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□ CASE REPORT □ Thrombolytic Therapy for Cardiac Arrest due to Pulmonary Embolism after Varicose Vein Surgery Bing Wu, Guang-ju Zhao, Huan Liang, Zhong-qiu Lu, Qiao-meng Qiu and Ying-ru Lu Abstract Anticoagulant therapy is the mainstay in the management of venous thromboembolism. Nevertheless, the situation is entirely different in the patients with submassive or massive pulmonary embolism (PE) and cardiac arrest, and the diagnosis and therapy strategy for such conditions are lacking. This patient, who presented with a cardiac arrest event after varicose vein surgery, was diagnosed as acute pulmonary embolism. She survived after administration of 50 mg recombinant tissue plasminogen activator (rt-PA) for over half an hour, along with continued anticoagulant therapy. Unfortunately, gastrointestinal and cerebral hemorrhaging occurred during the process. Key words: cardiac arrest, pulmonary embolism, thrombolytic therapy, varicose vein surgery, recombinant tissue plasminogen activator (Intern Med 51: 1899-1902, 2012) (DOI: 10.2169/internalmedicine.51.7149) Introduction Surgery is one of the recognized risk factors for deep venous thrombosis and pulmonary embolism. Several series have demonstrated pulmonary embolism after varicose vein surgery is low (1). However, if the embolism is massive and not recognized and treated timely, it may be rapidly fatal. Here we present a patient with early postoperative cardiac arrest who was diagnosed as acute pulmonary embolism after varicose vein surgery. The patient survived after administration of 50 mg recombinant tissue plasminogen activator (rt-PA) over half an hour, along with continuous anticoagulant therapy. Unfortunately, gastrointestinal and cerebral hemorrhaging occurred during the process. The diagnosis and therapy strategy of this condition are discussed. Case Report A 68-year-old woman (63 kg) was admitted to our hospital for treatment of primary varicose vein of the left lower extremity. In early March, partial stripping and high ligation of the left long saphenous vein were performed under general anesthesia. The surgery went well, and she was posi- tioned in bed postoperatively with both legs elevated and with an elastic bandage applied overnight. Low-molecularweight heparin (5,000 IU/day) was used to avoid deep vein thrombosis. Four days after admission, at 9:50 AM, after her morning walk, the patient suddenly lost consciousness. She was cyanotic, had mydriasis, and papillary light reflex was lost. Her heart rate decreased to 30-40 beats/min, cardio-pulmonary resuscitation (CPR) was started immediately. Endotracheal intubation was performed and mechanical ventilation was instituted. Epinephrine was given intravenously. No upper motor neuron signs, such as hyperreflexia, the Hoffmann sign and the Babinski sign, were noted during the process. Immediate ECG revealed sinus bradycardia with the typical S1-Q3-T3 pattern (Fig. 1). There were no significant changes in ST-T waves compared with previous ECG. Additionally, her troponin level was normal (0.03 μg/L) as well as CK-MB level (11 U/L). Bedside transthoracic echocardiography was performed by a technician from the echocardiography unit and it was interpreted in real-time by a senior cardiologist with experience in echocardiography. This revealed a significant dilated right atrium and ventricle, and left ventricular contractility was significantly reduced (Fig. 2). Coronary heart disease and cerebrovascular acci- Emergency Department, The First Affiliated Hospital of Wenzhou Medical College, P.R.China Received for publication December 19, 2011; Accepted for publication April 2, 2012 Correspondence to Dr. Zhong-qiu Lu, [email protected] 1899 Intern Med 51: 1899-1902, 2012 DOI: 10.2169/internalmedicine.51.7149 ter admission, her right upper limb muscle strength recovery was very good. Head computerized tomography (CT) showed that the hemorrhage was absorbed. She was discharged from the hospital two weeks later on warfarin, with return to premorbid condition. Discussion Figure 1. Electrocardiogram revealed sinus bradycardia with the typical S1-Q3-T3 pattern. dents were excluded and a diagnosis of acute pulmonary thromboembolism was made; rtPA (50 mg) was administered as an intravenous drip over half an hour for thrombolysis, along with continuous heparin therapy according to activated partial thromboplastin time (APTT, 50-70s). After 40 minutes of CPR, the patient resumed normal sinus rhythm, blood pressure was 127/65 mmHg, pulse was 120130 beats/min. We observed an improvement in oxygen saturation (>95%), an increase in blood pressure, absence of cyanotic and mydriasis. And then, she was admitted to the emergency intensive care unit at 13:00. After admission to EICU, The patient was placed on IV dobutamine and norepinephrine. However, the patient could not maintain hemodynamic stability. Her blood pressure was 70-90/40-50 mmHg, arterial blood gas values were pH= 7.040; PaO2=48.5 mmHg; PaCO2=72.5 mmHg; HCO3=-19.6 mmol/L; BE=-12.3 mmol/L. A spiral computerized tomographic angiography (CTA) of the chest was obtained as well as coronary angiography to exclude thrombolysis failure and coronary heart disease. CTA showed that the blood flow of the right pulmonary artery slowed down while coronary angiography was negative. A femoral arterial catheter was positioned and her blood pressure was measured as of 160/80 mmHg. Subsequently, the patient’s hemodynamic status continued to improve and achieved stability on decreasing doses of dobutamine and norepinephrine. In mid-March, five days after her loss of consciousness, mechanical ventilation was stopped. In addition, the patient’s prothrombin time (PT) was 16.6 seconds and APTT was 60.4 seconds. One day later, bloody stool was detected and repeat (complete blood count) CBC showed hemoglobin of 73 g/L, the diagnosis of gastrointestinal bleeding was made and she was treated with omeprazole while fasting. At this time, a PT of 16.2 seconds and an APTT of 40.2 seconds were detected. After five days, her clotting profile was retested and showed a PT of 17.5 seconds and an APTT of 54.3 seconds. The following day, the patient’s mouth became askew and the right upper limb muscle strength declined. A coagulation screen was taken. This revealed a PT of 18.3 seconds and an APTT of 43.7 seconds. Head computerized tomography (CT) showed intracranial bleeding (Fig. 3), and thus heparin was discontinued. At 2 months af- Pulmonary embolism is a well-known complication of major surgery but it is not always appreciated that it can occur even after minor interventions such as varicose vein surgery. In general, suspicion of PE is raised by clinical symptoms such as dyspnea, chest pain, or sustained hypotension without an alternative obvious cause. However, in the case of PE associated with unconsciousness and cardiac arrest/ PEA, the decision-making is difficult. Electrocardiographic signs of RV strain, such as inversion of T waves in leads V1 to V4, a QR pattern in lead V1, the classic S1Q3T3 type and incomplete or complete right bundle-branch block, may be helpful, particularly when of new onset (2, 3). Nevertheless, such changes are generally associated with the more severe forms of PE and may be found in right ventricular strain of any cause (4, 5). Bedside echocardiography is particularly helpful in emergency management decisions when computed tomography (CT) scan is not immediately available. Trans-esophageal echocardiography can provide high sensitivity (92%) and high specificity for the diagnosis of PE (near 100%) in the setting of CPR (6). In a patient with suspected PE who is in a critical condition (shock or hypotension), the absence of echocardiographic signs of RV overload or dysfunction practically excludes PE as a cause of hemodynamic compromise (4). Anticoagulant therapy is the mainstay in the management of venous thromboembolism. However, the situation is entirely different in those patients with submassive or massive PE and cardiac arrest. The European Society of Cardiology (ESC) Guidelines and other clinical practice guidelines of the American College of Chest physicians (ACCP) suggest that absolute indications for thrombolytic therapy are MPE with persistent hypotension or shock (4, 5). Drugs, such as streptokinase, urokinase and rtPA used for therapeutic thrombolysis have shown to lyse thrombi, resulting in salvaging of myocardium and improvement in patient outcome. rtPA is currently the recommended drug which can achieve a faster clot lysis with improved safety and better tolerance. In recent randomized trials, the 2 hours infusion of rtPA has led to faster angiographic and hemodynamic improvement compared with 24 hours infusion of urokinase, although lung scans obtained 24 hours after treatment were no different between the two groups (7). A more recent metaanalysis revealed no significant difference between the three regimens and crude analysis of summated data from all studies revealed that rtPA infusion had a lower mortality due to the initial PE than streptokinase (8). Considering the short duration of action, with a plasma half-life of 4-5minutes, rtPA should be given as a continu- 1900 Intern Med 51: 1899-1902, 2012 DOI: 10.2169/internalmedicine.51.7149 Figure 2. Bedside transthoracic echocardiography revealed a significant dilated right atrium and ventricle, and left ventricular contractility was significantly reduced. Figure 3. Head computerized tomography (CT) showed intracranial bleeding. 1901 Intern Med 51: 1899-1902, 2012 DOI: 10.2169/internalmedicine.51.7149 ous infusion in order to main adequate plasma concentrations at the site of the thrombus in order to cause lysis of the clot. In treatment of PE, the initial studies of rtPA generally used 2 hours of infusion (9). Nevertheless, the dose and infusion time of rtPA in management of PE-induced cardiac arrest is lacking evidence. Some reports in the literature, primarily case reports, state that rtPA 100 mg of over 15 minutes or intravenous bolus tenecteplase 0.5 mg/kg (50 mg maximum) can be considered. The present case showed that the 50 mg/30min infusion was also effective for this course of action. In fact, rapid administration of low dose rtPA (50 mg/30min) has been successfully used in management of acute myocardial infarction (10). Therefore, randomized multicenter trials will be needed for assessing the efficacy and safety of rapid administration of low dose rtPA in PE patients with cardiac arrest. The major complication of thrombolytic treatment is an increased incidence of bleeding compared with the use of heparin. A retrospective analysis found a significantly increased risk of intracranial hemorrhage in patients with hypertension and advancing age (11). Some other risk factors for bleeding include invasive procedures, an increased body mass index as well as dose and length of time of thrombolytic therapy (12). In the present case, 50 mg rtPA was used for thrombolysis, along with continuous heparin therapy according to APTT. Unfortunately, gastrointestinal and cerebral hemorrhaging occurred during the process. Moreover, a recent study revealed that the 50 mg/2h rt-PA regimen exhibits similar efficacy and less bleeding tendency than the 100 mg/2h regimen, especially in patients with a body weight of less than 65 kg (13). This evidence combined with our report prompt that optimizing rt-PA dosing is worthwhile when treating patients with cardiac arrest due to PE and should be adjunct to the guidelines. The authors state that they have no Conflict of Interest (COI). Acknowledgement This work was supported, in part, by the grant of key construction academic subject (medical innovation) of Zhejiang Province (11-CX26) References 1. Critchley G, Handa A, Maw A, et al. Complications of varicose vein surgery. Ann R Coll Surg Engl 79: 105-110, 1997. 2. Rodger M, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol 86: 807-809, A10, 2000. 3. Geibel A, Zehender M, Kasper W, et al. Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. Eur Respir J 25: 843-848, 2005. 4. Torbicki A, Perrier A, Konstantinides S, et al; ESC Committee for Practice Guidelines (CPG). 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 29: 22762315, 2008. 5. Warkentin TE, Greinacher A, Koster A, et al; American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl): 340S-380S, 2008. 6. Comess KA, DeRook FA, Russell ML, et al. The incidence of pulmonary embolism in unexplained sudden cardiac arrest with pulseless electrical activity. Am J Med 109: 351-356, 2000. 7. Meyer G, Sors H, Charbonnier B, et al. Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter doubleblind trial. The European Cooperative Study Group for Pulmonary Embolism. J Am Coll Cardiol 19: 239-245, 1992. 8. Capstick T, Henry MT. Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J 26: 864-874, 2005. 9. Goldhaber SZ, Kessler CM, Heit J, et al. Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 2: 293-298, 1988. 10. Li SH, Li ZZ, Zhu XL, et al. Curative effects of rapid administration of low dose rt-PA for 30 minutes and 60 minutes on acute myocardial infarction. Chin J Emeng Med 15: 345-347, 2006. 11. Lauer JE, Heger JJ, Mirro MJ. Hemorrhagic complications of thrombolytic therapy. Chest 108: 1520-1523, 1995. 12. Arcasoy SM, Kreit JW. Thrombolytic therapy of pulmonary embolism: a comprehensive review of current evidence. Chest 115: 1695-1707, 1999. 13. Wang C, Zhai Z, Yang Y, et al; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest 137: 254-262, 2010. Bing Wu and Guang-ju Zhao contributed equally Ⓒ 2012 The Japanese Society of Internal Medicine http://www.naika.or.jp/imindex.html 1902