American Journal of Emergency Medicine 33 (2015) 132.e1–132.e2
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Thrombolysis after initially unsuccessful cardiopulmonary resuscitation in presumed pulmonary embolism
Abstract The life-saving administration of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation (CPR) in 7 patients with presumed pulmonary embolism (PE) was reported. Seven patients who had cardiac arrest were admitted to our emergency department. The clinical diagnosis of all these patients was highly suspected with PE; therefore, 50 mg recombinant tissue plasminogen activator with 50-mL dilution was administered in a 15-minute period after initially unsuccessful CPR. Of 7 patients, 5 (71.4%) achieved return of spontaneous circulation after CPR and thrombolytic therapy, and 3 (42.9%) of 7 patients were discharged alive through successive treatments. A 90-day follow-up showed that 2 patients were neurologically intact, and 1 patient was mildly disabled. These results demonstrate that thrombolysis after initially unsuccessful CPR in presumed PE may have beneficial effects. Pulmonary embolism (PE) has an incidence of approximately 0.1% among the general population and accounts for 2% to 15% of unexpected sudden death, 2% of all cardiac arrest (CA), and 6.5% of noncardiac CA. Fulminant PE can cause CA in 41% of cases, with a mortality ranging from 65% to 95% [1]. Fulminant PE can produce CA through multiple mechanisms, most commonly by obstructive shock with severe dysfunction of the right ventricle, and other mechanisms include arrhythmias and vasovagal reflex [2]. Once CA occurs, external chest compression may be effective in fragmenting large emboli and thus re-establishing pulmonary circulation. However, when pulmonary artery is completely obstructed, simple chest compression is difficult to restore spontaneous circulation. Under this circumstance, other measures, such as thrombolysis, emergency thoracotomy, and embolectomy, should be tried. Among these, thrombolysis has attracted much attention because of its easy administration, rapid action, and physiopathologic benefits. Here, we reported administration of thrombolytic therapy in 7 patients with highly suspected PE after initially unsuccessful cardiopulmonary resuscitation (CPR) in our emergency department (ED). These 7 patients with CA were admitted to the ED of Beijing Chaoyang Hospital, which is an university hospital, from February 2013 to December 2013. The initial rhythm of these patients was pulseless electrical activity when arriving at the ED, and the time between occurrence of CA and arrival of ED ranged from 5 to 20 minutes (Table 1). CPR was started immediately according to the recommendations of 2010 CPR guidelines [3]. The initial CPR time ranged from 20 to 45 minutes. During this period, PE was highly suspected based on previous medical histories, symptoms, and laboratory results in these 7 patients (Table 2). Therefore, after obtaining written informed consent 0735-6757/© 2014 Elsevier Inc. All rights reserved.
forms from legal relatives, 50 mg recombinant tissue plasminogen activator (Alteplase, Boehringer Ingelheim, Ingelheim am Rhein, Germany) with 50-mL dilution was administered via peripheral intravenous infusion in a 15-minute period during ongoing CPR. The total CPR time ranged from 28 to 100 minutes. After CPR and thrombolytic therapy, 5 (71.4%) of 7 patients achieved return of spontaneous circulation (ROSC). These patients were admitted into the emergency intensive care unit to receive post-CA therapies. Patient 1 died at 3 days after ROSC because of heart failure. Patient 6 died during the subsequent hospital stay for pulmonary infection. Finally, 3 (42.9%) of 7 patients were discharged alive. The neurologic outcome was assessed by the Glasgow Outcome Score (GOS) [4]. The 90-day GOS of 3 patients was 5, 5, and 4, respectively, indicating that 2 patients were neurologically intact and 1 patient was moderately disabled (Table 3). Pulmonary embolism may cause a large number of CA with a high mortality. The high mortality is partly due to the fact that PE is often underestimated [5]. Therefore, clinical suspicion of PE as a cause of CA remains the key in timely treatment. In clinical practice, diagnosis of PE in cases of CA is difficult to establish; under such circumstance, the diagnosis is often a clinical one, mainly based on previous medical histories, symptoms, signs, and auxiliary examinations [6]. In our report, 5 of 7 patients had high-risk factors of PE, and the most suggestive symptoms of PE were dyspnea and syncope. In addition, electrocardiogram showed SIQIIITIII in 2 patients, and echocardiography showed right heart enlargement and pulmonary hypertension in 4 patients. Furthermore, D-dimer levels of these 7 patients were all significantly elevated (Table 2). Taken together, these symptoms and signs should reinforce the clinical suspicion of PE in the presence of CA. On the other hand, 2 patients with ROSC were confirmed to be PE through computed tomography of pulmonary artery and pulmonary radioisotope scanning, whereas another 3 patients with ROSC were highly suspected of PE because of right heart
Table 1 Clinical characteristics of 7 patients
1 2 3 4 5 6 7
Age (y)
Sex
Time between CA and arrival of ED (min)
Time between start of CPR and thrombolysis (min)
Total CPR time (min)
ROSC
56 40 48 22 59 85 76
Female Female Female Male Female Male Male
15 10 5 20 20 10 5
35 25 20 20 25 40 40
80 42 28 100 35 60 90
Yes Yes Yes No Yes Yes No
132.e2
Q. Yin et al. / American Journal of Emergency Medicine 33 (2015) 132.e1–132.e2
Table 2 Clinical evidences of PE in 7 patients High-risk factors of PE
D-dimer (mg/L)
Symptoms
1 None
Chest tightness for 1 d 5.92
2 None
Recurrent syncope for 11.85 1 mo Sudden dyspnea for 1 h 8.96
3 8 d after surgery of venous thrombus of left lower extremity 4 Pulmonary cancer
5 28 d after surgery of lumbar vertebrae
Dyspnea for 1 mo
2.75
Dyspnea and chest pain for 7 d
4.62
6 Lying on bed for 15 d because Dyspnea for 1 d of fracture of right lower extremity
3.95
7 Varicosity of left lower extremity
7.58
Syncope for 1 d
Other manifestations of PE
Diagnostic evidence of PE
Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Confirmed diagnosis: pulmonary radioisotope SIQIIITIII on electrocardiogram of other hospital scanning showed left PE SIQIIITIII on electrocardiogram of Confirmed diagnosis: CT of pulmonary artery other hospital showed right PE Suspected tumor embolus of pulmonary Suspected diagnosis: suspected tumor embolus artery on pulmonary enhanced CT of of pulmonary artery on pulmonary enhanced CT other hospital of other hospital Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension on echocardiography
Abbreviation: CT, computed tomography.
enlargement and pulmonary hypertension were significantly improved on echocardiography after thrombolysis (Table 2). The first use of thrombolysis during CPR in a patient with PE was reported by Renkes-Hegendorfer and Hermann in 1974 [7]. Since then, more than 100 cases of successful administration of thrombolysis in patients with confirmed or suspected PE during CPR have been published, when the thrombolysis was almost always used as a last resort [8]. Besides case series, clinical studies have also confirmed the effectiveness of thrombolysis [9,10]. However, currently, the use of thrombolysis in CA caused by PE has not been supported by prospective, randomized, controlled trials. Although thrombolysis is effective in saving patients with PE, many scientific societies have advised against its use during CPR, based on the opinion that ongoing CPR is a contraindication to thrombolytic treatment due to the risk of causing lethal bleeding complications. However, Janata et al [11] compared 36 patients who received thrombolysis with 30 patients without thrombolysis with CA due to PE in a retrospective study and concluded that although severe bleeding complications tend to occur more frequently in patients undergoing thrombolysis, the benefit of this treatment might outweigh the risk of bleeding. In our report, 50 mg recombinant tissue plasminogen activator with 50-mL dilution was administered via peripheral intravenous infusion in a 15-minute period during ongoing CPR. Of 7 patients, 5 (71.4%) achieved ROSC after CPR and thrombolytic therapy, and 3 (42.9%) of 7 patients were discharged alive through successive treatments. A 90-day follow-up found that 2 patients were neurologically intact and 1 patient was moderately disabled. Furthermore, there were no records of major bleeding complications in 5 patients
Table 3 Prognosis of 5 patients with ROSC
1 2 3 5 6
Time between ROSC and occurrence of neurological activities (h)
Time between ROSC and GCS 12 (h)
Survival discharge
90-d GOS
36 12 4 10 No
No 24 24 24 No
No Yes Yes Yes No
1 4 5 5 1
Abbreviation: GCS: Glasgow Coma Score.
with ROSC. These results demonstrate that thrombolysis is effective and safe in saving patients with CA caused by PE. In conclusion, outcome of CA depends largely on the existence of potential reversible causes. Proven or highly suspected thrombotic etiology is an indication for thrombolysis. In this extreme situation, use of thrombolysis should be strongly considered. Qin Yin, MD Xiao Li, MD Chunsheng Li, MD Emergency Department of Beijing Chaoyang Hospital Capital Medical University, Beijing, China E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.06.031 References [1] Kuisma M, Aläspaa A. Out-of-hospital cardiac arrests of non-cardiac origin: epidemiology and outcome. Eur Heart J 1997;18:1122–8. [2] Lualdi JC, Goldhaber SZ. Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications. Am Heart J 1995;130:1276–82. [3] Berg RA, Hemphill R, Abella BS, Aufderheide TP, Cave DM, Hazinski MF, et al. Part 5: Adult Basic Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S676–84. [4] Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1:480–4. [5] Silfvast T. Cause of death in unsuccessful prehospital resuscitation. J Intern Med 1991;229:331–5. [6] Courtney DM, Jeffrey AK. Prospective use of a clinical decision rule to identify pulmonary embolism as likely cause of outpatient cardiac arrest. Resuscitation 2005;65:57–64. [7] Renkes-Hegendorfer U, Hermann K. Successful treatment of a case of fulminant massive pulmonary embolism with streptokinase. Anaesthesist 1974;23:500–1. [8] 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. [9] Kurkciyan I, Meron G, Sterz F, Janata K, Domanovits H, Holzer M, et al. Pulmonary embolism as cause of cardiac arrest. Presentation and outcome. Arch Intern Med 2000;160:1529–35. [10] Er F, Nia AM, Gassanov N, Caglayan E, Erdmann E, Hoppe UC. Impact of rescuethrombolysis during cardiopulmonary resuscitation in patients with pulmonary embolism. PLoS ONE 2009;4:e8323. [11] Janata K, Holzer M, Kurkciyan I, Losert H, Riedmuller E, Pikula B, et al. Major bleeding complications in cardiopulmonary resuscitation—the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Resuscitation 2003;57:49–55.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Thrombolysis after initially unsuccessful cardiopulmonary resuscitation in presumed pulmonary embolism
Abstract The life-saving administration of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation (CPR) in 7 patients with presumed pulmonary embolism (PE) was reported. Seven patients who had cardiac arrest were admitted to our emergency department. The clinical diagnosis of all these patients was highly suspected with PE; therefore, 50 mg recombinant tissue plasminogen activator with 50-mL dilution was administered in a 15-minute period after initially unsuccessful CPR. Of 7 patients, 5 (71.4%) achieved return of spontaneous circulation after CPR and thrombolytic therapy, and 3 (42.9%) of 7 patients were discharged alive through successive treatments. A 90-day follow-up showed that 2 patients were neurologically intact, and 1 patient was mildly disabled. These results demonstrate that thrombolysis after initially unsuccessful CPR in presumed PE may have beneficial effects. Pulmonary embolism (PE) has an incidence of approximately 0.1% among the general population and accounts for 2% to 15% of unexpected sudden death, 2% of all cardiac arrest (CA), and 6.5% of noncardiac CA. Fulminant PE can cause CA in 41% of cases, with a mortality ranging from 65% to 95% [1]. Fulminant PE can produce CA through multiple mechanisms, most commonly by obstructive shock with severe dysfunction of the right ventricle, and other mechanisms include arrhythmias and vasovagal reflex [2]. Once CA occurs, external chest compression may be effective in fragmenting large emboli and thus re-establishing pulmonary circulation. However, when pulmonary artery is completely obstructed, simple chest compression is difficult to restore spontaneous circulation. Under this circumstance, other measures, such as thrombolysis, emergency thoracotomy, and embolectomy, should be tried. Among these, thrombolysis has attracted much attention because of its easy administration, rapid action, and physiopathologic benefits. Here, we reported administration of thrombolytic therapy in 7 patients with highly suspected PE after initially unsuccessful cardiopulmonary resuscitation (CPR) in our emergency department (ED). These 7 patients with CA were admitted to the ED of Beijing Chaoyang Hospital, which is an university hospital, from February 2013 to December 2013. The initial rhythm of these patients was pulseless electrical activity when arriving at the ED, and the time between occurrence of CA and arrival of ED ranged from 5 to 20 minutes (Table 1). CPR was started immediately according to the recommendations of 2010 CPR guidelines [3]. The initial CPR time ranged from 20 to 45 minutes. During this period, PE was highly suspected based on previous medical histories, symptoms, and laboratory results in these 7 patients (Table 2). Therefore, after obtaining written informed consent 0735-6757/© 2014 Elsevier Inc. All rights reserved.
forms from legal relatives, 50 mg recombinant tissue plasminogen activator (Alteplase, Boehringer Ingelheim, Ingelheim am Rhein, Germany) with 50-mL dilution was administered via peripheral intravenous infusion in a 15-minute period during ongoing CPR. The total CPR time ranged from 28 to 100 minutes. After CPR and thrombolytic therapy, 5 (71.4%) of 7 patients achieved return of spontaneous circulation (ROSC). These patients were admitted into the emergency intensive care unit to receive post-CA therapies. Patient 1 died at 3 days after ROSC because of heart failure. Patient 6 died during the subsequent hospital stay for pulmonary infection. Finally, 3 (42.9%) of 7 patients were discharged alive. The neurologic outcome was assessed by the Glasgow Outcome Score (GOS) [4]. The 90-day GOS of 3 patients was 5, 5, and 4, respectively, indicating that 2 patients were neurologically intact and 1 patient was moderately disabled (Table 3). Pulmonary embolism may cause a large number of CA with a high mortality. The high mortality is partly due to the fact that PE is often underestimated [5]. Therefore, clinical suspicion of PE as a cause of CA remains the key in timely treatment. In clinical practice, diagnosis of PE in cases of CA is difficult to establish; under such circumstance, the diagnosis is often a clinical one, mainly based on previous medical histories, symptoms, signs, and auxiliary examinations [6]. In our report, 5 of 7 patients had high-risk factors of PE, and the most suggestive symptoms of PE were dyspnea and syncope. In addition, electrocardiogram showed SIQIIITIII in 2 patients, and echocardiography showed right heart enlargement and pulmonary hypertension in 4 patients. Furthermore, D-dimer levels of these 7 patients were all significantly elevated (Table 2). Taken together, these symptoms and signs should reinforce the clinical suspicion of PE in the presence of CA. On the other hand, 2 patients with ROSC were confirmed to be PE through computed tomography of pulmonary artery and pulmonary radioisotope scanning, whereas another 3 patients with ROSC were highly suspected of PE because of right heart
Table 1 Clinical characteristics of 7 patients
1 2 3 4 5 6 7
Age (y)
Sex
Time between CA and arrival of ED (min)
Time between start of CPR and thrombolysis (min)
Total CPR time (min)
ROSC
56 40 48 22 59 85 76
Female Female Female Male Female Male Male
15 10 5 20 20 10 5
35 25 20 20 25 40 40
80 42 28 100 35 60 90
Yes Yes Yes No Yes Yes No
132.e2
Q. Yin et al. / American Journal of Emergency Medicine 33 (2015) 132.e1–132.e2
Table 2 Clinical evidences of PE in 7 patients High-risk factors of PE
D-dimer (mg/L)
Symptoms
1 None
Chest tightness for 1 d 5.92
2 None
Recurrent syncope for 11.85 1 mo Sudden dyspnea for 1 h 8.96
3 8 d after surgery of venous thrombus of left lower extremity 4 Pulmonary cancer
5 28 d after surgery of lumbar vertebrae
Dyspnea for 1 mo
2.75
Dyspnea and chest pain for 7 d
4.62
6 Lying on bed for 15 d because Dyspnea for 1 d of fracture of right lower extremity
3.95
7 Varicosity of left lower extremity
7.58
Syncope for 1 d
Other manifestations of PE
Diagnostic evidence of PE
Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Confirmed diagnosis: pulmonary radioisotope SIQIIITIII on electrocardiogram of other hospital scanning showed left PE SIQIIITIII on electrocardiogram of Confirmed diagnosis: CT of pulmonary artery other hospital showed right PE Suspected tumor embolus of pulmonary Suspected diagnosis: suspected tumor embolus artery on pulmonary enhanced CT of of pulmonary artery on pulmonary enhanced CT other hospital of other hospital Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension were improved on echocardiography after thrombolysis Right heart enlargement and pulmonary Suspected diagnosis: right heart enlargement hypertension on echocardiography and pulmonary hypertension on echocardiography
Abbreviation: CT, computed tomography.
enlargement and pulmonary hypertension were significantly improved on echocardiography after thrombolysis (Table 2). The first use of thrombolysis during CPR in a patient with PE was reported by Renkes-Hegendorfer and Hermann in 1974 [7]. Since then, more than 100 cases of successful administration of thrombolysis in patients with confirmed or suspected PE during CPR have been published, when the thrombolysis was almost always used as a last resort [8]. Besides case series, clinical studies have also confirmed the effectiveness of thrombolysis [9,10]. However, currently, the use of thrombolysis in CA caused by PE has not been supported by prospective, randomized, controlled trials. Although thrombolysis is effective in saving patients with PE, many scientific societies have advised against its use during CPR, based on the opinion that ongoing CPR is a contraindication to thrombolytic treatment due to the risk of causing lethal bleeding complications. However, Janata et al [11] compared 36 patients who received thrombolysis with 30 patients without thrombolysis with CA due to PE in a retrospective study and concluded that although severe bleeding complications tend to occur more frequently in patients undergoing thrombolysis, the benefit of this treatment might outweigh the risk of bleeding. In our report, 50 mg recombinant tissue plasminogen activator with 50-mL dilution was administered via peripheral intravenous infusion in a 15-minute period during ongoing CPR. Of 7 patients, 5 (71.4%) achieved ROSC after CPR and thrombolytic therapy, and 3 (42.9%) of 7 patients were discharged alive through successive treatments. A 90-day follow-up found that 2 patients were neurologically intact and 1 patient was moderately disabled. Furthermore, there were no records of major bleeding complications in 5 patients
Table 3 Prognosis of 5 patients with ROSC
1 2 3 5 6
Time between ROSC and occurrence of neurological activities (h)
Time between ROSC and GCS 12 (h)
Survival discharge
90-d GOS
36 12 4 10 No
No 24 24 24 No
No Yes Yes Yes No
1 4 5 5 1
Abbreviation: GCS: Glasgow Coma Score.
with ROSC. These results demonstrate that thrombolysis is effective and safe in saving patients with CA caused by PE. In conclusion, outcome of CA depends largely on the existence of potential reversible causes. Proven or highly suspected thrombotic etiology is an indication for thrombolysis. In this extreme situation, use of thrombolysis should be strongly considered. Qin Yin, MD Xiao Li, MD Chunsheng Li, MD Emergency Department of Beijing Chaoyang Hospital Capital Medical University, Beijing, China E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.06.031 References [1] Kuisma M, Aläspaa A. Out-of-hospital cardiac arrests of non-cardiac origin: epidemiology and outcome. Eur Heart J 1997;18:1122–8. [2] Lualdi JC, Goldhaber SZ. Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications. Am Heart J 1995;130:1276–82. [3] Berg RA, Hemphill R, Abella BS, Aufderheide TP, Cave DM, Hazinski MF, et al. Part 5: Adult Basic Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S676–84. [4] Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1:480–4. [5] Silfvast T. Cause of death in unsuccessful prehospital resuscitation. J Intern Med 1991;229:331–5. [6] Courtney DM, Jeffrey AK. Prospective use of a clinical decision rule to identify pulmonary embolism as likely cause of outpatient cardiac arrest. Resuscitation 2005;65:57–64. [7] Renkes-Hegendorfer U, Hermann K. Successful treatment of a case of fulminant massive pulmonary embolism with streptokinase. Anaesthesist 1974;23:500–1. [8] 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. [9] Kurkciyan I, Meron G, Sterz F, Janata K, Domanovits H, Holzer M, et al. Pulmonary embolism as cause of cardiac arrest. Presentation and outcome. Arch Intern Med 2000;160:1529–35. [10] Er F, Nia AM, Gassanov N, Caglayan E, Erdmann E, Hoppe UC. Impact of rescuethrombolysis during cardiopulmonary resuscitation in patients with pulmonary embolism. PLoS ONE 2009;4:e8323. [11] Janata K, Holzer M, Kurkciyan I, Losert H, Riedmuller E, Pikula B, et al. Major bleeding complications in cardiopulmonary resuscitation—the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Resuscitation 2003;57:49–55.
