Systemic inflammatory response syndrome

Systemic inflammatory response syndrome (SIRS) is a condition where there is widespread unregulated inflammation in the body. The term has fallen out of favour and is not used anymore.

Definition

SIRS is defined as having two or more of the following parameters:

Body temperature < 36℃ or >38℃
Heart rate > 90 bpm
Respiratory rate > 20/min
White blood cell count < 4000/µL or > 12000/µL

Etiology

Infectious causes
Non-infectious causes
- Severe burns
- Severe trauma
- Circulatory shock
- Pancreatitis
- Vasculitis
- Severe ischaemia
- Severe tissue injury

Pathomechanism

See the pathomechanism of sepsis below; they’re similar.

Sepsis

Sepsis is an acute life-threatening condition characterised by organ dysfunction caused by a dysregulated host response to infection, usually bacterial. It’s related to systemic inflammatory response syndrome (SIRS) in pathomechanism. It has a very high mortality rate and can lead to multiple organ dysfunction syndrome (MODS) and death.

Septic shock is defined as “A subset of sepsis in which underlying circulatory and cellular or metabolic abnormalities lead to substantially increased mortality risk.” As the name implies it implies the state where a person has sepsis and circulatory shock, often of the distributive type. A person is said to be in septic shock if:

The patient has sepsis, and:
Vasopressors are required to maintain a mean blood pressure of above 65 mmHg, and:
The serum level of lactate is > 2.0 mM

A third term, "severe sepsis" was used until 2016, when the Sepsis-3 guideline revised the definition of sepsis. Sepsis-3 also included the deviation from using SIRS criteria to using SOFA criteria.

Etiology

Primary infection
- Pneumonia
- Genitourinary infections
- Gastrointestinal infections
- Skin infections
- Soft tissue infections
Pathogens
- Gram positive bacteria
- Gram negative bacteria
Risk factors
- Age < 1 year
- Age > 65 year
- Comorbidities
  - Diabetes mellitus
  - Cancer
  - Obesity
  - Cirrhosis
  - Alcoholism
- Immunosuppression
- Being in an intensive care unit
- Invasive medical treatment
  - Endotracheal tube
  - Intravenous lines
  - Urinary catheters

The most common primary infection that leads to sepsis is pneumonia, especially community-acquired pneumonia. The pathogen is more frequently gram positive than gram negative; fungal, viral or parasitic etiology is rare.

Bacteraemia is found in 50% of cases of sepsis.

Pathomechanism

The underlying mechanism of sepsis is a hyperinflammatory systemic reaction. A normal, physiological immune response requires a balance of proinflammatory and anti-inflammatory signals. In sepsis, this balance is lost. The exact mechanism that leads to the loss of this balance is not well known. Hyperactivation of the innate immune system occurs, which leads to decreased oxygen delivery to tissues.

In gram negative bacteria the LPS molecule of their cell envelope is recognized by TLR4 receptors on macrophages and other immune cells. In gram positive bacteria the cell wall is recognized by TLR2 receptors on the same cells. The immune cells will then produce inflammatory cytokines like TNF-α, IL-1, IL-6 and IL-8. This has multiple consequences:

The endothelium will become dysfunctional, allowing fluid and other molecules to cross in the interstitium. Fluid is lost to the interstitium, decreasing the oxygenation of tissues
Cells will be damaged, releasing damage-associated molecular patterns (DAMP) that are recognized by immune cells and cause further inflammation

As fluid is lost to the interstitium, intravascular hypovolaemia occurs. DIC occurs due to endothelial dysfunction and intravascular hypovolaemia. Widespread tissue ischaemia and decreased tissue oxygenation causes widespread cell injury and thereby multisystem organ dysfunction.

Clinical features

Fever
Tachycardia
Tachypnoea
Features of organ dysfunction, depending on which organs are affected
- ARDS
- Hypotension
- Acute renal failure, oliguria
- Altered mental status
- DIC

Diagnosis and evaluation

Organ dysfunction must be present for the diagnosis of sepsis. The definition of “organ dysfunction” can itself be difficult to accurately establish. To help with this, a set of assessment criteria called “sequential organ failure assessment score” or SOFA score can help. These criteria assess the function of important organ systems like lungs, liver, CNS, kidneys, circulation and the coagulation and gives scores from 0 (normal function) to 4 (worst function). The score for each organ system is then summed up. Acute organ dysfunction is defined as an acute change in total SOFA score of 2 points or more.

Sepsis used to be evaluated by the criteria of “systemic inflammatory response syndrome” (SIRS), but that is not recommended anymore. Sepsis now has its own criteria (SOFA).

Diagnosis of sepsis can be difficult. A series of criteria called qSOFA (quick SOFA) can be used to screen for sepsis. qSOFA is said to be positive of 2 or more of the following criteria are present:

Altered mental status (GCS < 15)
Respiratory rate > 22 breaths per minute
Systolic blood pressure < 100 mmHg

If qSOFA is positive, blood cultures should be performed to look for the pathogen and the patient should be evaluated for organ dysfunction according to the SOFA system. Blood tests should be performed to measure the following:

CBC (complete blood count)
Procalcitonin – a serum protein that increases significantly in sepsis
CRP – which signals inflammation
Lactate – which is proportional to the degree of tissue hypoxia
Thrombocytes - thrombocytopaenia is common

Multiple organ dysfunction syndrome

Multiple organ dysfunction syndrome (MODS), also called multiple organ failure (MOF), is a clinical syndrome characterised by the development of progressive and potentially reversible dysfunction in 2 or more organs or organ systems. It’s often the result of acute insults like sepsis.

Like in sepsis, organ dysfunction can be diagnosed by the use of the SOFA criteria, or by the use of the MODS criteria.

Etiology

Sepsis
Severe trauma
Severe burns
Pancreatitis
Eclampsia

MODS is considered primary if it occurs early after the insult and can be directly attributable to the insult itself. An example is if renal failure develops due to rhabdomyolysis.

MODS is considered secondary if it occurs as a consequence of the host’s response to the insult. An example is if ARDS develops due to pancreatitis.

Trauma

Trauma is a sudden insult which can have severe impact on health. Trauma is a major cause of death in all age groups; especially road traffic accidents are responsible. They can range from simple bone fractures to poles sticking through your skull. We distinguish blunt and penetrating trauma.

We distinguish multiple trauma and polytrauma. Multiple trauma refers to the presence of multiple independent traumas, like if one simultaneously fractures multiple bones. Polytrauma refers to the presence of multiple severe, life-threatening traumas which worsen each other, for example in a severe car crash.

In this discussion we will discuss mostly polytraumatic patients.

Mortality of traumas

Mortality of trauma can occur in one of three possible periods:

Period	Time after trauma	Cause of death
Acute death	1 – 4 hours	Exsanguination, pneumothorax, acute heart failure
Early death	4 hours – 2 weeks	Single organ failure
Late death	> 2 weeks	MODS, sepsis

Pathophysiology

Acute death occurs if there is significant damage to an artery or vital organ like the heart or lungs. Pneumothorax, acute heart failure and exsanguination are common causes of death.

If no acute death occurs there can still be widespread tissue injury. SIRS can develop and cause distributive shock. Reperfusion injury can occur. These factors may be enough to kill the patient in the early phase, or they can lead to MODS and sepsis, which can kill the patient later.

Symptoms of a trauma patient

Hypotension
Tachycardia
Cool, moist skin with cyanosis
Oliguria
Apathy

Treatment

Treatment involves trying to maintain vital parameters. Fluid balance, electrolyte balance, oxygen supply, blood glucose and acid-base status should all be monitored and treated as necessary.