THE EVALUATION OF THE THE EVALUATION OF THE THROMBOLYTIC THERAPY IN THROMBOLYTIC THERAPY IN

MAJOR PULMONARY MAJOR PULMONARY EMBOLISMEMBOLISM

Selda KayaSelda Kaya11, , Ayşegül KaralezliAyşegül Karalezli11, H. , H. Canan HasanoğluCanan Hasanoğlu11, Ekrem Yeter , Ekrem Yeter 22

1. Pulmonary Diseases, Ankara 1. Pulmonary Diseases, Ankara Ataturk Training and Research Ataturk Training and Research

Hospital,Hospital,2. Cardiology, Ankara Ataturk 2. Cardiology, Ankara Ataturk

Training and Research Hospital,Training and Research Hospital,

IntroductionIntroduction

Major pulmonary embolism is one of Major pulmonary embolism is one of the most important issues of respiratory the most important issues of respiratory emergencies because of its high emergencies because of its high mortality. Recently it is still mortality. Recently it is still controversial to apply thrombolytic controversial to apply thrombolytic therapy to patients with massive therapy to patients with massive embolism and hemodynamically stable embolism and hemodynamically stable submassive ones with cardiac findings submassive ones with cardiac findings on echocardiography.on echocardiography.

IntroductionIntroduction

The aim of this study were to The aim of this study were to evaluate the clinical efficacy and evaluate the clinical efficacy and safety of thrombolytic therapy in safety of thrombolytic therapy in patients diagnosed as major patients diagnosed as major pulmonary embolismpulmonary embolism

Patients and methodPatients and method

In our department we evaluated 33 In our department we evaluated 33 patients who had the diagnosis of major patients who had the diagnosis of major pulmonary embolism via clinical pulmonary embolism via clinical symptoms, echocardiography and symptoms, echocardiography and computerized tomography. While 17 computerized tomography. While 17 patients ( group 1) were given tissue patients ( group 1) were given tissue plasminogen activator (r- TPA) 100 U/ L plasminogen activator (r- TPA) 100 U/ L in two hours at ICU, the others ( group in two hours at ICU, the others ( group 2) were given heparin. Clinical and 2) were given heparin. Clinical and laboratory findings were compared. laboratory findings were compared.

Patients and methodPatients and method

Symptoms and signs , predisposing Symptoms and signs , predisposing factors, blood gas analysis, the level factors, blood gas analysis, the level of D- dimer, the findings of of D- dimer, the findings of ECG,ECHO, CT-Angiography and ECG,ECHO, CT-Angiography and Doppler USG,treatments, side effects Doppler USG,treatments, side effects and complications were all recorded and complications were all recorded for our study population consisting for our study population consisting of patients 18 years of age or older. of patients 18 years of age or older.

Patients and methodPatients and method

Diagnostic criteria for massive embolism: Diagnostic criteria for massive embolism: Obstruction in at least % 50 of pulmonary Obstruction in at least % 50 of pulmonary

vascular bed or two and more lobar arteries vascular bed or two and more lobar arteries in spiral CT angiography in spiral CT angiography

Spiral CT angiography findings + Spiral CT angiography findings + cardiogenic shock and/or arterial cardiogenic shock and/or arterial hypotension hypotension

*Arterial hypotension is defined as systolic *Arterial hypotension is defined as systolic blood pressure <90 mmHg or a pressure blood pressure <90 mmHg or a pressure drop at least 40 mmHg for a time period > drop at least 40 mmHg for a time period > 15 min, if not due to new onset arrhythmia, 15 min, if not due to new onset arrhythmia, hypovolemia or sepsis.hypovolemia or sepsis.

Patients and methodPatients and method

Submassive embolism is defined as (*): Submassive embolism is defined as (*): Thrombus in at least one segmental pulmonary Thrombus in at least one segmental pulmonary

artery in spiral CT angiography, which can not be artery in spiral CT angiography, which can not be defined as massive .defined as massive .

Two- dimensional and Doppler echocardiographic Two- dimensional and Doppler echocardiographic findings indicating acute right ventricular findings indicating acute right ventricular pressure overload ( right atrial or ventricular pressure overload ( right atrial or ventricular dilatation, paradoxical septal motion, or dilatation, paradoxical septal motion, or pulmonary arterial hypertension), thrombus in the pulmonary arterial hypertension), thrombus in the right heart or pulmonary arteries in the absence right heart or pulmonary arteries in the absence of left ventricular or mitral valve disease. of left ventricular or mitral valve disease.

(*)Hemodynamic parameters were stable in this (*)Hemodynamic parameters were stable in this groupgroup

Patients and methodPatients and method

The patients who had no The patients who had no contraindications for thrombolytics were contraindications for thrombolytics were given r-TPA 100 U/ L in two hours at ICU given r-TPA 100 U/ L in two hours at ICU and they were monitorized for vital and they were monitorized for vital signs,blood gas analysis and side effects signs,blood gas analysis and side effects (group 1).(group 1).

Patients who had contradications for Patients who had contradications for thrombolytics were given heparin (group thrombolytics were given heparin (group 2).2).

Contraindications of r-TPAContraindications of r-TPA

Recent (within 2 months) cerebrovascular accident, or intracranial or Recent (within 2 months) cerebrovascular accident, or intracranial or intraspinal surgeryintraspinal surgery

Active intracranial disease( aneurysm, vascular malformation, neoplasm)Active intracranial disease( aneurysm, vascular malformation, neoplasm) Major internal bleeding,within the past 6 monthsMajor internal bleeding,within the past 6 months Uncontrolled hypertension( systolic blood pressure ≥ 200 or diastolic blood Uncontrolled hypertension( systolic blood pressure ≥ 200 or diastolic blood

pressure ≥ 110)pressure ≥ 110) Bleeding diathesis, including that associated with renal or hepatic diseaseBleeding diathesis, including that associated with renal or hepatic disease Recent (< 10 days) major surgery, puncture of a noncompressible vessel, Recent (< 10 days) major surgery, puncture of a noncompressible vessel,

organ, or obstetric deliveryorgan, or obstetric delivery Recent need for CPR because of major/minor traumaRecent need for CPR because of major/minor trauma Infective endocarditisInfective endocarditis PregnancyPregnancy Hemorrhagic retinopathyHemorrhagic retinopathy PericarditisPericarditis AneurysmAneurysm Arcasoy SM, Kreit JW. Chest 1999; 115: 1695- Arcasoy SM, Kreit JW. Chest 1999; 115: 1695-

707707

Recording of the findingsRecording of the findings

Symptoms and signs Symptoms and signs pretreatment and in 24 pretreatment and in 24 hourshours

Blood gase analysisBlood gase analysis pretreatment and in 24 pretreatment and in 24 hourshours

Systolic pulmonary artery pressure measurement Systolic pulmonary artery pressure measurement pretreatment and on the 7th day pretreatment and on the 7th day

The level of D- dimerThe level of D- dimer pretreatment and on the pretreatment and on the 3rd days( the cut- off level is 500ng/L,by ELISA)3rd days( the cut- off level is 500ng/L,by ELISA)

Data processing and analysis were performed Data processing and analysis were performed with SPSS program version 11.0. Categorical data with SPSS program version 11.0. Categorical data analyses were done by Fisher exact testanalyses were done by Fisher exact test

ResultsResults

The mean age of the group of 1 was The mean age of the group of 1 was 55.64 55.64 ±±12 (6 men, 11women)12 (6 men, 11women)

The mean age of the group of 2 was The mean age of the group of 2 was 61.1861.18±±15 (5 men, 11 women)15 (5 men, 11 women)

There were no statistically There were no statistically significant difference between the significant difference between the age of groups.age of groups.

Grup 1Grup 1 Grup 2Grup 2

pretreatmenpretreatmentt

postreatmepostreatmentnt

pretreatmenpretreatmentt

postreatmenpostreatmentt

Dyspnea Dyspnea 1717 11 1313 44

Palpitation Palpitation 44 00 55 33

Chest pain Chest pain 77 00 77 00

HaemoptysiHaemoptysiss

11 00 00 00

PresyncopePresyncope 99 00 44 00

Cyanosis Cyanosis 11 00 11 00

Predisposing factorsPredisposing factors

Predisposing Predisposing factorsfactors

Grup 1Grup 1 Grup 2Grup 2

Major operationMajor operation 77 66

Minor operationMinor operation 22 00

Cardiovasc. Diseases, Cardiovasc. Diseases, arrhythmiaarrhythmia

55 22

Long distance travel Long distance travel (>8s)(>8s)

22 00

Oral contraseptivesOral contraseptives 22 22

MalignancyMalignancy 22 11

TrombophiliaTrombophilia 11 00

Patients with one Patients with one risk factor or less risk factor or less

44 66

Results- diagnosis Results- diagnosis

-The positive findings of the lower -The positive findings of the lower extremity Doppler USG:extremity Doppler USG:

Group 1 Group 1 5 5

Group 2 Group 2 3 3-The mean pressure of the Pulmonary -The mean pressure of the Pulmonary

arteries arteries (pre- and postreatment ):(pre- and postreatment ):

Group1Group1 82/ 36 mm Hg 82/ 36 mm Hg

Grup2Grup2 52/ 34 mm Hg 52/ 34 mm Hg

Results- diagnosis- CT Results- diagnosis- CT angiography findingsangiography findings

Group 1Group 1 Group 2 Group 2

Bilateral main PA Bilateral main PA thrombus ( thr)thrombus ( thr)

1010 66

Right main PA thr.Right main PA thr. 1111 66

Left main PA thr.Left main PA thr. 11 44

Right atrial and Right atrial and main PA thr.main PA thr.

22 11

Pulmonary Pulmonary infarctioninfarction

22 22

Pleural effusionPleural effusion 66 55

Right spaces, main Right spaces, main PAPA

11 00

Results- Group 1Results- Group 1Group 1Group 1 pretratmentpretratment posttreatmentposttreatment ppHeart rateHeart rate 9494±±1818 8585±±1414 0,0700,070

Respiratory rateRespiratory rate 2323±±66 1818±±44 0,0010,001

Cystolic blood Cystolic blood pressurepressure

112112±±1919 120120±±1616 0,0730,073

Diastolik blood Diastolik blood pressurepressure

7070±±1111 8080±±1010 0,0060,006

(A-a)O2(A-a)O2 5959±±1212 3030±±1616 0,0000,000

PaO2PaO2 5454±±1111 7676±±2525 0,0000,000

PaCO2PaCO2 2727±±66 3232±±66 0,0000,000

SaturationSaturation 8686±±99 9393±±77 0,0000,000

pHpH 7,487,48±±0,050,05 7,467,46±±0,030,03 0,0010,001

D-dimerD-dimer 44084408±±19291929 22992299±±12771277 0,0000,000

Mean -PAPMean -PAP 5858±±1717 4040±±1212 0,0000,000

Results- Group 2Results- Group 2Group 2Group 2 pretreatmentpretreatment posttreatmentposttreatment ppHeart rateHeart rate 8787±±1414 79 79 ±±55 0,0110,011

Respiratory rateRespiratory rate 2020±±77 1818±±66 0,0080,008

Cystolic blood Cystolic blood pressurepressure

115115±±1414 120 120 ±±1010 0.1460.146

Diastolik blood Diastolik blood pressurepressure

7272±±1414 7878±±66 0,0330,033

(A-a)O2(A-a)O2 5252±±1616 3030±±1414 0,0000,000

PaO2PaO2 6060±±1313 7373±±1515 0,0000,000

PaCO2PaCO2 2828±±44 3030±±44 0,0000,000

saturationsaturation 8989±±77 9393±±33 0,0100,010

pHpH 7,497,49±±0,080,08 7,467,46±±0,030,03 0,0670,067

D-dimerD-dimer 58285828±±23422342 38213821 ± ±24172417 0.0260.026

Mean -PABMean -PAB 4949±±1313 4141±±1414 0,0570,057

Differences between the groups Differences between the groups

GROUPSGROUPS GROUP 1GROUP 1 GROUP 2GROUP 2

pretreatmentpretreatment posttreatmeposttreatmentnt

pretreatmenpretreatmentt

posttreatmentposttreatment PP

Heart rateHeart rate 9494±±1818 8585±±1414 8787±±1414 79 79 ±±55 >0,05>0,05

Respiratory Respiratory raterate

2323±±66 1818±±44 2020±±77 1818±±66 0,0080,008

Cystolic blood Cystolic blood pressurepressure

112112±±1919 120120±±1616 115115±±1414 120 120 ±±1010 >0,05>0,05

Diastolic Diastolic blood blood pressurepressure

7070±±1111 8080±±1010 7272±±1414 7878±±66 >0,05>0,05

(A-a)O2(A-a)O2 5959±±1212 3030±±1616 5252±±1616 3030±±1414 >0,05>0,05

Differences between the groupsDifferences between the groupsGROUPSGROUPS GROUP 1GROUP 1 GROUP 2GROUP 2

pretratmepretratmentnt

posttreatmenposttreatmentt

pretratmentpretratment posttreatmentposttreatment PP

PaO2PaO2 5454±±1111 7676±±2525 6060±±1313 7373±±1515 >0,05>0,05

PaCO2PaCO2 2727±±66 3232±±66 2828±±44 3030±±44 >0,05>0,05

saturationsaturation 8686±±99 9393±±77 8989±±77 9393±±33 >0,05>0,05

pHpH 7,497,49±±0,080,08 7,467,46±±0,030,03 7,497,49±±0,080,08 7,467,46±±0,030,03 >0,05>0,05

D-dimerD-dimer 58285828±±23423422

38213821 ± ±24172417 58285828±±23422342 38213821 ± ±24172417 >0,05>0,05

Mean -Mean -PABPAB

4949±±1313 4141±±1414 4949±±1313 4141±±1414 <0,05<0,05

Findings of Findings of ECHOCARDIOGRAPHY, ECGECHOCARDIOGRAPHY, ECG

There was statistically significant difference between There was statistically significant difference between mean pulmonary pressure levels among each group mean pulmonary pressure levels among each group before and after treatments.before and after treatments.

Mean pulmonary pressure of group 1 was significantly Mean pulmonary pressure of group 1 was significantly higher than group 2 before and after the therapy ( p< higher than group 2 before and after the therapy ( p< 0,005).0,005).

In echocardiographic evaluation, right heart dilatation In echocardiographic evaluation, right heart dilatation turned to normal in 6 of 16 patients in Group 1 and 4 of 11 turned to normal in 6 of 16 patients in Group 1 and 4 of 11 patients in Group 2. patients in Group 2.

Thrombus in right heart were detected by Thrombus in right heart were detected by echocardiography in 3 of 17 patients in Group 1. All of them echocardiography in 3 of 17 patients in Group 1. All of them disappeared by thrombolytic therapy after 1 weekdisappeared by thrombolytic therapy after 1 week

For both groups, ECG findings turned to normal significantly For both groups, ECG findings turned to normal significantly after the therapy ( p ≤ 0.04), but no significant differences after the therapy ( p ≤ 0.04), but no significant differences between the groups were observed. between the groups were observed.

Side effects( Group 1)Side effects( Group 1)

ageage D-dimerD-dimer Risk factorsRisk factors The type of The type of bleedingbleeding

treatmenttreatment

1.case1.case 63,M63,M 35263526 TUR-TUR-prosthatectomiprosthatectomiaa

Major Major hematturia, hematturia, hemorrhage hemorrhage vascular vascular puncture puncture sitessites

Blood Blood transfusiontransfusion

2.case2.case 38,w38,w 13631363 Oral Oral contraceptivcontraceptives,es,

ObesityObesity

epistaxisepistaxis Follow upFollow up

3.case3.case 55,M55,M 65456545 postoperativpostoperative e ImmobilizatioImmobilizationn

The The congestion congestion on the on the operating operating ocular area, ocular area, hemorrhage hemorrhage vascular vascular puncture sitespuncture sites

Follow upFollow up

4.case4.case 71,M71,M 63826382 Cigarette Cigarette smoking , smoking , HypertensionHypertension,,

BPHBPH

minor minor hematuriahematuria

Follow upFollow up

5.case5.case 58,W58,W 49974997 ImmobilizatioImmobilizationn

hemoptysishemoptysis Follow up Follow up

DiscussionDiscussion

The role of CT-Angiogrpahy and ECHO in the The role of CT-Angiogrpahy and ECHO in the diagnosis of major embolism is important. It diagnosis of major embolism is important. It is supportive to clinican for determinating of is supportive to clinican for determinating of pathologic extensive and treatment choice.pathologic extensive and treatment choice.

In case of sudden hypotension and changes In case of sudden hypotension and changes in blood gases, its ability in rapid diagnosis, in blood gases, its ability in rapid diagnosis, makes transthoracic ECHO important.The makes transthoracic ECHO important.The detection of intracardiac thrombus which detection of intracardiac thrombus which increase mortality and monitiorization of increase mortality and monitiorization of patient during thrombolytic treatment can patient during thrombolytic treatment can also be achieved by ECHO.also be achieved by ECHO.

DiscussionDiscussion

The trombolytic therapy can be prefered The trombolytic therapy can be prefered because of more rapid symptom control. because of more rapid symptom control. But it must be applied in ICU because of But it must be applied in ICU because of monitorization of side effects and rapid monitorization of side effects and rapid intervention.intervention.

In some cases with submassive embolisms, In some cases with submassive embolisms, thrombolytic treatment can be suggested thrombolytic treatment can be suggested especially without of improvement in especially without of improvement in saturation and hemodynamic parameters saturation and hemodynamic parameters

Conclusions Conclusions

Our study shows that, thrombolytic Our study shows that, thrombolytic therapy can be safely used for the therapy can be safely used for the treatment of major treatment of major thromboembolism. thromboembolism.

But studies with larger patient But studies with larger patient populations are needed on this populations are needed on this subject. subject.