DOBUTamine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Generic: 1 mg/mL (250 mL); 2 mg/mL (250 mL); 4 mg/mL (250 mL); 250 mg/20 mL (20 mL); 500 mg/40 mL (40 mL)

Pharmacology

Mechanism of Action

Dobutamine, a racemic mixture, stimulates myocardial beta₁-adrenergic receptors primarily by the (+) enantiomer and some alpha₁ receptor agonism by the (-) enantiomer, resulting in increased contractility and heart rate, and stimulates both beta₂- and alpha₁-receptors in the vasculature. Although beta₂ and alpha₁ adrenergic receptors are also activated, the effects of beta₂ receptor activation may equally offset or be slightly greater than the effects of alpha₁ stimulation, resulting in some vasodilation in addition to the inotropic and chronotropic actions (Leier 1988; Majerus 1989; Ruffolo 1987). Lowers central venous pressure and wedge pressure, but has little effect on pulmonary vascular resistance (Leier 1977; Leier 1978).

Pharmacokinetics/Pharmacodynamics

Metabolism

In tissues and hepatically to inactive metabolites

Excretion

Urine (as metabolites)

Onset of Action

IV: 1 to 10 minutes; Peak effect: 10 to 20 minutes

Half-Life Elimination

2 minutes

Use: Labeled Indications

Cardiac decompensation: Short-term management of patients with cardiac decompensation

Guideline recommendations:

Cardiogenic shock: The 2017 American Heart Association (AHA) scientific statement for the Contemporary Management of Cardiogenic Shock recommends dobutamine to maintain systemic perfusion and preserve end-organ performance in patients with cardiogenic shock. A vasopressor such as norepinephrine (preferred), vasopressin, or dopamine is typically the initial preferred therapy until hemodynamically stable. Once stable, consider adding or transitioning to an inotrope. However, an inotrope may be the preferred therapy for cardiogenic shock due to acute decompensated heart failure or in other cases when systolic blood pressure >90 mm Hg (ACCF/AHA [Yancy 2013]); AHA [van Diepen 2017]).

Inotropic support in advanced heart failure: Bridge therapy in stage D heart failure (HF) unresponsive to guideline-directed medical therapy and device therapy in patients awaiting heart transplant or mechanical circulatory support; short-term management of hospitalized patients with severe systolic dysfunction presenting with low blood pressure and significantly depressed cardiac output; long-term management (palliative therapy) in select patients with stage D HF unresponsive to guideline-directed medical therapy and device therapy who are not candidates for heart transplant or mechanical circulatory support (ACCF/AHA [Yancy 2013]).

Use: Off Label

Advanced life supportyes

Based on the American Heart Association (AHA) guidelines for post cardiac arrest care in adults, the use of dobutamine during the post-resuscitation phase of cardiac arrest may be used for inotropic support.

Myocardial dysfunction related to sepsis (positive inotropic agent)byes

Data from a number of clinical trials in patients with septic shock supports the use of dobutamine in the treatment of this condition Beale 2004, De Backer 1993, De Backer 1994, Gutierrez 1994, Hollenberg 2004, Jardin 1981, Martin 1990, Vallet 1993. Septic patients who have been adequately fluid resuscitated and have an adequate mean arterial pressure but low cardiac index (<2.5 L/minute/m²) may require dobutamine. Dobutamine may help reverse tissue hypoperfusion by increasing cardiac output.

Based on the Surviving Sepsis Campaign International Guidelines for the Management of Severe Sepsis and Septic Shock, a trial of dobutamine infusion may be given if persistent signs of hypoperfusion exist despite adequate intravascular volume repletion and use of vasopressor agents.

Stress echocardiography (diagnostic agent)ayes

Data from a number of clinical studies evaluating the use of dobutamine infusion during stress echocardiography for detecting coronary artery disease supports the use of dobutamine infusion as a diagnostic agent in patients who are incapable of physical exercise or who have contraindications (eg, bronchospastic airway disease) to pharmacologic vasodilator stressors. Wall motion abnormalities developing with increasing doses of dobutamine may help to identify ischemic and/or hibernating myocardium Fragasso 1999, Marcovitz 1992, Previtali 1991.

Based on the American Society of Nuclear Cardiology, dobutamine infusion administered as a secondary pharmacologic stressor is an effective and recommended alternative agent to detect obstructive coronary disease.

Contraindications

Hypersensitivity to dobutamine or sulfites (some contain sodium metabisulfate), or any component of the formulation; hypertrophic cardiomyopathy with outflow tract obstruction (formerly known as idiopathic hypertrophic subaortic stenosis [IHSS])

Note: When utilized for stress testing, additional contraindications according to the American Society of Nuclear Cardiology (ASNC) include patients with recent (<1 week) MI, unstable angina, severe aortic stenosis, atrial tachyarrhythmias with uncontrolled ventricular response, prior history of ventricular tachycardia, uncontrolled hypertension (>200/110 mm Hg), aortic dissection or large aortic aneurysm, and patients on beta blockers where heart rate and inotropic responses to dobutamine will be attenuated (ASNC [Henzlova 2009])

Dosage and Administration

Dosing: Adult

Cardiac decompensation: IV infusion:

Initial dose: 0.5 to 1 mcg/kg/minute (per the manufacturer); may also initiate at higher doses (eg, 2.5 mcg/kg/minute) depending on severity of decompensation with titration to desired response (Leier 1977).

Maintenance dose: 2 to 20 mcg/kg/minute. Note: In patients with heart failure, lower doses are preferred to minimize adverse effects (ACCF/AHA [Yancy 2013]; AHA [van Diepen 2017]).

Maximum dose: 40 mcg/kg/minute. The ACCF/AHA 2013 heart failure guidelines recommend a maximum dose of 20 mcg/kg/minute (ACCF/AHA [Yancy 2013]).

Adult Advanced Cardiovascular Life Support (ACLS) guideline recommendation (in the immediate post-cardiac arrest care setting) (off-label use): IV infusion: Initial: 5 to 10 mcg/kg/minute; titrate to effect (AHA [Peberdy 2010])

Stress echocardiography (diagnostic agent) (off-label use): IV infusion: Initial: 5 to 10 mcg/kg/minute; increase at 3-minute intervals to 20 mcg/kg/minute, then 30 mcg/kg/minute, and then 40 mcg/kg/minute. May coadminister atropine in patients who do not achieve target heart rate (ASNC [Henzlova 2009]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemodynamic support: Infants, Children, and Adolescents: Continuous IV or intraosseous infusion: Initial: 0.5 to 1 mcg/kg/minute, titrate gradually every few minutes until desired response achieved; usual range: 2 to 20 mcg/kg/minute (PALS [Kleinman 2010])

Reconstitution

Vials: Dilute 20 mL vial in ≥50 mL of a compatible IV solution; dilute 40 mL vial in ≥100 mL of a compatible IV solution. Maximum concentration: 5,000 mcg/mL (5 mg/mL).

Administration

Always administer via infusion device; administer into large vein.

Storage

Premixed solution: Store at 20°C to 25°C (68°F to 77°F). Pink discoloration of solution indicates slight oxidation, but no significant loss of potency.

Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Following dilution in a compatible solution, use within 24 hours.

Drug Interactions

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Calcium Salts: May diminish the therapeutic effect of DOBUTamine. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: Increased heart rate (10%), increased systolic blood pressure (8%), ventricular premature contractions (5%), angina pectoris (1% to 3%), chest pain (1% to 3%), palpitations (1% to 3%)

Central nervous system: Headache (1% to 3%)

Gastrointestinal: Nausea (1% to 3%)

Respiratory: Dyspnea (1% to 3%)

Frequency not defined:

Cardiovascular: Hypotension, ventricular ectopy

Endocrine & metabolic: Decreased serum potassium

<1%, postmarketing, and/or case reports: Cardiomyopathy (stress), eosinophilia, hypersensitivity reaction, localized phlebitis

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Ventricular arrhythmias, including nonsustained ventricular tachycardia and supraventricular arrhythmias, have been reported (Tisdale1995). Observe closely for arrhythmias in patients with acute heart failure; sudden cardiac death has been observed (O’Connor 1999; Pickworth 1992; Young 2000). Ensure that ventricular rate is controlled in atrial fibrillation/flutter before initiating; may increase ventricular response rate. In heart transplant candidates, institute appropriate measures to protect patient against risks of sudden cardiac death (Young 2000).
• Blood pressure effects: An increase in blood pressure is more common due to augmented cardiac output, but occasionally a patient may become hypotensive.
• Heart failure complications: An increased risk of hospitalization and death has been observed with prolonged use in New York Heart Association Class III/IV heart failure patients (O’Connor 1999).
• Tachycardia: May cause dose-related increases in heart rate.
• Ventricular ectopy: May exacerbate ventricular ectopy (dose-related).

Disease-related concerns:

• Aortic stenosis: Ineffective therapeutically in the presence of mechanical obstruction such as severe aortic stenosis.
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy to minimize the risk of arrhythmias (ACC/AHA/ESC [Zipes 2006]; Tisdale 1995).
• Hypovolemia: If needed, correct hypovolemia first to optimize hemodynamics.
• Active myocardial ischemia/myocardial infarction (post): Use with caution in patients with active myocardial ischemia or recent myocardial infarction; can increase myocardial oxygen demand.

Concurrent drug therapy issues:

• Monoamine oxidase inhibitors (MAO-I): Use with extreme caution in patients taking MAO inhibitors; prolong hypertension may result from concurrent use.

Dosage form specific issues:

• Sodium sulfite: Product may contain sodium sulfite.

Special populations:

• Elderly: Use with caution in the elderly; start at lower end of the dosage range.

Other warnings/precautions:

• Long-term therapy: According to the ACCF/AHA 2013 heart failure guidelines, long-term use of intravenous inotropic therapy without a specific indication or for reasons other than palliation is potentially harmful (ACCF/AHA [Yancy 2013]).

Monitoring Parameters

Blood pressure, ECG, heart rate, CVP, RAP, MAP; serum glucose, renal function; urine output; if pulmonary artery catheter is in place, monitor CI, PCWP, and SVR; ScvO₂ or SvO₂

Consult individual institutional policies and procedures.

Pregnancy

Pregnancy Considerations

Dobutamine should not be used as a diagnostic agent for stress testing during pregnancy; use should be avoided when other options are available (ESC [Regitz-Zagrosek 2018]). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant female. Appropriate medications should not be withheld due to concerns of fetal teratogenicity. Dobutamine use during the post-resuscitation phase may be considered; however, the effects of inotropic support on the fetus should also be considered. Doses and indications should follow current Advanced Cardiovascular Life Support (ACLS) guidelines (AHA [Jeejeebhoy 2015 ]).

Patient Education

What is this drug used for?

• It is used to help heart function in certain patients.
• It may be given to you for other reasons. Talk with the doctor.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Shortness of breath
• Fast heartbeat
• Abnormal heartbeat
• Severe dizziness
• Passing out
• Vision changes
• Injection site pain or irritation
• Severe headache
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.