Aim of the session:
• Overview of inotropes and vasoactive
• Discuss case examples
• Hopefully feel more confident in their use.
Inotropes are indicated in acute conditions where there is low cardiac output (CO),
such as cardiogenic shock following myocardial infarction, acute decompensated
heart failure and low CO states after cardiac surgery
Different vasopressors work by a variety of means:
The adrenergic group of vasopressors work by stimulating the sympathetic nervous
system. Drugs in this group include noradrenaline, adrenaline and phenylephrine
which work by narrowing blood vessels and dopamine which stimulates the heart.
Vasopressin and terlipressin are called non-adrenergic vasopressors. They do not
act upon the heart or blood vessels, but increase blood pressure by reducing water
loss through urination.
The main mechanism of action for most inotropes involves increasing intracellular
calcium, either by increasing influx to the cell during the action potential or increasing
release from the sarcoplasmic reticulum
Inotropes influence the contractility of the heart…
• Positive inotropes – increase the force of contractility
• Negative inotrope – reduce contractility(some calcium channel
Positive inotropes mimic the sympathetic nervous system that increasing
heart rate and contractility
Application to cardiogenic shock, acute heart failure, ventricular fibrillation
*drugs influencing the heart rate referred to as chronotropes
Its all about the OXYGEN!
For tissues to be oxygenated, 3 factors need to be considered:
1. Oxygen transfer across the alveolar-capillary membrane
2. Oxygen attachment to haemoglobin
3. Adequate cardiac output(CO) to move the oxyhaemoglobin compound to
This is what we are going to
be talking about
To increase CO we can…
1. Enhance circulating volume through fluid resuscitation (increasing preload)
2. Enhancing myocardial contractility with inotropes(their inotropic effect)
3. Manipulating heart rate with inotropes(their chronotropic effect)
Heart rate(HR) x Stroke Volume(SV)
Measuring cardiac output
• How do we commonly evaluate?
• How complex is this?
Tissue perfusion is dependent on mean arterial blood pressure (MAP), which is the product of CO and systemic
vascular resistance (SVR):*
MAP = CO × SVR
Reducing CO or SVR lowers the MAP and therefore reduces tissue perfusion.
CO is dependent on the stroke volume (SV) and heart rate (HR):
CO = HR × SV
Stroke Volume is a complex aspect!
Affected by preload, afterload and
Preload (the degree to which ventricles are stretched before
contracting) correlates with the end diastolic volume (the volume of
blood in a ventricle at the end of filling).
It is important to optimise preload by correcting fluid balance before
starting inotropes, since there is little point in increasing the
contractility of the heart if its chambers are not filled optimally.
Central venous pressure (CVP) can be used as a surrogate
measure of preload.
So how does this stay balanced?
Parasympathetic nervous system down regulates
Sympathetic nervous system up regulates
Lets talk drugs
In the context of the SNS, drugs:
• Mimic or impair(stimulate or block)
• Directly(Agonist or antagonist)
• Indirectly- releasing endogenous Norad(metaraminol,, ephedrine at a1)
In the context of the PNS, drugs work on:
• Nicotinic and muscarinic receptors with Ach as neurotransmitter
• M2 muscarinic receptors- heart
Autonomic control of myocardial
Sympathetic Nervous System,
adrenaline and certain drugs have
positive inotropic effects- increase
Parasympathetic Nervous System,
and certain drugs have negative
inotropic effects- reduce contractility
Receptor type Location Action
Peripheral, renal and coronary
Increase in Systemic Vascular
Decrease Insulin release
A2 Peripheral circulation.
Systemic Vascular resistance
Heart, Sinoatrial node and
Increase in contractility and heart
Lungs-bronchial smooth muscle;
peripheral and coronary
circulation-coronary arteries, AV
It’s all about the receptors…
Anticholinergic drug- works as a competitive antagonist in
muscarinic receptors(M2= heart)
M2 muscarinic receptors are located in the heart, where they
act to slow the heart rate down to normal sinus rhythm after
negative stimulatory actions of the parasympathetic nervous
system, by slowing the speed of depolarization
Atropine therefore blocks and slows down signals to the heart,
increasing the heart rate
Adrenaline (Epinephrine)- SNS
A non-selective b and a agonist
A sympathomimetic drug emulating the action of sympathetic nervous system.
Positive inotrope and chronotrope
Boosts cardiac function by increasing heart rate (chronotropy) and
contractility (ionotropy) – via β1 Agonist.
Vasoconstrictor at high dose… effecting alpha receptors
Vasodilator as low dose effecting β2 receptors resulting in bronchial smooth
Adrenaline 1mg/mL (1:1000) solution for injection.
Mainly an a1 Agonist
Because it acts mainly via a1 receptors in the heart, it is usually used as a
vasopressor (increasing Systemic Vascular Resistance(SVR) in order to maintain
Mean Arterial Pressure) rather than an actual inotrope.
Causes vasoconstriction(alpha-adrenergic action) and positive inotropic effect of the
heart and dilation of coronary arteries(beta-adrenergic action)
It is often used with other inotropes, such as dobutamine, to maintain adequate
Noradrenaline 1mg/mL concentrate for solution for infusion.
Dobutamine is mainly a direct acting inotropic as a ß1 agonist and therefore increases
cardiac contractility and with mild chronotropic effects on the heart rate.
It also acts at ß2 receptors causing vasodilation and decreasing afterload. In order to ensure
Does not cause the release of noradrenaline and therefore to ensure adequate MAP
dobutamine should be used in combination with a vasopressor (eg, noradrenaline).
The main side effects are increased heart rate, arrhythmias and an increased myocardial
oxygen demand. (These can cause myocardial ischaemia.)
Used for heart failure for the above reasons
Increase reabsorption of water by the renal tubules
Cause contraction of smooth muscle of the gastrointestinal tract and
all parts of the vascular bed, especially the capillaries, small arterioles
and venules with less effect on the smooth musculature of the large
Increases both systolic diastolic blood pressure
The pressor effect begins one to two minutes after intravenous
injection and lasts about 20 mins-1 hour
Positive inotropic effect on the heart and has a peripheral
Potent sympathomimetic-alpha agonist effects, mild beta 1 effects
Metaraminol 10mg/mL Solution for injection or infusion
Stimulates both alpha and beta-adrenergic receptors indirectly and
also releases endogenous noradrenaline from its storage
Often used in operating theatres due to strong direct evidence
base for anaesthetic hypotension.
Also used mostly in operating theatres
Produces vasocontriction that lasts longer than adrenaline and ephedrine
Responses are more sustained tham those to adrenaline, lasting 20minutes after
IV inj. and as long as 50mins after SC inj.
Its action on the heart vs adrenaline/ephedrine, is that it slows the HR and
increases the stroke output, producing no disturbance to the rhythm
Powerful postsynaptic alpha-receptor stimulant with little effect on the beta-
receptors of the heart
Phenylephrine 10mg/mL Solution for injection or infusion
Glyceryl trinitrate produces a dose related dilation of both arterial and
Decreases venous return to the heart, reducing left ventricular end
diastolic pressure and pulmonary capillary wedge pressure(preload)
Arteriolar relaxation reduces systemic vascular resistance and arterial
Also dilates the coronary arteries, although this effect is short-lived.
This is a complicated inotrope because it’s effect is dose-dependent .
At lower doses,(0.5–2 microgram/kg/min) it exerts mainly dopaminergic
(Neurotransmitter…) effects and blood pressure does not change or decreases slightly.
Causes renal and mesenteric vasodilation-renal plasma flow, GFR and Na+ excretion
At medium strength doses (2–10micrograms/kg/min) the ß1 inotropic effects are more
prominent and CO and Systolic BP increase. Total peripheral vasoconstriction is
relatively unchanged due to vasoconstriction (alpha effect) and muscle vasodilation(beta
At high doses (10–20micrograms/kg/min) a1 vasoconstriction is the main action. Systolic
and diastolic pressures increase
200 mg ampoules
Some less frequently
Isoprenaline- has a similar profile to dobutamine
but tends to cause more tachycardia. It is sometimes
used for bradycardic patients/ complete heart block
requiring inotropic support.
Milrionone- positive inotropic and vasodilatory
activity, ventricular dysfunction by increasing SV and
LV contractility producing pulmonary vasodilation
vasoactive, relaxation of vascular smooth muscle
and dilation of peripheral arteries and veins, non-
selective compared to GTN
failure, increases calcium sensitivity of
myocytes by binding to cardiac troponin C,
smooth muscle relaxation
Terlipressin- similar profile to vasopressin,
vasoconstriction on the splanchinic blood
vessels and reduces blood flow to the portal
Peripheral administration is emerging (as it is in anaesthetic practice in the perioperative period) with a
recent systematic review of over 1300 patients suggesting the risk of doing so being lower than is
D. H. Tian, C. Smyth, G. Keijzers, S. P. Macdonald, S. Peake, A. Udy and A. Delaney, “Safety of peripheral administration of
vasopressor medications: A systematic review,” Emergency Medicine Australasia, vol. 32, no. 2, pp. 220-227, 2020.
This review reported that extravasation events were uncommon (event rate 3.4%), with no reported
incidents of tissue necrosis or limb ischaemia.
The most common alternative to a PVC is the insertion of a central venous cannula (CVC)  .
Whilst the use of ultrasound-guided insertion will aid in the reduction of the incidence of such risks,
many remain clinically significant (such as pneumothorax, arterial injury, arrhythmias and catheter-
related infection) and so it seems sensible to consider circumstances wherein administration via PVC
may be preferable when there is a need for:
• stabilisation of critically unwell patients awaiting transfer to a critical care area;
• short term post-operative use;
• patient preference;
• or where central venous access would prove problematic.
The decision will ultimately come down to local policy and the responsible senior at the time.
Inotropes are usually only
used in clinical areas where
patients’ haemodynamics can
be monitored adequately.
Continuous monitoring of
MAP, CO and CVP allows
haemodynamic changes to be
detected and addressed
• Inotropic drugs are potentially dangerous so be very thorough
• Vascular access needs to be spot on
• On central lines always endeavour to use distal, brown
• Wear gloves when preparing/assisting
• Know what the drug does and why we use it
• Don’t EVER make a mistake with inotropes or disconnect
them without direction
Type 1 anaphylactic
Type 1 anaphylactic reaction
What will you need and
M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the parasympathetic nervous system, by slowing the speed of depolarization
The circled area is where SYMP and PARA (&drugs) will have an effect on HR
The sooner the drift line gets to TH – the sooner the HR
Vasopressors are drugs that cause blood vessels to narrow, thereby increasing blood pressure and hence the flow of blood. They are used to treat patients with septic shock, helping to restore blood flow to the vital organs and the rest of the body.
Think about preload and adequate fluid loading
SN located in the basal ganglia structure located in the midbrain that plays an important role in reward and movement
Epinephrine- alpha-1-adrenergic agonist effects-increased vasoconstriction, peripheral resistance and decreased mucosal edema
beta-1adrenergic agonist effects- increased inotropy and increased chronotropy
beta-2-adrenergic agonist effects-increased bronchodilation, decreased release of mediators of inflammations from mast cells and basophils.
Septic shock is when blood pressure drops to a dangerously low level after an infection. There is a high 02 demand to reduce cell death
Noradrenaline- Causes vasoconstriction(alpha-adrenergic action) and positive inotropic effect of the heart and dilation of coronary arteries(beta-adrenergic action)
Compared to dopamine, noradrenaline reduced deaths from any cause at 28 days by 11% (Relative Risk [RR] 0.89, 95% Confidence Interval [CI] 0.81 to 0.98).
Forty-five percent of people treated with noradrenaline died, compared with 52% treated with dopamine. This result came from a meta-analysis of 11 trials.
Noradrenaline reduced the risk of major adverse effects, such as irregular heart-beat, heart attack, stroke or reduction in blood supply (ischaemia) to the heart or limbs, by about two-thirds compared with dopamine (RR 0.34, 95% CI 0.14 to 0.84). This result came from a meta-analysis of just three trials. Meta-analysis of four trials found that noradrenaline reduced the risk of irregular heart beat by about a half compared to dopamine (RR 0.48, 95% CI 0.40 to 0.58).
No reduction in all-cause mortality or major adverse effects was demonstrated for noradrenaline compared to adrenaline, phenylephrine, vasopressin or terlipressin as any difference in mortality were not statistically significant.
Other outcomes, including length of stay in intensive care, were similar between the different vasopressors. However, noradrenaline did improve some other measures indicating stability of blood pressure and circulation, such as urine output.
Give adrenaline 1 mg IV (IO) as soon as possible for adult patients in cardiac arrest with a non-shockable rhythm.
Give adrenaline 1 mg IV (IO) after the 3rd shock for adult patients in cardiac arrest with a shockable rhythm.
Repeat adrenaline 1 mg IV (IO) every 3-5 minutes whilst ALS continues.
May consider vasopressin for treatment of asystole, but there is insufficient evidence to recommend for or against its use in PEA. Further studies are required. Epinephrine may be administered every 3 to 5 minutes during the attempted resuscitation; vasopressin may be substituted for the first or second epinephrine dose.
Dobutamine may be given simultaneously to norepinephrine in an attempt to improve cardiac contractility which is often performed in clinical practice.7 Other inotropes such as levosimendan or phosphodiesterase-inhibitors are of interest in CS based on their improvement of myocardial contractility without increasing oxygen requirements and potential for vasodilation. However, as shown in a recent Cochrane review, the current evidence for inotropes and vasodilators in CS is very limited.