Zhi-rong Zhang, Xia-qing Zhou, Zhao-kun Fan, Yin Shi, Ying-ying Shen, Chen Zhu, Wen Feng, Ling-cong Wang

1 Department of Intensive Care Unit, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China

2 Zhejiang Chinese Medical University, Hangzhou 310053, China

3 Department of Intensive Care Unit, the First Affiliated Rehabilitation Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310023, China

Dear editor,

A 21-year-old male student was admitted to the emergency department of our hospital due to chest distress, dyspnea for 1.5 hours, and loss of consciousness for one minute. Before admission, the patient had been advised rest for two months because of left ankle sprain, leading to less activity. At admission, the patient was unconscious, with facial cyanosis, and his limbs were cold. The heart rate (HR), blood pressure (BP), respiratory rate (RR), and pulse oxygen saturation (SPO2) were 146 beats/minute, 88/74 mmHg (1 mmHg=0.133 kPa), 27 breaths/minute, and 72%, respectively. Tracheal intubation was immediately performed and blood pressure was maintained at 80/65 mmHg with norepinephrine at a dosage of 2.08 mg/(kg·minute). However, the patient’s condition worsene d rapidly with two successive cardiac arrests. The return of spontaneous circulation (ROSC) was achieved after external chest compression (the fi rst set of chest compression lasted for ＞10 minutes and defi brillation was performed twice; the second set of chest compression lasted for few minutes). Laboratory data were obtained in succession. The arterial blood gas showed pH 6.866, partial pressure of carbon dioxide (PCO2) 73.4 mmHg, partial pressure of oxygen (PO2) 422 mmHg, standard bicarbonate (SB) 9.2 mmol/L, base excess (BE) -21.9 mmHg, lactic acid 14.8 mmol/L, and oxygen saturation 100%. General coagulation tests showed normal fi brinogen, activated partial thromboplastin time (APTT), thrombin time, prolonged prothrombin time (PT, 15.9 seconds), international normalized ratio (INR, 1.35), and increased D-dimer (DD, 15.43 mg/L fibrinogen equivalent units [FEU]). The level of troponin I was 1.4 mg/L. The electrocardiogram showed sinus tachycardia and SITIIIQIII. Bedside transthoracic echocardiography showed that the range of left ventricular ejection fraction was 70%, and pulmonary artery systolic pressure was 34 mmHg, with decreased systolic function and mild tricuspid regurgitation, without obvious enlargement of the right ventricle. Compression venous ultrasonography showed that deep veins of both lower extremities were filled without interruption. Therefore, the patient was considered to be at a high risk for acute pulmonary embolism (PE). Because of the extremely unstable hemodynamics, computed tomography pulmonary angiography (CTPA) was not performed immediately. The patient received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) insertion. Then, arterial perfusion cannula (Edwards Lifesciences, 18 Fr) was placed into the right femoral artery, and femoral venous cannula (Edwards Lifesciences, 22 Fr) was placed into the left femoral vein. Heparin was administered as an anticoagulant at 0.5 mg/kg for initiation of ECMO and subsequently at 2-20 mg/hour to maintain APTT in the range of 45-70 seconds. After ECMO, the norepinephrine dose decreased rapidly. In addition, transthoracic echocardiography showed dilatation of the right heart, mild pulmonary hypertension (pulmonary artery systolic pressure of 44 mmHg), and normal left ventricular function. Combined with ECMO, CTPA examination showed embolization of the lower-left pulmonary artery (Figure 1A), the middle and inferior lobe arteries of the right lung (Figure 1B), and their branches. After 38 hours of ECMO support, norepinephrine was discontinued and hemodynamics was stabilized. Subsequently, the ECMO was successfully removed after running for 63 hours, and 800 mL of red blood cells (RBCs) were administered because of blood loss. Heparin was continued for seven days as the anticoagulation therapy before changing to low-molecular-weight heparin (LMWH) (enoxaparin, Sanofi , 0.4 mL for q12h). On day 9 after admission, the reexamination of CTPA showed a signifi cant reduction in embolism as compared to the previous level. Moreover, transthoracic echocardiography showed normal cardiac atrioventricular size, mild tricuspid regurgitation, normal left ventricular diastolic and systolic functions, and pulmonary artery systolic pressure of 20 mmHg. After 14 days in the intensive care unit, the patient was transferred to the general ward due to improvement in his condition and the treatment was replaced with rivaroxaban for anticoagulation at 15 mg bid for three weeks, which was subsequently adjusted to 20 mg qd. Finally, he was discharged from the hospital on September 30, 2019. On December 27, 2019, the reexamination of CTPA did not show any signs of vascular stenosis (Figures 1C and D). The echocardiogram showed mild tricuspid regurgitation and pulmonary artery systolic pressure of 27 mmHg. Laboratory indexes of thrombophilia revealed that lupus anticoagulant, protein C, protein S, and antithrombin III were normal, and no variation was found in the whole exon sequencing of the patient. Hence, after three months, anticoagulation therapy was discontinued. The follow-up for five months showed no chest distress or dyspnea, but decreased activity endurance in the patient.

Figure 1. Results of computed tomography pulmonary angiography. A: embolization of the lower-left pulmonary artery (red arrow); B: embolization of the middle and inferior lobe arteries of the right lung (red arrow); C and D: no sign of pulmonary embolism.

DISCUSSION

High-risk PE with cardiac arrest is a critical condition. Thrombolytic therapy can improve pulmonary perfusion, reverse the right ventricular dysfunction,[1]and prevent the escalation of therapy in patients with acute PE.[2]Most guidelines recommend that thrombolysis is beneficial for patients with acute PE and hypotension, and is a widely accepted indication.[3,4]However, thrombolytic therapy is associated with increased risk of hemorrhage.[5]A previous study evaluated 104 patients who received alteplase for acute PE, and major bleeding occurred in 19.2% (20/104) of patients.[6]Another study also showed that the use of thrombolytics was associated with the risk of bleeding.[7]Prolonged external chest compression and catecholamine administration for systemic arterial hypotension were independent predictors of hemorrhage.[3,6]However, severe high-risk PE often requires high doses of catecholamine and even results in cardiac arrest followed by prolonged external chest compression. Clinicians are often hesitant to administer thrombolytic therapy, even in the highest-risk PE patients, because of the concern of major bleeding.

Despite the high risk of bleeding, thrombolytic therapy is recommended for patients with high-risk PE, especially those with severe shock and cardiac arrest. However, clinicians can wait when ECMO is working.[8]After full anticoagulation, the body’s fibrinolysis mechanism dissolves the fi brin and the clot. In patients unresponsive to anticoagulation, ECMO can serve as a bridge to other defi nitive advanced therapies (for example, thrombolysis orthromboembolectomy) to reduce the thrombus burden. Thus, most bleeding complications of thrombolysis can be avoided. Strikingly, ECMO needs anticoagulation similar to the thrombolysis strategy, in addition to the risk of bleeding. In the 13 studies published after 2009, 8% of major bleeding complications were observed if patients received anticoagulation for a low target APTT (＜60 seconds).[9]The incidence rate of severe bleeding events per 100 extracorporeal life support (ECLS) days was 19 events for patients with veno-arterial (VA) ECLS in a study among adult patients who had ECLS between March 1, 2010, and August 15, 2013.[10]ECMO in most high-risk PE patients can be withdrawn in 3-6 days.[11,12]The risk associated with ECMO is relatively limited.

Major bleeding events may have occurred if thrombolysis was conducted in our patient with cardiac arrest due to prolonged external chest compression and a high dose of catecholamines for systemic arterial hypotension. In a study of 10 cases, including nine patients with massive PE and cardiac arrest, all patients underwent thrombolysis before ECMO and developed bleeding complications (including puncture site, surgical wound, pelvic area, and hemothorax).[13]If thrombolysis failed, it would prolong the inadequate tissue perfusion time, increase the possibility of multiple organ dysfunction syndrome, and reduce the success rate of cerebral resuscitation.

For patients who choose ECMO treatment, the risk of cannulation-related injury and catheter-related blood stream infection will increase. In addition, the cost of ECMO is higher than that of thrombolytic therapy, which has to be considered in patients with limited economic resources.

CONCLUSIONS

Early ECMO therapy should be considered in highrisk PE patients complicated with cardiac arrest, if appropriate expertise and resources are available.

Funding:None.

Ethical approval:Not needed.

Conflicts of interests:The authors declare that they have no competing interests.

Contributors:ZRZ and XQZ contributed equally to this work. All authors contributed substantially to the writing and revision of this manuscript and approved of its contents.