to pregnancy and childbirth are due to maternal sepsis, with 95% of maternal sepsis deaths occurring in low- and middle-income countries (4). Each year, one million newborns die due to maternal infections, in particular maternal sepsis (5).
• Sepsis may be a clinical manifestation of infections acquired both outside and inside healthcare facilities. Healthcare-associated infection is one of the most common, if not the most common, type of adverse events occurring in the course of healthcare, affecting millions of patients worldwide every year (6). Because these infections are often resistant to antibiotics, they can cause rapid clinical deterioration.

General information

Sepsis is a life-threatening organ dysfunction caused by dysregulation of the body’s response to infection (7). If sepsis is not recognized early and treated promptly, it can cause septic shock, multiple organ failure, and death. Sepsis can be caused by any type of infectious pathogen. Antimicrobial resistance is a leading factor in the lack of clinical response to treatment and the rapid development of sepsis and septic shock. Among patients with sepsis caused by drug-resistant pathogens, there is an increased risk of hospital mortality.

Who is at risk?

Anyone with an infection can develop sepsis, but vulnerable populations such as the elderly, pregnant women, newborns, hospitalized patients, and those with HIV/AIDS, cirrhosis, cancer, kidney disease, autoimmune disease, and spleen (8).

Signs and symptoms

Sepsis is an emergency. However, the signs and symptoms of sepsis in patients may be different at different points in time, since such a clinical condition as sepsis can be caused by many pathogens and change its character at different stages. Warning signs and symptoms include a rise or fall in body temperature and chills, changes in mental status, shortness/rapid breathing, rapid heartbeat, weak pulse/low blood pressure, oliguria, blue or marbling of the skin, cold extremities, and severe pain or discomfort in the body ( 9-eleven). Suspicion of sepsis is the first step towards its early recognition and diagnosis.

Prevention

There are two main ways to prevent sepsis:
1. Prevention of microbial transmission and infection;
2. Prevention of complications of infection to the state of sepsis.

Infection prevention in the community includes good hygiene practices such as handwashing and safe food preparation, improving the quality and availability of water and sanitation, ensuring access to vaccines, especially for those at high risk of developing sepsis, and proper nutrition including breastfeeding newborns.
Prevention of nosocomial infections is generally ensured by having functioning infection prevention and control programs and appropriate teams of staff, good hygiene practices, including hand hygiene, along with cleanliness of the premises and proper operation of equipment.

Prevention of sepsis in both the community and in health care settings involves appropriate antibiotic treatment of infections, including regular assessment of patients for the rational use of antibiotics, prompt medical attention, and early detection of signs and symptoms of sepsis.
The effectiveness of infection prevention is clearly supported by scientific evidence. For example, with strict hand hygiene practices in health care settings, infections can be reduced by up to 50% (12), and in public places, these interventions can reduce the risk of diarrhea by at least 40% (13). Measures to improve water supply, sanitation and hygiene (WASH) can reduce the overall burden of disease worldwide by 10% ¹⁴ . Every year, vaccinations help prevent 2–3 million infection-related deaths (15).

Diagnosis and clinical management

In order to detect sepsis early and manage it properly in a timely manner, it is essential to recognize and not ignore the above signs and symptoms, and to identify certain biomarkers (particularly procalcitonin). Post-early detection, diagnostic procedures are important to help identify the causative agent of the infection that caused sepsis, since this determines the choice of targeted antimicrobial treatment. Antimicrobial resistance (AMR) can hinder the clinical management of sepsis, as it often requires empirical antibiotic selection. Therefore, it is necessary to understand the epidemiological parameters of the spread of AMR in these settings. Once the source of the infection has been identified, the most important task is to eliminate it, for example, by draining the abscess.
Fluid therapy is also important in the early management of sepsis to normalize circulating fluid volume. In addition, vasoconstrictor drugs may be required to improve and maintain tissue perfusion. Further measures for the correct management of sepsis are selected based on the data of repeated examinations and diagnostic measures, including monitoring of the patient’s vital signs.

Sepsis and the Sustainable Development Goals

Sepsis is a major cause of maternal death, as well as death of newborns and children under five years of age. For this reason, the control of sepsis will clearly contribute to the achievement of targets 3.1 and 3.2 of the Sustainable Development Goals (SDGs).

Sepsis is a highly relevant cause of maternal death, as well as death of newborns and children under five years of age. For this reason, the control of sepsis will clearly contribute to the achievement of targets 3.1 and 3.2 of the Sustainable Development Goals (SDGs).
The indicators for achieving these two SDG targets are maternal, newborn and under-five mortality rates. Sepsis occupies an important place among the causes of these preventable deaths. It is often the clinical condition that ultimately causes death in patients with HIV, tuberculosis, malaria and other infectious diseases mentioned in task 3.3, but it is usually not recorded as a cause of death in such patients and is not is included in the statistics on the indicators of the achievement of SDG target 3.3.
Sepsis is also important, though more indirectly, to other health-related targets under SDG 3. For example, prevention and/or proper diagnosis and management of sepsis is also relevant to adequate vaccine coverage, universal coverage of quality health services, compliance with the International Health Regulations, preparedness and provision of water and sanitation services. However, achieving universal prevention, diagnosis and management of sepsis remains a challenge.

WHO activities

In May 2017, the Seventieth World Health Assembly, based on a report by the WHO Secretariat, adopted a resolution on sepsis.

Resolution WHA70.7. Improving the prevention, diagnosis and clinical management of sepsis
Report of the WHO Secretariat A70/13. Improving the prevention, diagnosis and clinical management of sepsis
Several WHO headquarters-level programmes, in collaboration and coordination with WHO regional offices, are currently studying the public health impact of sepsis and providing guidance and support at country level on prevention, early and correct diagnosis, as well as timely and effective clinical management of sepsis in the interests of a comprehensive solution to this problem. The Global Infection Prevention and Control Team, located at WHO Headquarters in the Department of Service Delivery and Safety, coordinates sepsis activities and leads prevention efforts.

Bibliography

(1) Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med 2016; 193(3): 259-72.

(2) Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of pediatric and neonatal sepsis: a systematic review. The Lancet Respiratory medicine 2018; 6(3): 223-30.

(3) Laxminarayan R, Matsoso P, Pant S, et al. Access to effective antimicrobials: a worldwide challenge. Lancet 2016; 387(10014): 168-75.

(4) Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. The Lancet Global Health 2014; 2(6): e323-33.

(5) Reproductive, Maternal, Newborn, and Child Health: Disease Control Priorities, Third Edition (Volume 2). In: Black RE, Laxminarayan R, Temmerman M, Walker N, eds. Reproductive, Maternal, Newborn, and Child Health: Disease Control Priorities, Third Edition (Volume 2). Washington (DC): The International Bank for Reconstruction and Development / The World Bank(c) 2016 International Bank for Reconstruction and Development / The World Bank.; 2016.

(6) World Health Organization. WHO Report on the burden of endemic health care-associated infection worldwide. 2017-11-21 15:11:22 2011.

http://apps.who.int/iris/bitstream/handle/10665/80135/9789241501507_eng.pdf?sequence=1 (accessed April 10 2018).

(7) Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-10.

(8) Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. British Medical Journal 2016.

(9) United States Centers for Disease Control and Prevention. Healthcare Professional (HCP) Resources : Sepsis. 2018-02-01T06:23:15Z.

https://www.cdc.gov/sepsis/get-ahead-of-sepsis/hcp-resources.html (accessed April 10 2018).

(10) Global Sepsis Alliance. Toolkits. https://www.world-sepsis-day.org/toolkits/ (accessed April 10 2018).

(11) UK SepsisTrust. Education. 2018. https://sepsistrust.org/education/ (accessed April 10 2018).

(12) Luangasanatip N, Hongsuwan M, Limmathurotsakul D, et al. Comparative efficacy of interventions to promote hand hygiene in hospital: systematic review and network meta-analysis. british medical journal. 2015;351:h4728.

(13) UNICEF. UNICEF Data : Monitoring the Situation of Children and Women – Diarrhoeal Disease. https://data.unicef.org/topic/child-health/diarrhoeal-disease/ (accessed April 10 2018).

(14) Pruss-Ustun A, Bartram J, Clasen T, et al. Burden of disease from inadequate water, sanitation and hygiene in low- and middle-income settings: a retrospective analysis of data from 145 countries. Tropical medicine & international health : TM & IH 2014; 19(8): 894-905.

(15) World Health Organization. Fact sheet: Immunization coverage. 2018-04-10 14:55:37.

Septic shock – Vascular Innovation Center article

Septic shock is a systemic pathological reaction to severe infection. It is characterized by fever, tachycardia, tachypnea, leukocytosis when identifying the focus of the primary infection. At the same time, microbiological examination of blood often reveals bacteremia. In some patients with sepsis syndrome, bacteremia is not detected. When arterial hypotension and multiple systemic insufficiency become components of the sepsis syndrome, the development of septic shock is noted.

Causes and pathogenesis of septic shock:

The frequency of sepsis and septic shock has been steadily increasing since the thirties of the last century and, apparently, will continue to increase.
The reasons for this are:

1. The increasing use of invasive devices for intensive care, i.e. intravascular catheters, etc.

2. The widespread use of cytotoxic and immunosuppressive agents (in malignant diseases and transplantations), which cause acquired immunodeficiency.

3. Life expectancy increase in patients with diabetes mellitus and malignant tumors, who have a high level of predisposition to sepsis.

Bacterial infection is the most common cause of septic shock. In sepsis, the primary foci of infection are more often localized in the lungs, abdominal organs, peritoneum, and also in the urinary tract. Bacteremia is detected in 40-60% of patients in a state of septic shock. In 10-30% of patients in a state of septic shock, it is impossible to isolate a culture of bacteria whose action causes septic shock. It can be assumed that septic shock without bacteremia is the result of an abnormal immune reaction in response to stimulation with antigens of bacterial origin. Apparently, this reaction persists after the elimination of pathogenic bacteria from the body by the action of antibiotics and other elements of therapy, that is, it is endogenized.
Endogenization of sepsis can be based on numerous, mutually reinforcing and implemented through the release and action of cytokines, interactions of cells and molecules of innate immunity systems and, accordingly, immunocompetent cells.

Sepsis, systemic inflammatory response, and septic shock are consequences of an overreaction to stimulation by bacterial antigens of cells that carry out innate immune responses. The overreaction of the cells of the innate immunity systems and the reaction of T-lymphocytes and B-cells secondary to it cause hypercytokinemia. Hypercytokinemia is a pathological increase in the blood levels of agents of auto-paracrine regulation of cells that carry out innate immunity reactions and acquired immune reactions.

With hypercytokinemia, the content of primary pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 abnormally increases in the blood serum. As a result of hypercytokinemia and systemic transformation of neutrophils, endothelial cells, mononuclear phagocytes, and mast cells into cellular effectors of inflammation, an inflammatory process devoid of protective significance occurs in many organs and tissues. Inflammation is accompanied by alteration of the structural and functional elements of effector organs.

A critical deficiency of effectors causes multiple systemic insufficiency.

Symptoms and signs of septic shock:

The presence of two or more of the following signs indicates the development of a systemic inflammatory reaction:

• Body temperature higher than 38 ^o C or below 36 ^o C.

• Respiratory rate above 20/minute. Respiratory alkalosis with carbon dioxide in the arterial blood below 32 mm Hg. Art.

• Tachycardia with heart rate greater than 90/minute.

• Neutrophilia with an increase in the content of polymorphonuclear leukocytes in the blood to a level above 12×10 ⁹ /l, or neutropenia when the content of neutrophils in the blood is below 4×10 ^9/ l.

• A shift in the leukocyte formula, in which stab neutrophils make up more than 10% of the total number of polymorphonuclear leukocytes.

Sepsis is evidenced by two or more signs of a systemic inflammatory response in the presence of pathogenic microorganisms in the internal environment, confirmed by bacteriological and other studies.

Course of septic shock

In septic shock, hypercytokinemia increases the activity of nitric oxide synthetase in endothelial and other cells. As a result, the resistance of resistive vessels and venules decreases. A decrease in the tone of these microvessels reduces the total peripheral vascular resistance. Part of the cells of the body in septic shock suffers from ischemia due to disorders of the peripheral circulation. Peripheral circulation disorders in sepsis and septic shock are consequences of systemic activation of endotheliocytes, polymorphonuclear neutrophils, and mononuclear phagocytes.

Inflammation of this genesis is purely pathological in nature, occurs in all organs and tissues. A critical drop in the number of structural and functional elements of most effector organs is the main link in the pathogenesis of the so-called multiple systemic failure.

According to traditional and correct ideas, sepsis and a systemic inflammatory reaction are caused by the pathogenic action of gram-negative microorganisms.

In the occurrence of a systemic pathological reaction to invasion into the internal environment and blood of gram-negative microorganisms, the determining role is played by:

• Endotoxin (lipid A, lipopolysaccharide, LPS). This thermostable lipopolysaccharide makes up the outer coating of Gram-negative bacteria. Endotoxin, acting on neutrophils, causes the release of endogenous pyrogens by polymorphonuclear leukocytes.

• LPS-binding protein (LPBP), traces of which are determined in plasma under physiological conditions. This protein forms a molecular complex with endotoxin that circulates with the blood.

• Cell surface receptor of mononuclear phagocytes and endothelial cells. Its specific element is a molecular complex consisting of LPS and LPSBP (LPS-LPSSB).

Currently, the frequency of sepsis due to invasion of the internal environment of gram-positive bacteria is increasing. The induction of sepsis by gram-positive bacteria is usually not associated with the release of endotoxin by them. It is known that peptidoglycan precursors and other components of the walls of gram-positive bacteria cause the release of tumor necrosis factor-alpha and interleukin-1 by cells of the immune system. Peptidoglycan and other components of the walls of Gram-positive bacteria activate the complement system through an alternative pathway. Whole-body activation of the complement system causes systemic pathogenic inflammation and contributes to endotoxicosis in sepsis and the systemic inflammatory response.

It was previously thought that septic shock was always caused by endotoxin (lipopolysaccharide of bacterial origin) released by gram-negative bacteria. It is now generally accepted that less than 50% of cases of septic shock are caused by Gram-positive pathogens.

Disorders of the peripheral circulation in septic shock, adhesion of activated polymorphonuclear leukocytes to activated endotheliocytes – all this leads to the release of neutrophils into the interstitium and inflammatory alteration of cells and tissues. At the same time, endotoxin, tumor necrosis factor-alpha, and interleukin-1 increase the formation and release of tissue coagulation factor by endothelial cells. As a result, the mechanisms of external hemostasis are activated, which causes the deposition of fibrin and disseminated intravascular coagulation.

Arterial hypotension in septic shock is mainly a consequence of a decrease in total peripheral vascular resistance. Hypercytokinemia and an increase in the concentration of nitric oxide in the blood during septic shock causes the expansion of arterioles. At the same time, by means of tachycardia, the minute volume of blood circulation increases compensatory. Arterial hypotension in septic shock occurs despite a compensatory increase in cardiac output. Total pulmonary vascular resistance increases in septic shock, which can be partly attributed to the adhesion of activated neutrophils to activated pulmonary microvascular endotheliocytes.

The following main links in the pathogenesis of peripheral circulatory disorders in septic shock are distinguished:

1) an increase in the permeability of the microvascular wall;

2) an increase in the resistance of microvessels, which is enhanced by cell adhesion in their lumen;

3) low response of microvessels to vasodilating influences;

4) arteriolo-venular shunting;

5) drop in blood fluidity.

Hypovolemia is one of the factors of arterial hypotension in septic shock.

The following causes of hypovolemia (falling preload of the heart) in patients in a state of septic shock are distinguished:

1) dilatation of capacitive vessels;

2) loss of the liquid part of the blood plasma in the interstitium due to a pathological increase in capillary permeability.

It can be assumed that in the majority of patients in a state of septic shock, the drop in oxygen consumption by the body is mainly due to primary disorders of tissue respiration. In septic shock, mild lactic acidosis develops with normal oxygen tension in mixed venous blood.

Lactic acidosis in septic shock is thought to result from decreased pyruvate dehydrogenase activity and secondary accumulation of lactate, rather than a drop in peripheral blood flow.

Peripheral circulatory disorders in sepsis are systemic and develop with arterial normotension, which is supported by an increase in cardiac output. Systemic microcirculation disorders manifest themselves as a decrease in pH in the gastric mucosa and a drop in blood hemoglobin oxygen saturation in the hepatic veins. Hypoergosis of the cells of the intestinal barrier, the action of immunosuppressive links in the pathogenesis of septic shock – all this reduces the protective potential of the intestinal wall, which is another cause of endotoxemia in septic shock.

Diagnosis of septic shock

• Septic shock – sepsis (systemic inflammatory response syndrome plus bacteremia) in combination with a decrease in blood pressure syst. less than 90 mm Hg. Art. in the absence of visible reasons for arterial hypotension (dehydration, bleeding). The presence of signs of tissue hypoperfusion despite infusion therapy. Perfusion disorders include acidosis, oliguria, acute impairment of consciousness. In patients receiving inotropic drugs, perfusion disorders may persist in the absence of arterial hypotension.
• Refractory septic shock – septic shock lasting more than one hour, refractory to fluid therapy.

Treatment of septic shock:

1. Infusion therapy

• Catheterization of two veins.
• 300-500 ml IV crystalloid solution as a bolus followed by 500 ml IV crystalloid solution by drip over 15 minutes. Assess for venous hypertension and the presence of cardiac decompensation.
• In the presence of heart failure, catheterization is reasonable a. pulmonalis with a Swan-Ganz catheter to assess the volemic status: optimal PCWP = 12 mm Hg. Art. in the absence of AMI and 14-18 mm Hg. Art. in the presence of AMI;
• if after an infusion bolus the PCWP value exceeds 22 mmHg. Art., then progression of heart failure should be assumed and active infusion of crystalloids should be stopped.
• If, despite high left ventricular filling pressure values, arterial hypotension persists – dopamine 1-3-5 or more mcg/kg/min, dobutamine 5-20 mcg/kg/min.
• Calculated sodium bicarbonate to correct metabolic acidosis.

2.