Inotropes are a class of medications that alter the force or energy of heart contractions. They are primarily used to manage certain forms of heart failure and other cardiac conditions where the heart’s pumping ability is compromised. Inotropes can be broadly classified into positive and negative inotropes based on their effects on myocardial contractility.
Types of Inotropes
- Positive Inotropes
- Dobutamine
- Dopamine
- Epinephrine (Adrenaline)
- Norepinephrine (Noradrenaline)
- Milrinone
- Digoxin
- Negative Inotropes
- Beta-Blockers (e.g., Metoprolol, Propranolol)
- Calcium Channel Blockers (e.g., Verapamil, Diltiazem)
- Antiarrhythmic Drugs (e.g., Amiodarone)
Detailed Overview of Inotropes
Positive Inotropes
Positive inotropes increase the strength of the heart’s contractions, making them vital in managing acute heart failure and certain forms of shock.
- Dobutamine
Mechanism:
- Primarily stimulates beta-1 adrenergic receptors, enhancing myocardial contractility and stroke volume without significantly increasing heart rate.
Uses:
- Acute decompensated heart failure
- Cardiogenic shock
Preferred Route:
- Intravenous infusion
Dose:
- Initial: 2.5–5 micrograms/kg/min IV infusion
- Maintenance: Up to 20 micrograms/kg/min, titrated to response
- Maximum: Generally up to 20 micrograms/kg/min
Side Effects:
- Tachycardia
- Arrhythmias
- Hypotension (due to beta-2 effects)
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Cardiac output and perfusion parameters
- Dopamine
Mechanism:
- Dose-dependent effects:
- Low dose: Stimulates dopamine receptors causing vasodilation
- Moderate dose: Stimulates beta-1 receptors increasing heart rate and contractility
- High dose: Stimulates alpha-1 receptors causing vasoconstriction
Uses:
- Shock (cardiogenic, septic)
- Acute heart failure
Preferred Route:
- Intravenous infusion
Dose:
- Low dose: 2–5 micrograms/kg/min IV (renal dose)
- Moderate dose: 5–10 micrograms/kg/min IV (cardiac dose)
- High dose: >10 micrograms/kg/min IV (vasopressor dose)
- Maximum: Typically up to 20 micrograms/kg/min
Side Effects:
- Tachycardia
- Arrhythmias
- Vasoconstriction at high doses
- Nausea and vomiting
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Renal function (urine output)
- Epinephrine (Adrenaline)
Mechanism:
- Stimulates alpha and beta adrenergic receptors
- Increases heart rate (beta-1), myocardial contractility (beta-1), and causes vasoconstriction (alpha-1)
Uses:
- Anaphylactic shock
- Cardiac arrest
- Severe asthma exacerbations
- Septic shock (second-line agent)
Preferred Route:
- Intramuscular (IM) for anaphylaxis
- Intravenous (IV) bolus and infusion for cardiac arrest and shock
Dose:
- Anaphylaxis: 0.5 mg (0.5 mL of 1:1,000 solution) IM, repeated every 5 minutes if necessary
- Cardiac Arrest: 1 mg (10 mL of 1:10,000 solution) IV every 3-5 minutes during resuscitation
- Infusion: 0.05–0.5 micrograms/kg/min IV, titrated to response
- Maximum: Typically up to 1 microgram/kg/min, though higher doses may be considered in refractory cases
Side Effects:
- Tachycardia
- Arrhythmias
- Hypertension
- Hyperglycemia
- Lactic acidosis
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Blood glucose levels
- Lactate levels
- Norepinephrine (Noradrenaline)
Mechanism:
- Primarily stimulates alpha-1 adrenergic receptors causing vasoconstriction
- Also stimulates beta-1 adrenergic receptors, increasing myocardial contractility and heart rate to a lesser extent
Uses:
- First-line agent for septic shock
- Acute hypotension
Preferred Route:
- Intravenous infusion (central venous access preferred)
Dose:
- Initial: 0.05–0.1 micrograms/kg/min IV infusion
- Maintenance: Titrate to effect, usually 0.05–2 micrograms/kg/min
- Maximum: Up to 3 micrograms/kg/min, though higher doses may be used in refractory cases under close monitoring
Side Effects:
- Arrhythmias
- Hypertension
- Peripheral and visceral ischemia
- Reflex bradycardia
Monitoring:
- Continuous blood pressure monitoring
- Heart rate and rhythm
- Peripheral perfusion (e.g., capillary refill, limb temperature)
- Milrinone
Mechanism:
- Phosphodiesterase-3 inhibitor, which increases cyclic AMP levels, enhancing calcium influx into myocardial cells, thereby increasing contractility and causing vasodilation
Uses:
- Acute heart failure, often used when patients are unresponsive to other inotropes
Preferred Route:
- Intravenous infusion
Dose:
- Initial: 50 micrograms/kg IV bolus over 10 minutes
- Maintenance: 0.375–0.75 micrograms/kg/min IV infusion
- Maximum: Up to 0.75 micrograms/kg/min
Side Effects:
- Arrhythmias
- Hypotension
- Thrombocytopenia
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Renal function (creatinine, urine output)
- Digoxin
Mechanism:
- Inhibits the sodium-potassium ATPase pump, leading to an increase in intracellular calcium, which enhances myocardial contractility
Uses:
- Chronic heart failure
- Atrial fibrillation
Preferred Route:
- Oral or intravenous
Dose:
- Loading dose: 0.75–1.5 mg IV or PO, divided into multiple doses
- Maintenance: 0.125–0.25 mg daily
- Maximum: Individualized based on serum levels, typically not exceeding 0.25 mg/day without close monitoring
Side Effects:
- Arrhythmias
- Gastrointestinal disturbances
- Visual disturbances
Monitoring:
- Serum digoxin levels
- Renal function (creatinine)
- Electrolytes (potassium, magnesium)
- ECG for arrhythmias
Negative Inotropes
Negative inotropes decrease the strength of the heart’s contractions, reducing the workload on the heart. They are useful in managing conditions like hypertension, angina, and arrhythmias.
- Beta-Blockers
Examples: Metoprolol, Propranolol, Atenolol, Bisoprolol, Carvedilol
Mechanism:
- Block beta-adrenergic receptors, reducing the effects of adrenaline and noradrenaline. This leads to a decrease in heart rate and contractility
Uses:
- Hypertension
- Angina
- Heart failure
- Arrhythmias
- Post-myocardial infarction to prevent recurrence
Preferred Route:
- Oral or intravenous
Dose:
- Metoprolol: 50–100 mg twice daily orally, or 5 mg IV bolus
- Propranolol: 40–80 mg twice daily orally, or 1–3 mg IV bolus
- Maximum: Individualized based on specific beta-blocker and patient response
Side Effects:
- Bradycardia
- Fatigue
- Dizziness
- Depression
- Bronchoconstriction (especially with non-selective beta-blockers like propranolol)
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Respiratory status in patients with asthma or COPD
- Calcium Channel Blockers
Examples: Verapamil, Diltiazem
Mechanism:
- Inhibit the influx of calcium ions into cardiac and smooth muscle cells, reducing contractility and leading to vasodilation
Uses:
- Hypertension
- Angina
- Certain types of arrhythmias (e.g., supraventricular tachycardia)
Preferred Route:
- Oral or intravenous
Dose:
- Verapamil: 80–120 mg three times daily orally, or 2.5–10 mg IV bolus
- Diltiazem: 60–120 mg twice daily orally, or 0.25 mg/kg IV bolus
- Maximum: Individualized based on specific calcium channel blocker and patient response
Side Effects:
- Constipation
- Bradycardia
- AV block
- Edema
Monitoring:
- Blood pressure and heart rate
- ECG for arrhythmias
- Signs of heart failure
- Antiarrhythmic Drugs
Example: Amiodarone
Mechanism:
- Blocks potassium channels, prolonging repolarization. Also has sodium, calcium channel blocking effects, and non-competitive beta-blocking activity
Uses:
- Atrial fibrillation
- Ventricular tachycardia
- Ventricular fibrillation
Preferred Route:
- Oral or intravenous
Dose:
- Loading dose: 200 mg three times daily for 1 week, then 200 mg twice daily for another week
- Maintenance: 200 mg daily orally, or 150–300 mg IV bolus followed by infusion of 1 mg/min for 6 hours, then 0.5 mg/min
- Maximum: Typically not exceeding 400 mg/day orally, or 1200 mg/day IV
Side Effects:
- Pulmonary toxicity
- Liver toxicity
- Thyroid dysfunction
- Skin discoloration
- Bradycardia
- Hypotension
Monitoring:
- Pulmonary function tests
- Liver function tests (LFTs)
- Thyroid function tests
- ECG for arrhythmias
- Regular clinical assessment for side effects
Clinical Use of Inotropes
Indications
- Positive Inotropes: Used in acute decompensated heart failure, cardiogenic shock, septic shock, and other conditions requiring enhanced myocardial contractility.
- Negative Inotropes: Used in hypertension, angina, arrhythmias, heart failure management, and post-myocardial infarction to reduce cardiac workload.
Administration
- Intravenous Infusion: Preferred for acute settings to ensure rapid and controlled delivery (central venous access preferred for many agents).
- Oral: Common for chronic management of conditions like heart failure and hypertension.
Side Effects and Risks
Positive Inotropes
- Arrhythmias: Increased risk of abnormal heart rhythms due to enhanced myocardial excitability.
- Increased Myocardial Oxygen Consumption: Potential worsening of ischemia in patients with coronary artery disease.
- Hypotension: Some inotropes, like milrinone, can cause vasodilation leading to low blood pressure.
- Tachycardia: Elevated heart rate, which can further strain the heart.
Negative Inotropes
- Bradycardia: Excessive slowing of the heart rate.
- Hypotension: Low blood pressure, leading to dizziness and fainting.
- Heart Failure Exacerbation: In some cases, especially with calcium channel blockers or in acute settings.
- Fatigue and Weakness: Common due to reduced cardiac output.
- Bronchoconstriction: Particularly with non-selective beta-blockers in asthma or COPD patients.
Monitoring
Patients on inotropes require regular monitoring, including:
- Heart Rate and Rhythm: Using electrocardiogram (ECG) monitoring.
- Blood Pressure: To detect hypotension or hypertension.
- Oxygenation and Perfusion: Including measurement of oxygen saturation and capillary refill time.
- Renal Function: To detect any deterioration in kidney function, as inotropes can affect renal perfusion.
- Symptoms of Heart Failure: To manage any exacerbation or improvement.
- Specific Drug Levels: For drugs like digoxin to ensure therapeutic levels and avoid toxicity.
Conclusion
Inotropes are powerful medications used to manage severe heart failure, shock, and other critical cardiac conditions. While they can significantly improve cardiac output and patient symptoms, their use must be carefully monitored due to the potential for serious side effects. Both positive and negative inotropes have crucial roles in specific clinical scenarios, and their administration requires careful titration and monitoring in an intensive care or controlled outpatient setting.