Inotropic agents

Marlies Ostermann
London, UK
 Disclosures

Speaker honoraria: Fresenius, Biomerieux, Baxter

Research funding: Fresenius, LaJolla Pharma, Baxter, Biomerieux

Inotropes
Mechanical
support
Septic Shock

N Engl J Med 2013;369:1726

Sites of inotrope action
 Inotrope summary

Agent Adrenaline Noradrenaline Dopamine

Class endogenous endogenous endogenous
catecholamine catecholamine catecholamine
Mechanism β>α α>β DA > β > α

Effects β1 -> HR, inotropy, α1 -> SVR dose (mcg/kg/h)

CO β effects at higher 1-5 = DAR 1+2
α at higher doses doses 5-10 = β effects
preserves coronary and >10 = α effects
cerebral blood flow
β2 -> vasodilation,
bronchodilation
 Inodilator summary

Agent Levosimendan Milrinone Dobutamine

Class calcium sensitiser bipyridine inodilator synthetic
(inodilator) catecholamine

Mechanism modulates troponin C cAMP PDE-3 inhibitor β1 and β2

activates vascular ATP-
dependent K channels

Effects Inotropy Inotropy inotropy + VO2 +

Reduces SVR Reduces SVR & PVR myocardial work
CO CO mild HR
coronary perfusion
Haemodynamic support
Dobutamine

Synthetic catecholamine
Acts on β1 and β2 receptors (some α
affinity)

Pro: rapid action, short T1/2

Con: Arrhythmias, hypotension,
increased myocardial oxygen
consumption
 Milrinone

Phosphodiesterase inhibitor
Non-adrenergic

Pro: short T1/2, dose titration

Con: Arrhythmias, hypotension
Levosimendan
 Milrinone

Aim: systematic review and meta-analysis from the past 20 years to evaluate
the impact of milrinone on mortality in patients who undergo CABG surgery

Methods: systematic literature search of articles in patients who underwent CABG surgery
published between 1997 – 2017
Comparison: Milrinone compared to placebo or other standard therapies
 Milrinone
Mortality
Milrinone

Less MI
Less myocardial ischaemia
Less arrhythmias
No difference in mortality
 Milrinone

RCT
196 patients with cardiogenic shock

Primary outcome:
composite of hospital mortality, resuscitated cardiac arrest, receipt of cardiac transplant
or mechanical support, non-fatal MI, TIA or stroke, or initiation of RRT
Milrinone
Levosimendan
 Levosimendan
Outcomes among RCTs comparing levosimendan prior to cardiac surgery in high risk
patients with EF <35%
Levosimendan
Guidelines
Position papers
Position papers

Inotropes

The general recommendation is

to avoid their use when tissue
perfusion is restored and limit
the dose and the duration to
infusion to the lowest possible.
Guidelines
 Guidelines

Weak recommendations
Low quality of evidence
Management algorithm

inotrope
 Conclusions

• In patients with cardiogenic shock, inotropes may be needed to

improve oxygen delivery.

• There are no convincing data supporting any specific inotropic or

vasodilating therapy to reduce mortality in haemodynamically
unstable patients with cardiogenic shock or low cardiac output
syndrome.

• It is important to understand the benefits and side effects of the

chosen inotrope and to limit the dose and the duration to the
lowest possible.