Salvage of venoarterial extracorporeal membrane oxygenation following prolonged cardiopulmonary resuscitation and failure of catheter-directed thrombectomy for massive pulmonary embolism in a young patient

Dear editor,

Acute massive pulmonary embolism (PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2] Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy. Moreover, extracorporeal membrane oxygenation (ECMO) has been increasingly used as a bridge in definitive therapy for patients with severe cardiopulmonary dysfunction.[3,4] However, ECMO serves as a remedy when there is no alternative in many cases. We presented a case of a young male with acute massive PE who received catheter-based therapies, developed cardiac arrest and received continuous cardiopulmonary resuscitation (CPR) for half an hour. Veno-arterial ECMO (VA-ECMO) was then adopted as a rescue strategy, and he finally survived. He was diagnosed with thrombophilia, a rare genetic condition associated with a higher risk of thrombogenesis.[5]

CASE

A 38-year-old normal-sized male presented to the emergency department (ED) complaining of 5 h of shortness of breath, chest discomfort, palpitation, nausea, and vomiting. He denied chest pain, cough, fever, syncope, light-headedness, changes in bladder or bowel habits, prolonged immobilization, or contact with sick persons. He had no other medical history. However, it is worth noting that his father died at the age of 52 without a specific reason, and his only elder brother also died suddenly at the age of 35.

Upon arrival, he was apyretic (36.7 °C), tachycardic (121 beats/min), normotensive (116/67 mmHg; 1 mmHg=0.133 kPa), and had an oxygen saturation (SO₂) <90% on room air; however, his SO₂ improved to 94% with a nasal tube when oxygen was supplied at 5 L/min. Initial arterial blood gas (ABG) analysis suggested a compensatory normal pH value of 7.41, with a slightly lower partial pressure of carbon dioxide (pCO₂) of 28 mmHg, actual bicarbonate of 21.1 mmol/L, and base excess (BE) of -6.9 mmol/L. The coronavirus disease 2019 (COVID-19) nasopharyngeal nucleic acid test was negative. An electrocardiogram (ECG) demonstrated sinus tachycardia, an S wave in lead I, and a Q wave and inverted T wave in lead III (S1Q3T3 pattern, Figure 1), suggesting acute PE. Initial troponin-I, hemoglobin, and creatine kinase-myocardial band isoenzyme (CK-MB) were negative. D-dimer was elevated at 5.58 mg/L (reference range ≤0.5 mg/L), and B-type natriuretic peptide (BNP) was elevated at 357 pg/mL (reference range ≤100 pg/mL). An initial computed tomography pulmonary angiogram (CTPA) confirmed massive embolism in the bilateral pulmonary arteries, including the central (supplementary Figure 1), segmental, and subsegmental branches.

Figure 1.

Initial electrocardiogram (ECG) on arrival. ECG demonstrated S wave in lead I, Q wave and inverted T wave in lead III (S1Q3T3), a pattern associated with acute pulmonary embolism.

The patient was taken to the Cath Lab of conducting a pulmonary angiogram that demonstrated bilateral PE. He underwent direct catheter-based thrombectomy of bilateral pulmonary trunks with an 8-F catheter, exporting only a tiny number of thrombi. Urokinase (250,000 U over 15 min) was administered, and thrombi were repeatedly aspirated utilizing the AngioJet™ Thrombectomy System (Boston Scientific, USA). During the procedure, the patient’s clinical condition gradually deteriorated, and the SO₂ decreased to 88%. His symptoms of chest tightness and shortness of breath were aggravated, and his consciousness was blurred. Oral endotracheal intubation and volume-controlled ventilation were performed immediately. Blood pressure decreased gradually, and high-dose norepinephrine was injected intravenously, but it was still lower than 90/60 mmHg. The catheterization procedure was then stopped, and the patient was transferred to the intensive care unit (ICU) for advanced life support. His condition worsened, and he developed cardiac arrest. After CPR lasted for nearly 33 min, he regained spontaneous heart rhythm, and his hemodynamics were temporarily stable. Bedside echocardiography showed right heart dilation, right ventricular free wall hypokinesis with sparing of the apex (McConnel’s sign, Figure 2A, supplementary Video 1), ventricular septal contradictory movement, and D-shaped left ventricle with limited filling (Figure 2B, supplementary Video 2).

Figure 2.

An emergency bedside echocardiography. Echocardiography demonstrated right heart dilation, right ventricular free wall hypokinesis with sparing of the apex (red arrow), McConnel’s sign (A), ventricular septal contradictory movement (yellow arrow) and D-shaped left ventricle (B), suggestive of right ventricular strain in the setting of pulmonary embolism. RV: right ventricle; RA: right atrium; LV: left ventricle; LA: left atrium.

Due to his persistent hypotension and hyperlactatemia with blood lactic acid (BLA) concentrations of 10.8–11.6 mmol/L (reference range 0.5–2.2 mmol/L), VA-ECMO (ROTA FLOW, Maquet, Germany) was initiated at bedside (pump speed 3,560 revolutions/min, blood flow 4.5 L/min, gas flow 3.5 L/min, fraction of inspired O₂ [FiO₂] 60%). Mechanical ventilation (A/C, tidal volume 400 mL, respiratory rate 12 breaths/min, positive end-expiratory pressure 5 cmH₂O [1 cmH₂O=0.098 kPa], FiO₂ 75%) was also supplied. The patient received continuous intravenous unfractionated heparin (UFH) infusion (goal activated coagulation time 180–220 s every 1 h, activated partial thromboplastin time 60–80 s every 4 h). Vasopressors were discontinued over the next 4 to 8 h, and ventilation parameters were improved, with BLA returning to normal. The patient was weaned off ECMO on hospital day 3 after 36 h. The anticoagulant regimen was transitioned to low-molecular-weight heparin (fraxiparine, 50 U/kg every 12 h). He was extubated on hospital day 7.

The remainder of the therapeutic course was unremarkable. He was transferred to the general medicine floor on hospital day 12 without supplemental oxygen and discharged on day 14 with an oral anticoagulant (warfarin 3.125 mg/d). He was able to perform activities of daily living independently. Before discharge, a repeat CTPA was conducted to show volume reduction of pulmonary emboli, especially the emboli in the left pulmonary artery. The patient had no significant adverse events during the six-month follow-up.

Meanwhile, preliminary screening of the hyper-coagulable workup, including plasma concentrations of cardiolipin antibodies and lupus anticoagulants, as well as plasma activities of plasminogen, protein C, protein S, antithrombin III, and α-2 plasmin inhibitor, demonstrated lower activity of protein C at 31% (Ref. 70%–140%), suggesting the possibility of thrombophilia. Therefore, further genetic tests of both the patient and his healthy 12-year-old son were performed. The genetic tests confirmed three gene mutations, including one reported heterozygous mutation (p. Cys426Tyr in the ninth exon of protein C, which leads to protein C deficiency [http://www.hgmd.cf.ac.uk/ac/all.php]) and another two heterozygous mutations (c.-1491G>A and p. Gly464Ser) in protein C and ADAMTS 13 (ADAM metallopeptidase with thrombospondin type 1 motif 13), respectively, which have not been reported (Figure 3).

Figure 3.

Potential heterozygous mutations for thrombophilia or anticoagulant deficiency in the patient and his healthy son. Genetic tests of both the patient and his healthy 12-year-old son for congenital thrombophilia confirmed three heterozygous gene mutations, two (p. Cys426Tyr and c.-1491 G>A) in protein C and one (p. Gly464Ser) in the ADAMTS 13 gene, respectively.

DISCUSSION

Massive PE carries a substantial mortality burden and can be treated conventionally with systemic thrombolysis as a first-line algorithm,[6] catheter-based therapies, surgical embolectomy, or no reperfusion antithrombotics. ECMO seemed to provide a bridge to additional life-saving measures, especially in patients with severe cor pulmonale,[7,8] and served as a bridge during pharmacological or mechanical thrombolysis or embolectomy.[9-11] Due to the variety of treatments available alone or in combination, the optimal strategies are still controversial and are being explored. A recent systematic review including 50 case series or case reports comprising 128 patients who required ECMO found that initiation of ECMO before systemic and catheter-directed thrombolytic was a safe and effective therapy and offered acceptable outcomes.[10]

Although no randomized controlled trials have compared ECMO with usual treatments for patients with massive PE, some retrospective studies have explored “real-world” data. A pilot multicenter series[9] of 180 cases (of which 128 cases were treated without ECMO and 52 underwent ECMO) found that the overall 30-day mortality was 43% in those without ECMO and 61.5% in those with ECMO, suggesting that ECMO does not appear justified as a stand-alone treatment. Additionally, the 30-day mortality was 29.4% for ECMO+surgical embolectomy, 76.5% for ECMO+fibrinolysis and 77.7% for ECMO alone, suggesting that ECMO showed promise as a complement to surgical embolectomy. Another large-sample study also analyzed the use and outcome of ECMO in the absence or presence of adjunctive treatment strategies.[4] When compared with thrombolysis alone, the analysis indicated lower in-hospital mortality in patients who received embolectomy+VA-ECMO (OR=0.50, n=385), thrombolysis+VA-ECMO (OR=0.60, n=165) or VA-ECMO alone (OR=0.68, n=588). This result suggested that the use of VA-ECMO alone or as a part of the reperfusion approach offers survival advantages compared with thrombolysis alone.

Table 1.

Hospitalization timeline of the patient and the significan clinical events

The present patient with massive PE failed either catheter-directed embolectomy or thrombolysis and even deteriorated to cardiac arrest, which required prolonged CPR. It seemed that VA-ECMO was the sole solution to support the patient’s vital signs. Additionally, it seemed that there were some proposed improvements for cath-based procedures. Indeed, the 8F cath is small for large thrombi. The newest model allows the positioning of 22F cath to remove large clots. AngioJet is controversial for PE in the US.

Only approximately 7.1% of PE patients have congenital thrombophilia.[5] Moreover, unlike white people, in whom factor V Leiden and prothrombin G20210A mutations account for >60% of thrombophilia cases, the most common types of thrombophilia in the Chinese population are deficiencies in protein S (42%) and protein C (39%). The present case had two heterozygous mutations in protein C, one of which has been reported. Another mutation in ADAMTS 13 was first found in Chinese PE patients, but its pathogenicity is unclear.

CONCLUSION

VA-ECMO was an effective rescue strategy for massive PE patients who survived prolonged cardiac arrest. Congenital thrombophilia needs to be examined, especially in young patients with thrombogenesis.