Original article 167

Thrombolytic therapy in the treatment of acute sub-massive pulmonary embolism: a prospective observational study Soumya Patra, Navin Agrawal, Cholenhally Nanjappa Manjunath, Chamrajnagara M. Nagesh, Budnur C. Srinivas, Krishnappa Shankarappa Ravindranath and Babu Reddy The use of thrombolytic therapy in haemodynamically stable patients with sub-massive pulmonary embolism is still controversial. We conducted this study to observe the safety and efficacy of thrombolytic therapy in acute pulmonary embolism patients with normal blood pressure in a tertiary cardiac centre. In this study, 130 patients with sub-massive pulmonary embolism who had right-ventricular dysfunction were included and treated with thrombolytic therapy. Fortyone percent of patients in our study were within 40 years of age. Eighty-three percent of patients had clinical improvement. Both right-ventricular dysfunction and pulmonary artery systolic pressure were improved significantly following thrombolytic therapy from baseline (49 vs. 28 mmHg; P U 0.01; 95% confidence interval S13 to S56). Only 9% patients had died and two patients had intra-cerebral haemorrhage during this study. Thrombolytic therapy may be helpful in improving clinical course following sub-massive

Introduction Pulmonary embolism is the third most common acute cardiovascular disease after myocardial infarction and stroke [1]. Massive and sub-massive pulmonary embolism is a life-threatening emergency [2]. This condition is usually treated urgently with measures to attain haemodynamic stability and anticoagulation [3]. Administration of thrombolytic therapy results in the accelerated lysis of acute pulmonary embolism. However, these drugs, although potentially life-saving, can cause significant bleeding complications [4]. Pulmonary embolism with cardiogenic shock and hypotension is characterized as ‘massive’ in nature and an accepted indication for thrombolysis [5], but patients with acute pulmonary embolism in the absence of hypotension may also merit consideration [4]. In a recent study of normotensive patients with acute symptomatic pulmonary embolism, thrombolytic therapy was associated with a higher risk of death than no thrombolytic therapy, although in haemodynamically unstable patients, thrombolytic therapy was possibly associated with a lower risk of death than no thrombolytic therapy [2]. The clinical benefit of thrombolytic treatment in haemodynamically stable patients with pulmonary embolism and right-ventricular dysfunction (RVD) (sub-massive) remains to be defined. There is an ongoing trial which will be addressing the best possible treatment for sub-massive pulmonary embolism [6]. Risk stratification in acute pulmonary 0957-5235 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

acute pulmonary embolism, especially for those who had low risk of bleeding. Further randomized study with large sample size is needed for final conclusion. Blood Coagul Fibrinolysis 25:167–171 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Blood Coagulation and Fibrinolysis 2014, 25:167–171 Keywords: fibrinolytic therapy, pulmonary embolism, sub-massive Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bangalore, Karnataka, India Correspondence to Dr Soumya Patra, Postdoctoral Trainee, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bannerghatta Road, Bangalore, Karnataka 560069, India Tel: +91 9686480971; e-mail: [email protected] Received 13 June 2012 Accepted 25 August 2013

embolism is most important in determining which patients are the most appropriate candidates for thrombolysis, with careful consideration of contraindications [4]. So, the present study was undertaken to observe the safety and efficacy of the thrombolytic treatment in patients of acute pulmonary embolism with RVD, but without hypotension, and to generate support towards the administration of thrombolytic agents in the management of acute pulmonary embolism.

Participants and methods Study design

It was a prospective observational study. This study was conducted in a tertiary cardiac care institution from South India from November 2011 to May 2013. Eligibility criteria Inclusion criteria

Patients of age more than 18 years with acute pulmonary embolism (first symptoms 15 days or less before presentation) and confirmed by positive findings in computed tomography pulmonary angiogram (CTPA) along with RVD diagnosed through echocardiography were included. Exclusion criteria

Patients who met the following criteria were excluded from the study: DOI:10.1097/MBC.0000000000000015

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168 Blood Coagulation and Fibrinolysis 2014, Vol 25 No 2

(1) Symptoms started more than 15 days ago. (2) Administration of a thrombolytic agent in the previous 4 days or glycoprotein IIb/IIIa antagonists within the preceding 7 days. (3) Vena cava filter insertion or pulmonary thrombectomy in the previous 4 days. (4) Uncontrolled hypertension (SBP >180 mmHg and DBP >110 mmHg, or either of the two, at presentation). (5) Known hypersensitivity to streptokinase (STK), tenecteplase (TNK), or heparin. (6) Known coagulation disorder [including use of vitamin K antagonists (VKAs) and platelet count 10 min) in the past 2 weeks. (10) Patients who had SBP lower than 90 with or without cardiogenic shock. Ethics

The study protocol was approved by the Ethics Committee of the respective authority of our institution. Written informed consent was obtained from all patients, before inclusion in the study. Methods

Written proformas were filled up during inclusion of patients which contained epidemiological information (age, sex, occupation, and place), questionnaires for risk factor evaluation (smoking, drug history, malignancy, comorbid condition, and hypercoagulable state), information of clinical presentation (dyspnoea, chest pain, syncope, cardiac arrest, etc.) and clinical signs. Those patients who confirmed CTPA for acute pulmonary embolism were treated as per unit protocol with either TNK or STK. Most of our patients were from poor economic families, so mostly they were treated with STK. All the patients were prospectively studied; data were collected, compiled and analysed.

(4) (5) (6)

(7)

defined as the ratio of the end diastolic dimension of right/left ventricle (RV/LV) greater than 1 in the apical 4-chamber view and/or greater than 0.7 in the parasternal long axis, both in the absence of right-ventricular hypertrophy. Echocardiography was scheduled to be repeated 24 h and at discharge or 7 days after study treatment administration. The pulmonary artery systolic pressure (PASP) was calculated by using tricuspid valve regurgitation jet and inferior vena cava dimension [6]. D-dimer test/troponin T assay. CTPA. Complete haemogram, bleeding time, clotting time (CT), prothrombin time (PT), and activated plasma thromboplastin time (aPTT), renal function test, liver function test. Doppler venography/ultrasound abdomen if necessary.

Treatment of the study patients

All patients who fulfilled the inclusion criteria were treated with either infusion of STK or bolus injection of TNK. STK was given as 250 000 units of intravenous bolus and followed by 100 000 units/h infusion maximum up to 24–48 h, depending upon the reduction in PASP. TNK was given as an intravenous weight-adjusted bolus (given over 5 s) at a dose ranging from 30 to 50 mg, with a 5-mg step-up for every 10 kg body weight from less than 60 to at least 90 kg. All patients received unfractionated heparin (UFH) infusion of 1000 IU//h after giving bolus of TNK. Heparin dose was adjusted in order to achieve and maintain the aPTT at 2.0–2.5  control. VKAs were started after completion of thrombolytic therapy, and UFH was continued until the international normalized ratio (INR) was maintained in the therapeutic range (2.0–3.0) for 2 consecutive days. Outcomes

Patients were evaluated on the day of discharge and the outcome in this study was to determine the clinical improvement following thrombolysis, which was defined as improvement in the New York Heart Association (NYHA) class, dyspnoea, tachycardia, hypoxemia, and improvement in general well being along with reduction of either RVD and PASP, or both of them, seen at the time of pre-discharge echocardiography.

Investigations

Complication

All patients had undergone the following investigations:

The complications were as follows:

(1) Chest radiograph. (2) ECG: For all patients, standard 12-lead ECG was recorded on admission with a paper speed of 25 mm/s. The first available ECG was used for analysis. (3) Echocardiography: Baseline echocardiography was done within 24 h from the diagnosis of pulmonary embolism. For the purpose of this study, RVD was

(1) Composite of death from any cause. (2) Haemodynamic collapse defined as at least one of the following: (a) The need for cardiopulmonary resuscitation. (b) SBP below 90 mmHg for at least 15 min, or drop of SBP by at least 40 mmHg for at least 15 min, with signs of end-organ hypoperfusion

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Thrombolytic therapy in sub-massive pulmonary embolism Patra et al. 169

(cold extremities, or urinary output

Thrombolytic therapy in the treatment of acute sub-massive pulmonary embolism: a prospective observational study.

The use of thrombolytic therapy in haemodynamically stable patients with sub-massive pulmonary embolism is still controversial. We conducted this stud...
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