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Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

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Page 1: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Pulmonary hypertension in critical care

ICU Fellowship Training Radboudumc

Page 2: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Pulmonary hypertension

mPAP ≥ 25 mmHg at rest assessed by RHC

Page 3: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

PHT in critical careAcute/acute-on-chronic venous PHT

Secondary to LV failure with left atrial hypertension

Acute-on-chronic arterial PHT

Worsening of preexisting PHT due to natural progression, sepsis, ARDS, PE, drugs

Acute arterial PHT

Massive PE, ARDS, sepsis, drugs

Gayat E. Curr Opin Crit Care 2011;17:439-448

Page 4: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Normal RV

End-diastolic volume index 64 ± 13 ml/m2

Stroke volume index 43 ± 13 ml/m2

RVEF 62 ± 8 %

Redington AN. Br Heart J 1988;59:23-30

Page 5: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Redington AN. Br Heart J 1988;59:23-30

Page 6: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

PEEP

0

5

10

15

Step 1

Step 2

Step 3

Air-filled pericardial balloon

REF thermodilution catheter

Pinsky MR. Am Rev Respir Dis 1992;146:681-687

12 patients after cardiac surgery

Page 7: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

mL

0

35

70

105

140

PEEP (cm H2O)

0 5 10 15 0

EDV ESV

L/m

in

0

1

2

3

4

5

PEEP (cm H2O)

0 5 10 15 0

COm

mH

g

0

10

20

30

40

PEEP (cm H2O)

0 5 10 15 0

Pra (tm) SPpa (tm)

RVEF

0

0,1

0,2

0,3

0,4

0,5

PEEP (cm H2O)

0 5 10 15 0

RVEF

Page 8: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RV complianceNo consistent relationship

Page 9: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RV EDV and RVESVNormal slope 0.7

Page 10: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

First conclusion• In normal right ventricle changes in EDV occur

below RV stressed volume

• Conformational changes in RV shape rather than myocardial fiber stretch

• RV preload (= RV wall stretch) is constant with variation in RVEDV) meaning RV preload is independent of RV EDV

Page 11: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RV EDV and RvEFLineair for every individual patient

Page 12: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Important consequence

• If increasing RV volume increases RV preload and thus RV distending pressure, the RV is either hypertrophied with diastolic dysfunction or over distend as in acute cor pulmonale

Page 13: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Implications• CVP can never be used to predict fluid responsiveness

• Changes in CVP are an excellent measure to show that fluid resuscitation has exceeded the normal RV unstressed volume operating range

• If cardiac output increases by Starling mechanism, RV ESV must also increase which by pericardial constraint limits the effect of volume resuscitation

• Nothing beneficial with RV hypertrophy

Page 14: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Sepsis and fluid responsiveness

Osman D. Crit Care Med 2007;35:64-68

Page 15: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Clinical implications• Central venous pressure is only elevated in disease

• If CVP rises after a fluid challenge and remains so: STOP - think about ACP

• For an increase in CO the RV must dilate - this limits the effect of fluid resuscitation

• RV hypertrophy is a deal with the devil

Page 16: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Normal RV P-V relationVo

lum

e (c

c)Pr

essu

re (

mm

Hg) Pr

essu

re (

mm

Hg)

Volume (cc × 10-1)Time (s)

Time (s)

Redington AN. Br Heart J 1988;59:23-30

39 ± 4% of SV ejected before peak RV pressure Poorly defined isovolumetric contraction phase

43 ± 9% of SV ejected during pressure fall Poorly defined isovolumetric relaxation phase

Page 17: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Normal LV PV relation

Volume (cc × 10-1)

Pres

sure

10-1

mm

Hg

)

Redington AN. Br Heart J 1988;59:23-30

30 - 40% of RV output results from LV contraction

Page 18: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RV P-V relation with PHT

Pres

sure

(m

mH

g)

0

20

40

60

80

16080Volume (cc)

•Shape resembles normal LV •Decreased ejection during pressure rise and fall

Redington AN. Br Heart J 1990;63:45-49

Page 19: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

PAP increase

RVEF ⬇ RV dilatation

Isovol. CP ⬆ Ejection time ⬆

MVO2 ⬆

RV ischemia

RCA mainly perfused in diastole

RV output ⬇

T3 insufficiency

LV preload ⬇

Cardiac output ⬇

Organ failure

Septal displacement

Right ventricular pressure ⬆

Open FO

Hypoxemia

Page 20: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RC blood flow

Zong PU. Exp Biol Med 2005;230:507

Extraction 75%

Extraction 50%

Page 21: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

RC blood flow with PHT

Zong PU. Basic Res Cardiol 2002;97:392-398

Without NO blocked increase in MvO2 82% covered by increased flow

Page 22: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Gan C. Am J PhysiolHeart Circ Physiol 2006;290:H1528-1533End-diastole End-systole Early-diastole

Page 23: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Mild PHT induces LV diastolic dysfunction

E/E’

(lat

eral

)0

5

9

14

18

Control DD IPAH

** **

Kasner m. Am J Respir Crit Care Med 2012;186:181-189

Page 24: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Kasner m. Am J Respir Crit Care Med 2012;186:181-189

11% increase in cardiac output

Page 25: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Sztrymf B. Chest 2013

Page 26: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

TreatmentTreat or avoid RVF (main cause of death)

Treat underlying cause of PHT

No guidelines for the ICU!

Page 27: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Volume managementVolume overload is common and may aggravate RV dysfunction

With a dilated RV and IV septum shift first try iv diuretics followed by hemofiltration often under inotropic support

Page 28: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO
Page 29: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

VasopressorsNorepinephrine in case of severe systemic hypotension to improve RCA perfusion

Car

diac

Out

put (

L)

0,00

1,25

2,50

3,75

5,00

Baseline Pulmonary HT After fluid challenge After NE infusion

Bloo

d pr

essu

re

0

40

80

120

160

Baseline Pulmonary HT After fluid challenge After NE infusion

Ghignone M. Anesthesiology 1984;60:132-135

Page 30: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

VasopressorsSBP

(mmHg)MPAP

(mmHg)PVRI

(D.s.cmMPAP/MAP

(%)PVRI/SVRI

(%)

Baseline 91 ± 11.8 31.4 ± 5.3 257.8 ± 84.4 44.2 ± 5.3 12.4 ± 4.8

NE dose 1 (30% ⬆ SAP) 131.0 ± 4 37.3 ± 7 340.9 ± 78.4 38.1 ± 9.9 11.7 ± 5.9

NE dose 2 (50% ⬆ SAP) 152 ± 3.2 41.3 ± 7.8 442 ± 228.3 37.7 ± 8.6 13.3 ± 4.3

N = 10 - cardiac surgery and pulmonary hypertensionKwak YL. Anaesthesia 2002;57:9-14

Page 31: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

InotropesPDE inhibitors - strong recommendation

Levosimendan - only case records

Rieg AD. PLoS ONE 2013;8:e66195

Pre-constricted

Page 32: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Levosimendan and ARDS after sepsis

RCT Levosimendan (N=18) versus placebo (N=17)

Patients with septic ARDS (< 3 D)

Dose 0.2 μg/kg/min for 24 hours without loading dose

Primary endpoint ∆ RVEF after 24 hours

Morelli A. Crit Care Med 2006;34:2287-2293

Page 33: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Morelli A. Crit Care Med 2006;34:2287-2293

Page 34: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Morelli A. Crit Care Med 2006;34:2287-2293

Page 35: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

PHT in patients with ARDSLung damage per se (capillary destruction and obstruction by clots)

Muscularization by hypoxemia and hyper- capnia

Mechanical ventilation with increased alveolar distending pressures

Page 36: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Mechanical ventilationPrevent hypoxia, hypercapnia and high transalveolar pressures

Low tidal volume ventilation with low levels of PEEP unless a severe reduction in FRC is present

Page 37: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Low Tv and RV functionARDS (N = 145) with PAC

RVF defined as MPAP > 25 mmHg, CVP > PCWP and SV < 30 ml/m2

Tv 8.8 ± 1.9 ml/kg and Pplat 26 ± 6 cmH2O

RVF in 9.6% - no mortality difference (68%)

RVF No RVF P-valueTv (ml/kg) 9.7 ± 2.8 8.6 ± 1.8 < 0.05P 28 ± 6 25 ± 6 0.41

Osman D. Intensive Care Med 2009;35:69-76

Page 38: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Tv and RV function

0

20

40

60

80

Plateau pressure Day 1 (cm H2O)

18-26 27-35 > 35

56

32

13

Mortality (%) RVF (%)

Mor

talit

y (%

)0

25

50

75

100

Plateau pressure Day 1 (cm H2O)

18-26 27-35 > 35

Normal RVF

ARDS (N = 352)Jardin F. Intensive Care Med 2007;33:444-447

Page 39: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

TV and RV function

Intensive Care Med. 2013 Oct;39(10):1725-33

Inci

denc

e A

cute

Cor

Pu

lmon

ale

(%)

0

10

20

30

Boissier 2013 Lhéritier 2013Intensive Care Med. 2013 Oct;39(10):1734-42

Moderate to severe ARDS

N = 226 N = 200Risk: driving pressure ≥ 17 Risk: PaCO2 ≥ 60 mmHg

ACP is RV enlargement combined with systolic paradoxical septal motion

Page 40: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

PVR and FRC

PVR may ↓ with recruitment (low FRC)

PVR may ↓ with abolishment of HPV

PVR may ↓ with PaCO2 ↓

Page 41: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Hypercapnia and ARDS

N = 11 Severe ARDS

22 - 23

PaCO2 52 pH 7.30

PaCO2 71 pH 7.17

PaCO2 75 pH 7.20

0

0,5

1

1,5

LP HP/HR HP/LR

1,281,19

1,11

0,85

0,64

RV/LV area ratioES eccentricity index

** ** ** **

pH only factor independently associated with RV/LV area ratio and ES EI

Mekontso Dessap A. Intensive Care Med 2009;35:1850-1858

Page 42: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

ECCO2R?

Vieillard-Baron A. Intensive Care Med 2013;39:1836-1838

Page 43: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Vasodilators

IV vasodilators (NTG, Nitroprusside, PGE1) not recommended

Inhaled nitric oxide, prostacyclin (derivatives)

Sildenafil

Page 44: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

NO or Iloprost inhalation?M

PAP

(mm

Hg)

30

40

50

60

70

80

Baseline 1 NO (40 ppm) Baseline 2 Iloprost (14-17 mcg)

CO

(l/m

in)

0

1

2

3

4

5

6

Baseline 1 NO (40 ppm) Baseline 2 Iloprost (14-17 mcg)

PVR

(dyn

es*s

ec*c

m-5

)

0

500

1000

1500

2000

Baseline 1 NO (40 ppm) Baseline 2 Iloprost (14-17 mcg)

Prostacyclin compared to NO significantly lowers MPAP and PVR

significantly increases CO

Hoeper MM. J Am Coll Cardiol 2000;35:176-182

Page 45: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Nebulized iloprost

Sawheny E. Chest 2013;144:55-62

ARDS (N = 20)

No effect on hemodynamic or pulmonary mechanics

Page 46: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Bridge to transplant

Granton J. Semin Respir Crit Care Med 2013;34:700-713

Page 47: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO
Page 48: Pulmonary hypertension in critical careintensivistenopleiding.org/downloads-19/files/RV failure en PHT.pdf · Hypercapnia and ARDS N = 11" Severe ARDS 22 - 23 PaCO 2 52" pH 7.30 PaCO

Conclusions

PHT results in early changes in right and left ventricular function

RVF determines outcome

With RVF fluid therapy is rarely effective

Milrinone + NE are the agents of choice

Iloprost inhalation is feasible in MV patients