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.
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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