Sepsis

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INTRODUCTION

First, sepsis is a syndrome and not an individual disease. It is the 11th leading cause of death in the US. According to the Global Sepsis Alliance (GSA), “Sepsis is one of the most pressing healthcare challenges faced by the world today.”  The CDC shows sepsis hospital admissions “have grown from around 200 per 1000 inhabitants in 2000, to 340 in 2008. Also, in 2008 the costs for hospital treatment were US $14.8 billion, but these have increased by an annual rate of 11 percent.” According to Dr. Reinhardt “the main way it can be prevented is if it is recognized early and the patient receives adequate measures of treatment. Treatments, like antimicrobials and intravenous fluids must be initiated when the first signs of organ dysfunction appear. If they are given in the first few hours the survival rate may be up to 80 percent, but studies suggest with each hour of delay the mortality rate increases by five to eight percent.” (GSA – Stop Sepsis, Save Lives)

DEFINITION

Sepsis is a potentially deadly medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) that is triggered by an infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues. A popular term for sepsis is blood poisoning. Severe sepsis is the systemic inflammatory response, infection and the presence of organ dysfunction. Septic Shock is the combination of sepsis with abnormally decreased blood pressure.

(Also, here is another great video about SIRS from the same source.)

PATHOPHYSIOLOGY

At this point in time, the literature richly illustrates that no single mediator / system / pathway / pathogen drives the pathophysiology of sepsis (Am J Pathol. 2007 May; 170(5): 1435–1444. doi:10.2353/ajpath.2007.060872, Pathophysiology of Sepsis)

    • The basic pathophysiology of sepsis, severe sepsis, and septic shock includes:
      • Vasodilation
      • Third spacing due to capillary leak
      • Myocardial dysfunction.
    • Vascular endothelium is both a source and target of injury in SIRS / sepsis. Injury may be due to toxins such as LPS (endotoxin) or from ischemia itself. Tissue factor release leads to amplification of the inflammatory response and to DIC via the thrombin pathway. Thrombin not only catalyzes fibrin formation but also causes leukocyte adhesion which leads to further endothelial damage. As DIC progresses, clotting factors are consumed and bleeding occurs.
    • Clotting factors, pro-fibrinolytic, and anti-thrombin factors are consumed leading to loss of fibrinolysis & normal down-regulation of thrombin pathway. This phenomenon is both pro-inflammatory and pro-thrombotic.
    • Protein C depletion has been associated with increased mortality. This has led to a series of clinical trials utilizing protein C, activated protein C (APC), antithrombin III (AT-III), and tissue factor pathway inhibitor to try and disrupt this cycle. Activated protein C has in fact been shown to reduce mortality in severe sepsis in adults. Bleeding problems seems to outweigh the benefits in children.
    • Usually gram negative and usually originating in the urinary or respiratory systems
    • Frequent microbial causes of sepsis

 

IDENTIFYING SEPSIS

(Balk RA. Crit Care Clin 2000;16:337-52, Surviving Sepsis Campaign 2008 SSC Guidelines)

Differentials

TREATMENT

DESPERATE MEASURES

These measures can help improve immunohomeostasis (pro/antiinflamatory mediators), improve coagulation response with decreased organ thrombosis, and provide mechanical support for organ perfusion during an acute episode, and may buy some time, but may or may not reduce mortality.

NOVEL THERAPIES

QUALITY

REVIEWS

CLINICAL TRIALS

DR. RIVERS TALK

Dr. Emmanuel Rivers gave a talk on Severe Sepsis Management via the EMCrit Blog. The talk is broken down into the three links to each of the episodes provided below.

ADDITIONAL RESOURCES

In addition, here are some more great resources related to sepsis.

  1. Advances in Sepsis
  2. Crashing Patient Severe Sepsis
  3. Development and Implementation of a Multidisciplinary Sepsis Protocol
  4. EMCrit – Severe Sepsis Resources*
  5. EM Guidlines – Sepsis
  6. Global Sepsis Alliance
  7. International Sepsis Forum
  8. MedicineNet – Sepsis
  9. Medline Sepsis
  10. Sepsis Alliance
  11. Sepsis know from day 1
  12. Stanford SOM – Septris
  13. Surviving Sepsis
    1. The Surviving Sepsis Campaign (SSC) was developed by the European Society of Critical Care Medicine, the International Sepsis Forum,and the Society of Critical Care Medicine, to help meet the challenges of sepsis and to improve its management, diagnosis, and treatment. The agreement between the three founding organizations and funding for the campaign was concluded December 31, 2008. A generous grant has been received to continue the important work of the campaign. The grant funding extends through 2013. Assistance for US hospitals interested in implementing the bundles can be obtained through the Society of Critical Care Medicine’s Paragon program.
    2. Surviving Sepsis Protocol Checklist

Additional References

  1. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis De?nitions Conference
  2. Cleveland Clinic – Sepsis
  3. Genetic Polymorphisms in Sepsis and Septic Shock:Role in Prognosis and Potential for Therapy
  4. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers
  5. Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients
  6. Oxidative stress as a novel target in pediatric sepsis management
  7. The Pathogenesis of Sepsis
  8. Rapid Treatment of Severe Sepsis
  9. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club
  10. Thermo Scientific biomarker procalcitonin
  11. Time is tissue: Why emerging evidence on sepsis urges physicians to watch the clock
    Early volume resuscitation can help avoid organ dysfunction—if you act quickly after making a diagnosis

CONCLUSION

Sepsis poses a significant burden upon the US healthcare system, resulting in an estimated 750,000 hospital admissions, 570,000 Emergency Department visits, 200,000 deaths and $16.7 billion in medical expenditures annually, according to, the online journal article in PLOS ONE, Chronic Medical Conditions and Risk of Sepsis. Mortality rates remain high in severe sepsis, and despite recent therapeutic breakthroughs much remains to be done to advance our understanding and treatment of sepsis. Currently, anti-sepsis initiatives focus on acute care, with ED staff employing the “sepsis bundles,” a series of steps that includes aggressive administration of antibiotics, IV fluids and blood pressure-boosting medications, and management. Additionally, the  Surviving Sepsis Campaign 2012 guidelines will further suggest that in patients with elevated lactate levels as a marker of hypoperfusion, resuscitation should be targeted at normalizing lactate as rapidly as possible (grade 2C). Having said that, however, a normal lactate doesn’t indicate absence of shock. Other factors, such as the patient’s central venous oxygen saturation level, need to be considered as well. The Surviving Sepsis Campaign guidelines are sponsored by 27 medical organizations. Among them are the Society of Critical Care Medicine, ACEP, the Society of Hospital Medicine, the American College of Chest Physicians, the American Thoracic Society, the Infectious Diseases Society of America, the Surgical Infection Society, the Pediatric Acute Lung Injury and Sepsis Investigators, and a host of international groups. Hopefully, strategies will be developed to continue to improve and maximize our efforts towards ameliorating sepsis throughout the world.

3 thoughts on “Sepsis”

  1. Pingback: Biochemistry of the Coagulation Cascade and Platelet Aggregation « Pharmaceutical Intelligence

  3. Gladis

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