Action And Clinical Pharmacology: Dopamine exerts an inotropic effect on the myocardium resulting in an increased cardiac output. Dopamine produces less increase in myocardial oxygen consumption than isoproterenol and its use is usually not associated with a tachyarrhythmia. Clinical studies indicate that dopamine at low and intermediate therapeutic doses usually increases systolic and pulse pressure with either no effect or a slight increase in diastolic pressure, and total peripheral resistance is usually unchanged.
Blood flow to peripheral vascular beds may decrease while mesenteric flow increases. Dopamine has also been reported to dilate the renal vasculature presumptively by activation of a “dopaminergic” receptor. This action is accompanied by increases in glomerular filtration rate, renal blood flow, and sodium excretion. An increase in urinary output produced by dopamine is usually not associated with a decrease in osmolality of the urine.
Note: Dopamine is a rapidly acting compound. Cardiovascular effects are usually evident within 10 minutes and renal response usually occurs within 30 minutes. The half-life of dopamine is approximately 1.75 minutes.
Indications And Clinical Uses: For the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open heart surgery, renal failure and chronic cardiac decompensation as in congestive failure.
Where appropriate, restoration of blood volume with a suitable plasma expander or whole blood should be instituted or completed prior to dopamine administration.
Patients most likely to respond adequately to dopamine are those in whom physiological parameters, such as urine flow, myocardial function, and, blood pressure, have not undergone profound deterioration. The shorter the time interval between onset of signs and symptoms and initiation of therapy with volume correction and dopamine, the better the prognosis.
Poor Perfusion of Vital Organs: Urine flow appears to be one of the better diagnostic signs by which adequacy of vital organ perfusion can be monitored. Nevertheless, the physician should also observe the patient for signs of reversal of confusion or comatose condition. Loss of pallor, increase in toe temperature and/or adequacy of nail bed capillary filling may also be used as indices of adequate dosage. Clinical studies have shown that when dopamine is administered before urine flow has diminished to levels approximating 0.5 mL/minute, prognosis is more favorable. Nevertheless, in a number of oliguric or anuric patients, dopamine administration has resulted in an increase in urine flow which in some cases reached normal levels. Dopamine may also increase urine flow in patients whose output is within normal limits and thus may be of value in reducing the degree of pre-existing fluid accumulation. It should be noted that at doses above those optimal for the individual patient, urine flow may decrease, necessitating reduction of dosage. Concurrent administration of dopamine and diuretic agents may produce an additive or potentiating effect.
Low Cardiac Output: Increased cardiac output is related to dopamine’s direct inotropic effect on the myocardium. Increased cardiac output at low or moderate doses appears to be related to a favorable prognosis. Increase in cardiac output has been associated with either a static or decreased systemic vascular resistance (SVR). Static or decreased SVR associated with low or moderate increments in cardiac output is believed to be a reflection of differential effects on specific vascular beds with increased resistance in peripheral beds (i.e., femoral) and concomitant decrease in mesenteric and renal vascular beds. Redistribution of blood flow parallels these changes so that an increase in cardiac output is accompanied by an increase in mesenteric and renal blood flow. In many instances, the renal fraction of the total cardiac output has been found to increase. Increase in cardiac output produced by dopamine usually is not associated with substantial decreases in systemic vascular resistance.
Hypotension: Hypotension due to inadequate cardiac output can be managed by administration of low to moderate doses of dopamine, which have little effect on SVR. At high therapeutic doses, dopamine’s alpha-adrenergic activity becomes more prominent and thus may correct hypotension due to diminished SVR. As in the case of other circulatory decompensation states, prognosis is better in patients whose blood pressure and urine flow have not undergone profound deterioration. Therefore, it is suggested that the physician administer dopamine as soon as a definite trend towards decreased systolic and diastolic pressure becomes evident.
Manufacturers’ Warnings In Clinical States: Sensitivity to sulfites: Intropin contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown, and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Note: Dopamine should not be administered in the presence of uncorrected tachyarrhythmias or ventricular fibrillation.
Do not add Intropin to any alkaline diluent solution, since the drug is inactivated in alkaline solution.
Patients who have been treated with MAO inhibitors prior to the administration of dopamine will require substantially reduced dosage. Dopamine is metabolized by MAO, and inhibition of this enzyme prolongs and potentiates the effect of dopamine. Reduce starting dose in such patients to at least 10% of the usual dose.
Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of certain intravenously administered catecholamines. Use dopamine with extreme caution in patients inhaling cyclopropane or halogenated hydrocarbon anesthetics.
Pregnancy: Animal studies have revealed no evidence of teratogenic effects from dopamine. The drug may be used in pregnant women when, in the judgement of the physician the expected benefits outweigh the potential for risk to the fetus.
Children: The safety and efficacy of this drug in children has not been established. Dopamine has been used in a limited number of pediatric patients, but such use has been inadequate to fully define proper dosage and limitations for use.
Precautions: Prior to dopamine treatment hypovolemia should be fully corrected, if possible, with either whole blood or plasma as indicated.
If a disproportionate rise in the diastolic pressure (i.e. a marked decrease in the pulse pressure) or a decrease in urine flow is observed in patients receiving dopamine, the infusion rate should be decreased and the patient observed carefully for further evidence of predominant vasoconstrictor activity, unless such an effect is desired.
Extravasation: Check the infusion site frequently for free flow since several cases of necrosis and sloughing of surrounding tissue due to extravasation have been reported. Infuse dopamine into a large vein whenever possible to prevent the possibility of extravasation into tissue adjacent to the infusion site. Large veins of the antecubital fossa are preferred to veins in the dorsum of the hand or ankle. Less suitable infusion sites should be used only if the patient’s condition requires immediate attention. The physician should switch to more suitable sites as rapidly as possible.
Important: Peripheral Ischemia: No clinical experience exists in which phentolamine has been administered as an antidote for peripheral ischemia due to dopamine. However, the following is suggested, based on experience with other catecholamines: to prevent sloughing and necrosis in ischemic areas, infiltrate the area as soon as possible with 10 to 15 mL of saline solution containing from 5 to 10 mg of phentolamine, an a-adrenergic blocking agent. A syringe with a fine hypodermic needle should be used, and the solution liberally infiltrated throughout the ischemic area. Sympathetic blockage with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. Phentolamine should be given as soon as possible after the extravasation is noted.
Peripheral Vasoconstriction: Several cases of severe vasoconstriction leading to vascular stasis and gangrene of the extremities have been reported after dopamine administration. Patients with preexisting vascular disease such as cold injury, atherosclerosis, Raynaud’s disease and diabetic endarteritis seem to be particularly prone to severe peripheral vasoconstriction. Monitor patients closely for any changes in color or temperature of the skin in the extremities. If a change in skin color or temperature occurs which is thought to be the result of compromised circulation to the extremities, weigh the benefits of continued dopamine infusion against the risk of possible necrosis. As noted above, phentolamine should be available on a standby basis as an antidote for peripheral vasoconstriction.
Close monitoring of urine flow, cardiac output and blood pressure during dopamine infusion is necessary as in the case of any adrenergic agent.
Dopamine, particularly when infused in high doses, may facilitate disturbances in impulse formation such as ectopic beats, tachycardia, sinus bradycardia, sinus arrhythmia. With the occurrence of these symptoms, use dopamine with extreme caution, and if necessary reduce the dosage or if warranted, stop the dopamine infusion.
Dopamine administration in patients with primary pulmonary hypertension can cause pulmonary vasoconstriction which may be detrimental to the condition of these patients.
When dopamine is administered concurrently with diuretics, extra caution should be taken because it may produce an additive or potentiating effect.
Adverse Reactions: The most frequent adverse reactions observed in clinical evaluation of dopamine included ectopic beats, nausea, vomiting, tachycardia, anginal pain, palpitation, dyspnea, headache, hypotension and vasoconstriction.
Extravasation: Sloughing and necrosis of surrounding tissue due to extravasation when dopamine was infused into small veins has been reported. Peripheral Vasoconstriction: Peripheral ischemic changes leading to vascular stasis and gangrene have been reported. Patients with preexisting vascular disease may be particularly sensitive to dopamine’s vasoconstrictive effects (see Precautions).
Other adverse reactions which have been reported infrequently were aberrant conduction, bradycardia, piloerection, widened QRS complex, azotemia and elevated blood pressure.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: In case of accidental overdosage, as evidenced by excessive blood pressure elevation, reduce rate of administration or temporarily discontinue dopamine until patient’s condition stabilizes. Since dopamine’s duration of action is quite short, no additional remedial measures are usually necessary. If these measures fail to stabilize the patient’s condition, consider the use of the short-acting alpha adrenergic blocking agent, phentolamine.
Dosage And Administration: Intropin must be diluted before administration to patients.
Dilution: Transfer contents of 1 ampul or vial (yielding 5 mL of solution containing 200 mg dopamine) by aseptic technique to either a 250 or 500 mL bottle of 1 of the following sterile i.v. solutions: Sodium Chloride Injection USP; Dextrose (5%) Injection USP; Dextrose (5%) and Sodium Chloride (0.9%) Injection USP; 5% Dextrose in 0.45% Sodium Chloride Solution; Dextrose (5%) in Lactated Ringer’s Solution; Sodium Lactate (1/6 Molar) Injection USP; Lactated Ringer’s Injection USP.
These dilutions will yield a final concentration for administration as follows: 250 mL dilution: 800 µg/mL of dopamine; 500 mL dilution: 400 µg/mL of dopamine.
Intropin has been found to be stable for a minimum of 24 hours after dilution in the sterile i.v. solutions listed above. However, as with all i.v. admixtures, dilution should be made just prior to administration. Furthermore, all unused solution from the ampul or vial should be discarded.
Do not add Intropin Injection to 5% Sodium Bicarbonate or other alkaline i.v. solutions, since the drug is inactivated in alkaline solution.
See also Indications for additional information on patient’s management.
Administration Rate: After dilution, Intropin is administered i.v. through a suitable i.v. catheter or needle.
An i.v. drip chamber or other suitable metering device is essential for controlling the rate of flow in drops/minute. Each patient must be individually titrated to the desired hemodynamic and/or renal response with dopamine. In titrating to the desired increase in systolic blood pressure, the optimum dosage rate for renal response may be exceeded, thus necessitating a reduction in rate after the hemodynamic condition is stabilized.
Administration at rates greater than 50 µg/kg/min has been used in advanced circulatory decompensation states.
If unnecessary fluid expansion is of concern, adjustment of drug concentration may be preferred over increasing the flow rate of a less concentrated dilution.
Regimen: 1. When appropriate, increase blood volume with whole blood or plasma until central venous pressure is 10 to 15 cm H2O or pulmonary venous pressure is 14 to 18 mm Hg.
2. Begin administration of diluted solution at doses of 2 to 5 µg/kg/min dopamine in patients who are likely to respond to modest increments of heart force and renal perfusion.
In more seriously ill patients, begin administration of diluted solution at doses of 5 µg/kg/min dopamine and increase gradually using 5 to 10 µg/kg/min increments up to 20 to 50 µg/kg/min as needed. Check the urine output frequently, especially if doses of dopamine in excess of 50 µg/kg/min are required. Should urine flow begin to decrease in the absence of hypotension, consider a dopamine dosage reduction. Multiclinic trials have shown that more than 50% of the patients were satisfactorily maintained on doses of dopamine less than 20 µg/kg/min. In patients who do not respond to these doses with adequate arterial pressure or urine flow, additional increments of dopamine may be employed in an effort to produce an appropriate arterial pressure and central perfusion.
3. Treatment of all patients requires constant evaluation of therapy in terms of the blood volume, augmentation of myocardial contractility and distribution of peripheral perfusion. Adjust dopamine dosage according to the patient’s response.
4. As with all potent i.v. administered drugs, care should be taken to control the rate of administration so as to avoid inadvertent administration of a bolus of drug.
Availability And Storage: Each 5 mL ampul or single-dose vial contains: dopamine HCl 40 mg/mL (equivalent to 32.3 mg base). Nonmedicinal ingredients: sodium metabisulfite and water for injection USP. Tartrazine-free. Boxes of 10. Intropin is stable for a period of 5 years in ampul and 3 years in vial at room temperature (15 to 30°C).
INTROPIN® DuPont Pharma Dopamine HCl Sympathomimetic
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