Case Report

Successful prolonged resuscitation involving the use of tenecteplase without Neurological sequelae

Abstract

Prehospital cardiac arrest is associated with a very poor prognosis. We report a case of complete neurological recovery after prolonged resuscitation involving the use of tenecteplase in a patient with undifferentiated cardiac arrest with a return of spontaneous circulation after 1 hour of resuscitation, where basic life support was commenced immediately by a bystanding family member. Factors associated with an increased chance of survival from out- of-hospital cardiac arrest are discussed as well as the role of thrombolytics in cardiopulmonary resuscitation.

Most resuscitation attempts do not succeed and have to be abandoned. According to the current European Resuscitation Council (ERC) Guidelines, it is generally accepted that ongoing asystole for more than 20 minutes in the absence of a reversible cause, and with all Advanced life support measures in place, constitutes grounds for abandoning the resuscitation attempt [1]. Although the prognosis of patients having a cardiac arrest is generally poor, under certain circumstances, prolonging resuscitation can be highly successful. The overall survival of patients with an out-of- hospital cardiac arrest (OHCA) found in a nonshockable rhythm is very low (1.3%). According to Herlitz et al [2], 6 different factors independently associated with survival can be defined: age, witnessed cardiac arrest, place, bystander cardiopulmonary resuscitation (CPR), a short Ambulance response time, and defibrillation. When they are taken into account, survival varies between 12.6% and 0.15% [2]. Interventions that aim to improve outcome in cardiac arrest have proved disappointing. In particular, no drug has been proved to increase survival to discharge after cardiac arrest. Given that acute myocardial infarction and pulmonary embolism (PE) account for about 70% of cardiac arrest, the use of thrombolytic agents has been advocated. A large series of case reports, retrospective analyses, and some prospective studies have shown favorable results and have proposed plausible mechanisms to explain the role of thrombolytic agents in cardiac arrest [3-12]. They are, however, in contradiction to at least 2 large randomized trials that failed to demonstrate a benefit for alteplase in patients with pulseless

electric activity [13] or tenecteplase in patients with presumed cardiac cause of arrest and ventricular fibrillation or pulseless activity [14]. These results demonstrate that fibrinolysis cannot be generally recommended as standard treatment for patients with refractory OHCA. Accordingly, The Interna- tional Liaison Committee on Resuscitation [15] states, “Fibrinolysis should be considered in adult patients with cardiac arrest with proven or suspected pulmonary embolism. There are insufficient data to support or decline the routine use of fibrinolysis in cardiac arrest from other causes.”

We present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest with a return of spontaneous circulation after 1 hour of resuscitation, where basic CPR was commenced immedi- ately by a bystanding family member.

A 48-year-old man with no previous medical history apart from nicotine and alcohol abuse felt dizzy after carrying a sofa to the third floor of an apartment building with his son-in-law. Immediately after mentioning his condition, he collapsed. His son-in-law, a policeman, happened to have taken a basic life support (BLS) retraining the day before. He witnessed and recognized the arrest, called for help, and promptly started to perform BLS. Thirteen minutes after the arrest, an ambulance arrived at the scene. The emergency medical technicians continued the BLS measures and initiated oxygen Bag-mask ventilation. The patient was monitored using an automated external defibrillator. According to that device, there was no shockable rhythm detected. Two minutes later, the emergency physician reached the patient. Tracheal intubation was successful at the first attempt, an intravenous access was established via the left external jugular vein, and the first 1 mg bolus of epinephrine administered. Meanwhile, the electrodes of the standard external defibrillator were attached to the patient. The electrocardiogram still showed asystole. The end- tidal carbon dioxide was measured by mainstream capnogra- phy: the sensor reading was 6 to 7 mm Hg. Pulse oximetry could not be obtained. Thirteen minutes after the physician’s arrival at the scene, the patient still had no shockable rhythm and a low carbon dioxide output. The emergency physician then decided to administer tenecteplase because of the suspected diagnosis of PE. Five minutes after administration of the thrombolytic agent, capnography showed 40 mm Hg end-tidal carbon dioxide and pulse oximetry began to deliver a peripheral pulse curve and oxygen saturation readings between 95% and 96%.The patient’s rhythm changed to ventricular

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fibrillation. Cardiopulmonary resuscitation was continued with multiple shocks. Thirty-five minutes after arrival of the emergency physician, sinus rhythm could be recorded for the first time. The patient’s rhythm deteriorated to ventricular fibrillation once again but was responsive to defibrillation. During the whole period, the patient received a total of 6 mg epinephrine, 3 mg atropine, 10 mg morphine, and 80 mg tenecteplase. During preparation for transport to the nearest cardiac intensive care unit (CICU), the patient opened his eyes and tried to sit up and remove his tracheal tube. Consequently, the emergency physician applied 20 mg hypnomidate and 5 mg midazolam for sedation, as well as 20 mg cis-atracurium. During transport, blood pressure was maintained at proper levels with repetitive boli of phenylephrine. At handover to the CICU medical staff, 2 hours after the alarm, the patient was stable. The first arterial blood gas samples obtained at the intensive care unit showed the following values: pH 7.27, PaCO2 36 mm Hg, PaO2 79 mm Hg, base excess -10.4, aHCO₃

16.5 mmol/L, SaO2 98%. On arrival at the CICU, the

electrocardiogram showed no infarct-typical changes. Echo- cardiographic assessment showed significantly reduced left ventricular function, diffuse hypokinesia of the left ventricle, and marked hypokinesia of the interventricular septum. D-Dimer was greater than 6580 ug/L, troponin I 13010 ng/L, creatine kinase 476 U/L, creatine kinase-MB 194 U/L. When extubation took place on the following day, the patient was neurologically inconspicuous. Unfortunately, he developed sepsis with subsequent multiple organ failure with acute renal failure and adult respiratory distress syndrome requiring prolonged intensive care unit treatment and finally left the hospital 39 days after the event.

Three months after his cardiac arrest, the patient was admitted for exercise-induced chest pain. Coronary angio- graphy showed a high-grade stenosis of the Circumflex artery, which was successfully treated with a drug-eluting stent. Only 10 weeks later, the patient developed unstable angina and had to undergo emergency coronary artery bypass graft. Although duration of Cardiac resuscitation is an important predictive factor in determining outcome after cardiac arrest, good outcome can occur after prolonged resuscitation. Our case report is an example of survival without neurological sequelae after prolonged resuscitation in spite of the fact that the OHCA was not crew-witnessed and the patient was found in a nonshockable rhythm. Two important factors that increased the likelihood of survival in our particular case can be identified: bystander CPR and a short ambulance response time. It has been proposed that the major mechanism behind the observation that bystander CPR is associated with an increased chance of survival is the maintenance of ventricular fibrillation [16]. In a recently published survey, however, Herlitz et al [2] suggest that simply increasing the coronary perfusion pressure might improve the chance of a successful outcome. They found that bystander CPR was associated with an almost 2-fold increase in survival. We strongly believe that the importance of immediate initiation

of basic CPR must be stressed in basic CPR courses.

There is consensus in the literature on the inverse relationship between the ambulance response time and the chance of survival [2,17].

In keeping with The International Liaison Committee on Resuscitation [15], the emergency physician administered fibrinolysis on suspicion of PE. However, PE could not be confirmed in our case because of the delay between thrombolytic administration and imaging. In fact, consider- ing the patient’s clinical history, an acute myocardial infarction seems much more likely in retrospect. The effectiveness of thrombolytics during cardiac arrest include direct lysis of coronary and pulmonary thrombi, as well as systemic microfibrinolysis. It is known that a generalized Hypercoagulable state occurs during cardiac arrest. Systemic fibrinolysis may improve delivery of oxygen, glucose, and antiarrhythmic medications to cardiac and other tissues and improve the removal of metabolic by-products. By similar microcirculatory action in the central nervous system, fibrinolytic agents may positively affect neurological recovery after cardiac arrest [18]. In conclusion, despite the disappointing results from the Thrombolysis in Cardiac Arrest (TROICA) study, out-of-hospital thrombolysis during CPR in selected patients can be highly beneficial with excellent survival rates and neurological outcome, as recently demonstrated by Arntz et al [12]. Moreover, because there was no significant increase in symptomatic intracranial hemorrhage rate or major bleeds in the tenecteplase group, the Safety concerns could be largely refuted by the reports from the TROICA trial [14].

Sylvia Archan MD Gerhard Prause MD

Department of Anesthesiology and Intensive Care Medicine

Medical University of Graz 8036 Graz, Austria

E-mail address: [email protected]

Bernhard Kugler MD Sanatorium Hansa 8010 Graz, Austria

Rainer Gumpert MD Department of Traumatology Medical University of Graz 8036 Graz, Austria

Giorgio Giacomini MD

Department of Cardiology and Intensive Care Medicine

LKH Graz West 8020 Graz, Austria

doi:10.1016/j.ajem.2008.03.024

Case Report

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