Elsevier

Resuscitation

Volume 69, Issue 3, June 2006, Pages 399-406
Resuscitation

Clinical paper
Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions☆

https://doi.org/10.1016/j.resuscitation.2005.09.027Get rights and content

Summary

Background

Prospective and retrospective studies have shown that empiric use of fibrinolytic agents in sudden cardiac arrest is safe and may improve outcomes in sudden cardiac arrest. Use of fibrinolytic agents for this indication is increasing in response to these data.

Methods

A prospective multicenter observational trial was performed in three emergency departments (EDs) to determine the proportion of patients that respond to empiric fibrinolysis with tenecteplase (TNK) after failing to respond to Advanced Cardiac Life Support (ACLS) measures. Cardiac arrest patients unresponsive to ACLS, who were given TNK by their treating physician, were enrolled in an outcome registry. Return of spontaneous circulation (ROSC), survival, complications, and neurological outcomes were recorded.

Results

Fifty patients received TNK after a mean of 30 min of cardiac arrest and eight doses of ACLS medications. One hundred and thirteen concurrent control patients received standard ACLS measures. ROSC occurred in 26% of TNK patients (95% confidence interval (CI) 16–40%) compared to 12.4% (95% CI 6.9–20%) among ACLS controls (p = .04); 12% (4.5–24%) of TNK patients survived to admission compared to none in the control group (p = .0007); 4% (0.5–14%) survived to 24 h (p = NS); and 4% (0.5–14%) survived to hospital discharge (p = NS). All survivors had a good neurological outcome (Cerebral Performance Category (CPC) 1–2). One intracranial hemorrhage (ICH) occurred. No other significant bleeding complications were observed.

Conclusions

Empiric fibrinolysis with TNK in cardiac arrest is associated with increased ROSC and short term survival, and with survival to hospital discharge with good neurological function in patients who fail to respond to ACLS. Results may improve with earlier administration. Prospective controlled interventional trials are indicated to evaluate this promising new therapy.

Introduction

Sudden unexpected cardiac arrest is the most common cause of adult death. It is estimated to occur from 250,000 to 480,000 times yearly in the United States and is frequently the first and only manifestation of coronary artery disease (CAD).1, 2, 3, 4 Standard prehospital and emergency treatment using Advanced Cardiac Life Support (ACLS) measures have produced disappointing results, with overall survival rates ranging from 5 to 10%.5, 6, 7

Epidemiological studies suggest that coronary artery disease is the most common cause of sudden cardiac arrest, producing arrest within an hour of symptom onset by massive myocardial infarction (MI) or ischemia-related dysrhythmia in 56–88% of cases.2, 3, 8, 9 Pulmonary embolism is the next most common cause, estimated to produce 4.8–9.6% of cases.10, 11, 12, 13 The remainder of cases may be produced by intracranial hemorrhage (ICH), aortic dissection or aneurysmal rupture, and a variety of other causes.10

Systemic fibrinolysis is used in the treatment of patients suffering from acute MI and pulmonary embolism producing hemodynamic instability, thus fibrinolytic agents may be indicated in the large majority of sudden cardiac arrest patients. These agents have been avoided previously in the cardiac arrest setting due to concerns of potential bleeding complications produced by the trauma of chest compressions during cardiopulmonary resuscitation (CPR). However, several studies conducted in the early 1990s suggest that bleeding complications are not increased after fibrinolysis in combination with CPR.14, 15, 16, 17, 18, 19 In response to these data, case reports, retrospective studies, and prospective studies have begun to appear, suggesting that systemic fibrinolysis combined with CPR may improve both overall survival and neurological outcomes markedly.20, 21, 22, 23, 24, 25

Recognizing that the current literature on empiric fibrinolysis as a treatment for sudden cardiac arrest suggests a lack of harm and potentially large increases in survival, many clinicians consider empiric fibrinolytic agents in selected cases of cardiac arrest. Tenecteplase (TNK), an FDA approved fibrinolytic agent given as a single bolus injection, is attractive for use in the resuscitation setting because of its ease of administration, pharmacokinetic profile, and fibrin specificity resulting in a low incidence of bleeding.26 We performed a prospective multicenter non-randomized observational trial to record whether patients in cardiac arrest who do not respond to ACLS interventions may respond to empiric fibrinolysis with TNK.

Section snippets

Materials and methods

With approval from the institutional review board, a prospective multicenter observational outcomes registry was established. Surveillance of cardiac arrest treatment was established from January through September 2003 at three emergency departments (EDs) in two neighboring cities with a combined annual patient volume of approximately 130,000. These included one urban teaching hospital (ED volume 75,000 k/year), one suburban/rural teaching hospital (ED volume 38,000 k/year), and one urban

Results

During the study period, 50 patients who did not respond to standard ACLS measures received empiric fibrinolysis with TNK in the ED. An additional 113 patients received standard ACLS measures without fibrinolysis and were declared dead in the Emergency Department. An Utstein-style analysis diagram is shown (Figure 2). Patients in each group had similar sex distributions and comorbidities (Table 1). Patients who received fibrinolysis tended to be younger, more likely to have had a witnessed

Discussion

This prospective multicenter observational study of empiric fibrinolysis with tenecteplase in sudden cardiac arrest is, to the authors’ knowledge, the first in the United States. Similar to the European experience with tissue plasminogen activator (TPA), these results suggest improvement in cardiac arrest outcomes. Even though the administration of fibrinolysis was delayed for a mean of 30 min after cardiac arrest, ROSC occurred in approximately one quarter of patients. There was an increase in

Conclusion

In summary, this prospective observational trial found that empiric fibrinolysis with TNK during cardiac arrest unresponsive to standard ACLS measures is associated with an increased rate of ROSC, increased short term survival, and neurologically intact survival to hospital discharge. This is in concordance with several previous investigations utilizing systemic fibrinolysis in cardiac arrest. Combined with animal and human evidence of improved neurological outcome after cardiac arrest, these

Conflict of interest statement

None of the authors report any financial or personal conflicts of interest.

Acknowledgements

The authors gratefully acknowledge the support and assistance of Dia Dooley, CTC, and Drs. Aaron McKinney, Kevin King, and Lilane Rifenberg in the conduct of this investigation. A grant from the Investigator Sponsored Trial Program of Genentech, Inc. ($40,500) supported the administrative costs of the trial. No study medications were provided. Genentech had no input or control over the design or conduct of the trial, or in the development of the manuscript.

References (34)

  • W. Schreiber

    Thrombolytic therapy after cardiac arrest and its effect on neurological outcome

    Resuscitation

    (2002)
  • W. Lederer

    Long-term survival and neurological outcome of patients who received recombinant tissue plasminogen activator during out-of-hospital cardiac arrest

    Resuscitation

    (2004)
  • J. Johansson

    Antithrombin reduction after experimental cardiopulmonary resuscitation

    Resuscitation

    (2003)
  • D.M. Fatovich et al.

    A pilot randomised trial of thrombolysis in cardiac arrest (the TICA trial)

    Resuscitation

    (2004)
  • Z.J. Zheng

    Sudden cardiac death in the United States, 1989 to 1998

    Circulation

    (2001)
  • D.P. Zipes et al.

    Sudden cardiac death

    Circulation

    (1998)
  • E. Engelstein et al.

    Sudden cardiac death

    • Cited by (0)

    ☆

    A Spanish translated version of the summary of this article appears as Appendix in the online version at 10.1016/j.resuscitation.2005.09.027.

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