Vasopressors V: Inodilators

Start with Part IPart II, Part III, and Part IV. No skipping!

In the great dance of the heart and vasculature, we have seen inopressors (norepinephrine, epinephrine, dopamine) and pure vasopressors (phenylephrine, vasopressin). We can now come full circle by discussing the two most common inodilators: dobutamine and milrinone—even though technically, of course, they are not pressors at all.

Remember the definition of an inodilator: cardiosupportive effects (positive inotropy, chronotropy, etc) combined with arterial vasodilation, thus reducing cardiac afterload. Together, you make the heart squeeze harder while giving it less to squeeze against, exactly the combination you want when the pump is failing.

You may think we’ve skipped another, simpler category of drugs. What about “pure” inotropes, with no effect on vascular tone at all? Unfortunately, there aren’t any, at least not in the pharmacy. Electrical pacing can be used to increase heart rate, and devices like balloon pumps can promote forward flow. But it’s hard to pharmacologically isolate the heart; even specialized drugs like isoproterenol, the “chemical pacer,” tend to rely on beta receptors, which are present in the peripheral vasculature and unavoidably cause vasodilation when activated. The best we can do in most cases is to play it by ear: use an inopressor if the blood pressure is low, use an inodilator if the blood pressure is high… and combine an inodilator with a separate pressor if you need more flexibility.

The scenario: the patient is hypotensive, yet they also have a poor heart. Maybe the first is the primary problem, such as a septic patient in whom you discover an LV ejection fraction of 30%. Or maybe the heart is the main problem, as in a decompensated cardiogenic shock with resulting hypotension. Either way, you need an inotrope to increase cardiac output.

Beware! Starting an inodilator in a hypotensive patient can make the blood pressure bottom out due to the “dilator” part. This is especially true in the already-vasodilated state, and most of all with concomitant hypovolemia: nothing is quite so perilous as starting dobutamine on an underresuscitated septic patient. You are on firmer footing in the cardiogenic shock patient, but even there you must tread cautiously. Heart failure patients may benefit from a low afterload, but they still need a sufficient blood pressure to sustain life. Inodilators might increase blood pressure due to the improved cardiac output, decrease it due to the vasodilation, or cause little change if the effects are balanced. It’s hard to predict, and potentially hard to address.

So what can you do? You can start two drips: an inodilator plus a vasopressor.

Let’s say you go with dobutamine + norepinephrine. Now you have two tools. If there are signs of poor cardiac output (elevated lactate, poor urine output or mental status, cold skin, or advanced modalities like echocardiography or thermodilution), then titrate your dobutamine. Conversely, if the blood pressure is low—or becomes that way after starting dobutamine—then titrate the norepinephrine.

An alternative maneuver (mentioned in Part II) would be to use an epinephrine drip instead of an inodilator. This may allow you to avoid a separate pressor, but then, you lose the flexibility of having two separate knobs. (Now, you could combine a pressor plus low-dose epinephrine as your inotrope. But at that point you might as well just pick up a shift in the cardiac SICU.)

A more straightforward scenario is the pure heart failure patient who simply needs ongoing inotropic support. These are the end-stage patients whose hearts cannot provide enough forward flow on their own to perfuse the body and keep the lungs dry, even on optimal medical therapy. They do fine, however, on a continuous inotrope drip, and may sit for days that way on a cardiac unit until someone comes up with a destination plan (heart transplant, LVAD, or hospice care, sometimes even going home on their inotrope drip).

Let’s consider the two most common inodilators used in critical care. A third agent, levosimendan, despite having some appealing qualities, also suffers from the important downside of not yet being available in the US.


Probably our most popular inodilator, dobutamine (trade name Dobutrex) has been around the block. By beta-1 agonism it stimulates positive inotropy and chronotropy, although rather more of the former, meaning that tachycardia is usually not a problem until the dose gets high; you can run a reasonable dobutamine drip and get a decent boost in cardiac output without wacky arrhythmias in most cases. Simultaneously, by its beta-2 effects in the periphery, you get vasodilation.

An important caveat is that whether or not you see tachycardia, the heart is doing more work under the cruel whip of dobutamine, and myocardial demand has certainly increased. If the cause of cardiac failure is coronary ischemia, further disrupting the oxygen supply-demand balance in the myocardium may not have a salutary effect. (Dobutamine can actually be used as the pharmacological stimulus in cardiac stress tests.)

Dosing is from 1–20 mcg/kg/min in most cases; often as little as 5 mcg/kg/min is all you need. Peripheral access is generally acceptable; there is a small risk of phlebitis, more due to its mildly caustic diluent than to the active ingredient itself, which would obviously cause vasodilation rather than constriction were it to infiltrate.


Milrinone, like vasopressin, steps off the beaten path by using non-catecholamine-based receptors. It is actually a phosphodiasterase inhibitor, leading to increased levels of cAMP and hence increased calcium-mediated myocardial contractility, while simultaneously yielding vasodilation from smooth muscle relaxation. Importantly, it is a particularly potent dilator of the pulmonary vasculature, which may make it the drug of choice in pulmonary hypertension and right heart failure; recall that pulmonary hypertension is often treated with PDE inhibitors like sildenafil.

Its non-catecholamine mechanism may give it particular utility in patients with poor beta-receptor sensitivity, such as those on beta-blockers (nearly ubiquitous in the heart failure cohort); indeed, some data suggest that even without metoprolol or carvedilol on the med list, many heart failure patients experience some intrinsic downregulation in beta-1 receptor sensitivity from the disease itself.

Milrinone does tend to provoke even more significant vasodilation, and hence more hypotension, than dobutamine. It often needs a concomitant pressor. Additionally, it is cleared renally, and hence needs renal dose adjustments or may simply be a bad idea in those with crummy kidneys. On the flip side, it probably increases myocardial oxygen consumption less than dobutamine, and often provokes less tachycardia.

Dose is by continuous infusion, usually between .25–.5 mcg/kg/min, titrated in increments of .125. It comes on reasonably quickly, but can take a good 6 hours to clear, so it’s not as titratable as dobutamine or epinephrine—better used as a background agent, like the “vasopressin” of inotropes. A loading dose can be used, but can be a little scary and is usually unnecessary.

Are we done? Almost—come back for Part VI, when we’ll discuss a pressor that’s not quite a pressor…

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