Author: Alasdair Munro, Simin Nikou, Charlotte Davies / Editor: Elizabeth Herrieven / Codes: RP6, RP7, SLO3 / Published: 03/12/2024

Inotropes and vasopressors are drug groups commonly bandied around in treatment strategies in Emergency Department (ED), but very little more than their basic indications has been written on RCEMLearning. We know our anaesthetic colleagues can write books on this from their FRCA knowledge – but what should we in the ED really know? As with many things, there are no real concrete or evidence-based answers as to which to use and when, but here are some thoughts and definitions. For a more erudite discussion, do have a listen to the Tasty Morsels of Critical Care episode on vasopressors and inotropes.1 

The significant piece of dogma worth highlighting, is that vasopressors can be administered peripherally, and do not have to be administered centrally.2

Definitions

CO = HR x SV
It makes sense that the output of the heart is the product of how fast it beats (heart rate) multiplied by how much it squeezes (stroke volume). In some patients, the faster the heart beats, the lower the stroke volume, as no filling occurs during diastole – that’s why some tachycardic patients will have signs of shock because of their low cardiac output (CO). We can increase the CO by increasing the heart rate (normally only in bradycardic patients) or increasing the stroke volume (by increasing preload by filling with fluid, and increasing venous return from sympathetic activation).3

MAP = CO X SVR (Mean Arterial Pressure Calculator)

If we want to increase the MAP (mean arterial pressure), we can do this by altering CO or SVR (systemic vascular resistance). A lot of blood pressure targets are written using the MAP, so having an understanding of what it means is useful. 

SVR is adjusted by vasoconstriction triggered by vascular alpha1 adrenoreceptors. 

There are lots of ways of measuring and estimating cardiac parameters. 

Fig. 1 Proposed classification of vasoactive agents4

Both vasopressors and inotropes have a purple label. I liked the pretty labels trialled – but they didn’t have a significant effect. Icon label development5

Vasopressors increase blood pressure by inducing vasoconstriction which in turn increases the mean arterial pressure (MAP). Vasopressors include pure vasoconstrictors (phenylephrine and vasopressin) and inoconstrictors (dopamine, norepinephrine, and epinephrine, which cause vasoconstriction as well as increasing cardiac output). All vasopressors trigger a sympathetic response to induce vasoconstriction. 

Inotropes increase blood pressure by enhancing cardiac output. They increase the stroke volume and cardiac output by directly stimulating the myocytes. B adrenergic inotropes specifically increase heart rate.6 

  • Inodilators (e.g. dobutamine and milrinone)

Inodilators enhance cardiac output directly, but also reduce afterload, which often also helps increase the cardiac output. They are especially helpful in cardiogenic shock and low-output heart failure. Their side effects include hypotension (as they trigger vasodilation), tachycardia (calcium overload) and myocardial ischaemia (from myocardial hypoxia).  

  • Inoconstrictors (dopamine, norepinephrine, epinephrine)

In the absence of severe hypotension, an inodilator is preferred over an inoconstrictor for increasing cardiac output. 

Thinking about the pathology can help you direct your drug choice, and echo/FICE can also help to guide your choice and enable you to quickly and simply assess filling status and contractility. 

Fig. 2 Vasopressor chart via LITFL7

Drugs

There are some excellent comparison tables on LIFTL so have a look over there for specific details. We’re going to run through the varying drugs in an anecdotal order of the ones we use most commonly, and discuss why we use them, and when we probably shouldn’t. There is a published algorithm to help you decide which: 

1. Adrenaline

Adrenaline is probably the most commonly used agent in my department because it is currently in all of the cardiac arrest algorithms. It’s familiar. It’s a vasotrope and an inotrope. We would suggest using it first line in anaphylaxis, cardiac arrest, and when it’s familiar. Watch out for cardiac ischaemia, and adrenaline-induced lactic acidosis. It can be given peripherally, centrally and IM. If given peripherally in non-arrest scenarios it is advised to dilute to 10mcg/ml and give 1ml boluses at a time to create a “dirty epi” drip. 

Fig. 3 Epinephrine by @DocScribbles

2. Metaraminol

We like metaraminol as it’s not controversial to give it peripherally. It’s a vasoconstrictor that encourages release of noradrenaline.  It needs mixing up – normally 1 vial (10mg in 1ml) is mixed with 19ml water for injection to make 10mg in 20ml = 0.5mg/ml. It can then be injected IV and titrated to blood pressure. It can be used as an infusion. It has a bit of a longer half-life than some drugs, so may cause hypertension. 

3. Noradrenaline

Fig. 4 Noradrenaline by @DocScribbles

Noradrenaline is a favourite everywhere for patients with sepsis. There’s a preference for it to be given through a central line rather than peripherally, but many departments are starting to accept peripheral use and are writing guidelines. There are loads of FOAMEd posts discussing the misconception that short term vasopressors must be central – look at RebelEM, first10EM to start with. Noradrenaline is a vasopressor and inotrope.

4. Phenylephrine

Phenylephrine can be used when you want something definitely OK to give peripherally. It can be complicated to mix up, and probably for that reason, we don’t use it very often in ED. It can also cause tachyphylaxis.

Fig. 5 Phenylephrine by @DocScribbles

10mg (one syringe or vial) is diluted in 500ml of fluid. When I was a trainee we diluted a syringe in 100ml, then took out a ml (2mg), then diluted into a 10ml syringe to make 200mcg/ml strength doses. These gentle doses could then be given easily.

5. Vasopressin

Fig. 6 Vasopressin by @DocScribbles

Vasopressin can be useful in mixed overdoses involving beta blockers or TCAs where high doses of noradrenaline/adrenaline may have limited effect – vasopressin can act as an alternative agent.

Vasopressin use in ED might be uncommon, however it is the vasopressor of choice in patients with devastating brain injuries who are being prepared for organ donation.

6. Dobutamine

Fig. 7 Dobutamine by @DocScribbles

I think, they use dobutamine more on the wards (CCU) than we do in ED now that most of our patients with MI go straight to the cath lab. With increasing demands on the health service, I suspect we might be seeing more patients that need dobutamine – the agent of choice for hypotension due to heart failure or cardiogenic shock. Dobutamine acts as a bridging agent before definitive treatment – like a balloon pump. It’s worth mentioning pressors in heart failure are associated with arrhythmia and death, so their use should be balanced.8

Dobutamine augments myocardial contractility via beta receptors, and produces a strong dose-dependent increase in SV and CO with moderate increases in HR. At low dose, it lowers the SVR. The net effects of dobutamine on MAP depend on the relative changes in CO and SVR from baseline values, and uptitration of dobutamine can have unpredictable effects on MAP.

Be careful using dobutamine as it may produce hypotension when CO increases modestly and SVR declines significantly, as in vasodilatory shock when baseline CO is relatively high and SVR is low.

Dobutamine produces a dose-dependent increase in heart rate, with low doses (up to 5 μg/kg/min) increasing the stroke volume via inotropic effects without significant tachycardia, but doses >10 μg/kg/min produce worsening tachycardia. Dobutamine has a short half life (less than two minutes).

Once the patient gets to a cardiac centre, they often use milrinone or enoximone – but personally, I’ve never seen those used in ED.

7. Calcium

The evidence around calcium is weak, but it has inotropic and vasopressor actions, and is readily available. Check an ionised result on the blood gas (especially if you’ve transfused blood), and give the calcium – it can have a surprising effect. Ionised calcium is likely to be more accurate (and quicker) than corrected calcium but because of the way it is analysed, the blood gas result may be inaccurate in the presence of extreme alkalosis or acidosis.

Which one to use?

Anaphylaxis – adrenaline. Always. Have a look at the AMEX4 research. 

Asthma – adrenaline is almost certainly the best option, as it also reduces bronchospasm.

Sepsis – noradrenaline. The surviving sepsis guidelines say use noradrenaline first. You might find it quicker to draw up something else – but norad is the guideline. The responsiveness of vascular A1R is decreased in sepsis and warm/vasodilatory shock states, requiring higher vasopressor doses to maintain SVR. 

Post sedation – whichever agent you feel most comfortable with. Prevention of hypotension is better than cure. 

Heart failure and post MI – if you are familiar with it, dobutamine has good effects on the heart so will be preferred. 

Pregnant Patient – any upper will be fine, but be really careful as any pressors can really drop placental blood flow and compromise the baby.

Other Useful Summaries

References

  1. Neill A. Tasty Morsels of Critical Care 043 | Inotropes and vasopressors. Emergency Medicine Ireland, 2021.
  2. Legrand M, Zarbock A. Ten tips to optimize vasopressors use in the critically ill patient with hypotension. Intensive Care Med, 2022. 48:736–739
  3. RCEMLearning Reference – Shock. 2021.
  4. Jentzer JC, Coons JC, Link CB, Schmidhofer M. Pharmacotherapy update on the use of vasopressors and inotropes in the intensive care unit. J Cardiovasc Pharmacol Ther. 2015 May;20(3):249-60.
  5. Lusk C, Catchpole K, Neyens DM, et al. Improving safety in the operating room: Medication icon labels increase visibility and discrimination. Appl Ergon. 2022 Oct;104:103831.
  6. Jentzer JC, et al. Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit. Journal of Cardiovascular Pharmacology and Therapeutics. 2015;20(3):249-260.
  7. Nickson C. Inotropes, vasopressors and other vasoactive agents. Life in the Fast Lane (LITFL), 2024.
  8. Hansen BL, Kristensen SL, Gustafsson F. Use of Inotropic Agents in Advanced Heart Failure: Pros and Cons. Cardiology. 2024;149(5):423-437.
  9. Centre for Trauma Sciences. TRAUMAtalks