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]

Synonyms and keywords: sepsis syndrome; septic shock; septicemia

Overview

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.

Diagnostic Criteria

SIRS

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:

• 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 P_aCO₂ < 32 mm Hg

Sepsis

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

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

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:

• 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

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

• 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

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.

Identifying sepsis cases on a large scale for organizational improvement

Method	Details	Gold standard	Correlation(as reported)	Variance (as calculated by correlation^2)
Darby administrative	Claims (including comorbid diagnoses), demographics for 2012.	Same criteria for 2013	0.53	28%
Darby administrative plus laboratory	Claims (including comorbid diagnoses), demographics. Pro-BNP, albumin, troponin, bilirubin, BUN, and sodium for 2012	Same criteria for 2013	0.93	86%
Rhee administrative	administrative definitions using explicit sepsis codes	CDC ASE mortality rates for same year (unadjusted)	0.61	37%
Rhee administrative	administrative definitions using implicit sepsis codes	CDC ASE mortality rates for same year (unadjusted)	0.69	48%
Rhee administrative	administrative definitions using explicit sepsis codes	CDC ASE mortality rates for same year (adjusteded)	0.68	47%
Rhee administrative	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.

• 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.
• In another study, automated EHR data performed well compared to physician reviews of charts.
• In EHR data, using SIRS or QSOFA alone is not as good as combining these.
• Using administrative data is much improve if laboratory data is included. Ther Pearson correlation coefficient improved from 0.53 to 0.93. This is equivalent to increasing the proportion of variance explained from 28% to 86%.
• Subsequent work by Rhee improved correlation with clinical data

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

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".