🍥Vasoplegic shock in ICU 🏥

🔥 Vasoplegic shock is a critical condition contributing to up to two-thirds of ICU shock cases. Most commonly seen in sepsis and post-cardiopulmonary bypass (CPB), it carries a 25–50% mortality rate 💀💔 .

💥 What is Vasoplegic Shock?

🔎 No clear consensus definition exists, but vasoplegic shock is characterized by:

➡️ Sustained hypotension due to pathologic vasodilation 🩸⬇️.

➡️ Increasing vasopressor requirements 💊💉.

➡️ Evidence of capillary leak 🌊 and tissue hypoperfusion 😨.

➡️Vasoplegia is excessive vasodilation WITHOUT tissue hypoperfusion,

➡️ Vasoplegic shock involves organ dysfunction 🚨.

💡 A standardized definition would improve research and clinical management!

🔬 Mechanisms of Vasoplegic Shock

Vasoplegic shock arises from systemic inflammation, leading to:

🔹 Vasodilation 🌀

🔹 Vascular hyporesponsiveness 😵

🔹 Capillary leak & microvascular dysfunction 🏴☠️

🔹 Tissue hypoxia 🫁🫀

🔬 How Does Inflammation Lead to Vasoplegia?

🦠 DAMPs (Damage-Associated Molecular Patterns) – Released from injured tissue.

🦠 PAMPs (Pathogen-Associated Molecular Patterns) – Derived from microorganisms. 👀 Both activate Toll-like receptors (TLRs), triggering the release of:

• Interleukin-1 (IL-1) 🔥
• Interleukin-6 (IL-6) 🦠
• Tumor necrosis factor-alpha (TNF-α) 💥
• Interferon-gamma (IFN-γ) 🛑

🧪 These cytokines trigger pathways that reduce vascular tone & lead to shock! 🚨

🌀 1️⃣ Vasodilation – The Main Driver of Vasoplegia

• Inflammatory cytokines ⏩ increase nitric oxide (NO) production 🛠️.
• iNOS (Inducible Nitric Oxide Synthase) upregulation leads to massive NO production 🌫️.
• NO activates guanylate cyclase, which lowers intracellular calcium, leading to vascular smooth muscle relaxation 🏋️♂️⛔.
• K-ATP channel activation causes hyperpolarization of vascular smooth muscle, further impairing contraction ⚡😵.

👉 End result? Uncontrolled vasodilation → Severe hypotension 🩸⬇️.

😵 2️⃣ Vascular Hyporesponsiveness – Why Don’t Pressors Work?

Even with high-dose vasopressors, the vessels fail to constrict due to:

❌ Catecholamine receptor downregulation – Too much adrenaline, noradrenaline, and angiotensin II leads to receptor fatigue 🎭.

❌ Vasopressin depletion – Chronic vasopressin release depletes stores 🏦.

❌ Metabolic acidosis – Worsens receptor desensitization ⚡.

🩺 Clinical Implication: Standard vasopressors become ineffective without multimodal support!

🩸 3️⃣ Microcirculatory Dysfunction – Capillary Leak & Hypoxia

Vasoplegic shock leads to microcirculatory collapse, causing:

🧊 Capillary leak due to glycocalyx degradation.

🩸 Microthrombi formation → Blood stasis & ischemia.

🫁 Alveolar-capillary damage → ARDS.

🚨 Final Outcome? 📉 Intravascular hypovolemia + Edema + Organ hypoperfusion = Multiorgan failure 💀.

🔎 Causes of Vasoplegic Shock

Systemic inflammation plays a central role, but the triggers vary. Here are the most common causes seen in ICU & OR settings:

🚨 Top Causes of Vasoplegia

💡 Key Insight: Post-cardiac surgery vasoplegia has an incidence of 5–25%, and risk factors include poor ventricular function, prolonged CPB, & ACE inhibitor use pre-op!

📋 Assessment & Initial Management

🩺 Clinical Presentation

🚑 Classic signs of vasoplegic shock include:

• Hypotension (MAP < 65 mmHg) 📉
• Low diastolic blood pressure (<40–50 mmHg) 💔
• Warm extremities with bounding pulses (except post-CPB) 🔥
• Tachycardia (relative to cardiac index) 💓
• High cardiac output with low systemic vascular resistance (SVRI < 800 dyn·s/cm⁵) ⚡

💡 But beware! Vasoplegic shock often coexists with hypovolemia & cardiogenic shock—a thorough workup is essential!

📊 Hemodynamic Monitoring

Different methods exist for assessing vasoplegic shock.

🔎 Key Diagnostic Clues

📍 Normal/high ScvO₂ (Central Venous Oxygen Saturation) despite tissue hypoxia 🩸. 📍 Lactate elevation, but can be misleading (due to aerobic metabolism in adrenaline use). 📍 Peripheral perfusion assessment (CRT > 3 sec, mottling score) is as good as lactate levels!

🎯 Blood Pressure Targets

🔵 Goal MAP: ≥65 mmHg

🔵 Higher MAP (75–85 mmHg) does NOT improve mortality in septic shock patients even in elderly groups.

🔵 Radial vs. Femoral Pressure Gradient:

✅ Femoral MAP often > Radial MAP in vasoplegic shock post-CPB.

✅ Resolution of shock is marked by equalization of radial & femoral pressures!

💧 The Role of Fluids in Vasoplegic Shock

🚑 Do Fluids Help?

✔️ IV fluids are the first-line intervention, but over-resuscitation worsens edema & capillary leak 🚱.

✔️ 30 mL/kg is recommended in sepsis, but beyond this, fluid responsiveness must be tested!

🔬 How to Assess Fluid Responsiveness?

💡 Key Point: Fluid resuscitation will NOT fix vasoplegic shock alone—it must be combined with vasopressor therapy!

🩸 Vasopressor Therapy: The Lifeline for Vasoplegic Shock

🔹 Fluids alone are insufficient – we need vasopressors to counteract pathologic vasodilation 🚨.

🔹 A multimodal approach, targeting different receptors, is optimal for achieving hemodynamic stability without excessive drug-specific side effects ⚖️.

🔹 Key question: Which vasopressors should we use? Let’s break it down!

🚀 First-Line Vasopressors

1️⃣ Noradrenaline (Norepinephrine) – The Workhorse 💪

💉 Mechanism:

✔️ Strong α1-agonist, mild β1 activity

✔️ Increases MAP by vasoconstriction

✔️ Some venoconstriction helps maintain preload

📌 Dosing: Start 0.05–0.1 µg/kg/min, titrate as needed.

📉 Risks & Adverse Effects:

❌ Tachyarrhythmias (higher than vasopressin).

❌ Digital ischemia in high doses (>1 µg/kg/min).

❌ Weak association with AKI in cardiac surgery patients.

💡 Key Takeaway:

✔️ Noradrenaline is the first-line vasopressor in septic & vasoplegic shock 🏆.

✔️ Early initiation is recommended before excessive fluid loading 💧.

✔️ High doses (>1 µg/kg/min) are associated with 40% mortality 📉💀.

2️⃣ Vasopressin – The Noradrenaline-Sparing Agent 🏥

💉 Mechanism:

✔️ Non-catecholaminergic 🛑 (acts on V1 receptors).

✔️ Potentiates catecholamine effects & inhibits NO production 🚫🧪.

✔️ Preserves pulmonary circulation (less effect on PVR).

📌 Dosing: Fixed dose 0.02–0.04 units/min (not titrated).

📉 Risks & Adverse Effects:

❌ Digital ischemia (higher than noradrenaline).

❌ Mesenteric ischemia risk (but only at high doses >0.06 units/min).

💡 Key Takeaway:

✔️ Best used as a second-line agent when noradrenaline >0.2 µg/kg/min 🏆.

✔️ Reduces risk of atrial fibrillation compared to catecholamines 💓.

3️⃣ Adrenaline (Epinephrine) – The Heavy Hitter 🥊

💉 Mechanism:

✔️ Strong β1 & α1 activity, moderate β2 effects.

✔️ Increases cardiac output & heart rate 💓.

✔️ Used in refractory shock OR when inotropic support is needed.

📌 Dosing: 0.01–0.1 µg/kg/min (low doses → β effects, high doses → α effects).

📉 Risks & Adverse Effects:

❌ Tachyarrhythmias (highest among vasopressors) ⚡💓.

❌ Hyperlactatemia & hyperglycemia (from β2 effects).

❌ Can worsen myocardial ischemia in CAD patients.

💡 Key Takeaway:

✔️ Best used when both vasopressor & inotropic support are needed 💪.

✔️ Not first-line due to metabolic side effects.

4️⃣ Dopamine – No Longer Recommended 🚫

💉 Mechanism:

✔️ Dose-dependent receptor activation (low → D1, moderate → β1, high → α1).

📉 Risks & Adverse Effects:

❌ Increased arrhythmias vs. noradrenaline ⚡💔.

❌ Associated with increased mortality in septic shock 📉.

💡 Key Takeaway: 🚫 Dopamine should NOT be used in vasoplegic shock!

🚨 Rescue Agents for Refractory Vasoplegia

When high-dose noradrenaline & vasopressin fail, we turn to alternative vasopressors:

1️⃣ Methylene Blue – The NO Inhibitor 🧪

💉 Mechanism:

✔️ Inhibits iNOS & guanylate cyclase, preventing excessive NO production 🛑.

✔️ Selective vasoconstriction in dilated vascular beds.

📌 Dosing: 1–2 mg/kg IV over 15–30 min (can repeat in 6 hrs).

📉 Risks & Adverse Effects:

❌ Methemoglobinemia & hemolysis in G6PD deficiency.

❌ Serotonin syndrome risk if used with SSRIs 🚨.

❌ Splanchnic ischemia in high doses (>7 mg/kg).

💡 Key Takeaway:

✔️ Considered in catecholamine-resistant vasoplegia.

✔️ Can be useful post-cardiac surgery 💉🫀.

2️⃣ Angiotensin II – The New Kid on the Block 🆕

💉 Mechanism:

✔️ Potent vasoconstriction via AT-II receptor activation.

✔️ No inotropic effects (unlike catecholamines).

📌 Dosing: 20–40 ng/kg/min, max 200 ng/kg/min.

📉 Evidence: 📊 ATHOS-3 Trial:

• More effective than noradrenaline alone in raising MAP 🚀.
• Lower SOFA scores at 48 hrs 🏥.
• Improved renal function in AKI (post hoc analysis).

💡 Key Takeaway:

✔️ Good option for refractory vasoplegia, but limited availability 🌍.

✔️ More studies needed to assess impact on mortality.

3️⃣ Hydroxocobalamin (Vitamin B12) – Experimental Therapy 🤔

💉 Mechanism:

✔️ Inhibits iNOS, counteracting NO-induced vasodilation.

✔️ Enhances hydrogen sulfide clearance, another vasodilator.

📌 Dosing: 5 g IV over 10–15 min.

📉 Risks & Adverse Effects:

❌ Turns urine & plasma dark orange-red 🟠 (can trigger false alarms in dialysis machines).

❌ May cause transient hypokalemia 🩸.

💡 Key Takeaway:

✔️ Limited data, mostly case reports in cardiac surgery.

✔️ Consider as a last-resort vasopressor 🛑.

🩸 Adjuvant Therapies in Vasoplegic Shock

Beyond vasopressors, adjuvant therapies play a crucial role in optimizing hemodynamics and improving outcomes.

1️⃣ Renal Replacement Therapy (RRT) – When & Why? 🏥💧

🔹 Metabolic acidosis is common in vasoplegic shock.

🔹 Increased lactate can worsen oxidative stress.

🔹 Early RRT may improve acid-base balance and hemodynamics.

📌 Key Indications for RRT in Vasoplegic Shock:

✅ Severe metabolic acidosis (pH < 7.2, HCO₃ < 15 mmol/L).

✅ Refractory hyperkalemia (>6.5 mmol/L).

✅ Severe fluid overload with respiratory distress 🌊.

✅ Oliguria/anuria despite diuretics.

💡 Key Takeaway:

✔️ RRT helps correct metabolic acidosis, which may enhance vasopressor response.

✔️ Balance is needed—excessive ultrafiltration may worsen hypoperfusion ❌.

2️⃣ Corticosteroids – Game Changer or Just Another Adjunct? 🏥💊

📌 Mechanism of Action:

✔️ Suppresses systemic inflammation 🔥.

✔️ Restores vascular responsiveness to catecholamines 💉.

✔️ Enhances mineralocorticoid effects (improves sodium/water retention).

📊 Clinical Evidence from Large Trials: 🔬 APROCCHSS Trial (2018)

• Hydrocortisone + Fludrocortisone → ↓ 90-day mortality in septic shock (43% vs. 49%).
• Faster shock resolution & lower vasopressor requirements.

🔬 ADRENAL Trial (2018)

• Hydrocortisone alone → No mortality benefit but reduced time on vasopressors.
• No increased adverse events.

📌 Dosing Recommendation:

💉 Hydrocortisone 200 mg/day IV (divided doses or continuous infusion) for ≤7 days.

📉 Potential Risks:

❌ Hyperglycemia (requires insulin therapy).

❌ Increased risk of secondary infections.

❌ Slight increase in myopathy risk with prolonged use.

💡 Key Takeaway:

✔️ Corticosteroids should be considered in vasoplegic shock requiring high-dose vasopressors 💪.

✔️ Best evidence supports hydrocortisone + fludrocortisone.

3️⃣ Vitamin C & Thiamine – The Sepsis Cocktail? 🧪🍊

📌 Mechanism of Action:

✔️ Vitamin C reduces oxidative stress & stabilizes catecholamines.

✔️ Thiamine (Vitamin B1) prevents lactic acidosis by improving pyruvate metabolism.

📊 Clinical Evidence:

🔬 VITAMINS Trial (2020) – No mortality benefit with Vitamin C + Thiamine + Hydrocortisone in septic shock ❌.

🔬 CITRIS-ALI Trial (2019) – High-dose Vitamin C worsened adverse events 🚨.

📌 Dosing:

• Thiamine (200 mg IV q12h) may be beneficial in thiamine-deficient patients.
• High-dose Vitamin C is NOT recommended due to increased adverse effects ❌.

💡 Key Takeaway:

✔️ Avoid high-dose Vitamin C in vasoplegic shock 🚫.

✔️ Thiamine may be useful in specific cases (e.g., chronic alcohol use, malnutrition).

🚀 Future Directions in Vasoplegic Shock Therapy

🔬 What’s on the Horizon?

1️⃣ Selective iNOS Inhibitors – Blocking excessive nitric oxide production without affecting baseline vasoregulation.

2️⃣ Endothelin-1 Modulators – Regulating vascular tone without excessive vasoconstriction.

3️⃣ Personalized Vasopressor Therapy – Using biomarkers to guide therapy (e.g., vasopressin levels, angiotensin II sensitivity testing).

🏁 Final Takeaways

✔️ Vasoplegic shock is highly fatal (25–50% mortality), requiring early recognition & multimodal treatment 🚨.

✔️ Noradrenaline is the first-line vasopressor, followed by vasopressin as an adjunct.

✔️ Refractory vasoplegia may require methylene blue, angiotensin II, or hydroxocobalamin 🏥.

✔️ Corticosteroids help in patients requiring high-dose vasopressors 💊.

✔️ Avoid high-dose Vitamin C, but consider thiamine in select cases 🍊.

✔️ RRT may be beneficial for metabolic acidosis correction but should be used judiciously.

📚 Reference

Mistry RN, Winearls JE. Management of Vasoplegic Shock. BJA Education. 2025;25(2):65-73. doi: 10.1016/j.bjae.2024.10.004.