How to manage catecholamine resistance in shock?

Management of Catecholamine-Resistant Shock

When shock persists despite adequate fluid resuscitation and standard catecholamine therapy, immediately escalate to epinephrine (0.05-0.3 mcg/kg/min) in pediatric patients or add vasopressin (0.01-0.03 units/min) in adults, while simultaneously reassessing fluid status and correcting any absolute adrenal insufficiency with hydrocortisone. 1

Initial Recognition and Assessment

Catecholamine resistance occurs when patients remain hypotensive with evidence of poor perfusion despite:

• Adequate fluid resuscitation (typically 40-60 mL/kg in children) 1
• High-dose dopamine (>10 mcg/kg/min) or equivalent catecholamine support 1
• Persistent signs of shock: altered mental status, cool extremities, oliguria, elevated lactate (>2 mmol/L), or metabolic acidosis 1, 2

Critical pitfall: Before escalating vasopressors, verify adequate fluid loading status. Studies demonstrate that patients on high-dose catecholamines may actually be under-resuscitated, and forced volume challenge can reduce catecholamine requirements substantially. 3

Hemodynamic Phenotyping

Catecholamine-resistant shock presents in three distinct patterns that require different therapeutic approaches: 1

Low Cardiac Index, High SVR (Cold Shock)

• First-line therapy: Add vasodilators (nitroprusside or nitroglycerin) to reduce afterload 1
• Alternative: Substitute milrinone or inamrinone if toxicity develops from nitroprusside/nitroglycerin 1
• Caution: Long elimination half-lives of phosphodiesterase inhibitors can cause slowly reversible hypotension and arrhythmias, especially with renal/hepatic dysfunction 1

Low Cardiac Index, Low SVR (Mixed Shock)

• Add norepinephrine to epinephrine to increase diastolic blood pressure and SVR 1
• Once adequate blood pressure achieved, add dobutamine or phosphodiesterase inhibitors (preferably enoximone with minimal vasodilatory properties) to improve cardiac index 1
• Target ScvO2 >70% and cardiac index >3.3 L/min/m² 1

High Cardiac Index, Low SVR (Warm Shock)

• Add vasopressin 0.01-0.03 units/min as catecholamine-sparing agent 1, 4
• Titrate by 0.005 units/min every 10-15 minutes until target blood pressure achieved 4
• Limited data exists for doses >0.07 units/min in septic shock 4

Stepwise Escalation Algorithm

Pediatric Patients (Based on ACCM Guidelines)

At 15 minutes (Fluid-Refractory Shock):

• Begin dopamine up to 10 mcg/kg/min OR epinephrine 0.05-0.3 mcg/kg/min 1
• Titrate epinephrine for cold shock; norepinephrine for warm shock 1

At 60 minutes (Catecholamine-Resistant Shock):

• Administer hydrocortisone if at risk for absolute adrenal insufficiency 1
• Establish central venous access and monitor CVP 1
• Target normal MAP-CVP and ScvO2 >70% 1

Persistent Catecholamine-Resistant Shock:

• Place pulmonary artery catheter, PICCO, or use Doppler ultrasound to guide therapy 1
• Target cardiac index 3.3-6.0 L/min/m² 1
• Adjust vasopressors, inotropes, and vasodilators based on hemodynamic phenotype 1

Adult Patients

First-line escalation:

• Epinephrine over dopamine (lower mortality, fewer arrhythmias) 1
• Norepinephrine over dopamine (fewer side effects) 1, 5

Second-line for high catecholamine requirements:

• Add vasopressin 0.01 units/min, titrate up by 0.005 units/min every 10-15 minutes 1, 4
• No consensus exists on optimal threshold for initiating vasopressin, but consider when norepinephrine exceeds 0.5 mcg/kg/min 1

Alternative catecholamine-sparing agents:

• Angiotensin II for refractory vasodilatory shock 6, 7
• Methylene blue (1-2 mg/kg) for severe vasoplegia 7, 8
• Hydroxocobalamin as adjunctive therapy 7

Critical Monitoring Parameters

Hemodynamic targets: 1

• Mean arterial pressure appropriate for age (MAP-CVP normal for age)
• Cardiac index >3.3 and <6.0 L/min/m²
• ScvO2 >70%
• Capillary refill ≤2 seconds
• Urine output >1 mL/kg/h (pediatrics) or >0.5 mL/kg/h (adults)
• Lactate clearance and normalization of anion gap

Continuous reassessment required: Hemodynamic states can completely change over time despite persistent shock. 1

Adjunctive Therapies

Corticosteroids

• Hydrocortisone for absolute adrenal insufficiency in catecholamine-resistant shock 1
• Consider in patients at risk: chronic steroid use, hypothalamic-pituitary-adrenal axis suppression 1

Thyroid Hormone

• Triiodothyronine (T3) replacement for documented hypothyroidism in refractory shock 1

Metabolic Optimization

• Maintain glucose 80-150 mg/dL with insulin infusion if needed 1
• Correct ionized calcium to normal levels 1
• Ensure adequate glucose delivery with D10% isotonic solution at maintenance rate 1

Common Pitfalls to Avoid

Inadequate fluid resuscitation: The most critical error is escalating catecholamines without ensuring adequate preload. Use passive leg raise testing, CVP monitoring, or advanced hemodynamic monitoring to guide ongoing fluid therapy. 1, 3

Ignoring hemodynamic phenotype: Blindly adding vasopressors to high SVR shock worsens cardiac output. Always assess whether the patient needs afterload reduction, increased inotropy, or increased SVR. 1, 2

Excessive catecholamine dosing: High-dose catecholamines increase risk of arrhythmias, myocardial ischemia, and splanchnic hypoperfusion. Add non-catecholamine vasopressors (vasopressin) rather than escalating catecholamines indefinitely. 5, 6, 9

Delayed recognition of mechanical causes: Rule out pericardial effusion, pneumothorax, and intra-abdominal hypertension (>12 mmHg) before assuming purely vasoplegic shock. 1

Using etomidate for intubation: Avoid etomidate in septic shock patients due to adrenal suppression. 1

Refractory Shock Considerations

When shock persists despite maximal medical therapy:

• Neonates: Consider ECMO (80% survival in newborn sepsis) after excluding metabolic disorders, cyanotic heart disease, or hemodynamically significant PDA 1
• Children: ECMO candidacy for refractory shock unresponsive to all interventions 1
• Mechanical circulatory support may be necessary for cardiogenic shock component 2