Dobutamine

Indications

Dobutamine Hydrochloride is indicated when inotropic support is necessary for the treatment of patients with hypoperfusion states in whom cardiac output is insufficient to meet circulatory demands. Dobutamine Hydrochloride is also indicated when inotropic support is required for the treatment of patients in whom abnormally increased ventricular filling pressures introduce the risk of pulmonary congestion and oedema.

Pharmacology

Dobutamine exerts positive inotropic effect on the myocardium by stimulating β1-adrenergic receptors, thereby increasing myocardial contractility, stroke vol and cardiac output.

Dosage And Administration

Recommended Dosage: The rate of infusion needed to increase cardiac output has ranged from 2.5 to 10 mcg/kg/min in the majority of patients. Frequently, doses up to 20 mcg/kg/min are required for adequate haemodynamic improvement. On rare occasions, infusion rates up to 40 mcg/kg/min have been reported.

The rate of administration and the duration of therapy should be adjusted according to the patient's response, The indicators are: haemodynamic parameters such as heart rate and rhythm, arterial pressure, and, whenever possible, cardiac output and measurements of ventricular filling pressures and signs of pulmonary congestion. Concentrations up to 5,000 mg/L have been administered to humans. The final volume administered should be determined by the fluid requirements of the patient. Rather than abruptly discontinuing therapy with Dobutamine Hydrochloride, it is often advisable to decrease the dosage gradually.

Rates of Infusion Based on Concentration of Dobutamine Hydrochloride. The rates of fluid infusion that are required to deliver specific dosages are a function of the concentration of Dobutamine Hydrochloride in the infusate. The following table provides a guideline of infusion rates (mL/kg/min) required for 3 frequently used concentrations of Dobutamine Hydrochloride (250, 500, and 1000 mg/L).

Because of its short half-life, Dobutamine Hydrochloride must be administered as a continuous intravenous infusion. Following the initiation of a constant rate infusion, or upon changing the rate, a steady-state dobutamine plasma concentration is achieved within approximately 10 minutes. Thus, loading doses or bolus injections are not necessary and are not recommended.

Interaction

The potency of Dobutamine Hydrochloride may be decreased if the patient is given b-adrenergic receptor antagonists. In such a case, the unopposed a-agonist effects of Dobutamine Hydrochloride may become apparent, including peripheral vasoconstriction and hypertension. Conversely, a-adrenergic blockade may make the b-1 and b-2 effects apparent, resulting in tachycardia and vasodilatation.

There has been no overt indication of medicine interactions in clinical studies in which Dobutamine Hydrochloride was administered concurrently with other medicines, including digitalis preparations, furosemide, spironolactone, lidocaine, nitroglycerin, nitroprusside, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and paracetamol.

Contraindications

Dobutamine Hydrochloride is contraindicated in patients who have shown previous manifestations of hypersensitivity to Dobutamine Hydrochloride.

Side Effects

Increased Heart Rate, Blood Pressure, And Ventricular Ectopic Activity: A 10- to 20-mm increase in systolic blood pressure and an increase in heart rate of 5 to 15 beats/minute have been noted in most patients (see WARNINGS regarding exaggerated chronotropic and pressor effects). Approximately 5% of patients have had increased premature ventricular beats during infusions. These effects are dose related.

Hypotension: Precipitous decreases in blood pressure have occasionally been described in association with dobutamine therapy. Decreasing the dose or discontinuing the infusion typically results in rapid return of blood pressure to baseline values. In rare cases, however, intervention may be required and reversibility may not be immediate.

Reactions At Sites Of Intravenous Infusion: Phlebitis has occasionally been reported. Local inflammatory changes have been described following inadvertent infiltration. Isolated cases of cutaneous necrosis (destruction of skin tissue) have been reported.

Miscellaneous Uncommon Effects: The following adverse effects have been reported in 1% to 3% of patients: nausea, headache, anginal pain, nonspecific chest pain, palpitations, and shortness of breath. Isolated cases of thrombocytopenia have been reported.

Administration of dobutamine, like other catecholamines, can produce a mild reduction in serum potassium concentration, rarely to hypokalemic levels.

Longer-Term Safety: Infusions of up to 72 hours have revealed no adverse effects other than those seen with shorter infusions.

Pregnancy And Lactation

Since there are no adequate and well controlled studies in pregnant women, Dobutamine Hydrochloride should not be used during pregnancy unless the potential benefits outweigh the potential risks to the foetus.

It is not known whether this medicine is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when Dobutamine Hydrochloride is administered to a nursing woman. If a mother requires dobutamine treatment, breastfeeding should be discontinued for the duration of the treatment.

Precautions And Warnings

During the administration of Dobutamine Hydrochloride, as with any parenteral catecholamine, heart rate and rhythm, arterial blood pressure, and infusion rate should be monitored closely. When initiating therapy, electrocardiographic monitoring is advisable until a stable response is achieved.

Overdose Effects

Signs And Symptoms: Toxicity from dobutamine hydrochloride is usually due to excessive cardiac β- receptor stimulation. The duration of action of dobutamine hydrochloride is generally short (T½= 2 minutes) because it is rapidly metabolized by catechol-0-methyltransferase. The symptoms of toxicity may include anorexia, nausea, vomiting, tremor, anxiety, palpitations, headache, shortness of breath, and anginal and nonspecific chest pain. The positive inotropicand chronotropic effects of dobutamine on the myocardium may cause hypertension, tachyarrhythmias, myocardial ischemia, and ventricular fibrillation. Hypotension may result from vasodilation.

Treatment: To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

The initial actions to be taken in a dobutamine hydrochloride overdose are discontinuing administration, establishing an airway, and ensuring oxygenation and ventilation. Resuscitative measures should be initiated promptly. Severe ventricular tachyarrhythmias may be successfully treated with propranolol or lidocaine. Hypertension usually responds to a reduction in dose or discontinuation of therapy.

Protect the patient's airway and support ventilation and perfusion. If needed, meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. If the product is ingested, unpredictable absorption may occur from the mouth and the gastrointestinal tract. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emisis of lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of dobutamine hydrochloride

Therapeutic Class

Inotropic-sympathomimetics

Storage Conditions

Store between 15-30° C.