Shock vs Sepsis vs SIRS: Key Differentiators

​

1. Definitions:

Systemic Inflammatory Response Syndrome (SIRS)

SIRS describes a non-specific systemic inflammatory state, triggered by infectious or non-infectious insults.

SIRS Criteria (Traditional)

Presence of ≥2 of:

• Temperature >38°C or <36°C
• Heart rate >90/min
• Respiratory rate >20/min or PaCO₂ <32 mmHg
• WBC >12,000 or <4,000 or >10% bands

SIRS can occur in:

• Trauma
• Burns
• Pancreatitis
• Post-operative states
• Infections

SIRS is not equivalent to infection.

Sepsis (Sepsis-3 Definition)

According to the Surviving Sepsis Campaign and consensus definitions:

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.

Operationalized as:

• Suspected/confirmed infection
• Increase in SOFA score ≥2

Septic Shock

A subset of sepsis characterized by:

• Persistent hypotension requiring vasopressors
• Serum lactate >2 mmol/L despite adequate fluid resuscitation

This carries a mortality >40%.

Shock (Broad Definition)

Shock is a state of circulatory failure leading to inadequate tissue perfusion and cellular hypoxia.

Major Types:

1. Hypovolemic
2. Cardiogenic
3. Obstructive
4. Distributive (includes septic shock)

Sepsis can lead to shock—but shock can occur without infection.

2. Advanced Pathophysiology

SIRS: Cytokine Storm Without Specificity

SIRS involves:

• Activation of innate immune pathways
• NF-κB pathway stimulation
• Release of TNF-α, IL-1, IL-6
• Endothelial activation

Key concept:

SIRS reflects systemic inflammation but does not imply organ failure.

Sepsis: Dysregulated Host Response

Sepsis involves:

1. Immune Dysregulation

• Excess pro-inflammatory mediators
• Simultaneous anti-inflammatory response
• Immune paralysis phase

2. Endothelial Dysfunction

• Increased permeability
• Capillary leak
• Microvascular thrombosis

3. Coagulation Cascade Activation

• Tissue factor activation
• Reduced anticoagulant pathways
• Risk of DIC

4. Mitochondrial Dysfunction

• Impaired oxygen utilization
• Cytopathic hypoxia

5. Autonomic Dysregulation

• Vasodilation
• Reduced systemic vascular resistance (SVR)

Sepsis is not simply “infection plus SIRS”—it represents organ dysfunction driven by maladaptive inflammation.

Shock: Cellular Oxygen Delivery Failure

Shock pathophysiology centers around:

DO_2 = CO \times CaO_2

Where:

• DO₂ = Oxygen delivery
• CO = Cardiac output
• CaO₂ = Arterial oxygen content

In septic shock:

• SVR ↓ (vasoplegia)
• CO may initially ↑
• Later myocardial depression

In cardiogenic shock:

• CO ↓
• SVR ↑ (compensatory)

In hypovolemic shock:

• Preload ↓ → CO ↓

Shock implies global hypoperfusion, which may or may not be infectious.

4. Clinical Trial Evidence

Early Goal-Directed Therapy (EGDT)

Rivers Trial (2001)

• Showed mortality reduction with protocolized sepsis resuscitation.

ProCESS, ARISE, ProMISe Trials

• Compared EGDT vs usual care.
• Found no significant mortality difference.
• Emphasized importance of early antibiotics and fluids rather than rigid protocols.

Surviving Sepsis Campaign (Latest Updates)

Key recommendations:

• Administer broad-spectrum antibiotics within 1 hour.
• 30 mL/kg crystalloid for hypotension or lactate ≥4.
• Norepinephrine as first-line vasopressor.
• Lactate re-measurement.

Vasopressor Evidence

• Norepinephrine superior to dopamine (less arrhythmias).
• Vasopressin as adjunct.

Lactate-Guided Therapy

Elevated lactate correlates with:

• Increased mortality
• Tissue hypoperfusion

However:

• Lactate may be elevated due to adrenergic stimulation, not only hypoxia.

5. Clinical Differentiation in Practice

Bedside Red Flags

Suggestive of Sepsis :

• Altered mental status
• Hypotension
• Oliguria
• Elevated creatinine
• Bilirubin elevation

Suggestive of Septic Shock :

• MAP <65 despite fluids
• Lactate >2
• Cool extremities (late stage)

Suggestive of Non-Septic Shock :

• MI history → cardiogenic
• Trauma → hypovolemic
• Massive PE → obstructive

6. Diagnostic Workup

Laboratory Evaluation

• CBC with differential
• Serum lactate
• Blood cultures (before antibiotics)
• ABG
• Renal and liver function
• Coagulation profile

Imaging

• Chest X-ray
• Ultrasound
• CT scan if source unclear

SOFA vs qSOFA

Tool	Use
SOFA	ICU organ dysfunction scoring
qSOFA	Rapid bedside screening

qSOFA :

• RR ≥22
• SBP ≤100
• Altered mentation

≥2 suggests poor outcome risk.

7. Management Overview

SIRS (Non-Infectious)

• Treat underlying cause
• Monitor for organ dysfunction

Sepsis

1. Early antibiotics
2. Source control
3. IV fluids
4. Organ support

Septic Shock

• Norepinephrine first-line
• Consider vasopressin
• Hydrocortisone if refractory
• Mechanical ventilation if needed

Non-Septic Shock

Depends on etiology:

• MI → revascularization
• Hemorrhage → blood products
• PE → thrombolysis

8. Complications

• ARDS
• Acute kidney injury
• DIC
• Multiorgan failure
• ICU-acquired weakness

9. Red-Flag Warnings

⚠️ Hypotension + altered sensorium = treat as shock until proven otherwise.

⚠️ Lactate >4 mmol/L = high mortality risk.

⚠️ Delay in antibiotics increases mortality.

⚠️ Normal blood pressure does NOT exclude early sepsis.

⚠️ Elderly patients may present afebrile.

10. Practical Clinical Pearls

• SIRS is sensitive but not specific.
• Sepsis requires organ dysfunction.
• Shock is about perfusion failure.
• Septic shock is distributive shock due to infection.
• Always search for source control.
• Early intervention saves lives.

11. Frequently Asked Questions (FAQ)

1. Is SIRS still used in modern practice?

Yes, but mainly descriptively. Sepsis-3 shifted focus to organ dysfunction.

2. Can someone have sepsis without fever?

Yes. Elderly and immunocompromised patients may be afebrile.

3. Is lactate always due to hypoxia?

No. Catecholamine surge can elevate lactate independently.

4. What is the mortality of septic shock?

Approximately 40% or higher.

5. Does every infection cause sepsis?

No. Sepsis requires dysregulated response with organ dysfunction.

At Medspacedaily, we advocate for precision in terminology and evidence-based intervention.

Recognizing the difference between inflammation, infection, and circulatory collapse can be life-saving.

Share this article with colleagues, trainees, and healthcare professionals. Early recognition saves lives—evidence guides action.

Key References

1. Singer M et al. Sepsis-3 definitions. JAMA. 2016.
2. Rivers E et al. Early Goal-Directed Therapy. NEJM. 2001.
3. ProCESS Investigators. NEJM. 2014.
4. ARISE Trial Investigators. NEJM. 2014.
5. Surviving Sepsis Campaign Guidelines. 2021 Update.
6. WHO Global Sepsis Report.
7. Cecconi M et al. Consensus on circulatory shock. Intensive Care Medicine.