Sepsis

Life-threatening response to infection

Sepsis
Synonyms	N/A
Pronounce
Field	Infectious disease
Symptoms	Fever increased heart rate low blood pressure increased breathing rate low urine output absent or near absent urine output severe pain confusion
Complications	Multiple organ dysfunction syndrome temporary, transient, or permanent organ damage extra corporeal membrane oxygenation blood filtration or dialysis
Onset	May be rapid (less than three hours) or prolonged (several days)
Duration
Types	N/A
Causes	Immune response triggered by an infection
Risks	Young or old age cancer diabetes major trauma asthma Chronic Obstructive Pulmonary Disease multiple myeloma burns
Diagnosis	Systemic inflammatory response syndrome (SIRS), qSOFA
Differential diagnosis
Prevention	influenza vaccination, vaccines, pneumonia vaccination
Treatment	Intravenous fluids, antimicrobials, vasopressors
Medication
Prognosis	10 to 80% risk of death; These mortality rates (they are for a range of conditions along a spectrum: sepsis, severe sepsis, and septic shock) may be lower if treated aggressively and early, depending on the organism and disease, the patient's previous health, and the abilities of the treatment location and its staff
Frequency	In 2017 there were 48.9 million cases and 11 million sepsis-related deaths worldwide (according to WHO)
Deaths

Sepsis

Sepsis treatment

Streptococcus pyogenes 01 thumbnail

Serratia mercescens etiological agent of neontal sepsis colony morphology on MacConkey agar

Personification of septicemia, carrying a spray can marked "Poison"

Blood culture bottles: orange cap for anaerobes, green cap for aerobes, and yellow cap for blood samples from children

Patient of an intensive care unit of a German hospital (2015) with severe sepsis

Sepsis Steps. Training tool for teaching the progression of sepsis stages

Phenotypic strategy switches of microbes capable of provoking sepsis

Intravenous fluids being given

Sepsis is a life-threatening medical condition that arises when the body’s response to an infection causes widespread inflammation. It can lead to tissue damage, organ failure, and death if not treated promptly. Sepsis occurs when the body releases chemicals into the bloodstream to fight an infection, but instead, these chemicals trigger widespread inflammation. The inflammation can lead to blood clotting, impaired blood flow, and a disruption in the function of organs, such as the heart, kidneys, and liver.

Pathophysiology of Sepsis

The pathophysiology of sepsis involves a complex immune response to infection. When the body detects an infection, the immune system produces inflammatory markers like cytokines and chemokines. In sepsis, however, this immune response becomes dysregulated, leading to excessive inflammation. This inflammatory cascade can impair the function of vital organs. The process is often referred to as a "cytokine storm," where a massive release of cytokines contributes to widespread vascular permeability, resulting in leakage of fluids into tissues and low blood pressure.

Sepsis can be caused by any type of infection, but it is more common in people with weakened immune systems, the elderly, and those with chronic diseases such as diabetes, cancer, or liver disease. The most common sources of infection leading to sepsis include:

• Pneumonia (infection in the lungs)
• Urinary tract infection (UTI)
• Abdominal infections, such as appendicitis or bowel perforation
• Skin or wound infections
• Bloodstream infections (bacteremia)

Sepsis is classified into different stages, ranging from sepsis to severe sepsis and septic shock, depending on the degree of organ dysfunction and blood pressure abnormalities.

Incidence and Prevalence

Sepsis is a leading cause of mortality worldwide. It is estimated that in the United States alone, approximately 1.7 million people develop sepsis each year, and about 270,000 of these individuals die as a result. The incidence of sepsis has been rising, partly due to the increasing number of individuals with chronic conditions, the aging population, and advances in medical technology that allow people with severe infections to survive longer but also expose them to potential complications such as sepsis.

According to a study published in *The Lancet*, the global burden of sepsis has grown, with an estimated 48.9 million cases worldwide in 2017. It remains a major public health issue, and early recognition and treatment are critical for improving outcomes.

Importance of Early Detection

Early recognition of sepsis is crucial, as prompt treatment can drastically improve survival rates. Key signs and symptoms of sepsis include fever, increased heart rate, increased respiratory rate, confusion, and low blood pressure. However, symptoms can vary, and in some cases, sepsis may present subtly, particularly in older adults or those with underlying medical conditions. Recognizing sepsis early can lead to the initiation of appropriate treatments, such as intravenous antibiotics and fluids, and can reduce the risk of organ failure.

Sepsis protocols have been developed for early detection and management, particularly in emergency settings. These protocols include the use of the "Sepsis Six" bundle, which is a set of six key interventions aimed at improving the chances of recovery for sepsis patients:

• Administer oxygen
• Take blood cultures
• Give intravenous antibiotics
• Give intravenous fluids
• Measure serum lactate levels
• Urinary catheterization to monitor urine output

Failure to identify and treat sepsis early can lead to complications, including the progression to septic shock, multi-organ failure, and death.

Sepsis vs. Septic Shock

It is essential to distinguish between sepsis and septic shock, as septic shock is a more severe form of sepsis. Septic shock is characterized by persistent hypotension (low blood pressure) despite adequate fluid resuscitation and is associated with a high mortality rate. In septic shock, the body's response to infection results in severe vasodilation (widening of the blood vessels), decreased blood flow to vital organs, and organ failure. It requires immediate medical intervention, often including vasopressor medications to raise blood pressure.

Septic shock often occurs in individuals who are already critically ill or have underlying medical conditions that weaken the immune system. Early identification and aggressive treatment are essential to prevent death in these cases.

Diagnosis of Sepsis

Diagnosing sepsis can be challenging due to the broad range of symptoms and the variety of underlying infections that may cause it. Early diagnosis is critical for improving outcomes and initiating appropriate treatment. The diagnosis of sepsis generally involves a combination of clinical evaluation, laboratory tests, and imaging studies.

Clinical Diagnosis

The clinical diagnosis of sepsis is based on the presence of systemic inflammatory response syndrome (SIRS) in the context of a known or suspected infection. The following criteria are commonly used to define SIRS:

• Temperature: >38.3°C (100.9°F) or <36°C (96.8°F)
• Heart rate: >90 beats per minute
• Respiratory rate: >20 breaths per minute or arterial carbon dioxide tension (PaCO2) <32 mm Hg
• White blood cell count: >12,000/µL or <4,000/µL, or >10% immature bands (left shift)

Sepsis is diagnosed when a known or suspected infection is present along with two or more of the above SIRS criteria. However, the presence of SIRS alone does not confirm sepsis. Clinical judgment, based on the patient’s history and examination findings, is crucial in making an accurate diagnosis.

Laboratory Tests

Laboratory tests are essential for confirming sepsis, identifying the source of infection, and guiding treatment decisions. Common tests include:

• Blood cultures: Blood cultures are taken to identify the causative microorganism. Multiple sets of blood cultures (from different sites) should be obtained before antibiotics are started.
• Complete blood count (CBC): A CBC can show elevated or decreased white blood cells, indicating infection or inflammation.
• C-reactive protein (CRP) and procalcitonin: These inflammatory markers can help assess the severity of infection and guide the initiation of antibiotics. Procalcitonin levels, in particular, are often elevated in bacterial infections.
• Lactate levels: Elevated lactate levels are indicative of tissue hypoperfusion (lack of adequate blood supply), which is a common consequence of sepsis. Lactate measurement can also help monitor the effectiveness of treatment.
• Arterial blood gas (ABG): An ABG can help assess respiratory function and the acid-base balance of the patient, which may be disturbed in sepsis.

Imaging Studies

Imaging studies are used to identify the source of infection in cases where the infection’s origin is unclear. Common imaging techniques include:

• Chest X-ray: For suspected pneumonia or other respiratory infections.
• Abdominal ultrasound or CT scan: For suspected abdominal infections such as appendicitis or bowel perforation.
• Urinary tract imaging: For suspected urinary tract infections or kidney abscesses.

Early imaging can help identify sources of infection and guide the management of sepsis.

Treatment of Sepsis

The treatment of sepsis aims to control the infection, reduce inflammation, support organ function, and improve circulation. The sooner treatment is initiated, the better the chances of survival. The primary components of sepsis treatment include antimicrobial therapy, fluid resuscitation, vasopressor support, and organ support.

Antimicrobial Therapy

The cornerstone of sepsis treatment is the administration of antibiotics. Broad-spectrum antibiotics are usually started immediately, even before the results of blood cultures are available, because sepsis can progress rapidly. The choice of antibiotics may be adjusted once the specific pathogen is identified and its sensitivities are known. In some cases, antifungal or antiviral medications may also be necessary.

• Initial empirical antibiotic therapy: Empirical therapy includes a combination of broad-spectrum antibiotics that cover a wide range of pathogens, including Gram-positive and Gram-negative bacteria, fungi, and sometimes viruses. Common choices include:

• Ceftriaxone or Piperacillin-tazobactam (broad-spectrum antibiotics)
• Vancomycin or Meropenem (for resistant organisms like MRSA)
• Fluconazole (for suspected fungal infections)

• Tailored therapy: Once the causative pathogen is identified, antibiotic therapy should be narrowed to target the specific microorganism, minimizing unnecessary antibiotic use and reducing the risk of resistance.

The duration of antimicrobial therapy is typically 7 to 10 days, but it may be longer depending on the infection site and the patient’s response to treatment.

Fluid Resuscitation

Sepsis often leads to low blood pressure and inadequate blood flow to vital organs. Therefore, early and aggressive fluid resuscitation is vital to restore blood pressure and improve organ perfusion. The goal is to maintain a mean arterial pressure (MAP) of at least 65 mm Hg and ensure adequate organ perfusion.

• Crystalloids (e.g., normal saline or Ringer’s lactate) are the first-line fluids used for resuscitation. The initial fluid bolus is typically 30 mL per kilogram of body weight, and additional fluids may be given based on the patient's response.
• Colloids (e.g., albumin) may be used in specific cases when crystalloids are insufficient.

Fluid resuscitation should be monitored closely with frequent assessments of urine output, blood pressure, and lactate levels to evaluate the patient’s response.

Vasopressors

In cases of septic shock, where fluid resuscitation does not restore normal blood pressure, vasopressors are used to constrict blood vessels and increase blood pressure. The first-line vasopressor is usually norepinephrine. Other options include dopamine, epinephrine, and vasopressin. Vasopressors are titrated to maintain a MAP of at least 65 mm Hg and ensure adequate perfusion to vital organs.

Organ Support

Sepsis can lead to organ failure, and supportive therapies may be needed to maintain organ function. Common forms of organ support include:

• Mechanical ventilation: For patients with respiratory failure or hypoxia due to sepsis-induced lung injury.
• Renal replacement therapy (dialysis): For patients with acute kidney injury resulting from sepsis.
• Nutritional support: Enteral or parenteral nutrition may be required to support healing and recovery in critically ill patients.

Early and aggressive treatment with appropriate antimicrobial therapy, fluid resuscitation, and vasopressors, combined with organ support as needed, is crucial to improving outcomes for sepsis patients.

Complications of Sepsis

Sepsis can lead to a wide range of complications, some of which can be life-threatening. The severity and type of complications depend on the patient's overall health, the timeliness of treatment, and the degree of organ dysfunction. Common complications of sepsis include:

Septic Shock

Septic shock is a severe manifestation of sepsis in which there is a significant drop in blood pressure that does not respond to fluid resuscitation. This condition results from widespread vasodilation, increased vascular permeability, and poor perfusion of vital organs. Septic shock is associated with high mortality rates, especially when it leads to multiple organ dysfunction. Patients with septic shock require immediate and aggressive treatment with vasopressors to restore blood pressure and improve organ perfusion.

• Symptoms: Persistent hypotension, altered mental status, tachycardia, tachypnea, and reduced urine output.
• Management: In addition to fluids and vasopressors, treatment involves supportive care and close monitoring of organ function.

Organ Dysfunction and Failure

One of the most severe complications of sepsis is the failure of one or more organs. The organs most commonly affected by sepsis include:

• Kidney failure: Sepsis can cause acute kidney injury (AKI) due to hypoperfusion, leading to the need for renal replacement therapy (e.g., dialysis).
• Liver failure: The liver may be damaged due to reduced blood flow, leading to jaundice, coagulopathy, and elevated liver enzymes.
• Respiratory failure: Sepsis-induced acute respiratory distress syndrome (ARDS) can cause severe hypoxia and require mechanical ventilation.
• Cardiac dysfunction: Sepsis can impair the heart’s ability to pump blood effectively, leading to low cardiac output and ischemia in vital organs.

The severity of organ dysfunction is a major determinant of patient outcomes, and early recognition of organ failure is critical for initiating appropriate interventions.

Coagulopathy and Disseminated Intravascular Coagulation (DIC)

Sepsis can cause abnormalities in the coagulation system, leading to disseminated intravascular coagulation (DIC). In DIC, small blood clots form throughout the circulatory system, which can lead to tissue ischemia and organ damage. At the same time, the coagulation factors become consumed, resulting in an increased risk of bleeding.

• Symptoms: Bruising, bleeding from mucous membranes, and petechiae.
• Management: Treatment involves managing the underlying infection, correcting the coagulopathy, and, in some cases, using blood products such as platelets, clotting factors, or heparin to manage DIC.

Long-term Effects and Sepsis-Related Organ Dysfunction Syndrome (SODS)

Some individuals who survive sepsis may experience long-term complications, including Sepsis-Related Organ Dysfunction Syndrome (SODS), which manifests as persistent physical and mental impairment. This condition affects the ability of the patient to return to their normal life and is commonly referred to as Post-Sepsis Syndrome (PSS).

• Physical impairments: Muscle weakness, joint pain, reduced mobility, and persistent fatigue.
• Cognitive impairments: Memory problems, difficulty concentrating, and anxiety or depression.
• Quality of life: Survivors of sepsis often report a reduced quality of life due to ongoing health issues and emotional distress.

Sepsis survivors may require rehabilitation, including physical therapy, psychological support, and vocational rehabilitation.

Prognosis of Sepsis

The prognosis of sepsis depends on several factors, including the severity of the infection, the underlying health conditions of the patient, and the speed at which treatment is initiated. Early recognition and aggressive treatment are associated with a much better prognosis.

Mortality Rates

Sepsis is a leading cause of death worldwide, and mortality rates can be as high as 25-50% for patients with severe sepsis or septic shock. Mortality is higher in patients who develop multiple organ dysfunction or fail to respond to initial treatment.

• Septic shock: The mortality rate for septic shock can be as high as 40-50% even with intensive care treatment.
• Severe sepsis: Mortality rates for severe sepsis (without shock) may be lower but still significant, particularly in older adults and those with comorbidities.

The survival rate improves with early identification and rapid administration of appropriate treatment, especially antimicrobial therapy, fluid resuscitation, and vasopressors. Mortality is higher in those with advanced age, immunocompromised status, and comorbid conditions such as diabetes, chronic kidney disease, and cardiovascular diseases.

Factors Influencing Prognosis

Several factors influence the prognosis of sepsis, including:

• Age: Older patients are at greater risk of mortality and complications due to a weakened immune response and the presence of chronic diseases.
• Comorbidities: Patients with underlying conditions such as heart disease, diabetes, cancer, or chronic lung disease have worse outcomes.
• Severity of the infection: The type of infection and its severity (e.g., pneumonia, urinary tract infection, abdominal infection) influence prognosis. Infections caused by resistant organisms or fungi tend to have worse outcomes.
• Organ function: The extent of organ dysfunction, particularly kidney, liver, and respiratory failure, can significantly impact survival chances.
• Timeliness of treatment: Early recognition of sepsis and prompt administration of appropriate antibiotics and supportive care are critical for improving prognosis.

Recovery and Rehabilitation

Patients who survive sepsis may experience a prolonged recovery period, which can vary based on the severity of the infection and organ dysfunction. Many patients experience significant physical and cognitive impairments, as mentioned earlier, requiring rehabilitation and ongoing medical care.

• Physical rehabilitation: Physical therapy is often required to address muscle weakness and joint stiffness that can result from prolonged hospital stays, mechanical ventilation, or immobilization.
• Psychological rehabilitation: Mental health support is crucial for addressing the psychological toll of sepsis, including anxiety, depression, and post-traumatic stress disorder (PTSD).
• Long-term monitoring: Regular follow-up with healthcare providers is recommended to monitor for any delayed complications or the recurrence of infection.

Prevention of Sepsis Recurrence

Preventing recurrence of sepsis involves addressing the underlying causes and improving general health. Key strategies include:

• Vaccination: Vaccination against certain infections, such as pneumococcus, meningococcus, and influenza, can reduce the risk of sepsis.
• Chronic disease management: Proper management of chronic conditions, such as diabetes and heart disease, can help reduce the risk of infection and sepsis.
• Infection control practices: Strict infection control measures in hospitals, including hand hygiene and the careful management of invasive devices, can prevent healthcare-associated infections that may lead to sepsis.

Prevention of Sepsis

Preventing sepsis is a multifaceted effort that involves both individual and public health measures. The goal is to reduce the risk factors associated with sepsis and to prevent the infections that commonly lead to sepsis. Effective prevention strategies include vaccination, proper hygiene, infection control practices, and managing underlying health conditions.

Vaccination

Vaccines are a powerful tool in preventing certain infections that can lead to sepsis. Some of the key infections that vaccines can help prevent include:

• Pneumococcal infection: The pneumococcal vaccine protects against Streptococcus pneumoniae, a common cause of pneumonia, meningitis, and bloodstream infections that can lead to sepsis.
• Influenza: The annual flu vaccine reduces the risk of influenza, which can cause viral pneumonia and sepsis, especially in older adults and those with chronic health conditions.
• Meningococcal infection: The meningococcal vaccine helps prevent Neisseria meningitidis, a bacteria that can cause meningitis and bloodstream infections, which are often complicated by sepsis.
• Hepatitis B: The hepatitis B vaccine prevents viral infections that can lead to liver failure and, in severe cases, sepsis.

Vaccination programs targeting high-risk groups, such as the elderly, infants, and immunocompromised individuals, can significantly reduce the incidence of sepsis caused by vaccine-preventable infections.

Infection Control Practices

Good infection control practices, especially in healthcare settings, are crucial in preventing sepsis. In hospitals and clinics, healthcare-associated infections (HAIs) are a significant source of sepsis. Key infection control measures include:

• Hand hygiene: Proper handwashing and the use of alcohol-based hand sanitizers by healthcare workers and patients can reduce the transmission of pathogens that cause sepsis.
• Aseptic technique: When performing invasive procedures, such as inserting catheters or performing surgeries, maintaining a sterile environment is essential to prevent infections that could lead to sepsis.
• Antibiotic stewardship: Appropriate use of antibiotics is essential to prevent the development of antibiotic-resistant bacteria, which are more difficult to treat and can lead to sepsis. Overuse or misuse of antibiotics can also increase the risk of developing infections that cause sepsis.

In community settings, infection control also involves practices such as:

• Wound care: Proper cleaning and dressing of wounds can prevent bacterial infections that might lead to sepsis.
• Managing chronic conditions: Keeping chronic diseases such as diabetes, asthma, and heart disease under control can help reduce the risk of infections and sepsis.

Hygiene and Safe Practices

At an individual level, good hygiene practices are essential to prevent infections that can lead to sepsis. These include:

• Regular handwashing: Frequent handwashing with soap and water or using hand sanitizer can reduce the spread of infectious agents, especially after using the restroom, before eating, and after handling contaminated items.
• Safe food handling: Properly cooking and storing food can prevent foodborne illnesses that can lead to infections and sepsis, such as Salmonella or Listeria.
• Proper personal hygiene: Regular bathing, oral hygiene, and safe sexual practices help prevent infections that might cause sepsis.
• Use of personal protective equipment (PPE): In high-risk settings (e.g., healthcare, laboratories), PPE such as gloves, masks, and gowns should be used to prevent exposure to infectious agents.

Managing Chronic Conditions

People with chronic health conditions, such as diabetes, chronic kidney disease, cancer, or immunodeficiencies, are at higher risk of developing infections that can progress to sepsis. Therefore, managing these conditions effectively is key to reducing the risk of sepsis. Some management strategies include:

• Diabetes management: Keeping blood sugar levels under control can help prevent infections, especially skin infections, urinary tract infections (UTIs), and respiratory infections.
• Cancer care: Patients undergoing cancer treatments, such as chemotherapy, are at increased risk of infection due to immunosuppression. Prompt diagnosis and treatment of infections can prevent sepsis.
• Immunosuppression management: Patients with HIV/AIDS or those on immunosuppressive therapy should work closely with healthcare providers to prevent and manage infections effectively.

Early Recognition and Treatment

Early recognition and prompt treatment of infections can prevent them from progressing to sepsis. Key strategies include:

• Educating the public: Public health campaigns can raise awareness about the signs and symptoms of infection and sepsis. Early warning signs of sepsis include fever, chills, rapid breathing, confusion, and decreased urine output.
• Improved healthcare access: Ensuring that individuals have access to quality healthcare and timely medical interventions can prevent infections from escalating into sepsis.

Sepsis Awareness and Education

Public education and awareness about sepsis are essential to early detection and prevention. Healthcare providers, patients, and their families should be educated on the risks, signs, and symptoms of sepsis. Educational programs can include:

• Public health campaigns: Government agencies and non-profit organizations can launch awareness campaigns to teach people about sepsis and its early signs. Examples include the "Sepsis Alliance" in the United States and the "UK Sepsis Trust" in the United Kingdom.
• Training for healthcare workers: Healthcare providers should receive regular training on the identification and treatment of sepsis. This training should focus on early recognition, the use of screening tools, and prompt intervention.
• Patient education: Patients admitted to hospitals or clinics should be informed about their risk for sepsis, especially if they have underlying health conditions or are undergoing invasive procedures.

Public Health Implications of Sepsis

Sepsis has significant public health implications due to its high incidence, mortality rate, and the potential for long-term health complications. The global burden of sepsis is substantial, with an estimated 49 million cases and 11 million sepsis-related deaths each year. This makes sepsis a leading cause of morbidity and mortality worldwide, especially in low- and middle-income countries where healthcare infrastructure may be lacking.

Global Burden of Sepsis

The burden of sepsis is disproportionately high in low- and middle-income countries, where access to healthcare, sanitation, and vaccines may be limited. In these settings, sepsis is often associated with maternal infections, malnutrition, and lack of access to timely medical care. Addressing the global burden of sepsis requires:

• Improved healthcare access: Strengthening healthcare systems in underserved regions can help provide timely care and prevent sepsis from becoming a major cause of death.
• Infection prevention and control: Implementing basic infection prevention measures, such as clean water access, sanitation, and vaccines, can drastically reduce the incidence of infections that lead to sepsis.

Sepsis as a Global Health Priority

Sepsis is increasingly recognized as a global health priority. In 2017, the World Health Assembly adopted a resolution to improve the prevention, diagnosis, and treatment of sepsis worldwide. This resolution encourages member states to develop national sepsis action plans, improve surveillance, and ensure access to essential medicines and treatments.

Key international initiatives

• Global Sepsis Alliance: An international non-governmental organization that advocates for sepsis awareness and research.
• The Sepsis Program of the WHO: This program aims to improve the quality of care for sepsis patients and reduce its global burden.
• Sepsis Research: Ongoing research efforts focus on improving diagnostic tools, developing new treatments, and understanding the underlying pathophysiology of sepsis.

See also

• Septic shock
• Systemic inflammatory response syndrome
• Infection

References

Classification	ICD-11: 1G40 , 1G41 ICD-10: A40 , A41 , T81.4 , T88.0 MeSH: D018805 DiseasesDB: 11960
External resources	MedlinePlus: 000666 Scholia: Q183134

Sepsis Resources
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