1. Volume administration Overload Hypovolemia

2. Volume and the failing RV Volume overload Increased wall tension Reduced contractility

3.  41 acutely ill patients receiving 300 cc albumin over 30 minutes  All patients had an RVEF-capable Swan-Ganz catheter  Measurements included RVEDVI, calculated from (CI/HR) / RVEF Chest 1990;98:1450-4

4. Volume challenge and RV response

5. Findings  Patients with high baseline RVEDVI did not benefit from volume loading  In all other patients RVESVI and RVEDVI did increase similarly with volume  CVP is a poor predictor of volume responsiveness  (Normal) RV output is preload-dependent  In the failing RV, judicious volume management is necessary, and fluid removal may eventually help with recovery

6. Volume status  Gentle volume challenge in the early stage of RV failure (only shown for acute PE)  Close monitoring of fluid status either with echo or using the CVP waveform, trend(, and number)  Excessive volume loading may worsen RV performance (RV distention, TR, ventricular interdependence)  Diuretics or ultrafiltration may be indicated, but have not been studied in this population  Loop diuretic resistance in chronic heart failure sometimes requires addition of a thiazide diuretic drug

7. Cardiac output Contractility Cardiac output Tachyarrhythmia Increased afterload (Systemic hypotension)

8. Sympathomimetic inotropes  Improves contractility (RVSWI and RVEF) despite an increase in mPAP  Never studied in patients with pulmonary hypertension  Up to 5 mcg/kg/min  Increases CO, reduces PVR and SVR  Less tachycardiac than dopamine  Higher doses can cause systemic hypotension EpinephrineDobutamine Intensive Care Med 1997;23:664-70 Crit Care Med 2003;31:1140-6

9. Sympathomimetic inotropes  Primarily chronotropic agent  Described in the heart transplant population  Can cause significant arrhythmias  Dopamine increases CO  Almost always causes (at least) mild tachycardia  Increases PVR/SVR ratio IsoproterenolDopamine Crit Care Med 1991;19:60-7 Br Heart J 1975;37:482-5 J Pediatr 2002;140:373-5

10. PDE inhibitors

11.  They all augment contractility and produce vasodilation  Mild tachycardia is common  Good human data exists for LV dysfunction, but is somewhat scarce for RV failure  Potential advantage is pulmonary vasodilation, which is via PDE3-receptors and not specific  Can cause significant systemic hypotension Ann Thorac Surg 1997;63:814-21 Clin Transplant 2010;24:515-9

12. Cardiac output  Dobutamine should be used for RV failure; the dose should not be higher than 10 mcg/kg/min  Higher doses may cause tachycardia, arrhythmias, and systemic hypotension  Epinephrine is probably preferred in the setting of low arterial blood pressure  PDE inhibitors like milrinone are probably similar to dobutamine, but act via a different receptor system and are more potent pulmonary vasodilators

13. Pulmonary vascular resistance  RV is a high-volume low-pressure chamber  It has about 1/6 of the LV’s muscle mass  There is little tolerance to acute increases in afterload (From Braunwald, 1984)

14. Targets for reducing PVR N Engl J Med 2004;351:1425-36 Inhaled agents are always preferred in the acute setting

15. Nitric oxide  Rapid half-life, inactivated by hemoglobin  Virtually no systemic vasodilation, need for continuous application  Studied in a variety of perioperative settings, small studies  NO improves hemodynamics, but has not been shown to improve outcomes  High cost (for how long?)

16. Nitric oxide in LVAD patients?  150 patients undergoing LVAD with increased preoperative PVR  NO versus placebo, option of open-label NO in the presence of RV failure  Primary endpoint: RV failure  Secondary endpoints:  Length-of-stay  RVAD rate  No significant differences J Heart Lung Transplant 2011;30:870-8

17. Alternatives  Safe and effective in the setting of cardiac surgery  Easy to administer  Potential cost-saver  PDE5 inhibitor  Relatively selective  As effective as NO  Synergistic effect  No differences in systemic blood pressure Inhaled epoprostenolOral sildenafil J Thorac Cardiovasc Surg 2004;127:1058-67 NO = $3000 vs. EPO = $150 NO = $3000 vs. EPO = $150 Circulation 2002;105:2398-403

18.  58 patients with increased PVR  Comparison of hemodynamic effects  NO and prostacyclin equally lowered PVR, mPAP, and TPG as well as they increased CO  Nitroprusside lowered PVR, but also SVR and had to be discontinued in 62% of the cases due to low systemic blood pressure J Card Surg 2005;20:171-6

19. Am J Respir Crit Care Med 1996;153:1985-7 Circles = S a O 2 Diamonds = MAP Squares = F i O 2

20. Importance of maintaining systemic blood pressure  RCA perfusion throughout the cardiac cycle  As PVR approaches SVR, coronary perfusion will decrease  Adequate perfusion pressure needed to prevent RV ischemia  Maintain positive SVR/PVR or MAP/mPAP ratio Aortic pressure Coronary flow

21. Which vasopressor?  Potential vasoconstriction, but improved PVR/SVR ratio in most studies  Additional positive inotropic effect via beta- receptor  Improved coronary blood flow during exercise by endogenous norepinephrine  Some small, but promising studies  Potent peripheral vasoconstrictor  Potential pulmonary vasodilation NorepinephrineVasopressin Anaesthesia 2002;57:9-14 Exp Biol Med 2002;227:238-50 Eur J Cardiothorac Surg 2006;29:952-6 Am J Physiol 1994;267:H2413-9

22. Anesthesiology 1984;60:132-5 In the presence of increased RV afterload, volume expansion causes deterioration of ventricular function likely due to increased wall stress Distention imposes increased wall stress, this can cause RV ischemia Volume-induced RV dysfunction was reversed by norepinephrine Ventricular interdependence caused SV to decrease despite constant or slightly increased LVEDP

23. Summary I Pulmonary hypertension is a serious disease associated with increased perioperative mortality Worsening RV dysfunction determines of symptoms and outcome Important to distinguish pulmonary arterial and pulmonary venous hypertension

24. Summary II Treatment of underlying disease and influencing factors is mandatory Supportive therapy includes: Careful ptimization of volume status Maintenance of RV perfusion pressure Enhancing RV contractility Reduction of RV afterload

25. Thank you!