II-26. Septic shock: mechanism and treatment principles

敗血症性ショックの機序と治療の原則

Septic Shock — Definition

The most prevalent type of shock; damage often results from the host reaction to the microbe (immune response + coagulation changes), not the microbe itself

1991 definitions

SIRS (≥2 of): core temp ≥38 or <36 °C; HR >90/min; RR >20/min or pCO₂ <32 mmHg; WBC >12 or <4 ×10⁹/L or >10% immature forms
Sepsis = SIRS + confirmed/probable infection
Severe sepsis = sepsis + organ failure from hypoperfusion (oliguria, acute CNS disorder, lactate >4 mM) or sepsis-induced hypotension
Septic shock = sepsis + arterial hypotension persisting despite adequate fluid resuscitation

2015 definitions

Sepsis = life-threatening organ dysfunction from a dysregulated host response to infection
Septic shock = sepsis subset needing vasopressors to keep MAP >65 mmHg + lactate >2 mM/L

Mechanism of Development

Pathogen PAMPs activate PRRs (TLR family) → innate immune response
Immune cells release cytokines/chemokines/interferons → SIRS, compensatory anti-inflammatory response (CARS), endothelial changes, coagulation
Cell damage → DAMPs → further WBC activation
Endothelial activation: ↑permeability → leukocyte transmigration → edema → ↑O₂ diffusion distance → tissue hypoxia → ↓mitochondrial ATP → anaerobic metabolism → ↑lactate (marker of tissue hypoxia)
Coagulation activation: ↓anticoagulants (antithrombin, TFPI, activated protein C), ↑tissue factor + PAI → thrombosis → microcirculatory blockage
Vasodilation → blood volume insufficient to fill dilated vessels → ↓venous return → ↓BP

Hemodynamic Phases

Hyperdynamic (vasodilative): ↓TPR (massive vasodilation) → ↑CO + ↑venous O₂ saturation; patient may look healthy but is in danger
Hypodynamic (vasoconstrictive): ↓venous return → ↓CVP → ↓preload → ↓CO → cyanosis; SYM → ↑HR; TPR may rise or fall

Post-Sepsis Syndrome

Cognitive disorders (main): persistent inflammation → endothelial dysfunction → ↓cerebral flow → hypoxia; BBB damage → neuroinflammation (microglia/astrocyte activation); ↑AChE + ↓hippocampal ACh receptors → impaired neurotransmission
Also: insomnia, fatigue, dyspnea/chest pain, muscle/joint pain, vision disorders, hair loss, poor concentration, low self-esteem

Treatment Principles

Goals: improve cardiac pump function; maintain MAP & normalize shock index (HR/SBP); ensure vital-organ perfusion; optimize tissue O₂
General: prevention, early diagnosis, eliminate cause; lay patient down, keep still & warm; elevate lower limbs (↑venous return); oxygenation/ventilation; pain relief
Fluids/blood: RBC concentrate, thrombocytes, fresh frozen plasma, tranexamic acid, isotonic saline
Sympathomimetics: noradrenaline (distributive/septic, ↑TPR); adrenaline (anaphylaxis); dobutamine (cardiogenic — β1 inotrope without vasoconstriction)
Other agents: vasopressin, milrinone/levosimendan, glyceryl trinitrate/nitroprusside (cardiogenic); H₁ antagonists + methylprednisolone/hydrocortisone (anaphylaxis/refractory); fludrocortisone (neurogenic/Addisonian)

一問一答

▶In septic shock, what mainly causes the damage — the microbe or the host?

Damage often results from the host reaction (immune response + coagulation changes), not the microbe itself.

▶What are the SIRS criteria (1991)?

≥2 of: core temp ≥38 or <36°C; HR >90/min; RR >20/min or pCO₂ <32 mmHg; WBC >12 or <4 ×10⁹/L or >10% immature forms.

▶How were sepsis and septic shock defined in 1991?

Sepsis = SIRS + confirmed/probable infection; septic shock = sepsis + arterial hypotension persisting despite adequate fluid resuscitation.

▶How are sepsis and septic shock defined in the 2015 criteria?

Sepsis = life-threatening organ dysfunction from a dysregulated host response to infection; septic shock = sepsis needing vasopressors to keep MAP >65 mmHg + lactate >2 mM/L.

▶How do PAMPs initiate the septic response?

Pathogen PAMPs activate pattern recognition receptors (PRRs, e.g., the TLR family) → innate immune response.

▶Why is lactate a key marker in septic shock?

Endothelial activation → edema → ↑O₂ diffusion distance → tissue hypoxia → anaerobic metabolism → ↑lactate, marking inadequate tissue oxygenation.

▶Why does vasodilation reduce venous return in septic shock?

Massive vasodilation means the blood volume is insufficient to fill the dilated vessels → ↓venous return → ↓BP.

▶How does coagulation activation contribute to septic shock?

↓Anticoagulants (antithrombin, TFPI, activated protein C) and ↑tissue factor + PAI → thrombosis → microcirculatory blockage.

▶What characterizes the hyperdynamic phase of septic shock?

↓TPR from massive vasodilation → ↑CO + ↑venous O₂ saturation; the patient may look healthy but is in danger.

▶What characterizes the hypodynamic phase of septic shock?

↓Venous return → ↓CVP → ↓preload → ↓CO → cyanosis; SYM → ↑HR; TPR may rise or fall.

▶What is the main feature of post-sepsis syndrome?

Cognitive disorders: persistent inflammation → endothelial dysfunction → ↓cerebral flow → hypoxia; BBB damage → neuroinflammation; ↑AChE + ↓hippocampal ACh receptors → impaired neurotransmission.

▶What are the treatment goals in shock?

Improve cardiac pump function, maintain MAP & normalize shock index (HR/SBP), ensure vital-organ perfusion, and optimize tissue O₂.

▶Why are the lower limbs elevated in shock management?

To increase venous return to the heart.

▶Which sympathomimetic is preferred in distributive/septic shock and why?

Noradrenaline, because it raises TPR to counter the pathological vasodilation.

▶Which sympathomimetics are used in anaphylactic and cardiogenic shock?

Adrenaline for anaphylaxis; dobutamine (β1 inotrope without vasoconstriction) for cardiogenic shock.

▶What role do DAMPs play in sepsis development?

Cell damage releases DAMPs, which further activate white blood cells, amplifying the inflammatory response.

▶What is severe sepsis (1991 definition)?

Sepsis + organ failure from hypoperfusion (oliguria, acute CNS disorder, lactate >4 mM) or sepsis-induced hypotension.

▶How does endothelial activation cause tissue hypoxia in sepsis?

↑Permeability → leukocyte transmigration → edema → ↑O₂ diffusion distance → tissue hypoxia → ↓mitochondrial ATP → anaerobic metabolism.

▶Which blood products and agents are used for fluid/blood resuscitation in shock?

RBC concentrate, thrombocytes, fresh frozen plasma, tranexamic acid, and isotonic saline.

▶Why might a hyperdynamic septic patient appear deceptively well?

High CO and high venous O₂ saturation from vasodilation make them look healthy, yet they are in danger as venous return is failing.