Sepsis diagnostic criteria

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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]; Parth Vikram Singh, MBBS[3]

Synonyms and keywords: sepsis syndrome; septic shock; septicemia

## Overview[edit | edit source]

The 1992 statement from the ACCP/ SCCM Consensus Conference introduced into common parlance the systemic inflammatory response syndrome (SIRS) which represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response. Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection, whereas severe sepsis refers to sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion. Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.[1][2][3][4][5]

## Diagnostic Criteria[edit | edit source]

### SIRS[edit | edit source]

SIRS criteria identify 88% of patients who have severe sepsis (infection plus organ failure). 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:[6][7][8]

* Hypotension
* 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 PaCO2 < 32 mm Hg

### Sepsis[edit | edit source]

Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Diagnostic criteria for sepsis are as follows:

Sepsis = infection (documented or suspected) and some of the following:

General variables

* Fever (>38.3°C)
* Hypothermia (core temperature <36°C)
* Heart rate >90/min–1 or more than two SD above the normal value for age
* Tachypnea
* Altered mental status
* Significant edema or positive fluid balance (>20 mL/kg over 24 hr)
* Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes

Inflammatory variables

* Leukocytosis (WBC count >12,000 μL–1)
* Leukopenia (WBC count <4000 μL–1)
* Normal WBC count with greater than 10% immature forms
* Plasma C-reactive protein more than two SD above the normal value
* Plasma procalcitonin more than two SD above the normal value

Hemodynamic variables

* Arterial hypotension (SBP <90mm Hg, MAP <70mm Hg, or an SBP decrease >40mm Hg in adults or less than two SD below normal for age)

Organ dysfunction variables

* Arterial hypoxemia (Pao2/Fio2 <300)
* Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
* Creatinine increase >0.5mg/dL or 44.2 μmol/L
* Coagulation abnormalities (INR >1.5 or aPTT >60 s)
* Ileus (absent bowel sounds)
* Thrombocytopenia (platelet count <100,000 μL–1)
* Hyperbilirubinemia (plasma total bilirubin >4mg/dL or 70 μmol/L)

Tissue perfusion variables

* Hyperlactatemia (>1 mmol/L)
* Decreased capillary refill or mottling

### Severe Sepsis[edit | edit source]

Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion.

Severe sepsis = sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection)

* Sepsis-induced hypotension (SBP of <90 mm Hg or MAP <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below normal for age in the absence of other causes of hypotension)
* Lactate above upper limits laboratory normal
* Urine output <0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation
* Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source
* Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source
* Creatinine >2.0 mg/dL (176.8 μmol/L)
* Bilirubin >2 mg/dL (34.2 μmol/L)
* Platelet count <100,000 μL
* Coagulopathy (international normalized ratio >1.5)

### Septic Shock[edit | edit source]

Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.

* Septic shock in adult patients refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.
* Septic shock in pediatric patients is defined as 1) a suspected infection manifested by hypothermia or hyperthermia, and 2) clinical signs of inadequate tissue perfusion including any of the following:[9]

* Decreased or altered mental status
* Decreased urine output 􏰁<1 ml/kg/h
* Bounding peripheral pulses (warm shock)
* Diminished peripheral pulses compared with central pulses (cold shock)
* Wide pulse pressure (warm shock)
* Prolonged capillary refill >􏰃2 seconds (cold shock)
* Flash capillary refill (warm shock)
* Mottled or cool extremities (cold shock)

* Septic shock in newborns manifests as tachycardia, respiratory distress, poor feeding, poor tone, poor color, tachypnea, diarrhea, or reduced perfusion, particularly in the presence of a maternal history of chorioamnionitis or prolonged rupture of membranes.

### Refractory Septic Shock[edit | edit source]

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 the 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[edit | edit source]

* 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[edit | edit source]

The criteria for diagnosing an adult with sepsis does 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.

### Pediatrics Sepsis[edit | edit source]

In pediatrics, the Phoenix 2024 criteria—also known as Phoenix Pediatric Sepsis (PPS)—are now recommended to define sepsis and septic shock. These criteria apply to children aged 1 month to <18 years and aim to identify life-threatening organ dysfunction due to infection.[10]

Sepsis with Suspected/Confirmed Infection can be identified as a Phoenix Score of at least 2 points:

Respiratory (0-3 points)

* 0 Points: PaO2:FiO2 > 400 or Sp02:Fi02 > 292 (only calculated if Sp02 </=97%)
* 1 Point: PaO2:FiO2 < 400 on any Respiratory Support or Sp02:Fi02 < 292 (on support)
* 2 Points: PaO2:FiO2 100 – 200 on Mechanical Ventilation or Sp02:Fi02 148-220 on IMV
* 3 Points: PaO2:FiO2 < 100 or Sp02:Fi02 <148

Cardiovascular (0-6 points)

* 0 Points: No Vasoactive Medication, Lactate < 5 mmol/L
* 1 Point each: 1 Vasoactive Medication, Lactate 5-10.9 mmol/L
* 2 Points each: >/= 2 Vasoactive Medications, Lactate >/ 11 mmol/L

Aged-Based Mean Arterial Pressure (mmHg) (0-2 points)  | AGE  | 0 Points  | 1 Point  | 2 Points

|
|
|

< 1 month  | >30 mmHg  | 17-30 mmHg  | < 17 mmHg
1-11 mos  | >38 mmHg  | 25-38 mmHg  | < 25 mmHg
1 – < 2yrs  | >43 mmHg  | 31-43 mmHg  | <31 mmHg
2 – <5 yrs  | >44 mmHg  | 32-44 mmHg  | <32 mmHg
5 – < 12yrs  | >48 mmHg  | 36-48 mmHg  | <36 mmHg
12 – 17 yrs  | >51 mmHg  | 38-51 mmHg  | <38 mmHg
Coagulation (0-1 points)

* 0 Points: Platelets >/= 100×10^3, INR </= 1.3, D-Dimer </= 2 mg/L, Fibrinogen >/= 100 mg/dL
* 1 Point: Platelets < 100×10^3, INR > 1.3, D-Dimer > 2 mg/L, Fibrinogen < 100 mg/dL

Neurological (0-2 points)

* 0 Points: GCS > 10, Pupils Reactive
* 1 Point: GCS </= 10
* 2 Points: Fixed Pupils

## Identifying sepsis cases on a large scale for organizational improvement[edit | edit source]

Method  | Details  | Gold standard  | Correlation(as reported)  | Variance (as calculated by correlation^2)

|
|
|
|

Darby administrative[11] | Claims (including comorbid diagnoses), demographics for 2012.  | Same criteria for 2013  | 0.53  | 28%
Darby administrative plus laboratory[11] | Claims (including comorbid diagnoses), demographics. Pro-BNP, albumin, troponin, bilirubin, BUN, and sodium for 2012  | Same criteria for 2013  | 0.93  | 86%
Rhee administrative[12] | administrative definitions using explicit sepsis codes  | CDC ASE mortality rates for same year (unadjusted)  | 0.61  | 37%
Rhee administrative[12] | administrative definitions using implicit sepsis codes  | CDC ASE mortality rates for same year (unadjusted)  | 0.69  | 48%
Rhee administrative[12] | administrative definitions using explicit sepsis codes  | CDC ASE mortality rates for same year (adjusteded)  | 0.68  | 47%
Rhee administrative[12] | administrative definitions using implicit sepsis codes  | CDC ASE mortality rates for same year (adjusteded)  | 0.70  | 49%

Variation in the identification of sepsis using administrative and claims data, including for the identification of septic shock, has been documented by Rhee et al[13].

* In one example, claims data was compared to clinical data extracted from the electronic health record for detecting sepsis-3 and the claims data performed with much variation in quality[13].
* In another study, automated EHR data performed well compared to physician reviews of charts[14].
* In EHR data, using SIRS or QSOFA alone is not as good as combining these[15].
* Using administrative data is much improve if laboratory data is included. Ther Pearson correlation coefficient improved from 0.53 to 0.93[11]. This is equivalent to increasing the proportion of variance explained from 28% to 86%.
* Subsequent work by Rhee improved correlation with clinical data[12]

The stability of administrative data over time has been used to argue for the validity of administrative data[11].

Variation in reported cases to the New York State Department of Health (NYSDOH), as part of Rory's Regulations, may be "driven more by under-recognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement"[16].

## References[edit | edit source]

1. ↑ "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". Critical Care Medicine. 20 (6): 864–874. 1992-06. ISSN 0090-3493. PMID 1597042. Check date values in: `|date=` (help)
2. ↑ Levy, Mitchell M.; Fink, Mitchell P.; Marshall, John C.; Abraham, Edward; Angus, Derek; Cook, Deborah; Cohen, Jonathan; Opal, Steven M.; Vincent, Jean-Louis; Ramsay, Graham; SCCM/ESICM/ACCP/ATS/SIS (2003-04). "2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference". Critical Care Medicine. 31 (4): 1250–1256. doi:10.1097/01.CCM.0000050454.01978.3B. ISSN 0090-3493. PMID 12682500. Check date values in: `|date=` (help)
3. ↑ Dellinger, R. Phillip; Carlet, Jean M.; Masur, Henry; Gerlach, Herwig; Calandra, Thierry; Cohen, Jonathan; Gea-Banacloche, Juan; Keh, Didier; Marshall, John C.; Parker, Margaret M.; Ramsay, Graham; Zimmerman, Janice L.; Vincent, Jean-Louis; Levy, Mitchell M.; Surviving Sepsis Campaign Management Guidelines Committee (2004-03). "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock". Critical Care Medicine. 32 (3): 858–873. ISSN 0090-3493. PMID 15090974. Check date values in: `|date=` (help)
4. ↑ Dellinger, R. Phillip; Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine (2008-01). "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. ISSN 1530-0293. PMID 18158437. Check date values in: `|date=` (help)
5. ↑ Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborn, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Konrad; Kleinpell, Ruth M.; Angus, Derek C.; Deutschman, Clifford S.; Machado, Flavia R.; Rubenfeld, Gordon D.; Webb, Steven A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup (2013-02). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Critical Care Medicine. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. ISSN 1530-0293. PMID 23353941. Check date values in: `|date=` (help)
6. ↑ 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)CS1 maint: Multiple names: authors list (link)
7. ↑ 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.
8. ↑ 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.CS1 maint: Multiple names: authors list (link)
9. ↑ Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; Decaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazuzta, Jose; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Kache, Saraswati; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron (2009-02). "Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine". Critical Care Medicine. 37 (2): 666–688. doi:10.1097/CCM.0b013e31819323c6. ISSN 1530-0293. PMID 19325359. Check date values in: `|date=` (help)
10. ↑ Meyer NJ, Prescott HC (December 2024). "Sepsis and Septic Shock". N Engl J Med. 391 (22): 2133–2146. doi:10.1056/NEJMra2403213. PMID 39774315 Check `|pmid=` value (help).
11. ↑ 11.0 11.1 11.2 11.3 Darby JL, Davis BS, Barbash IJ, Kahn JM (2019). "An administrative model for benchmarking hospitals on their 30-day sepsis mortality". BMC Health Serv Res. 19 (1): 221. doi:10.1186/s12913-019-4037-x. PMC 6458755. PMID 30971244.CS1 maint: Multiple names: authors list (link)
12. ↑ 12.0 12.1 12.2 12.3 12.4 Rhee C, Li Z, Wang R, Song Y, Kadri SS, Septimus EJ; et al. (2020). "Impact of Risk Adjustment Using Clinical vs Administrative Data on Hospital Sepsis Mortality Comparisons". Open Forum Infect Dis. 7 (6): ofaa213. doi:10.1093/ofid/ofaa213. PMC 7320830 Check `|pmc=` value (help). PMID 32617377 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
13. ↑ 13.0 13.1 Rhee C, Jentzsch MS, Kadri SS, Seymour CW, Angus DC, Murphy DJ; et al. (2019). "Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons". Crit Care Med. 47 (4): 493–500. doi:10.1097/CCM.0000000000003554. PMC 7970408 Check `|pmc=` value (help). PMID 30431493.CS1 maint: Multiple names: authors list (link)
14. ↑ Valik JK, Ward L, Tanushi H, Müllersdorf K, Ternhag A, Aufwerber E; et al. (2020). "Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population: observational study using electronic health records data". BMJ Qual Saf. 29 (9): 735–745. doi:10.1136/bmjqs-2019-010123. PMC 7467502 Check `|pmc=` value (help). PMID 32029574 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
15. ↑ Prasad PA, Fang MC, Abe-Jones Y, Calfee CS, Matthay MA, Kangelaris KN (2020). "Time to Recognition of Sepsis in the Emergency Department Using Electronic Health Record Data: A Comparative Analysis of Systemic Inflammatory Response Syndrome, Sequential Organ Failure Assessment, and Quick Sequential Organ Failure Assessment". Crit Care Med. 48 (2): 200–209. doi:10.1097/CCM.0000000000004132. PMC 7494056 Check `|pmc=` value (help). PMID 31939788.CS1 maint: Multiple names: authors list (link)
16. ↑ Xiaoqiang W, Vennison SJ, Huirong L, Ben-Dov E, Zaritsky A, Boussiba S (1997). "Mosquito larvicidal activity of transgenic Anabaena strain PCC 7120 expressing combinations of genes from Bacillus thuringiensis subsp. israelensis". Appl Environ Microbiol. 63 (12): 4971–4. doi:10.1128/AEM.63.12.4971-4974.1997. PMC 168827. PMID 9406420.CS1 maint: Multiple names: authors list (link)

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