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:Fulminant pulmonary embolism successfully treated with thrombolysis

Franco Casazza M.D, Amedeo Bongarzoni M.D,., Giuseppe Guenzati M.D., Guido Tassinario M.D., Antonio Mafrici M.D. 
Department of Cardiology,  Ospedale San Carlo Borromeo  - Milano.

















For correspondence : Franco Casazza MD, Via Nikolajevka 12,20152, Milan, Italy.
E-mail: franco.casazza@fastwebnet.it





Keywords: pulmonary embolism; echocardiography cardiorespiratory  arrest; cardiopulmonary resuscitation, alteplase



Abstract

Objective.  To describe the case of a patient successfully resuscitated with a double bolus  of  alteplase for a high- risk pulmonary embolism (PE) complicated by cardiac arrest.
Case summary. A 70 year-old man, with a history of major depression and arterial hypertension, was admitted to the emergency department for severe hypotension and  suspected abuse of anti anxiety drugs. Due to the rapid deterioration of his clinical conditions a bed-side echocardiography was rapidly performed, that was  compatible with acute pulmonary embolism,. During  echocardiography, the patient developed a  pulseless electrical activity with residual cardiac contractility (pseudo PEA)  that evolved into pulseless electrical activity without cardiac contractility  (true PEA).  After 20 minutes of cardiopulmonary resuscitation (CPR), empirical alteplase 50 mg  + 50 mg was administered intravenously over 5 minutes, with restoration of spontaneous circulation. PE was confirmed by computed tomographic angiography. His hospital stay was complicated by non-hemorrhagic neurological impairment that resulted in quadriplegia.
Conclusion. In patients presenting with fulminant PE, early thrombolysis during CPR manoeuvres may be effective in reducing the mortality rate.



Fulminant pulmonary embolism (FPE) can be defined as a sudden circulatory collapse  usually associated with cardiac arrest (CA) resulting in extremely high mortality rates, estimated between 65% and 95%.
The suggested mechanisms of CA are as follows: 1) obstructive shock with severe dysfunction  of the right ventricle, possibly causing coronary insufficiency and acute myocardial infarction (AMI);  2) arrhythmias, presumably caused either by the cardiac strain or by myocardial ischemia or AMI;  3) a vasovagal reflex produced by the impact of the embolism on the pulmonary arteries, inducing a high-grade block or asystole (7). Although FPE can cause any type of CA, the commonest presentations are asystole and pulseless electrical activity (PEA) (1). At the onset of CA, external cardiac massage (ECM) can be effective, at least experimentally (2), by fragmenting the large embolisms and thus freeing the pulmonary artery and re-establishing spontaneous circulation. However, when the obstruction of the pulmonary circulation is total, ECM may fail and �desperate measures� can be attempted, including systemic thrombolysis, emergency thoracotomy, femoro-femoral cardiopulmonary bypass, embolectomy, or other mechanical approaches (3). Among these measures, thrombolysis is the most feasible therapy, because of its rapid administration and action and its easy availability.
We describe a  case of a patient with FPE,  successfully treated with a  thrombolysis  and resuscitation manoeuvres.

Case study. An overweight  70-year-old man  with a history of major depression and hypertension, was admitted to the emergency department for severe hypotension, and  suspected abuse of anti anxiety drugs. He was taking lisinopril, amlodipine, nebivolol, sertraline, pramipexole, valproic acid and diazepam.
At admission, the patient was pale and diaphoretic with a systolic blood pressure of 70 mmHg,  a heart rate of 120 beats/min and a respiratory rate of 30 breaths/min. The initial electrocardiogram (ECG) showed  sinus tachycardia , incomplete RBBB, S1-Q3 pattern  and T wave inversion in leads V1-V4.  SpO2 was 80%, pH 6.9, PaCO2 20 mm Hg, and PaO2 50 mm Hg.  Bedside echocardiography revealed  a massively dilated and hypokinetic right ventricle with a diskynetic iv septum and a small,  vigorously contracting left ventricle. A presumptive diagnosis of massive pulmonary embolism was made and 7.000 units of unfractionated iv heparin were promptly administered . While performing  echocardiography, he had a CA with a documented pulseless electrical activity with residual mild cardiac contractility (pseudo PEA) (video 1) which evolved into a pulseless electrical activity without cardiac contractility (true PEA). Appropriate cardiopulmonary resuscitation (CPR) was started and  was continued for twenty minutes, along with a total dose of 10 mg of  iv epinephrine.  Empirical alteplase 50 mg + 50 mg was administered intravenously over 5 minutes with restoration of spontaneous circulation (ROSC), 5 minutes after the last bolus. The subsequent clinical course was complicated by ventricular tachycardia degenerated into ventricular fibrillation, treated with DC shock 300 J. The echocardiography showed a recovery of myocardial contractility (video 2). When stable conditions were achieved,  a contrast computed tomography demonstrated extensive proximal and  bilateral pulmonary emboli (Fig 1) and the patient was transferred to the general intensive care unit. Echocardiography  performed 24 hours after the CA showed a moderately dilated-hypokynetic right ventricle and a paradoxical septal motion indicating  a residual right ventricular pressure overload . A brain scan excluded intracranial hemorrhage. His hospital stay was complicated by non-hemorrhagic neurological complications that resulted in quadriplegia. One month after admission, the patient was transferred to a neurological rehabilitation unit.

Discussion
The management of patients presenting with acute PE must be tailored according to the PE risk categories.  Patients with high-risk PE should be considered for aggressive therapy to reduce the risk of short-term mortality. At the moment,  alteplase is the only approved tissue plasminogen activator for PE treatment and is the most commonly used and investigated agent: the approved regimen is the i.v. infusion of 100 mg over 2 hours. In the setting of CA, however, the ability to administer alteplase as a bolus is attractive, given that CPR will likely not be continued for the duration of the 2 hour alteplase infusion in cases where ROSC has not been obtained. One alteplase dose that has been evaluated and compared with the approved 100 mg over 2 hours regimen is 0.6 mg/kg (maximum 50 mg) bolus dose given over 2 to 15 minutes. The most recent American College of Chest Physician guidelines state that bolus administration is indicated in PE-associated cardiac arrest (4) . Various alteplase dosing schemes have been successfully reported in the literature in FPE while receiving CPR, including  a) a single bolus of 50 mg or 100 mg, b) 0.6 to 1 mg/kg (maximum  dose of 100 mg), c) a double bolus of 50 mg (total 100 mg) separated by 15 to 30 minutes (5). Because of  lack of head-to head comparisons, it is unclear  which regimen has the most favorable efficacy-to-safety profile. The overall evidence suggests that fibrinolysis may be beneficial in achieving ROSC in FPE patients, reducing mortality, and preserving neurological function even in cases of prolonged CPR. This efficacy does not appear to be counterbalanced by an excessive risk of fatal bleeding. The quality of the current literature, however, precludes any firm conclusions from being drawn. The present case has the  distinctive features to demonstrate the lifesaving effect of a double thrombolytic bolus, along with the CPR manoeuvres,  in restoring a spontaneous cardiac rhythm in a patient  with massive PE and PEA and the major role of the bedside echocardiography. This ready to use examination made it possible to correctly diagnose the aetiology of the dramatic clinical picture and to promptly start the rescue treatments. Echocardiography documented  the progressive  loss of cardiac  contractility which ended  to a complete mechanical arrest  and the recovery of wall motion after thrombolysis and CPR. No bleeding complications occurred despite a vigorous cardiac massage. 




References

1. Charlap S, Kahlam S, Lichstein E, et al: Electromechanical dissociation: diagnosis, pathophysiology, and management. Am Heart J 1989; 118:355�360.
2. Borst RH First results of emergency treatment in massive fulminant lung embolism by means of a rapidly injected streptokinase in a high initial dose. Anaesthesist 1980; 29:39�45.
3. Kurose M, Okamoto K, Sato T, et al: Extracorporeal life support for patients undergoing prolonged external cardiac massage. Resuscitation 1993; 25:35�40
4. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy
for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e419S-e494S.
5. Ruiz-Bailen M, Ramos Cuadra JA, Aguayo-de-Hoyos E. Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: A review
 Crit Care Med 2001; 29:2211�2219. 





FIGURE LEGEND

Fig 1: extensive proximal and  bilateral pulmonary emboli at computed tomographic angiography

















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