What is the step-by-step approach for starting, escalating, and de-escalating vasopressors (Epinephrine (adrenaline), Norepinephrine (noradrenaline), and Vasopressin) in pediatric patients with hypotension?

Practical Step-by-Step Vasopressor Management in Pediatric Patients

Start with epinephrine 0.05-0.3 mcg/kg/min for cold shock or norepinephrine 0.1-1.0 mcg/kg/min for warm shock after initial fluid resuscitation of 40-60 mL/kg, escalate by adding vasopressin 0.0002-0.002 units/kg/min when catecholamines reach 0.25 mcg/kg/min, and de-escalate vasopressin first followed by gradual catecholamine weaning once perfusion normalizes. 1, 2

Initial Assessment and Fluid Resuscitation

Immediate Actions (0-15 minutes)

• Administer rapid 20 mL/kg isotonic crystalloid or 5% albumin boluses by push or pressure bag, repeating up to 200 mL/kg in the first hour while monitoring for rales, gallop rhythm, or hepatomegaly 1
• Most children require 40-60 mL/kg in the first hour before vasopressors become necessary 1
• Correct hypoglycemia with D10%-containing isotonic solution at maintenance rates and correct hypocalcemia immediately 1
• Establish peripheral IV access initially; if second peripheral IV/intraosseous catheter is available, begin peripheral inotrope (low-dose dopamine or epinephrine) while establishing central venous line 1

Hemodynamic Classification

• Cold shock: Poor perfusion, prolonged capillary refill >2 seconds, cool extremities, weak pulses - indicates low cardiac output with high systemic vascular resistance 1
• Warm shock: Bounding pulses, flash capillary refill <1 second, warm extremities - indicates high cardiac output with low systemic vascular resistance 1

Starting Vasopressors: First-Line Agents

For Cold Shock (Low Cardiac Output)

• Epinephrine 0.05-0.3 mcg/kg/min via central line as first-line agent 1
• Preparation using "Rule of 6": 0.6 × body weight (kg) = milligrams of epinephrine diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 2, 3
• Alternative standard concentration: 4 mg epinephrine in 250 mL D5W = 16 mcg/mL 2
• If peripheral access only: use dilute solution with carrier fluid running at adequate flow rate to ensure timely cardiac delivery 1
• Monitor for peripheral infiltration/ischemia and reduce dose if alpha-adrenergic effects (vasoconstriction) occur at higher concentrations 1

For Warm Shock (Low Systemic Vascular Resistance)

• Norepinephrine 0.1-1.0 mcg/kg/min via central line as first-line agent 1, 2
• Preparation using "Rule of 6": 0.6 × body weight (kg) = milligrams of norepinephrine diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 2
• Standard concentration: 4 mg norepinephrine in 250 mL D5W = 16 mcg/mL 2, 4
• Target mean arterial pressure ≥65 mmHg or age-appropriate perfusion pressure (MAP - central venous pressure) 1, 2

Dopamine Alternative (Not Preferred)

• Dopamine 2-20 mcg/kg/min can be used but is not recommended as first-line due to higher mortality and arrhythmia risk compared to epinephrine/norepinephrine 1, 3
• If used: 2-5 mcg/kg/min for dopaminergic effects, 5-10 mcg/kg/min for beta-effects, >10 mcg/kg/min for alpha-effects 3
• Preparation: 0.6 × body weight (kg) = milligrams diluted to 100 mL saline; then 1 mL/h = 0.1 mcg/kg/min 3

Escalation Strategy: When First-Line Fails

Step 1: Optimize First-Line Agent (15-30 minutes)

• For epinephrine: Titrate up to 0.3 mcg/kg/min maximum before adding second agent 1
• For norepinephrine: Titrate up to 1.0 mcg/kg/min (some sources allow up to 2.0 mcg/kg/min) before adding second agent 2
• Reassess fluid status - occult hypovolemia is common cause of vasopressor resistance 1, 4
• Consider hydrocortisone 1-2 mg/kg/day (stress coverage) to 50 mg/kg/day if at risk for adrenal insufficiency (purpura fulminans, prior steroid exposure, hypothalamic/pituitary abnormality) 1

Step 2: Add Vasopressin (30-60 minutes)

• When catecholamines reach 0.25 mcg/kg/min and hypotension persists, add vasopressin 1, 2
• Pediatric vasopressin dosing: 0.0002-0.0005 units/kg/min initially, titrate to maximum 0.002 units/kg/min 2
• Adult equivalent: 0.03-0.04 units/min (do not exceed this in adults) 1, 2
• Vasopressin acts as catecholamine-sparing agent and overcomes receptor desensitization 1
• Critical: Two pediatric RCTs showed no mortality benefit with vasopressin/terlipressin, so reserve as rescue therapy only 1

Step 3: Consider Additional Agents for Refractory Shock

• For persistent cold shock with low cardiac output: Add milrinone 0.25-0.75 mcg/kg/min (loading dose 50 mcg/kg over 10-60 minutes may cause hypotension, use cautiously) 1
• Milrinone is type III phosphodiesterase inhibitor that improves contractility and reduces systemic vascular resistance without receptor dependence 1
• Requires normal renal function for clearance 1
• For warm shock not responding to norepinephrine + vasopressin: Consider adding low-dose epinephrine 0.05-0.1 mcg/kg/min for additional inotropy 1

Monitoring During Escalation

Continuous Monitoring Requirements

• Pulse oximetry, continuous ECG, continuous intra-arterial blood pressure (place arterial line as soon as practical) 1, 2
• Central venous pressure and central venous oxygen saturation (ScvO2 target >70%) 1
• Urine output (target >1 mL/kg/h) 1, 2
• Core temperature, glucose, calcium, INR, lactate, anion gap 1

Therapeutic End Points

• Capillary refill ≤2 seconds 1
• Age-appropriate heart rate (not tachycardic) 1
• Normal pulses with no differential between peripheral and central pulses 1
• Warm extremities 1
• Normal mental status 1
• Cardiac index 3.3-6.0 L/min/m² 1
• ScvO2 >70% 1
• Lactate clearance and normal anion gap 1

De-escalation Protocol: Weaning Vasopressors

When to Begin De-escalation

• Start weaning when perfusion normalizes: capillary refill ≤2 seconds, age-appropriate heart rate, warm extremities, adequate urine output, normal lactate 1
• Patient must be hemodynamically stable for at least 4-6 hours before initiating wean 4
• Ensure adequate intravascular volume before weaning 4

De-escalation Sequence (Reverse Order of Addition)

Step 1: Wean Vasopressin First

• Decrease vasopressin by 0.0001-0.0002 units/kg/min every 2-4 hours 2
• Monitor blood pressure every 15 minutes during initial wean 2
• If blood pressure drops >10 mmHg or perfusion worsens, pause wean for 2-4 hours then retry 2
• Discontinue vasopressin completely before weaning catecholamines 2

Step 2: Wean Milrinone (if used)

• Decrease milrinone by 0.1-0.25 mcg/kg/min every 4-6 hours 1
• Monitor cardiac output and systemic vascular resistance if available 1
• Watch for return of high systemic vascular resistance state 1

Step 3: Wean Primary Catecholamine (Epinephrine or Norepinephrine)

• For epinephrine: Decrease by 0.02-0.05 mcg/kg/min every 2-4 hours 1
• For norepinephrine: Decrease by 0.05-0.1 mcg/kg/min every 2-4 hours 2, 4
• "Reduce gradually, avoiding abrupt withdrawal" per FDA labeling 4
• Monitor perfusion markers continuously during wean 1
• If patient deteriorates, return to previous dose and wait 4-6 hours before retry 4

Failed Wean Management

• If unable to wean after 48-72 hours of stability, reassess for:
  • Ongoing infection/sepsis source 1
  • Adrenal insufficiency (consider hydrocortisone if not already given) 1
  • Myocardial dysfunction (consider echocardiography) 1
  • Occult bleeding or third-spacing 1

Critical Pitfalls to Avoid

Administration Errors

• Never use dopamine as first-line agent - associated with higher mortality and arrhythmias compared to epinephrine/norepinephrine 1
• Never use low-dose dopamine for "renal protection" - no benefit and strongly discouraged 1, 2
• Never mix catecholamines with sodium bicarbonate or alkaline solutions - causes inactivation 2
• Never give vasopressors without adequate fluid resuscitation first - causes severe organ hypoperfusion despite "normal" blood pressure 2

Extravasation Management

• If extravasation occurs with any catecholamine, immediately infiltrate phentolamine 0.1-0.2 mg/kg (up to 10 mg) diluted in 10 mL normal saline intradermally at site 2, 3
• Peripheral administration carries extravasation risk but is acceptable temporarily if central access delayed 1, 2
• Maximum peripheral doses: epinephrine 0.25 mcg/kg/min, norepinephrine 1.0 mcg/kg/min, dopamine 15 mcg/kg/min 5

Dosing Errors

• Never exceed vasopressin 0.002 units/kg/min in children (0.04 units/min in adults) - higher doses reserved for salvage therapy only 2
• Never use epinephrine >0.3 mcg/kg/min without reassessing for hypovolemia - likely indicates inadequate volume resuscitation 1
• Epinephrine increases lactate independent of perfusion (Cori cycle) - making lactate harder to interpret as perfusion marker 1

Monitoring Failures

• Never rely on blood pressure alone in children - they maintain blood pressure through vasoconstriction and tachycardia until cardiovascular collapse is imminent 1
• Always assess perfusion clinically: capillary refill, extremity temperature, pulse quality, mental status 1
• Place arterial line as soon as practical for continuous blood pressure monitoring during titration 1, 2