t-PA 4 PE in ED Adrian Skinner ED registrar Auckland Hospital 28/11/02

Introduction Case report Recent literature review Discussion of indications for thrombolysis in PE

Case Report Mr N.H. Presenting complaint14/09/02 Increasing S.O.B. 3-4 days Increasing S.O.B. 3-4 days Chest Pains Several days Chest Pains Several days

Recent History 24 August Admission Rapid AF Admission Rapid AF CXR : heart size upper limit of normal CXR : heart size upper limit of normal Rx. Amiodarone Rx. Amiodarone Appendicectomy : normal appendix Appendicectomy : normal appendix 9 September Persistent cough Persistent cough GP CXR normal GP CXR normal

Other Past History Hyperlipidaemia Rx. bezafibrate Rx. bezafibrate NKDA NKDA

Family History Mother warfarinised in later life ? reason ? reason

Social History Lives with wife Retired commercial cleaner Ex smoker (40 years ago) Ethanol : 1 flagon beer/fortnight

Examination Temperature 34.2C (tympanic) HR 140,HSDNM RR 55, TML, normal breath sounds BP 104/60 Central cyanosis O 2 saturation 84% Cool peripheries Abdomen normal No pedal oedema

ECG

ABG (oxygen 15L/min) pH 7.42 pO kPa pCO HCO BE -9.3 Lactate 5.7 sO % pO 2 (A-a) = 9.94 kPa

FBC and coagulation Hb 158 WCC 10.9 Platelets 643 INR 1.3 APTT 27

Biochemistry Sodium 137 Potassium 4.1 Glucose 15.2 Creatinine 0.16 Troponin-T 0.18

CXR Lost at GLH Looked OK to us DCCM staff ? Oligaemic left lung field

ECHO – trans-thoracic

Treatment High flow oxygen IV fluid : 3 litres normal saline Enoxaparin 80mg Thrombolysis t-PA 100mg over 2 hours front loaded t-PA 100mg over 2 hours front loaded

Clinical progress Rapid improvement towards completion of t-PA infusion HR 110 HR 110 RR RR MAP 90 MAP 90 O 2 saturation 100% on high-flow oxygen O 2 saturation 100% on high-flow oxygen Transferred to DCCM via CT scanner

ECG post t-PA

CTPA

Further progress DCCM 1 day Transferred to GLH respiratory medicine Discharged day 7 Repeat ECHO 1/10 RVSP 33mmHg + RAP Haematology review 25/10 Improving effort tolerance Improving effort tolerance Cardiology 4/11 NSR 70/min normal effort tolerance NSR 70/min normal effort tolerance GP remains well

ECG 4/11/02

Acute Pulmonary Embolism Clinical course and outcome dependent on 1) Extent of pulmonary arterial obstruction 1) Extent of pulmonary arterial obstruction 2) Pre-existing cardiopulmonary disease 2) Pre-existing cardiopulmonary disease 2) Potential for recurrent thrombo-embolic events 2) Potential for recurrent thrombo-embolic events

Mortality All PE < 5% PE with RV dysfunction 10-15% PE with shock > 30%

Prognostic value of Troponin-T 56 Patients with confirmed PE Graded as massive (n=17), moderate (n=26), small (n=13) Graded as massive (n=17), moderate (n=26), small (n=13) Troponin positive (> 0.1ng/ml) 50%,50%,0% 50%,50%,0% In-hospital deaths (n=9) SyncopeOR 7.1 ( ) SyncopeOR 7.1 ( ) ShockOR 11.4 ( ) ShockOR 11.4 ( ) Troponin +ve OR 29.6 (CI ) Troponin +ve OR 29.6 (CI ) InotropesOR 37.6 ( ) InotropesOR 37.6 ( ) VentilationOR 78.8 ( ) VentilationOR 78.8 ( ) Giannitsis et al Circulation 2000;102:

Giannitsis et al

Thrombolysis for PE Early trials from 1970’s Small numbers Multiple therapeutic regimens Haemodynamically unstable patients excluded Mortality in Haemodynamically stable 5-10%

First RCT in massive PE Streptokinase + Heparin ‘v’ Heparin only Study stopped early after 8 enrolments 4 streptokinase patients alive and well Clinical improvement within 1 hour Clinical improvement within 1 hour 4 heparin-only all died To date the only RCT in massive PE Sanchez et al J Thromb Thrombolysis 1995;2(3):

PE + RV dysfunction Grifoni et al Circulation 2000;101:

PE with right ventricle dilatation 128 patient monocentre registry Massive PE and RV dysfunction No shock or hypotension No shock or hypotension Thrombolysis ‘v’ heparin Significant improvement in perfusion scan at 7 days with lysis 4 deaths in lysis group None in heparin group Hamel et al CHEST 120; 1 July 2001 =:

Massive PE + pulmonary hypertension or RV dysfunction RCT (n=256) alteplase + heparin ‘v’ heparin No hypotension or shock Deaths 3.4% v 2.2% p=0.71 Treatment escalation 10.2% v 24.6% p= % v 24.6% p=0.006 Konstantinides et al NEJM 347, No.15;10 Oct 2002:

Conclusions Patients with massive PE benefit from thrombolysis Current research suggests that there may be a subgroup of those with evidence of RV dysfunction who will benefit from thrombolysis Further research required to determine this group Trans thoracic ECHO is an important part of initial evaluation