Cardiogenic Shock searching for the recent

1. Cardiogenic Shocksearching for the recent • Dr. Yasser Ahmed Salem • Lecturer of anesthesia • Ain shams University

2. Objectives • Acute right heart syndrome • Takotsubo cardiomyopathy • Pharmacotherapy • Future of heart transplantation • Non pharmacologic therapy

3. Acute right heart syndrome • Increase in RV afterload • RV dilates deterioration of contractility • Right atrial and RV end-diastolic pressure rise • Cardiac output fall

4. Preload: volume entering ventricles Afterload: resistance ventricles must overcome to circulate blood Contractility: Power of contraction

5. Precipitating events • Acute or acute on top of chronic pulmonary embolism • Deterioration of chronic pulmonary arterial hypertension • ALI, ARDS or sepsis • Lung resection • LV failure or LV assist device • Cardiac surgery • Heart, lung or liver transplantation

6. Right Heart Intolerance Positive inotropes CO RV LV 45 mmHg 150 mmHg AFTERLOAD (MEAN PRESSURE)

7. Management Reverse precipitating events Maintain perfusion pressure Control contributing factors (acidemia, anemia, infection, arrhythmia) RV failure Optimize fluid volume Oxygenation and lung protection Inotropy Pulmonary vasodilators

8. Optimize fluid volume • Ventricular interdependence • Cautious fluid administration (bolus and observe response) • Dilated IVC on echo, unlikely to respond • Consider cautious diuresis • Massive fluid overload, consider CVVH

9. Maintain perfusion pressure • Norepinephrine, Dopamine, Epinephrine AIM • To treat systemic hypotension (no clear winner) • To maintain RV coronary perfusion without pulmonary vasoconstriction or impaired myocardial performance

10. Inotropy Dobutamine (catechol), milrinone (PDE3I) • Systemic vasodilators • dobut tachy • mil decrease BP, often need pressors • Mild pulmonary vasodilators • May be used in combination with more potent pulmonary vasodilators (like inhaled NO or PGI2) to increase CO and further lower PA pressure • No clear winner Bradford et al, J Cardiovasc Pharmacol 2000; 36:146

11. Pulmonary vasodilators • Decrease PVR and impedance to reduce RV afterload • Increase RV stroke volume and cardiac output • Avoid systemic hypotension and maintain coronary perfusion ( ↓PVR/SVR) • Avoid hypoxemia (from worsened ventilation/perfusion relationships)

12. Inhaled prostaglandins • PGI2 (Prostacyclin) • Potent vasodilator, decrease platelet aggregation • Strong evidence for efficacy in Class IV PAH (improve functional status and survival) • Given as continuous IV infusion starting at 2 - 4 ng/kg/min, increased as tolerated • Systemic vasodilator, may worsen hypoxemia • Inhaled form is more specific pulmonary vasodilator • Inhaled ilioprost • given as separate buffs 25 μ gm every 20 min De Wet et al, J Thorac Cardiovasc Surg 2004; 127: 1061 Kramm et al, Eur J Cardiothor Surg, 2005

13. Inhaled prostaglandins

14. Inhaled NO • Potent vasodilator - stimulates soluble guanylate cyclase in vascular smooth muscle, increase intracellular cGMP • Usually improves O2 - by enhancing blood flow to ventilated areas • Virtually no systemic side effects; immediately inactivated by hemoglobin (forms methemoglobin) • Given by titration in concentrations of 5-40 ppm (little gain > 20 ppm)

15. limitations • Withdrawal problems very common (2/3) – Drop SBP, O2 sats, increase PVR – ? Related to suppression of endogenous eNOS • Methemoglobin and NO2 may accumulate • Very expensive! Up to $3000/day

16. Phosphodiesterase 5 inhibitors • Potent acute pulmonary vasodilators by slowing metabolism of cGMP • Potentiate the effect of iNO or prostacyclin, reduce rebound • Also systemic vasodilators so must be used with great caution in hypotensive patients • prelim evidence suggests more selectivity by inhaled route Ruiz M et al, J Heart Lung Txplant 2006

17. Takotsubo cardiomyopathy

18. Takotsubo cardiomyopathy

19. Takotsubo cardiomyopathy

20. Figure 1. Proposed pathophysiology of takotsubo cardiomyopathy. Hessel E A , London M J Anesth Analg 2010;110:674-679

24. Objectives • Acute right heart syndrome • Takotsubo cardiomyopathy • Pharmacotherapy • Future of heart transplantation • Non pharmacologic therapy

25. Pharmacotherapy

27. ATP β-Adreno- receptor SR (Ca++) Enzyme

28. ATP SR Ca++ β-Adreno- receptor SR (Ca++) Enzyme Ca++ Ca++ cAMP

29. ATP SR Ca++ β-Adreno- receptor SR (Ca++) Enzyme Ca++ Ca++ cAMP PDE PDEI

31. Dopexamine • Newly developed synthetic catecholamine, structurally related to dopamine, dobutamine • Increase splanchnic(gut, kidney, liver, spleen) blood flow ← stimulation of DA1 receptor • Increase in stroke volume, heart rate • Decrease in peripheral vascular resistance ← b2 receptor • Significant increase UO • Inhibitory action in the neuronal catecholamine uptake mechanism → positive inotropic action

32. Fenoldopam • HTN • significant and sustained reduction in blood pressure ( average decrease in diastolic BP 20mmHg) • increased renal blood flow, urine volume sodium excretion, potassium excretion • CHF • dose related increase in CO by primarily decreasing systemic vascular resistance • no direct inotropic effect

33. Phosphodiesterase inhibitor • Bypiridine -amrinone -milrinone • Imidazole -enoximone -piroximone

34. Phosphodiesterase inhibitor • Noncatecholamine, nonadrenergic • Inhibition of type III Phophodiesterase ( predominantly in cardiac muscle) • secondary increase in cyclic adenomonophosphatase • increase in calcium channel entry into the cell • positive inotropic action • Decrese pulmonary vascular resistance • increase cyclic guanidine monophosphate, secondary to incresing NO from endothelium • B-agonist additive • improvement of myocardial performance

35. Amrinone • Treatment of patient with CHF • Perioperative period • positive inotropic and vasodilator action undergoing cardiac surgery • Augment ventricular performance in vascular surgery • pulmonary HTN, chronic pulmonary obstruction in children

36. Milrinone • Second generation phosphodiesterase III inhibitor • Positive inotropic and vasodilating activities • 20 times of amrinone • increase CO without increasing the overall myocardial oxygen consumption • Thrombocytopenia • active amrinone metabolite n-acetyl amrinone • no reduction in platelet count

37. Enoximone • Imidazole PDE inhibitor derivative • CHF awaiting cardiac transplatation, undergoing CPB • Cardiac and vascular profile • similar to other PDE III inhibitor • Two potential advantage • Oral administration • Low incidence of associated dysrhythmia

38. LEVOSIMENDAN

40. Dosing • 6 - 12 µg/kg bolus over 10 min then • 0.05 – 0.2 µg/kg/min for 24 h • Correction on hypovolemia • Correction of potassium and magnesium • Tight monitoring of blood pressure for 6 h • Norepinephrine may be added

46. Future of heart transplant

47. The problem!!!!!!! Comparison of 1- and 5-year survival after hospitalization for heart failure Obviously irreversible damage ! Dilated Cardiomyopathy

48. More deaths from heart failure than from any other CV disease 5.3 million symptomatic patients; estimated 10 million in 2037 Incidence: About 550,000 new cases/year Prevalence is 1% between the ages of 50 and 59, progressively increasing to >10% over age 80 12 10 10 8 5.3 Heart Failure Patients in US (Millions) 6 3.5 4 2 0 1991 2005 2037* The problem!!!!!!! Obviously Big Growing Problem! American Heart Association. 2008 Heart and Stroke Statistical Update.

49. Heart transplantation • Heart transplantation remains a viable solution for many of these patients • Shortages in donor supply have limited this valuable resource to <2500 patients per year • An estimated 10% to 20% of patients die annually on the waiting list SPARITY

50. Number Of Heart Transplants Reported By Year - Worldwide J Heart Lung Transplant 2007;26: 769-781