Inotropes & Vasopressors in Shock

• Sympathetic nervous system is activated
• Release of endogenous catecholamines
• Epinephrine
• Norepinephrine
• Excitation of adrenoreceptors
• α1
• Β1
• Β2
• (Dopaminergic)
• Hypothalamo-pituitary-adrenal (HPA) axis activation
• Stress hormone release (i. e cortisol & ADH)

Action

- α1, β1, β2 agonism

• Lower dose: β > α (inotropy)
• Higher dose: α > β (vasoconstriction)

Dose

• 1-20 mcg/min or 0.01 - 0.5 mcg/kg/min

Clinical Use

• Refractory shock, adjunct (2nd or 3rd line)
• Consider in patients with cardiogenic shock component
• Anaphylaxis (β2 bronchodilates, mitigates airway mucosal edema)
• Cardiac arrest

Action

- α1 >> β1, β2 agonism

• Primary vasoconstrictor - increases SBP, DBP, PP
• Weak inotrope, Minimal chronotropy

Dose

• 2-30 mcg/min or 0.05-0.5 mcg/kg/min

Clinical Use

• 1st line septic shock (surviving sepsis guidelines)
• Suggested for undifferentiated & cardiogenic shock

Note

• Potential rate limiting tachycardia/tachyarrhythmias

Action

Pure α agonist

Dose

• 20-200mcg/min
• Bolus dose: 100-200 mcg Q 3-5 min

Clinical Use

• Septic shock in patients who do not tolerate norepinephrine
• Anesthetic induced hypotension
• Shock in pts w/ Aortic/Mitral Stenosis
• Hypotension from simultaneous ingestion sildenafil & nitrates
• To decrease outflow tract gradient in pts w/ obstructive hypertrophic cardiomyopathy

Notes

• Least arrhythmogenic
• Potential for reflex bradycardia
• Unopposed alpha – ischemic effects

Action

Vasopressin receptor agonism

• V1→ Vasoconstricts vascular smooth muscle = ↑ SVR
• V2 → Reabsorbs H2O from renal collecting duct = ↓ UOP
• ↑ vascular sensitivity to catecholamines (augments pressor effect)
• Attenuates ATP activated K channels & NO production (BP augmentation)
• Reverses adrenergic rec down regulation

Dose

0.04 units/min

Clinical Use

• Adjunct to Norepinephrine in refractory shock
• Pts with Aortic/Mitral Stenosis, pulmonary HTN
• GI Hemorrhage
• Hemorrhagic shock (post hemorrhage control)

Notes

• Preserved effect in acidosis & hypoxia (unlike catecholamines)

Action

– dose dependent

• Low dose (2.5-5 mcg/kg/min) - D1 & D2 (vasodilation & increased blood flow)
• Medium dose (5-10 mcg/kg/min) - β
• High dose (10-20 mcg/kg/min) - α
• Unclear relationship in clinical practice

Clinical Use

• ACLS Guidelines for management of symptomatic bradycardia not responsive to atropine or pacing

Notes

• High arrhythmogenicity
• ↑ myocardial oxygen demand

Action

Strong β, minimal α agonism

• Β1:β2 - binds 3:1 ratio
• Strong inotrope, weaker chronotropy

Dose

• 2.5-20mcg/kg/min (usual inotropic range: 5-10 mcg/kg/min)

Clinical Use

• Shock with ↓ CO
• Decompensated HF

Notes

• Hypotension (Start with low doses and titrate up, may need concurrent vasopressor)
• Tolerance (days)
• Increases myocardial oxygen demand
• Arrhythmogenic (malignant ventricular arrhythmias)

Action

Pure β agonism

• Strong chronotrope & inotrope
• Strong systemic & mild pulmonary vasodilatory effects

Dose

• 1-10 mcg/min

Clinical Use

• Brady arrhythmias, Heart Block, Torsade de Pointes

Notes

• Generally restricted to Cardiology

Phosphodiesterase inhibitors (i. e. Milrinone)

Action

PDE 3 inhibition - Increased intracellular cAMP

• Potent inotrope & vasodilator
• Diastolic relaxation (lusitropy)
• Reduces preload, afterload, SVR

Dose

• 0.125- 0.75 mcg/kg/min

Clinical Use

• Shock with ↓ CO
• Decompensated HF, if adrenergic recs downregulated/desensitized in chronic HF

Notes

- Increases myocardial oxygen demand

• Methylene Blue (inhibition guanylate cyclase – reducing NO production, refractory shock)
• Angiotensin II (vasodilatory shock, refractory)
• Calcium-Sensitizing agents (levosimendan, heart failure)

• f Shock

• Hemorrhagic
• Critical reduction circulating plasma volume

• Septic
• Neurogenic
• Anaphylactic

Cardiogenic

• Tamponade, tension PTX, massive PE
• IVC compression
• High PEEP