Vasopressors and Inotropes

Dobutamine	Dopamine
Epinephrine	inamrinone - INOCOR ®
Midodrine - PROAMATINE ®	Milrinone - PRIMACOR ®
Norepinephrine - LEVOPHED ®	Phenylephrine - NeoSynephrine ®
Vasopressin - Pitressin ®

Dobutamine

Synthetic catecholamine (beta-1 agonist). Increases contractility and to a lesser extent heart rate. Little direct effect on BP. Uses: refractory CHF or hypotensive patients in whom vasodilators cannot be used because of effects on BP.

Onset of action: 1-10 minutes. Peak effect: 10-20 minutes. Half-life: 2 minutes. Excretion: Urine (as metabolites).

Adult (usual): 2.5 to 20 mcg/kg/minute. Maximum: 40 mcg/kg/min. Titrate to desired response. Administer into large vein. Usual doses to increase cardiac output are 2.5 to 15 mcg/kg/minute IV.

Drip rate (500mg/250 ml) ml/hr = wt(kg) x (mcg/min) x 0.03.
Supplied: 12.5 mg/ml (20 ml, 40 ml, 100 ml)

Dopamine

Used to support BP, CO and renal perfusion in shock.

Dosing (Adult):
Refractory CHF: initial dose: 0.5 to 2 mcg/kg/min.
Renal: 1 to 5 mcg/kg/min.
Severely ill patient: initially 5 mcg/kg/min, increase by 5 to 10 mcg/kg/min (q10 to 30 min) up to max of 50 mcg/kg/min.
Cardiac life support (initial): 2 to 5 mcg/kg/min - titrated to effect. Infusion may be increased by 1-4 mcg/kg/minute at 10 to 30 minute intervals until optimal response is obtained. If dosages >20-30 mcg/kg/minute are needed, a more direct-acting pressor may be more beneficial (ie, epinephrine, norepinephrine). [0.5 to 2 mcg/kg/min-dopa; 2-10-dopa/beta; >10-primarily alpha.]

Used to support BP, CO and renal perfusion in shock. IMPORTANT NOTE: Renal shutdown may occur at doses greater than 50 micrograms/kilogram/minute. The infusion rate should be reduced if urine flow decreases without adequate peripheral effects. Administer into large vein to prevent the possibility of extravasation (central line administration).

Calculation of drip rate (ml/hr) 400mg/250 ml: wt(kg) x mcg/min x 0.0375.

The predominant effects of dopamine are dose-related

At low rates of infusion (0.5-2 mcg/kg/min) dopamine causes vasodilation that is presumed to be due to a specific agonist action on dopamine receptors in the renal, mesenteric, coronary, and intracerebral vascular beds. The vasodilation in these vascular beds is accompanied by increased glomerular filtration rate, renal blood flow, sodium excretion, and urine flow. Hypotension sometimes occurs. An increase in urinary output produced by dopamine is usually not associated with a decrease in osmolality of the urine.

At intermediate rates of infusion (2-10 mcg/kg/min) dopamine acts to stimulate the beta1-adrenoceptors, resulting in improved myocardial contractility, increased SA rate and enhanced impulse conduction in the heart. There is little, if any, stimulation of the b2-adrenoceptors (peripheral vasodilation). Dopamine causes less increase in myocardial oxygen consumption than isoproterenol, and its use is not usually associated with a tachyarrhythmia. Clinical studies indicate that it usually increases systolic and pulse pressure with either no effect or a slight increase in diastolic pressure. Blood flow to the peripheral vascular beds may decrease while mesenteric flow increases due to increased cardiac output. At low and intermediate doses, total peripheral resistance (which would be raised by alpha activity) is usually unchanged.

At higher rates of infusion (10-20 mcg/kg/min) there is some effect on alpha-adrenoceptors, with consequent vasoconstrictor effects and a rise in blood pressure. The vasoconstrictor effects are first seen in the skeletal muscle vascular beds, but with increasing doses, they are also evident in the renal and mesenteric vessels. At very high rates of infusion (above 20 mcg/kg/min), stimulation of alpha-adrenoceptors predominates and vasoconstriction may compromise the circulation of the limbs and override the dopaminergic effects of dopamine, reversing renal dilation and naturesis.

Epinephrine

Dosing (Adult): Refractory hypotension (refractory to dopamine/dobutamine): Continuous IV infusion: 1 mcg/min (range: 1-10 mcg/minute) - titrate dosage to desired effect. Usual rate: 1 to 4 mcg/min. Severe cardiac dysfunction may require doses >10 mcg/minute (up to max of 20 mcg/min in a 70kg patient).

Administration: Central line administration only.

Endotracheal: Doses (2-2.5 x IV dose) should be diluted to 10 ml with NS or distilled water prior to administration.

Anaphylaxis (adult): 0.3 mg IM (0.3 ml of a 1:1000 solution). May be repeated if severe anaphylaxis persists - repeat q10 to 15 minutes prn or give 0.1 to 0.25 mg IV (1:10,000) over 5-10min repeat q5 to 15 minutes as needed or start continuous infusion: 1 to 4 mcg/min.

Asthma: inhalational form: start with 1 inhalation, then wait at least 1 min. If not relieved, use once more. Do not use again for at least 3 hr. Asthma: subcutaneous (SC) form: 0.2-0.5 mg (0.2-0.5 ml of a 1:1000 solution) SC every 2 hr as required. In severe attacks, may repeat dose every 20 min for a maximum of 3 doses.

Cardiac arrest: 1 mg IV initially; may be repeated as necessary q 3-5 min.

inamrinone - INOCOR ®

Phosphodiesterase inhibitor with positive inotropic and vasodilator activity.

FDA labeled indications: CHF, acute (short-term treatment). Non-FDA labeled indications: Cardiac surgery/low cardiac output states. Inotropic support (Advance cardiac life support).
Dosing (Adult): CHF (short term): initial: 0.75 mg/kg IV bolus over 2-3 min, may repeat in 30 minutes. Maint: 5-10 mcg/kg/min IV infusion. Recommended total daily dose, not to exceed 10 mg/kg.

Renal Dosing
Renal failure: Crcl<10 ml/min: Administer 50% to 75% of dose.

Midodrine - PROAMATINE ®

Orthostatic hypotension: 10 mg po tid at 3-4 hr intervals (during daytime hours). Doses greater than 30 mg/day have been tolerated by some patients, but safety has not been established.

Renal Dosing
Renal impairment: 2.5 mg tid - gradually increasing as tolerated.

[Supplied 2.5, 5 mg tablet]

Milrinone - PRIMACOR ®

Phosphodiesterase inhibitor with positive inotropic and vasodilator activity.
Venodilator: 0 Arterial dilator: ++ Inotropic effect: +++

Calculation of drip rate: 50 mg/250ml (ml/hr) = wt (kg) x 0.3 x mcg/kg/min.

Dosing (Adult):
CHF: initial loading dose, 50 mcg/kg IV over 10min, then 0.375 to 0.75 mcg/kg/min IV (Usual: 0.5 mcg/kg/min). Cardiac surgery: 15min before separation from cardiopulmonary bypass, 50 mcg/kg IV over 20 minutes followed by a continuous infusion of 0.5 mcg/kg/min IV for a minimum of 4hr.

Recommended infusion rates: renal insufficiency
Creatinine Clearance (mL/min/1.73 m ²)	Infusion Rate (mcg/kg/min)
5	0.20
10	0.23
20	0.28
30	0.33
40	0.38
50	0.43

Supplied: Injection (soln): 1 mg/ml (10 ml, 20 ml, 50 ml)

Norepinephrine - LEVOPHED ®

Alpha receptor & Beta-1 agonist. Used to maintain BP in hypotensive states. Most potent vasoconstrictor (Norepi >>> phenylephrine).

Dosage (initial): 8 to 12 mcg/min -titrate to BP (Usual target: SB:80-100 or MAP=80). Usual maintenance: 2 to 4 mcg/min. Note: doses as high as 0.5 to 1.5 mcg/kg/min for 1-10days have been used in septic shock.

Note: Norepinephrine dosage is stated in terms of norepinephrine base and intravenous formulation is norepinephrine bitartrate. Norepinephrine bitartrate 2 mg = Norepinephrine base 1 mg.

Usual range: 8-30 mcg/minute. Range used in clinical trials: 0.01-3 mcg/kg/minute. ACLS dosage range: 0.5 to 30 mcg/minute.
Administer into large vein to avoid the potential for extravasation.

Calculation of drip rate 8 mg/ 250 ml (ml/hr) = mcg/min x 1.875.
Supplied: Injection (soln): 1 mg/ml - 4 ml

Phenylephrine - NeoSynephrine ®

Alpha agonist. May be given IM,SC, IV push, or by continuous infusion.

Treat mild/moderate hypotension, also PSVT.

IV infusion: usual initial rate: 0.1 to 0.18 mg/min (100 to 180mcg/min) (titrate).
Usual maintenance rate: 40-60 mcg/min.
Maximum rate: infusion rates as high as 10 mcg/kg/min may be required in shock.

IV bolus therapy: 0.1 to 0.5 mg/dose every 10-15 minutes as needed (initial dose should not exceed 0.5 mg) PSVT: 0.5 mg rapid IV push, subsequent doses may be increased in increments of 0.1 to 0.2mg.

Calculation of drip rate (40 mg/250) (ml/hr) = (mg/min) x 375.

Vasopressin - Pitressin ®

ADH analog (Posterior pituitary hormone).
Dosing (Adults):
Diabetes insipidus: Note: Dosage is highly variable - titrated based on serum and urine sodium and osmolality in addition to fluid balance and urine output. 5-10 units IM/SQ 2-4 times daily as needed (dosage range 5-60 units/day). Abdominal distention: 5 units IM stat, then 10 units every 3-4 hours.

GI hemorrhage: Continuous IV infusion: 0.5 milliunits/kg/hour (0.0005 unit/kg/hour). Double dosage as needed every 30 minutes to a maximum of 10 milliunits/kg/hour.
IV: Initial: 0.2-0.4 unit/minute, then titrate dose as needed. If bleeding stops, continue at same dose for 12 hours, taper off over 24-48 hours.
Out-of-hospital asystole (unlabeled use): Adults: 40 units IV. If spontaneous circulation is not restored in 3 minutes, then repeat dose.
Pulseless VT/VF: 40 units IV (as a single dose only). If no IV access - administer 40 units diluted with NS (to a total volume of 10 ml) endotracheally.

Vasodilatory shock/septic shock: Vasopressin may be used in patients with refractory shock despite adequate fluid resuscitation and the use of high-dose conventional catecholamines such as norepinephrine and dopamine, however, further studies are needed to determine its exact place in therapy. Current evidence does not support the use of vasopressin as a replacement for norepinephrine or dopamine as a first-line agent.

The recommended infusion rate for vasopressin in the treatment of shock in adults is 0.01– 0.04 units/min. This dosage range is reported to be effective in about 85% of patients with norepinephrine resistant hypotension. Doses greater than 0.04 units/min may lead to cardiac arrest.

O'Brien A et al reported rapid rebound hypotension as a common problem after treatment with vasopressin is stopped. Potential side effects of vasopressin infusion range from ischemic skin lesions to possible intestinal ischemia. Vasopressin therapy may also result in decreased cardiac output and hepatosplanchnic flow.

Supplied: Injection: 20 units/ml (0.5 ml, 1 ml, 10 ml)

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

Receptor pharmacology
Agent	Alpha-1	Beta-1	Beta-2	Dopaminergic	1° Clinical effects
Dobutamine	0/+	++++	++	0	CO+, SVR -
Dopamine 0.5-2 ug/kg/min 5-10 ug/kg/min 10-20 ug/kg/min	0 + ++	+ ++ ++	0 0 0	++ ++ ++	CO+, SVR+ CO+, SVR+ SVR++
Epinephrine	+++	+++	++	0	CO++, SVR<-->/+
Norepinephrine	+++	++	0	0	CO <-->/+ , SVR++
Phenylephrine	+++	0	0	0	CO <-->/+ , SVR++

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