Dopamine

Dopamine
1. Endogenous Catecholamine with Dopaminergic and B1 activity
2. Has largely been replaced by Norepinephrine as a Vasopressor in adult shock (but still used in pediatric shock)
3. Increases cardiac contractility, systolic Blood Pressure and to a lesser extent Heart Rate
4. Has dose related effects with preserved renal and CNS perfusion at lower doses

Dopamine is an endogenous Catecholamine
Dopamine is synthesized in vivo from Tyrosine (via Dopa)
Two Dopamine receptors are identified (D1, D2)
1. Activation of either receptor inhibits Neuronal firing
2. Apomorphine is an endogenous D2 Agonist
3. Many Antipsychotics inhibit adenylate cyclase release on D1 receptor activation
Dopaminergic Pathways
1. Substantia Nigra to striatum (nigrostriatal pattern, affected in Parkinsonism)
2. Medulla Chemoreceptor Trigger Zone (Vomiting)
3. Hypothalamus to the pituitary intermediate lobe (Prolactin release)

Half life of Dopamine is short and requires infusion
1. As with other Catecholamines, rapidly metabolized by COMT and MAO (A in brain, B peripherally)
Low dose (2-5 mcg/kg/min)
1. Increases splanchnic flow
2. Increases coronary perfusion
3. Increases cerebral flow
4. Increases renal perfusion
  1. Previously recommended for oliguric Renal Failure
  2. No longer recommended due to lack of GFR effect
Mid-dose (5-10 mcg/kg/min)
1. Direct Beta Adrenergic Receptor effects
  1. Increases cardiac contractility
  2. No effect on Blood Pressure
  3. No effect on Heart Rate
2. Stimulates Norepinephrine release
  1. Effect blunted if Norepinephrine stores depleted
High Dose (10-20 mcg/kg/min)
1. Increase in Blood Pressure
2. Tachycardia may be significant
3. Vasoconstriction of renal and splanchnic beds (with decreased GFR)

Has largely been replaced by Norepinephrine as a Vasopressor in adult shock (but still used in pediatric shock)
Hemodynamically significant Hypotension
1. Systolic Blood Pressure under 90 mmHg
2. Poor Tissue perfusion
  1. Oliguria or Anuria
  2. Altered Level of Consciousness
3. No Hypovolemia
Hypotension following Resuscitation
1. Symptomatic Bradycardia
2. Return of Spontaneous Circulation

Dopamine has been largely replaced by Norepinephrine in adults in U.S.
1. Theoretically safer than Norepinephrine when used peripherally
  1. However Norepinephrine is often initially used via a reliable peripheral IV safely
2. Theoretically with greater renal protection than other Vasopressors
  1. Does not appear to offer any significant benefit over other Vasopressors in renal protection
In children, Dopamine is still a first-line Vasopressor despite risks
1. See the adverse effects (e.g. Dysrhythmia) below
2. Dopamine is asssociated with a three fold increased mortality in septic children
  1. Ventura (2015) Crit Care Med 43(11): 2292-302 +PMID: 26323041 [PubMed]

Preparation
1. Start with 1 ampule Dopamine (400 mg)
2. Option 1: Dissolve 400 mg (1 ampule) Dopamine in 250 ml D5W
  1. Final Concentration: 1600 mcg/ml
  2. Weight 70 kg: Infusion rate 13 ml/h provides 5 mcg/kg/min
3. Option 2: Dissolve 800 mg (2 ampules) Dopamine in 250 ml D5W
  1. Final Concentration: 3200 mcg/ml
  2. Weight 70 kg: Infusion rate 6.5 ml/h provides 5 mcg/kg/min
Start Dose: 5 mcg/kg/min
Titrate: increase by 5 to 10 mcg/min every 10 min to 5-20 mcg/kg/min (maximum 50 mcg/kg/min) to clinical response
1. Perfusion
2. Urine Output
3. Mean arterial pressure or systolic Blood Pressure

Tachycardia
1. Increases myocardial oxygen demand
Arrhythmias
1. Premature Ventricular Contraction (PVC)
2. Supraventricular Tachycardia (SVT)
3. Ventricular Tachycardia (VT)
Hypertensive Crisis
Increases Pulmonary artery wedge pressure
1. May worsen pulmonary congestion
2. May provoke Congestive Heart Failure
Gastrointestinal
1. Nausea and Vomiting

Avoid Dopamine dose over 20 ug/kg/min
1. Results in severe Vasoconstriction and ischemia
2. Consider adding Norepinephrine if inadequate BP
Use caution with Dopamine in Congestive Heart Failure
1. Consider adding Vasodilator
  1. Nitroprusside
  2. Nitroglycerin
2. Consider using Dobutamine instead of Dopamine
Taper Dopamine gradually to avoid Hypotension
Use Dopamine via central venous catheter
1. Extravasation causes severe local tissue ischeme and necrosis
2. Antidote for extravasation
  1. Phentolamine 5-10 mg diluted in 10-15 ml NS
  2. Infiltrate area of extravasation with Phentolamine

Sodium Bicarbonate inactivates Dopamine
1. Also occurs with Epinephrine
Monoamine Oxidase Inhibitors potentiate Dopamine effect
1. Use only one tenth of regular dose
Bretylium effects may be synergistic with Dopamine
Phenytoin may cause Hypotension with Dopamine