a b s t r a c t

A triad of circulatory collapse, right ventricular dilatation, and large alveolar dead space is proposed for the rapid diagnosis and treatment of massive pulmonary embolism. A 17 year-old female on oral contraceptives collapsed at home becoming incoherent with shallow breathing. Paramedics initiated Mechanical chest compression and transported the patient to our emergency department, arriving minimally responsive with undetectable blood pressure but having positive corneal reflexes and bradycardia with wide QRS. The trachea was intubated and goal-directed echocardiography revealed marked right ventricular dilatation with septal flattening. The arterial PCO₂ was 40 mmHg with an end-tidal PCO₂ of 8 mmHg, revealing a large alveolar dead space. Persistent hypo- tension, bradycardia, and fading alertness despite epinephrine and norepinephrine infusions prompted resump- tion of chest compression. intravenous alteplase (10 mg bolus over 10 min followed by 90 mg over 110 min) begun 125 min after collapse improved hemodynamic function within 10 min allowing discontinuation of chest compression. Five and a half hours after starting alteplase, the patient was hemodynamically stable and had normal end-tidal PCO₂. A CT-angiogram showed the pulmonary arteries free of emboli but a thrombus in the right common iliac vein. The patient recovered fully and was discharged home on warfarin 8 days later. Based on this and other reports, we propose a triad of circulatory collapse, right ventricular dilatation, and large alveolar dead space for the rapid diagnosis and treatment of massive pulmonary embolism, with systemic fibrinolysis as the first-line intervention.

Circulatory collapse after massive pulmonary embolism is a life- threatening emergency [1]. We report a patient who arrived to our emergency department in circulatory collapse requiring chest compres- sion to sustain blood pressure and alertness in whom the triad of circu- latory collapse, right ventricular dilatation, and large alveolar dead space led to the rapid diagnosis and treatment of massive pulmonary embolism.

A 17-year old female on oral contraceptives for 7 months collapsed at home. Paramedics initiated chest compression using a LUCAS device. The patient arrived to our emergency department 43 min after collapse minimally responsive with undetectable blood pressure and pulse but with corneal reflexes. The ECG showed Right bundle branch block (RBBB) and bradycardia (Fig. 1). Tracheal intubation revealed an end- tidal PCO₂ (P_ETCO₂) b 10 mmHg and goal-directed echocardiography showed marked right ventricular dilatation with septal flattening and D-shaped left ventricle (Fig. 2 and Cardiac video). Epinephrine and nor- epinephrine infusions were started (Fig. 3). An arterial PCO₂ was

* Corresponding author at: Resuscitation Institute, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States.

E-mail address: [email protected] (R.J. Gazmuri).

40 mmHg with a P_ETCO₂ of 8 mmHg and lactic acidosis (Table 1). Persis- tent hypotension, bradycardia, and fading alertness prompted resump- tion of chest compression with LUCAS device. The P_ETCO₂ increased to 17 mmHg and alertness returned. A left femoral artery line was placed (Fig. 3). Alteplase was administered intravenously (10 mg over 10 min followed by 90 mg over 110 min) starting 125 min after collapse. Hemo- dynamic function improved within 10 min allowing discontinuation of chest compression. A CT-angiogram five and a half hours after starting alteplase showed the pulmonary arteries free of emboli but a right com- mon iliac vein thrombus. Before the CT-angiogram, her Blood pressure and heart rate had improved, the RBBB resolved, and the P_ETCO₂ in- creased to 33 mmHg. An echocardiogram showed normal left and right ventricular function. The patient was discharged home on warfarin 8 days later fully recovered.

Massive pulmonary embolism has an overall mortality of approxi- mately 30% approaching 70% if cardiac arrest occurs [1]. Most deaths occur within 1 h. A central feature is right ventricular dilatation with in- terventricular septal flattening resulting in a D-shaped left ventricle (Fig. 2 and Cardiac video) and impaired left ventricular filling. These fea- tures can be recognized by goal-directed echocardiography [2,3]. An- other central feature recognized nearly six decades ago by late

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Fig. 1. (A) Baseline lead II electrocardiogram recorded two months before the event. (B) Prehospital lead II electrocardiogram recorded the day of the event showing the initial rhythm upon arrival of the rescue crew and the last rhythm upon delivery of the patient to the emergency department 30 min later.

Professor Eugene D. Robin et al. [4,5] – though no sufficiently empha- sized today – is increased alveolar dead space. Alveoli that are ventilated and perfused return gas with essentially the same PCO₂ as the PaCO₂. Al- veoli that are ventilated but not perfused return gas that contains essen- tially no PCO₂ with the P_ETCO₂ reflecting their relative contributions. Alveolar dead space can be recognized by concurrently measuring PaCO₂ and P_ETCO₂ and its percentage (i.e., PaCO₂ – P_ETCO₂/PaCO₂ x 100) roughly reflecting the percentage of pulmonary circuit occluded [4,6,7].

Fig. 2. Parasternal short-axis view using a SonoSite X-Porte (FUJIFILM SonoSite, Inc.) upon arrival to the emergency department showing a dilated right ventricle with septal flattening resulting in a D-shaped left ventricle (also see Supplemental Cardiac video).

Chest compression with LUCAS device provided critical hemody- namic stability after failure of catecholamine infusion. The benefit likely resulted from assisting the right ventricle [8,9] and possibly from help- ing emboli fragmentation [8]. Yet, sustained hemodynamic stability oc- curred only after starting alteplase [10].

FDA approved agents for pulmonary embolism include alteplase, urokinase, and streptokinase. Alteplase is human tissue plasminogen activator and is administered intravenously (100 mg over 2 h optionally administering the initial 10 mg as bolus). Urokinase and streptokinase and are naturally occurring polypeptides administered as bolus follow- ed by a 12-h to 24-h infusion [11,12]. Alteplase is preferred given its shorter infusion time and faster clot lysis with lower bleeding rate [13]. Alteplase has an initial half-life of 5 min and a fibrinolytic activity that persists for approximately 1 h after infusion [14]. The risk of bleed- ing is outweighed by the risk of death even if CPR is required [15-18]. Use of systemic fibrinolysis as First-line treatment has been recom- mended for massive pulmonary embolism and circulatory collapse [1], without precluding subsequent interventions – e.g., direct pulmonary artery fibrinolysis or pulmonary embolectomy.

The absence of pulmonary artery Filling defects and hemodynamic

improvement five and a half hours after initiation of alteplase suggests that emboli detectable by CT-angiography had already lysed. Our pa- tient was on oral contraceptives, known to promote thrombophilia [19,20]. We postulate that a freshly formed Venous thrombus embolized and was rapidly lysed by alteplase. In a mouse model of carotid Artery thrombosis and in patients with stroke, the thrombus age was shown to be an important time determinant for the beginning of vascular re- canalization and for the rate of complete recanalization after fibrinolysis [21]. Most patients with acute stroke had good-to-moderate thrombus resolution after 60 min when alteplase was started within 121- 150 min of symptom onset.

R.J. Gazmuri et al. / American Journal of Emergency Medicine 35 (2017) 936.e1–936.e4 96.e3

Fig. 3. Hemodynamic and end-tidal PCO₂ (P_ETCO₂) changes in relation to chest compression using a LUCAS device, infusion of catecholamines, and administration of alteplase over four and half hours.

Table 1

arterial blood gases, P_ETCO₂, and arterial lactate

^a Estimation of the percentage of ventilated but not perfused lung (i.e., alveolar dead space).

Accordingly, a triad of Hemodynamic collapse, right ventricular dila- tation, and large alveolar dead space is proposed for the rapid diagnosis and treatment of massive pulmonary embolism. Chest compressions with a piston device could provide right ventricular assist while addi- tional interventions are performed. A short-acting fibrinolytic agent de- livered intravenously should be considered as first-line intervention without precluding additional interventions if systemic fibrinolysis fails. Supplementary data to this article can be found online at http://dx.

doi.org/10.1016/j.ajem.2016.12.039.

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