Sepsis is perhaps the primary disease of critical care. It has an incredibly high incidence and significant mortality and morbidity associated with it. Despite this, our understanding of it is still evolving, as it our knowledge about the best way to manage it.
A major challenge with the academic approach to sepsis is its heterogenous nature, and this has also manifested itself in the difficulty in defining it clearly. The international definitions have evolved over the years since it was first defined. The initial definitions originated from the ACCP/SCCM consensus meetings in 1991 and 2001 relate to the SIRS criteria.
As such, sepsis had previously been defined as: The Systemic Inflammatory Response Syndrome (SIRS) arising as a result of infection. SIRS was defined by the presence of 2 or more of:
Temperature <36 or >38 degrees celsius
Heart rate > 90bpm
Hyperventilation: a respiratory rate >20 bpm or pCO2 32 mmHg
White blood cell count >12,000 cell/microL or <4000/microL
There were also definitions for subgroups of sepsis: Severe sepsis - sepsis associated with organ dysfunction Septic shock - sepsis induced hypotension persisting despite adequate fluid resuscitation.
This has been updated with the latest definition (Sepsis 3) by the ESICM/SCCM sepsis redefinition task force, published in 2016.
This defines sepsis as - a life-threatening organ dysfunction due to a dysregulated response to infection. Objectively, this is defined as an increase in Sequential Organ Failure Assessment (SOFA) Score of 2 or more points in the presence of presumed infection. This definition is used to help identify those patients with ‘a bad infection’ as this definition imparts a mortality of at least 10%.
Septic shock is a subset of sepsis where underlying circulatory and cellular/metabolic dysfunction are profound enough to significantly increase mortality. This can be recognised by the need for vasopressors to maintain a MAP >65 mmHg despite adequate fluid resuscitation, and by having a lactate >2 mmol/L. In this group of patients, hospital mortality is greater than 40%. Patients needing vasopressors or having an elevated lactate are both at an increased risk of mortality, but not as high as those with both, as above.
In essence, sepsis = infection + badness.
There still is debate about the use of these definition, primarily focusing on their respective sensitivity and specificity in different scenarios. The problem arises from the fact that sepsis is a syndrome without a gold standard test to judge definitions against. The Sepsis-3 authors recognised that the SIRS definition of sepsis was unhelpful, as it primarily focused on the inflammatory features which represent the host’s response to infection. As such, these features are common in multiple patients with multiple different presentations who never have poor outcomes (poor discriminant validity), and are commonly adaptive. And yet, they are also absent in a decent proportion of critically ill patients with sepsis (poor concurrent validity), as the excessive inflammatory response is not the only dysregulated host response possible. The authors felt that the definition of sepsis had to represent a ‘bad infection’, where there was a significant greater risk to the patient, and therefore a greater urgency for management.
Overall, I think that the definition is useful in aiding our understanding that sepsis is different from an uncomplicated infection, and is associated with a significantly higher mortality rate which warrant swift and aggressive medical care.
The Sepsis-3 group introduced a novel screening tool for detecting these patients, called qSOFA (the q standing for quick). They describe that the following 3 features, when in the presence of a presumed infection, are indicators of a poor outcome:
Respiratory rate >/=22 bpm
Altered mental state
SBP < 100 mmHg
If any of these 3 are present, then it should trigger a consideration of sepsis as the cause of that patient’s presentation. This is in essence a quick look for the most detectable signs of organ dysfunction, either if a respirator/metabolic, neurological or cardiovascular nature. They described how this performed similarly to SIRS criteria in this screening role. Many clinical institutions still screen for sepsis using the SIRS criteria. Indeed, the qSOFA score is still await further validation testing.
Last updated: 22nd March 2017 Tom Heaton
Links & References
Singer, M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016. 315(8): 801-810