The Role of Extracorporeal Membrane Oxygenation Support after Pulmonary Thrombo-Endarterectomy

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare consequence of acute or chronic pulmonary embolism. Pulmonary endarterectomy (PEA) is the gold standard treatment: expert centers are able to offer this challenging procedure with low in-hospital mortality, excellent hemodynamic results, and significant improvement in exercise tolerance and quality of life. Despite careful preoperative selection and increasing technical experience in PEA, some patients may suffer from life-threatening complications requiring extracorporeal life support (ECLS). ECLS is necessary in case of heart failure, respiratory failure, or both. According to different indications and timing, cardiopulmonary failure after PEA should be managed with a tailored approach: veno-venous or veno-arterial support, and central or peripheral cannulation. In the present chapter, causes, management strategies, and outcomes of perioperative ECLS for PEA are discussed.

1. Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare consequence of acute or chronic pulmonary embolism (PE). It has been estimated that it occurs in about 3% of acute PE survivors [1]. CTEPH has unique pathogenesis and a potentially curative surgical treatment other than pulmonary transplantation: for these reasons it represents the 4th group of pulmonary hypertensions (PH), according to the Nice classification [2]. CTEPH has been defined as “dual compartments vascular disease” because the occlusive disease due to fibrotic organization of thromboembolic lesions is associated with arterial wall hypertrophy and vasospasm of non-occluded segments, which leads to progressive development of PH and to right ventricular (RV) dysfunction [3, 4, 5]. Diagnosis and clinical management of CTEPH requires a dedicated multidisciplinary high-skilled team that could offer the entire range of therapeutical options: from medical therapy to balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) [6]. PEA is the treatment of choice in CTEPH [7]: technically, the operation is performed through full median sternotomy, cardiopulmonary bypass, myocardial arrest and myocardial protection, intermittent deep hypothermic circulatory arrest (DHCA). Patients should be carefully selected in order to balance surgical risk and optimal outcomes. Preoperative anatomical and hemodynamic information are crucial for preoperative risk stratification and surgical feasibility assessment. Nowadays, expert centers are able to offer this challenging procedure with low in-hospital mortality (<5%), excellent hemodynamic results, and significant improvement in exercise tolerance and quality of life [8].

Nevertheless, despite careful selection, some patients may suffer from life-threatening perioperative cardiorespiratory decompensation requiring extracorporeal life support (ECLS): in the present chapter, we are going to discuss causes, management strategies, and outcomes of perioperative ECLS for PEA.

2. Perioperative role and indications of ECLS in PEA

The mechanism of PH in CTEPH is multifactorial: the first step is due to the fibrotic organization of acute emboli that chronically occlude proximal pulmonary arteries (main, lobar, and segmental), the second step is the redistribution of blood flow and increase of shear stress in nonoccluded segments. Then micro-vasculopathy (affecting muscular pulmonary arteries, capillaries, and veins) progressively induces the increase in PVR, onset of symptoms, and, at last, RV dysfunction and failure [4, 5].

Timely diagnosis and treatment prevent from worsening of PH and reduce perioperative morbidity and mortality because a more compromised hemodynamic status is at higher risk of perioperative need for ECLS [9].

Basically, there are three main indications for ECLS:

• pure respiratory failure defined as hypoxia with pulse oximetry oxygen saturation (SO₂) less than 90% despite mechanical ventilation with 100% fraction of inspired oxygen (FiO₂), without preexisting hemodynamic failure;

• pure hemodynamic failure defined as circulatory failure precluding weaning from CPB or new-onset cardiogenic shock requiring maximal inotropic, without prior respiratory failure;

• mixed respiratory and hemodynamic failure defined as any combination of signs of both respiratory and hemodynamic failure [9, 10, 11].

Patients could require ECLS with three different therapeutical approaches or strategies:

• Bridge to surgery: the target is hemodynamic stabilization in patients with preoperative acute severe cardiorespiratory decompensation;

• Bridge to recovery (BTR): post-cardiotomy mechanical support if weaning from CPB is not possible or in case of organ failure in intensive care unit;

• Bridge to transplantation (BTT): in case of impossible weaning from ECLS in patients eligible for lung or heart-lung transplantation [9, 11].

The vast majority of patients are referred in stable conditions with long-standing symptoms but, in a few cases, such as in acute-on-chronic PE or massive main trunk involvement, patients could rapidly deteriorate with respiratory failure and/or cardiogenic shock due to RV failure: in these cases, PEA should not be further deferred, but ECLS could be the only chance of preoperative stabilization, especially in non-expert centers, allowing urgent PEA as next step [9, 12].

In stable patients, an appropriate preoperative evaluation allows the risk stratification of postoperative heart and lung failure: many clinical features may represent a red flag, and surgeons should forecast and plan the appropriate strategy, including ECLS and, even, organ transplantation [9, 11].

The anatomical location of thromboembolic lesions, assessed with multimodal imaging, is extremely important: distal lesions are not a contraindication, but they make surgery technically demanding, also in expert hands. High PVR increases the risk of an unsuccessful procedure and persistent residual PH, especially in case of unfavorable anatomy [9, 13].

However, distal lesions and high PVR alone must not be considered formal contraindications for surgery. In many series, patients with a need for ECLS often demonstrated preoperative high PVR and previous signs and symptoms of RV failure [9, 11, 13, 14, 15].

Regardless of the preoperative clinical profile, PEA patients are prone to specific severe complications tightly linked to surgical trauma, such as reperfusion edema/injury, bronchial or parenchymal bleeding, residual pulmonary hypertension, and RV failure.

As originally described by Jamieson, PEA consists of a “true endarterectomy”: the surgeon must identify a subintimal cleavage plane in order to be radical, removing entirely the fibrotic tissue from main trunk to subsegmental arteries. It is important to inspect and free all the pulmonary vascular segments: it has been demonstrated that hemodynamic improvement and prognosis are proportional to number of reopened segments [16, 17].

On the other side, good surgical results could be burdened by extensive parenchymal edema due to a large re-perfused territory. Reperfusion edema occurs in up to 20% of cases and, probably, it is the most common complication after PEA. The pathogenesis is not completely explained but it is due to a dysfunction of capillary-alveolar membrane at the level of previously occluded territories. Different degrees of reperfusion edema can be managed with a stepwise approach: in uncomplicated initial stages, optimization of mechanical ventilatory support and maximization of diuretic therapy should be adequate. However, in complicated cases, with massive lung involvement and refractory respiratory failure, bridge-to-recovery ECLS is often necessary [10, 14].

Another technical challenge of PEA is to carry out the endarterectomy not too deep, avoiding transmural lesions that can cause parenchymal bleeding: it is a rare, but life-threatening complication, with a prevalence between 0.5 and 2% of cases. Technical problems, the fragility of the endarterectomies wall and the presence of parenchymal infarcted areas may contribute to hemorrhagic complications after reperfusion [18, 19]. Precautionary measures include a careful endarterectomy and proper pulmonary venting during reperfusion/rewarming period. Moreover, an intraoperative double check is routinely performed, first with the “bubble technique” during gentle ventilation and then with bronchoscopy during re-warming, once a normal core temperature is reached. Typically, bleeding starts just after weaning from CPB, because of the increase in pulmonary pressure. If bleeding is mild, complete re-coagulation could be sufficient. In case of severe parenchymal or endobronchial hemorrhage, ECLS with bridge-to-recovery strategy represents a life-saving tool, associated with mechanical and/or pharmacological local hemostasis and optimal reversal of post-CPB coagulopathy [19, 20].

Residual PH after PEA ranges from 8.2% to 44.5% [21]. It is due to micro-vasculopathy, incomplete revascularization of pulmonary vascular tree or both; predictors of residual PH have been reported: high preoperative PVR, distal surgical material, and associated medical conditions (splenectomy, ventriculoatrial shunt, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis). Unsuccessful procedures with persistent PH in addition to surgical trauma (long CPB time, DHCA, reperfusion lung injury) can lead to an RV overload and failure requiring ECLS [10, 22, 23].

In summary, clinical indications for ECLS can be divided into different groups:

• those with proximal occlusion and good surgical results that suffer massive parenchymal edema due to a large reperfused territory;

• those with a bad preoperative hemodynamic profile, RV failure and distal occlusion, who have a minimal decrease of PH after satisfactory PEA. In these cases, the small and peripheral disease is the main cause of failure;

• those with parenchymal bleeding secondary to technical problems and fragility of the denuded vessels, and the presence of areas of infarcted lung parenchyma which may contribute to hemorrhage after reperfusion.

3. Surgical strategies and ECLS setup

Many centers reported their experience in PEA, focusing on perioperative ECLS: there is no consensus on the best strategy, because of multiple possible indications and approaches, but many authors recommend a prompt, aggressive treatment with ECLS before severe end-stage organ hypoperfusion, possibly with a tailored approach [15, 18].

Table 1 summarizes the most relevant series in the last two decades.

References	Year	Study design	No. of cases (%)	Strategy		Timing
Thistlethwaite PA et al. [14]	2006	Retrospective	20/1790 (1.1)	VV	Peripheral	Post
Ogino O et al. [18]	2006	Retrospective	8/88 (9.1)	VA	Peripheral	Post
Berman M et al. [24]	2008	Retrospective	7/127 (5.5)	VA	Central	Post
Nierlich P et al. [9]	2015	Retrospective	31/161 (19.3)	VA	Peripheral	Pre-Post
Boulate et al. [11]	2016	Retrospective	31/829 (3.7)	VA-VV	Central-Peripheral	Post
Donahoe L et al. [15]	2016	Retrospective	6/144 (4.0)	VA-VV	Central-Peripheral	Post
Guth S et al. [19]	2016	Retrospective	16/396 (4.0) 8/396 (2.0)	VA	Central	Post
Kelava M et al. [12]	2018	Retrospective	14/150 (9.3)	VA-VV		Pre-Post
Martin-Suarez S et al. [10]	2019	Retrospective	19/154 (12.3)	VA-VV	Central-Peripheral	Post
Sugiyama K et al. [25]	2019	Retrospective	4/35 (11)	VA		Post

Table 1.

Literature reports on type of strategy.

VA veno-arterial, VV veno-venous.

ECLS can be set up as veno-venous (VV) or veno-arterial (VA) support. Isolated potentially reversible respiratory failure requiring VV-ECLS is an infrequent scenario, because of the aforementioned vitious circles triggered by complications after PEA: often respiratory failure (hypoxia), high PVR and increased lung stiffness offers an excessive hemodynamic barrage to RV, leading to heart failure.

The group of San Diego advocates the use of VV-ECLS in selected patients because of its technical advantages (physiologic flow and no influence on ventricular pre- and after-load, simple and quick implantation; peripheral and percutaneous access, avoiding redo-sternotomy; on the other side, it is burdened by a significant risk of bleeding, infectious and thromboembolic complications if support is prolonged) [14]. Standard VV-ECLS is achieved through bi-femoral or jugulo-femoral cannulation; the use of dual lumen cannula (Avalon Elite, Avalon Laboratories, Rancho Dominguez, CA, USA) reduces invasiveness and further simplifies the procedure.

Particular care must be taken in titrating pump flow in order to increase oxygen delivery without any recirculation between the drainage and reinfusion cannulas.

VA-ECLS is preferred by many centers because it provides efficient RV unloading, and reduces transpulmonary flow, parenchymal edema, and/or bleeding. Furthermore, the increased afterload due to arterial inflow improves the filling and diastolic performance of the left ventricle, as well as preventing RV distension and leftward septal shift. But there are some drawbacks, especially in case of peripheral setting, such as unphysiological retrograde perfusion that is at high risk of stroke, “Harlequin syndrome” and limb ischemia [9, 10, 11, 24].

Cannulation could be peripheral or central. The standard peripheral setting involves femoro-femoral cannulation, but other cannulation sites such as the subclavian artery can be a viable option: an upper extremity configuration allows mobility and even re-habilitation, especially in case of BTT strategy. Technically, femoro-femoral approach is a straightforward procedure that can be easily done in stable conditions while CPB is already ongoing. If feasible, the chest can be definitively closed, reducing the risk of infection and supporting recovery in more physiological conditions. Moreover, cannulas can be removed in the ICU. Of course, troubles with lower limb ischemia or other vascular complications may occur and periodically checked and eventually treated with distal reperfusion [9, 10].

Furthermore, considering flows ranging from 2.5–4 L/min, external oxygenator allows reduction of the mechanical ventilation protecting impaired alveolo-capillary units from barotrauma or high oxygen exposure.

If ECLS is started in the operating room for impossible weaning from CPB, some authors suggest central VA configuration, because it decreases RV afterload, and ensures a pulsatile blood flow into the lung vessels, avoiding overflow episodes during the early postoperative period. Preventive VA-ECMO should be a reasonable BTR strategy that mitigates the negative effects of both critical pulmonary reperfusion syndrome and severe RVF, after PEA procedures [11, 15].

In summary, VV-ECLS should be the treatment of choice for pulmonary reperfusion injury, manifested as pulmonary edema with preserved right heart function, particularly if it occurs in the intensive care unit after PEA. For persistent residual PH and ongoing RV failure, central VA ECLS was excellent providing both oxygenation and effective unloading of the right heart and pulmonary vessels [15].

Regardless of the management strategy, unfortunately, ECLS is burdened by bleeding, infective, and thromboembolic complications, thus patients must be weaned from ECLS as soon as possible.

4. Results and outcomes

The need for postoperative ECLS ranges between 1 and 19%; incidence tends to decrease with experience and in high-volume centers. Mean support time ranges between 4 and 5 days. Successful weaning rate range between 43 and 100% [10, 11, 14, 15, 18, 19, 24, 25].

The main risk factor for ECLS was high PVR often associated with distal thromboembolic disease (Jamieson type 4), while predictors of mortality after ECLS were elder age, high PVR, RV failure, reperfusion injuries, and parenchymal bleeding [9, 10, 11, 14, 15].

Considering postoperative hemodynamics, PVR was significantly better in non-ECLS patients [9, 24, 25].

Only two studies reported postoperative BTT strategy: in these cases, survival was about 50% and, according to Boulate and colleagues, survival was similar in BTT and BTR strategies [9, 11].

In general, in comparison with patients not requiring ECLS, long-term survival was significantly lower in ECLS patients [9].

On the other side, early hemodynamic improvement in patients with successful BTR-ECLS persisted in the midterm, confirming the benefit of PEA also in patients with severe CTEPH. This observation is consistent with microvascular disease reversal within a few weeks after PEA as previously suggested in human and animal models [11].

Interestingly, in case of parenchymal bleeding Guth and colleagues tailored the approach to reaching excellent results with 100% of successful weaning: prompt institution of ECLS systems with heparin-coated circuits instead of conventional extracorporeal circulatory support during PEA surgery allows complete restoration of blood coagulation with protamine with a minimal risk of clot formation inside the oxygenator: the majority of patients were treated in the operating theater with very short term support and avoiding long-term complications.

In our experience, ECLS was needed in 12.3% of patients who underwent PEA. The duration of ECMO was 11 ± 8 days and successful weaning was achieved in 52.6% of cases, of these 70% were discharged. Also, in our experience, high PVR was associated with a high risk of ECLS. Surprisingly, the PAPs were lower in the nonsurvivor group: this could be a flag of RV dysfunction function, not able to produce adequate pulmonary flow and pulsatility [10].

5. Conclusions

In conclusion, ECLS represents a successful treatment option for patients who experience cardiopulmonary failure after PEA: patients with a more compromised preoperative hemodynamic profile and distal thromboembolic lesions are at high risk of the need for ECLS. Multiple strategies are available for treatment and there is no consensus about the optimal approach: timely and tailored approaches offer the best results.