Vasopressor

See Also

Background

See specific medications (follow links) for preparation and dosing protocols
Vasopressors are typically used via Central Line access
1. However may be used peripherally for stabilization in first 1-2 hours (see precautions below)
2. Push Dose Pressors are typically used via Peripheral IV Access (see below)

Precautions
General

Vasopressors are second-line therapy for Hypotension after cause-specific measures
1. Start with at least 30 ml/kg of crystalloid in Septic Shock
2. Replace acute blood loss with blood
Frequently reevaluate volume status, perfusion markers (e.g. Lactic Acid) and Hypotension response
1. See Hypotension
2. See Rapid Ultrasound in Shock

Precautions
Peripheral Vasopressor administration

Do not use Vasopressors via unreliable, small or deep peripheral site
1. Use only larger bore, reliable superficial IVs that can be closely monitored
2. Avoid peripheral hand IV or Ultrasound-guided deep brachial (occult extravasation risk)
Best to transition within first 2 hours to Central Line Vasopressor delivery
Monitor peripheral IV closely for extravasation
Peripheral Vasopressor delivery appears safe for short-term use (studies looked at 12-24 hours)
1. Recent studies have demonstrated Norepinephrine peripheral safety
2. Push Dose Pressors (see below) also appear safe
3. Ricard (2013) Crit Care Med 4(9): 2108-15 +PMID:23782969 [PubMed]
4. Cardenas-Garcia (2015) J Hosp Med 10(9): 581-5 +PMID:26014852 [PubMed]
5. Nguyen (2020) Am J Emerg Med +PMID: 31959524 [PubMed]
Peripheral Vasopressor Extravasation management
1. Direct others to obtain reliable access (other peripheral IV, IO Line, Central Line)
2. Leave infiltrating catheter in place until following measures are completed
3. Use the infiltrating catheter to withdraw as much infused Vasopressor from the site
4. Phentolamine Mesylate SQ Immediately (even if skin site has not yet whitened)
  1. Dilute Phentolamine vial (5 mg/ml) in 9 ml Normal Saline
  2. Inject diluted phentolamine 0.1 to 0.2 mg/kg (up to 10 mg) SQ into extravasation site
  3. Second dose may be needed
5. Consult plastic surgery
References
1. Orman and Weingart (2016) EM:Rap 16(5): 12-3

Preparations
Push Dose Pressors (Bolus Dose Pressors)

Indications
1. Temporizing measure in severe Hypotension (MAP <60 mmHg)
2. Bolus pressors typically via peripheral IV (prior to central access)
General
1. Used initially prior to central Intravenous Access
2. Medications are used in diluted form
3. Both Epinephrine and Phenylephrine have onset of action within 1 minute
4. Phenylephrine duration of action 10-20 minutes
5. Epinephrine duration of action 5-10 minutes
6. Precaution: Dosing errors are common (double check concentration and dose)!
  1. Label all syringes with medication and concentration
  2. Holden (2018) Ann Emerg Med 71(1): 83-92 +PMID:28601272 [PubMed]
Epinephrine (diluted to 10 mcg/ml)
1. Epineprhine 10 mcg/ml 0.5 to 2 ml (5-20 mcg) every 2-5 minutes
2. See Epinephrine for dilution approach (do not use undiluted cardiac Epinephrine)
Intravenous Phenylephrine
1. Phenylephrine (diluted to 10 mcg/ml) 0.5 to 2 ml (50-200 mcg) every 2-5 minutes
2. See Phenylephrine for dilution approach (do not use undiluted Phenylephrine)
Norepinephrine
1. Norepinephrine is typically premixed at 16 mcg/ml (no dilution needed)
2. Dose: 0.5 to 1 ml (8 to 16 mcg)
3. Onwochei (2017) Anesth Analg 125(1): 212-8 +PMID:28248702 [PubMed]
References
1. Swaminathan and Weingart in Herbert (2018) EM:Rap 18(11): 3-4

Preparations
Pressor Infusions - Alpha adrenergic agents (primarily)

Norepinephrine
1. Indications
  1. Preferred first-line Vasopressor in adults
2. Receptor Activity
  1. Alpha-1 agonist
  2. Lower beta adrenergic activity
3. Dosing (adults)
  1. Weight Based (preferred)
    1. Start at 0.05 mcg/kg/min
    2. Unlikely to benefit from titration above 0.3 mcg/kg/min
  2. Non-weight based
    1. Start at 5 mcg/min (some recommend starting at 0.5 to 1.0 ug/min)
    2. Typical dose range: 2 to 30 mcg/min
4. Effects
  1. Strong Vasoconstrictor
  2. Minimal chronotropic activity
5. Adverse effects
  1. Reflex Bradycardia
  2. Tachyarrhythmia
  3. May precipitate Myocardial Ischemia or infarction
Epinephrine
1. Receptor Activity
  1. Alpha-1 agonist
  2. Lower beta adrenergic activity
2. Dosing
  1. Vasopressor dosing: 1-10 mcg/min
  2. Inotropic dosing: 0.01 to 0.08 mcg/kg/min
  3. Push dose (see above): 5-20 mcg every 2-5 min
  4. ACLS (pulseless arrhythmia): 1 mg bolus
3. Effects
  1. Strong inotropy
  2. Strong chronotropy
4. Adverse effects
  1. May precipitate Myocardial Ischemia or infarction
Dopamine
1. Indications
  1. Has been the preferred first-line Vasopressor in children (but significant risks)
  2. Largely replaced by Norepinephrine in adults in U.S.
  3. Theoretically safer than Norepinephrine when used peripherally
    1. However Norepinephrine is often initially used via a reliable peripheral IV safely
  4. Theoretically with greater renal protection than other Vasopressors
    1. Does not appear to offer any significant benefit over other Vasopressors in renal protection
2. Receptor Activity
  1. Alpha-1 agonist
  2. Moderate beta adrenergic activity
  3. Low Dopaminergic activity
3. Dosing
  1. Infusion: 2 to 20 mcg/min
4. Effects
  1. Precursor to Norepinephrine
  2. Inotropy and chronotropy at moderate doses
  3. Strong Vasoconstrictor at higher doses
5. Adverse Effects
  1. Increased risk for dysrhythmia
  2. Three fold increased mortality in septic children
    1. Ventura (2015) Crit Care Med 43(11): 2292-302 +PMID: 26323041 [PubMed]
Phenylephrine
1. Indications
  1. Primarily used as a push-dose pressor (see above), especially by anesthesia
2. Receptor Activity
  1. Exclusively alpha-1 agonist
3. Dosing
  1. Infusion: 25-200 mcg/min
  2. Push Dose Pressor: 50-200 mcg every 2-5 min prn
4. Effects
  1. Strong peripheral Vasoconstrictor (with increased Afterload)
  2. Minimal chronotropic activity
5. Adverse effects
  1. Reflex Bradycardia
  2. Cardiogenic Shock (avoid use in reduced ejection fraction)

Preparations
Pressor Infusions - Beta adrenergic agents (primarily)

Precautions
1. Inotropic and chronotropic agents with risk for worsening Hypotension
2. Exercise caution in Hypotension
3. Most providers use in combination with a low dose pure Vasopressor (e.g. Norepinephrine)
Dobutamine
1. Receptor Activity
  1. Primarily Beta-1 Agonist
  2. Also activity as a Beta-2 Agonist
2. Dosing
  1. Infusion: 5-40 mcg/kg/min
3. Effects
  1. Strong inotropy
  2. Moderate chronotropy
  3. Mild Vasodilation
4. Adverse effects
  1. Increases myocardial oxygen demand
  2. Arrhythmogenic
Milrinone
1. Mechanism
  1. PDE inhibitor blocks breakdown of cyclic Adenosine monophosphate, sustains Catecholamine activity
2. Receptor Activity
  1. Beta-1 Agonist
  2. Beta-2 Agonist
3. Dosing
  1. Infusion: 0.125 to 0.5 mcg/kg/min
4. Adverse Effects
  1. Hypotension risk (avoid in hypovolemia)
5. Effects
  1. Strong inotropy, increases Stroke Volume
  2. Decreases Afterload by dilating arterioles
Isoproteronol
1. Indications
  1. Hypotension due to Bradycardia
2. Receptor Activity
  1. Beta-1 Agonist
  2. Beta-2 Agonist
3. Dosing
  1. Infusion: 2 to 10 mcg/min
4. Effects
  1. Strong inotropy
  2. Strong chronotropy
  3. No significant vascular effect (although may decrease systemic vascular resistance)
  4. Cardiac Output not appreciably affected

Preparations
Pressor Infusions - Other sites of activity

Vasopressin
1. Indications
  1. Adjunct to other Vasopressors (e.g. Norepinephrine) in refractory Hypotension (especially Septic Shock)
2. Receptor Activity
  1. Exclusively at vasopressin receptors (some on vasculature)
3. Dosing
  1. Infusion: 0.01 to 0.04 units/min
4. Adverse effects
  1. Higher doses may be associated with ischemia
5. Effects
  1. Increases systemic vascular resistance while still maintaining CNS and cardiac blood flow
  2. Effective, even in severe acidosis

Resources

EM-Crit Blog (Scott Weingart)
1. http://emcrit.org/wp-content/uploads/push-dose-pressors.pdf

References

Goldberg (2015) Crit Dec Emerg Med 29(3): 9-19
McCollum in Herbert (2019) EM:Rap 19(7):4-6