Dobutamine

Registered South African indications:

• Ionotropic support
  - Heart failure
  - Myocardial infarction
  - Cardiac surgical procedures

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to sodium metabisulphite or other sulphates
• Marked mechanical obstruction affecting ventricular filling or outflow, or both, such as;
  - Cardiac tamponade
  - Severe valvular aortic stenosis
  - Constrictive pericarditis
  - Hypertrophic obstructive cardiomyopathia
  - Idiopathic hypertrophic subaortic stenosis
• Hypovolaemia unless it has been corrected by volume replacement
• Uncontrolled serious ventricular arrhythmias

Cardiac stress test

• Recent myocardial infarction (within 30 days)
• Aortic dissection
• Aortic aneurysm
• Unstable angina
• Uncontrolled hypertension
• Uncontrolled arrhythmias (including uncontrolled atrial fibrillation)
• Known severe ventricular arrhythmias
• Electrolyte imbalance
• Severe anaemia
• Phaeochromocytoma

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Atrial flutter
• Atrial fibrillation
• Myocardial infarction
• Patients with markedly reduced ventricular compliance e.g. cardiac tamponade, valvular aortic stenosis, idiopathic hypertrophic subaortic stenosis
• Severe hypotension complicating cardiogenic shock (mean arterial pressure <70mm Hg)
• Pre-existing hypertonia
• Advanced heart failure
• Diabetic patients
• Ischaemic heart disease

Cardiac stress testing

• Unstable angina
• Bundle branch block
• Any cardiac condition that could make them unsuitable for exercise stress testing
• Recent history of monoamine oxidase inhibitor therapy
• Hyperthyroidism
• Risk factors for cardiac rupture e.g. recent myocardial infarction

Forms avail. in SA and covered in this monograph: inj

Positive ionotropic support
- In the treatment of low output cardiac failure normally associated with myocardial infarction, open-heart surgery, cardiomyopathies, septic shock and cardiogenic shock

• IV: Initial: 2.5μg/kg/min; Titrate based on response if necessary in 10-30min intervals; Dose range: 2.5-10μg/kg/min; Max dose: 40μg/kg/min

---

Occasionally, a dose as low as 0.5μg/kg/min will elicit a response

---

Dose should be adjusted individually according to heart rate and rhythm, blood pressure and urinary flow

---

During prolonged continuous infusion (48-72hrs), a decrease in haemodynamic response may occur, which makes an increase in dose necessary

---

Dosage should be titrated until desired haemodynamic response is achieved or until side effects limit a further increase in dosage

---

In patients with heart failure, lower doses are preferred to minimize adverse effects

---

Treatment should be gradually discontinued

---

Must be admin. by IV infusion as a dilute solution. The following sterile solutions for IV infusion may be used: sodium chloride solution 0.9% (9mg/ml), glucose solution 5% (50mg/ml), dextrose solution 5% (50mg/ml), or Ringers lactate solution

---

Cardiac stress testing (additional agent may be required) 
- In cases where exercise stress testing is not feasible

• IV: Initial: 5μg/kg/min; Titrate to 10, 20, 30, 40μg/kg/min after 3min intervals; Max dose: 40μg/kg/min

---

Dobutamine in cardiac stress testing should only be undertaken in premises which already perform exercise stress testing and all normal care and precautions required for such testing are also required, including availability of a defibrillator and personnel specially trained in resuscitation are present

---

Atropine may be added during further infusion of the peak dose

---

Continuous electrocardiogram monitoring is required and the infusion may be terminated in the event of ST-segment depression of >0.2mV (2mm) measured 80ms after the last J point, a ST-segment elevate of >0.1mV (1mm) in patients without history of myocardial infarction, or any significant cardiac arrhythmias

---

The infusion of dobutamine should be terminated if the heart rate reaches 85% of the age-predicted maximum, systolic blood pressure rises above 220mmHg or a symptomatic decrease in systolic blood pressure >40 mmHg from baseline, new cardiac wall motion abnormalities, severe chest pain or any non-tolerable adverse effect occurs

Paed. forms avail. in SA and covered in this monograph: inj

Ionotropic support
- In low cardiac output hypoperfusion states resulting from decompensated heart failure, following cardiac surgery, cardiomyopathies and in cardiogenic or septic shock

• IV: Initial: 5μg/kg/min; Titrate to response; Dose range: 2-20μg/kg/min

---

Occasionally, a dose as low as 0.5-1.0μg/kg/min will produce a response

---

Minimum effective dosage for children may be higher than for adults

---

Exercise caution when applying high doses because there is also reason to believe that the maximum tolerated dosage for children is lower than the one for adults

---

Most adverse reactions are observed when dosage ≥7.5μg/kg/min - reducing or termination of the rate of dobutamine infusion results in rapid reversal of undesirable effects

---

Required dose for children cannot be determined a priori and should be titrated in order to allow for the supposedly smaller 'therapeutic width' in children

Pregnancy

• Caution
• There are no adequate data on the safety of dobutamine in human pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition and postnatal development, but it is not known whether dobutamine crosses the placenta
• The potential risk for humans is unknown. Dobutamine should not be used during pregnancy unless the potential benefits to the woman outweigh the potential risks to the foetus

Breastfeeding

• Caution; not recommended
• It is not known whether dobutamine is excreted in animal or human breast milk
• A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with dobutamine should be made taking into account the benefit of breastfeeding to the child and the benefit of dobutamine therapy to the woman

Renal Impairment

• Caution; no information available
  Since the effect of dobutamine on impaired renal function is not known, close monitoring is advisable

Hepatic Impairment:

• Caution; no information available 
  Since the effect of dobutamine on impaired hepatic function is not known, close monitoring is advisable

Elderly

• Positive ionotropic support: Caution; no dose adjustment recommended
  Close monitoring is required for blood pressure, urine flow and peripheral tissue perfusion
• Cardiac stress testing: Caution; dose adjustment recommended
  IV: Initial: 5μg/kg/min; Titrate in 5μg/kg/min increments after 8min intervals; Max 20μg/kg/min
  Continuous ECG monitoring is essential and the infusion terminated in the event of >3mm ST-segment depression or any ventricular arrhythmia. Infusion should also be terminated if heart rate reaches the age/sex maximum, systolic blood pressure >220mm Hg or any side effects occur

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Myoclonus

Cardiovascular Disorders

• Increased heart rate
• Palpitations
• Severe chest pain
• Irregular heartbeats
• Arrhythmia
• Ventricular tachycardia
• Coronary artery spasm
• Electrocardiogram ST-segment elevation
• Atrial fibrillation
• Ventricular fibrillation
• Left ventricular outflow tract obstruction
• Myocardial ischaemia
• Myocardial infarction
• Eosinophilic myocarditis
• Fatal cardiac rupture
• Hypertension
• Hypotension
• Slight vasoconstriction
• Systolic blood pressure
• Tachycardia

Respiratory Disorders

• Shortness of breath
• Bronchospasm
• Asthma
• Elevation of pulmonary wedge pressure
  - Pulmonary congestion
  - Pulmonary oedema

Gastrointestinal Disorders

• Nausea

Genitourinary Disorders

• Urinary urgency

Endocrine and Metabolic Disorders

• Catecholamines

Skin and Subcutaneous Tissue Disorders

• Cutaneous necrosis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
  - Rash
  - Fever
  - Eosinophilia
  - Bronchospasm
• Sodium metabisulphite
  - Anaphylaxis
• Phlebitis
• Local inflammatory changes

Others

• Non-specific chest pain
• Inadvertent infiltration

• Beta-adrenergic blocking agents
  - Propranolol
  - Metoprolol
• Dipyridamole
• Heart rate lowering agents
  - Beta-blockers
• Atropine sulphate
• General anaesthetics
  - Halothane anaesthesia
  - Cyclopropane anaesthesia
• Beta-receptor blocking drugs
• Peripheral vasodilators
  - Nitrates
  - Sodium nitroprusside
• Theophylline
• Dopamine
• Peripheral vasoconstrictor agents
  - Noradrenaline
• ACE-inhibitors
  - Captopril
• Entacapone
• Antipsychotics
• Doxapram
• Ergotamine
• Methysergide
• Oxytocin

• Blood pressure
• Electrocardiogram
• Heart rate
• Central venous pressure
• Right atrial pressure
• Mean arterial pressure
• Glucose
• Renal function
• Urine output

None routine. Specific cases may require

If pulmonary artery catheter is in place

• Monitor cardiac index
• Pulmonary capillary wedge pressure
• Systemic vascular resistance
• ScvO2/SvO2

Dobutamine is a selective beta-adrenergic agonist whose mechanism of action is complex. It is believed that the beta-adrenergic effects result from stimulation of adenyl cyclase activity. In therapeutic doses, dobutamine also has mild beta-2 and alpha-1 adrenergic receptor agonist effects, which are relatively balanced and result in minimal net direct effect on systemic vasculature. Dobutamine does not cause release of endogenous norepinephrine. The main effect of therapeutic doses of dobutamine is cardiac stimulation. The beta-1-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. Dobutamine facilitates atrioventricular conduction and shortens or causes no important change in intraventricular conduction.

Injection (per 20ml) 250mg

• Cardiject (Ranbaxy)
• Dobutamine-Fresenius (Fresenius Kabi)
• Dobutrex (Sandoz) originator
• Micro-Dobutamine (Micro Healthcare)