CARDIOGENIC SHOCK- HOW CAN WE IMPROVE THE PROGNOSIS

VASOACTIVE DRUGS

Alain Rudiger, MDUniversity Hospital Zurich, Switzerland

Heart Failure Meeting of the ESCSevilla, May 25th 2015

Conflict of interests

Honoraria were received from:•AOP Orphan (esmolol, vernakalant) for lectures•BAXTER (esmolol) for expert meetings and lectures•NOVARTIS (human relaxin-2) for advisory board meetings•ORION (levosimendan) for expert meetings

Case report

• 33-year old woman

• 1-week history of common cold, cough, fever (39°C), diarrhoea and vomiting

• 2-day history of fatigue, weakness and dyspnoea

• Co-morbidity: anxiety disorder

Case report

On admission:•Somnolent•Cold periphery, mottled skin•BP 75/35 mmHg, HR 130 /min•RR 30 /min

Case report

Case report

Case report

Case report

Case report

Echocardiography:•Pericardial tamponade with RV collapse

After drainage:•Severely impaired LV ejection fraction (28%) with hypokinesia basal and midventricular, apical akinesia (Takotsubo-like)

Case report

Coronary angiography:•No coronary artery disease•Biopsies taken for histology

Serology•Positive for influenza type B

Case report

Management: •Drainage of pericardial effusion•Start with inotropes (milrinone up to 20 mcg/min) •MAP goal >55 mmHg, no noradrenaline required

Improvement of lactate levels (6 to 3.2 mmol/l) over the next hours

Case report

Next morning:•Echo: Worsening of contractility (despite inotropes)•Decreasing urine output•Rising lactate levels

Case report

a-v ECMO in the awake patient

Case report

ECMO weaning:•Day 7: Administration of levosimendan •Day 8: Reduction of ECMO blood flow (500 ml every 4h)•Day 9: ECMO removal under dobutamine (200 mcg/min) •Day 10: Reduction and stop dobutamine

Start ACE inhibitor

Normalisation of cardiac function

The AHF syndromes

Cardiogenic shock Pulmonary edema Congestive HF

Typical scenario Fulminant myocarditis

Hypertensive emergency in diastolic HF

Malcompliance in dilated cardiomyopathy

Signs and symptoms Tissue hypoperfusion (lactate >2 mmol/l);Organ dysfunction (ecephalopathy, renal failure, liver dysfunction)

Dyspnoea at rest; Bilateral rales; Hypoxemia (SaO2 <90%)

Dyspnoea at exercise;Weight gain, ascites, peripheral oedema

Diagnostic test ABGA (lactate, metabolic acidosis)

Chest x-ray NT-proBNP

The AHF syndromes

Zannad F. Eur J Heart Fail 2006; 8: 697-705

How can we improve the prognosis

□ Appropriate fluid management

□ Reasonable use of inotropes and vasopressors

□ Novel concepts

Cardiogenic shock Pulmonary edema Congestive HF

Volemia Intravascular hypovolemia (low fluid intake, fluid losses, diuretics)

Fluid redistribution Hypervolemia (weight gain, ascites, peripheral oedema)

Diuretic use Contraindicated Careful (furosemide 10 mg i.v. push)

Indicated (furosemide infusion 1-10mg/h)

Fluids Fluid challenge recommended

If shock develops Fluid restriction

Fluid balance target Urine output 0.3-0.5 ml/kg/h

Neutral fluid balance Negative fluid balance

Fluid management

Intravascular hypovolemia due to

•Excessive use of i.v. diuretics

•Increased perspiratio insensibilis

•Reduced fluid intake

Frank Starling mechanism

250 ml of Ringer lactate over 15 minutes i.v.

Fluid challenge

Vasoactive drugs

Cardiogenic shock Pulmonary edema Decompensated CHF

Blood pressure Low (or normal) High Normal

Inotropes Dobutamine, adrenaline, milrinone, levosimendan

Not indicated Not indicated

Vasoactive drugs Vasopressors (noradrenaline)

Vasodilators (nitroprusside)

Vasodilators (nitrates)

Hemodynamic targets

MAP 55-75 mmHg, Lactate < 2.2 mmol/lSvO2 > 60%CI >2.2 l/min/m2

MAP 65-85 mmHg Individual targets

SOAP II study:Subgroup of patients with cardiogenic shock (n=280)

De Backer D. N Engl J Med 2010; 362: 779-89

Log rank p=0.03

Vasopressors

NoradrenalineDopamine

Arrigo M. Intensive Care Med 2015: 41: 912-5

Inotropes

Stimulation of 1-receptors: adrenaline, dobutamine

Rudiger A. Crit Care Med 2007; 35: 1599-1608

Dobutamine

1 and 2 receptor agonist:

Positive inotropic and chronotropic effects, vasodilation

CI , HR , systemic and pulmonary BP or = or

• Half-life 2 minutes

• Dose 2-5 g/kg/min (no bolus required)

• High doses needed if patient is treated with beta-blockers

• Tolerance after 48h

Phosphodiesterase-inhibitors: milrinone

Rudiger A. Crit Care Med 2007; 35: 1599-1608

Milrinone

Phosphodiasterase III-inhibitor

Postive inotropic and chronotropic effects, vasodilation

CI , HR , BP

• Half-life 2 hours

• Dose 5-20 g/min (bolus required)

Levy B. Crit Care Med 2011: 39: 450-5

Dobutamine + NoradrenalineAdrenaline

Mebazaa A. Intensive Care Med 2011; 37:290-301

Smith G. Br Med J 2003; 327: 1459-61

What is the problem with inotropes?

• Catecholamines have dangerous side effects !

• Catecholamines are overused !

Rudiger A. Crit Care Med 2010; 38: S608-12

Adverse effects

Arrigo M. Intensive Care Med 2015: 41: 912-5

Adverse effects

Singer M. PLoS Med 2005; 2: e167

Follath F. Intensive Care Med 2011; 37: 619-26

12%

39%

Overuse

How can the use of inotropes be reduced ?

• Only use inotropes in patients with cardiogenic shock (low contractility, low cardiac output, signs of organ dysfunctions)

• Chose reasonable targets (MAP, SvO2, lactate)

• Reduce the dose of inotropes to a minimum

• Consider alternatives

Levosimendan

Calcium sensitizer: positive inotropic and lusitropic effects,

Activation of K+(ATP) channels: vasodilation, preconditioning

CI , HR = or , systemic and pulmonary BP

Dose:

Infusion 0.05-0.2 mcg/kg/min for 24h

Papp Z. Int J Cardiol 2012; 159: 82-7

Arrigo M. Intensive Care Med 2015: 41: 912-5

Levosimendan

Levosimendan

How to prevent adverse effects of levosimendan:

• Omit bolus

• Expect hypotension after 2-3 hours

• Optimize intravascular filling

• Withhold diuretics and vasodilators

• Treat hypotension with fluids and noradrenaline

• Correct electrolytes to reduce the risk of arrhythmia

Mebazaa A. Intensive Care Med 2011; 37:290-301

Levosimendan

Greco T. Br J Anesth 2015; 114: 746-56

Sommer W. Art Org 2015 [epub ahead of print]

From: twitter.com/winchester_jj/status/444916588387381248

Summary

Summary

How to improve the prognosis of cardiogenic shock?

• Treat underlying heart disease

• Correct intravascular fluid deficit

• Only use inotropes in cardiogenic shock

• Anticipate adverse drug effects

Summary

How to improve the prognosis of cardiogenic shock?

• Chose reasonable (hemodynamic) targets

• Reduce the dose of inotropes to a minimum

• Consider awake ECMO as bridge to – decision– bridge (for transplantation) – recovery

Thank you!

alain.rudiger@usz.ch