Vol 81, No 5 (2023)
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Published online: 2023-03-04

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ECMO in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension as a bridge to therapy

Alejandro Cruz-Utrilla12, Elena Puerto García-Martín23, Laura Domínguez Pérez23, Anibal Ruiz Curiel24, Andrés Quezada25, Alejandro Durante López23, Lourdes Vicent23, Roberto Martín Asenjo23, Williams Hinojosa12, Andrea Eixerés26, Laura Forcén Acebal27, María Galindo28, Fernando Arribas Ynsaurriaga24910, Pilar Escribano-Subias12910, Héctor Bueno24910
Pubmed: 36871299
Kardiol Pol 2023;81(5):500-504.

Abstract

Not available

Short communication

ECMO in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension as a bridge to therapy

Alejandro Cruz-Utrilla12Elena Puerto García Martín23Laura Domínguez Pérez23Anibal Ruiz Curiel24Andrés Quezada25Alejandro Durante López23Lourdes Vicent23Roberto Martín Asenjo23Williams Hinojosa12Andrea Eixerés26Laura Forcén Acebal27María Galindo28Fernando Arribas Ynsaurriaga24910Pilar Escribano-Subias12910Héctor Bueno24910
1Pulmonary Hypertension Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
2European Reference Network of Rare Respiratory Disease (ERN-Lung), Brussels, Belgium
3Intensive Cardiac Care Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
4Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
5Department of Pneumology, Hospital Universitario 12 de Octubre, Madrid, Spain
6Department of Cardiac Surgery, Hospital Universitario 12 de Octubre, Madrid, Spain
7Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid
8Department of Reumatology, Hospital Universitario 12 de Octubre, Madrid, Spain
9Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
10Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain

Correspondence to:

Pilar Escribano-Subias, MD,

Pulmonary Hypertension Unit, Department of Cardiology,

Hospital Universitario 12 de Octubre,

Avenida de Córdoba S/N. 28041, Madrid, C. Madrid, Spain,

phone: +34 629 019 500.

e-mail: pilar.escribano.subias@gmail.com

Copyright by the Author(s), 2023

DOI: 10.33963/KP.a2023.0055

Received: September 3, 2022

Accepted: January 4, 2023

Early publication date: February 28, 2023

INTRODUCTION

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are severe diseases in which pulmonary vasculopathy may cause the failure of the right ventricle and ventilatory lung function [1]. The use of pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty in CTEPH [2, 3] and pulmonary vasodilators in both entities has led to an important increase in life expectancy [4]. Cardiogenic shock (CS) is a catastrophic complication in these patients, either as the initial presentation or developed after a triggering event in previously stable cases [5]. In recent years, the use of extracorporeal membrane oxygenation (ECMO) in patients with refractory CS or massive pulmonary embolism (PE) has expanded. This may be an option in critically ill patients with PAH or CTEPH. However, evidence in this setting is scarce [6]. A multidisciplinary approach to determine a specific strategy in each case is crucial [7]. We present the first results of a newly created ECMO program in CS as a bridge to therapy (BTTh) for PAH/CTEPH in our critical cardiovascular care unit (CCCU).

METHODS

We included consecutive patients with PAH or CTEPH needing ECMO from January 2021 until June 2022 in the Hospital Universitario 12 de Octubre (Madrid, Spain). Clinical management was decided individually upon daily consensus, including PAH and CCCU specialists in coordination with other specialists of the multidisciplinary pulmonary hypertension (PH) unit. This unit is one of the two Spanish reference centers for PH, with the capacity for lung transplantation and complete interventional management of PAH and CTEPH. All patients signed informed consent before their inclusion in the Spanish Registry of Pulmonary Hypertension (REHAP).

RESULTS AND DISCUSSION

An ECMO was implanted in four patients in that period as a BTTh, with a veno-arterial (VA) configuration in two cases and venovenous (VV) in the remaining two. Weaning of the mechanical support was possible in three patients, and hospital discharge was possible in two cases (Table 1). Only one patient is still alive after two years of follow-up.

Table 1. PAH and CTEPH cases undergoing ECMO in the 2020–2021 period

Case 1

Case 2

Case 3

Case 4

Case 1

Case 2

Case 3

Case 4

Previous condition

Age, years

46

32

56

59

Sex

Female

Female

Male

Female

Weight, kg

55

95

89

85

BMI, kg/m2

22.6

34.9

29.7

31.2

PH group

PAH associated with CTD

PAH associated with overlap mixed CTD and primary biliary cirrhosis

CTEPH

CTEPH

Time to diagnosis of PH

7 years

3 weeks

12 months

2 months

Predominant clinical status on admission

Respiratory insufficiency

Cardiogenic shock

Respiratory insufficiency

Cardiogenic shock

Previous treatment

Bosentan, tadalafil, and selexipag

Ursobilane, levothyroxine, and omeprazole

Tadalafil and ambrisentan

Insulin and enoxaparin

HR, bpm

100

110

115

100

Situation prior ECMO cannulation

BP, mm Hg

110/66

110/65

95/55

127/89

pH

7.52

7.49

7.31

Pre-ECMO lactic acid, mmol/l

1.8

1.5

0.7

10

PaCO2, mm Hg

20

41

29

PaO2, mm Hg)

108

46

68

Creatinine, mg/dl

1.21

0.55

1.36

1.99

Hemoglobin, g/dl

11

12.8

11.3

10.3

Platelet count, cc

91000

32000

81000

161000

NT-proBNP, pg/ml

2992

4495

8295

Baseline oxygen saturation, %

60

98

86

91

TTE parameters

RV diameter, mm

37

61

63

54

Diastolic EI

1.2

1.9

1.2

1.6

Estimated RVSP, mm Hg

109

117

70

86

TAPSE, mm

14

14

19

13

S’, cm/s

15

8

14

8

FAC, %

27

10

20

22.5

TR, 0–4

1

4

2–3

4

RA area, cm2

19

23

39

22

LVIV, cc/m2

43

67

LV diameter, mm

35

27

37

41

LVEF, %

72

60

72

60

LV diastolic function, 1–4

2

2

2

2

IVC, dilated

Yes

Yes

Yes

Yes

IVC, collapse >50%

No

No

No

No

Pericardial effusion, 0–4

2–3

1

1

0

RV hemodynamics

mPAP, mm Hg

71

70

45

52

RAP, mm Hg

6

14

19

28

RVSP, mm Hg

94

120

85

96

PCWP, mm Hg

9

14

16

a

Cardiac output, l/min

4

2.6

Cardiac index, l/min/m2

2.5

1.5

PVR (WU)

15.5

11

Associated conditions

Neumonitis of unknown origin

12-week pregnancy, severe thrombocytopenia, and alveolar hemorrhage

Interstitial edema after initiation of intravenous epoprostenol

Subacute PE on a previously unknown chronic CTEPH

ECMO

Time from ICCU admission to ECMO implantation, days

6

5

1

1

Initial configuration

VV

VA

VV

VA

Configuration change

No

VAV and VV

VAV (peripheral and central)

No

Distal perfusion cannula during VA or VAV ECMO

No

No

Yes

Yes

Initial blood flow, lpm

3.3

3.2

3.3

3.4

Initial sweep gas flow rate (lpm) and FiO2 ECMO (%). HFNC (lpm/FiO2) or LFNC (lpm)

7 and 1. HFNC 40/0.9.

0.3 and 0.6. HFNC 30/100.

3 and 1. HFNC 50/40.

2 and 0.8. LFNC a 0.5.

Duration of ECMO support, days

12

21

34

13

Peak lactic acid, mmol/l, during ECMO

2.9

6.4

0.7

10

Hemoglobin, g/dl, nadir

8.9

9.3

8.7

7.8

Platelet count, cc, nadir

34 000

16 000

41 000

52 000

Serious bleeding event

Yes

Yes

Yes

No

Transfusion required

Yes

Yes

Yes

Yes

Membrane thrombosis

No

No

Yes

No

Cerebral, lower limb, or another embolic event

No

No

No

No

Clinically significant lower limb ischemia

No

No

No

Peak creatinine, mg/dl, during ECMO

1.92

0.76

2.06

2.2

Requires CRRT

No

No

Yes

No

Definite infection requiring antibiotic

Yes

No

Yes

Yes

Type of infection

Pneumonia

Pneumonia

Urinary tract infection and bacteremia

Antibiotic without confirmed infection

Yes

Treatment while being on ECMO

Pulmonary vasodilators

PDE5 inhibitor

Tadalafil

Sildenafil

Tadalafil

Endothelin receptor antagonist

Macitentan

Macitentan

Inhaled vasodilator

Intravenous or subcutaneous prostacyclins

Epoprostenol 8 ng/kg/min

Epoprostenol 20 ng/kg/min

Epoprostenol 8 ng/kg/min

Inotropic support

Dobutamine

Dobutamine

Dobutamine

Dobutamine

Vasopressors

No

Norepinephrine

Norepinephrine and vasopressin

No

Systemic vasodilator

No

No

No

Nitroprusside

Maximum ventilatory support

HFNC

HFNC

IMV (maximum PEEP of 18 cm H2O)

LFNC

Duration of mechanical ventilation, days

Duration of HFNC, days

24

25

12

Tracheostomy during hospitalization

No

No

Yes

No

Additional treatments

Corticosteroids

Pregnancy termination, corticosteroids, cyclophosphamide, rituximab, and immunoglobulin G

Balloon pulmonary angioplasty

Pulmonary endarterectomy

Outcome

Discharged alive

Discharged alive

Died while on ECMO

Weaned from ECMO. Death in the post- operative period of PEA

ICCU length of stay, days

25

30

32

14

Hospital length of stay, days

67

46

38

27

Case 1. A 46-year-old woman with previously known PAH associated with systemic sclerosis on triple vasodilator therapy and severe immunosuppressive therapy presented a rapid respiratory deterioration attributed to immune-related pneumonitis. Considering the severity of respiratory insufficiency, the patient needed mechanical support with VV-ECMO. Treatment with corticosteroids caused rapid clinical amelioration, allowing ECMO weaning and patient discharge. Eleven months later, the patient died due to severe COVID-19 bilateral pneumonia.

Case 2. A 32-year-old woman without known PAH was admitted to the hospital in CS. She was found to be 12 weeks pregnant at that moment. A VA-ECMO was implanted as a bridge to pregnancy termination, which was then successfully carried out. Nevertheless, she developed severe thrombocytopenia and an alveolar hemorrhage, which caused a progressive decline in lung function, whereby we changed the configuration of the ECMO to VAV. After initiation of immunosuppressive drugs and up-titration of pulmonary vasodilators and a dramatic hemodynamic improvement, the patient could be weaned from ECMO. She was finally discharged on triple vasodilator therapy.

Case 3. A 56-year-old male with severe distal CTEPH presented severe bilateral interstitial edema after the initiation of intravenous epoprostenol, which finally needed VV-ECMO implantation. Due to further hemodynamic impairment, a switch to VA-ECMO was done. After stabilization, balloon pulmonary angioplasty (BPA) was used as a rescue therapy. Despite an initial improvement after three BPA procedures, he presented severe repetitive episodes of hemoptysis, which required tracheal intubation and mechanical ventilation. The patient died due to ventilator-associated pneumonia after 34 days of mechanical support while being still supported by ECMO at that moment.

Case 4. A 59-year-old woman presented with CS and severe respiratory insufficiency. The initial evaluation revealed a probable subacute episode of PE on top of a previously unknown central CTEPH. Treatment with percutaneous mechanical thrombectomy was administered. During the procedure, the patient further deteriorated hemodynamically, and a VA-ECMO was emergently implanted in the cath laboratory. The patient remained stable for one week when elective PEA was done, with excellent results. The ECMO was withdrawn two days after surgery. Thirteen days later, while being clinically stable at that moment, the patient died suddenly due to a new episode of massive PE.

ECMO as a BTTh may be a useful option in critically ill patients with PAH or CTEPH. Our results are in line with those published by Rosenzweig et al. [8]. In that last study, survival of 31.6% was facilitated by ECMO as a bridge to recovery (BTR), and more than 75% of patients survived until ECMO decannulation. The selection of candidates for mechanical support is of critical importance [9]. Likely, the reduction of right ventricular pressure overload and increase in systemic blood pressure are key features involved in the hemodynamic improvement after ECMO cannulation. Additionally, the reduction in the hypoxic pulmonary vasoconstrictive response and of the right-to-left shunting might also be beneficial effects of ECMO implantation. Our experience suggests that cases with acute decompensation triggered by factors like immune disorders or pregnancy could be good candidates for ECMO as a BTTh. We presented a case of VA-ECMO as a bridge to pregnancy termination, representing one of the first reports in the literature [10]. CTEPH is a more challenging scenario for ECMO support, as ventilatory impairment and coagulation disturbances are usually more advanced. Nevertheless, ECMO during the postoperative period of PEA as a BTR has usually good results [2]. The use of ECMO as a bridge to lung transplantation in Spain demonstrates good results [11]. A complementary and interesting option for end-stage patients, or those waiting for lung transplantation, could be the creation of an interatrial septostomy [12].

ECMO management in pulmonary hypertension requires specific considerations. The initial configuration should be based on the severity of hemodynamic impairment and respiratory insufficiency, trying to minimize the need for tracheal intubation and mechanical ventilation, considering the high risk of clinical deterioration during sedation in cases of right ventricular dysfunction. In candidates for lung transplantation, tracheal intubation should also be avoided, as this is a relative contraindication for transplantation. We opted for VA-ECMO when a more profound shock was established (Society for Cardiovascular Angiography and Intervention [SCAI] index stage D in both cases) and for initial VV-ECMO when respiratory impairment was the predominant problem (SCAI index C). The dose of inotropic or vasopressor therapy was similar in both groups, with comparable vasoactive-inotropic scores. CCCU specialists should also be aware of the possibility of upper-body hypoxemia since the perfusion of coronary arteries and the brain in VA-ECMO is frequently provided by deoxygenated blood, especially when lung gas exchange is impaired. In cases of baseline impaired lung function or expectation of worsening after cannulation, an initial axillar configuration or switching to VAV-ECMO could provide adequate oxygenation for the upper body. After the initiation and up-titration of pulmonary vasodilators, with hemodynamic improvement, the arterial cannula can often be removed. In these cases, if respiratory amelioration continues, ECMO weaning is feasible. Thrombocytopenia is another relevant aspect. In our series, three patients started with a moderate or severe reduction of the platelet count, all of them with bleeding episodes. None of our patients had ischemic or embolic events. Therefore, our protocol recommends the maintenance of high ECMO flows and low coagulation times, especially in patients at risk of bleeding events.

In conclusion, we report the initial experience of a multidisciplinary PH unit with ECMO support as a BTTh in patients with PAH or CTEPH. The positive results, with ECMO weaning possible in three of four critically ill cases, emphasize the need to maintain a coordinated approach involving different specialists in this complex scenario.

Article information

Conflict of interest: None declared.

Funding: None.

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