Thrombolysis During Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Pulmonary Embolism Increases 30-Day Survival

Findings From the French National Cardiac Arrest Registry
Published:August 02, 2019DOI:


      Pulmonary embolism (PE) represents 2% to 5% of all causes of out-of-hospital cardiac arrest (OHCA) and is associated with extremely unfavorable prognosis. In PE-related OHCA, inconsistent data showed that thrombolysis during cardiopulmonary resuscitation may favor survival.


      This was a retrospective, observational, multicenter study from July 2011 to March 2018. All adults with OHCA, treated by a mobile ICU and with a diagnosis of PE confirmed on hospital admission, were included. The primary end point was 30-day survival in a weighted population.


      Of the 14,253 patients admitted to hospitals, 328 had a final diagnosis of PE and 246 were included in the analysis. In the group that received thrombolysis during resuscitation (n = 58), 14 (24%) received alteplase, 43 (74%) received tenecteplase, and one (2%) received streptokinase. Thirty-day survival was higher in the thrombolysis group than in the control group (16% vs 6%; P = .005; adjusted log-rank test) but the good neurologic outcome was not significantly different (10% vs 5%; adjusted relative risk, 1.97; 95% CI, 0.70-5.56). Median duration of stay in the ICU was 1 (0-5) day for the thrombolysis group and 1 (0-3) day for the control group ( P = .23).


      In patients with OHCA with confirmed PE and admitted with recuperation of spontaneous circulation in the hospital, there was significantly higher 30-day survival in those who received thrombolysis during cardiopulmonary resuscitation compared with patients who did not receive thrombolysis.

      Key Words


      BLS ( basic life support), CPC ( Glasgow-Pittsburgh Cerebral Performance Category), CPR ( cardiopulmonary resuscitation), CTPA ( CT pulmonary angiography), IPTW ( inverse probability of treatment weighting), MICU ( mobile ICU), OHCA ( out-of-hospital cardiac arrest), PE ( pulmonary embolism), RéAC ( French National OHCA Registry), ROSC ( return of spontaneous circulation)
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        • Nichol G.
        • Thomas E.
        • Callaway C.
        • et al.
        Regional variation in out-of-hospital cardiac arrest incidence and outcome.
        JAMA. 2008; 300: 1423-1431
        • Ong M.
        • Shin S.
        • De Souza N.
        • et al.
        Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: the Pan Asian Resuscitation Outcomes Study (PAROS).
        Recuscitation. 2015; 96: 100-108
        • Engdahl J.
        • Holmberg M.
        • Karlson B.W.
        • Luepker R.
        • Herlitz J.
        The epidemiology of out-of-hospital “sudden” cardiac arrest.
        Resuscitation. 2002; 52: 235-245
        • Böttiger B.W.
        • Arntz H.-R.
        • Chamberlain D.A.
        • et al.
        Thrombolysis during resuscitation for out-of-hospital cardiac arrest.
        N Engl J Med. 2008; 359: 2651-2662
        • Bougouin W.
        • Marijon E.
        • Planquette B.
        • et al.
        Pulmonary embolism related sudden cardiac arrest admitted alive at hospital: management and outcomes.
        Resuscitation. 2017; 115: 135-140
        • Heradstveit B.E.
        • Sunde K.
        • Sunde G.-A.
        • Wentzel-Larsen T.
        • Heltne J.-K.
        Factors complicating interpretation of capnography during advanced life support in cardiac arrest—a clinical retrospective study in 575 patients.
        Resuscitation. 2012; 83: 813-818
        • Hess E.P.
        • Campbell R.L.
        • White R.D.
        Epidemiology, trends, and outcome of out-of-hospital cardiac arrest of non-cardiac origin.
        Resuscitation. 2007; 72: 200-206
        • Kuisma M.
        • Alaspää A.
        Out-of-hospital cardiac arrests of non-cardiac origin: epidemiology and outcome.
        Eur Heart J. 1997; 18: 1122-1128
        • Kürkciyan I.
        • Meron G.
        • Sterz F.
        • et al.
        Pulmonary embolism as a cause of cardiac arrest: presentation and outcome.
        Arch Intern Med. 2000; 160: 1529-1535
        • Böttiger B.W.
        • Bode C.
        • Kern S.
        • et al.
        Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial.
        Lancet. 2001; 357: 1583-1585
        • Abu-Laban R.B.
        • Christenson J.M.
        • Innes G.D.
        • et al.
        Tissue plasminogen activator in cardiac arrest with pulseless electrical activity.
        N Engl J Med. 2002; 346: 1522-1528
        • Fatovich D.M.
        • Dobb G.J.
        • Clugston R.A.
        A pilot randomised trial of thrombolysis in cardiac arrest (the TICA trial).
        Resuscitation. 2004; 61: 309-313
        • Jerjes-Sanchez C.
        • Ramirez-Rivera A.
        • de Lourdes Garcia M.
        • et al.
        Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial.
        J Thromb Thrombolysis. 1995; 2: 227-229
        • Sharifi M.
        • Bay C.
        • Skrocki L.
        • Rahimi F.
        • Mehdipour M.
        • MOPETT Investigators
        Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial).
        Am J Cardiol. 2013; 111: 273-277
        • Chatterjee S.
        • Chakraborty A.
        • Weinberg I.
        • et al.
        Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.
        JAMA. 2014; 311: 2414-2421
        • Li X.
        • Fu Q.
        • Jing X.
        • et al.
        A meta-analysis of cardiopulmonary resuscitation with and without the administration of thrombolytic agents.
        Resuscitation. 2006; 70: 31-36
        • Logan J.K.
        • 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: 789-796
        • Lavonas E.J.
        • Drennan I.R.
        • Gabrielli A.
        • et al.
        Part 10: Special circumstances of resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2015; 132: S501-S518
        • Truhlář A.
        • Deakin C.D.
        • Soar J.
        • et al.
        European Resuscitation Council guidelines for resuscitation 2015: Section 4: Cardiac arrest in special circumstances.
        Resuscitation. 2015; 95: 148-201
        • Adnet F.
        • Lapostolle F.
        International EMS systems: France.
        Resuscitation. 2004; 63: 7-9
        • Jacobs I.
        • Nadkarni V.
        • Bahr J.
        • et al.
        Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa).
        Circulation. 2004; 110: 3385-3387
        • Hubert H.
        • Tazarourte K.
        • Wiel E.
        • et al.
        Rationale, methodology, implementation, and first results of the French out-of-hospital cardiac arrest registry.
        Prehosp Emerg Care. 2014; 18: 511-519
        • Patel S.
        • Kazerooni E.A.
        • Cascade P.N.
        Pulmonary embolism: optimization of small pulmonary artery visualization at multi-detector row CT.
        Radiology. 2003; 227: 455-460
        • Torbicki A.
        • Perrier A.
        • Konstantinides S.
        • et al.
        Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC).
        Eur Heart J. 2008; 29: 2276-2315
        • Konstantinides S.V.
        • Torbicki A.
        • Agnelli G.
        • et al.
        • Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)
        2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.
        Eur Heart J. 2014; 35: 3033-3073
        • Jaber W.A.
        • Fong P.P.
        • Weisz G.
        • et al.
        Acute pulmonary embolism.
        J Am Coll Cardiol. 2016; 67: 991-1002
        • Brookhart M.A.
        • Schneeweiss S.
        • Rothman K.J.
        • Glynn R.J.
        • Avorn J.
        • Stürmer T.
        Variable selection for propensity score models.
        Am J Epidemiol. 2006; 163: 1149-1156
        • Le Borgne F.
        • Giraudeau B.
        • Querard A.H.
        • Giral M.
        • Foucher Y.
        Comparisons of the performance of different statistical tests for time-to-event analysis with confounding factors: practical illustrations in kidney transplantation.
        Stat Med. 2016; 35: 1103-1116
        • Bougouin W.
        • Lamhaut L.
        • Marijon E.
        • et al.
        Characteristics and prognosis of sudden cardiac death in Greater Paris: population-based approach from the Paris Sudden Death Expertise Center (Paris-SDEC).
        Intensive Care Med. 2014; 40: 846-854
        • Lederer W.
        • Lichtenberger C.
        • Pechlaner C.
        • Kroesen G.
        • Baubin M.
        Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out-of-hospital cardiac arrest.
        Resuscitation. 2001; 50: 71-76
        • Janata K.
        • Holzer M.
        • Kürkciyan I.
        • 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
        • Hao Q.
        • Dong B.R.
        • Yue J.
        • Wu T.
        • Liu G.J.
        Thrombolytic therapy for pulmonary embolism.
        Cochrane Database Syst Rev. 2018; 12: CD004437
        • Pokorna M.
        • Necas E.
        • Skripsky R.
        • Kratochvil J.
        • Andrlik M.
        • Franek O.
        How accurately can the aetiology of cardiac arrest be established in an out-of-hospital setting? Analysis by “concordance in diagnosis crosscheck tables.”.
        Resuscitation. 2011; 82: 391-397
        • Bougouin W.
        • Marijon E.
        • Planquette B.
        • et al.
        Factors associated with pulmonary embolism-related sudden cardiac arrest.
        Circulation. 2016; 134: 2125-2127
        • Breitkreutz R.
        • Price S.
        • Steiger H.V.
        • et al.
        Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial.
        Resuscitation. 2010; 81: 1527-1533
        • MacCarthy P.
        • Worrall A.
        • McCarthy G.
        • Davies J.
        The use of transthoracic echocardiography to guide thrombolytic therapy during cardiac arrest due to massive pulmonary embolism.
        Emerg Med J. 2002; 19: 178-179
        • Torbicki A.
        • Galié N.
        • Covezzoli A.
        • et al.
        Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry.
        J Am Coll Cardiol. 2003; 41: 2245-2251
        • Link M.S.
        • Berkow L.C.
        • Kudenchuk P.J.
        • et al.
        Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2015; 132: S444-S464
        • Soar J.
        • Nolan J.P.
        • Böttiger B.W.
        • et al.
        European Resuscitation Council guidelines for resuscitation 2015: Section 3: adult advanced life support.
        Resuscitation. 2015; 95: 100-147
        • Aagaard R.
        • Caap P.
        • Hansson N.C.
        • Bøtker M.T.
        • Granfeldt A.
        • Løfgren B.
        Detection of pulmonary embolism during cardiac arrest—ultrasonographic findings should be interpreted with caution.
        Crit Care Med. 2017; 45: e695-e702
        • Austin P.C.
        The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments.
        Stat Med. 2014; 33: 1242-1258

      Linked Article

      • Response
        CHESTVol. 157Issue 5
        • In Brief
          We thank Drs Patel and Bergl for their interest and comments regarding our article on thrombolysis during resuscitation of out-of-hospital cardiac arrest (OHCA) caused by pulmonary embolism (PE).1 They highlight some limitations of our study that we will clarify point by point.
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      • Confirm, Don’t Conform Toward Thrombolysis in Acute Pulmonary Embolism in Out-of-Hospital Cardiac Arrest
        CHESTVol. 157Issue 5
        • In Brief
          In a recent issue of CHEST (December 2019), using the French National Cardiac Arrest Registry to identify pulmonary embolism (PE)-related out-of-hospital cardiac arrests (OHCAs), Javaudin et al1 found higher 30-day suval in those who received thrombolysis during CPR compared with patients who did not receive thrombolysis, after weighting the population using seven variables.1 Although the authors’ conclusions may stoke our collective curiosity, we would like to explore methodologic concerns that may limit their soundness.
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