What is the appropriate dosing of pressors, such as norepinephrine (vasopressor) and epinephrine (adrenergic receptor agonist), for a typical adult patient with hypotension (low blood pressure) in a critical care setting?

Vasopressor Dosing in Critical Care

First-Line Agent and Initial Dosing

Norepinephrine is the first-choice vasopressor for hypotensive adults in critical care, with an initial infusion rate of 0.5-1 mL/min (2-4 mcg/min base) titrated to achieve a mean arterial pressure (MAP) of 65 mmHg. 1, 2

Norepinephrine Preparation and Administration

• Standard dilution: Add 4 mg (4 mL vial) to 1,000 mL of 5% dextrose solution, creating a concentration of 4 mcg/mL 2
• Initial rate: Start at 2-3 mL/min (8-12 mcg/min base), then adjust to maintain MAP 65 mmHg 2
• Maintenance range: Typically 0.5-1 mL/min (2-4 mcg/min base or approximately 0.03-0.05 mcg/kg/min) 2
• Route: Administer through central venous access when possible, though peripheral administration is safe for early initiation 3
• Monitoring: Titrate every 10-15 minutes based on MAP and perfusion markers 4

Critical Dosing Thresholds

• Mortality threshold: Doses exceeding 0.5 mcg/kg/min of norepinephrine are associated with 96% mortality risk 5
• Futility threshold: All patients receiving >3.8 mcg/kg/min died in observational studies 5
• High-dose range: Occasionally doses up to 68 mg/day (17 vials) may be necessary, but occult hypovolemia must be excluded 2

Blood Pressure Targets

Target MAP of 65 mmHg initially for most patients, with individualization based on specific conditions. 1, 4

Standard Target

• Initial goal: MAP ≥65 mmHg after adequate fluid resuscitation 1, 4
• Rationale: Below this threshold, autoregulation in critical vascular beds is lost and perfusion becomes linearly pressure-dependent 1

Adjusted Targets for Specific Populations

• Chronic hypertension: Increase target to MAP ≥70 mmHg or maintain within 40 mmHg of baseline systolic pressure 4, 2
• Elderly patients (>75 years): Consider lower target of 60-65 mmHg, which may reduce mortality 4
• Spinal cord injury: Maintain MAP ≥70 mmHg during first week to limit neurological worsening 4
• Elevated intra-abdominal pressure: Increase MAP targets to compensate for reduced organ perfusion pressure 4

Perfusion Assessment Beyond MAP

• Monitor concurrently: Lactate clearance, urine output (>0.5 mL/kg/h), mental status, skin perfusion, and capillary refill 1, 4, 6
• Trans-kidney perfusion pressure: Calculate MAP minus central venous pressure (CVP); maintain >60 mmHg for renal protection 4
• Critical pitfall: MAP alone does not reflect cardiac output or adequate tissue perfusion 4, 6

Second-Line Vasopressor: Epinephrine

Add epinephrine when norepinephrine alone fails to maintain adequate blood pressure, starting at 0.05 mcg/kg/min and titrating up to 2 mcg/kg/min. 1, 7

Epinephrine Preparation and Dosing

• Standard dilution: Add 1 mg (10 mL from syringe) to 1,000 mL of 5% dextrose, creating 1 mcg/mL concentration 7
• Initial rate: 0.05 mcg/kg/min (approximately 3.5 mcg/min for 70 kg patient) 7
• Titration: Increase by 0.05-0.2 mcg/kg/min every 10-15 minutes to achieve desired MAP 7
• Maximum rate: Up to 2 mcg/kg/min (approximately 140 mcg/min for 70 kg patient) 7
• Weaning: Decrease incrementally every 30 minutes over 12-24 hours after hemodynamic stabilization 7

Mortality Threshold for Epinephrine

• High-risk threshold: Doses >0.5 mcg/kg/min associated with 96% mortality 5
• Futility threshold: All patients receiving >9.6 mcg/kg/min died in observational studies 5

Push-Dose Epinephrine for Acute Hypotension

• Indication: Temporary correction of documented hypotension during transport or peri-intubation 8
• Dose: 10-20 mcg IV (1:100,000 dilution) every 2 minutes 8
• Goal: SBP ≥90 mmHg or MAP ≥65 mmHg 8
• Effect: Median MAP increase of 13 mmHg with minimal heart rate change 8
• Safety: Rare adverse events when properly dosed; single case of transient extreme hypertension without harm 8

Additional Vasopressor Options

Vasopressin

• Indication: Add to norepinephrine to raise MAP or decrease norepinephrine dose 1
• Dose: Up to 0.03 units/min (maximum 0.04 units/min) 1
• Contraindication: Do not use as single initial vasopressor 1
• Salvage therapy: Doses >0.03-0.04 units/min reserved for failure of other agents 1

Dopamine

• Limited role: Alternative only in highly selected patients with low tachyarrhythmia risk and bradycardia 1
• Dose: 2-20 mcg/kg/min titrated to SBP >90 mmHg 1
• Preparation: 400 mg in 500 mL of 5% dextrose 1
• Evidence: Inferior to norepinephrine in septic shock 1

Phenylephrine

• Very limited role: Not recommended except when norepinephrine causes serious arrhythmias, cardiac output is high with persistent low BP, or as salvage therapy 1
• Peri-intubation use: Bolus doses of 50-200 mcg may temporarily improve BP but do not reduce cardiovascular collapse 1

Practical Algorithm for Vasopressor Initiation

Step 1: Assess Volume Status

• Fluid resuscitation first: Correct hypovolemia before or concurrent with vasopressor initiation 1
• Exception: Severe shock with critically low diastolic BP requires immediate vasopressor as emergency measure 1

Step 2: Start Norepinephrine

• Access: Establish central venous access; peripheral acceptable for early initiation 6, 3
• Initial dose: 2-3 mL/min (8-12 mcg base/min) of 4 mcg/mL solution 2
• Target: MAP ≥65 mmHg (adjust for chronic hypertension or age) 4

Step 3: Titrate and Monitor

• Frequency: Adjust every 10-15 minutes 4
• Endpoints: MAP target PLUS lactate clearance, urine output, mental status 1, 4
• Arterial line: Place for continuous monitoring as soon as practical 6

Step 4: Add Second Agent if Inadequate Response

• First choice: Add epinephrine 0.05 mcg/kg/min, titrate up to 2 mcg/kg/min 1, 7
• Alternative: Add vasopressin 0.03 units/min 1
• Reassess volume: Suspect occult hypovolemia if requiring high doses 2

Step 5: Recognize Futility

• Norepinephrine >0.5 mcg/kg/min: 96% mortality risk; reassess goals of care 5
• Epinephrine >0.5 mcg/kg/min: Similar mortality threshold 5
• Consider: Mechanical circulatory support, ECMO, or transition to comfort measures 9

Critical Pitfalls to Avoid

• Do not delay vasopressors waiting for complete fluid resuscitation in severe shock with low diastolic BP 1
• Do not use MAP alone as endpoint; always assess tissue perfusion markers 1, 4, 6
• Do not assume MAP 65 mmHg is adequate for patients with chronic hypertension—increase target to ≥70 mmHg 4
• Do not ignore elevated CVP when assessing renal perfusion; calculate trans-kidney perfusion pressure (MAP-CVP >60 mmHg) 4
• Do not use dopamine as first-line agent; norepinephrine has superior outcomes 1
• Do not continue escalating doses beyond 0.5 mcg/kg/min without reassessing volume status and considering mechanical support 5
• Do not abruptly discontinue vasopressors; wean gradually over 12-24 hours 7, 2

Special Considerations

Anaphylaxis

• Epinephrine is first-line: Not norepinephrine 1
• Pediatric dopamine dosing: 2-20 mcg/kg/min using "rule of 6" preparation 1
• Fluid resuscitation: 1-2 L normal saline at 5-10 mL/kg in first 5 minutes for adults; up to 30 mL/kg in first hour for children 1

Peri-Intubation Hypotension

• Insufficient evidence for vasopressors versus fluids alone in preventing cardiovascular collapse 1
• If used: Push-dose phenylephrine 50-200 mcg or ephedrine 5-25 mg may temporarily improve BP 1
• Preferred approach: Optimize resuscitation before intubation and use induction agents with less hypotensive effect 1

Pregnancy/Postpartum

• SBP threshold: Use <85 mmHg (not <90 mmHg) from 20 weeks gestation through 3 days postpartum 4
• Norepinephrine: Remains first-line agent titrated to MAP 65 mmHg in maternal sepsis 4

1, 4, 6, 7, 2, 9, 5, 8, 3