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Blood culture bottles: orange label for anaerobes, green label for aerobes, and yellow label for blood samples from children
Classification and external resources
Specialty Infectious disease
ICD-10 A40 – A41
ICD-9-CM 995.91
DiseasesDB 11960
MedlinePlus 000666
MeSH D018805

Sepsis () is a whole-body

  • Sepsis at DMOZ
  • SIRS, Sepsis, and Septic Shock Criteria

External links

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup; Dellinger, RP; Levy, MM; Rhodes, A; et al. (2013). "Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012" (PDF).  
  2. ^ a b c d "Sepsis Questions and Answers".  
  3. ^ a b c d e f Jui, Jonathan (2011). "Ch. 146: Septic Shock". In Tintinalli, Judith E.; Stapczynski, J. Stephan; Ma, O. John; Cline, David M.; et al. Tintinalli's Emergency Medicine: A Comprehensive Study Guide (7th ed.). New York:  
  4. ^ a b Deutschman, CS; Tracey, KJ (April 2014). "Sepsis: Current dogma and new perspectives".  
  5. ^ a b Patel, GP; Balk, RA (January 15, 2012). "Systemic steroids in severe sepsis and septic shock".  
  6. ^ a b c Martí-Carvajal, AJ; Solà, I; Gluud, C; Lathyris, D; Cardona, AF (12 December 2012). "Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients.". The Cochrane database of systematic reviews 12: CD004388.  
  7. ^ a b c Jawad, I; Lukšić, I; Rafnsson, SB (June 2012). "Assessing available information on the burden of sepsis: Global estimates of incidence, prevalence and mortality" (PDF). Journal of Global Health 2 (1): 010404.  
  8. ^ Martin, GS (June 2012). "Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes".  
  9. ^ a b c d Bone, R; Balk, R; Cerra, F; Dellinger, R; et al. (1992). "Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine" (PDF).  
  10. ^ a b Angus, DC; van der Poll, T (August 29, 2013). "Severe sepsis and septic shock".  
  11. ^ a b SCCM/ESICM/ACCP/ATS/SIS; Levy, MM; Fink, MP; Marshall, JC; et al. (April 2003). "2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference" (PDF).  
  12. ^ a b Felner, Kevin; Smith, Robert L. (2012). "Ch. 138: Sepsis". In McKean, Sylvia; Ross, John J.; Dressler, Daniel D.; Brotman, Daniel J.; et al. Principles and Practice of Hospital Medicine. New York:  
  13. ^ MedlinePlus Encyclopedia Sepsis. Retrieved November 29, 2014.
  14. ^ a b c Munford, Robert S.; Suffredini, Anthony F. (2014). "Ch. 75: Sepsis, Severe Sepsis and Septic Shock". In Bennett, John E.; Dolin, Raphael;  
  15. ^ Bloch, KC (2010). "Ch. 4: Infectious Diseases". In McPhee, Stephen J.; Hammer, Gary D. Pathophysiology of Disease (6th ed.). New York:  
  16. ^ Ramachandran, G (January 2014). "Gram-positive and gram-negative bacterial toxins in sepsis: A brief review".  
  17. ^ Delaloye, J; Calandra, T (January 2014). "Invasive candidiasis as a cause of sepsis in the critically ill patient".  
  18. ^ "American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis" (PDF).  
  19. ^ a b c Wacker, C; Prkno, A; Brunkhorst, FM; Schlattmann, P (May 2013). "Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis".  
  20. ^ a b c d Soong, J; Soni, N (June 2012). "Sepsis: Recognition and treatment".  
  21. ^ Abraham, E; Singer, M (2007). "Mechanisms of sepsis-induced organ dysfunction" (PDF).  
  22. ^ Ranieri, VM; Rubenfeld, GD; Thompson, BT; Ferguson, ND; et al. (June 2012). "Acute respiratory distress syndrome: The Berlin definition".  
  23. ^ "Meet the new ARDS: Expert panel announces new definition, severity classes". PulmCCM. Matthew Hoffman. 
  24. ^ International Consensus Conference on Pediatric Sepsis; Goldstein, B; Giroir, B; Randolph, A (2005). "International Pediatric Sepsis Consensus Conference: Definitions for sepsis and organ dysfunction in pediatrics".  
  25. ^ a b Backes, Y; van der Sluijs, KF; Mackie, DP; Tacke, F; Koch, A; Tenhunen, JJ; Schultz, MJ (September 2012). "Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review".  
  26. ^ Mayr, FB; Yende, S; Angus, DC (January 2014). "Epidemiology of severe sepsis".  
  27. ^ a b Satar, M; Ozlu, F (September 2012). "Neonatal sepsis: A continuing disease burden" (PDF).  
  28. ^ a b c d e f g h Ely, E. Wesley; Goyette, Richert E. (2005). "Ch. 46: Sepsis with Acute Organ Dysfunction". In Hall, Jesse B.; Schmidt, Gregory A.; Wood, Lawrence D.H. Principles of Critical Care (3rd ed.). New York:  
  29. ^ Shukla, P; Rao, GM; Pandey, G; Sharma, S; et al. (September 5, 2014). "Therapeutic interventions in sepsis: Current and anticipated pharmacological agents".  
  30. ^ Park, BS; Lee, JO (December 2013). "Recognition of lipopolysaccharide pattern by TLR4 complexes".  
  31. ^ Cross, AS (January 2014). "Anti-endotoxin vaccines: Back to the future".  
  32. ^ Fournier, B; Philpott, DJ (July 2005). "Recognition of Staphylococcus aureus by the innate immune system".  
  33. ^ Leentjens, J; Kox, M; van der Hoeven, JG; Netea, MG; et al. (June 15, 2013). "Immunotherapy for the adjunctive treatment of sepsis: From immunosuppression to immunostimulation. Time for a paradigm change?".  
  34. ^ Antonopoulou, A; Giamarellos-Bourboulis, EJ (January 2011). "Immunomodulation in sepsis: State of the art and future perspective".  
  35. ^ Nimah, M; Brilli, RJ (2003). "Coagulation dysfunction in sepsis and multiple organ system failure" (PDF).  
  36. ^ a b Marik, PE (June 2014). "Iatrogenic salt water drowning and the hazards of a high central venous pressure".  
  37. ^ a b c d Marik, PE (June 2014). "Early management of severe sepsis: concepts and controversies".  
  38. ^ Daniels, R. (11 March 2011). "Surviving the first hours in sepsis: getting the basics right (an intensivist's perspective)".  
  39. ^  
  40. ^ Hirasawa, H; Oda, S; Nakamura, M (September 7, 2009). "Blood glucose control in patients with severe sepsis and septic shock".  
  41. ^ Sterling, SA; Miller, WR; Pryor, J; Puskarich, MA; Jones, AE (26 June 2015). "The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis.". Critical care medicine.  
  42. ^ Sabatine, [edited by] Marc S. (2014). Pocket medicine (Fifth edition. ed.). [S.l.]: Aspen Publishers, Inc.  
  43. ^ a b c d e Dellinger, RP; Levy, MM; Carlet, JM; Bion, J; et al. (January 2008). "Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008".  
  44. ^ Fluids in Sepsis and Septic Shock Group; Rochwerg, B; Alhazzani, W; Sindi, A; et al. (September 2014). "Fluid resuscitation in sepsis: A systematic review and network meta-analysis".  
  45. ^ a b Perel, P; Roberts, I; Ker, K (2013). "Colloids versus crystalloids for fluid resuscitation in critically ill patients".  
  46. ^ Zarychanski, R; Abou-Setta, AM; Turgeon, AF; Houston, BL; et al. (February 2013). "Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: A systematic review and meta-analysis".  
  47. ^ Haase, N; Perner, A; Hennings, LI; Siegemund, M; et al. (2013). "Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: Systematic review with meta-analysis and trial sequential analysis".  
  48. ^ Serpa Neto, A; Veelo, DP; Peireira, VG; de Assunção, MS; et al. (February 2014). "Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature".  
  49. ^ Patel, A; Laffan, MA; Waheed, U; Brett, SJ (July 22, 2014). "Randomised trials of human albumin for adults with sepsis: A systematic review and meta-analysis with trial sequential analysis of all-cause mortality".  
  50. ^ TRISS Trial Group; Scandinavian Critical Care Trials Group; Holst, LB; Haase, N; et al. (October 9, 2014). "Lower versus higher hemoglobin threshold for transfusion in septic shock".  
  51. ^ Cherfan, AJ; Arabi, YM; Al-Dorzi, HM; Kenny, LP (May 2012). "Advantages and disadvantages of etomidate use for intubation of patients with sepsis".  
  52. ^ Chan, CM; Mitchell, AL; Shorr, AF (November 2012). "Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis".  
  53. ^ Gu, WJ; Wang, F; Tang, L; Liu, JC (September 25, 2014). "Single-dose etomidate does not increase mortality in patients with sepsis: A systematic review and meta-analysis of randomized controlled trials and observational studies".  
  54. ^ Volbeda M, Wetterslev J, Gluud C, Zijlstra JG, van der Horst IC, Keus F (July 2015). "Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis". Intensive Care Med 41 (7): 1220–34.  
  55. ^ a b c American College of Critical Care Medicine; Marik, PE; Pastores, SM; Annane, D; et al. (2008). "Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine" (PDF).  
  56. ^ a b c d Early Goal-Directed Therapy Collaborative Group;  
  57. ^ Fuller, BM; Dellinger, RP (June 2012). "Lactate as a hemodynamic marker in the critically ill.". Current opinion in critical care 18 (3): 267–72.  
  58. ^ a b Dell'anna, AM; Taccone, FS (19 June 2015). "Early-goal directed therapy for septic shock: is it the end?". Minerva anestesiologica.  
  59. ^ Rusconi, AM; Bossi, I; Lampard, JG; Szava-Kovats, M; Bellone, A; Lang, E (16 May 2015). "Early goal-directed therapy vs usual care in the treatment of severe sepsis and septic shock: a systematic review and meta-analysis.". Internal and emergency medicine.  
  60. ^ Shane, AL; Stoll, BJ (January 2014). "Neonatal sepsis: progress towards improved outcomes".  
  61. ^ Camacho-Gonzalez, A; Spearman, PW; Stoll, BJ (April 2013). "Neonatal infectious diseases: evaluation of neonatal sepsis".  
  62. ^ a b Alejandria, MM; Lansang, MA; Dans, LF; Mantaring, JB 3rd (September 2013). "Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock".  
  63. ^ Szakmany, T; Hauser, B; Radermacher, P (September 2012). "N-acetylcysteine for sepsis and systemic inflammatory response in adults".  
  64. ^ Russel, JA (October 2008). "The current management of septic shock".  
  65. ^ Best Evidence in Emergency Medicine Investigator, Group; Carpenter, CR; Keim, SM; Upadhye, S; et al. (October 2009). "Risk stratification of the potentially septic patient in the emergency department: The mortality in the emergency department sepsis (MEDS) score".  
  66. ^ Jackson, JC; Hopkins, RO; Miller, RR; Gordon, SM; et al. (November 2009). "Acute respiratory distress syndrome, sepsis, and cognitive decline: A review and case study".  
  67. ^ Lyle, NH; Pena, OM; Boyd, JH; Hancock, RE (September 2014). "Barriers to the effective treatment of sepsis: antimicrobial agents, sepsis definitions, and host-directed therapies".  
  68. ^ Munford, Robert S. (2011). "Ch. 271: Severe Sepsis and Septic Shock". In Longo, Dan L.; Fauci, Anthony S.; Kasper, Dennis L.; Hauser, Stephen L.; et al. Harrison's Principles of Internal Medicine (18th ed.). New York:  
  69. ^ a b Sutton, JP; Friedman, B (September 2013). "Trends in Septicemia Hospitalizations and Readmissions in Selected HCUP States, 2005 and 2010".  
  70. ^ Martin, GS; Mannino, DM; Eaton, S; Moss, M (2003). "The epidemiology of sepsis in the United States from 1979 through 2000".  
  71. ^ Hines, AL; Barrett, ML; Jiang, HJ; Steiner, CA (April 2014). "Conditions with the Largest Number of Adult Hospital Readmissions by Payer, 2011.".  
  72. ^ Koh, GC; Peacock, SJ; van der Poll, T; Wiersinga, WJ (April 2012). "The impact of diabetes on the pathogenesis of sepsis".  
  73. ^ Rubin, LG; Schaffner, W (July 2014). "Clinical practice. Care of the asplenic patient".  
  74. ^ Vincent, Jean-Louis (2008). "Ch. 1: Definition of Sepsis and Non-infectious SIRS". In Cavaillon, Jean-Marc; Adrie, Christophe. Sepsis and Non-infectious Systemic Inflammation: From Biology to Critical Care.  
  75. ^ Marshall, JC (July 2013). "Sepsis: Rethinking the approach to clinical research".  
  76. ^ Shear, MJ (1944). "Chemical treatment of tumors, IX: Reactions of mice with primary subcutaneous tumors to injection of a hemorrhage-producing bacterial polysaccharide".  
  77. ^ Luderitz, O; Galanos, C; Lehmann, V; Nurminen, M; et al. (1973). "Lipid A: Chemical structure and biologic activity".  
  78. ^ Heppner, G; Weiss, DW (1965). "High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures".  
  79. ^ O'Brien, AD; Rosenstreich, DL; Scher, I; Campbell, GH; et al. (1980). "Genetic control of susceptibility to Salmonella typhimurium in mice: Role of the LPS gene".  
  80. ^ Poltorak, A; Smirnova, I; He, X; Liu, M-Y; et al. (1998). "Genetic and physical mapping of the Lps locus: Identification of the toll-4 receptor as a candidate gene in the critical region".  
  81. ^ Poltorak, A; He, X; Smirnova, I; Liu, MY; et al. (1998). "Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene".  
  82. ^ a b Torio, CM; Andrews, RM (August 2013). "National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011".  
  83. ^ Pfuntner, A; Wier, LM; Steiner, C (December 2013). "Costs for Hospital Stays in the United States, 2011".  
  84. ^ "History".  
  85. ^ "About Us - About the Sepsis Alliance". Retrieved 8 October 2015. 


  1. ^ The term "ALI" appears to have fallen out of favor, based on the "Berlin definition"[22][23]



A large international collaboration entitled the "Surviving Sepsis Campaign" was established in 2002[84] to educate people about sepsis and to improve patient outcomes with sepsis. The Campaign has published an evidence-based review of management strategies for severe sepsis, with the aim to publish a complete set of guidelines in subsequent years.[43]


Sepsis was the most expensive condition treated in U.S. hospital stays in 2011, at an aggregate cost of $20.3 billion for nearly 1.1 million hospitalizations.[82] Costs for sepsis hospital stays more than quadrupled since 1997 with an 11.5 percent annual increase.[83] By payer, it was the most costly condition billed to Medicare, the second-most costly billed to Medicaid and the uninsured, and the fourth-most costly billed to private insurance.[82]


Society and culture

It was discovered in 1965 that a strain of C3H/HeJ mice were immune to the endotoxin-induced shock.[78] The genetic locus for this effect was dubbed Lps. These mice were also found to be hypersusceptible to infection by gram-negative bacteria.[79] These observations were finally linked in 1998 by the discovery of the toll-like receptor gene 4 (TLR 4).[80] Genetic mapping work, performed over a period of five years, showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 must account for the lipopolysaccharide resistance phenotype. The defect in the TLR4 gene that led to the endotoxin resistant phenotype was discovered to be due to a mutation in the cytoplasm.[81]

By the end of the 19th century, it was widely believed that microbes produced substances that could injure the mammalian host and that soluble toxins released during infection caused the fever and shock that were commonplace during severe infections. Pfeiffer coined the term endotoxin at the beginning of the 20th century to denote the pyrogenic principle associated with Vibrio cholerae. It was soon realised that endotoxins were expressed by most and perhaps all gram-negative bacteria. The lipopolysaccharide character of enteric endotoxins was elucidated in 1944 by Shear.[76] The molecular character of this material was determined by Luderitz et al. in 1973.[77]

process. Though severe systemic toxicity had already been observed, it was only in the 19th century that the specific term – sepsis – was used for this condition. purulent used the term "blood rot" for diseases linked to severe Avicenna In the eleventh century, [75] (sepsis) was introduced by Hippocrates in the fourth century BC, and it meant the process of [74] The term "σήψη"


Several medical conditions increase a person's susceptibility to infection and developing sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as cancer, diabetes, or the absence of a spleen; and major trauma and burns.[2][72][73]

Sepsis occurs in 1-2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated.[28] A study by the Agency for Healthcare Research and Quality (AHRQ) of selected States found that there were approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010.[69] It is the second-leading cause of death in non-coronary intensive care unit (ICU) patients, and the tenth-most-common cause of death overall (the first being heart disease).[70] Children under 12 months of age and elderly people have the highest incidence of severe sepsis.[28] Among U.S. patients who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care.[69] A study of 18 U.S. States found that, amongst Medicare patients in 2011, septicemia was the second most common principal reason for readmission within 30 days.[71]

Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized.[4][43] The worldwide incidence of sepsis is estimated to be 18 million cases per year.[67] In the United States sepsis affects approximately 3 in 1,000 people,[20] and severe sepsis contributes to more than 200,000 deaths per year.[68]


Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most sepsis patients makes the incidence of this difficult to quantify or to study.[66]

There are a number of prognostic stratification systems such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person's age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.[65]

Approximately 20–35% of people with severe sepsis and 30–70% of people with septic shock die.[64] Lactate is a useful method of determining prognosis with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L have a mortality of less than 15%.[20]


Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit.[43] However, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality.[6] It was removed from sale in 2011.[6]

Monoclonal and polyclonal preparations of intravenous immunoglobulin (IVIG) do not lower the rate of death in newborns and adults with sepsis.[62] Evidence for the use of IgM-enriched polyclonal preparations of IVIG is inconsistent.[62] A 2012 Cochrane review concluded that N-acetylcysteine does not reduce mortality in those with SIRS or sepsis and may even be harmful.[63]




In the original trial, early goal directed therapy was found to reduce mortality from 46.5% to 30.5% in those with sepsis,[56] and the Surviving Sepsis Campaign has been recommending its use.[1] However, three more recent large randomized control trials (ProCESS, ARISE, and ProMISe), did not demonstrate a 90-day mortality benefit of early goal directed therapy versus the standard therapy in severe sepsis.[58] It is likely that some parts of EGDT are more important than others.[58] Following these trials the use of EGDT is still considered reasonable.[59]

Early goal directed therapy (EGDT) is an approach to the management of severe sepsis during the initial 6 hours after diagnosis.[43] It is a step-wise approach, with the physiologic goal of optimizing cardiac preload, afterload, and contractility.[56] It includes giving early antibiotics.[56] It involves monitoring of hemodynamic parameters and specific interventions to achieve key resuscitation targets which include maintaining a central venous pressure between 8-12 mmHg, a mean arterial pressure of between 65-90 mmHg, a central venous oxygen saturation (ScvO2) greater than 70% and a urine output of greater than 0.5 ml/kg/hour. The goal is to optimize oxygen delivery to tissues and achieve a balance between systemic oxygen delivery and demand.[56] An appropriate decrease in serum lactate may be equivalent to ScvO2 and easier to obtain.[57]

Early goal directed therapy

The use of steroids in sepsis is controversial,[5] and the studies performed so far do not give a clear picture as to whether and when glucocorticoids should be used.[54] The 2012 Surviving Sepsis Campaign recommends against their use in those with septic shock if intravenous fluids and vasopressors stabilize the person's cardiovascular function.[1] During critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. This has been termed critical illness–related corticosteroid insufficiency.[55] Treatment with corticosteroids might be most beneficial in those with septic shock and early severe ARDS, whereas its role in others such as those with pancreatitis or severe pneumonia is unclear.[55] However, the exact way of determining corticosteroid insufficiency remains problematic. It should be suspected in those poorly responding to resuscitation with fluids and vasopressors. ACTH stimulation testing is not recommended to confirm the diagnosis.[55] The method of stopping glucocorticoid drugs is variable, and it is unclear whether they should be slowly decreased or simply abruptly stopped.


It is recommended that the head of the bed be raised if possible to improve ventilation.[1] Paralytic agents should be avoided unless ARDS is suspected.[1]

Etomidate is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death.[51][52] The small amount of evidence there is, however, has not found a change in the risk of death with etomidate.[53]


If the person has been sufficiently fluid resuscitated but the mean arterial pressure is not greater than 65 mmHg, vasopressors are recommended. Norepinephrine (noradrenaline) is recommended as the initial choice. If a single vasopressor is not enough to raise the blood pressure, epinephrine (adrenaline) or vasopressin may be added. Dopamine is typically not recommended. Dobutamine may be used if heart function is poor or blood flow is insufficient despite sufficient fluid volumes and blood pressure.[1]


Crystalloid solutions are recommended initially.[1] Crystalloid solutions and albumin are better than other fluids (such as hydroxyethyl starch) in terms of risk of death.[44] Starches also carry an increased risk of acute kidney injury,[45][46] and need for blood transfusion.[47][48] Various colloid solutions (such as modified gelatin) carry no advantage over crystalloid.[45] Albumin also appears to be of no benefit over crystalloids.[49] Packed red blood cells are recommended to keep the hemoglobin levels between 70 and 90 g/L.[1] A 2014 trial; however, found no difference between a target hemoglobin of 70 or 90 g/L.[50]

Intravenous fluids are titrated (measured and adjusted) in response to heart rate, blood pressure, and urine output; restoring large fluid deficits can require 6 to 10 liters of crystalloids.[28] In cases of severe sepsis and septic shock where a central venous catheter is used to measure blood pressures dynamically, fluids should be administered until the central venous pressure (CVP) reaches 8–12mmHg.[36] Once these goals are met, the central venous oxygen saturation (ScvO2), i.e., the oxygen saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the ScvO2 is less than 70%, blood may be given to reach a hemoglobin of 10 g/dL and then inotropes are added until the ScvO2 is optimized.[28] In those with acute respiratory distress syndrome (ARDS) and sufficient tissue blood fluid, more fluids should be given carefully.[1]

Intravenous fluids

[43] Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures.[1] Antibiotic regimens should be reassessed daily and narrowed if appropriate.[37] Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a

In severe sepsis and septic shock, broad-spectrum antibiotics (usually two or a β-lactam antibiotic with broad coverage) are recommended.[1][37] Some recommend they be given within 1 hour of making the diagnosis stating that for every hour delay in the administration of antibiotics, there is an associated 6% rise in mortality.[20][37] Others did not find a benefit with early administration.[41] Two sets of blood cultures should be obtained before starting antibiotics if this can be done without delaying the administration of antibiotics.[42]


Apart from the timely administration of fluids and hemodialysis in kidney failure, mechanical ventilation in lung dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary by parenteral nutrition—is important during prolonged illness.[1] In those with high blood sugar levels, insulin to bring it down to 7.8-10 mmol/L (140–180 mg/dL) is recommended with lower levels potentially worsening outcomes.[40] Medication to prevent deep vein thrombosis and gastric ulcers may also be used.[1]

Early recognition and focused management can improve the outcomes in sepsis. Current professional recommendations include a number of actions ("bundles") to be taken as soon as possible after diagnosis. Within the first three hours someone with sepsis should have received antibiotics, and intravenous fluids if there is evidence of either low blood pressure or other evidence for inadequate blood supply to organs (as evidenced by a raised level of lactate); blood cultures should also be obtained within this time period. After six hours the blood pressure should be adequate, close monitoring of blood pressure and blood supply to organs should be in place, and the lactate should be measured again if it was initially raised.[1] A related bundle, the "sepsis six", is in widespread use in the United Kingdom; this requires the administration of antibiotics within an hour of recognition, blood cultures, lactate and hemoglobin determination, urine output monitoring, high-flow oxygen, and intravenous fluids.[38][39]


A systemic inflammatory response syndrome can also occur in patients without the presence of infection, for example in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis.[9] The low blood pressure seen in those with sepsis is the result of various processes including excessive production of chemicals that dilate blood vessels such as nitric oxide, a deficiency of chemicals that constrict blood vessels such as vasopressin, and activation of ATP-sensitive potassium channels.[36] In those with severe sepsis and septic shock, this sequence of events leads to a type of circulatory shock known as distributive shock.[37]

[35] Cytokines such as

Host factors

There are a number of microbial factors which can cause the typical septic inflammatory cascade. An invading pathogen is recognized by its pathogen-associated molecular patterns (PAMPs). Examples of PAMPs include lipopolysaccharides and flagellin in gram-negative bacteria, muramyl dipeptide in the peptidoglycan of the gram-positive bacterial cell wall, and CpG bacterial DNA. These PAMPs are recognized by the innate immune system's pattern recognition receptors (PRRs), which can be membrane-bound or cytosolic.[33] There are four families of PRRs: the toll-like receptors, the C-type lectin receptors, the NOD-like receptors and the RIG-I-like receptors. The association of a PAMP and a PRR will invariably cause a series of intracellular signalling cascades. Consequentially, transcription factors like nuclear factor-kappa B and activator protein-1 will up-regulate the expression of pro-inflammatory and anti-inflammatory cytokines.[34]

Bacterial virulence factors such as glycocalyx and various adhesins allow colonization, immune evasion, and establishment of disease in the host.[28] Sepsis caused by gram-negative bacteria is thought to be largely due to the host's response to the lipid A component of lipopolysaccharide, also called endotoxin.[30][31] Sepsis caused by gram-positive bacteria can result from an immunological response to cell wall lipoteichoic acid.[32] Bacterial exotoxins that act as superantigens can also cause sepsis.[28] Superantigens simultaneously bind major histocompatibility complex and T-cell receptors in the absence of antigen presentation. This forced receptor interaction induces the production of pro-inflammatory chemical signals (cytokines) by T-cells.[28]

Microbial factors

Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and to the status of the host's immune system.[28] The early phase of sepsis characterized by excessive inflammation (which can sometimes result in a cytokine storm) can be followed by a prolonged period of decreased functioning of the immune system.[29] Either of these phases can prove fatal.


In common clinical usage, neonatal sepsis refers to a bacterial blood stream infection in the first month of life, such as meningitis, pneumonia, pyelonephritis, or gastroenteritis,[27] but neonatal sepsis can also be due to infection with fungi, viruses, or parasites.[27] Criteria with regard to hemodynamic compromise or respiratory failure are not useful because they present too late for intervention.

Neonatal sepsis

The differential diagnosis for sepsis is broad and has to look at (to exclude) the noninfectious conditions that can cause the systemic signs of SIRS: alcohol withdrawal, acute pancreatitis, burns, pulmonary embolus, thyrotoxicosis, anaphylaxis, adrenal insufficiency, and neurogenic shock.[12][26]

Differential diagnosis

A 2013 systematic review and meta-analysis concluded moderate-quality evidence exists to support use of the procalcitonin level as a method to distinguish sepsis from non-infectious causes of SIRS.[19] The same review found the test's sensitivity to be 77% and the specificity to be 79%. The authors suggested procalcitonin may serve as a helpful diagnostic marker for sepsis, but cautioned that its level alone cannot definitively make the diagnosis.[19] A 2012 systematic review found that soluble urokinase-type plasminogen activator receptor (SuPAR) is a nonspecific marker of inflammation and does not accurately diagnose sepsis.[25] However, this same review concluded that SuPAR has prognostic value as higher SuPAR levels are associated with an increased rate of death in those with sepsis.[25]


Consensus definitions, however, continue to evolve, with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.[11]

More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.[24]

Examples of end-organ dysfunction include the following:[21]

End-organ dysfunction

According to the American College of Chest Physicians and the Society of Critical Care Medicine, there are different levels of sepsis: sepsis, severe sepsis, and septic shock.[9]


If the SIRS criteria are negative it very unlikely the person has sepsis; however, if they are positive there is just a moderate probability that the person has sepsis.[9]

Within six hours, if blood pressure remains low despite initial fluid resuscitation of 30 ml/kg, or if initial lactate is ≥ 4 mmol/L (36 mg/dL), chest x-ray consistent with pneumonia (with focal opacification); or petechiae, purpura, or purpura fulminans can also be evident of infection.

Within the first three hours of suspected sepsis, diagnostic studies should include through the skin and one drawn through each vascular access device (such as an IV catheter) in place more than 48 hours.[1] However, bacteria are present in the blood in only about 30% of cases.[19] Another possible method of detection is by polymerase chain reaction. If other sources of infection are suspected, cultures of these sources, such as urine, cerebrospinal fluid, wounds, or respiratory secretions, should also be obtained, as long as this does not delay the use of antibiotics.[1]

Early diagnosis is necessary to properly manage sepsis, as initiation of early goal directed therapy is key to reducing mortality from severe sepsis.[1]

Systemic inflammatory response syndrome[18]
Finding Value
Temperature <36 °C (96.8 °F) or >38 °C (100.4 °F)
Heart rate >90/min
Respiratory rate >20/min or PaCO2<32 mmHg (4.3 kPa)
WBC <4x109/L (<4000/mm³), >12x109/L (>12,000/mm³), or 10% bands


Infections leading to sepsis are usually bacterial but can also be fungal or viral.[14] While gram-negative bacteria were previously the most common cause of sepsis, in the last decade gram-positive bacteria, most commonly staphylococci, are thought to cause more than 50% of cases of sepsis.[15] Other commonly implicated bacteria include Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species.[16] Fungal sepsis accounts for approximately 5% of severe sepsis and septic shock cases; the most common cause of fungal sepsis is infection by Candida species of yeast.[17]

The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract.[14] Typically, 50% of all sepsis cases start as an infection in the lungs. No definitive source is found in one third to one half of cases.[14]


The drop in blood pressure seen in sepsis may lead to shock. This may result in light-headedness. Bruising or intense bleeding may also occur.[13]

[12] In addition to symptoms related to the provoking cause, sepsis is frequently associated with either

Signs and symptoms


  • Signs and symptoms 1
  • Cause 2
  • Diagnosis 3
    • Definitions 3.1
    • End-organ dysfunction 3.2
    • Biomarkers 3.3
    • Differential diagnosis 3.4
    • Neonatal sepsis 3.5
  • Pathophysiology 4
    • Microbial factors 4.1
    • Host factors 4.2
  • Management 5
    • Antibiotics 5.1
    • Intravenous fluids 5.2
    • Vasopressors 5.3
    • Ventilation 5.4
    • Steroids 5.5
    • Early goal directed therapy 5.6
    • Newborns 5.7
    • Other 5.8
  • Prognosis 6
  • Epidemiology 7
  • History 8
  • Society and culture 9
    • Economics 9.1
    • Education 9.2
  • Notes 10
  • References 11
  • External links 12

[10].Hippocrates The condition has been described at least since the time of [10][9]

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