Elephant specific information, if available, is in blue.

Chemistry – Dobutamine HCl is a synthetic inotropic agent related structurally to dopamine. It occurs as a white, to off-white, crystalline powder with a pKa of 9.4. Dobutamine is sparingly soluble in water and alcohol.

Storage/Stability/Compatibility – Dobutamine injection should be stored at room temperature (15-30°C). It must be further diluted before administration (see Preparation of Solution below); diluted solutions should be used within 24 hours.

Dobutamine is compatible with the usually used IV solutions (D5W, sodium chloride 0.45% & 0.9%, dextrose-saline combinations, lactated Ringer’s) and is reported to be compatible with the following drugs: amiodarone HCl, atropine sulfate, dopamine HCl, epinephrine HCl, hydralazine HCl, isoproterenol HCl, lidocaine HCl, meperidine HCl, metaraminol bitartrate, morphine sulfate, nitroglycerin, norepinephrine (levarterenol) bitartrate, phentolamine mesylate, phenylephrine HCl, procainamide HCl, propranolol HCl, and verapamil HCl.

Dobutamine may be incompatible with the following agents: aminophylline, bretylium tosylate, bumetamide, calcium chloride or gluconate, diazepam, digoxin, furosemide, heparin (inconsistent results), regular insulin, magnesium sulfate, phenytoin sodium, potassium chloride (at high concentrations only – 160 mEq/l), potassium phosphate, and sodium bicarbonate.

Pharmacology – Dobutamine is considered a direct beta1-adrenergic agonist. It also has mild beta2- and alpha1-adrenergic effects at therapeutic doses. These effects tend to balance one another and cause little direct effect on the systemic vasculature. In contrast to dopamine, dobutamine does not cause the release of norepinephrine. It has relatively mild chronotropic, arrhythmogenic, and vasodilative effects.

Increased myocardial contractility and stroke volumes result in increased cardiac output. Decreases in left ventricular filling pressures (wedge pressures) and total peripheral resis­tance occur in patients with a failing heart. Blood pressure and cardiac rate generally are unaltered or slightly increased because of increased cardiac output. Increased myocardial contractility may increase myocardial oxygen demand and coronary blood flow.

Uses/Indications – Dobutamine is used as a rapid-acting injectable positive inotropic agent for short term treatment of heart failure.

Pharmacokinetics – Because it is rapidly metabolized in the GI tract and is not available after oral administration, dobutamine is only administered intravenously (as a constant infusion). After intravenous administration, the onset of action generally occurs within 2 minutes and peaks after 10 minutes.

Dobutamine is metabolized rapidly in the liver and other tissues and has a plasma half-life of approximately 2 minutes in humans. The drug’s effects diminish rapidly after cessation of therapy.

Pharmacokinetic data for domestic animals is apparently unavailable. It is unknown if dobutamine crosses the placenta or into milk.

Contraindications/Precautions – Dobutamine is contraindicated in patients with known hypersensitivity to the drug or with idiopathic hypertropic subaortic stenosis (IHSS). The injectable formulation contains sodium bisulfite as a preservative which has been documented to cause allergic-type reactions in some human patients. Hypovolemic states must be corrected before administering dobutamine. Because it may increase myocardial oxygen demand and increase infarct size, dobutamine should be used very cautiously after myocardial infarction. Dobutamine can enhance atrioventricular conduction, animals with atrial fibrillation should be digitalized prior to receiving dobutamine.

Adverse Effects/Warnings – The most commonly reported adverse effects in humans are: ectopic beats, increased heart rate, increased blood pressure, chest pain, and palpitations. Similar adverse effects could be expected for veterinary patients. At usual doses these ef­fects are generally mild and will not necessitate halting therapy, but dosage reductions should be performed. Other, more rare adverse effects reported include: nausea, headache, vomiting, leg cramps, paresthesias, and dyspnea.

Overdosage – Symptoms reported with excessive dosage include tachycardias, increased blood pressure, nervousness, and fatigue. Because of the drug’s short duration of action, temporarily halting therapy is usually all that is required to reverse these effects.

Drug Interactions – beta-Blockers (e.g., propranolol) may antagonize the cardiac effects of dobutamine, and result in a preponderance of alpha adrenergic effects and increased to­tal peripheral resistance. Use of halothane or cyclopropane with dobutamine may result in increased incidences of ventricular arrhythmias. Synergistic effects (increased cardiac output and reduced wedge pressure) may result if dobutamine is used with nitroprusside.
Insulin requirements may increase in diabetic patients receiving dobutamine.
Oxytocic drugs may induce severe hypertension when used with dobutamine in obstetric patients.

Doses – Dobutamine is administered as a constant rate intravenous infusion only.
Horses:
a) 1 – 5 micrograms/kg/minute (Muir and McGuirk 1987b)
b) 2 – 10 micrograms/kg/minute IV infusion (Robinson 1987)

Elephants:
a) In an African elephant under general anesthesia, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min).

Elephant References:
a) Heard,D.J., Kollias,G.V., Webb,A.I., Jacobson,E.R., and Brock,K.A. 1988. Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants. Journal of the American Veterinary Medical Association 193:254-256 Excerpts: Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures. Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13
mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia. After IM or IV administration of etorphine (1.9 ± 0.56 micrograms/kg), the mean time to lateral recumbency was 20 ± 6.6 and 3 ± 0.0 minutes, respectively. The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 ± 12 beats/min, 106 ± 19 mm of Hg, and 10 ± 3 breaths/min, respectively.

Cardiac arrhythmias were detected during 2 procedures. In one elephant paroxysmal ventricular tachycardia was detected and the procedure terminated when the arrhythmia failed to stabilize after multiple doses of lidocaine (1 mg/kg, IV). In another elephant, second degree atrioventricular block returned to normal sinus rhythm after IV administration of atropine (0.04 mg/kg).

In one elephant, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min).

Immediately after induction in another elephant, profound respiratory depression (< 1breath/minute) and palpably weak arterial pulse were identified. Intravenous administration of diprenorphine at half the recommended reversal dose resulted in improvement of respiration and palpable arterial pulse, without the elephant developing signs of complete anesthetic reversal.

Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia. Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine. Note: A correction appeared in a later volume 193(6): p.721.

Monitoring Parameters –
1) Heart rate and rhythm, blood pressure if possible
2) Urine flow
3) Ideally, measurement of central venous or pulmonary wedge pressures and car­diac output

Client Information – This drug should only be used by professionals familiar with its use and in a setting where adequate patient monitoring can be performed.

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

Veterinary-Approved Products: None

Human-Approved Products:
Dobutamine HCl Injection 12.5 mg/ml in 20 ml vial; Dobutrex® (Lilly); Generic (Rx)

Preparation of Solution – The solution for injection must be further diluted to a concen­tration no greater than 5 mg/ml (total of at least 50 ml of diluent) before administering.

Generally, it is added to D5W, normal saline (if not severely sodium restricted) or other compatible IV solution. The following approximate concentrations will result if 1 vial (250 mg) is added either 250, 500, or 1000 ml IV solutions:
1 vial (250 mg) in: 250 ml ≈ 1000micrograms/ml
” 500 ml ≈ 500micrograms/ml
” 1000 ml ≈ 250micrograms/ml
A mechanical fluid administration control device should be used, if available, to administer dobutamine. When using a mini-drip IV administration set (60 drops ≈ 1 ml), 1 drop contains approximately 8.3 micrograms at the 500 micrograms/ml concentration.