Sepsis

Sepsis is a life-threatening medical condition caused by a dysregulated immune response to an infection. While the body's immune system is meant to fight germs, in sepsis, this response becomes uncontrolled. This reaction causes injury to the body's own tissues and organs.

Sepsis can be triggered by many different organisms, including bacteria, viruses, and fungi. Bacteria, specifically Gram-negative and Gram-positive types, are the most frequent causes. In children, viral pathogens and diarrheal illnesses are more common triggers. Because the response is systemic, it affects the entire body rather than staying at the site of the original infection.

The mechanism of sepsis involves a complex interaction between pathogens and the host's immune system. It often begins when an invading pathogen is recognized by pathogen-associated molecular patterns, or PAMPs. These are specific molecules, like lipopolysaccharides in Gram-negative bacteria, that signal a threat. The innate immune system uses pattern recognition receptors (PRRs) to detect these PAMPs. This detection triggers intracellular signaling cascades. These cascades cause transcription factors to increase the expression of pro-inflammatory cytokines.

This can lead to a cytokine storm, which is an excessive inflammatory response. This inflammation can cause endothelial injury and activate platelets, leading to microvascular thrombosis, or small blood clots. These clots can eventually progress to multiple organ dysfunction syndrome.

Sepsis can progress through different stages of severity. The initial stage involves a dysregulated response to infection. This may lead to severe sepsis, which is characterized by organ dysfunction and significantly reduced blood flow. One sign of poor blood flow is low urine output or high blood lactate levels. The most critical stage is septic shock. This is defined as low blood pressure caused by sepsis that does not improve after receiving fluid replacement.

In septic shock, oxidative stress occurs, and circulating levels of copper and vitamin C decrease. The condition can also lead to an immunosuppression state, sometimes called compensatory anti-inflammatory response syndrome. During this phase, many immune cells, such as lymphocytes and macrophages, undergo apoptosis, or programmed cell death.

Medical professionals use specific criteria to diagnose sepsis. The current standard is the quick SOFA score, or qSOFA. This has replaced the older SIRS system for diagnosis. To meet the qSOFA criteria, a patient must show at least two of three signs: an increased breathing rate, a change in the level of consciousness, or low blood pressure.

Common physical symptoms include fever, though the elderly or immunocompromised may show a low or normal temperature instead. Other symptoms include a fast heart rate, confusion, and edema, which is swelling. Doctors also look for symptoms related to the primary infection site, such as a cough for pneumonia or painful urination for a kidney infection.

The history of sepsis management changed significantly with the development of antibiotics. Before the 1950s, Gram-positive bacteria were the primary cause of sepsis. After antibiotics were introduced, Gram-negative bacteria became the predominant cause between the 1960s and 1980s. However, since the 1980s, Gram-positive bacteria, such as staphylococci, have caused more than 50% of cases.

Understanding these shifts helps researchers predict which types of antimicrobial medications might be most effective in different eras and regions.

Sepsis is a major global health challenge with staggering statistics. In 2017, sepsis affected approximately 49 million people. This resulted in 11 million deaths, representing one in five deaths worldwide.

The risk of death is highly dependent on the severity of the condition. The risk of death is as high as 30% for sepsis, 50% for severe sepsis, and 80% for septic shock. Most cases, about 85%, occur in low or middle-income countries. Specifically, 40% of all global cases occur in Sub-Saharan Africa.

Treatment requires immediate and intensive medical intervention. Doctors typically start with intravenous (IV) fluids and antimicrobial medications to fight the infection.

If blood pressure remains low after fluid replacement, medications to raise blood pressure are necessary. Patients often require care in an intensive care unit (ICU). In severe cases, mechanical ventilation may be used to support the lungs, and dialysis may be needed to support the kidneys.

Doctors may also use a central venous catheter or an arterial line to monitor the bloodstream and guide treatment decisions.