PULMONARY EMBOLISM

INTRODUCTION
PULMONARY EMBOLISM
• More than 500000 patients are diagnosed with
pulmonary emboli in the United States
annually, resulting in approximately 200000
deaths
• The clinical presentation of acute pulmonary
embolism is variable
• It is estimated that more than half of all
patients with pulmonary emboli remain
undiagnosed
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• Accurate diagnosis with appropriate
imaging and praecox treatment decrease
mortality down to 2 to 8%
St
• Without treatment, pulmonary embolism is
associated with a mortality rate of
approximately 30%, primarily the result of
recurrent embolism
Hy
INTRODUCTION
Virchow’s Triad & Clotting
• All aspects of this triad
can be disrupted in:
Vascular damage
– Cancer patients
– Surgical / trauma patients
– Pregnancy/ puerperium
Absolute Risk of DVT in Hospitalized Patients*
VTE: DVT and PE are a single
disease entity
Approximately 50% of patients
Patient Group
Medical patients
General surgery
Major gynecologic surgery
Major urologic surgery
Neurosurgery
Stroke
Hip or knee arthroplasty, hip fracture Sx
Major trauma
Spinal cord injury
Critical care patients
with proximal DVT of the leg
have asymptomatic PE
Migration
In patients with proven with
PE post orthopaedic surgery,
DVT occurred 90% of the time
DVT (mainly asymptomatic)
is found in around 80%
of patients with PE
Embolus
Thrombus
*
Girard P, et al. Chest. 1999;116:903-908.
RISK FACTORS
•
•
•
•
•
Immobilization
Surgery within the last three months
Stroke
History of venous thromboembolism
Malignancy
DVT Prevalence, %
10–20
15–40
15–40
15–40
15–40
20–50
40–60
40–80
60–80
10–80
Rates based on objective diagnostic testing for DVT in patients not receiving thromboprophylaxis.
Geerts, et al. Seventh ACCP conference. Chest 126: 3Supplement, Sept 2004. 338S-400S
RISK FACTORS
A prospective study of risk factors for
pulmonary embolism in women (112000
subjects) found an increased risk associated
with:
– obesity (multivariate relative risk 2,9)
– heavy cigarette smoking (relative risk 1,9
with 25-30 cigarettes/day and 3,3 with >35
cigarettes/day)
– hypertension (relative risk 1,9)
Risk assessment
Population at risk
Frequency of VT by risk
factors
VTE incidence
RISK FACTORS
• Factor V Leiden mutation should be
particularly suspected, being seen in up to
40% of cases.
• High concentrations of factor VIII are
present in 11% of the western population
and confer a 6-fold risk for venous
thromboembolism.
CLINICAL MANIFESTATIONS
• Patients with symptomatic
thrombosis
may
have
pulmonary embolism.
deep venous
asymptomatic
• In 350 patients with proven DVT:
- PE (lung scan or angiographic evidence) was
present in 56%
- while symptoms were absent in 26% of
patients with a confirmed diagnosis of
pulmonary embolism
CLINICAL MANIFESTATIONS
• 65 to 90% of pulmonary emboli arise from
the lower extremities
• The majority of patients with pulmonary
embolism have no symptoms or signs of
lower extremity venous thrombosis at the
time of diagnosis (less than 30% in PIOPED
study)
X
La tromboembolia polmonare
Procedure diagnostiche della TEP acuta
•Esami di I livello:
•È tra le cause più frequenti di mortalità ospedaliera,
spesso correlate a TVP degli arti inferiori
•Diagnosi clinica difficile per scarsità ed aspecificità
di sintomi e segni
Rx torace, ECG, Ecocardiografia, Emogasanalisi, Ddimero( aspecifici, di significato “orientativo”)
•Esami di II livello:
Scintigrafia polmonare V/P, Angiopneumografia,
•La diagnosi accurata è di fondamentale importanza
anche in relazione alle scelte terapeutiche e relative
possibili complicanze
Tomografia Computerizzata Spirale,
Eco-Color-Doppler venoso degli arti inferiori
( per lo studio dell’ eventuale focolaio emboligeno )
RX torace
Diagnosi
•
•
•
•
•
•
•
Laboratorio ( dimer, wbc, etc)
EKG
Blood gases
Troponin
BNP
US
Rx
•Solo il 19% dei pazienti affetti da TEP acuta
presenta alterazioni evidenti dell’ Rx torace
•Paradossalmente,
un
radiogramma
normale
associato allo sviluppo improvviso di dispnea ed
ipossia può avvalorare il sospetto di TEP.
Può evidenziarsi oligoemia distrettuale
•A volte aree di iperdensità parenchimale ed
aumento di calibro dell’artedia polmonare sede del
trombo.
Scintigrafia polmonare V/P
•Indagine non invasiva
Aumento di calibro
a. polmonare
•Segni indiretti di TEP ( difetto di perfusione a valle
dell’ embolia; difetto di vascolarizzazione in zone
normalmente ventilate )
•Referto di tipo probabilistico ( possibilità di esami
non diagnostici)
Oligoemia
Angiopneumografia
•Già ritenuta gold standard nella diagnosi di TEP
( sede ed estensione dell’ occlusione )
•La percentuale di esami non diagnostici è maggiore nei
pazienti con patologia cardio-respiratoria nota ed in
quelli con radiogramma toracico non negativo
Tomografia computerizzata
•Indagine non invasiva, di ampia diffusione
•Mortalità: 0, 5%
•Complicanze: maggiori 1%; minori 5%
•Elevata
variabilità
interosservatore
nel
riconoscimento di emboli subsegmentari ( Stein –
Circulation, 1992 )
•Attualmente riveste significato in chiave
interventistica per casi selezionati di TEP massiva
•Consente la visualizzazione diretta dei trombi
nelle arterie polmonari
•Permette la contemporanea valutazione del
parenchima polmonare, mediastino e cavità
pleuriche
TC Convenzionale
Compie un solo giro di 360° per ogni
scansione, è quindi possibile acquisire dati
relativi ad una singola sezione di volume
corporeo,poco adatta ad uno studio
vascolare.
Possibile evidenziare trombi nelle A.
Polmonari, solo utilizzando adeguate
quantità di m.d.c.(almeno 200 cc)
TC multistrato (2-4-8-16... corone
di detettori)
•Migliora significativamente la possibilità di
visualizzare piccoli trombi in rami subsegmentari.
•Consente lo studio, con un unico test diagnostico
non invasivo, di eventuali trombi venosi addominopelvici e degli arti inferiori.
TC Spirale (ad unico detettore)
Acquisire dati relativi ad un volume
corporeo continuo e predeterminato
Elaborare le immagini al fine di ottenere
ricostruzioni bi o tri dimensionali delle
strutture esaminate
Si evidenziano trombosi segmentarie
TC: premessa tecnica
•La tecnica “spirale” permette di ridurre i tempi di
scansione e l’ entità della collimazione rispetto alla
TC “tradizionale”
•Indispensabile ottenere omogenea opacizzazione
dell’ albero arterioso polmonare mediante
adeguata somministrazione e. v. di m. d. c.
TC: parametri tecnici
•Collimazione: 3 mm ( 5 nei pazienti dispnoici )
•Spostamento del tavolo: 5 mm/rot ( 10 )
•Intervallo di ricostruzione: 2 mm ( 3 )
Segni TC di TEP acuta
•Alterazioni
vascolari:
difetto di riempimento
completo
•Volume di acquisizione: dall’ arco aortico alle
vene polmonari inferiori
•M. d. c.: 70-80 ml alla concentrazione di 300
mgI/ml, con flusso di 3 ml/sec
•Delay: 15” ( bolus tracking )
Segni TC di TEP acuta
•Alterazioni vascolari:
difetto di riempimento
parziale
TROMBOSI PARZIALE
A.POLMONARE.SIN
Ostruzione segmentaria di entrambe le aa.
polmonari lobari inferiori
Segni TC di TEP acuta
•Alterazioni
vascolari:
trombo “flottante” a.
polmonare ds
Trombo flottante nell’a.
lobare inferiore dx
Segni TC di TEP acuta
•Alterazioni parenchimali:
infarto polmonare
OPACITÀ PARENCHIMALE
TRIANGOLARIFORME
TC spirale
•Limiti: rami subsegmentari
•Prevalenza di trombi isolati a livello
subsegmentario:
5% ( Remy-Jardin 1996 )
5, 6% ( PIOPED 1990 )
17% ( Oser 1996 )
36% ( Goodman 1995 )
Conclusioni
•La presenza di segni di elevata o intermedia probabilità
di TEP derivanti dalla clinica e da indagini diagnostiche
di I livello deve indirizzare il paziente verso la TC
spirale, metodica considerata di estrema importanza
nella diagnostica non invasiva di tale patologia
•Essa, condotta con tecnica di studio rigorosa ed
appropriata, permette di esprimere un giudizio accurato
sulla presenza, gravità ed estensione del processo
tromboembolico
( Romano L – Imaging Integrato di PS del Distretto
Toraco-Addominale, 2001 )
Thrombolytic Therapy
PE
• Two-hour high-dose t-PA or urokinase
effective.
• Improves resolution at 24 hours but not at 7
days.
• Role in massive embolism accepted.
• Role in submassive, major embolism
controversial.
Thrombolysis for PE
Thrombolysis for DVT
•
Improvement of Perfusion
Pooled analysis of eight randomized trials
Repeat Venography
No Change
Marked Lysis
Thrombolysis
38%
45%
78%
10%
Major
Bleeding
13%
Thrombolysis
Heparin
2 hours
1 day
1 week
1 month
12%
30%
45%
58%
0%
10%
40%
60%
(n=188)
Heparin
(n=144)
Hirsh et al, 1996
• Accelerates resolution
• No effect on extent of resolution
• No effect on frequency of recurrence
3.5%
Dalen et al, 1997
Classification of Acute PE
• Massive PE with shock or syncope
• Major PE with right-ventricular dysfunction
• Major PE with normal right-ventricular
function
• Minor PE
Recommended Treatment of
Acute PE
• Massive PE with shock or syncope
– Thrombolysis or surgery
• Major PE with right-ventricular dysfunction
– Anticoagulants (Dalen)
– Thrombolysis (Goldhaber)
• Major PE without right-ventricular
dysfunction
– Anticoagulants
• Minor PE
Hyers et al, 1998
– Anticoagulants
Goldhaber,
1999
Dalen et al, 1997
Goldhaber, 1998
Nass et al, 1999
Goldhaber, 1999
Nass et al, 1999
Thrombolysis for Massive PE
Heparin (10,000 U bolus + 1000 U/hr IV) versus
streptokinase (1.5 million U IV over 60 min) + heparin
Patients (8)
• Cardiogenic shock; HR 124; Pa02 46
(4/4 heparin patients had already deteriorated on hepari
Randomized Trial of Alteplase
versus Heparin in Normotensive
Patients
With Acute PE
Heparin
(n=55)
Alteplase
(n=46)
P
Recurrent PE
5 (9%)
0
0.06
Death
2 (3.6%)
0
All events occurred in patients with right-ventricular dysfunction.
Mortality
Jerjes-Sanchez et al, 1995
Heparin
Streptokinase + Heparin
4/4
0/4
Goldhaber et al, 1993
Management Strategy and
Prognosis for Pulmonary
Embolism (MAPPET)
• 719 patients without cardiogenic shock
Heparin or Thrombolysis in
Hemodynamically Stable Major
Acute PE With Right-Ventricular
Dysfunction
128 consecutive patients (matched but not randomized)
between 1992 and 1997
• 169 received thrombolytic therapy:
30-day mortality 4.7%; recurrent PE 7.7%;
major bleeding 21.9%
• 550 received heparin:
30-day mortality 11.1%; recurrent PE 18.7%;
major bleeding 7.8%
Konstantinides et al, 1997
Pulmonary Embolectomy
• Can be life saving in patients with massive PE.
• In consecutive series of 96 patients, mortality was
37% (Meyer et al, 1991).
• Cardiac arrest and associated cardiopulmonary
disease were independent predictors of death.
• Elective pulmonary embolectomy was life saving
in selected patients with chronic thromboembolic
pulmonary hypertension (Moser et al, 1990).
PE recurrence %
Bleeding %
Severe
Intracranial
Death %
Thrombolysis
(n=64)
Heparin
(n=64)
4.7
4.7
15.6
9.4
4.7
0
0
0
0.001
0.028
0.24
0
0.12
6.25
P
1.0
Hamel et al, 1998
Randomized Trial of Caval
Interruption
• Initial benefit in preventing PE offset by
excess of recurrent DVT in the longer term
in the absence of anticoagulant.
• Therefore, caval filter not recommended for
this patient population in the long term.
Decousus et al, 1998
Evaluation of Inferior Venacaval Filter
in Patients With Proximal Venous
Thrombosis
IVC Filter No Filter
Symptomatic PE at day 12
Total PE at day 12
Recurrent DVT at 2 years
5
2
9 (4.8%)*
2
(1.1%)
37 (20.8%)21 (11.6%)†
Treatment of VTE
•
•
•
•
Anticoagulants
Thrombolytic Therapy
Caval Interruption
Surgical Removal
All patients received 3 months of anticoagulants; primary end-point data
unavailable for 28 patients.
*P=0.03
†P=0.02
Decousus et al, 1998
IVC filters are a substitute for
anticoagulation!
• IVC filters without anticoagulation will protect
patient from PE
• IVC filters are safe
• IVC filters save the pt needing anticoagulants
•IVC filters are thrombogenic
•Pt needs to be protected from the filter asap
•Use removable IVC filter if possible
•Use only when you have to
•Always resume anticoagulation asap
IVC Filters
• Alternative to surgical IVC interruption, based on case
series with poor documentation of outcome
• Goal: block further serious PE in a pt w/ LE DVT (proximal),
when antithrombotic Rx is impossible
• IVC filters are thrombogenic, IVC clots can occur on filters,
lead to PE anyway, and to increased DVT
• Always add antithrombotic Rx ASAP, after filter insertion
• IVC filters are NOT appropriate substitute for antithrombotic
Rx
• IVC filters reduce PE by 50% (@ day 12), but double
recurrent LE DVT despite anticoagulation for 3 months
Decousous H, et al. NEJM (338):409-415;1998.
[ASH 03
Abstract # 185]
IVC Filters:
ACCP ’04 Guidelines
IVC filters
• In most patients with DVT, recommend
against the routine use of anticoagulants with
vena cava filters (Grade 1A)
• Suggest placement of IVC filter in:
– Patients with contraindication for anticoagulation
or a complication of it (grade 2C)
– Patients with recurrent VTE despite adequate
anticoagulation (Grade 2C)
• 60 patients
• Various clinical
indications
• Recovery IVC filter
• 50/50 removal attempts
successful
• Mean: 64 d post
insertion (range 1-161)
Buller, et al. Seventh ACCP conference. Chest 126: 3Supplement, Sept 2004. 401S-428S
[ASH 03
Abstract # 185]
IVC filters
• 60 patients
• 1 pt. had “large thrombus” in filter; filter
• Various
clinical
migrated
indications
• 9 pts. had “small to moderate sized thrombus”
• Recovery
IVC filter
• 3 incidents
of “caval thrombosis with filter in
• 50/50 situ”
removal attempts
successful
• 1 asymptomatic PE @ time of filter removal
• Mean:
d post
Günther• 164
filter
fracture
insertion (range 1-161)
- Güther-Tulip™ (2 weeks per company)
Tulip™
- Güther-Tulip™ (2 weeks per company)
GüntherTulip™