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Successful resuscitation with thrombolysis of a presumed fulminant pulmonary embolism during cardiac arrest
American Journal of Emergency Medicine (2013) 31, 453.e1–453.e3
www.elsevier.com/locate/ajem
Case Report Successful resuscitation with thrombolysis of a presumed fulminant pulmonary embolism during cardiac arrest Abstract Our case describes an episode of fulminant pulmonary embolism that was accompanied by cardiac arrest. A 41year-old woman who had cardiac arrest with pulseless electrical activity was transferred to the emergency department. With an initially unsuccessful cardiopulmonary resuscitation period of 22 minutes, spontaneous circulation returned after a bolus injection of urokinase. The patient was discharged without any complication and sequela through successive treatment. We conclude that empiric thrombolysis during cardiopulmonary resuscitation in patients with presumed massive pulmonary embolism and prolonged resuscitation can be highly beneficial with better survival rates and neurologic prognosis. Pulmonary embolism (PE) remains a common disease whose diagnosis is frequently overlooked, hence carries a high risk of mortality. It causes up to 15% of hospital deaths [1] despite of treatment with the appropriate prophylactic. Furthermore, in 41% of cases, fulminant PE can produce cardiac arrest (CA), which is the major predictor of PE mortality, ranging from 65% to 95% [2]. Thrombolysis treatment is supposed to be the most feasible therapy because it is available and can be administered rapidly and easily in the emergency department (ED). Current advanced cardiac life support (ACLS) guidelines state that there is insufficient evidence to recommend for or against the routine use of thrombolytic drugs for CA [3]. Here, we report a case of a 41-year-old woman who survived after administration of urokinase during cardiopulmonary resuscitation (CPR) based on the presumptive diagnosis of PE. Fulminant PE was confirmed later, and the patient was treated effectively with thrombolysis ongoing CPR. The 41-year-old woman was transferred to ED complaining of sudden chest pain and shortness of breath preceded by unconsciousness half an hour before presentation. Her left leg had been immobilized and dropsy after foot surgery 12 days 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
ago. Vital signs on presentation were heart rate 33 beats per minute, blood pressure 0/0 mmHg, and slow irregular respiration. Cardiopulmonary resuscitation protocol was initiated, and a single dose of epinephrine 1 mg was administered immediately. After she was intubated without pharmacologic support, CPR was continued, and 2 additional doses of epinephrine 1 mg were added as ACLS protocol. After 22 minutes of CPR, the patient remained unresponsive with narrow-complex, pulseless electrical activity (PEA) at a rate of 125 beats per minute. Without detecting peripheral pulse pressures, the monitor demonstrated a continued narrow complex tachycardia. The rhythm is usually defined as pseudo-PEA, and patients with it have better chance of survival than patients presenting in slow, wide QRS complex rhythms [4]. Thus, we decided to continue resuscitation and try to detect the possible cause of CA. Based on history and presentation, the patient had high likelihood of PE. A fast clinical probability assessment was done according to the British Thoracic Society guidelines [5]. A high probability existed because the following 3 factors were present: (1) clinical features compatible with PE, (2) the absence of other reasonable clinical explanation, and (3) the presence of a major risk factor. Then, a bolus dose of 1400000 U of urokinase was administered via peripheral venous for treatment of the patient. After another 6 minutes of resuscitation, the return of spontaneous circulation was achieved, and the patient's blood pressure was increased to 69/47 mm Hg without additional doses of epinephrine. After deep vein catheter was inserted, the patient was then given dopamine (20 mg/kg per minute) intravenously. Approximately 35 minutes later, the patient achieved a stable spontaneous circulation under continuous vasopressor support. Bedside echocardiography revealed an enlarged right ventricle with bowing of the septum and pulmonary artery hypertension (right ventricular systolic pressure, 60 mm Hg). Computed tomographic pulmonary angiographies was then performed and revealed large bilateral thrombi in the main pulmonary arteries (Fig. 1A and B). Computed tomography of the brain revealed no acute hemorrhage and infarction. Approximately 2 hours after CPR, the patient became awake and alert, and she was transferred to the intensive care unit
453.e2
Case Report
Fig. 2 Computed tomographic pulmonary showing disappearance of the bilateral thrombi in pulmonary arteries 2 weeks after thrombolysis treatment.
Fig. 1 A, Computed tomographic image showing large thrombi in the right main and left upper pulmonary arteries. B, Computed tomographic image showing large thrombi in right main pulmonary.
with dopamine (12 mg/kg per minute). A second dose of 1400000 U of urokinase was given 6 hours after the first one, and the dose of dopamine was decreased to 8 mg/kg per minute. Then, bedside echocardiography revealed that right ventricular systolic pressure decreased to 30 mm Hg. Two weeks after the thrombolysis treatments, another computed tomographic pulmonary angiographies revealed that the bilateral thrombi in the main pulmonary arteries disappeared (Fig. 2). After 3 weeks of observation and anticoagulant therapy, the patient was discharged without major bleeding complications or neurologic damage. Our case describes an episode of fulminant PE that was accompanied by CA in ED. After an initially unsuccessful CPR period of 22 minutes, spontaneous circulation returned after a bolus injection of urokinase. Indeed, the patient was discharged postarrest with no neurologic damage. The etiologies correlated with this prognosis may be associated with pseudo-PEA, which is frequently caused by hypovolemia, tachydysrhythmias, decreased cardiac contractility, or obstructions to circulation, such as fulminant PE, tamponade, and tension pneumothorax [6]. Successful treatment of PEA arrests depends on early identification and immediate correction of potentially reversible etiologies [7]. In this particular case, the pathologic cause of the arrest was
fulminant PE, which remains a challenge to the emergency physician with regard to diagnosis and treatment. Approximately 5% of patients with PE will present with hemodynamic instability or respiratory distress, and the mortality rate ranges from 22% to 53% [8]. With accurate diagnosis, early treatment with fibrinolytic therapy may relieve mortality. However, limited options had been available to provide accurate diagnosis for the patients with continuous CPR in many cases. Routine fibrinolytic treatment given during CPR is still in dispute. Some studies and case series showed that survival rates in patients with massive PE (MPE) necessitating CPR may exceed 9.5% to 100% when thrombolysis was started during resuscitation, apparently higher than those without thrombolysis treatment (5%-35%) [9,10]. Despite that thrombolysis could reduce mortality, its use has never become widespread because no clinical trial or study of good scientific level has clearly demonstrated its benefit. However, one of the important reasons for CPR failure is that it does not resolve the problem that causes the CA such as MPE and acute myocardial infarction (AMI) [2]. Furthermore, MPE and AMI account for over 70% of nontraumatic CA with a high mortality rate despite of correct CPR [11]. In these cases, many patients might have lost their chance of survival without thrombolysis based on presumptive diagnosis of MPE or AMI. A prospective clinical trial showed that, after initially 15-minute unsuccessful conventional CPR procedures, thrombolytic therapy combined with heparin was safe and might improve the prognosis of patients with nontraumatic CA [12]. In the past, many researchers have advised against thrombolysis during or after CPR based on the assumption of hemorrhagic complications and some contraindications or thrombolysis [13]. However, a series of retrospective studies found no increase in fatal hemorrhagic complications among patients with AMI who underwent CPR and received thrombolysis [14]. In another retrospective study, controlled analysis of the hemorrhagic complications of thrombolytic treatment in PE found a 1.9% incidence of cerebral hemorrhage [15]. Furthermore, causes of CA such as subarachnoid or intracerebral hemorrhage are contra-
Case Report
453.e3
indications for thrombolysis, but patient prognosis in this setting is dismal, and other contraindications such as trauma or gastrointestinal hemorrhage are readily identifiable in ED [16]. Thrombolysis is of proven safety and efficiency in CA, and thrombolytic agents during CPR can improve the survival rate to discharge and neurologic function [13]. In patients with CA and without known PE, routine fibrinolytic treatment is not recommended by current ACLS [3]. However, approximately 450000 Americans have CA annually [17]; about 80% of the cases occurs at home, with a death rate of over 90%. More than half of the survivors have permanent brain damage [18]. Given the poor prognosis associated with CA, the risk:benefit ratio favors active treatment, which means that fibrinolysis should be considered to CA with suspected PE. Especially with rhythm of pseudo-PEA, patients may have better survival benefit with routine fibrinolytic treatment. Six trials with 481 patients have compared various thrombolytic regimens using recombinant tissue plasminogen activator (rt-PA), streptokinase, and urokinase. In conclusion, no single agent has been shown to be more effective than any other, although the theoretical risk of worsening hypotension with streptokinase was identified in patients with circulatory compromise [16]. In our case, 2 doses of urokinase were administered via peripheral venous for treatment of the patient. As opposed to other thrombolytic agents, bolus injection of urokinase is a familiar therapeutic concept in the treatment of MPE and AMI. The agent rt-PA has been successfully used for MPE in a few cases during and after CPR but is associated with a significant higher rate of intracerebral complications and also costs a lot more than urokinase [19]. Cardiac arrest occurring in patients in the intensive care unit and ED is frequently witnessed. The prognosis depends on the existence of potential reversible causes. In many cases, accurate diagnosis for the patients is difficult to provide considering the complexity of the situation of individual patients. Empiric thrombolysis during CPR in patients with presumed MPE or prolonged resuscitation can be highly beneficial, with excellent survival rates and neurologic prognosis. Tao Zhu MD Konhan Pan MD Department of Emergency Medicine Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou, 310016, China Qiang Shu MD Department of Cardiothoracic Surgery Children's Hospital Zhejiang University School of Medicine Hangzhou, 310003, China E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2012.06.032
References [1] Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002;121:877-905. [2] Bailen MR, Cuadra JA, Aguayo De Hoyos E. Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: a review. Crit Care Med 2001;29:2211-9. [3] Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122: S829-61. [4] Paradis NA, Martin GB, Goetting MG, Rivers EP, Feingold M, Nowak RM. Aortic pressure during human cardiac arrest. Identification of pseudo-electromechanical dissociation. Chest 1992;101:123-8. [5] British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470-83. [6] Desbiens NA. Simplifying the diagnosis and management of pulseless electrical activity in adults: a qualitative review. Crit Care Med 2008;36:391-6. [7] Mehta C, Brady W. Pulseless electrical activity in cardiac arrest: electrocardiographic presentations and management considerations based on the electrocardiogram. Am J Emerg Med 2012;30:236-9. [8] Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386-9. [9] Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997;30:1165-71. [10] Chartier L, Bera J, Delomez M, Asseman P, Beregi JP, Bauchart JJ, et al. Free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. Circulation 1999;99:2779-83. [11] Perkins ZB, Mitchell C, Donald O. Prehospital thrombolysis of a massive pulmonary embolus. Emerg Med J 2008;25:303-4. [12] Bottiger BW, Bode C, Kern S, Gries A, Gust R, Glatzer R, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet 2001;357:1583-5. [13] Koroneos A, Koutsoukou A, Zervakis D, Politis P, Sourlas S, Pagoni E, et al. Successful resuscitation with thrombolysis of a patient suffering fulminant pulmonary embolism after recent intracerebral haemorrhage. Resuscitation 2007;72:154-7. [14] Ruiz-Bailen M, Aguayo de Hoyos E, Diaz-Castellanos MA. Role of thrombolysis in cardiac arrest. Intensive Care Med 2001;27: 438-41. [15] Kanter DS, Mikkola KM, Patel SR, Parker JA, Goldhaber SZ. Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors. Chest 1997;111: 1241-5. [16] Harris T, Meek S. When should we thrombolyse patients with pulmonary embolism? A systematic review of the literature. Emerg Med J 2005;22:766-71. [17] Callans DJ. Out-of-hospital cardiac arrest–the solution is shocking. N Engl J Med 2004;351:632-4. [18] Albert CM, Chae CU, Grodstein F, Rose LM, Rexrode KM, Ruskin JN, et al. Prospective study of sudden cardiac death among women in the United States. Circulation 2003;107:2096-101. [19] Ouriel K, Gray B, Clair DG, Olin J. Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis. J Vasc Interv Radiol 2000;11:295-8.
www.elsevier.com/locate/ajem
Case Report Successful resuscitation with thrombolysis of a presumed fulminant pulmonary embolism during cardiac arrest Abstract Our case describes an episode of fulminant pulmonary embolism that was accompanied by cardiac arrest. A 41year-old woman who had cardiac arrest with pulseless electrical activity was transferred to the emergency department. With an initially unsuccessful cardiopulmonary resuscitation period of 22 minutes, spontaneous circulation returned after a bolus injection of urokinase. The patient was discharged without any complication and sequela through successive treatment. We conclude that empiric thrombolysis during cardiopulmonary resuscitation in patients with presumed massive pulmonary embolism and prolonged resuscitation can be highly beneficial with better survival rates and neurologic prognosis. Pulmonary embolism (PE) remains a common disease whose diagnosis is frequently overlooked, hence carries a high risk of mortality. It causes up to 15% of hospital deaths [1] despite of treatment with the appropriate prophylactic. Furthermore, in 41% of cases, fulminant PE can produce cardiac arrest (CA), which is the major predictor of PE mortality, ranging from 65% to 95% [2]. Thrombolysis treatment is supposed to be the most feasible therapy because it is available and can be administered rapidly and easily in the emergency department (ED). Current advanced cardiac life support (ACLS) guidelines state that there is insufficient evidence to recommend for or against the routine use of thrombolytic drugs for CA [3]. Here, we report a case of a 41-year-old woman who survived after administration of urokinase during cardiopulmonary resuscitation (CPR) based on the presumptive diagnosis of PE. Fulminant PE was confirmed later, and the patient was treated effectively with thrombolysis ongoing CPR. The 41-year-old woman was transferred to ED complaining of sudden chest pain and shortness of breath preceded by unconsciousness half an hour before presentation. Her left leg had been immobilized and dropsy after foot surgery 12 days 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
ago. Vital signs on presentation were heart rate 33 beats per minute, blood pressure 0/0 mmHg, and slow irregular respiration. Cardiopulmonary resuscitation protocol was initiated, and a single dose of epinephrine 1 mg was administered immediately. After she was intubated without pharmacologic support, CPR was continued, and 2 additional doses of epinephrine 1 mg were added as ACLS protocol. After 22 minutes of CPR, the patient remained unresponsive with narrow-complex, pulseless electrical activity (PEA) at a rate of 125 beats per minute. Without detecting peripheral pulse pressures, the monitor demonstrated a continued narrow complex tachycardia. The rhythm is usually defined as pseudo-PEA, and patients with it have better chance of survival than patients presenting in slow, wide QRS complex rhythms [4]. Thus, we decided to continue resuscitation and try to detect the possible cause of CA. Based on history and presentation, the patient had high likelihood of PE. A fast clinical probability assessment was done according to the British Thoracic Society guidelines [5]. A high probability existed because the following 3 factors were present: (1) clinical features compatible with PE, (2) the absence of other reasonable clinical explanation, and (3) the presence of a major risk factor. Then, a bolus dose of 1400000 U of urokinase was administered via peripheral venous for treatment of the patient. After another 6 minutes of resuscitation, the return of spontaneous circulation was achieved, and the patient's blood pressure was increased to 69/47 mm Hg without additional doses of epinephrine. After deep vein catheter was inserted, the patient was then given dopamine (20 mg/kg per minute) intravenously. Approximately 35 minutes later, the patient achieved a stable spontaneous circulation under continuous vasopressor support. Bedside echocardiography revealed an enlarged right ventricle with bowing of the septum and pulmonary artery hypertension (right ventricular systolic pressure, 60 mm Hg). Computed tomographic pulmonary angiographies was then performed and revealed large bilateral thrombi in the main pulmonary arteries (Fig. 1A and B). Computed tomography of the brain revealed no acute hemorrhage and infarction. Approximately 2 hours after CPR, the patient became awake and alert, and she was transferred to the intensive care unit
453.e2
Case Report
Fig. 2 Computed tomographic pulmonary showing disappearance of the bilateral thrombi in pulmonary arteries 2 weeks after thrombolysis treatment.
Fig. 1 A, Computed tomographic image showing large thrombi in the right main and left upper pulmonary arteries. B, Computed tomographic image showing large thrombi in right main pulmonary.
with dopamine (12 mg/kg per minute). A second dose of 1400000 U of urokinase was given 6 hours after the first one, and the dose of dopamine was decreased to 8 mg/kg per minute. Then, bedside echocardiography revealed that right ventricular systolic pressure decreased to 30 mm Hg. Two weeks after the thrombolysis treatments, another computed tomographic pulmonary angiographies revealed that the bilateral thrombi in the main pulmonary arteries disappeared (Fig. 2). After 3 weeks of observation and anticoagulant therapy, the patient was discharged without major bleeding complications or neurologic damage. Our case describes an episode of fulminant PE that was accompanied by CA in ED. After an initially unsuccessful CPR period of 22 minutes, spontaneous circulation returned after a bolus injection of urokinase. Indeed, the patient was discharged postarrest with no neurologic damage. The etiologies correlated with this prognosis may be associated with pseudo-PEA, which is frequently caused by hypovolemia, tachydysrhythmias, decreased cardiac contractility, or obstructions to circulation, such as fulminant PE, tamponade, and tension pneumothorax [6]. Successful treatment of PEA arrests depends on early identification and immediate correction of potentially reversible etiologies [7]. In this particular case, the pathologic cause of the arrest was
fulminant PE, which remains a challenge to the emergency physician with regard to diagnosis and treatment. Approximately 5% of patients with PE will present with hemodynamic instability or respiratory distress, and the mortality rate ranges from 22% to 53% [8]. With accurate diagnosis, early treatment with fibrinolytic therapy may relieve mortality. However, limited options had been available to provide accurate diagnosis for the patients with continuous CPR in many cases. Routine fibrinolytic treatment given during CPR is still in dispute. Some studies and case series showed that survival rates in patients with massive PE (MPE) necessitating CPR may exceed 9.5% to 100% when thrombolysis was started during resuscitation, apparently higher than those without thrombolysis treatment (5%-35%) [9,10]. Despite that thrombolysis could reduce mortality, its use has never become widespread because no clinical trial or study of good scientific level has clearly demonstrated its benefit. However, one of the important reasons for CPR failure is that it does not resolve the problem that causes the CA such as MPE and acute myocardial infarction (AMI) [2]. Furthermore, MPE and AMI account for over 70% of nontraumatic CA with a high mortality rate despite of correct CPR [11]. In these cases, many patients might have lost their chance of survival without thrombolysis based on presumptive diagnosis of MPE or AMI. A prospective clinical trial showed that, after initially 15-minute unsuccessful conventional CPR procedures, thrombolytic therapy combined with heparin was safe and might improve the prognosis of patients with nontraumatic CA [12]. In the past, many researchers have advised against thrombolysis during or after CPR based on the assumption of hemorrhagic complications and some contraindications or thrombolysis [13]. However, a series of retrospective studies found no increase in fatal hemorrhagic complications among patients with AMI who underwent CPR and received thrombolysis [14]. In another retrospective study, controlled analysis of the hemorrhagic complications of thrombolytic treatment in PE found a 1.9% incidence of cerebral hemorrhage [15]. Furthermore, causes of CA such as subarachnoid or intracerebral hemorrhage are contra-
Case Report
453.e3
indications for thrombolysis, but patient prognosis in this setting is dismal, and other contraindications such as trauma or gastrointestinal hemorrhage are readily identifiable in ED [16]. Thrombolysis is of proven safety and efficiency in CA, and thrombolytic agents during CPR can improve the survival rate to discharge and neurologic function [13]. In patients with CA and without known PE, routine fibrinolytic treatment is not recommended by current ACLS [3]. However, approximately 450000 Americans have CA annually [17]; about 80% of the cases occurs at home, with a death rate of over 90%. More than half of the survivors have permanent brain damage [18]. Given the poor prognosis associated with CA, the risk:benefit ratio favors active treatment, which means that fibrinolysis should be considered to CA with suspected PE. Especially with rhythm of pseudo-PEA, patients may have better survival benefit with routine fibrinolytic treatment. Six trials with 481 patients have compared various thrombolytic regimens using recombinant tissue plasminogen activator (rt-PA), streptokinase, and urokinase. In conclusion, no single agent has been shown to be more effective than any other, although the theoretical risk of worsening hypotension with streptokinase was identified in patients with circulatory compromise [16]. In our case, 2 doses of urokinase were administered via peripheral venous for treatment of the patient. As opposed to other thrombolytic agents, bolus injection of urokinase is a familiar therapeutic concept in the treatment of MPE and AMI. The agent rt-PA has been successfully used for MPE in a few cases during and after CPR but is associated with a significant higher rate of intracerebral complications and also costs a lot more than urokinase [19]. Cardiac arrest occurring in patients in the intensive care unit and ED is frequently witnessed. The prognosis depends on the existence of potential reversible causes. In many cases, accurate diagnosis for the patients is difficult to provide considering the complexity of the situation of individual patients. Empiric thrombolysis during CPR in patients with presumed MPE or prolonged resuscitation can be highly beneficial, with excellent survival rates and neurologic prognosis. Tao Zhu MD Konhan Pan MD Department of Emergency Medicine Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou, 310016, China Qiang Shu MD Department of Cardiothoracic Surgery Children's Hospital Zhejiang University School of Medicine Hangzhou, 310003, China E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2012.06.032
References [1] Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002;121:877-905. [2] Bailen MR, Cuadra JA, Aguayo De Hoyos E. Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: a review. Crit Care Med 2001;29:2211-9. [3] Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122: S829-61. [4] Paradis NA, Martin GB, Goetting MG, Rivers EP, Feingold M, Nowak RM. Aortic pressure during human cardiac arrest. Identification of pseudo-electromechanical dissociation. Chest 1992;101:123-8. [5] British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470-83. [6] Desbiens NA. Simplifying the diagnosis and management of pulseless electrical activity in adults: a qualitative review. Crit Care Med 2008;36:391-6. [7] Mehta C, Brady W. Pulseless electrical activity in cardiac arrest: electrocardiographic presentations and management considerations based on the electrocardiogram. Am J Emerg Med 2012;30:236-9. [8] Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386-9. [9] Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997;30:1165-71. [10] Chartier L, Bera J, Delomez M, Asseman P, Beregi JP, Bauchart JJ, et al. Free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. Circulation 1999;99:2779-83. [11] Perkins ZB, Mitchell C, Donald O. Prehospital thrombolysis of a massive pulmonary embolus. Emerg Med J 2008;25:303-4. [12] Bottiger BW, Bode C, Kern S, Gries A, Gust R, Glatzer R, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet 2001;357:1583-5. [13] Koroneos A, Koutsoukou A, Zervakis D, Politis P, Sourlas S, Pagoni E, et al. Successful resuscitation with thrombolysis of a patient suffering fulminant pulmonary embolism after recent intracerebral haemorrhage. Resuscitation 2007;72:154-7. [14] Ruiz-Bailen M, Aguayo de Hoyos E, Diaz-Castellanos MA. Role of thrombolysis in cardiac arrest. Intensive Care Med 2001;27: 438-41. [15] Kanter DS, Mikkola KM, Patel SR, Parker JA, Goldhaber SZ. Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors. Chest 1997;111: 1241-5. [16] Harris T, Meek S. When should we thrombolyse patients with pulmonary embolism? A systematic review of the literature. Emerg Med J 2005;22:766-71. [17] Callans DJ. Out-of-hospital cardiac arrest–the solution is shocking. N Engl J Med 2004;351:632-4. [18] Albert CM, Chae CU, Grodstein F, Rose LM, Rexrode KM, Ruskin JN, et al. Prospective study of sudden cardiac death among women in the United States. Circulation 2003;107:2096-101. [19] Ouriel K, Gray B, Clair DG, Olin J. Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis. J Vasc Interv Radiol 2000;11:295-8.