The Expert Clinician

CASE CONFERENCES The Expert Clinician Section Editors: Peter Clardy, M.D., and Charlie Strange, M.D.

A Young Man with a Mediastinal Mass and Sudden Cardiac Arrest Matthew W. Vanneman, Karim Fikry, Sadeq A. Quraishi, and William Schoenfeld Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts ORCID ID: 0000-0003-3877-782X (M.W.V.).

In Brief A previously healthy 23-year-old man presented to the emergency department with dyspnea and orthopnea and was found to have a large mediastinal mass on computed tomographic imaging of the chest. Diagnostic evaluation revealed T-cell acute lymphoblastic leukemia. He was hemodynamically stable and requiring intermittent continuous positive airway pressure, when shortly after receiving his first dose of chemotherapy, he developed respiratory distress before rapidly progressing to a pulseless arrest.

Case Vignette A previously healthy 23-year-old man presented to a nearby emergency department complaining of worsening dyspnea and orthopnea. Respiratory symptoms progressed over 4 weeks, requiring him to sleep upright in a reclining chair for the previous week. He denied fever, cough, chest pain, or lower extremity edema. A basic metabolic panel and complete blood count were normal. Arterial blood gas tensions measured while the man breathed ambient air showed a pH of 7.41, PaCO2 of 28 mm Hg, and PaO2 of 89 mm Hg. A chest radiograph showed

mediastinal widening, and chest computed tomography (CT) revealed a 10 3 13 3 16 cm anterior mediastinal mass with severe compression of the trachea, superior vena cava, and left upper and lower lobes (Figure 1). He was transferred to the surgical intensive care unit at our hospital for further management. On Hospital Day 1, a biopsy was obtained from the mediastinal mass. Examination of frozen sections suggested T-cell acute lymphoblastic leukemia (T-ALL). A transthoracic echocardiogram (TTE) demonstrated a small pericardial effusion but was otherwise normal. He was evaluated by the oncology service. Given his profound tracheal compression and potential airway compromise, a decision was made to start chemotherapy before final pathologic diagnosis. On Hospital Day 3, a peripherally introduced central venous catheter was placed for induction chemotherapy. Thirty minutes after receiving doxorubicin, vincristine, and methylprednisolone, the patient complained of dizziness and nausea. He became disoriented, diaphoretic, and tachypneic. His heart rate was 114 beats/min and his blood pressure was 62/38 mm Hg. His arterial oxygen saturation was 96% on supplemental oxygen at a fraction of inspired oxygen of 1.0 administered via a face mask with continuous

positive airway pressure at 5 cm H2O. An electrocardiogram showed sinus tachycardia without conduction abnormalities or ST-T wave changes. Five minutes later, despite escalating doses of phenylephrine and epinephrine for hemodynamic support, the patient became unresponsive and pulseless.

Questions 1. What are the most likely causes of cardiac arrest in this patient? 2. What are the best diagnostic methods to differentiate reversible causes of cardiac arrest in patients with a mediastinal mass? 3. What therapeutic interventions should be considered? [Continue onto next page for answers]

(Received in original form April 12, 2015; accepted in final form June 23, 2015 ) Supported by the U.S. National Institutes of Health (grant #L30 GM102903; S.A.Q.). Correspondence and requests for reprints should be addressed to Matthew Vanneman, M.D., Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine, 55 Fruit Street, Gray-Bigelow 444, Boston, MA 02114. E-mail: [email protected] This article has an online supplement, which is accessible from this issue’s table of contents online at www.atsjournals.org Ann Am Thorac Soc Vol 12, No 8, pp 1235–1239, Aug 2015 Copyright © 2015 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201504-212CC Internet address: www.atsjournals.org

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CASE CONFERENCES Diagnostic Reasoning

Figure 1. Computed tomographic scan of the patient’s chest with intravenous contrast. (A) Axial view cephalad to the tracheal bifurcation. Note the large mediastinal mass (MM), compressing the trachea (white arrow). (B) Coronal view. The mass severely compresses the left lung (black arrow), left innominate vein, and superior vena cava (white arrow).

Rapid diagnosis of reversible causes of cardiovascular collapse in a patient with a mediastinal mass is critical to guide prompt, corrective therapeutic intervention. Possible etiologies of cardiac arrest in our patient included (1) pericardial effusion causing tamponade physiology; (2) direct cardiac compression by the mediastinal mass; (3) hypoxic cardiac arrest from tracheal compression; (4) positional superior vena cava syndrome causing decreased venous return; (5) massive pulmonary embolism (PE); (6) anaphylaxis or a malignant arrhythmia related to one of the chemotherapeutic agents; or (7) chemotherapy-induced stress cardiomyopathy (also known as takotsubo cardiomyopathy) (1–5). Given the broad differential diagnosis, we prioritized TTE for initial assessment of this patient’s hemodynamic status. Bedside TTE can be pivotal in differentiating the cause and directing treatment of cardiac arrest of unclear etiology (6). Possible TTE findings that may have guided therapy in this patient include (1) tamponade physiology and cardiac compression with or without pericardial effusion, (2) signs of right heart strain and dysfunction consistent with a massive pulmonary embolism, (3) a hyperdynamic left ventricle with low filling volumes and collapsibility of the inferior vena cava suggestive of anaphylaxis, (4) poor right atrial and

Table 1. Causes of cardiac arrest, transthoracic echocardiogram findings, and therapeutic interventions in mediastinal mass syndrome Cause of Cardiac Arrest Cardiac tamponade from pericardial effusion Cardiac compression from mass Massive PE Anaphylaxis Dynamic SVC syndrome Stress (takotsubo) cardiomyopathy

TTE Findings

Therapeutic Interventions

Pericardial effusion with diastolic collapse of RA and/or RV Obliteration of RA and/or RV chamber preventing RV filling, RVOT obstruction Dilated, hypokinetic RV with contractile apex (“McConnell’s sign”), interventricular septal flattening Low end-diastolic LV volume, hyperdynamic LV, IVC collapsibility RA inflow tract obstruction, underfilled RV Depressed LVEF, LV apical wall motion abnormalities, and akinesis (“apical ballooning”)

Emergency pericardiocentesis or pericardial window, emergency ECLS Positional change, emergency surgical debulking, emergency ECLS Anticoagulation, thrombolysis, surgical thrombectomy, emergency ECLS Epinephrine, diphenhydramine, and glucocorticoid administration, emergency ECLS Positional change, SVC stenting, emergency ECLS Intraaortic balloon pump, emergency ECLS

Definition of abbreviations: ECLS = extracorporeal life support; IVC = inferior vena cava; LV = left ventricle; LVEF = left ventricular ejection fraction; PE = pulmonary embolism; RA = right atrium; RV = right ventricle; RVOT = right ventricular outflow tract; SVC = superior vena cava; TTE = transthoracic echocardiogram.

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CASE CONFERENCES right ventricular filling associated with dynamic superior vena cava collapse, or (5) a poorly contractile left ventricle with a severely depressed ejection fraction and a dilated, akinetic cardiac apex indicative of stress cardiomyopathy (Table 1).

patient was cannulated for venoarterial ECLS during CPR, 54 minutes after the initiation of CPR. A transesophageal echocardiogram visualized thrombus in the main, left, and right pulmonary arteries, and a CT angiogram ultimately confirmed a saddle embolus (Figure 3).

Subsequent Clinical Course and Diagnosis

Discussion

After acute decompensation, the patient received cardiopulmonary resuscitation (CPR), 2 L of lactated Ringer’s solution, 25 mg of intravenous diphenhydramine, 100 mg of intravenous hydrocortisone, and 2 mg of intravenous epinephrine, with a return of spontaneous circulation within 5 minutes. Bedside echocardiography demonstrated a markedly dilated, hypokinetic right ventricle with preserved apical contractility (McConnell’s sign), intraventricular septal deviation into the left ventricle, a poorly filled left ventricle, and a small pericardial effusion without tamponade or cardiac compression from the mass (Figure 2; and see Videos E1–E3 in the online supplement). Given evidence of right ventricular failure not observed on the admission TTE, massive pulmonary embolism was considered the most likely diagnosis. During the echocardiographic examination, the patient’s blood pressure dropped to 63/42 mm Hg. Despite ongoing vasopressor support with epinephrine and norepinephrine, he progressed to a pulseless electrical activity cardiac arrest. Advanced cardiac life support was restarted and he was intubated for mechanical ventilation. Emergency thrombolysis with tissue plasminogen activator was considered; however, because the patient was in persistent circulatory arrest refractory to vasopressor therapy requiring continuous CPR, it seemed unlikely that thrombolysis alone would quickly lyse sufficient thrombus to allow for a return of spontaneous circulation. Furthermore, given prolonged CPR, it was also likely that even successful thrombolysis would result in a stunned, poorly contractile myocardium requiring substantial circulatory support. Accordingly, an emergency extracorporeal life support (ECLS) consultation was requested. The

A massive mediastinal mass represents an uncommon but potentially deadly clinical entity. Clinical symptoms of an anterior mediastinal mass may include facial swelling from impaired venous drainage from the superior vena cava, dysphagia from esophageal narrowing, or dyspnea secondary to pericardial effusion, cardiac compression, or dynamic tracheal stenosis (1). Symptoms of orthopnea are particularly ominous, suggesting significant tracheal compression and a high risk for mediastinal mass syndrome (2). Mediastinal mass syndrome is characterized by acute respiratory and cardiovascular decompensation on initiation of positive pressure ventilation (2). Positive pressure ventilation impairs cardiac output by increasing intrathoracic pressure and blunting venous return. A mediastinal mass is often associated with a pericardial effusion, or may exert direct compression of the superior vena cava, right ventricle, or right ventricular outflow tract, resulting in tamponade-like physiology (1). Ample venous return is critical for maintaining adequate cardiac output in the setting of extrinsic cardiac compression, and positive pressure ventilation may result in refractory hypotension and cardiovascular collapse (7). Mediastinal mass syndrome may also cause tracheal or bronchial compression, resulting in poor ventilation, : : V/Q mismatching, refractory hypoxemia, and cardiac arrest. Double-lumen endotracheal tubes may stent open areas of tracheal and bronchial compression, ensure adequate ventilation, correct hypoxemia, and reverse hypoxemic cardiac arrest in such cases (8). Hypercoagulability, from an underlying malignancy, may also contribute to cardiovascular collapse in patients

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Figure 2. Transthoracic echocardiography after return of spontaneous circulation. (A) Apical four-chamber view demonstrates an enlarged right ventricle (RV) with bowing of the intraventricular septum (IVS) into the left ventricle (LV) during systole. (B) Parasternal short axis view at the midpapillary level shows RV dilation, IVS bowing, and LV compression (“D-sign”). (C) Subxiphoid view also shows an enlarged RV with deviation of the IVS into the LV during systole. EFF = pericardial effusion; LA = left atrium; LIV = liver; RA = right atrium.

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CASE CONFERENCES CPR, with survival rates ranging from 62 to 73% (13). In cardiac arrest from mediastinal mass syndrome, early ECLS should be considered to restore circulation and potentially improve mortality as well as neurologic outcome. If cardiovascular collapse is multifactorial, it is likely that no single intervention such as pericardiocentesis, thrombolysis, superior vena cava stenting, or endotracheal intubation may be sufficient to restore spontaneous circulation. The time required to diagnose the cause of cardiovascular collapse and successfully execute multiple life-saving interventions may result in devastating neurologic sequelae or death. Furthermore, when cardiac arrest in mediastinal mass syndrome is secondary to direct cardiac compression, CPR is unlikely to provide effective circulatory support, as chest compressions will cause the mass to collapse the right ventricle, preventing right ventricular filling. In this situation, ECLS is the only modality available to restore circulation and prevent death. When the cause of cardiac arrest in mediastinal mass syndrome is uncertain, immediate ECLS cannulation should be considered to provide circulatory support and maximize the chance of a meaningful neurologic recovery.

Figure 3. Computed tomographic scan of the patient’s chest with intravenous contrast after stabilization with extracorporeal life support. (A) Axial view at the level of the pulmonary artery bifurcation. Note the near-complete contrast filling defect in both the left and right pulmonary arteries, suggestive of a saddle pulmonary embolism (arrows). Also note the massively dilated pulmonary artery (PA), which is 1.5-fold larger than the adjacent aorta (Ao). (B) Axial view at level of right and left ventricles (RV and LV, respectively). The RV is dilated with intraventricular septal flattening and poor contrast flow into the LV, secondary to acute RV failure.

with a mediastinal mass. ALL is associated with an up to 20% risk of venous thromboembolism, with the most common type being an upper extremity deep venous thrombosis associated with a central venous catheter (9). Massive pulmonary embolism may result in cardiovascular collapse secondary to acute right-heart failure. TTE may help diagnose mediastinal mass syndrome in patients too unstable for other imaging modalities (10). Echocardiographic signs of right ventricular dilation, dysfunction, and intraventricular septal bowing or flattening are suggestive of a massive PE, 1238

especially in the setting of new-onset hypotension (11). Patients requiring cardiopulmonary resuscitation secondary to massive PE have an estimated in-hospital mortality as high as 65% (12). Treatment options for massive PE include anticoagulation alone or in combination with systemic thrombolysis, catheter-directed thrombolysis, surgical pulmonary embolectomy, and ECLS. ECLS offers the potential advantage of prompt return of circulation and perfusion while other treatment modalities are instituted. ECLS has shown promise in two large case series of patients with massive PE requiring

Answers 1. What are the most likely causes of cardiac arrest in this patient? The cause of cardiac arrest was massive pulmonary embolism. 2. What are the best diagnostic methods to differentiate reversible causes of cardiac arrest in patients with a mediastinal mass? Bedside echocardiography can rapidly distinguish causes of cardiac arrest and guide clinical management. 3. What therapeutic interventions should be considered? Extracorporeal life support can stabilize patients with massive pulmonary embolism and allow time to address the underlying causes of cardiac arrest in mediastinal mass syndrome.

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CASE CONFERENCES Follow-Up While receiving ECLS, the patient underwent catheter-directed thrombolysis on Postarrest Day 1, Hospital Day 5. A follow-up echocardiogram obtained on Hospital Day 7 demonstrated improvement of the pericardial effusion and biventricular function. After the patient was decannulated from ECLS and extubated, he awoke and was appropriately interactive. He was transferred to the oncology service on Hospital Day 23 to receive chemotherapy for T-ALL. The patient was discharged home on Hospital Day 40.

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Bedside echocardiogram can rapidly distinguish among various causes of reversible cardiac arrest and directs real-time clinical decision making. ECLS can provide hemodynamic support for patients with massive pulmonary embolism and cardiac arrest while awaiting definitive therapy with improved mortality and good neurologic outcomes.

References 1 Blank RS, de Souza DG. Anesthetic management of patients with an anterior mediastinal mass: continuing professional development [article in English, French]. Can J Anaesth 2011;58:853–859, 860–867. 2 Erdos ¨ G, Tzanova I. Perioperative anaesthetic management of mediastinal mass in adults. Eur J Anaesthesiol 2009;26:627–632. 3 Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology 2010;115:155–162. 4 Smith SA, Auseon AJ. Chemotherapy-induced takotsubo cardiomyopathy. Heart Fail Clin 2013;9:233–242, x. 5 Kitazawa S, Kitazawa R, Kondo T, Mori K, Matsui T, Watanabe H, Watanabe M. Fatal cardiac tamponade due to coronary sinus thrombosis in acute lymphoblastic leukaemia: a case report. Cases J 2009;2:9095. 6 Walley PE, Walley KR, Goodgame B, Punjabi V, Sirounis D. A practical approach to goal-directed echocardiography in the critical care setting. Crit Care 2014;18:681. 7 Rath L, Gullahorn G, Connolly N, Pratt T, Boswell G, Cornelissen C. Anterior mediastinal mass biopsy and resection: anesthetic

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Patients with hemodynamic collapse from mediastinal mass syndrome may benefit from emergency ECLS as CPR may be ineffective, cardiogenic shock is often multifactorial, and no single intervention may promptly restore spontaneous circulation. n

Author disclosures are available with the text of this article at www.atsjournals.org. Acknowledgment: The authors thank Arielle Butterly, M.D., for thoughtful comments on and revisions of this manuscript.

techniques and perioperative concerns. Semin Cardiothorac Vasc Anesth 2012;16:235–242. Lee J, Rim YC, In J. An anterior mediastinal mass: delayed airway compression and using a double lumen tube for airway patency. J Thorac Dis 2014;6:E99–E103. Vu K, Luong NV, Hubbard J, Zalpour A, Faderl S, Thomas DA, Yang D, Kantarjian H, Kroll MH. A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center. Cancer Med 2015;4:27–35. Chung-Esaki H, Knight R, Noble J, Wang R, Coralic Z. Detection of acute pulmonary embolism by bedside ultrasound in a patient presenting in PEA arrest: a case report. Case Rep Emerg Med 2012; 2012:794019. Perera P, Lobo V, Williams SR, Gharahbaghian L. Cardiac echocardiography. Crit Care Clin 2014;30:47–92, v. Sanchez O, Planquette B, Meyer G. Management of massive and submassive pulmonary embolism: focus on recent randomized trials. Curr Opin Pulm Med 2014;20:393–399. Yusuff HO, Zochios V, Vuylsteke A. Extracorporeal membrane oxygenation in acute massive pulmonary embolism: a systematic review. Perfusion (In press)

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