Hemodynamic Drugs

This chapter focuses on drugs that are given by intravenous infusion to modulate blood pressure and blood flow. The following drugs are described: dobutamine, dopamine, epinephrine, nicardipine, nitroglycerin, nitroprusside, norepinephrine, and phenylephrine. Each is presented in alphabetical order.

I. Dobutamine

Dobutamine is a synthetic catecholamine with both positive inotropic and vasodilator effects (i.e., an inodilator).

A. Actions

Dobutamine is a β-adrenergic receptor agonist, and binds to β₁– and β₂-receptors in a 3:1 ratio (see Table 45.1) (1,2). Activation of β₁-receptors (in cardiac muscle) produces positive inotropic and chronotropic effects, while activation of β₂-receptors (in vascular smooth muscle) promotes vasodilation.
The principal effects of dobutamine include (1,2):
- A dose-dependent increase in cardiac output (due to augmentation of stroke volume more than heart rate).
- A decrease in ventricular filling pressures.
- A decrease in systemic vascular resistance.
- Blood pressure can be decreased, unchanged, or in-creased, depending on the balance between changes in stroke volume and systemic vascular resistance.

Table 45.1 Dosing and Receptor Binding Affinities for Catecholamine Drugs

Drug	Usual Dose Range	Adrenergic Receptors
Drug	Usual Dose Range	α₁	β₁	β₂
Dobutamine	3–20 μg/kg/min	—	+++++	++
Dopamine	3–10 μg/kg/min	—	++++	++
	11–20 μg/kg/min	+++	++++	++
Epinephrine	1–15 μg/min	+++++	++++	+++
Norepinephrine	2–20 μg/min	+++++	+++	++
Phenylephrine	0.1–0.2 mg/min	+++++	—	—

B. Clinical Uses

According to the American Heart Association guidelines on the management of heart failure (3), dobutamine should be reserved for cases of severe systolic dysfunction that have progressed to cardiogenic shock or impending shock. Because dobutamine does not reliably raise the blood pressure, hypotension should be corrected with a vasoconstrictor agent before dobutamine is used.
The Surviving Sepsis Campaign guidelines on severe sepsis and septic shock (4) recommends dobutamine when fluids and vasoconstrictor drugs do not normalize the central venous O₂ saturation (see Chapter 9).
Dobutamine is NOT appropriate for the management of heart failure caused by impaired ventricular filling (i.e., “diastolic” heart failure).

C. Drug Administration

Dobutamine is given by continuous intravenous infusion without an initial loading dose.
The initial dose rate is 3–5 βg/kg/min, which can be in-creased in increments of 3–5 βg/kg/min, if necessary. At dose rates above 20 βg/kg/min, the risk of adverse events usually outweighs the benefit (3,4).

D. Adverse Effects

The adverse effects of dobutamine are related to cardiac stimulation:

Dobutamine infusions are usually accompanied by a mild increase in heart rate (10–15 beats/min), but greater increments in heart rate (≥30 beats/min) can occur in individual patients (2). Malignant tachyarrhythmias are uncommon during dobutamine infusions.
Dobutamine increases myocardial O₂ consumption, and this can hasten depletion of energy stores in the failing myocardium. This concern is one of the reasons that dobutamine is recommended only as a short-term (≤72 hrs) intervention (3).

II. Dopamine

Dopamine is an endogenous catecholamine that serves as both a neurotransmitter and a precursor for norepinephrine synthesis. About 25% of a dose of dopamine is taken up into adrenergic nerve terminals and metabolized to norepinephrine (5).

A. Actions

1. Low Dose Rates

At low dose rates (<3 βg/kg/min), dopamine selectively activates dopamine-specific receptors in the renal and
splanchnic circulations, which promotes vasodilation and enhanced blood flow in these regions (5). The renal effects of low-dose dopamine are minimal or absent in patients with acute renal failure (6).

2. Intermediate Dose Rates

At intermediate dose rates (3–10 βg/kg/min), dopa-mine stimulates β-receptors in the heart and systemic circulation, and produces cardiovascular changes very similar to those described for dobutamine.

3. High Dose Rates

At high dose rates (>10 βg/kg/min), dopamine produces a dose-dependent activation of β-receptors, resulting in widespread vasoconstriction and a progressive increase in blood pressure.

B. Clinical Uses

The popularity of dopamine as a hemodynamic support drug has waned considerably in recent years because of troublesome tachyarrhythmias and reports of increased mortality associated with the drug (7). Relevant issues regarding dopamine use are summarized below.

Low-dose dopamine was once used in an attempt to increase glomerular filtration rate in patients with acute renal failure, but this practice does not hasten renal recovery (6) and is no longer recommended.
Dopamine is no longer a preferred vasopressor in septic shock, and is recommended only for patients with relative or absolute bradycardia and a minimal risk of tachy-arrhythmias (4).
Dopamine is a consideration in cardiogenic shock because the combined β- and β-agonist actions can raise the blood pressure while also providing positive inotropic support.

C. Drug Administration

Like all vasoconstrictors, dopamine can cause extensive tissue necrosis if extravasation occurs, so the drug should be delivered into a large, central vein.
Dopamine is given by continuous intravenous infusion, without an initial loading dose.
- The initial dose rate is 3–5 βg/kg/min, and this can be titrated upwards every few minutes, if necessary, to achieve the desired effect.
- Dose rates of 3–10 βg/kg/min are optimal for augmenting cardiac output.
- Dose rates >10 βg/kg/min are usually needed to raise the blood pressure.
- The maximum dose rate is usually 20 βg/kg/min; higher dose rates are often accompanied by undesirable levels of tachycardia without additional vasopressor effects.

D. Adverse Effects

Tachyarrhythmias are the most common adverse effect; sinus tachycardia and atrial fibrillation are reported in 25% of patients receiving dopamine infusions (7).
Other adverse effects of dopamine include gangrene of the digits (5), splanchnic hypoperfusion (5), increased intraocular pressure (9), and delayed gastric emptying (10).

III. Epinephrine

Epinephrine is an endogenous catecholamine that is released by the adrenal medulla in response to physiological stress. It is the most potent naturally-occurring β-agonist.

A. Actions

Epinephrine is a non-selective β- and β-receptor agonist, and produces dose-dependent increases in heart rate, stroke volume, and blood pressure (11,12).
β-receptor stimulation produces a non-uniform peripheral vasoconstriction, with the most prominent effects in the subcutaneous, renal, and splanchnic circulations. The risk of splanchnic ischemia is one of the major concerns with epinephrine administration (12).
Epinephrine has the following metabolic effects (11,12):
- β-receptor activation promotes lipolysis and glycolysis, and increases lactate production; the latter effect is often accompanied by hyperlactatemia. (These effects are not prominent with the other, less potent, β-agonists.)
- β-receptor stimulation inhibits insulin secretion and promotes hyperglycemia.

B. Clinical Uses

Epinephrine is a first-line drug in the resuscitation of cardiac arrest and anaphylactic shock (see Chapters 9 and 15).
Epinephrine is also a popular hemodynamic support drug in the early postoperative period following cardiopulmonary bypass surgery.
Concerns about the risk for adverse effects have limited the popularity of epinephrine as a vasopressor drug in septic shock, and it is usually reserved for cases that are refractory to conventional vasopressor agents (e.g., norepinephrine) (12).

C. Drug Administration

Because of its vasoconstrictor actions, epinephrine should be delivered into a large, central vein.
The epinephrine dosing regimens for circulatory support are as follows (11):
- CARDIAC ARREST: 1 mg as IV bolus every 3–5 minutes until return of spontaneous circulation.
- ANAPHYLACTIC SHOCK: Start infusion at 5 μg/min, and increase dose rate by 2–5 μg/min, if necessary, to achieve the target blood pressure. Usual dose range is 5–15 μg/min.
- SEPTIC SHOCK OR POST-BYPASS CIRCULATORY SUPPORT: Start infusion at 1–2 μg/min, and increase dose rate by 1–2 μg/min, if necessary, to achieve the desired blood pressure. Usual dose range is 1–10 μg/min.