AHFS Class:

• Selective beta-1-Adrenergic Agonists 12:12.08.08

Generic Name(s):

• DOBUTamine Hydrochloride

Dobutamine hydrochloride is a synthetic sympathomimetic that is structurally related to dopamine and generally is considered a relatively selective β₁-adrenergic agonist.

Cardiac Decompensation

Dobutamine hydrochloride is used for inotropic support in the short-term management of cardiac decompensation caused by depressed contractility from organic heart disease or cardiac surgical procedures.113,114,116,165 The drug may be ineffective in patients with marked mechanical obstruction such as severe valvular aortic stenosis.113,114

Safety and efficacy of dobutamine or other cyclic AMP (cAMP)-dependent inotropic agents in the long-term (e.g., exceeding 48 hours) treatment of patients with congestive heart failure have not been established, irrespective of their route of administration.114 In controlled studies in patients with congestive heart failure using chronic oral therapy with cAMP-dependent inotropic agents, symptoms were not consistently alleviated, and an increased risk of hospitalization and death, particularly in patients with New York Heart Association (NYHA) class IV symptoms, was associated with such therapy.114

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

When used for inotropic support in patients with myocardial dysfunction after cardiac surgery, dobutamine has been shown in clinical studies to effectively increase cardiac output; however, the effects of the drug on clinically important outcomes and survival are not known.116,117 Although some data indicate that dobutamine may be preferable to other catecholamines (e.g., dopamine) in the period immediately following cardiopulmonary bypass surgery,118 additional studies are needed.116,117

Inotropic agents such as dobutamine also are used in the treatment of septic or cardiogenic shock to improve myocardial contractility and maintain systemic perfusion.153,159,161,165 The Surviving Sepsis Campaign International Guidelines for Management of Severe Sepsis and Septic Shock recommend a trial of dobutamine (alone or in addition to a vasopressor) in patients with septic shock if myocardial dysfunction is present, as evidenced by elevated cardiac filling pressures and low cardiac output, or if there is ongoing hypoperfusion despite adequate intravascular volume and mean arterial pressure.153 Although the manufacturers of dobutamine hydrochloride state that safety of the drug following myocardial infarction (MI) has not been established (see Cautions: Precautions and Contraindications),113,114 dobutamine often is used for temporary inotropic support in patients with cardiogenic shock, a condition caused principally by acute MI.159,161,162,165 Early revascularization is the standard of care in patients with cardiogenic shock; use of inotropes in this setting should be individualized and guided by hemodynamic monitoring.161,162

Advanced Cardiovascular Life Support

Inotropic agents such as dobutamine also have been used for postresuscitation stabilization† after cardiac arrest in patients who require additional support of cardiac output and blood pressure.403,404

Cardiac Diagnostic Testing

Dobutamine has been used as a pharmacologic stress test agent† during echocardiography in patients who are unable to undergo exercise testing.120,122,124,125,126,127 Dobutamine also has been used as an alternative to exercise stress testing in patients undergoing myocardial perfusion imaging†.119,121,123,128,129,130 However, coronary vasodilating agents (e.g., adenosine, dipyridamole, regadenoson) are the drugs of choice for this use; dobutamine generally is recommended only in patients who have contraindications (e.g., bronchospastic airway disease) to these vasodilators.119,121,123

Administration

Dobutamine hydrochloride is administered by IV infusion using an infusion pump or other apparatus to control the flow rate.113,114 One manufacturer recommends that a precision volume-control IV set be used when administering the drug.114 Care should be taken to control the rate of infusion to prevent rapid IV (“bolus”) administration.114

Dobutamine also has been administered by intraosseous (IO) 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

Commercially available dobutamine hydrochloride injection concentrate must be further diluted with a compatible IV solution (see Chemistry and Stability: Stability) before IV infusion; 20 mL of concentrate should be diluted in at least 50 mL of diluent and 40 mL of concentrate should be diluted in at least 100 mL of diluent.113 The concentration of dobutamine hydrochloride administered should be individualized according to dosage and fluid requirements of the patient; concentrations up to 5000 mcg/mL have been administered.113 Following dilution, solutions of dobutamine should be used within 24 hours.113

Commercially available prediluted solutions of dobutamine hydrochloride in 5% dextrose injection should not be administered unless the solution is clear and the container is undamaged; unused portions should be discarded.114 The flexible containers should not be used in series connections, and additives should not be introduced into the injection containers.114

Dobutamine injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.113 Dobutamine hydrochloride solutions should not be admixed with alkalinizing substances (e.g., sodium bicarbonate) since the drug is inactivated in alkaline solution.113,114 One manufacturer states that dobutamine hydrochloride should not be used in conjunction with other drugs or solutions containing both sodium bisulfite and ethanol.113 The manufacturer's labeling should be consulted for proper methods of administration and other associated precautions.113,114,115

Standardize 4 Safety

Standardized concentrations for dobutamine 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

Dosage of dobutamine hydrochloride is expressed in terms of dobutamine.113,114

Cardiac Decompensation

Individual response to dobutamine is variable, and infusion rate should be titrated to achieve the desired clinical response.113,114

Dobutamine infusion should be initiated at a slow rate (e.g., 0.5-1 mcg/kg per minute) and carefully adjusted at intervals of a few minutes according to the patient's response as indicated by heart rate, blood pressure, urine flow, presence of ectopic heartbeats, and, whenever possible, by measurement of central venous or pulmonary capillary wedge pressure and cardiac output.113,114 Clinical studies have shown that the rate of infusion usually needed to increase cardiac output is 2-20 mcg/kg per minute.113,114 Rarely, infusion of doses as great as 40 mcg/kg per minute has been required.113,114

When dobutamine is used in geriatric patients, the initial dosage 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.114

Advanced Cardiovascular Life Support

If dobutamine is used for postresuscitation stabilization† in adults following cardiac arrest, the usual initial dosage range is 5-10 mcg/kg per minute.404 In pediatric patients, the usual dosage range is 2-20 mcg/kg per minute by IV or IO infusion.403 Rate of infusion should be titrated based on cardiac output and blood pressure response.403

Cardiovascular Effects

The principal adverse effects of dobutamine hydrochloride include ectopic heartbeats, increased heart rate, angina, chest pain, palpitation, and elevations in blood pressure. In most patients, heart rate increases 5-15 beats per minute and systolic blood pressure increases by 10-20 mm Hg. Occasionally, however, patients experience an increase in heart rate of 30 beats per minute or greater or an increase in systolic blood pressure of 50 mm Hg or greater. Patients with preexisting hypertension may be predisposed to developing an exaggerated pressor response. All of these adverse cardiovascular effects are usually dose related, and dosage should be reduced or temporarily discontinued if they occur. Rarely, dobutamine has caused ventricular tachycardia.

Precipitous decreases in blood pressure also have been described occasionally; blood pressure generally will return to baseline following dosage reduction or discontinuance of the infusion. However, intervention rarely may be required and the effects on pressure may not be readily reversible.

Dermatologic and Sensitivity Reactions

Manifestations suggestive of hypersensitivity, including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally in patients receiving dobutamine hydrochloride.113,114

Other Adverse Effects

Other less frequent adverse effects include nausea, vomiting, tingling sensation, paresthesia, dyspnea, headache, fever, and mild leg cramps; pruritus of the scalp during IV infusion of dobutamine has been reported in at least one patient. Isolated cases of thrombocytopenia have been reported. Like other drugs with β₂-agonist activity, dobutamine may produce slight decreases in serum potassium concentrations; hypokalemia may occur rarely. Inadvertent overdosage has also reportedly caused nervousness and fatigue. Phlebitis at the site of IV infusion of dobutamine has been reported occasionally. Inadvertent subcutaneous infiltration of dobutamine has caused local inflammatory changes and local pain without local ischemia; however, isolated cases of cutaneous necrosis have been reported.

Precautions and Contraindications

Before administration of dobutamine, hypovolemia should be corrected with an appropriate plasma volume expander.113,114 The ECG, blood pressure and, when possible, cardiac output and pulmonary wedge pressure should be monitored.113,114 Because dobutamine increases atrioventricular conduction, patients with atrial fibrillation are at risk of developing a rapid ventricular response and, therefore, should be digitalized prior to administration of dobutamine. Experience with the use of dobutamine following acute myocardial infarction (MI) is limited.113,114 The possibility that dobutamine may intensify or extend myocardial ischemia has not been ruled out.113,114 Therefore, the drug should be used with extreme caution following MI.

Like other drugs with β₂-agonist activity, dobutamine may produce slight reductions in serum potassium concentrations and hypokalemia may occur rarely.113,114 Consideration should be given to monitoring serum potassium concentrations during dobutamine therapy.113,114

Commercially available injections of dobutamine hydrochloride or dobutamine hydrochloride in 5% dextrose may contain sulfites that can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.113,114 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.113,114

Dobutamine is contraindicated in patients with idiopathic hypertrophic subaortic stenosis or with known hypersensitivity to the drug or any ingredient in the formulation.113,114

Pediatric Precautions

Some manufacturers state that safety and efficacy of dobutamine injection have not been evaluated in pediatric patients.113 Other manufacturers state that dobutamine increases cardiac output and systemic blood pressure in pediatric patients of all age groups.114 In premature neonates, however, dobutamine is less effective than dopamine in increasing systemic blood pressure without causing undue tachycardia and has not been shown to provide any additional benefit when administered to such infants who are already receiving optimal dopamine therapy.114

Geriatric Precautions

Clinical studies of dobutamine hydrochloride did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.114 Clinical experience suggests that substantial hypotension associated with dobutamine therapy may occur more frequently in geriatric patients.114 One manufacturer of dobutamine hydrochloride in 5% dextrose recommends that if dobutamine is used in geriatric patients, the initial dosage 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.114

Pregnancy, Fertility, and Lactation

Pregnancy

Safe use of dobutamine during pregnancy has not been established. Reproduction studies in rats or rabbits (at up to or 2 times, respectively, the usual human dose on a mg/kg basis) have not revealed evidence of harm to the fetus. Dobutamine should be used in pregnant women only if clearly needed. The effect of dobutamine on labor and delivery is not known.

Fertility

Studies to evaluate the potential of dobutamine to affect fertility have not been performed.

Lactation

It is not known whether dobutamine is distributed into human milk.113 Because many drugs are distributed into human milk, caution should be exercised when dobutamine is administered to a nursing woman.113 If a nursing woman requires dobutamine therapy, breast-feeding should be discontinued for the duration of drug therapy.113

In clinical studies, dobutamine hydrochloride was administered concomitantly with atropine, cardiac glycosides (digoxin), furosemide, heparin, lidocaine, morphine, nitroglycerin, isosorbide dinitrate, potassium chloride, folic acid, protamine, acetaminophen, or spironolactone with no evidence of any drug interactions.113,114

Beta-Adrenergic Blocking Agents

In animals, the cardiac effects of dobutamine are antagonized by β-adrenergic blocking agents such as propranolol and metoprolol, resulting in predominance of α-adrenergic effects and increased peripheral resistance.

General Anesthetics

Ventricular arrhythmias have been reported in animals receiving usual doses of dobutamine during halothane or cyclopropane anesthesia; therefore, caution should be used when administering dobutamine to patients receiving these general anesthetics.

Sodium Nitroprusside

Concomitant use of dobutamine and sodium nitroprusside may potentiate effects on cardiac output and pulmonary wedge pressure.113,114

Pharmacology

Dobutamine hydrochloride directly stimulates β₁-adrenergic receptors and is generally considered a selective β₁-adrenergic agonist, but the mechanisms of action of the drug are complex.100,101 It is believed that the β-adrenergic effects result from stimulation of adenyl cyclase activity. In therapeutic doses, dobutamine also has mild β₂- and α₁-adrenergic receptor agonist effects, which are relatively balanced and result in minimal net direct effect on systemic vasculature.100 Unlike dopamine, dobutamine does not cause release of endogenous norepinephrine. The main effect of therapeutic doses of dobutamine is cardiac stimulation. While the positive inotropic effect of the drug on the myocardium appears to be mediated principally via β₁-adrenergic stimulation, experimental evidence suggests that α₁-adrenergic stimulation may also be involved and that the α₁-adrenergic activity results mainly from the (-)-stereoisomer of the drug.100,101

The β₁-adrenergic effects of dobutamine exert a positive inotropic effect on the myocardium and result in an increase in cardiac output due to increased myocardial contractility and stroke volume in healthy individuals and in patients with congestive heart failure. Increased left ventricular filling pressure decreases in patients with congestive heart failure. In therapeutic doses, dobutamine causes a decrease in peripheral resistance; however, systolic blood pressure and pulse pressure may remain unchanged or be increased because of augmented cardiac output. With usual doses, heart rate is usually not substantially changed. Coronary blood flow and myocardial oxygen consumption are usually increased because of increased myocardial contractility.

Electrophysiologic studies have shown that dobutamine facilitates atrioventricular conduction and shortens or causes no important change in intraventricular conduction. The tendency of dobutamine to induce cardiac arrhythmias may be slightly less than that of dopamine and is considerably less than that of isoproterenol or other catecholamines. Pulmonary vascular resistance may decrease if it is elevated initially and mean pulmonary artery pressure may decrease or remain unchanged. Unlike dopamine, dobutamine does not seem to affect dopaminergic receptors and causes no renal or mesenteric vasodilation; however, urine flow may increase because of increased cardiac output.

Pharmacokinetics

Absorption

Orally administered dobutamine hydrochloride is rapidly metabolized in the GI tract. Following IV administration, the onset of action of dobutamine occurs within 2 minutes. Peak plasma concentrations of the drug and peak effects occur within 10 minutes after initiation of an IV infusion. The effects of the drug cease shortly after discontinuing an infusion.

Distribution

It is not known if dobutamine crosses the placenta or is distributed into milk.

Elimination

The plasma half-life of dobutamine is about 2 minutes. Dobutamine is metabolized in the liver and other tissues by catechol- O -methyltransferase to an inactive compound, 3- O -methyldobutamine, and by conjugation with glucuronic acid. Conjugates of dobutamine and 3- O -methyldobutamine are excreted mainly in urine and to a minor extent in feces.

Chemistry and Stability

Chemistry

Dobutamine is a synthetic sympathomimetic drug which is structurally related to dopamine. Dobutamine hydrochloride occurs as a white to off-white, crystalline powder and is sparingly soluble in water and in alcohol. Dobutamine has a pK_a of 9.4.

Dobutamine hydrochloride is commercially available as a sterile solution of the drug (a racemic mixture) in water for injection. Commercially available concentrates for injection contain sulfites. Hydrochloric acid and/or sodium hydroxide may be added during manufacture of the commercially available concentrate for injection to adjust the pH between 2.5-5.5.

Dobutamine hydrochloride also is commercially available as prediluted solutions of the drug in 5% dextrose.114 Hydrochloric acid and/or sodium hydroxide may be added during manufacture of dobutamine hydrochloride in 5% dextrose injection to adjust pH to approximately 3 (range: 2.5-5.5); sodium metabisulfite and edetate disodium dihydrate are added as stabilizers.114 The commercially available injections of the drug in 5% dextrose are sterile, nonpyrogenic solutions of dobutamine hydrochloride; the injections containing 1, 2, or 4 mg/mL of dobutamine have osmolarities of 263, 270, or 284 mOsm/L, respectively.114

Stability

Dobutamine hydrochloride for injection concentrate should be stored at 20-25°C.113

Commercially available solutions of dobutamine hydrochloride in 5% dextrose should be protected from excessive heat or freezing and stored at room temperature (20-25°C);114,115 however, some manufacturers state that brief exposure of the solutions to temperatures up to 40°C does not adversely affect the products.115 Dobutamine hydrochloride for injection concentrate is compatible with the following IV solutions: 5 or 10% dextrose, 5% dextrose and 0.45 or 0.9% sodium chloride, 5% dextrose in lactated Ringer's, lactated Ringer's, 0.9% sodium chloride, Isolyte^®-M with 5% dextrose, Normosol^®-M in 5% dextrose, 20% Osmitrol^®, or (1/6) M sodium lactate injection.113 Dobutamine hydrochloride solutions diluted for IV infusion should be used within 24 hours.113

Because of potential physical incompatibilities, it is recommended that dobutamine hydochloride solutions not be admixed with other drugs.113,114 Solutions of the drug are incompatible with sodium bicarbonate injection or other strongly alkaline solutions and should not be used in conjunction with other drugs or diluents containing both sodium bisulfite and ethanol.113,114 Pink discoloration of solutions of dobutamine hydrochloride indicates slight oxidation of the drug; however, there is no important loss of potency if the drug is administered within the recommended time period.114 Unused portions of dobutamine hydrochloride solutions should be discarded.114

Some commercially available preparations of dobutamine hydrochloride in 5% dextrose injection (e.g., Lifecare^®) are provided in plastic containers fabricated from a specially formulated nonplasticized, thermoplastic co-polyester (CR3).114 Water can permeate from inside the container into the overwrap in amounts insufficient to affect the solution substantially.114 Solutions in contact with the plastic container also can leach out some of the chemical components in very small amounts; however, safety of the plastic has been confirmed with biological testing.114

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.

Only references cited for selected revisions after 1984 are available electronically.

100. Leier CV, Unverferth DV. Dobutamine. Ann Intern Med . 1983; 99:490-6. [PubMed 6625384]

101. Ruffolo RR Jr. The mechanism of action of dobutamine. Ann Intern Med . 1984; 100:313-4. [PubMed 6140893]

102. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use; warning statement: final rule [21 CFR Part 201]. Fed Regist . 1986; 51:43900-5.

103. Eli Lilly and Company. Dobutrex^® (dobutamine hydrochloride) solution prescribing information. Indianapolis, IN: 1999 Feb.

105. Robison-Strane SR, Bubik JS. Dobutamine-induced fever. Ann Pharmacother . 1992; 26:1523-4. [PubMed 1482808]

106. Gensia Laboratories, Inc. Dobutamine hydrochloride injection prescribing information. Irvine, CA; 1993 Apr.

107. Abbott Laboratories. Dobutamine in 5% dextrose injection prescribing information. North Chicago, IL: 1998 Aug.

108. Food and Drug Administration. Dobutamine in 5% dextrose in flexible containers [September 1, 1999; Abbott]. MedWatch drug labeling changes. Rockville, MD; September 1999. From FDA website ([Web]).

109. Food and Drug Administration. Dobutamine in 5% dextrose in plastic container [April 21, 1999; Baxter]. MedWatch drug labeling changes. Rockville, MD; April 1999. From FDA website ([Web]).

113. Hospira. Dobutamine injection prescribing information. Lake Forest, IL; 2005.

114. Hospira. Dobutamine in 5% dextrose injection prescribing information. Lake Forest, IL; 2006 June.

115. Baxter. Dobutamine hydrochloride in 5% dextrose injection prescribing information. Deerfield, IL; 2014 April.

116. Gillies M, Bellomo R, Doolan L et al. Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery -- a systematic literature review. Crit Care . 2005; 9:266-79. [PubMed 15987381]

117. Mebazaa A, Pitsis AA, Rudiger A et al. Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Crit Care . 2010; 14:201. [PubMed 20497611]

118. Salomon NW, Plachetka JR, Copeland JG. Comparison of dopamine and dobutamine following coronary artery bypass grafting. Ann Thorac Surg . 1982; 33:48-54. [PubMed 6978111]

119. Elhendy A, Bax JJ, Poldermans D. Dobutamine stress myocardial perfusion imaging in coronary artery disease. J Nucl Med . 2002; 43:1634-46. [PubMed 12468513]

120. Rodgers GP, Ayanian JZ, Balady G et al. American College of Cardiology/American Heart Association Clinical Competence statement on stress testing: a report of the American College of Cardiology/American Heart Association/American College of Physicians--American Society of Internal Medicine Task Force on Clinical Competence. J Am Coll Cardiol . 2000; 36:1441-53. [PubMed 11028516]

121. Klocke FJ, Baird MG, Lorell BH et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation . 2003; 108:1404-18. [PubMed 12975245]

122. Douglas PS, Khandheria B, Stainback RF et al. ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography: a report of the American College of Cardiology Foundation Appropriateness Criteria Task Force, American Society of Echocardiography, American College of Emergency Physicians, American Heart Association, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance endorsed by the Heart Rhythm Society and the Society of Critical Care Medicine. J Am Coll Cardiol . 2008; 51:1127-47. [PubMed 18342240]

123. Henzlova MJ, Duvall WL, Einstein AJ et al. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. J Nucl Cardiol . 2016; :.

124. Mertes H, Sawada SG, Ryan T et al. Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients. Circulation . 1993; 88:15-9. [PubMed 8319327]

125. Poldermans D, Fioretti PM, Forster T et al. Dobutamine stress echocardiography for assessment of perioperative cardiac risk in patients undergoing major vascular surgery. Circulation . 1993; 87:1506-12. [PubMed 8491005]

126. Chuah SC, Pellikka PA, Roger VL et al. Role of dobutamine stress echocardiography in predicting outcome in 860 patients with known or suspected coronary artery disease. Circulation . 1998; 97:1474-80. [PubMed 9576428]

127. Das MK, Pellikka PA, Mahoney DW et al. Assessment of cardiac risk before nonvascular surgery: dobutamine stress echocardiography in 530 patients. J Am Coll Cardiol . 2000; 35:1647-53. [PubMed 10807472]

128. Schinkel AF, Elhendy A, Biagini E et al. Prognostic stratification using dobutamine stress 99mTc-tetrofosmin myocardial perfusion SPECT in elderly patients unable to perform exercise testing. J Nucl Med . 2005; 46:12-8. [PubMed 15632027]

129. Schinkel AF, Elhendy A, van Domburg RT et al. Prognostic value of dobutamine-atropine stress (99m)Tc-tetrofosmin myocardial perfusion SPECT in patients with known or suspected coronary artery disease. J Nucl Med . 2002; 43:767-72. [PubMed 12050321]

130. Elhendy A, Schinkel AF, van Domburg RT et al. Risk stratification of patients with angina pectoris by stress 99mTc-tetrofosmin myocardial perfusion imaging. J Nucl Med . 2005; 46:2003-8. [PubMed 16330563]

153. Dellinger RP, Levy MM, Rhodes A et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med . 2013; 39:165-228. [PubMed 23361625]

159. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation . 2008; 117:686-97. [PubMed 18250279]

161. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O'Gara PT et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2013; 61:e78-140.

162. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2014; 64:e139-228. [PubMed 25260718]

165. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation . 2013; 128:e240-327.

249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]

250. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]

401. Neumar RW, Otto CW, Link MS et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation . 2010; 122(18 Suppl 3):S729-67.

403. Kleinman ME, Chameides L, Schexnayder SM et al. Part 14: pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation . 2010; 122(18 Suppl 3):S876-908.

404. Peberdy MA, Callaway CW, Neumar RW et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation . 2010; 122(18 Suppl 3):S768-86.