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{| class="infobox" style="float: right;"
| style="vertical-align: middle; padding: 5px;" align=center | [[File:Siren.gif|30px|link=Sepsis resident survival guide]]
| style="vertical-align: middle; padding: 5px;" align=center | [[Sepsis resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Sepsis}}
{{Sepsis}}
{{CMG}}
{{CMG}};  '''Associate Editor(s)-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, M.B.B.S.]] [mailto:psingh@perfuse.org]
 
{{SK}} sepsis syndrome; septic shock; septicemia


==Overview==
==Overview==
'''Sepsis''' is a serious medical condition characterized by a whole-body [[Inflammation|inflammatory]] state caused by [[infection]].
Sepsis is a condition characterized by a whole-body [[Inflammation|inflammatory]] state caused by [[infection]]. [[Septic shock]] is a serious [[medicine|medical]] condition caused by decreased tissue perfusion and oxygen delivery as a result of [[infection]] and [[sepsis]].  It can cause [[multiple organ failure]] and [[death]]. Its most common victims are children, [[immunodeficiency|immunocompromised]] individuals, and the elderly. This is because their [[immune system]]s cannot cope with the infection as well as those of full-grown adults.<ref name="pmid23983879">{{cite journal |vauthors=Karnatovskaia LV, Festic E |title=Sepsis: a review for the neurohospitalist |journal=Neurohospitalist |volume=2 |issue=4 |pages=144–53 |year=2012 |pmid=23983879 |pmc=3726110 |doi=10.1177/1941874412453338 |url=}}</ref>
Traditionally the term sepsis has been used interchangeably with septicaemia and septicemia ("blood poisoning"). However, these terms are no longer considered synonymous; septicemia is considered a subset of sepsis.
 
==Pathophysiology==
The immunological response that causes sepsis is a systemic inflammatory response causing widespread activation of [[inflammation]] and [[coagulation]] pathways. This may progress to dysfunction of the [[septic shock|circulatory system]] and, even under optimal treatment, may result in the [[multiple organ dysfunction syndrome]] and eventually [[death]]. A subclass of [[distributive shock]], shock refers specifically to decreased tissue [[perfusion]] resulting in end-organ dysfunction. [[Cytokines]] [[TNFα]], [[interleukin|IL]]-1β, [[interferon]] γ, [[IL-6]] released in a large scale inflammatory response results in massive [[vasodilation]], increased [[capillary]] permeability, decreased systemic vascular resistance, and [[hypotension]].  Hypotension reduces tissue perfusion pressure and thus tissue [[Hypoxia (medical)|hypoxia]] ensues.  Finally, in an attempt to offset decreased [[blood pressure]], [[ventricular]] dilatation and [[myocardium|myocardial]] dysfunction will occur.<ref name="pmid28448952">{{cite journal |vauthors=Minasyan H |title=Sepsis and septic shock: Pathogenesis and treatment perspectives |journal=J Crit Care |volume=40 |issue= |pages=229–242 |year=2017 |pmid=28448952 |doi=10.1016/j.jcrc.2017.04.015 |url=}}</ref><ref name="pmid25870671">{{cite journal |vauthors=Pop-Began V, Păunescu V, Grigorean V, Pop-Began D, Popescu C |title=Molecular mechanisms in the pathogenesis of sepsis |journal=J Med Life |volume=7 Spec No. 2 |issue= |pages=38–41 |year=2014 |pmid=25870671 |pmc=4391358 |doi= |url=}}</ref><ref name="pmid20887193">{{cite journal |vauthors=Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG |title=The pathogenesis of sepsis |journal=Annu Rev Pathol |volume=6 |issue= |pages=19–48 |year=2011 |pmid=20887193 |pmc=3684427 |doi=10.1146/annurev-pathol-011110-130327 |url=}}</ref><ref name="pmid14767363">{{cite journal |vauthors=Cunneen J, Cartwright M |title=The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment |journal=AACN Clin Issues |volume=15 |issue=1 |pages=18–44 |year=2004 |pmid=14767363 |doi= |url=}}</ref><ref name="pmid24292568">{{cite journal |vauthors=Chaudhry H, Zhou J, Zhong Y, Ali MM, McGuire F, Nagarkatti PS, Nagarkatti M |title=Role of cytokines as a double-edged sword in sepsis |journal=In Vivo |volume=27 |issue=6 |pages=669–84 |year=2013 |pmid=24292568 |pmc=4378830 |doi= |url=}}</ref>
 
==Classification==
In rough order of severity, these are [[bacteremia]] or [[fungemia]]; [[septicemia]]; [[sepsis]], severe sepsis or sepsis syndrome; septic shock; refractory septic shock; [[multiple organ dysfunction syndrome]], and [[death]].


==Sepsis <ref name="pmid18158437">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL |title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 |journal=[[Critical Care Medicine]] |volume=36 |issue=1 |pages=296–327 |year=2008 |month=January |pmid=18158437 |doi=10.1097/01.CCM.0000298158.12101.41 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=36&issue=1&spage=296 |accessdate=2012-09-16}}</ref>, <ref>Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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. Chest. 1992 Jun;101(6):1644-55. PMID 1303622.</ref>==
==Causes==
Sepsis is considered present if infection is highly suspected or proven and two or more of the following [[systemic inflammatory response syndrome]] (SIRS) criteria are met:
The process of [[infection]] by [[bacteria]] or [[fungi]] can result in systemic signs and symptoms that are variously described. The condition develops as a response to certain [[microbe|microbial]] molecules which trigger the production and release of cellular mediators, such as [[tumor necrosis factors]] (TNF); these act to stimulate immune response.<ref name="pmid12851245">{{cite journal |vauthors=Annane D, Aegerter P, Jars-Guincestre MC, Guidet B |title=Current epidemiology of septic shock: the CUB-Réa Network |journal=Am. J. Respir. Crit. Care Med. |volume=168 |issue=2 |pages=165–72 |year=2003 |pmid=12851245 |doi=10.1164/rccm.2201087 |url=}}</ref><ref name="pmid17192537">{{cite journal |vauthors=Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C |title=An intervention to decrease catheter-related bloodstream infections in the ICU |journal=N. Engl. J. Med. |volume=355 |issue=26 |pages=2725–32 |year=2006 |pmid=17192537 |doi=10.1056/NEJMoa061115 |url=}}</ref><ref name="pmid24335434">{{cite journal |vauthors=Mayr FB, Yende S, Angus DC |title=Epidemiology of severe sepsis |journal=Virulence |volume=5 |issue=1 |pages=4–11 |year=2014 |pmid=24335434 |pmc=3916382 |doi=10.4161/viru.27372 |url=}}</ref>


* [[Heart rate]] > 90 beats per minute
==Differentiating Sepsis from other Diseases==
* [[Temperature]] < 36 (96.8 °F) or > 38 °C (100.4 °F)
Sepsis must be differentiated from other syndromes presnting with fever, hypotension such as the [[acute bacterial endocarditis]], myocardial ring [[abscess]], [[subacute bacterial endocarditis]] and [[bacterial meningitis]].<ref name="pmid28477737">{{cite journal |vauthors=Machowicz R, Janka G, Wiktor-Jedrzejczak W |title=Similar but not the same: Differential diagnosis of HLH and sepsis |journal=Crit. Rev. Oncol. Hematol. |volume=114 |issue= |pages=1–12 |year=2017 |pmid=28477737 |doi=10.1016/j.critrevonc.2017.03.023 |url=}}</ref><ref name="isbn0-683-06754-0">{{Cite book  | last1 = Parrillo | first1 = Joseph E. | last2 = Ayres | first2 = Stephen M. | title = Major issues in critical care medicine | date = 1984 | publisher = William  Wilkins | location = Baltimore | isbn = 0-683-06754-0 | pages =  }}</ref><ref name="isbn9781405179263">{{cite book | author = Judith S. Hochman, E. Magnus Ohman | authorlink = | editor = | others = | title = Cardiogenic Shock | edition = | language = | publisher = Wiley-Blackwell | location = | year = 2009 | origyear = | pages = | quote = | isbn = 9781405179263 | oclc = | doi = | url = | accessdate = }}</ref>
* [[Tachypnea]] > 20 breaths per minute or, on [[blood gas]], a P<sub>a</sub>CO<sub>2</sub> < 32 mm Hg
* [[White blood cell]] count < 4000 cells/mm³ or > 12000 cells/mm³ (< 4 x 10<sup>9</sup> or > 12 x 10<sup>9</sup> cells/[[litre|L]]), or > 10% band forms (immature white blood cells / bandemia).


Consensus definitions however continue to evolve with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.<ref>Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.</ref>
==Epidemiology and Demographics==
The hospitalization rate of those with a principal diagnosis of septicemia or sepsis more than doubled from 2000 through 2008. During the same period, the hospitalization rate for those with septicemia or sepsis as a principal or as a secondary diagnosis increased by 70% from 221 to 377 for every 100,000 people. Reasons for these increases may include an aging population with more chronic illnesses, greater use of invasive procedures, immunosuppressive drugs, [[chemotherapy]], [[transplantation]], and increasing microbial resistance to [[antibiotics]].<ref name="urlProducts - Data Briefs - Number 62 - June 2011">{{cite web |url=http://www.cdc.gov/nchs/data/databriefs/db62.htm |title=Products - Data Briefs - Number 62 - June 2011 |format= |work= |accessdate=2012-09-17}}</ref>
==Risk Factors==
Factors responsible for increased risk of sepsis may include an aging population with more chronic illnesses; greater use of invasive procedures, immunosuppressive drugs, chemotherapy, and transplantation; and increasing microbial resistance to antibiotics. Other patients population at increased risk are ICU admits, immunocompromised, bacteremic, with [[community acquired pneumonia]], and with [[genetic predisposition]].<ref name="pmid28523249">{{cite journal |vauthors=Ballouz T, Aridi J, Afif C, Irani J, Lakis C, Nasreddine R, Azar E |title=Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia |journal=Front Cell Infect Microbiol |volume=7 |issue= |pages=156 |year=2017 |pmid=28523249 |pmc=5415554 |doi=10.3389/fcimb.2017.00156 |url=}}</ref><ref name="urlProducts - Data Briefs - Number 62 - June 2011">{{cite web |url=http://www.cdc.gov/nchs/data/databriefs/db62.htm |title=Products - Data Briefs - Number 62 - June 2011 |format= |work= |accessdate=2012-09-17}}</ref><ref name="urlProducts - Data Briefs - Number 62 - June 2011">{{cite web |url=http://www.cdc.gov/nchs/data/databriefs/db62.htm |title=Products - Data Briefs - Number 62 - June 2011 |format= |work= |accessdate=2012-09-17}}</ref>


==Severe sepsis <ref name="pmid18158437">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL |title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 |journal=[[Critical Care Medicine]] |volume=36 |issue=1 |pages=296–327 |year=2008 |month=January |pmid=18158437 |doi=10.1097/01.CCM.0000298158.12101.41 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=36&issue=1&spage=296 |accessdate=2012-09-16}}</ref>==
==Natural History, Complications and Prognosis==
Patients are defined as having "severe sepsis" if they have sepsis plus
There are many complications associated with sepsis, especially because it is a systemic phenomenon. Sepsis is a severe condition, and the prognosis of the patient will depend greatly on the condition and overall health of the patient. Many factors, such as age, hosts immune response, site of [[infection]], type of infection, appropriate [[antibiotic]] therapy, and restoration of circulation of perfusion contribute to the overall prognosis.<ref name="pmid26398704">{{cite journal| author=Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL et al.| title=The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. | journal=Am J Respir Crit Care Med | year= 2016 | volume= 193 | issue= 3 | pages= 281-7 | pmid=26398704 | doi=10.1164/rccm.201505-0995OC | pmc=4803059 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26398704  }} </ref><ref name="pmid25776936">{{cite journal| author=Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R| title=Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis. | journal=N Engl J Med | year= 2015 | volume=  | issue=  | pages=  | pmid=25776936 | doi=10.1056/NEJMoa1415236 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25776936  }} </ref>
* signs of systemic [[hypoperfusion]]
<ref name="pmid25668750">{{cite journal| author=Capp R, Horton CL, Takhar SS, Ginde AA, Peak DA, Zane R et al.| title=Predictors of Patients Who Present to the Emergency Department With Sepsis and Progress to Septic Shock Between 4 and 48 Hours of Emergency Department Arrival. | journal=Crit Care Med | year= 2015 | volume=  | issue=  | pages=  | pmid=25668750 | doi=10.1097/CCM.0000000000000861 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25668750  }} </ref><ref name="pmid26901543">{{cite journal| author=Williams JM, Greenslade JH, Chu K, Brown AF, Lipman J| title=Severity Scores in Emergency Department Patients With Presumed Infection: A Prospective Validation Study. | journal=Crit Care Med | year= 2016 | volume= 44 | issue= 3 | pages= 539-47 | pmid=26901543 | doi=10.1097/CCM.0000000000001427 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26901543  }} </ref><ref name="pmid12626967">{{cite journal |author=Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW |title=Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule |journal=Crit. Care Med. |volume=31 |issue=3 |pages=670-5 |year=2003 |pmid=12626967 |doi=10.1097/01.CCM.0000054867.01688.D1}}</ref><ref name="pmid26903335">{{cite journal| author=Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A et al.| title=Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). | journal=JAMA | year= 2016 | volume= 315 | issue= 8 | pages= 762-74 | pmid=26903335 | doi=10.1001/jama.2016.0288 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26903335  }} </ref> <ref>GitHub Contributors. Prognosticating in sepsis with decision aids: a living systematic review. GitHub. Available at https://github.com/openMetaAnalysis/Sepsis-prognosticating-with-decision-aids/blob/master/README.md. Accessed January 26, 2017.</ref>
** [[Capillary refilling time]] > 3 seconds
** Urine output <.5mL/kg for atleast 1 hour or requirement of [[renal replacement therapy]]
* End organs dysfunction
** Left ventricular systolic dysfunction (echocardiographic findings / cardiac index)
** Acute changes in sensorium / abnormal EEG findings
** [[Disseminated intravascular coagulation]]
** [[Thrombocytopenia]] < 100,000 platelets/mL
** [[Acute respiratory distress syndrome]] ([[ARDS]])
** Skin mottlings
* Serum [[lactate]] > 2 mmol/L.


==Septic shock <ref name="pmid18158437">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL |title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 |journal=[[Critical Care Medicine]] |volume=36 |issue=1 |pages=296–327 |year=2008 |month=January |pmid=18158437 |doi=10.1097/01.CCM.0000298158.12101.41 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=36&issue=1&spage=296 |accessdate=2012-09-16}}</ref>==
==Diagnosis==
[[Septic shock]] is defined as [[sepsis]] with refractory arterial [[hypotension]]. Refractory arterial [[hypotension]] is further defined as:
===History and Symptoms===
* Mean systemic blood pressure (SBP) of < 60 mm Hg or < 80 mm Hg (in hypertensives) despite adequate fluid resuscitation.
Symptoms of sepsis are often related to the underlying infectious process. When the infection crosses into the bloodstream the resulting symptoms of sepsis occur fever, chills, and rigors, confusion, anxiety, difficulty breathing, fatigue and malaise, nausea and vomiting.<ref name="pmid17962288">{{cite journal |vauthors=Lever A, Mackenzie I |title=Sepsis: definition, epidemiology, and diagnosis |journal=BMJ |volume=335 |issue=7625 |pages=879–83 |year=2007 |pmid=17962288 |pmc=2043413 |doi=10.1136/bmj.39346.495880.AE |url=}}</ref><ref name="Juneja2012">{{cite journal|last1=Juneja|first1=Deven|title=Severe sepsis and septic shock in the elderly: An overview|journal=World Journal of Critical Care Medicine|volume=1|issue=1|year=2012|pages=23|issn=2220-3141|doi=10.5492/wjccm.v1.i1.23}}</ref><ref name="pmid23983879">{{cite journal |vauthors=Karnatovskaia LV, Festic E |title=Sepsis: a review for the neurohospitalist |journal=Neurohospitalist |volume=2 |issue=4 |pages=144–53 |year=2012 |pmid=23983879 |pmc=3726110 |doi=10.1177/1941874412453338 |url=}}</ref>
** Adequate fluid resuscitation is defined as infusion of following at the said rates:
===Physical Examination===
*** 20 to 30 mL/kg of starch,
The physical examination of sepsis shows findings of the causative system as well as some generalized features.<ref name="pmid18158437">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL |title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 |journal=[[Critical Care Medicine]] |volume=36 |issue=1 |pages=296–327 |year=2008 |month=January |pmid=18158437 |doi=10.1097/01.CCM.0000298158.12101.41 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=36&issue=1&spage=296 |accessdate=2012-09-16}}</ref><ref>Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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. Chest. 1992 Jun;101(6):1644-55. PMID 1303622.</ref>
*** 40 to 60 mL/kg of saline solution
===Laboratory Findings===
*** Measured [[pulmonary capillary wedge pressure]] - 12 to 20 mmHg
The international guideline committee for diagnosis of septic shock recommends obtaining appropriate [[culture]]s that may include at least two [[blood cultures]], [[urine]], [[cerebrospinal fluid]], wounds, respiratory secretions, or other body fluid cultures before [[antimicrobial]] therapy is initiated. If such cultures do not cause significant delay in antibiotic administration, then other tests that may be done include [[blood gases]], kidney function tests, [[platelet count]], [[white blood cell count]], [[blood]] differential, [[fibrin]] degradation products, and [[peripheral smear]].<ref name="pmid28444409">{{cite journal |vauthors=Darmon M, Ostermann M, Cerda J, Dimopoulos MA, Forni L, Hoste E, Legrand M, Lerolle N, Rondeau E, Schneider A, Souweine B, Schetz M |title=Diagnostic work-up and specific causes of acute kidney injury |journal=Intensive Care Med |volume= |issue= |pages= |year=2017 |pmid=28444409 |doi=10.1007/s00134-017-4799-8 |url=}}</ref><ref name="pmid23983879">{{cite journal |vauthors=Karnatovskaia LV, Festic E |title=Sepsis: a review for the neurohospitalist |journal=Neurohospitalist |volume=2 |issue=4 |pages=144–53 |year=2012 |pmid=23983879 |pmc=3726110 |doi=10.1177/1941874412453338 |url=}}</ref>
*** [[Central venous pressure]] of 8 to 12 mmHg
* Maintenance of the systemic mean blood pressure of >60 mmHg or >80 mmHg (in hypertensives) despite adequate fluid resuscitation requires
** [[Dopamine]] > 5 mcg/kg/min
** [[Norepinephrine]] < 0.25 mcg/kg/min
** [[Epinephrine]] < 0.25 mcg/kg/min
==Refractory septic shock==
[[Refractory Septic shock]] is defined as [[sepsis]] with refractory arterial [[hypotension]] and maintenance of the systemic mean blood pressure of >60 mmHg or >80 mmHg (in hypertensives) despite adequate fluid resuscitation requires
** [[Dopamine]] > 15 mcg/kg/min
** [[Norepinephrine]] > 0.25 mcg/kg/min
** [[Epinephrine]] > 0.25 mcg/kg/min
** Adequate fluid resuscitation is defined as infusion of following at the said rates:
*** 20 to 30 mL/kg of starch,
*** 40 to 60 mL/kg of saline solution
*** Measured [[pulmonary capillary wedge pressure]] - 12 to 20 mmHg
*** [[Central venous pressure]] of 8 to 12 mmHg
==Multiple organ dysfunction syndrome==
* It is defined as a progressive organ dysfunction that require interventions for maintenance of homeostasis.
* It is the most severe manifestation of either SIRS or sepsis continuum.
* Primary MODS can be directly connected to the source of infection. However, secondary MODS occurs as a result of host response to the primary insult.
* Parameters used to judge MODS are:
** Liver - Serum bilirubin
** Nervous system - Glasgow coma scale
** Hematology - Platelet count
** Renal - Serum creatinine
** Respiratory - PO2/FiO2 ratio
** Cardiovascular - Pressure-adjusted heart rate = Heart rate multiplied by the ratio of central venous pressure and mean arterial pressure


==Neonatal sepsis==
===Chest X Ray===
The criteria for diagnosing an adult with sepsis do not apply to infants under one month of age ([[neonatal sepsis]]). In infants, only the presence of infection plus a "constellation" of signs and symptoms consistent with the systemic response to infection are required for diagnosis.
There are no specific chest X-ray findings associated with sepsis but may show the features consistent with the primary source of [[infection]].


==Systemic Inflammatory Response Syndrome <ref name="pmid18158437">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL |title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 |journal=[[Critical Care Medicine]] |volume=36 |issue=1 |pages=296–327 |year=2008 |month=January |pmid=18158437 |doi=10.1097/01.CCM.0000298158.12101.41 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=36&issue=1&spage=296 |accessdate=2012-09-16}}</ref>, <ref>Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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. Chest. 1992 Jun;101(6):1644-55. PMID 1303622.</ref>==
===CT===
Criteria for SIRS were agreed in 1992.<ref>{{cite journal |author= |title=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 |journal=Crit. Care Med. |volume=20 |issue=6 |pages=864-74 |year=1992 |pmid=1597042 |doi=}}</ref> SIRS can be diagnosed when two or more of the following are present<ref name=tslotou>Tslotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005 Mar;11(3):RA76-85. PMID 15735579. [http://www.medscimonit.com/pub/vol_11/no_3/4318.pdf Full Text].</ref>:
There are no specific CT findings associated with sepsis but may show the features consistent with the primary source of [[infection]].
* [[Heart rate]] > 90 beats per minute
* [[Temperature]] < 36 (96.8 °F) or > 38 °C (100.4 °F)
* [[Tachypnea]] > 20 breaths per minute or, on [[blood gas]], a P<sub>a</sub>CO<sub>2</sub> < 32 mm Hg
* [[White blood cell]] count < 4000 cells/mm³ or > 12000 cells/mm³ (< 4 x 10<sup>9</sup> or > 12 x 10<sup>9</sup> cells/[[litre|L]]), or > 10% band forms (immature white blood cells / bandemia).


==Severe SIRS==
===MRI===
* When two or more of the systemic inflammatory response syndrome criteria are met without evidence of infection, patients may be diagnosed simply with "[[SIRS]]."
There are no specific MRI findings associated with sepsis but may show the features consistent with the primary source of [[infection]].
* Patients with SIRS and acute organ dysfunction may be termed "severe SIRS."


==Difference between SIRS and sepsis==
===Echocardiography or Ultrasound===
SIRS with a suspected or proven infection is called [[sepsis]].  
There are no specific echocardiography or ultrasound finidngs associated with sepsis but may show the features consistent with the primary source of [[infection]].


Simply stated:  
==Treatment==
:'''SIRS + infection = sepsis'''
===Medical Therapy===
According to IDSA, "Surviving Sepsis Campaign" guidelines, the management protocol for sepsis include screening for high-risk patients; taking bacterial cultures soon after the patient arrived at the hospital; starting patients on broad-spectrum intravenous [[antibiotic]] therapy before the results of the cultures are obtained; identifying the source of [[infection]] and taking steps to control it (e.g., [[abscess]] drainage); administering intravenous fluids to correct a loss or decrease in blood volume; and maintaining glycemic (blood sugar) control.<ref name="urlProducts - Data Briefs - Number 62 - June 2011">{{cite web |url=http://www.cdc.gov/nchs/data/databriefs/db62.htm |title=Products - Data Briefs - Number 62 - June 2011 |format= |work= |accessdate=2012-09-17}}</ref><ref name="pmid2826633">{{cite journal |author=Wiedermann CJ, Adamson IY, Pert CB, Bowden DH |title=Enhanced secretion of immunoreactive bombesin by alveolar macrophages exposed to silica |journal=[[Journal of Leukocyte Biology]] |volume=43 |issue=2 |pages=99–103|pmid=2826633 |doi= |url=http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=2826633 |accessdate=2012-09-17}}</ref><ref name="pmid23353941">{{cite journal| author=Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM et al.| title=Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. | journal=Crit Care Med | year= 2013 | volume= 41 | issue= 2 | pages= 580-637 | pmid=23353941 | doi=10.1097/CCM.0b013e31827e83af | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23353941  }} </ref><ref name="pmid23361625">{{cite journal| author=Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM et al.| title=Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. | journal=Intensive Care Med | year= 2013 | volume= 39 | issue= 2 | pages= 165-228 | pmid=23361625 | doi=10.1007/s00134-012-2769-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23361625  }} </ref><ref name="pmid26109396">{{cite journal| author=Rhodes A, Phillips G, Beale R, Cecconi M, Chiche JD, De Backer D et al.| title=The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). | journal=Intensive Care Med | year= 2015 | volume= 41 | issue= 9 | pages= 1620-8 | pmid=26109396 | doi=10.1007/s00134-015-3906-y | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26109396  }} </ref><ref name="pmid25275252">{{cite journal| author=Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R et al.| title=Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. | journal=Crit Care Med | year= 2015 | volume= 43 | issue= 1 | pages= 3-12 | pmid=25275252 | doi=10.1097/CCM.0000000000000723 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25275252  }} </ref><ref name="pmid23631750">{{cite journal| author=Miller RR, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR et al.| title=Multicenter implementation of a severe sepsis and septic shock treatment bundle. | journal=Am J Respir Crit Care Med | year= 2013 | volume= 188 | issue= 1 | pages= 77-82 | pmid=23631750 | doi=10.1164/rccm.201212-2199OC | pmc=PMC3735248 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23631750  }} </ref><ref name="pmid23631750"/><ref name="pmid27085369">{{cite journal| author=Leisman D, Wie B, Doerfler M, Bianculli A, Frances Ward M, Akerman M et al.| title=Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay. | journal=Ann Emerg Med | year= 2016 | volume=  | issue=  | pages=  | pmid=27085369 | doi=10.1016/j.annemergmed.2016.02.044 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27085369  }} </ref><ref name="pmid26573784">{{cite journal| author=Narayanan N, Gross AK, Pintens M, Fee C, MacDougall C| title=Effect of an electronic medical record alert for severe sepsis among ED patients. | journal=Am J Emerg Med | year= 2016 | volume= 34 | issue= 2 | pages= 185-8 | pmid=26573784 | doi=10.1016/j.ajem.2015.10.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26573784  }} </ref><ref name="pmid25867906">{{cite journal| author=Semler MW, Weavind L, Hooper MH, Rice TW, Gowda SS, Nadas A et al.| title=An Electronic Tool for the Evaluation and Treatment of Sepsis in the ICU: A Randomized Controlled Trial. | journal=Crit Care Med | year= 2015 | volume= 43 | issue= 8 | pages= 1595-602 | pmid=25867906 | doi=10.1097/CCM.0000000000001020 | pmc=PMC4506222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25867906  }} </ref><ref>GitHub Contributors. Sepsis alerts to improve diagnosis: a living systematic review. GitHub. Available at https://github.com/openMetaAnalysis/Sepsis-alerts-to-improve-diagnosis/blob/master/README.md. Accessed March 15, 2017.</ref><ref name="pmid27229639">{{cite journal| author=Harrison AM, Gajic O, Pickering BW, Herasevich V| title=Development and Implementation of Sepsis Alert Systems. | journal=Clin Chest Med | year= 2016 | volume= 37 | issue= 2 | pages= 219-29 | pmid=27229639 | doi=10.1016/j.ccm.2016.01.004 | pmc=4884325 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27229639  }} </ref>


==See also==
===Surgery===
*[[Anaphylactic shock]]
Surgical intervention is not recommended for the management of sepsis
*[[Cardiogenic shock]]
===Prevention===
*[[Neurogenic shock]]
Prevent infections that can lead to sepsis by cleaning scrapes and wounds and getting regular vaccination against infections that cause sepsis can help in the prevention of sepsis.<ref name="urlQ & A | Sepsis | CDC">{{cite web |url=https://www.cdc.gov/sepsis/basic/qa.html |title=Q & A &#124; Sepsis &#124; CDC |format= |work= |accessdate=}}</ref>
*[[Sepsis]]
*[[Shock (medical)|Shock]]
* [[Septic shock]]
*[[Systemic inflammatory response syndrome]] (SIRS)
[[Category:Medical emergencies]]
[[Category:Intensive care medicine]]
[[Category:Causes of death]]
[[Category:Infectious disease]]
[[Category:Emergency medicine]]


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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[[Category:Intensive care medicine]]
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[[Category:Infectious disease]]

Latest revision as of 00:08, 30 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]

Synonyms and keywords: sepsis syndrome; septic shock; septicemia

Overview

Sepsis is a condition characterized by a whole-body inflammatory state caused by infection. Septic shock is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis. It can cause multiple organ failure and death. Its most common victims are children, immunocompromised individuals, and the elderly. This is because their immune systems cannot cope with the infection as well as those of full-grown adults.[1]

Pathophysiology

The immunological response that causes sepsis is a systemic inflammatory response causing widespread activation of inflammation and coagulation pathways. This may progress to dysfunction of the circulatory system and, even under optimal treatment, may result in the multiple organ dysfunction syndrome and eventually death. A subclass of distributive shock, shock refers specifically to decreased tissue perfusion resulting in end-organ dysfunction. Cytokines TNFα, IL-1β, interferon γ, IL-6 released in a large scale inflammatory response results in massive vasodilation, increased capillary permeability, decreased systemic vascular resistance, and hypotension. Hypotension reduces tissue perfusion pressure and thus tissue hypoxia ensues. Finally, in an attempt to offset decreased blood pressure, ventricular dilatation and myocardial dysfunction will occur.[2][3][4][5][6]

Classification

In rough order of severity, these are bacteremia or fungemia; septicemia; sepsis, severe sepsis or sepsis syndrome; septic shock; refractory septic shock; multiple organ dysfunction syndrome, and death.

Causes

The process of infection by bacteria or fungi can result in systemic signs and symptoms that are variously described. The condition develops as a response to certain microbial molecules which trigger the production and release of cellular mediators, such as tumor necrosis factors (TNF); these act to stimulate immune response.[7][8][9]

Differentiating Sepsis from other Diseases

Sepsis must be differentiated from other syndromes presnting with fever, hypotension such as the acute bacterial endocarditis, myocardial ring abscess, subacute bacterial endocarditis and bacterial meningitis.[10][11][12]

Epidemiology and Demographics

The hospitalization rate of those with a principal diagnosis of septicemia or sepsis more than doubled from 2000 through 2008. During the same period, the hospitalization rate for those with septicemia or sepsis as a principal or as a secondary diagnosis increased by 70% from 221 to 377 for every 100,000 people. Reasons for these increases may include an aging population with more chronic illnesses, greater use of invasive procedures, immunosuppressive drugs, chemotherapy, transplantation, and increasing microbial resistance to antibiotics.[13]

Risk Factors

Factors responsible for increased risk of sepsis may include an aging population with more chronic illnesses; greater use of invasive procedures, immunosuppressive drugs, chemotherapy, and transplantation; and increasing microbial resistance to antibiotics. Other patients population at increased risk are ICU admits, immunocompromised, bacteremic, with community acquired pneumonia, and with genetic predisposition.[14][13][13]

Natural History, Complications and Prognosis

There are many complications associated with sepsis, especially because it is a systemic phenomenon. Sepsis is a severe condition, and the prognosis of the patient will depend greatly on the condition and overall health of the patient. Many factors, such as age, hosts immune response, site of infection, type of infection, appropriate antibiotic therapy, and restoration of circulation of perfusion contribute to the overall prognosis.[15][16] [17][18][19][20] [21]

Diagnosis

History and Symptoms

Symptoms of sepsis are often related to the underlying infectious process. When the infection crosses into the bloodstream the resulting symptoms of sepsis occur fever, chills, and rigors, confusion, anxiety, difficulty breathing, fatigue and malaise, nausea and vomiting.[22][23][1]

Physical Examination

The physical examination of sepsis shows findings of the causative system as well as some generalized features.[24][25]

Laboratory Findings

The international guideline committee for diagnosis of septic shock recommends obtaining appropriate cultures that may include at least two blood cultures, urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluid cultures before antimicrobial therapy is initiated. If such cultures do not cause significant delay in antibiotic administration, then other tests that may be done include blood gases, kidney function tests, platelet count, white blood cell count, blood differential, fibrin degradation products, and peripheral smear.[26][1]

Chest X Ray

There are no specific chest X-ray findings associated with sepsis but may show the features consistent with the primary source of infection.

CT

There are no specific CT findings associated with sepsis but may show the features consistent with the primary source of infection.

MRI

There are no specific MRI findings associated with sepsis but may show the features consistent with the primary source of infection.

Echocardiography or Ultrasound

There are no specific echocardiography or ultrasound finidngs associated with sepsis but may show the features consistent with the primary source of infection.

Treatment

Medical Therapy

According to IDSA, "Surviving Sepsis Campaign" guidelines, the management protocol for sepsis include screening for high-risk patients; taking bacterial cultures soon after the patient arrived at the hospital; starting patients on broad-spectrum intravenous antibiotic therapy before the results of the cultures are obtained; identifying the source of infection and taking steps to control it (e.g., abscess drainage); administering intravenous fluids to correct a loss or decrease in blood volume; and maintaining glycemic (blood sugar) control.[13][27][28][29][30][31][32][32][33][34][35][36][37]

Surgery

Surgical intervention is not recommended for the management of sepsis

Prevention

Prevent infections that can lead to sepsis by cleaning scrapes and wounds and getting regular vaccination against infections that cause sepsis can help in the prevention of sepsis.[38]

References

  1. ↑ 1.0 1.1 1.2 Karnatovskaia LV, Festic E (2012). "Sepsis: a review for the neurohospitalist". Neurohospitalist. 2 (4): 144–53. doi:10.1177/1941874412453338. PMC 3726110. PMID 23983879.
  2. ↑ Minasyan H (2017). "Sepsis and septic shock: Pathogenesis and treatment perspectives". J Crit Care. 40: 229–242. doi:10.1016/j.jcrc.2017.04.015. PMID 28448952.
  3. ↑ Pop-Began V, Păunescu V, Grigorean V, Pop-Began D, Popescu C (2014). "Molecular mechanisms in the pathogenesis of sepsis". J Med Life. 7 Spec No. 2: 38–41. PMC 4391358. PMID 25870671.
  4. ↑ Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG (2011). "The pathogenesis of sepsis". Annu Rev Pathol. 6: 19–48. doi:10.1146/annurev-pathol-011110-130327. PMC 3684427. PMID 20887193.
  5. ↑ Cunneen J, Cartwright M (2004). "The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment". AACN Clin Issues. 15 (1): 18–44. PMID 14767363.
  6. ↑ Chaudhry H, Zhou J, Zhong Y, Ali MM, McGuire F, Nagarkatti PS, Nagarkatti M (2013). "Role of cytokines as a double-edged sword in sepsis". In Vivo. 27 (6): 669–84. PMC 4378830. PMID 24292568.
  7. ↑ Annane D, Aegerter P, Jars-Guincestre MC, Guidet B (2003). "Current epidemiology of septic shock: the CUB-Réa Network". Am. J. Respir. Crit. Care Med. 168 (2): 165–72. doi:10.1164/rccm.2201087. PMID 12851245.
  8. ↑ Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C (2006). "An intervention to decrease catheter-related bloodstream infections in the ICU". N. Engl. J. Med. 355 (26): 2725–32. doi:10.1056/NEJMoa061115. PMID 17192537.
  9. ↑ Mayr FB, Yende S, Angus DC (2014). "Epidemiology of severe sepsis". Virulence. 5 (1): 4–11. doi:10.4161/viru.27372. PMC 3916382. PMID 24335434.
  10. ↑ Machowicz R, Janka G, Wiktor-Jedrzejczak W (2017). "Similar but not the same: Differential diagnosis of HLH and sepsis". Crit. Rev. Oncol. Hematol. 114: 1–12. doi:10.1016/j.critrevonc.2017.03.023. PMID 28477737.
  11. ↑ Parrillo, Joseph E.; Ayres, Stephen M. (1984). Major issues in critical care medicine. Baltimore: William Wilkins. ISBN 0-683-06754-0.
  12. ↑ Judith S. Hochman, E. Magnus Ohman (2009). Cardiogenic Shock. Wiley-Blackwell. ISBN 9781405179263.
  13. ↑ 13.0 13.1 13.2 13.3 "Products - Data Briefs - Number 62 - June 2011". Retrieved 2012-09-17.
  14. ↑ Ballouz T, Aridi J, Afif C, Irani J, Lakis C, Nasreddine R, Azar E (2017). "Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia". Front Cell Infect Microbiol. 7: 156. doi:10.3389/fcimb.2017.00156. PMC 5415554. PMID 28523249.
  15. ↑ Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL; et al. (2016). "The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock". Am J Respir Crit Care Med. 193 (3): 281–7. doi:10.1164/rccm.201505-0995OC. PMC 4803059. PMID 26398704.
  16. ↑ Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R (2015). "Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis". N Engl J Med. doi:10.1056/NEJMoa1415236. PMID 25776936.
  17. ↑ Capp R, Horton CL, Takhar SS, Ginde AA, Peak DA, Zane R; et al. (2015). "Predictors of Patients Who Present to the Emergency Department With Sepsis and Progress to Septic Shock Between 4 and 48 Hours of Emergency Department Arrival". Crit Care Med. doi:10.1097/CCM.0000000000000861. PMID 25668750.
  18. ↑ Williams JM, Greenslade JH, Chu K, Brown AF, Lipman J (2016). "Severity Scores in Emergency Department Patients With Presumed Infection: A Prospective Validation Study". Crit Care Med. 44 (3): 539–47. doi:10.1097/CCM.0000000000001427. PMID 26901543.
  19. ↑ Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW (2003). "Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule". Crit. Care Med. 31 (3): 670–5. doi:10.1097/01.CCM.0000054867.01688.D1. PMID 12626967.
  20. ↑ Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A; et al. (2016). "Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. 315 (8): 762–74. doi:10.1001/jama.2016.0288. PMID 26903335.
  21. ↑ GitHub Contributors. Prognosticating in sepsis with decision aids: a living systematic review. GitHub. Available at https://github.com/openMetaAnalysis/Sepsis-prognosticating-with-decision-aids/blob/master/README.md. Accessed January 26, 2017.
  22. ↑ Lever A, Mackenzie I (2007). "Sepsis: definition, epidemiology, and diagnosis". BMJ. 335 (7625): 879–83. doi:10.1136/bmj.39346.495880.AE. PMC 2043413. PMID 17962288.
  23. ↑ Juneja, Deven (2012). "Severe sepsis and septic shock in the elderly: An overview". World Journal of Critical Care Medicine. 1 (1): 23. doi:10.5492/wjccm.v1.i1.23. ISSN 2220-3141.
  24. ↑ Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008". Critical Care Medicine. 36 (1): 296–327. doi:10.1097/01.CCM.0000298158.12101.41. PMID 18158437. Retrieved 2012-09-16. Unknown parameter |month= ignored (help)
  25. ↑ Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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. Chest. 1992 Jun;101(6):1644-55. PMID 1303622.
  26. ↑ Darmon M, Ostermann M, Cerda J, Dimopoulos MA, Forni L, Hoste E, Legrand M, Lerolle N, Rondeau E, Schneider A, Souweine B, Schetz M (2017). "Diagnostic work-up and specific causes of acute kidney injury". Intensive Care Med. doi:10.1007/s00134-017-4799-8. PMID 28444409.
  27. ↑ Wiedermann CJ, Adamson IY, Pert CB, Bowden DH. "Enhanced secretion of immunoreactive bombesin by alveolar macrophages exposed to silica". Journal of Leukocyte Biology. 43 (2): 99–103. PMID 2826633. Retrieved 2012-09-17.
  28. ↑ Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Crit Care Med. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. PMID 23353941.
  29. ↑ Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012". Intensive Care Med. 39 (2): 165–228. doi:10.1007/s00134-012-2769-8. PMID 23361625.
  30. ↑ Rhodes A, Phillips G, Beale R, Cecconi M, Chiche JD, De Backer D; et al. (2015). "The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study)". Intensive Care Med. 41 (9): 1620–8. doi:10.1007/s00134-015-3906-y. PMID 26109396.
  31. ↑ Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R; et al. (2015). "Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study". Crit Care Med. 43 (1): 3–12. doi:10.1097/CCM.0000000000000723. PMID 25275252.
  32. ↑ 32.0 32.1 Miller RR, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR; et al. (2013). "Multicenter implementation of a severe sepsis and septic shock treatment bundle". Am J Respir Crit Care Med. 188 (1): 77–82. doi:10.1164/rccm.201212-2199OC. PMC 3735248. PMID 23631750.
  33. ↑ Leisman D, Wie B, Doerfler M, Bianculli A, Frances Ward M, Akerman M; et al. (2016). "Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay". Ann Emerg Med. doi:10.1016/j.annemergmed.2016.02.044. PMID 27085369.
  34. ↑ Narayanan N, Gross AK, Pintens M, Fee C, MacDougall C (2016). "Effect of an electronic medical record alert for severe sepsis among ED patients". Am J Emerg Med. 34 (2): 185–8. doi:10.1016/j.ajem.2015.10.005. PMID 26573784.
  35. ↑ Semler MW, Weavind L, Hooper MH, Rice TW, Gowda SS, Nadas A; et al. (2015). "An Electronic Tool for the Evaluation and Treatment of Sepsis in the ICU: A Randomized Controlled Trial". Crit Care Med. 43 (8): 1595–602. doi:10.1097/CCM.0000000000001020. PMC 4506222. PMID 25867906.
  36. ↑ GitHub Contributors. Sepsis alerts to improve diagnosis: a living systematic review. GitHub. Available at https://github.com/openMetaAnalysis/Sepsis-alerts-to-improve-diagnosis/blob/master/README.md. Accessed March 15, 2017.
  37. ↑ Harrison AM, Gajic O, Pickering BW, Herasevich V (2016). "Development and Implementation of Sepsis Alert Systems". Clin Chest Med. 37 (2): 219–29. doi:10.1016/j.ccm.2016.01.004. PMC 4884325. PMID 27229639.
  38. ↑ "Q & A | Sepsis | CDC".

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