American Journal of Emergency Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Correspondence
Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy☆,☆☆
To the Editor, We read with avid interest the article “Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism” as recently published by Logan et al [1]. We wish to concur with the authors in recognizing that thrombolytic administration for massive pulmonary embolism (PE) as a cause of cardiac arrest is a well-recognized but often overlooked therapeutic strategy in clinical practice and also recognize the clinical uncertainty involving the dosing regimen of thrombolytic therapy in this clinical scenario. Consequently, we present 2 clinical cases of massive PE and resultant pulseless electrical activity (PEA) cardiac arrest, in which a hybrid dosing strategy of thrombolytic therapy resulted in successful outcomes. Case 1: An 82-year-old white woman presented to the emergency department (ED) for a transient syncopal episode; blood pressure, 118/73 mm Hg; heart rate, 119 per minute; respiratory rate, 24 per minute; and oxygen saturation (SpO2) of 85% on room air. Laboratory testing revealed a lactic acidosis of 6.8 mmol/L and a brain natriuretic peptide level of 848 pg/mL (normal, b449 pg/mL). The electrocardiogram revealed sinus tachycardia with a right bundle branch block and an S1Q3 pattern. Ventilation perfusion scanning revealed multiple bilateral mismatched segmental and subsegmental perfusion defects consistent with a high probability for PE. Emergent echocardiography revealed moderate right ventricular dilatation with moderate hypokinesis; pulmonary artery pressures were not estimated. The patient was therapeutically anticoagulated with enoxaparin sodium (Lovenox) but developed worsening hypoxemia and metabolic acidosis with a subsequent PEA cardiac arrest. Immediate cardiopulmonary resuscitation (CPR) was initiated followed by multiple rounds of epinephrine; a bolus of 50-mg tissue plasminogen activator (tPA) was also administered with return of spontaneous circulation after 37 minutes. A follow-up infusion of 50-mg intravenous tPA over 2 hours was performed. Therapeutic hypothermia was not attempted post–cardiac arrest because the patient evidenced bleeding from puncture sites involving the internal jugular vein and antecubital veins. After 24 hours, the patient was fully awake and alert with hemodynamic stability. She was extubated 48 hours later to 2 L/m oxygen via nasal cannula along with rapid weaning of vasopressors. A
☆ Institution of report: Mercy Hospital, Saint Louis. ☆☆ Financial Disclosures: None.
follow-up echocardiogram approximately 1 year later revealed no evidence of right ventricular dilatation with normal right ventricular systolic function and pulmonary pressures. Case 2: A 68-year-old white woman presented to the ED with acute dyspnea; blood pressure, 94/76 mm Hg; heart rate, 168 per minute; respiratory rate, 36 per minute, and SpO2 86% on room air. Laboratory testing revealed a lactic acidosis of 10 mmol/L and a brain natriuretic peptide level of 8232 pg/mL. The electrocardiogram revealed atrial fibrillation with a rapid ventricular response, incomplete right bundle branch block, and an S1Q3T3 pattern. Emergent echocardiography revealed severe right ventricular dilatation and severe hypokinesis; pulmonary artery pressures were not estimated. The patient rapidly deteriorated in the ED and necessitated endotracheal intubation for worsening respiratory distress and hypoxemia, culminating in a PEA cardiac arrest. Immediate CPR was initiated. Presumptive thrombolytic therapy with a bolus of 50-mg tissue tPA was administered with return of spontaneous circulation after 45 minutes. A follow-up infusion of 50-mg intravenous tPA over 2 hours was performed, along with therapeutic infusion of unfractionated heparin. Targeted temperature management with therapeutic hypothermia was performed post–cardiac arrest. Subsequent venous Doppler studies of the lower extremities demonstrated acute deep venous thrombosis of the right femoral vein. The patient eventually necessitated a tracheostomy but was successfully decannulated in a long-term acute care facility without the need for supplemental oxygen. The 2010 Advanced Cardiac Life Support Guidelines recommend thrombolytics for presumed or known PE during a code situation (class IIa, level of evidence B) [2]. According to the scientific statement published by American Heart Association regarding management of massive PE, which is defined as an acute PE with sustained hypotension (systolic blood pressure b90 mm Hg) for at least 15 minutes or requiring inotropic support not caused by other than PE, the recommended dosing of thrombolytics is tPA 100 mg infused over 2 hours [3]. However, the British Thoracic Guidelines from 2003 recommend a 50-mg bolus of tPA during cardiac arrest if massive PE is suspected clinically or even if cardiac arrest is likewise “imminent” [4]. Previous studies have suggested that a bolus regimen of tPA produces accelerated thrombolysis [5], although a tPA infusion appeared more effective in a metaanalysis by Capstick et al [6]. Both our patients experiencing PEA arrests were administered a hybrid dosing regimen of a 50-mg tPA bolus followed by a further 50 mg over the next 2 hours. We postulate that such a dosage regimen for both proven and
0735-6757/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Katyal A, et al, Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.03.053
2
Correspondence / American Journal of Emergency Medicine xxx (2015) xxx–xxx
presumptive therapy of PE causing cardiac arrest may provide an accelerated effect and combine the benefit of thrombolysis with mitigation of bleeding risk. The most feared complication of thrombolytic therapy is hemorrhage, particularly intracranial. An analysis of data from 5 clinical trials using thrombolytics in acute PE reported a risk of intracranial hemorrhage of 1.9% [7], although subsequent data from the International Cooperative Pulmonary Embolism Registry demonstrated a risk as high as 3% as far as intracranial hemorrhage is concerned [8]. Likewise, there is concern about bleeding risk in patients receiving thrombolytics with prolonged CPR (N10 minutes). In a retrospective cohort study, although thrombolytics were associated with greater risk of major bleeding (not statistically significant), there was no relationship to duration of CPR [9]. However, data from all these studies uniformly advocate careful patient selection before administration of fibrinolytic therapy [10]. Therefore, we urge routine consideration of thrombolytic therapy by emergency and critical care physicians in clinical scenarios such as the aforementioned cases, using sound clinical judgment on a case-by-case basis, especially given the narrow window of opportunity to potentially impact outcomes.
Anup Katyal, MD Critical Care Medicine, Mercy Clinic and Hospital Saint Louis 621 S. New Ballas Rd, Tower B, Ste 4006 St. Louis, MO 63141 Dayton Dmello, MD, MBA Pulmonary, Critical Care and Sleep Medicine Mercy Clinic and Hospital, St. Louis, MO 63141 Corresponding author. Tel.: + 314 251 4966; fax: 314 251 4588 E-mail address: [email protected]
Robert W. Taylor, MD Critical Care Medicine, Mercy Clinic and Hospital Saint Louis 621 S. New Ballas Rd, Tower B, Ste 4006 St. Louis, MO 63141
http://dx.doi.org/10.1016/j.ajem.2015.03.053
References [1] Logan J, Pantle H, Huiras P, Bessman E, Bright L. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism. Am J Emerg Med 2014;32:789–96. [2] Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S829–61. [3] Jaff MR, McMurthy MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep venous thrombosis and chronic thromboembolic pulmonary hypertension: A scientific statement from American Heart Association. Circulation 2011;123:1788–830. [4] British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470–84. [5] Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, et al. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 1990;98(6):147. [6] Capstick T, Henry MT. Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J 2005;26:864–74. [7] 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;111:241–5. [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] 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 2005;57:49–55. [10] Piazza G, Goldhaber S. Fibrinolysis for acute pulmonary embolism. Vasc Med 2010;15(5):419–28.
Please cite this article as: Katyal A, et al, Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.03.053
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Correspondence
Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy☆,☆☆
To the Editor, We read with avid interest the article “Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism” as recently published by Logan et al [1]. We wish to concur with the authors in recognizing that thrombolytic administration for massive pulmonary embolism (PE) as a cause of cardiac arrest is a well-recognized but often overlooked therapeutic strategy in clinical practice and also recognize the clinical uncertainty involving the dosing regimen of thrombolytic therapy in this clinical scenario. Consequently, we present 2 clinical cases of massive PE and resultant pulseless electrical activity (PEA) cardiac arrest, in which a hybrid dosing strategy of thrombolytic therapy resulted in successful outcomes. Case 1: An 82-year-old white woman presented to the emergency department (ED) for a transient syncopal episode; blood pressure, 118/73 mm Hg; heart rate, 119 per minute; respiratory rate, 24 per minute; and oxygen saturation (SpO2) of 85% on room air. Laboratory testing revealed a lactic acidosis of 6.8 mmol/L and a brain natriuretic peptide level of 848 pg/mL (normal, b449 pg/mL). The electrocardiogram revealed sinus tachycardia with a right bundle branch block and an S1Q3 pattern. Ventilation perfusion scanning revealed multiple bilateral mismatched segmental and subsegmental perfusion defects consistent with a high probability for PE. Emergent echocardiography revealed moderate right ventricular dilatation with moderate hypokinesis; pulmonary artery pressures were not estimated. The patient was therapeutically anticoagulated with enoxaparin sodium (Lovenox) but developed worsening hypoxemia and metabolic acidosis with a subsequent PEA cardiac arrest. Immediate cardiopulmonary resuscitation (CPR) was initiated followed by multiple rounds of epinephrine; a bolus of 50-mg tissue plasminogen activator (tPA) was also administered with return of spontaneous circulation after 37 minutes. A follow-up infusion of 50-mg intravenous tPA over 2 hours was performed. Therapeutic hypothermia was not attempted post–cardiac arrest because the patient evidenced bleeding from puncture sites involving the internal jugular vein and antecubital veins. After 24 hours, the patient was fully awake and alert with hemodynamic stability. She was extubated 48 hours later to 2 L/m oxygen via nasal cannula along with rapid weaning of vasopressors. A
☆ Institution of report: Mercy Hospital, Saint Louis. ☆☆ Financial Disclosures: None.
follow-up echocardiogram approximately 1 year later revealed no evidence of right ventricular dilatation with normal right ventricular systolic function and pulmonary pressures. Case 2: A 68-year-old white woman presented to the ED with acute dyspnea; blood pressure, 94/76 mm Hg; heart rate, 168 per minute; respiratory rate, 36 per minute, and SpO2 86% on room air. Laboratory testing revealed a lactic acidosis of 10 mmol/L and a brain natriuretic peptide level of 8232 pg/mL. The electrocardiogram revealed atrial fibrillation with a rapid ventricular response, incomplete right bundle branch block, and an S1Q3T3 pattern. Emergent echocardiography revealed severe right ventricular dilatation and severe hypokinesis; pulmonary artery pressures were not estimated. The patient rapidly deteriorated in the ED and necessitated endotracheal intubation for worsening respiratory distress and hypoxemia, culminating in a PEA cardiac arrest. Immediate CPR was initiated. Presumptive thrombolytic therapy with a bolus of 50-mg tissue tPA was administered with return of spontaneous circulation after 45 minutes. A follow-up infusion of 50-mg intravenous tPA over 2 hours was performed, along with therapeutic infusion of unfractionated heparin. Targeted temperature management with therapeutic hypothermia was performed post–cardiac arrest. Subsequent venous Doppler studies of the lower extremities demonstrated acute deep venous thrombosis of the right femoral vein. The patient eventually necessitated a tracheostomy but was successfully decannulated in a long-term acute care facility without the need for supplemental oxygen. The 2010 Advanced Cardiac Life Support Guidelines recommend thrombolytics for presumed or known PE during a code situation (class IIa, level of evidence B) [2]. According to the scientific statement published by American Heart Association regarding management of massive PE, which is defined as an acute PE with sustained hypotension (systolic blood pressure b90 mm Hg) for at least 15 minutes or requiring inotropic support not caused by other than PE, the recommended dosing of thrombolytics is tPA 100 mg infused over 2 hours [3]. However, the British Thoracic Guidelines from 2003 recommend a 50-mg bolus of tPA during cardiac arrest if massive PE is suspected clinically or even if cardiac arrest is likewise “imminent” [4]. Previous studies have suggested that a bolus regimen of tPA produces accelerated thrombolysis [5], although a tPA infusion appeared more effective in a metaanalysis by Capstick et al [6]. Both our patients experiencing PEA arrests were administered a hybrid dosing regimen of a 50-mg tPA bolus followed by a further 50 mg over the next 2 hours. We postulate that such a dosage regimen for both proven and
0735-6757/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Katyal A, et al, Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.03.053
2
Correspondence / American Journal of Emergency Medicine xxx (2015) xxx–xxx
presumptive therapy of PE causing cardiac arrest may provide an accelerated effect and combine the benefit of thrombolysis with mitigation of bleeding risk. The most feared complication of thrombolytic therapy is hemorrhage, particularly intracranial. An analysis of data from 5 clinical trials using thrombolytics in acute PE reported a risk of intracranial hemorrhage of 1.9% [7], although subsequent data from the International Cooperative Pulmonary Embolism Registry demonstrated a risk as high as 3% as far as intracranial hemorrhage is concerned [8]. Likewise, there is concern about bleeding risk in patients receiving thrombolytics with prolonged CPR (N10 minutes). In a retrospective cohort study, although thrombolytics were associated with greater risk of major bleeding (not statistically significant), there was no relationship to duration of CPR [9]. However, data from all these studies uniformly advocate careful patient selection before administration of fibrinolytic therapy [10]. Therefore, we urge routine consideration of thrombolytic therapy by emergency and critical care physicians in clinical scenarios such as the aforementioned cases, using sound clinical judgment on a case-by-case basis, especially given the narrow window of opportunity to potentially impact outcomes.
Anup Katyal, MD Critical Care Medicine, Mercy Clinic and Hospital Saint Louis 621 S. New Ballas Rd, Tower B, Ste 4006 St. Louis, MO 63141 Dayton Dmello, MD, MBA Pulmonary, Critical Care and Sleep Medicine Mercy Clinic and Hospital, St. Louis, MO 63141 Corresponding author. Tel.: + 314 251 4966; fax: 314 251 4588 E-mail address: [email protected]
Robert W. Taylor, MD Critical Care Medicine, Mercy Clinic and Hospital Saint Louis 621 S. New Ballas Rd, Tower B, Ste 4006 St. Louis, MO 63141
http://dx.doi.org/10.1016/j.ajem.2015.03.053
References [1] Logan J, Pantle H, Huiras P, Bessman E, Bright L. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism. Am J Emerg Med 2014;32:789–96. [2] Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S829–61. [3] Jaff MR, McMurthy MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep venous thrombosis and chronic thromboembolic pulmonary hypertension: A scientific statement from American Heart Association. Circulation 2011;123:1788–830. [4] British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470–84. [5] Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, et al. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 1990;98(6):147. [6] Capstick T, Henry MT. Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J 2005;26:864–74. [7] 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;111:241–5. [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] 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 2005;57:49–55. [10] Piazza G, Goldhaber S. Fibrinolysis for acute pulmonary embolism. Vasc Med 2010;15(5):419–28.
Please cite this article as: Katyal A, et al, Thrombolytic therapy for cardiac arrest secondary to acute pulmonary embolism: an oft overlooked strategy, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.03.053
