Hemodynamics of Sepsis

3 parts | 1 story 

1. Pathophysiology & classification – what actually goes wrong

2. Clinical exhibition – how it appears at the bedside

3. Management – fix problems in the order they occur

PART 1 — PATHOPHYSIOLOGY AND CLASSIFICATION

When a pathogen enters the body, the immune system responds with inflammation.

Inflammation is mediated by cytokines. They exist in three functional groups:

1. Pro-inflammatory – IL-6 → immune activation

2. Anti-inflammatory – IL-10 → immune braking

3. Antiviral – Interferons → viral suppression

In health, these systems remain balanced.

Cytokine signalling activates nitric oxide (NO) pathways.

1. Physiological response → eNOS → small, regulated NO → adaptive vasodilation

2. Sepsis response → direct iNOS induction → large, sustained NO production → loss of vascular tone and catecholamine responsiveness

This is not excess inflammation alone — this is loss of control.

Sepsis is a dysregulated host response to infection that leads to organ dysfunction.

Three Dominant Targets of Injury (pathophysiology-based (dominant phenotype) classification)

1️⃣ Vasculature — Vasoplegia-Dominant Sepsis (This is distributive shock.)

• iNOS-driven NO → vascular smooth muscle paralysis

• SVR has collapsed due to loss of vascular tone

• BP falls despite adequate or high CO

2️⃣ Heart — Flow-Failure-Dominant Sepsis

• Persistent inflammation affects the pump (Impaired calcium handling, β-receptor down-regulation, Myocardial stunning) -> This is septic cardiomyopathy: Often reversible, Load-dependent, & EF may be misleading

• Take care of Preload, Pump, & Afterload

3️⃣ Mitochondria — Utilisation failure-Dominant Sepsis

• NO combines with superoxide → peroxynitrite -> Electron transport chain damage -> Oxygen cannot be utilised

• This is cytopathic hypoxia. Oxygen is present, but cells cannot use it.

Pathophysiology-based classification (dominant phenotype)

1. Vasoplegia (early seps)

2. Cardiomyopathy

3. Mitochondrial dysfunction (Late sepsis)

These overlap, but dominance matters clinically.

PART 2 — CLINICAL EXHIBITION

1. Vasoplegia → Pressure Failure

Clinical features:

• Hypotension

• Warm peripheries (early)

• Wide pulse pressure

• Poor response to fluids alone (advanced)

Key concept: This is not volume loss — it is tone loss.

2. Cardiomyopathy → Flow Failure

Flow failure occurs via three mechanisms:

a) Preload failure

• Capillary leak

• Relative hypovolemia

b) Pump failure

• Septic myocardial depression

• Low effective stroke volume

c) Afterload excess

• High-dose vasopressors; Weak heart pumping against resistance

3. Shock Reframed: DO₂–VO₂ Mismatch

• Flow is meaningless without proper content. We need energy (ATP)

• Energy production requires: Glucose & Oxygen

• Glucose mismatch → hypoglycemia → immediate, obvious, rapidly correctable

• Oxygen mismatch → silent, progressive, lethal. Hence, oxygen economics matter.

• Shock is not hypotension. Shock = failure to match oxygen delivery (DO₂) with oxygen utilisation (VO₂).

• Oxygen Content:

  • • Hb-bound 98.5%

    • Dissolved 1.5%

    • 1 g Hb carries 1.34 ml O₂ at 100% saturation

• We do not measure VO₂ directly at the bedside. Arterial saturation tells you what you give. Venous saturation tells you what was taken. DO2 = (Hb x SaO2 x 1.34) + (PaO2 x 0.003). Comparing arterial and venous oxygen, Hb and 1.34 are constants. Saturation is the variable. 

• Venous saturation tells:

  • • Whether delivery meets demand

    • Whether the extraction is excessive

    • Whether utilisation has failed

PART 3 — MANAGEMENT: FIX IN THE SAME ORDER DAMAGE OCCURS

STEP 1 — Restore Stressed Volume (Before Pressors)

• Crystalloids first

• Improves venous return (Preload)

• Add pressors if required; Target effective perfusion, not MAP

STEP 2 — Restore FLOW (Cardiac Output)

Flow has three levers:

1. Preload → fluids

2. Pump → inotropes when indicated

3. Afterload → de-escalate excess pressors

Echo is essential here.

STEP 3 — FLOW IS MEANINGLESS WITHOUT CONTENT

Oxygen delivery = Flow × Content

Manage content:

• Hemoglobin → transfuse when delivery is inadequate

• aturation → oxygen, ventilation, lung recruitment

A normal BP with poor content is still in shock.

STEP 4 —  VO₂ REDUCTION: BUY TIME

When you cannot increase delivery, reduce demand:

• Control fever

• Treat pain

• Reduce agitation

• Manage anxiety

• Sedate appropriately

• Reduce the work of breathing

Sometimes sedation saves organs.

STEP 5 — Mitochondrial Failure = Prognostic Zone

Once utilisation fails:

• Lactate persists despite adequate DO₂

• Mortality rises sharply

This phase is about damage control, not cure.

SUMMARY

Shock is not blood pressure. Shock is a failure of oxygen economics.

Sepsis starts as a vascular problem

Becomes a flow problem

Ends as an energy failure

Management

1. Restore tone

2. Fix flow

3. Optimise content.

4. Recognise utilisation failure early.