Management of Hypotension and Cardiogenic Shock
Michael M. Givertz
I. GENERAL PRINCIPLES
A. Background.
1. Hypotension and cardiogenic shock are frequently encountered in the intensive care setting as the final result of a heterogeneous group of disorders.
2. End-organ perfusion generally becomes compromised when the systolic arterial pressure falls below 90 mm Hg or when mean arterial pressure falls below approximately 60 mm Hg. Cardinal manifestations include
a. Oliguria and worsening renal function.
b. Metabolic acidosis due to increased production and decreased clearance of lactate.
c. Mental status changes ranging from confusion to coma.
d. Cool, clammy skin due to intense vasoconstriction. In patients with distributive shock and low systemic vascular resistance (SVR), extremities may be warm and flushed.
3. Cardiogenic shock is a consequence of severe cardiac pump failure and is characterized by decreased cardiac output, increased SVR, and increased pulmonary capillary wedge pressure. Major causes include:
a. Massive myocardial infarction; myocardial infarction complicated by ventricular septal, free wall, or papillary muscle rupture; and right ventricular infarction (see Chapter 34).
b. Advanced nonischemic cardiomyopathy with refractory heart failure.
c. Fulminant myocarditis or stress cardiomyopathy.
e. Massive pulmonary embolism, pericardial tamponade, or severe pulmonary hypertension.
4. Although definitive management requires therapy directed at the underlying cause of hypotension (e.g., antibiotics for sepsis, corticosteroids for adrenal insufficiency, blood transfusion for bleeding), intravenous (IV) vasoactive agents are at times necessary to maintain perfusion to vital organs while the underlying etiology of hypotension is investigated and definitive measures have been instituted.
5. When IV medications are insufficient to maintain vital organ perfusion, consideration should be given to temporary mechanical circulatory support with an intraaortic balloon pump (IABP), percutaneous
ventricular assist device (VAD), or extracorporeal membrane oxygenation (ECMO).
ventricular assist device (VAD), or extracorporeal membrane oxygenation (ECMO).
B. Adrenergic receptor physiology.
1. With few exceptions, vasopressors and positive inotropes are sympathomimetic amines that bind to and stimulate adrenergic receptors. The characteristic hemodynamic effects of individual agents depend to a great extent on selective binding to various adrenergic receptors.
a. α1-Adrenergic receptors.
i. Present in smooth muscle cells of many vascular beds, including the arterioles supplying the skin, mucosa, skeletal muscles, and kidneys, as well as peripheral venules.
ii. Stimulation causes vasoconstriction and is the most common mechanism of vasopressor action.
iii. Receptors in the myocardium appear to mediate a modest positive inotropic effect with little change in heart rate (HR).
b. β1-Adrenergic receptors.
i. Predominant adrenergic receptors in the heart.
ii. Stimulation causes a positive inotropic and chronotropic response.
c. β2-Adrenergic receptors.
i. Stimulation causes relaxation of smooth muscle in the bronchial tree, gastrointestinal tract, and uterus.
ii. Mediate vasodilation of arterioles supplying skeletal muscle.
d. Dopaminergic receptors (DA1 and DA2).
i. Mediate renal, coronary, cerebral, and mesenteric vasodilation.
ii. Stimulate natriuresis.
2. Receptor selectivity of sympathomimetic amines can be drug and/or dose dependent. Examples include:
a. β2-receptors are more sensitive to epinephrine than are α1-receptors.
b. Dose-dependent actions of dopamine (see Section II.A.3.b).
3. Overall clinical effects of a drug include both the direct sequelae of adrenergic receptor stimulation and the reflex response of homeostatic forces (e.g., norepinephrine-mediated α1-adrenergic stimulation induces increased vagal tone, which opposes the positive chronotropic effects of β1-adrenergic stimulation, resulting in little overall change in HR).
II. PHARMACOLOGIC TREATMENT
A. Commonly used vasopressors and positive inotropes (Table 25-1).
1. Epinephrine (Adrenalin).
a. An endogenous catecholamine, which is the least selective of the vasopressor agents, and a potent agonist of α- and β-adrenergic receptors.
b. Doses used clinically (1 to 10 µg/min) result in α-mediated venous and arterial constriction and β-mediated increased HR and myocardial contractility. The latter effect is mitigated by increased afterload.
c. Blood flow to skeletal muscles is increased owing to β2-mediated vasodilation.
d. Used to reverse hypotension with or without bradycardia following cardiopulmonary bypass.
TABLE 25-1 Dose Range, Receptor Activity, and Predominant Hemodynamic Effects of IV Vasoactive Drugs Commonly Used to Treat Hypotension | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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e. Plays a central role in cardiovascular resuscitation and management of anaphylaxis (see Chapter 140).
f. Because of adverse effects on renal and splanchnic blood flow and potential for inducing myocardial ischemia and tachyarrhythmias, epinephrine is considered a second-line agent in the management of hypotension secondary to septic shock.
g. May cause restlessness, tremor, headache, and palpitations.
2. Norepinephrine (Levophed).
a. An endogenous catecholamine with potent α1– and β1-adrenergic activity but little β2-agonism.
b. Predominant effect is dose-dependent vasoconstriction of arterial resistance vessels and veins. Cardiac effects of β1-stimulation are counterbalanced by increased afterload and reflex vagal activity induced by elevated SVR.
c. Clinically used doses (0.5 to 30 µg/min) result in potent vasoconstriction. Generally infused as a second-line agent in cases of severe distributive shock, but several studies suggest that in adults with hyperdynamic septic shock, use of norepinephrine as the initial agent is more likely to result in improved blood pressure and survival compared to dopamine.
d. Adverse effects include increased myocardial oxygen consumption and excessive renal and mesenteric vasoconstriction. Renal ischemia may be of particular concern in patients with hemorrhagic shock.
e. Extravasation often causes tissue necrosis and may lead to skin sloughing, and should be managed with local infiltration of phentolamine (see Section III.F).
3. Dopamine (Intropin).
a. An endogenous catecholamine that functions as a central neurotransmitter and synthetic precursor to norepinephrine.
b. Stimulates dopaminergic and adrenergic receptors in a dose-dependent manner; also stimulates release of norepinephrine from nerve terminals.
i. Low dose (<5 µg/kg/min): predominantly stimulates dopaminergic receptors in renal, mesenteric, and coronary vessels. In normal subjects, low-dose dopamine augments renal blood flow with little effect on blood pressure. The strategy of using low-dose dopamine as a renoprotective agent in critically ill patients has not been shown to be effective in controlled studies.
ii. Moderate dose (5 to 10 µg/kg/min): Predominant effect is β1-mediated augmentation of myocardial contractility and HR.
iii. High dose (>10 µg/kg/min): Overall hemodynamic effect resembles that of norepinephrine and is mediated by α1-adrenergic receptor stimulation.
c. As an agent with both inotropic and vasopressor activity, moderate- to high-dose dopamine has the versatility to be used as a first-line agent in hypotension of unknown etiology. However, in the setting of severe hypotension due to septic shock, a more potent α-adrenergic agonist such as norepinephrine may be more effective in restoring perfusion pressure.
