Acute hypotension may occur in a variety of settings such as severe hemorrhage, decreased blood volume, cardiac arrhythmias, neurologic disease or accidents, adverse reactions or overdose of medications such as antihypertensive drugs, and infection. If cerebral, renal, and cardiac perfusion is maintained, hypotension itself does not usually require vigorous direct treatment. Rather, placing the patient in the recumbent position and ensuring adequate fluid volume while the primary problem is determined and treated is usually the correct course of action. The use of sympathomimetic drugs merely to elevate a blood pressure that is not an immediate threat to the patient may increase morbidity. However, sympathomimetics may be required in cases of sustained hypotension with evidence of tissue hypoperfusion.
Shock is a complex acute cardiovascular syndrome that results in a critical reduction in perfusion of vital tissues and a wide range of systemic effects. Shock is usually associated with hypo-tension, an altered mental state, oliguria, and metabolic acidosis. If untreated, shock usually progresses to a refractory deteriorating state and death. The three major forms of shock are septic, cardiogenic, and hypovolemic. Volume replacement and treatment of the underlying disease are the mainstays of the treatment of shock. If vasopressors are needed, adrenergic agonists with both α and β activity are preferred. Pure β-adrenergic stimulation increases blood flow but also increases the risk of myocardial ischemia. Pure α-adrenergic stimulation increases vascular tone and blood pressure but can also decrease cardiac output and impair tissue blood flow. Norepinephrine provides an acceptable balance and is considered the vasopressor of first choice: it has predominantly α-adrenergic properties, but its modest β-adrenergic effects help to maintain cardiac output. Administration generally results in a clinically significant increase in mean arterial pressure, with little change in heart rate or cardiac output. Dopamine has no advantage over norepinephrine because it is associated with a higher incidence of arrhythmias and mortality. However, dobutamine is arguably the inotropic agent of choice when increased cardiac output is needed.
B. Chronic Orthostatic Hypotension
On standing, gravitational forces induce venous pooling, resulting in decreased venous return. Normally, a decrease in blood pressure is prevented by reflex sympathetic activation with increased heart rate, and peripheral arterial and venous vasoconstriction. Impairment of autonomic reflexes that regulate blood pressure can lead to chronic orthostatic hypotension. This is more often due to medications that can interfere with autonomic function (eg, imipramine and other tricyclic antidepressants, α blockers for the treatment of urinary retention, and diuretics), diabetes, and other diseases causing peripheral autonomic neuropathies, and less commonly, primary degenerative disorders of the autonomic nervous system, as in the case study described at the beginning of the chapter.
Increasing peripheral resistance is one of the strategies to treat chronic orthostatic hypotension, and drugs activating α receptors can be used for this purpose. Midodrine, an orally active α1 agonist, is frequently used for this indication. Other sympathomimetics, such as oral ephedrine or phenylephrine, can be tried. A novel approach to treat orthostatic hypotension is droxidopa, a synthetic (L-threo-dihydrophenylserine, L-DOPS) molecule that has been approved by the FDA to treat neurogenic orthostatic hypotension. It is a prodrug that is converted to norepinephrine by the aromatic L-amino acid decarboxylase (dopa-decarboxylase), the enzyme that converts L-dopa to dopamine.
C. Cardiac Applications
Epinephrine is used during resuscitation from cardiac arrest. Current evidence indicates that it improves the chance of returning to spontaneous circulation, but it is less clear that it improves survival or long-term neurologic outcomes and this is an area of active investigation.