Surgical Critical Care

The Sepsis Six Samurai – Part 1

Support bacteria. It’s the only culture most people have.


How many times have you heard the phrase “this patient is septic”? And how many of these patients were actually septic?

The definition of sepsis has changed over the years and a little bit of confusion exists on its correct definition… Not mentioning the best management reserved for these patients.

Let’s start (as most times) with a case scenario…

Kenny is a 45-year-old man admitted three days ago because of fever and pain in the right iliac fossa. The exams performed on admission diagnosed acute appendicitis. A broad-spectrum antibiotic was started and he underwent emergency laparoscopic appendectomy.

The first two postoperative days passed smoothly, but on the third one, he became feverish.

Lab exams showed leukocytosis (WCC 14’450/mm3) and increased C-reactive protein (114 mg/L). Blood gas was done, and it reported a mild metabolic acidosis (pH 7.32; HCO3- 17.8 mmol/L; Lac 3.2 mmol/L).

Now, the question is: is the patient septic?

The answer is quite simple: we don’t know… We don’t have enough elements to give a proper answer. We can suppose the patient has an infection going on… probably a collection… However, we cannot say either he is septic or he isn’t.

Definition of Sepsis

Sepsis is important because it is the primary cause of death from infection.

According to the Sepsis-3 Campaign, sepsis is not a specific illness but a syndrome presenting with various signs and symptoms. The exact pathophysiology and pathobiology behind this syndrome have not been completely understood yet. It seems sepsis encompasses both exogenous and endogenous processes, leading to an early disproportionate pro- and anti-inflammatory response along with major modifications in nonimmunologic pathways, such as cardiologic, neurologic, metabolic, etc…

In other words, sepsis cannot just be considered as the direct effects of an infecting pathogen on the human body, but as the dysregulated immunologic and nonimmunologic host response to the infection. This means the major culprit of this pathological process is not the pathogen involved, but the host… the patient’s body…

Trying to make it simpler… You have a dam with a crack in it. Water starts pouring out from the crack, and the crack starts getting bigger. The water that comes out from the dam floods the small-town downhill, creating a lot of damage. The first thing to do in this case is to stop the water from pouring out from the dam. But if you just repair the crack, you won’t solve the problem in the village, because it is still flooded. So, you need to operate on many points: pumping the water away, reinforcing the buildings, bringing food to the villagers, etc… The infection is just the crack, not the water… The water is the host response to the crack…

In the end, the official definition of sepsis according to the Sepsis-3 Campaign is “a life-threatening organ dysfunction caused by a dysregulated host response to infection”.

Systemic Inflammatory Response Syndrome (SIRS)

Let’s make a single step backward and spend a couple of lines talking about SIRS.

During Med School, we remember our professors teaching SIRS was the first step toward the sepsis. The hypothetical sequence was SIRS, sepsis, severe sepsis, and septic shock.

But what’s SIRS?

SIRS is defined as the presence of at least two of the following criteria:

  • Body temperature >38°C or <36°C;
  • Heart rate >90 bpm;
  • Respiratory rate >20 bpm or pCO2 <32 mmHg;
  • White blood cell count >12’000/mm3 or <4’000/mm3 or >10% immature bands.

Moreover, the old sepsis definition involved the presence of SIRS and a confirmed source of infection.

Clearly, these definitions cannot be accepted, and the reason why can be easily explained by the following example… If you go out for a run, after a few minutes your heart rate may be way higher than 90 bpm, and the same can be said for the respiratory rate… More, if you have an infected sebaceous cyst, at the end of the run you’ll meet all the criteria to be defined as septic… But you are not!!!

For these reasons, the concept of SIRS is no longer accepted by the Sepsis-3 Campaign.

Diagnosis of Sepsis

Unfortunately, no gold standard diagnostic test exists to confirm the septic status. What matters in septic patients is organ dysfunction, because it is the reason why patients die. The infection can be suspected, and subsequently confirmed by blood cultures, but it takes time to have the results… and septic patients don’t have time.

Therefore, the first fundamental step to take is to identify septic patients as soon as possible, and the only way is to keep a high level of suspicion.

As we said earlier, the mainstream of sepsis is organ dysfunction. Therefore, in all patients with a suspected infection, the possible presence of organ dysfunction should be assessed with appropriate tools. On the other hand, sometimes an unexplained organ dysfunction may be the only manifestation of sepsis. However, it should be said that organ dysfunction may be localized to a single organ and/or hidden by a preexisting acute illness, chronic comorbidities, medications, and interventions.

This explains how treacherous sepsis may be.

Sequential Organ Failure Assessment (SOFA) score is a good score to evaluate the presence of organ dysfunction. Furthermore, the higher the SOFA score, the higher the risk of death.

The SOFA score can be calculated as follows (we suggest using an online calculator):

[PaO2/FiO2 (mmHg)]
[Platelets (x103/mL)]
[Bilirubin (mg/dL)]
[Hypotension (mmHg)]
NoMAP <70Dop ≤5 or Dob (any dose)Dop>5, Epi ≤0.1, or Nor ≤0.1Dop >15, Epi >0.1, or Nor >0.1
Central nervous system
[Glasgow coma scale]
[Creatinine (mg/dL)
Urine output (mL/die)]
MAP=mean arterial pressure; Dop=dopamine; Dob=dobutamine; Epi=epinephrine; Nor=norepinephrine

It has been established that, depending on patients’ baseline conditions, a SOFA score ≥2 identifies a 2- to 25-fold increased risk of dying (i.e. mortality ≈10%) compared with patients with a lower SOFA score. Therefore, sepsis was defined as an acute change in total SOFA score ≥2 points secondary to an infection. Yet, the SOFA score is not user-friendly in the everyday routine and it has been designed specifically for ICU patients.

To overcome these limitations, a new score, very similar to the SOFA score, was introduced. This new tool, the so-called quick SOFA score (or qSOFA), is user-friendly and does not require any lab exams. So, it can be easily performed bedside and it allows to determine if patients with suspected infection are at high risk. Moreover, the predictive validity of the qSOFA score was similar to that of the SOFA score for patients outside the ICU.

The qSOFA is composed of 3 criteria:

  • Respiratory rate ≥22 bpm;
  • Glasgow Coma Scale ≤13;
  • Systolic blood pressure ≤100 mmHg.

The qSOFA does not make the diagnosis, but it allows to screen and stratify patients. Diagnosis needs the original SOFA score.

Beware that failure to reach a qSOFA or a SOFA score equal or higher than 2 doesn’t mean you can underestimate the patient’s severity, delaying prompt investigations and/or therapy.

Remember, sepsis follows the same rule as all the other medical conditions: they are not static, they may change over time.

Definition of Septic Shock

Septic shock is defined as a septic condition where circulatory and cellular metabolism abnormalities substantially increase mortality. Patients with septic shock have about 40-50% of mortality.

In practice, septic shock is encountered when, despite adequate fluid resuscitation, the patient requires vasopressors (e.g. epinephrine or norepinephrine) to maintain a Mean Arterial Pressure (MAP) ≥65 mmHg and his/her serum lactate level >2 mmol/L.

We can conclude our first part of the journey now. Next time we are going to see how to treat these patients.

Stay tuned…

  1. Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10.
  2. Seymour CW, et al. Assessment of clinical criteria for sepsis for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;762-74.
  3. Howell MD, et al. Management of sepsis and septic shock. JAMA 2017;317:847-8.
  4. Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304-77.
  5. Plevin R, et al. Update in sepsis guidelines: what is really new? TSACO 2017;0:1-6.
How to Cite This Post

Bellio G, Marrano E. The Sepsis Six Samurai – Part 1. Surgical Pizza. Published on February 6, 2021. Accessed on June 24, 2022. Available at [].


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