AHFS Class:

• Selective beta-1-Adrenergic Agonists 12:12.08.08

Generic Name(s):

• Dopamine Hydrochloride

Dopamine hydrochloride, an endogenous catecholamine that is the immediate precursor of norepinephrine, is a sympathomimetic agent with prominent dopaminergic and β₁-adrenergic effects at low to moderate doses and α-adrenergic effects at high doses.112,115

Shock

Dopamine hydrochloride is used as adjunctive therapy to correct hemodynamic imbalances (e.g., increase cardiac output and blood pressure) in the treatment of shock.100,112,115 In patients who require vasopressor support, individual hemodynamic abnormalities must be identified and monitored so that therapy can be adjusted as necessary.

Vasopressors such as dopamine are used in the management of shock to restore blood pressure and tissue perfusion after initial fluid resuscitation is attempted.153,154,155,156,157,158,159,163 The Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock recommend norepinephrine as the first-line vasopressor of choice in adults with septic shock; if adequate blood pressure is not achieved, vasopressin or epinephrine may be added.153,155,158 Although dopamine was used widely in the past as a first-line vasopressor agent in patients with septic shock, more recent evidence indicates that the drug is associated with a greater risk of adverse effects (e.g., arrhythmias) and possibly also an increased risk of death compared with norepinephrine.153,154,155,158,163 In a multicenter randomized study (Sepsis Occurrence in Acutely Ill Patients II [SOAP II]) comparing the effects of dopamine and norepinephrine in patients with septic, cardiogenic, or hypovolemic shock, no substantial difference in 28-day mortality was observed between the vasopressors; however, use of dopamine was associated with more arrhythmic events in the overall population and an increased rate of death in the subgroup of patients with cardiogenic shock.154 In current expert guidelines, dopamine is considered an alternative vasopressor to norepinephrine only in highly selected patients with septic shock (e.g., those with low risk of tachyarrhythmias and bradycardia).153

Vasopressors also have been used to provide hemodynamic support in other types of shock (e.g., cardiogenic, hemorrhagic), generally as a temporary measure until the underlying cause can be treated.152,157,158,159,160,161,162,165 Some evidence suggests that early use of vasopressors in patients with hemorrhagic shock may be deleterious compared with aggressive fluid resuscitation; however, additional studies are needed to confirm this finding.152,157,160 Dopamine may be particularly useful in the management of cardiogenic shock (including that associated with acute myocardial infarction) because of the drug's net hemodynamic effects; however, some evidence (e.g., from the SOAP II study) suggests an increased risk of mortality compared with norepinephrine when used in patients with this type of shock.115,154,161,162 Early revascularization is the standard of care in patients with cardiogenic shock; use of vasopressors in this setting should be individualized and guided by hemodynamic monitoring.161,162 Some experts state that dopamine may be considered for the treatment of drug-induced hypovolemic shock when the patient is unresponsive to fluid volume expansion and inotropic and/or vasopressor support is required.112 The use of dopamine in low cardiac output syndrome following open heart surgery has been shown to increase long-term survival. However, because dobutamine lowers peripheral resistance over a wide dosage range, is not dependent on release of endogenous catecholamines for its effects, and is cardioselective, that drug may be preferable in the period immediately following cardiopulmonary bypass surgery.

Dopamine may increase cardiac output, blood pressure, and urine flow in patients with shock; however, the exact effects of the drug are dose related and based on the patient's clinical status at the time of administration.115 In low or intermediate doses, dopamine usually does not produce sufficient peripheral vasoconstriction to cause a rise in blood pressure; therefore, the dose should be rapidly increased until adequate blood pressure is obtained.115 If hypotension persists, a more potent vasoconstrictor such as norepinephrine may be required.115 Dopamine appears to be most effective when therapy is initiated shortly after the signs and symptoms of shock appear and before physiologic parameters such as blood pressure and myocardial function undergo severe deterioration and before urine flow has decreased to less than 0.3 mL/minute.115 However, the drug may increase urine flow, in some cases to normal levels, in patients with oliguria or anuria.115 Urine flow may also increase in patients with normal urine output and thereby reduce preexisting fluid accumulation.115

An α-adrenergic blocking agent such as phentolamine may be used to counteract the peripheral vasoconstriction produced by high doses of dopamine. Concomitant use of dopamine and a diuretic such as hydrochlorothiazide or furosemide may produce diuresis in patients who do not respond to dopamine or a diuretic alone. However, because dopamine acts as a proximal-tubule diuretic, the increased solute delivery to the distal tubular cells may increase distal oxygen consumption and potentially increase the risk of renal medullary ischemia in patients at risk of renal failure.101,108

Advanced Cardiovascular Life Support

Dopamine is used in advanced cardiovascular life support (ACLS)† for the treatment of symptomatic bradycardia in adults, particularly if associated with hypotension; although not a first-line drug, dopamine may be considered in patients who are unresponsive to atropine therapy, or as a temporizing measure while awaiting availability of a pacemaker.400,401

Dopamine also has been used during the resuscitation period for management of patients in cardiac arrest.112 High-quality cardiopulmonary resuscitation (CPR) and defibrillation are integral components of ACLS and the only proven interventions to increase survival to hospital discharge.400,401 Other resuscitative efforts, including drug therapy, are considered secondary and should be performed without compromising the quality and timely delivery of chest compressions and defibrillation.400,401 The principal goal of pharmacologic therapy during cardiac arrest is to facilitate the return of spontaneous circulation (ROSC), and epinephrine is considered the drug of choice for this use.400,401 Vasoactive drugs such as dopamine may be used for hemodynamic support following resuscitation from cardiac arrest.403,404 (See Uses: Advanced Cardiovascular Life Support and Cardiac Arrhythmias, in Epinephrine 12:12.12.)

Acute Renal Failure

Previous data from animal studies and some clinical studies in a limited number of healthy or critically ill adults indicated that low-dose (e.g., less than 5 mcg/kg per minute) infusions of dopamine may increase renal and mesenteric perfusion and improve renal function as a result of selective stimulation of renal dopaminergic receptors and subsequent renal vasodilation.107,109,110 However, more recent studies have failed to demonstrate any benefit from such therapy, and routine use of low-dose (“renal dose”) dopamine therapy for the prevention or amelioration of acute renal failure in critically ill patients is no longer recommended.102,105,106,107,108,112,153,156 In a randomized, double-blind, placebo-controlled study, adults in an intensive care unit (ICU) at risk for acute renal failure who received dopamine as a continuous, low-dose (2 mcg/kg per minute) infusion had similar peak serum creatinine concentrations during treatment, similar durations of ICU and hospital stay, and similar survival to ICU or hospital discharge compared with those receiving placebo.101 Other studies in patients at high risk for renal failure receiving low-dose dopamine infusions (generally less than 2-3 mcg/kg per minute) have demonstrated similar findings.101,102,105,106,107,108 In a study in a small number of hemodynamically stable, critically ill patients, infusion of dopamine 3 mcg/kg per minute increased creatinine clearance, diuresis, and fractional excretion of sodium; however, these beneficial effects (except for diuresis) generally diminished after 24 hours, indicating the possibility of tolerance to the effects of dopamine.110 In addition, alterations in clearance and metabolism in critically ill patients may result in high interindividual variability in plasma dopamine concentrations for a given infusion rate (dosage) of the drug, making it difficult or impossible to guarantee a selective effect of the drug in this patient population.101,102,103,110 Low-dose infusions of dopamine are not without risk and may be associated with adverse effects such as suppression of respiratory drive,101,102,104,106 increased cardiac output and myocardial oxygen consumption,101,102,104,106 arrhythmias,101,102,104,106 hypokalemia,101,102,104 hypophosphatemia,101,102,104 gut ischemia,101,102,104 and disruption of metabolic and immunologic homeostasis.101,102,104,107

Heart Failure

Dopamine is used for short-term inotropic support in patients with refractory heart failure† to maintain systemic perfusion and preserve end-organ function.165 Because positive inotropic agents have not demonstrated improved outcomes in patients with heart failure and can be potentially harmful (e.g., increased risk of arrhythmias), particularly when used long term, the American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) recommend that these drugs be reserved for patients with severe systolic dysfunction who have low cardiac index and evidence of systemic hypoperfusion and/or congestion, or for palliative therapy in those with end-stage heart failure.165 To minimize the risk of adverse effects, the lowest possible dosage should be used and the patient should be evaluated regularly for the need for continued inotropic therapy.165

Low-dose dopamine infusion has been used in combination with loop diuretics to augment diuresis and improve renal blood flow in patients with acute decompensated heart failure†; however, the currently available evidence does not support routine use of dopamine for this purpose.115,116,165,166,168,169,170,174 Although some studies have suggested that dopamine may prevent worsening of renal function related to diuretic use in patients with acute decompensated heart failure, more recent studies generally have not confirmed this benefit.165,166,167,168,169,170,174

Administration

Dopamine hydrochloride is administered by IV infusion using an infusion pump or other apparatus to control the rate of flow.115,116 Precise control of the infusion rate is essential to avoid inadvertent administration of a bolus dose.115 To minimize the risk of necrosis, infusion of dopamine should be given into a large vein, preferably the antecubital vein.115 Less suitable veins (e.g., hand or ankle vein) should be used only when required, but the site should be switched to a preferred vein as soon as possible. Care must be taken to avoid extravasation because local necrosis may result . 115

Dopamine also has been administered by intraosseous infusion† in the setting of advanced cardiovascular life support (ACLS), generally when IV access is not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.401,403

IV Administration

The commercially available dopamine hydrochloride injection concentrate must be diluted prior to administration;115 alternatively, commercially available solutions of dopamine hydrochloride in 5% dextrose may be used without dilution.116 The concentration of dopamine is dependent upon the dosage and fluid requirements of the individual patient. One suggested solution for infusion may be prepared by diluting 10 mL of the injection concentrate containing 40 mg of dopamine hydrochloride per mL (a total of 400 mg of dopamine hydrochloride) with either 250 or 500 mL of one of the following solutions: 0.9% sodium chloride, 5% dextrose, 5% dextrose with 0.9% sodium chloride, 5% dextrose with 0.45% sodium chloride, lactated Ringer's, 5% dextrose in lactated Ringer's, or (1/6) M sodium lactate; dilution with 250 mL of solution will yield a final concentration of 1600 mcg/mL and dilution with 500 mL of solution will yield a final concentration of 800 mcg/mL.115

Dopamine hydrochloride injections should be inspected visually for discoloration and/or particulate matter prior to administration whenever solution and container permit.115,116 Solutions darker than slightly yellow or that are discolored in any other way should not be used.115,116 Dopamine in 5% dextrose should not be infused into an umbilical artery catheter.116 The drug should be administered via a controlled-infusion device (pump), preferably a volumetric pump; dopamine should not be administered using an ordinary, gravity-controlled IV administration set.115,116 Dopamine in 5% dextrose in flexible containers (e.g., LifeCare^®) should not be used in series connections.116

The manufacturer's prescribing information should be consulted for proper methods of administration and other associated precautions.115,116

Standardize 4 Safety

Standardized concentrations for dopamine have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 249,250Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249,250Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249,250 For additional information on S4S (including updates that may be available), see [Web].249,250

Dosage

Shock

The rate and duration of dopamine hydrochloride infusion should be individualized and carefully adjusted to achieve the desired hemodynamic and renal response as indicated by heart rate, blood pressure, urine flow, and, whenever possible, measurement of central venous or pulmonary wedge pressure and cardiac output.115,116

Dopamine hydrochloride infusion is usually initiated at a rate of 2-5 mcg/kg per minute in patients who are likely to respond to modest increases in cardiac contractility and renal perfusion.115 The infusion rate may be increased by 1-4 mcg/kg per minute at 10- to 30-minute intervals until the optimal response is attained. In more severely ill patients, dopamine hydrochloride infusion should be initiated at a rate of 5 mcg/kg per minute, and increased gradually in increments of 5-10 mcg/kg per minute, up to 20-50 mcg/kg per minute as needed.115 Once optimal hemodynamic effects have been achieved, the lowest possible dosage that maintains these effects should be used. In general, most patients can be maintained at an infusion rate less than 20 mcg/kg per minute; however, infusion rates exceeding 50 mcg/kg per minute have been used safely in advanced states of circulatory decompensation.115

In patients with occlusive vascular disease, some clinicians recommend that dopamine hydrochloride therapy be initiated with an infusion rate of 1 mcg/kg per minute or less because of the risk of local ischemia.59 Such patients should be monitored closely for any signs or symptoms of compromised circulation during the infusion; if this occurs, the rate should be decreased or the infusion discontinued.115

Patients who have been receiving monoamine oxidase (MAO) inhibitors within the previous 2-3 weeks should receive initial doses of dopamine hydrochloride of no greater than 10% of the usual dose.115

At high dosages in patients in whom unnecessary expansion of fluid volume is a concern, administration of a more concentrated solution of dopamine hydrochloride (concentrations as high as 3.2 mg/mL have been used) may be preferable to increasing the flow rate of a dilute solution.116 Urine output should be measured frequently when doses exceeding 50 mcg/kg per minute are employed.115 When adjusting dosage to obtain the desired systolic blood pressure, optimal dosage for renal response may be exceeded and urine output may decrease.115 If urine flow begins to decrease in the absence of hypotension, reduction of the rate of infusion should be considered.115

If a disproportionate increase in diastolic pressure (i.e., a marked decrease in pulse pressure) is observed in patients receiving dopamine, the rate of dopamine infusion should be decreased, and the patient observed carefully for further evidence of predominant vasoconstrictor activity, unless such an effect is desired.115 (See Cautions: Precautions and Contraindications.) Dosage reduction also may be required if a decrease in established urine flow rate, increase in tachycardia, or new dysrhythmia occurs.116

Studies have not been conducted to specifically inform dosage recommendations in pediatric patients; however, clinical experience indicates that dosing in pediatric patients is generally similar to that in adults.115,116

The manufacturer states that if dopamine hydrochloride is used in geriatric patients, the initial dosage usually should be at the low end of the dosage range since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group than in younger patients.116

When discontinuing an infusion, it may be necessary to gradually decrease the dose of dopamine while expanding blood volume with IV fluids to prevent a recurrence of hypotension.115 In patients who have been receiving moderate to high doses of dopamine, some clinicians recommend that the final dosage should not be less than 5 mcg/kg per minute in order to avoid hypotension.

Advanced Cardiovascular Life Support

When used in ACLS for the treatment of symptomatic bradycardia in adults†, the usual initial dosage range of dopamine hydrochloride is 2-10 mcg/kg per minute; dosage should be titrated according to patient response.401 Infusion rates exceeding 10 mcg/kg per minute are associated with vasoconstrictive effects.401 If used for postresuscitation stabilization in adults, a dopamine hydrochloride infusion rate of 5-10 mcg/kg per minute has been recommended.404

If dopamine hydrochloride is used for postresuscitation stabilization in pediatric patients†, the usual IV or intraosseous† infusion rate is 2-20 mcg/kg per minute.403 Although dosages exceeding 5 mcg/kg per minute stimulate the cardiac β-adrenergic receptors, this effect may be reduced in infants.403 Infusion rates exceeding 20 mcg/kg per minute may result in excessive vasoconstriction.403

Heart Failure

In the short-term treatment of patients with severe, refractory heart failure†, some clinicians recommend that dopamine hydrochloride infusion be initiated at a rate of 0.5-2 mcg/kg per minute. The usual dosage range of dopamine hydrochloride in patients with heart failure is 5-10 mcg/kg per minute.165 Although dosages exceeding 5 mcg/kg per minute stimulate the cardiac β-adrenergic receptors, this effect may be reduced in patients with congestive heart failure.403

To minimize the risk of adverse effects, the lowest possible dosage of dopamine should be used and the patient should be evaluated regularly for the need for continued inotropic therapy.165

Adverse Effects

Dopamine hydrochloride may cause ectopic heartbeats, tachycardia, angina, palpitation, vasoconstriction, hypotension, dyspnea, nausea, vomiting, and headache. Other less frequent adverse effects include cardiac conduction abnormalities, widened QRS complex, bradycardia, hypertension, azotemia, anxiety, and piloerection. Ventricular arrhythmias may occur with very high doses. Dopamine may cause elevations in serum glucose although the concentrations usually do not rise above normal limits. A few cases of peripheral cyanosis also have been reported in patients receiving dopamine.

Gangrene of the extremities has occurred when high doses of dopamine were administered for prolonged periods and in patients with occlusive vascular disease receiving low doses of dopamine, and extravasation of dopamine may result in tissue necrosis and sloughing of surrounding tissues. (See Cautions: Precautions and Contraindications.)

Precautions and Contraindications

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes. Blood volume depletion should be corrected as fully as possible before dopamine therapy is instituted. In an emergency, the drug may be used as an adjunct to fluid replacement or as a temporary supportive measure to maintain coronary and cerebral artery perfusion until volume replacement can be completed, but dopamine must not be used as sole therapy in hypovolemic patients. Additional volume replacement may also be required during or after administration of the drug because of the effects of dopamine on urine flow. Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia; in addition, monitoring of central venous or pulmonary arterial diastolic pressure is necessary to avoid overloading the cardiovascular system, diluting serum electrolyte concentrations, and precipitating congestive heart failure or pulmonary edema. Hypoxia, hypercapnia, and acidosis (which may also reduce the effectiveness and/or increase the incidence of adverse effects of dopamine) must be identified and corrected prior to, or concurrently with, administration of the drug.115

During administration of dopamine, blood pressure and urine flow and, when possible, cardiac output and pulmonary wedge pressure should be monitored.115 If excessive vasoconstriction (as indicated by a disproportionate increase in diastolic blood pressure and a decrease in pulse pressure), decreased urine output, increased heart rate, or an arrhythmia occurs, the rate of infusion of dopamine should be decreased or temporarily suspended and the patient should be observed closely. If blood pressure or urine output fails to respond to discontinuance of the drug, administration of a short-acting α-adrenergic blocking agent such as phentolamine should be considered. If hypotension occurs during dopamine infusion, the infusion rate should be increased rapidly in order to increase blood pressure. If hypotension persists, dopamine should be discontinued and a drug with greater vasoconstricting properties such as norepinephrine should be administered. When discontinuing an infusion, it may be necessary to decrease the dose of dopamine gradually while expanding blood volume with IV fluids to prevent a recurrence of hypotension.115 Sudden cessation of dopamine infusion may result in marked hypotension.

Patients with a history of occlusive vascular disease (e.g., atherosclerosis, arterial embolism, Raynaud's disease, cold injury, diabetic endarteritis, Buerger's disease) should be carefully monitored during dopamine therapy for decreased circulation to the extremities indicated by changes in color or temperature of the skin or pain in the extremities.115 If such manifestations occur, they may be corrected by decreasing the rate of infusion or discontinuing dopamine;115 however, these changes occasionally have persisted and progressed after discontinuing the drug. The potential benefits of continuing dopamine should be weighed against the possible risk of necrosis. Some clinicians recommend IV administration of 5-10 mg of phentolamine mesylate if discoloration of the extremities occurs. To reverse ischemia induced by dopamine†, 10 mg of chlorpromazine IV followed by a chlorpromazine infusion of 0.6 mg/minute has been used.

Caution should be used to avoid extravasation of the drug. Dopamine should be administered through a large vein whenever possible, preferably in the antecubital fossa rather than the hand or ankle.115 One manufacturer states that administration into an umbilical arterial catheter is not recommended. If larger veins are unavailable and the condition of the patient requires that the hand or ankle veins be used to administer dopamine, the injection site should be changed to a larger vein as soon as possible.115 The site of infusion should be continuously monitored for free flow.115 If extravasation occurs, 10-15 mL of 0.9% sodium chloride injection containing 5-10 mg of phentolamine mesylate should be infiltrated (using a syringe with a fine hypodermic needle) liberally throughout the affected area.115 Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours; therefore, phentolamine should be administered as soon as possible after extravasation is noted.115 In children, phentolamine mesylate doses of 0.1-0.2 mg/kg, up to a maximum of 10 mg per dose, may be administered.

Commercially available formulations of dopamine hydrochloride injection may contain sodium metabisulfate, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.115,116 The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.115

Dopamine should be used with caution in patients with ischemic heart disease. The drug is contraindicated in patients with pheochromocytoma and in patients with uncorrected tachyarrhythmias or ventricular fibrillation.115,116

Pediatric Precautions

The manufacturer states that safety and efficacy of IV dopamine infusions have not been established in children;115 however, the drug has been used in pediatric patients of all age groups from neonate onward.116 In pediatric patients, dopamine is recommended as an appropriate drug for the treatment of shock when the patient is unresponsive to fluids and systemic vascular resistance is low.403 Except for vasoconstrictive effects caused by inadvertent infusion of dopamine into the umbilical artery, adverse effects unique to the pediatric population have not been identified, nor have adverse effects identified in adults been found to be more common in pediatric patients.116 Although dopamine reportedly has been administered at rates as high as 125 mcg/kg per minute in some neonates, the usual dosage in children has been similar to that in adults on a mcg/kg per minute basis.116

Geriatric Precautions

Clinical studies of dopamine hydrochloride did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.116 Clinical experience to date has not identified any differences in responses between geriatric and younger patients.116 If dopamine hydrochloride is used in geriatric patients, the initial dosage of the drug usually should be at the low end of the dosage range, and caution should be exercised since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group than in younger patients.116

Mutagenicity and Carcinogenicity

In the Ames microbial ( Salmonella ) mutagen test (with or without metabolic activation), there was a reproducible dose-dependent increase in the number of revertant colonies with strains TA100 and TA98 at dopamine dosages approaching maximal solubility. However, such small increases were considered inconclusive evidence of mutagenicity. In a mammalian mutagenicity assay using L5178Y TK± mouse lymphoma cells, dopamine was associated with toxicity and increases in mutant frequencies at concentrations of 750 mcg/mL without metabolic activation and 3000 mcg/mL with activation. No increases in mutant frequencies occurred at lower concentrations. In the in vivo mouse and male rat bone marrow micronucleus tests, no clear evidence of clastogenic potential was found at IV dosages up to 224 and 30 mg/kg of dopamine hydrochloride, respectively.

Long-term studies in animals have not been performed to date to evaluate the carcinogenic potential of dopamine.

Pregnancy and Lactation

Pregnancy

Reproduction studies in rats and rabbits using IV dopamine hydrochloride dosages up to 6 mg/kg daily during organogenesis have not revealed evidence of teratogenicity or embryotoxicity; however, maternal toxicity (e.g., decreased body weight gain, death) was observed in rats. In a study in rats, subcutaneous dosages of 10 mg/kg for 30 days markedly prolonged metestrus and increased mean pituitary and ovary weights. After similar administration to pregnant rats, either throughout gestation or for 5 days beginning on day 10 or 15 of gestation, decreased body weight gain, increased mortality, and slight increases in cataract formation occurred in the offspring.

There are no adequate and well-controlled studies to date using dopamine hydrochloride in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.115 It is not known whether dopamine crosses the placenta.115 When dopamine is administered for advanced cardiovascular life support (ACLS) during cardiopulmonary resuscitation, the drug may decrease blood flow to the uterus; however, the woman must be resuscitated for survival of the fetus.112 If a vasopressor (e.g., dopamine) is used during labor in conjunction with oxytocic drugs, the vasopressor effect may be potentiated and result in severe hypertension.115 (See Drug Interactions: Oxytocic Drugs.)

Lactation

It is not known whether dopamine is distributed into human milk.115 Because many drugs are distributed into milk, the drug should be used with caution in nursing women.115

Monoamine Oxidase Inhibitors

Because dopamine is metabolized by monoamine oxidase (MAO), the effects of the drug are prolonged and intensified by MAO inhibitors.115 Patients who have been receiving MAO inhibitors within the previous 2-3 weeks should receive initial doses of dopamine of no greater than 10% of the usual dose.115

- and Beta-Adrenergic Blocking Agents

The cardiac effects of dopamine are antagonized by β-adrenergic blocking agents such as propranolol and metoprolol, and the peripheral vasoconstriction caused by high doses of dopamine is antagonized by α-adrenergic blocking agents.115 Dopamine-induced renal and mesenteric vasodilation is not antagonized by either α- or β-adrenergic blocking agents, but, in animals, is antagonized by haloperidol or other butyrophenones, phenothiazines, and opiates.

General Anesthetics

Ventricular arrhythmias and hypertension may occur when usual doses of dopamine are administered during halothane (or other halogenated hydrocarbon) or cyclopropane anesthesia.115 Extreme caution should be used when administering dopamine to patients receiving these general anesthetics which increase cardiac irritability.115

Phenytoin

Administration of IV phenytoin to patients receiving dopamine has resulted in hypotension and bradycardia; some clinicians recommend that phenytoin be used with extreme caution, if at all, in patients receiving dopamine.

Oxytocic Drugs

When a vasopressor agent (e.g., dopamine) is used in conjunction with oxytocic drugs, the pressor effect may be potentiated and result in severe hypertension.115

Other Drugs

The diuretic effects of low dosages of dopamine may be additive with or potentiated by diuretics (e.g., hydrochlorothiazide or furosemide).115 The pressor response of dopamine may be potentiated by tricyclic antidepressants.115 The concomitant use of dopamine with other vasopressors or vasoconstrictors (e.g., ergonovine) may result in severe hypertension.116

Laboratory Test Interferences

Dopamine suppresses pituitary secretion of thyrotropin (thyroid-stimulating hormone, TSH), growth hormone, and prolactin.116

Acute Toxicity

Acute overdosage of dopamine may result in excessive elevation of blood pressure. The rate of infusion of dopamine should be decreased or the drug should be discontinued temporarily until the patient is stabilized. Because of dopamine's short duration of action, these measures usually provide adequate management of toxicity. In cases of severe toxicity, administration of a short-acting α-adrenergic blocking agent (e.g., phentolamine) should be considered. (See Uses: Other Uses in Phentolamine 12:16.04.04.)

Pharmacology

Dopamine stimulates adrenergic receptors of the sympathetic nervous system.112 The drug principally has a direct stimulatory effect on β₁-adrenergic receptors, but also appears to have an indirect effect by releasing norepinephrine from its storage sites. Dopamine also appears to act on specific dopaminergic receptors in the renal, mesenteric, coronary, and intracerebral vascular beds to cause vasodilation. The drug has little or no effect on β₂-adrenergic receptors. In IV doses of 0.5-2 mcg/kg per minute, the drug acts predominantly on dopaminergic receptors; in IV doses of 2-10 mcg/kg per minute, the drug also stimulates β₁-adrenergic receptors. In higher therapeutic doses, α-adrenergic receptors are stimulated and the net effect of the drug is the result of α-adrenergic, β₁-adrenergic, and dopaminergic stimulation. The main effects of dopamine depend on the dose administered.112 In low doses, cardiac stimulation and renal vascular dilation occur and in larger doses vasoconstriction occurs.112 It is believed that α-adrenergic effects result from inhibition of the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas β-adrenergic effects result from stimulation of adenyl cyclase activity.

The β₁-adrenergic effects of dopamine exert a positive inotropic effect on the myocardium and result in an increase in cardiac output because of increased myocardial contractility and stroke volume in healthy individuals and in patients with shock or congestive heart failure.112 Systolic blood pressure and pulse pressure may be increased as a result of increased cardiac output; however, peripheral vasodilation and the resulting decrease in peripheral resistance may counteract these effects. Blood pressure, therefore, may remain unchanged or be only slightly elevated. Heart rate is usually not substantially changed. Coronary blood flow and myocardial oxygen consumption are usually increased as a result of increased myocardial contractility. Like other catecholamines, dopamine may facilitate atrioventricular conduction and increase myocardial excitability; however, the tendency of dopamine to induce cardiac arrhythmias may be slightly greater than that of dobutamine but is considerably less than that of isoproterenol and other catecholamines. Dopamine has variable effects on pulmonary vascular resistance and pulmonary artery pressure.

In low to moderate doses, dopamine causes renal and mesenteric vasodilation which is not antagonized by either α- or β-adrenergic blocking agents, atropine, or antihistamines and is therefore presumed to be the result of an action on dopaminergic receptors.112 Renal vasodilation results in increased renal blood flow and glomerular filtration rate.115 Urine flow is variably affected, but usually increases. Sodium excretion may increase, even in the absence of increased renal blood flow. The renal effects of dopamine may be at least partly due to intrarenal vascular changes and/or an inhibition of renal tubular sodium reabsorption. The osmolality of the urine usually does not decrease with increased urinary output.

In high doses (within and above the therapeutic range), α-adrenergic effects become more prominent and may result in increased peripheral resistance and renal vasoconstriction. This vasoconstriction may decrease previously augmented renal blood flow and urine output. Blood flow to peripheral vascular beds may decrease while mesenteric blood flow is increased because of increased cardiac output; however, with increasing doses of dopamine, mesenteric blood flow also decreases. In the absence of severe volume depletion, both systolic and diastolic blood pressures are increased because of increased cardiac output and increased peripheral resistance. Left ventricular filling pressure may be increased or decreased in patients with congestive heart failure. Heart rate response is variable. Blood pressure may return to normal if hypotension initially existed and may increase to hypertensive levels with excessive doses.

Pharmacokinetics

Absorption

Orally administered dopamine is rapidly metabolized in the GI tract. Following IV administration, the onset of action of dopamine occurs within 5 minutes, and the drug has a duration of action of less than 10 minutes.

Distribution

Dopamine is widely distributed in the body but does not cross the blood-brain barrier to a substantial extent. The apparent volume of distribution of the drug in neonates ranges from 0.6-4 L/kg. It is not known if dopamine crosses the placenta.

Elimination

Dopamine has a plasma half-life of about 2 minutes. In neonates, the elimination half-life of dopamine reportedly is 5-11 minutes.

Dopamine is metabolized in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol- O -methyltransferase to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid. In patients receiving MAO inhibitors, the duration of action of dopamine may be as long as 1 hour. About 25% of a dose of dopamine is metabolized to norepinephrine within the adrenergic nerve terminals.

Dopamine is excreted in urine principally as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid. A very small fraction of a dose is excreted unchanged. Following administration of radiolabeled dopamine, approximately 80% of the radioactivity reportedly is excreted in urine within 24 hours.

In critically ill infants and children, the clearance rate of dopamine reportedly ranges from 48-168 mL/kg per minute, with the higher values reported in the younger patients.

Chemistry and Stability

Chemistry

Dopamine is an endogenous catecholamine that is the immediate precursor of norepinephrine. Dopamine hydrochloride occurs as a white to off-white, crystalline powder that may have a slight odor of hydrochloric acid.115 Dopamine hydrochloride is freely soluble in water and soluble in alcohol.115 Dopamine hydrochloride concentrate for injection may contain an antioxidant (e.g., sodium metabisulfite) and has a pH of 2.5-5.115

Commercially available dopamine hydrochloride in dextrose injections are sterile, nonpyrogenic, isotonic solutions of the drug. Some commercially available dopamine hydrochloride injections containing 200, 400, or 800 mg in 250 mL of 5% dextrose injections have osmolarities of 261-270, 269-275, or 286-295 mOsm/L, respectively; hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 3.3-3.8 (range: 2.5-4.5).

Stability

Commercially available dopamine hydrochloride injection is sensitive to and should be protected from light. Yellow, brown, or pink to purple discoloration of solutions containing dopamine hydrochloride indicates decomposition of the drug, and solutions that are darker than slightly yellow or discolored in any way should not be used. Commercially available dopamine hydrochloride injections should be stored at 20-25°C; the injections should not be frozen.115,116

Some commercially available preparations of dopamine hydrochloride in 5% dextrose are provided in plastic containers.116 The amount of water that can permeate from the container into the overwrap is insufficient to significantly affect the injection.116 Solutions in contact with the plastic can leach out some of the chemical components in very small amounts; however, safety of the plastic has been confirmed during biological testing.116

Dopamine hydrochloride is stable for at least 24 hours after dilution with the following solutions: 0.9% sodium chloride, 5% dextrose, 5% dextrose with 0.9% sodium chloride, 5% dextrose with 0.45% sodium chloride, lactated Ringer's, 5% dextrose in lactated Ringer's, or (1/6) M sodium lactate.115 Dopamine hydrochloride is incompatible with alteplase, amphotericin B, iron salts, oxidizing agents, and sodium bicarbonate and other alkaline solutions. In addition, commercially available dopamine hydrochloride injection should not be admixed with alkalinizing substances (e.g., sodium bicarbonate) since the drug is inactivated in alkaline solution.115 Specialized references should be consulted for specific compatibility information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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