Inflammation Early systemic inflammation is the hallmark of sepsis. Sepsis begins with two simultaneous factors: Identification of infection byproducts released from the invading microbes Recognition of warning signals by cell surface receptors on specific populations of immune, epithelial and endothelial cells These byproducts and warning signals are known as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs and DAMPs bind to receptors on a subpopulation of immune, epithelial and endothelial cells. These receptors include: Toll-like receptors nucleotide-binding oligomerization domain (NOD)-like receptors Retinoic acid-inducible gene (RIG)-like receptors mannose-binding lectin and scavenger receptors Binding of these receptors ignites signaling pathways involved in inflammatory and immune responses. Specific fragments of invading organisms (bacteria, fungi, etc) and injured tissue recruit pro-inflammatory intermediates to the infected region. These intermediates then activate a variety of proteins, such as mitogen-activated protein kinases (MAPKs), Janus kinases (JAKs) or signal transducers and activators of transcription (STATs) and nuclear translocation of nuclear factor-κΒ (NF-κΒ), that activate expression of early activation genes.   The pro-inflammatory intermediate NF-κΒ activates several early activation genes of inflammatory cytokines including: Tumor necrosis factor (TNF) IL-1 IL-12 IL-18 type I interferons (IFNs) These cytokines then activate the second group of inflammatory cytokines and chemokines such as:

Very few studies have been done on the quality of life following sepsis. Most patients that survive sepsis remain in the hospital. More than half die within 3 months of developing sepsis. Approximately, 60% experience psychological impairments. A few others experience a life similar to the one they had prior to hospitalization and may return. However, most are discharged to nursing homes or rehabilitation facilities.  Mortality following discharge from the hospital is highest for older individuals (older than 55) and those that were hospitalized in the intensive care unit for more than 2 weeks.  Many patients that survive sepsis experience a syndrome called post-ICU syndrome. This condition is defined by the presence of insomnia, nightmares, fatigue, depression, loss of cognitive function and low self-esteem. At least three of these symptoms are experienced by nearly half of surviving patients. Other observed cognitive deficits include verbal learning and memory impairments for up to 2 years post-hospital discharge, general brain dysfunction, and post-traumatic stress disorder (PTSD). Survivors of sepsis are 10% more likely to experience cognitive impairment and to experience new impairments than individuals that did not have sepsis. The etiology of impairments resulting from sepsis, much like the quality of life following sepsis, is unknown.

The best way to prevent sepsis is to prevent infection. This is especially important for individuals with risk factors for sepsis. Ways to prevent sepsis in the community include: Vaccination of high-risk populations (i.e. vaccinating the elderly against pneumococcal pneumonia, vaccinating young adults for meningococcal infections) such as: Advanced stage cancer patients Patients with type I diabetes Individuals with end-stage renal disease Patients with congestive heart failure Patients with chronic obstructive pulmonary disease Practice good hygiene Maintain mobility to reduce frailty Maintain a nutritional diet Treat wound infections Sepsis and septic shock are more common in hospital settings due to the plethora of pathogens in this environment.  Thus, sepsis can be more difficult to treat in clinics. Preventative measures that can be taken in the hospital include reducing exposure to this environment. These measures include: Reducing length of patient stay Reducing frequency of invasive procedures Reducing frequency of duration of invasive procedures Washing hands Using antibacterial devices Changing catheters often Constant monitoring of the patient’s status Immediate treatment of any signs of sepsis Financial burden can also be a deterrent to practices that spread sepsis since sepsis is the most expensive disease to treat in hospitals in the United States.