Pulmonary hypertension and right ventricular failure
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1 Pulmonary hypertension and right ventricular failure Sven-Erik Ricksten Dept. Anaesthesiology and Intensive Care, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
2 Pulmonary circulation and the right ventricle (RV) Low resistance, low pressure, high capacitance circuit 3-4 fold increase in RV stroke volume with no major change in pulmonary artery pressure
3 Pulmonary circulation and the right ventricle (RV) RV stroke work is 1/6 of the LV Crescent-shaped geometry with a high compliance Poor tolerance to an increase in RV afterload cm
4 Matthews and McLaughlin Current Cardiology Reviews 2008;4:49-59
5 Pulmonary hypertension MPAP > 25 mmhg or SPAP > 55 mmhg RV hypertrophy/failure Classification: -Pulmonary arterial hypertension -primary, idiopatic pulmonary hypertension (sporadic, familial) -related to collagen diseases (sclerodermi, lupus, RA) -portopulmonary hypertension -Pulmonary venous hypertension (LV failure, valve disease) -Pulmonary hypertension assoc. with lung disease -Pulmonary hypertension caused by thromboembolic disease
6 (MPAP - PCWP) = CO x PVR MPAP = PCWP + (CO x PVR)
7 RV pressure load RV wall tension RV ischemia RV coronary perf. pressure Cardiac output MAP RV decompensation Increased RV volume Leftward septal shift LV distensibility LV preload RV output The pathophysiology of acute right ventricular failure in pulmonary hypertension
8 RV pressure load vasodilator i.v. RV wall tension RV ischemia RV coronary perf. pressure Cardiac output MAP RV decompensation Increased RV volume Leftward septal shift LV distensibility LV preload RV output The pathophysiology of pulmonary hypertension acute right ventricular failure
9 RV pressure load vasodilator i.v. RV coronary perf. pressure vasodilator i.v. RV wall tension RV ischemia Cardiac output MAP RV decompensation Increased RV volume Leftward septal shift LV distensibility LV preload RV output The pathophysiology of pulmonary hypertension acute right ventricular failure
10 Intravenous vasodilators and pulmonary selectivity (PVR/SVR ratio) Kieler-Jensen et al J Heart Lung Transplant 1995;14:436
11 EDRF = NO
12 Inhaled NO mechanisms of action
13 Effects of inhaled NO on the PVR/SVR ratio *** Kieler-Jensen et al J Heart Lung Transplant 1995;14:436
14 Inhaled NO in ARDSinduced RVF Twenty-six patients with RVF because of ARDS Incremental concentrations of inhaled NO (mean 35 ppm) Bhorade et al Am J Respir Crit Care Med 1999;159:
15 Inhaled NO in ARDS-induced RVF PVR ** Cardiac output ** SVR MPAP **
16 Inhaled NO in cardiac surgery High preoperative PVR in valvular heart disease Endothelial dysfunction after cardiopulmonary bypass
17 Rich et al Anesthesiology 1993;78:1028 Inhaled NO before and after MVR or CABG Before CPB INO: 20 ppm After CPB INO: 20 ppm
18 Inhaled NO in heart transplantation Kieler-Jensen et al J Heart Lung Transplant 1995;14:
19 Inhaled NO in heart transplantation PVR Cardiac output * ** * SVR MPAP ** **
20 RV pressure-volume curve after heart transplantation - effects of inhaled NO (20ppm) PVR: 254 to 178 dynes x sec x cm-5 SV: 72 to 83 ml RVEF: 28% to 37% RVEDV: 258 to 225 ml
21 Inhaled NO in RVF after posterior AMI Thirteen patients with RV infarction and cardiogenic shock Inhalation of NO (80 ppm) Inglessis et al J Am Coll Cardiol 2004;44:
22 -12% -13% -36% 23% Inglessis et al J Am Coll Cardiol 2004;44:
23 Limitations with NO for inhaled therapy of postoperative pulmonary hypertension Rebound pulmonary hypertension Toxicity: NO 2, methemoglobinemia Equipment Cost
24 Inhaled alternatives to NO?
25 Inhaled prostacyclin (PGI 2 ) for the treatment of RVF
26
27 Inh PGI 2 Alveolus EC
28 Haraldsson et al J Cardiothoracic Vasc Anesth 1996;10: Effects of aerosolized PGI 2 on PVR after cardiac surgery ** ** ** C C 10 C 20 µg/ml PGI 2
29 Inhaled PGI 2 in one patient with RVF after heart transplantation
30 Inhaled milrinone for treatment of pulmonary hypertension and RV failure
31 Haraldsson et al Anesth Analg 2001,93:1439
32 Inhaled prostaglandins and milrinone - doses Prostacyclin /Flolan ): 10 µg/ml, 5-10 ml/h Iloprost (Ilomedin ): 10 µg/ml, µg x 6-9 Treprostinil (Remodulin ): µg x 4 Milrinone: 1 mg/ml, 5-10 ml/h
33
34
35 Combined treatment of RVF with inhaled PGI 2 plus inhaled milrinone
36 Haraldsson et al Anesth Analg 2001,93:1439
37 PVR -27% -46% -38% Effects of combined inhalation with PGI 2 and milrinone in one patient with severe pulmonary hypertension and RVF.
38 PDEI (milrinone) _ ATP camp + PGI2 The rationale for the use of combined inhalation with PGI 2 and a phosphodiesterase inhibitor (PDEI)
39
40 Inhaled therapies in RVF correlates for success High PVR (> 250 dynes x sec x cm -5 ) Reversible, not fixed high PVR Isolated RVF LV failure or biventricular is a contraindication!!
41 More aspects on the management of isolated RVF Selective pulmonary vasodilation (inhaled NO, PGI 2, milrinone Optimise RV preload (CVP mmhg) High systemic pressure improves RV perfusion and LV assist - norepinephrine
42 Systolic ventricular interaction LV contributes with 60% of RV pressure and stroke volume
43 Diastolic ventricular interaction in RVF Failing RV
44 Systolic ventricular interaction - RVF Left ventricular Failing RV
45 Effects of norepinephrine on systemic and pulmonary vascular resistance
46 More aspects on the management of isolated RVF Selective pulmonary vasodilation (inhaled NO, PGI 2, milrinone Optimise RV preload (CVP mmhg) High systemic pressure improves LV assist and RV perfusion - norepinephrine Inotropic support
47 Inotropic agents Norepinephrine Epinephrine Dopamine Dobutamine Dopexamine Isoprenalin Levosimendan Milrinone vasoconstriction vasodilation
48 More aspects on the management of isolated RVF Optimise RV preload (CVP mmhg) High systemic pressure improves LV assist and RV perfusion Selective pulmonary vasodilation (inhaled NO, PGI 2, milrinone Inotropic support (dopamine, milrinone, noradrenaline) ECMO/RVAD
49 Extracorporeal circulatory support
50
51
52 Perkutaneous RVAD, TandemHeart
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54
55
56
57 Inhaled NO in patients receiving LVAD
58 Circulation 1997;96:291 8 patients with RV dysfunction; -CI < 2.5 l/min/m2 -MPAP > 25 mmhg, -RVEF < 30% Catecholamines, PDE-3 inhibitors, nitrates, PGI 2 Inhaled NO 5-40 ppm
59 Wagner et al Circulation 1997;96:291
60
61 Prerequisites for a succesful treatment of RV failure with an inhaled vasodilator Pulmonary hypertension caused by a high PVR (> 240) PVR should not be fixed Isolated RV failure
62 (MPAP - PCWP) = CO x PVR MPAP = PCWP + (CO x PVR)
63 PVR (>240) Systemic hypoperfusion Adequate systemic perfusion Normal filling pressures (CVP < PCWP) Normotension (SVR ) Elevated filling pressure(s) (CVP and/or PCWP ) Hypotension, RVF (CVP > PCWP) No treatment Intravenous vasodilators Inhaled vasodilators
64 Inhaled NO should be used in the treatment of postoperative pulmonary hypertension if: Pulmonary vascular resistance is high and reversible plus Systemic hypoperfusion is present plus Isolated RV failure Graft dysfunction after lung transplantation
65
66 Righ ventricular failure (RVF) Lung disease (RVF:1/2000 COPD, ARDS) Sepsis Pulmonary embolism (RVF independent risk factor) Cardiomyopathy (ischemic, dilatative) (RVF independent risk factor) Heart transplantation/heart surgery (RVF leading cause of death) Primary pulmonary hypertension Coronary artery disease (RV infarction + RVF, 8-fold increase in mortality) 50% of patients with posterior-ami develop RVF Valvular heart disease
67 Why should we treat pulmonary hypertension in cardiac surgery? Preoperative pulmonary hypertension is an independent predictor of postoperative mortality Cardiac surgery with CPB may induce pulmonary vasoconstriction: -protamine - heparin -endothelial dysfunction
68
69 Why should we treat pulmonary hypertension in cardiac surgery? Perioperative pulmonary hypertension is an independent predictor of postoperative mortality Cardiac surgery with CPB may induce pulmonary vasoconstriction: -protamine - heparin -endothelial dysfunction Perioperative pulmonary hypertension may cause refractory right ventricular failure (RVF) with a mortality of 40-60% Incidence of severe refractory RVF: -heart transplantation 2-3% -LVAD 20-30%
70 The pulmonary selectivity of intravenous vasodilators (PVR/SVR ratio ) Kieler-Jensen et al J Heart Lung Transplant 1995;14:436
71 Inhaled NO mechanisms of action
72 Lancet 1991;338:1173
73 Inhaled NO in cardiac surgery
74 Inhaled NO after mitral valve replacement (MVR) -22% INO: ppm Girard et al Anesthesiology 1992;77:880
75 Rich et al Anesthesiology 1993;78:1028 Inhaled NO before and after MVR or CABG Before CPB INO: 20 ppm After CPB INO: 20 ppm
76 Before CPB After CPB Rich et al Anesthesiology 1993;78:1028
77 Inhaled NO after MVR or CABG Fullerton et al Ann Thorac Surg 1997;63:1251 n=25 INO: 40 ppm n=15
78 Severe postoperative pulmonary hypertension (n=14) Dobutamine/dopamine ± norepinephrine Maintained RV function Randomized crossover design: -Inhaled NO (40 ppm) -PGE1 (0,1µg/kg/min) -Nitroglycerin (3-5 µg/kg/min) Anesth Analg 1999,89:1108
79 Schmid et al Anesth Analg 1999,89:1108
80 Schmid et al Anesth Analg 1999,89:1108
81 ** ** Schmid et al Anesth Analg 1999,89:1108
82 Inhaled NO in heart transplantation
83 Girard et al J Cardiothoracic Vasc Anesth 1993;7: 481
84 Girard et al J Cardiothoracic Vasc Anesth 1993;7: 481
85 Girard et al J Cardiothoracic Vasc Anesth 1993;7: 481
86 Uncomplicated heart transplantation (n=9) Preoperative PVR: ( ), TPG: (6-20 mmhg) NO inhalation: 5, 10 and 20 ppm J Heart lung Transplant 1995;14:436 Intravenous PGI 2, PGE 1 and sodium nitroprusside (SNP) to decrease MAP from 90 to 75 mmhg
87 Inhaled NO in heart transplantation PVR Cardiac output * ** * SVR MPAP ** **
88 PVR (%) SVR (%) CO (%) CVP (mmhg)
89 Effects of inhaled NO on the PVR/SVR ratio *** Kieler-Jensen et al J Heart Lung Transplant 1995;14:436
90 Inhaled NO in heart transplant recipients Author Year Dose NO (PPM) PVR MPAP CVP CO MAP SVR Kieler- Jensen % -11% -15% 11% ns ns Auler % ns ns 17% ns -16% Ardehali % -16% ns ns ns ns Khan ? -19% -21% 20% ns?
91 Wagner et al Circulation 1997;96:291
92 Inhaled NO vs N 2 in LVAD recipients - a randomised study Argenziano et al Ann Thoracic Surg 1998; 65:340
93 Inhaled vs N 2 in LVAD recipients - a randomised study Argenziano et al Ann Thoracic Surg 1998; 65:340
94 What are the effects of inhaled NO on pulmonary serial vascular resistances?
95 Pulmonary serial vascular resistances MPAP Pre PCP Post LAP (PCWP) CO...
96 Benzing and Geiger Acta Anaesthesiol Scand 1994; 38:640
97 Pulmonary serial vascular resistances MPAP Pre PCP Post LAP (PCWP) CO... Pre = MPAP - PCP CO PVR = Pre + Post Post = PCP - PCWP CO
98 Effects of inhaled NO on longitudinal distribution of pulmonary vascular resistance in ARDS -23% -12% -34% Benzing Geiger 1994 Acta Anaesthesiol Scand; 38:640
99 Inhaled NO in heart transplant candidates with elevated pulmonary vascular resistance
100 12 heart transplant candidates PVR > 200 dynes x sec x cm -5 Inhaled NO: 20, 40, 80 ppm Kieler Jensen et al J Heart Lung Transplant 1994;13:366
101 Kieler Jensen et al J Heart Lung Transplant 1994;13:366
102 Inhaled NO in heart transplant candidates with high PVR Author Year Dose NO (PPM) PVR MPAP PCWP TPG CO Kieler- Jensen % ns 18% -34% ns Semigran % ns 28% -36% ns Loh % ns 23% -35% ns Haraldsson % -7% 21% -42% ns Sablotzki A % -15% ns -17% ns
103 Pulmonary serial vascular resistances and capacitances MPAP Pre PCP Post LAP (PCWP) CO... NO has a predominant vasodilating effect on the pulmonary venous vasculature. - decreases pulmonary capillary pressure - shifts blood volume from the arterial to venous capacitance vessels
104 Does inhaled NO affect outcome in cardiac surgery or heart transplantation?
105 Inhaled NO vs. i.v PGE 1 during weaning from CPB after heart transplantation Seventy patients randomised to: -Inhaled NO, n=35 (4-24 ppm) -PGE 1 iv, n=35 (8-24 ng/kg/min) Treatment started immediately prior to weaning from CPB MPAP maintained < 25 mmhg Measurements: after induction, 10, 30, 1 h, 6h after weaning Isoprenalin 0.02 µg/kg/min and epinephrine/ norepinephrine if MAP < 65 mmhg Rajek et al Anesth Analg 2000;90:523
106 PGE I PGE I INO INO INO PGE I Failed weaning from CPB: -Inhaled NO, n=0 -Intravenous PGE1, n=6 p<0.03 Rajek et al Anesth Analg 2000;90:523
107 Potapov et al J heart Lung Tranplant 2011; Inhaled NO after LVAD implantation: a randomised doubleblind placebo-controlled trial 150 patients undergoing LVAD implantation PVR 200 dyne/sec/cm-5 Randomised to: -ino (40 ppm) -in 2 Inhalation for: -48 hours, until extubation, study-defined RVD Cross-over to open label ino was allowed < 48 h, if RVD criteria were met
108 Inhaled NO after LVAD implantation: a randomised doubleblind placebo-controlled trial RVD criteria -ino: 9.6% -placebo: 15.6% (p=0.330) Median time on mechanical ventilation -ino 2 days -placebo 3 days (p=0.077) 35 patients crossed-over to open label ino -ino: n=15 (21%) -placebo: n=20 (26%) 18 patients crossed-over before RVD criteria were met Potapov et al J heart Lung Tranplant 2011;30.870
109 Conclusions on ino in cardiac surgery patients : Induces a selective pulmonary vasodilation Has a predominant vasodilating effect on the venous vasculature Improves RV function in patients with high, reversible PVR and RV failure Facilitates weaning from CPB in heart transplantation Prevents RV failure in LVAD insertion? Useful in the evaluation of heart transplant candidates with high PVR
110
111 Systolic ventricular interaction LV contributes with 60% of RV pressure and stroke volume
112 Treatment of RVF Optimise RV preload (CVP mmhg) High systemic pressure improves RV perfusion and LV assist - norepinephrine
113 Effects of inhaled PGI2 on rate of platelet aggregation in vitro Haraldsson et al Intensive Care Medicine 2000;26:
114 Diastolic ventricular interaction
115 Roeleveld et al Radiology 2005;234:
116 Systolic ventricular interaction - RVF Left ventricular Failing RV
117 Effects of aerosolized PGI 2 on central hemodynamics Haraldsson et al J Cardiothoracic Vasc Anesth 1996;10:
118 Inhaled therapies for RVF Inhaled prostacyclin (PGI 2 ) Inhaled iloprost Inhaled treprostinil Inhaled milrinone Inhaled sildenafil
119 The pulmonary selectivity of intravenous vasodilators (PVR/SVR ratio ) Kieler-Jensen et al J Heart Lung Transplant 1995;14:436
120 Inhaled NO after MVR or CABG Fullerton et al Ann Thorac Surg 1997;63:1251 n=25 INO: 40 ppm n=15
121 Lancet 1991;338:1173
122 Inhaled NO in RVF after heart transplantation
123 Pulmonary circulation and the right ventricle (RV) Low resistance, low pressure, high capacitance circuit 3-4 fold increase in RV stroke volume with no change in pulmonary artery pressure RV stroke work is 1/6 of the LV RV wall thickness < 0.6 cm Crescent shaped geometry with a high compliance Poor tolerance to an increase in RV afterload
124 Pulmonary circulation and the right ventricle (RV) RV stroke work is 1/6 of the LV RV wall thickness < 0.5 cm Crescent shaped geometry with a high compliance Poor tolerance to an increase in RV afterload
125 Inhaled NO causes a selective pulmonary vasodilation and improves RV function in: ARDS Cardiac surgery (CABG, MVR, AVR) Heart transplantation Right ventricular myocardial infarction Left ventricular assist device (LVAD) Lung transplantation (one-lung ventilation) Porto-pulmonary hypertension
126 Is there a spill-over of PGI 2 to the systemic circulation when inhaled? Haraldsson et al Intensive Care Medicine 2000;26:
127 Inhaled PGI 2 on bleeding time after CPB Haraldsson et al Intensive Care Medicine 2000;26:
128 Inhaled PGI 2 on 6 h chest tube drainage Haraldsson et al Intensive Care Medicine 2000;26:
129 What are the effects of inhaled NO on pulmonary serial vascular resistances?
130 Pulmonary serial vascular resistances MPAP Pre PCP Post LAP (PCWP) CO...
131 Benzing and Geiger Acta Anaesthesiol Scand 1994; 38:640
132 Pulmonary serial vascular resistances MPAP Pre PCP Post LAP (PCWP) CO... Pre = MPAP - PCP CO PVR = Pre + Post Post = PCP - PCWP CO
133 Effects of inhaled NO on longitudinal distribution of pulmonary vascular resistance in ARDS -23% -12% -34% Benzing Geiger 1994 Acta Anaesthesiol Scand; 38:640
134 Pulmonary serial vascular resistances and capacitances MPAP Pre PCP Post LAP (PCWP) CO... NO has a predominant vasodilating effect on the pulmonary venous vasculature. - decreases pulmonary capillary pressure - shifts blood volume from the arterial to venous capacitance vessels
135 Management of patients with right ventricular failure
136 Right ventricular failure (RVF) Cardiac conditions Coronary artery disease (RV infarction) Valvular heart disease Cardiomyopathy (ischemic, dilatative) Heart surgery (CABG, AVR, MVR) Heart transplantation Post-LVAD Extra-cardiac conditions Pulmonary embolism Lung disease (COPD, ARDS) Primary pulmonary hypertension Sepsis Lung transplantation Post-thromboendarterectomy RVF rarely occurs in the setting of normal pulmonary vascular resistance!
137 Treatment of severe cor pulmonale with inhaled iloprost (5 µg x 6) SPAP (mmhg) Tricuspid annulus (mm) RA area (cm 2 ) Inferior cava (mm) NT-proBNP (pg/ml) TAPSE (mm) Baseline 3-days treatment
138 Inhaled vs i.v. milrinone after mitral valve surgery Wang et al Adv Ther 2009;26: PVRI Cardiac output SVRI MAP ** ** ** ** **
139 RVF LV assist RV output Hypotension LV preload
140 Inhaled prostaglandins - doses Prostacyclin: 10 µg/ml, 5-10 ml/ h Iloprost: 10 µg/ml, µg x 6-9 Treprostinil: µg x 4
141 Inh PGI 2 PGI 2 Alveolus EC
142 Six hours of PGI 2 inhalation (10 µg/ml) after cardiac surgery: No increase in systemic levels of 6-keto-PGF 1 -α No increase in bleeding time No increase in bleeding Haraldsson et al Intensive Care Medicine 2000;26:
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