Inotropes & Inodilatateurs

Alexandre Mebazaa Département d’Anesthésie-Réanimation

Hôpitaux Universitaires Saint Louis – Lariboisière

Université Paris 7; INSERM – UMR 942

Inotropes and inodilatateurs

• Ils sont encore TROP utilisés en France et

dans le monde

• Ils ne doivent être utilisés que quand il y a

des signes patents de baisse de la

perfusion

• Leur durée d’utilisation doit être courte

Cecconi et al Intensive Care Medicine, 2014

0

0.5

1.0

0 100 200 300 400

normal SBP

high SBP

Cardiogenic Shock

Number of Days

Surv

ival R

ate

, %

68%

38%

17%

EFICA Study:

the 3 main clinical scenarios of AHF

Zannad F, Mebazaa A, et al. Eur J Heart Fail. Eur J Heart Fail. 2006;8:697-705

Mistakes we did for years concerning the use of catecholamines

Acute heart failure: we did not explain well enough that AHF is about CONGESTION and rarely low cardiac output (CO)

Catecholamines: we did not insist on « low CO » beeing the only indication of catecholamines

Cardiogenic shock: we only looked at short-term effect of catecholamines and missed long-term effects

What we should learn today

« Tailored » therapy: restrict the use of catecholamines to patients with low CO

New inotropic agents:

– Need of short & long term beneficial effect

– Myocardial protection

VP Harjola et al, Eur J Heart Failure 2015

CardShock Study (clinicaltrials.gov NCT01374867)

Principal investigator

Veli-Pekka Harjola

Harjiola VP et al, EJHF in press 2015

CardShock: patients characteristics

VP Harjola et al, Eur J Heart Failure 2015

Crit Care Medicine 2013

Diastolic blood pressure is lower in

non-survivors of cardiogenic shock

Rigamonti et al. Crit Care Medicine 2013

hours

Diastolic blood pressure is THE independant

factor of 28-d mortality in cardiogenic shock

Rigamonti et al. Crit Care Medicine 2013

Arrigo M & Mebazaa A, Intensive Care Medicine, in press 2015

Arrigo M & Mebazaa A; Intensive Care Med, 2015; 5: 912-915

Ishihara et al.

Invasive hemodynamics at baseline and after

treatment in AHF: results of a meta-analysis

Card

iac i

nd

ex

3-8 hours after treatment

Card

iac i

nd

ex

Shiro Ishihara et al.

Vasodilators does as well as inotropes on congestion:

results of a meta-analysis

Green: placebo

Red: Inotropes

Blue: vasodilators

Mebazaa et al Intensive Care Medicine 2011

Mebazaa et al Intensive Care Medicine 2011

inotropes

ALARM-HF: IV treatment at admission

Vasoactive agents are used

excessively

Follath et al Intensive Care Medicine 2011

(n=4953)

(n=4167)

(n=1930)

(n=1617)

Effect of IV drugs given during the first 48 hours

in AHF patients on in-hospital mortality

Mebazaa et al Intensive Care Medicine 2011

All cohort

Any inotrope N=

Unadjusted 2.87 (2.20 – 3.76)

Adjusted* 2.94 (2.23 – 3.87)

By inotrope (adjusted*)

Dopamine 1.47 (1.05 – 2.05)

Dobutamine 1.54 (1.20 – 1.98)

Epinephrine 3.57 (2.37 – 5.37)

Norepinephrine 2.51 (1.73 – 3.64)

Levosimendan 0.50 (0.29 – 0.88)

0 5 10 15 20 25 30

0.0

0

.1

0.2

0

.3

0.4

0

.5

0.6

Days

In-h

osp

ital

mo

rtality

Whole cohort

Dopamine

Dobutamine

Epinephrine

Norepinephrine

Levosimendan

Diuretics

Vasodilatators

Mebazaa et al Intensive Care Medicine 2011

Effect of IV drugs in-hospital mortality: propensity

score analysis

An Investigator-initiated European

Multicenter Study on Cardiogenic Shock

CardShock Study

clinicaltrials.gov NCT01374867

Treatment in during first 96 h Medication (0-

96h) % of all patients ACS Non-ACS p-value

Epinephrine 46 (22) 40 (24) 6 (15)

Norepinephrine 165 (76) 136 (78) 29 (69)

Dopamine 56 (26) 51 (29) 5 (12) 0.03

Dobutamine 108 (50) 90(52) 18 (44)

Levosimendan 52 (24) 39 (22) 13 (31)

Milrinone 8 (4) 7(4) 1 (3)

Nitrates 32 (15) 23 (13,4) 9 (22)

Other vasoactives 11 (5) 9 (5) 2 (5)

Among inopressors, dopamine might

be worse than NE in cardiogenic shock

De Backer D et al NEJM 2010

Pirracchio et al. PLOS one 2013

Flow chart

Pirracchio et al. PLOS one 2013

Inotropes/vasoactive agents

Pirracchio et al. PLOS one 2013

combined regimen

KM: in-hospital mortality

Pooled data: n= 988

Propensity score

combined regimen

Inopressors alone

Epi/NE/dopa

combined regimen

Inopressors alone

Epi/NE/dopa

Pirracchio et al. PLOS one 2013

Sensitivity analysis

Pirracchio et al. PLOS one 2013

In summary

• We should better use the current agents in

cardiogenic shock:

less vasopressors alone, patient should

not only be managed with the objective to

improve blood pressure

• We need new inotropic agents that are

– active on both systolic and diastolic function

– much safer

– With a benefical long term effect

Mebazaa et al. Intensive Care Medicine 2015

Pirracchio et al. PLOS one 2013

The message is:

Vasopressors alone are harmful; better combine inotropes+vasopressors

Flow chart

Pirracchio et al. PLOS one 2013

Inotropes/vasoactive agents

Pirracchio et al. PLOS one 2013

KM: in-hospital mortality

Pooled data: n= 988

Propensity score

combined regimen

Inopressors alone

Epi/NE/dopa

combined regimen

Inopressors alone

Epi/NE/dopa

Pirracchio et al. PLOS one 2013

Cardiogenic shock and in-hospital mortality

days

Pro

bab

ilit

y o

f s

urv

ival

inodilators > combined > inopressors (LS/Dobu/PDEI) (E/NE/Dopa)

Algorithm of hemodynamic

management in the critically ill

Signs of congestion

+

High or preserved BP

Vasodilators

+

Low dose diuretics

Algorithm of hemodynamic

management in the critically ill

Signs of congestion

+

High or preserved BP

Low BP

- Cardiac output?

- Volemia?

Vasodilators

+

Low dose diuretics

Algorithm of hemodynamic

management in the critically ill

Signs of congestion

+

High or preserved BP

Low BP

- Cardiac output?

- Volemia?

No or few signs of

low CO

Vasodilators

+

Low dose diuretics

venous congestion?

Diuretics +++

or UF

yes no

reassess

Algorithm of hemodynamic

management in the critically ill

Signs of congestion

+

High or preserved BP

Low BP

- Cardiac output?

- Volemia?

No or few signs of

low CO

Cardiogenic shock: evidences or high

suspicion of low CO

Vasodilators

+

Low dose diuretics

Favor the combination

vasopressor + inotrope

venous congestion?

Diuretics +++

or UF

yes no

reassess

Mebazaa et al. Intensive Care Medicine 2015

Current percutaneous mechanical

support devices for cardiogenic shock

Thiele H et al, Eur Heart J 2015

Carpentier et al , Lancet 2015

H Thiele et al. Eur Heart J 2015

Use of mechanical support for

multiorgan system dysfunction

prevention and therapy.

Inotropes and inodilatateurs

• Ils sont encore TROP utilisés en France et

dans le monde

• Ils ne doivent être utilisés que quand il y a

des signes patents de baisse de la

perfusion

• Leur durée d’utilisation doit être courte