Bolus thrombolytic infusion during prolonged refractory cardiac arrest of undiagnosed cause

Abstract

Acute myocardial infarction (AMI) and pulmonary embolism (PE) account for about 70% of cardiac arrest. Although thrombolytic therapy is an effective therapy for both AMI and PE, it is not routinely recommended during cardiopulmonary resuscitation (CPR) for fear of life threatening bleeding complications. Numerous case reports and retrospective studies have suggested a beneficial effect of thrombolytics in cardiac arrest secondary to AMI and PE; however, we present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest (undiagnosed cause) after prolonged conventional resuscitation without success.

Despite advances in resuscitation research, cardiac arrest still carries a poor prognosis. More than 70% of cases are caused by acute myocardial infarction (AMI) or pulmonary embolism (PE).¹,² Although thrombolytic therapy is an effective therapy for both AMI³ and PE,⁴ it is not routinely recommended during cardiopulmonary resuscitation (CPR), owing to fear of life threatening bleeding complications. We present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest (undiagnosed cause) after prolonged conventional resuscitation without response to conventional resuscitative efforts.

CASE REPORT

A 19 year old woman was admitted to the medical intensive care unit for respiratory failure secondary to Guillian‐Barré syndrome. She was intubated, and treatment was initiated with daily plasma exchange therapy. On hospital day 7, she was extubated because of marked improvement in clinical status. Post‐extubation, she complained of sudden onset chest pain and dyspnoea while resting in a cardiac chair. Within 5 minutes of symptom onset, she suddenly developed asystole. Advanced cardiac life support measures were implemented, including intubation and external chest compression. Ventricular fibrillation set in and she received three attempts at defibrillation, with administration of atropine, epinephrine, sodium bicarbonate, lidocaine, and magnesium sulphate. Her rhythm changed to pulseless electrical activity (PEA) and she remained without return of spontaneous circulation for 18 minutes. In the face of persistent PEA, the patient was given bolus injection of 100 U of recombinant human tissue plasminogen activator (rh‐tPA) through a femoral venous catheter. Approximately 3 minutes after the rh‐tPA infusion, she had return of spontaneous circulation with wide complex tachycardia, which converted to sinus rhythm following administration of amiodarone. Post‐resuscitation, blood pressure was 146/85 mm Hg and heart rate was 151 beats/min. An electrocardiogram 30 minutes post‐resuscitation revealed a new right bundle branch pattern with strain. There was minor bleeding from intravenous sites, which was managed conservatively. Venous Doppler study 2 hours after resuscitation was negative for deep venous thrombosis. A contrast computed tomogram performed approximately 4 hours after resuscitation did not show any evidence of pulmonary embolism or deep venous thrombosis. Two weeks later, she was haemodynamically stable with persistent peripheral weakness but no observable sequelae related to her cardiac arrest.

DISCUSSION

The American College of Cardiology (ACC) and the American Heart Association (AHA), in a joint task force report listed CPR as a “relative minor contraindication” for patient selection for thrombolytic therapy.⁵ Over the past two decades, numerous case reports, case series, and retrospective studies have suggested that thrombolysis during CPR can lead to return of spontaneous circulation (ROSC) with improved neurological outcomes in patients with PE and AMI.⁶,⁷,⁸,⁹

In a retrospective study of 21 patients with cardiac arrest after massive PE who were treated with bolus thrombolytics during CPR, a significantly higher rate of ROSC was observed in the thrombolysis group compared with a control group that did not receive thrombolysis during CPR (81% v 43%; p = 0.03).⁸ A pilot randomized trial of thrombolysis in cardiac arrest¹⁰ included 35 patients with out of hospital cardiac arrest, of whom 19 received tenecteplase and 16 placebo. ROSC occurred in eight patients (42%) receiving tenecteplase and one placebo (6%) (36% difference, 95% confidence interval 11% to 61%). A multicentre trial of tenecteplase in out of hospital cardiac arrest¹¹ is underway, with results expected in 2006.

Recent guidelines by ACC/AHA no longer contain the contraindication of thrombolytics during CPR.¹² While most of the clinical evidence suggests beneficial effect of thrombolysis in cardiac arrest secondary to AMI or PE, our case documents a beneficial outcome in undifferentiated cardiac arrest and prolonged unsuccessful conventional resuscitation. The temporal relationship between thrombolytic administration and ROSC after prolonged unsuccessful CPR suggests a beneficial effect in our patient. Although pulmonary embolism was suspected as the aetiology of cardiac arrest in our patient, it could not be confirmed because of the delay between thrombolytic administration and imaging.

The effectiveness of thrombolytics during CPR can be explained by two proposed mechanisms. Firstly, it acts locally at the site of coronary³ or pulmonary vessel⁴,¹³ thrombosis, leading to rapid correction of underlying pathology. Secondly, it has a neuroprotective effect secondary to its action on microcirculatory reperfusion.¹⁴ Cardiac arrest and CPR are associated with a striking activation of blood coagulation, without adequate activation of endogenous fibrinolysis, leading to microthromboses throughout the entire microcirculation.¹⁵,¹⁶ Thrombolytic agents thus lead to immediate improvement in cerebral microcirculatory reperfusion and myocardial contractility.¹⁷,¹⁸

Given the current poor outcome of prolonged unresponsive cardiac arrest, the potential benefits of thrombolysis during CPR may outweigh the risk of major bleeding complications. Single bolus injection of a thrombolytic agent should be considered in this scenario.

CONCLUSION

Bolus thrombolytic administration during refractory CPR may facilitate spontaneous return of circulation even in patients with undiagnosed cause. Current clinical data, although encouraging, is insufficient to recommend routine use of bolus thrombolytic during CPR in all patients. There is a need for randomised prospective studies to investigate the effect of thrombolytic therapy in patients with prolonged unsuccessful cardiopulmonary resuscitation and to identify patients who would benefit from such intervention.

Abbreviations

ACC - American College of Cardiology

AHA - American Heart Association

AMI - acute myocardial infarction

CPR - cardiopulmonary resuscitation

PE - pulmonary embolism

PEA - pulseless electrical activity

rh‐tPA - recombinant human tissue plasminogen activator

ROSC - return of spontaneous circulation