Early administration of antibiotics and source identification The first line treatment for septic shock is typically early administration of antibiotics and intake of several fluids such as red blood cells and ionotropic drugs. A combination of antimicrobial treatments is the best way to treat sepsis in the initial stages until the microbes responsible for the infection are identified. The appropriate and specific antibiotic to use can be determined from microbiological cultures. Only after initial treatment should vasopressors be administered. In addition to early administration of antibiotics is identifying the source of the infection using imaging. Oxygen and Mechanical Ventilation Another common treatment for sepsis is the administration of oxygen using a mask or early endotracheal intubation. Oxygen is provided in order to reduce oxygen consumption by the body induced by increased breathing. Early Antibiotic Treatment As mentioned earlier, treatment with antibiotics early can make a difference in sepsis severity. A study found that the likelihood of survival decreases 7.6% every hour in which the first antibiotic treatment is delayed, while progression of septic shock increases 8% each hour. However, other studies suggest that there may not be a significant difference in severity and when the initial antibiotic treatment is provided.  The standard of care for antibiotics is that they are given within the first 3 h if the patient is admitted from the emergency unit and 1 h if admitted to the ICU from another service.

Corticosteroids Corticosteroids may be used following fluid intake and treatment with vasoactive drugs if no improvement in lactate levels is seen after the first 6 h. The corticosteroids allow for the vasoactive drugs to be gently withdrawn from the system. It has also been shown that when low or high doses of corticosteroids are given over a long period of time, they reduce mortality rates and shortened the amount of time spent in shock (and thus reduce the time the patient needs to be on vasopressors). Blood Glycemia Regulation High blood sugar levels can promote the development of organ failure in extremely ill patients. Thus treatments to control blood sugar may be provided in conjunction with primary sepsis treatment. Glycemia is controlled by regulating nutrition and other blood sugar level influencers. Patients may also be treated with insulin infusion therapy that is both aggressive but maintains glycemia levels at 140 mg/dL. Just as hyperglycemia can be harmful to patients in critical condition, so can hypoglycemia. Low blood sugar increases mortality and can undermine glycemia regulation therapy. More important than preventing high or low blood sugar is to prevent major fluctuations in blood sugar. Supportive Measures In addition to adjunctive and primary therapies, support mechanisms are also needed to maintain the health of patients with sepsis or septic shock.

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.