t-PA 4 PE in EDt-PA 4 PE in EDAdrian SkinnerAdrian Skinner

ED registrarED registrarAuckland HospitalAuckland Hospital

28/11/0228/11/02

IntroductionIntroduction

Case reportCase report

Recent literature reviewRecent literature review

Discussion of indications for thrombolysis Discussion of indications for thrombolysis in PEin PE

Case Report Mr N.H.Case Report Mr N.H.

Presenting complaintPresenting complaint 14/09/0214/09/02

Increasing S.O.B. 3-4 daysIncreasing S.O.B. 3-4 days

Chest Pains Several daysChest Pains Several days

Recent HistoryRecent History

24 August24 August Admission Rapid AFAdmission Rapid AF CXR : heart size upper limit of normalCXR : heart size upper limit of normal Rx. AmiodaroneRx. Amiodarone Appendicectomy : normal appendixAppendicectomy : normal appendix

9 September9 September Persistent coughPersistent cough GP CXR normalGP CXR normal

Other Past HistoryOther Past History

HyperlipidaemiaHyperlipidaemia Rx. bezafibrateRx. bezafibrate NKDANKDA

Family HistoryFamily History

Mother warfarinised in later lifeMother warfarinised in later life ? reason? reason

Social HistorySocial History

Lives with wifeLives with wife

Retired commercial cleanerRetired commercial cleaner

Ex smoker (40 years ago)Ex smoker (40 years ago)

Ethanol : 1 flagon beer/fortnightEthanol : 1 flagon beer/fortnight

ExaminationExamination

Temperature 34.2C (tympanic)Temperature 34.2C (tympanic)HR 140,HSDNMHR 140,HSDNMRR 55, TML, normal breath soundsRR 55, TML, normal breath soundsBP 104/60BP 104/60Central cyanosisCentral cyanosis

OO2 2 saturation 84%saturation 84%

Cool peripheriesCool peripheriesAbdomen normalAbdomen normalNo pedal oedema No pedal oedema

ECGECG

ABG (oxygen 15L/min)ABG (oxygen 15L/min)

pH 7.42pH 7.42

pOpO2 2 6.64 kPa6.64 kPa

pCOpCO2 2 3.033.03

HCOHCO33-- 14.4 14.4

BE -9.3BE -9.3Lactate 5.7Lactate 5.7

sOsO2 2 84.7%84.7%

pOpO2 2 (A-a) = 9.94 kPa(A-a) = 9.94 kPa

FBC and coagulationFBC and coagulation

Hb 158Hb 158

WCC 10.9WCC 10.9

Platelets 643Platelets 643

INR 1.3INR 1.3

APTT 27APTT 27

BiochemistryBiochemistry

Sodium 137Sodium 137

Potassium 4.1Potassium 4.1

Glucose 15.2Glucose 15.2

Creatinine 0.16Creatinine 0.16

Troponin-T 0.18Troponin-T 0.18

CXRCXR

Lost at GLHLost at GLH

Looked OK to usLooked OK to us

DCCM staff ? Oligaemic left lung fieldDCCM staff ? Oligaemic left lung field

ECHO – trans-thoracicECHO – trans-thoracic

TreatmentTreatment

High flow oxygenHigh flow oxygen

IV fluid : 3 litres normal salineIV fluid : 3 litres normal saline

Enoxaparin 80mgEnoxaparin 80mg

ThrombolysisThrombolysis t-PA 100mg over 2 hours front loadedt-PA 100mg over 2 hours front loaded

Clinical progressClinical progress

Rapid improvement towards completion of Rapid improvement towards completion of t-PA infusiont-PA infusion HR 110HR 110 RR 20-30RR 20-30 MAP 90MAP 90 OO2 2 saturation 100% on high-flow oxygensaturation 100% on high-flow oxygen

Transferred to DCCM via CT scannerTransferred to DCCM via CT scanner

ECG post t-PAECG post t-PA

CTPACTPA

Further progressFurther progress

DCCM 1 dayDCCM 1 day

Transferred to GLH respiratory medicineTransferred to GLH respiratory medicine

Discharged day 7Discharged day 7

Repeat ECHO 1/10 RVSP 33mmHg + RAPRepeat ECHO 1/10 RVSP 33mmHg + RAP

Haematology review 25/10Haematology review 25/10 Improving effort toleranceImproving effort tolerance

Cardiology 4/11Cardiology 4/11 NSR 70/min normal effort toleranceNSR 70/min normal effort tolerance

GP remains wellGP remains well

ECG 4/11/02ECG 4/11/02

Acute Pulmonary EmbolismAcute Pulmonary Embolism

Clinical course and outcome dependent onClinical course and outcome dependent on 1) Extent of pulmonary arterial obstruction1) Extent of pulmonary arterial obstruction 2) Pre-existing cardiopulmonary disease2) Pre-existing cardiopulmonary disease 2) Potential for recurrent thrombo-embolic 2) Potential for recurrent thrombo-embolic

eventsevents

MortalityMortality

All PE < 5%All PE < 5%

PE with RV dysfunction 10-15%PE with RV dysfunction 10-15%

PE with shock > 30%PE with shock > 30%

Prognostic value of Prognostic value of Troponin-TTroponin-T

56 Patients with confirmed PE56 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)Troponin positive (> 0.1ng/ml) 50%,50%,0%50%,50%,0%

In-hospital deaths (n=9)In-hospital deaths (n=9) SyncopeSyncope OR 7.1 (1.2-33.3)OR 7.1 (1.2-33.3) ShockShock OR 11.4 (2.1-63.4)OR 11.4 (2.1-63.4) Troponin +ve Troponin +ve OR 29.6 (CI 3.3-265.3)OR 29.6 (CI 3.3-265.3) InotropesInotropes OR 37.6 (5.8-245.6)OR 37.6 (5.8-245.6) VentilationVentilation OR 78.8 (9.5-653.2)OR 78.8 (9.5-653.2)

Giannitsis et al Circulation 2000;102:211-217Giannitsis et al Circulation 2000;102:211-217

Giannitsis et alGiannitsis et al

Thrombolysis for PEThrombolysis for PE

Early trials from 1970’sEarly trials from 1970’s

Small numbersSmall numbers

Multiple therapeutic regimensMultiple therapeutic regimens

Haemodynamically unstable patients Haemodynamically unstable patients excludedexcluded

Mortality in Haemodynamically stable Mortality in Haemodynamically stable patients @ 5-10%patients @ 5-10%

First RCT in massive PEFirst RCT in massive PE

Streptokinase + Heparin ‘v’ Heparin onlyStreptokinase + Heparin ‘v’ Heparin onlyStudy stopped early after 8 enrolmentsStudy stopped early after 8 enrolments4 streptokinase patients alive and well4 streptokinase patients alive and well Clinical improvement within 1 hourClinical improvement within 1 hour

4 heparin-only all died4 heparin-only all diedTo date the only RCT in massive PETo date the only RCT in massive PE

Sanchez et al J Thromb Thrombolysis Sanchez et al J Thromb Thrombolysis 1995;2(3):227-2291995;2(3):227-229

PE + RV dysfunctionPE + RV dysfunction

Grifoni et al Circulation 2000;101: 2817-2822Grifoni et al Circulation 2000;101: 2817-2822

PE with right ventricle dilatationPE with right ventricle dilatation

128 patient monocentre registry 1992-1997128 patient monocentre registry 1992-1997

Massive PE and RV dysfunctionMassive PE and RV dysfunction No shock or hypotensionNo shock or hypotension

Thrombolysis ‘v’ heparinThrombolysis ‘v’ heparin

Significant improvement in perfusion scan at 7 Significant improvement in perfusion scan at 7 days with lysisdays with lysis

4 deaths in lysis group4 deaths in lysis group

None in heparin groupNone in heparin groupHamel et al CHEST 120; 1 July 2001 =: 120-125Hamel et al CHEST 120; 1 July 2001 =: 120-125

Massive PE + pulmonary Massive PE + pulmonary hypertension or RV dysfunctionhypertension or RV dysfunction

RCT (n=256) alteplase + heparin ‘v’ RCT (n=256) alteplase + heparin ‘v’ heparinheparin

No hypotension or shockNo hypotension or shock

Deaths 3.4% v 2.2% p=0.71Deaths 3.4% v 2.2% p=0.71

Treatment escalationTreatment escalation 10.2% v 24.6% p=0.00610.2% v 24.6% p=0.006

Konstantinides et al NEJM 347, No.15;10 Oct 2002: Konstantinides et al NEJM 347, No.15;10 Oct 2002: 1143-11501143-1150

ConclusionsConclusions

Patients with massive PE benefit from Patients with massive PE benefit from thrombolysisthrombolysis

Current research suggests that there may be a Current research suggests that there may be a subgroup of those with evidence of RV subgroup of those with evidence of RV dysfunction who will benefit from thrombolysisdysfunction who will benefit from thrombolysis

Further research required to determine this Further research required to determine this groupgroup

Trans thoracic ECHO is an important part of Trans thoracic ECHO is an important part of initial evaluationinitial evaluation