Transcript pH measurement via a non traditional site of capillary blood gas

PULMONARY EMBOLISM
AND DEEP VENOUS THROMBOSIS
James Huffman
11.13.2008
Thanks to Dr. Gil Curry, Dr. Nadim Lalani
Outline


Epidemiology / Pathophysiology
DVT
 Anatomy
 Clinical
Presentation
 Diagnostic Approach
 Pre-test
probability
 Labs
 Imaging
 Real-Life
Algorithm
 Treatment
Outline

PE
 Clinical
Presentation
 Diagnostic Approach
 Pre-test
probability
 Labs
 EKG
 Imaging

X-ray, CT, MR
 Real-Life
Algorithm
Focus: the bottom line
Epidemiology
 VTE is a ‘spectrum’ :
Simple superficial thrombophlebitis to fatal PE
 Est incidence : 100 /100 000
 1/3 of cases are PE
 Increases dramatically with age (sharp increase after the age of 45)
 DVT:





Only 1/3 of pts investigated for DVT have it
“silent” PE present in 40-60% of pts with DVT
In asymptomatic pts w/ proven DVT, up to 1/3 will have undiagnosed PE
With treatment 50% have residual clot up to 1y
Without treatment 50% recurrence w/ in 3 mo
Epidemiology
 PE:
 10% fatal w/ in 1st Hour
 75% pt w/ PE have DVT (2/3 proximal vein)
 Classic presentations are less common than atypicals and asymptomatic
VTE is common
 20% have “pleuritic CP” in ED
 5-10% PE have shock as initial presentation
 Despite treatment, kills 1-8%
 Complications:
 postphlebitic syndrome [40%]
 pulmonary HTN [4%]
Pathophysiology of Thrombosis



Fibrinogen is converted to fibrin in response to vasc.
Injury and inflammation
Fibrin is 1° structural framework of embolized clots
and excessive fibrin deposition provides the nidus of
VTE
VTE is the end-product of imbalanced clot formation and
breakdown
What promotes this imbalance of fibrin deposition and
removal?
Virchow’s Triad
White, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003.
1.
2.
3.
Injury to the vascular endothelium
Alterations in blood flow
Hypercoagulability
Anything else associated with
imbalanced clot formation?
Age – likely through a combination
of the above mechanisms
Coagulation Cascade
Coagulation Cascade
PTT
PT/INR
Heparin
Warfarin
Anatomy


Depth

Deep

Superficial*
Proximal


Popliteal v. or higher
Distal
*Superficial femoral vein is a
member of the deep group
Case 1

55♀: Referred to ED for pain, redness and swelling
of right calf
 WIC
today: Sent to ED with note:
History

Started 3/7 ago
Denies previous DVT
Has been on IV combo chemotherapy for ovarian Ca diagnosed six
months ago (extensive pelvic lymph node involvement – which has
improved as per recent U/S)
Fell day before this started and “twisted her knee”

All this is good – what are your main goals with history?





Determine pre-test probability of DVT
Look for other causes
DVT: History is Risk Assessment
Hypercoagulability:

Autoimmune Disease and Immune Deficiency




Not just SLE! Remember IBD
Cancer
Chemotherapy: especially breast CA
Coagulopathy:
 Factor V Leiden. Present in 7% pop = 50%
 Protein C, protein S & antithrombin III deficiency = 15% DVT.
 Resistance to aPC
 Lupus anticoagulant
 Prothrombin G20210A
 antiphospholipid antibodies
 others
DVT: History is Risk Assessment
Stasis:





Immobility: Not just surgery – remember other conditions (oldies!)
Heart Disease (AMI & CHF): independent of bedrest
Travel ?Duration / proximity?
Hyperlipiedmia
Polycythemia
Endothelial Injury:



Stroke
Vascular surgery
PVD
Others:

Age, race, prior DVT, blood types, tissue antigens, homocysteine
Case 1 Continued
When you examine her what do you expect to find?
P/E:
Generalised tenderness to her calf
Exquisite pain in popliteal fossa along vein
Edema, erythema and warmth
Swollen 3.5 cm
Homan’s Sign +
What do you think of this?
Physical is Risk Assessment
Anand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)
Classically:
Leg tenderness , Homan’s Sign
Swelling
Pitting edema
Dilated superficial veins
Erythema
Calor
Neither sensitive nor specific
OR’s between 2- 4
Physical is Risk Assessment
Anand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)
DVT: H&P Bottom Line

Neither is sensitive or specific
 i.e.

you can’t rule-in or rule-out a DVT
Use them to decide pre-test probability
Clinical Prediction Rule: Evolution
Landefeld et. Al 1990
354 pts suspected of DVT that underwent venography
5 clinical predictors identified:
1 or more  95% Sens [92-100] 20% spec [15-25]
 Swelling above the knee
 Swelling below the knee
 Recent immobility
 Fever
 Cancer
Absence of all  only 5% DVT
Pretest Probability
Wells, P., et al. 1995. Accuracy of Clinical Assessment of Deep Vein Thrombosis. Lancet:345; 1326-30



First Wells Criteria
Based on literature
review and clinical
experience of
investigators
Study showed value in
stratifying pretest
probability with
respect to eliminating
need for repeat u/s
Pretest Probability
Wells, P, et al. 1997. Lancet:350;1795.

Revised Wells score through logistic regression analysis

Prospectively validated using same treatment algorithm (next slide)

593 patients from two Canadian tertiary care centres

Score ≥ 3 (high risk), 1 or 2 (moderate risk), <1 (low risk)
Pretest Probability
Wells, P, et al. 1997. Lancet:350;1795.

593 pts w/ suspect DVT

Stratified low, mod, high risk  compression U/S /veno

3% of Low risk, 17% of moderate risk, 75% of high risk pts had DVT

Concluded that Clinical probability + U/S safe [0.6% missed]
Pretest Probability

This algorithm re-presented in JAMA rational clinical
examination series
Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this patient have deep vein
thrombosis? JAMA. 1998 Dec 2;280(21):1828-9.

What’s missing?
The N’Dimer!
D-Dimer Testing
 U/S not a perfect test
 Degradation product of fibrin
 Non-specific
 PPV bad
 +ve: surgery, trauma, hemorrhage,
CA, pregnancy, sepsis, >80 yrs old
 Sensitivity variable
 Need Pre-test probability to r/o DVT
Assay
Sensitivity Specificity
Whole blood
agglutination
(SimpliRED)
80-85%
70-90%
Latex
agglutination
90-95%
40-90%
Rapid ELISA
95-100%
30-60%
CHR uses
D-Dimer Testing
Wells, P., et al. 2003. NEJM: 349(13); pp1227-35
RCT (N=1096)
D-Dimer vs no D-Dimer
DVT Likely = Wells ≥ 2
# of U/S per pt decreased in
D-dimer group (0.78 vs 1.34)
D-Dimer Testing
Wells, P., et al. 2003. NEJM: 349(13); pp1227-35



“Modified” Wells Criteria
Used SimpliRED and IL-Test assays
(less sens)
Conclusion:

Clinical prediction rule + DDimer can safely r/o DVT
Case 1 continued

Pretest probability?






Active cancer (1)
Localized tenderness (1)
Calf swelling (1)
So she gets either 4 or 2 points = DVT likely
Edema (1)
Other Diagnosis? Compression by pelvic nodes? (Doesn’t matter – score
would still be “not low risk”)
What about the D-Dimer – Would you order it?



Doesn’t matter – it was sent already
Level positive at 1.77C
Both CMAJ and Well’s protocols would have you order it anyway (we’ll
discuss)
What next Einstein?
Ultrasound
American Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66

Well studied

Widely available

Proven accurate for Dx symptomatic prox DVT


Like CT/PE provides other Dx: hematomas, baker’s cysts, lymphad,
aneurism, thrombophlebitis and abscess
Has been advanced by the combination of compression and
doppler
Bottom line: U/S is the test of choice for DVT
Duplex Ultrasound
Stork, A. 2005. Calgarian J of PPT Slides. 1(1) pp1
Two parts
i) Compression
- Tech applies pressure
- clot  not compressible
ii) Doppler (B mode)


Shows blood flow
Ultrasound
Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83
EDE

Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32.
 Retrospective
analysis 1994
 EPs trained to perform colour doppler US (20-30 studies
each)
 100% sensitive, 75% specific for acute DVT
2

false-positives were in chronic DVT
Frazee BW, et al. J Emerg Med 2001;20(2):107–12.
 Prospectively
LCUS
demonstrated 95.7% NPV for EP performed
Naughty by Nature - “Feel me flow”
EDE – ED Flow

Blaivas M, et al. Acad Emerg Med. 2000;7(2):120–6.



Theodoro D, et al. Am J Emerg Med. 2004;22(3):197–200.



Median exam time of 3m 28s
98% correlation with vascular lab-performed studies on same pts
125m reduction in time to pt disposition with EP-performed US
Kappa = 0.9, 99% agreement (154/156 cases)
Jang T, et al. Acad Emerg Med. 2004;11(3):319–22.




8 emerg residents (4 PGY-1, 2 PGY-2, 2 PGY-3)
1h focused training (didactic and practice on 2 healthy volunteers)
SN = 100%, SP = 91.8%, avg scan time = 11.7min (self-reported)
4 false-positives (chronic DVT), 0 false-negatives
Ultrasound: Limitations


Obese, ++edema, immobilsation devices (x-fix)
Doesn’t see isolated thrombi in iliac or superficial femoral veins within abductor
canal MRI better

Pelvic masses may cause noncompressibility in absence of thrombus  false +’ve

Most importantly: U/S doesn’t return to normal after acute DVT

Therefore use impedance plethysmography for recurrent DVT

U/S - 60-70% of studies return to normal at one year

IP – 90% return to normal within a year
CT-Venography
Goodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6



PIOPED II Data
711 pts with CT-V and sonography
Results:
 95.5%
concordance for dx or exclusion of proximal DVT
 Kappa = 0.809
 Simlar results across all subgroups (asymptomatic,
symptomatic, previous DVT)
Bottom Line Thus Far?
1.
Hx/PE help us decide pretest probability (Wells)
2.
We add in a sensitive Test (D-Dimer)
3.
And a sensitive confirmatory test (U/S)
‘Cause Stone Cold says so!
Real-Life Approach
Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.
Or…the 1620h approach
Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83
CHR Approach


The next 4 slides describe the current Calgary
Health Region approach
Not many people use this as it is a bit outdated but
I’ve kept the slides here for your interest
Wells Criteria for Probability of DVT
Clinical Hx/Sign
1.
Malignancy
Criteria
receiving active treatment for cancer
Points
LOW PROB
< 0 points
1.0
OR have received treatment for cancer in past 6 mo.
OR are receiving palliative care for cancer
2.
Limb immobilization
Paralysis
1.0
MOD PROB
1 or 2 points
OR Paresis
OR Recent casting of lower extremity
3.
Patient immobilization
bedrest (except access to BR) > 3 days
1.0
OR surgery in previous 4 weeks
4.
Localized tenderness
5.
Entire leg swollen
6.
Calf swelling
Along distribution of deep venous system
1.0
1.0
>3cm when compared with asymptomatic leg
1.0
Measured 10cm below the tibial tuberosity
7.
Pitting edema
Greater in the symptomatic leg
1.0
8.
Collateral superficial veins
dilated
Non-varicose veins
1.0
9.
Alternative Dx as likely or
more likely than that of
DVT
No specific criteria – use Hx, Physical, CXR, EKG, and labs to
decide
-2.0
HIGH PROB
>3 points
LOW PROBABILITY DVT
D-Dimer
Neg
STOP
Normal
STOP
Positive
CUS legs
DVT
TREAT
MODERATE PROBABILITY DVT
D-Dimer
Neg
Positive
STOP
CUS legs
Normal
DVT
CUS leg
TREAT
in 1 week
Normal
Positive
STOP
TREAT
HIGH PROBABILITY DVT
CUS legs
Normal
DVT
Venography
TREAT
Normal
Positive
STOP
TREAT
Case 1 Continued



Okay back to it…
U/S shows popliteal vein DVT
Management Doctor?
Treatment
Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

Goals:
 Short
Term:
 Prevent
 Long
extension of thrombus and/or PE
Term:
 Prevent
recurrent events
 Prevent complications



Chronic Venous Insufficiency
 Pain
 Vericose Veins
 Ulcers
Postphlebitc syndrome
Pulmonary Hypertension
Medical Management
Rosen’s Emergency Medicine 6th Edition

Used to be  admit  start UFH and Warfarin

Now know that LMWH equally efficacious and ?more safe

Many centres now go for either tinzaparin (175 U/kg OD) or Enoxaparin
(1mg/kg BID)

UFH (80U/kg IV bolus then 18U/kg/h infusion)

Unless contraindications, can start AC in ED

[Warfarin (10mg) Required for at least 3 months] not all cases

Goal INR is usually 2-3
Fixed dose subcutaneous low molecular weight heparins versus adjusted dose
unfractionated heparin for venous thromboembolism
Van Dongen C. Cochrane Review 2005

22 studies (n = 8867)

Major hemorrhages (19 trials)



Thrombotic complications (18
trials)



LMWH = 151/4181 (3.6%)
UFH 211/3941 (5.4%)
OR 0.68; (0.55 to 0.84


Mortality (18 trials)



Thrombus size was reduced
(12 trials)



LMWH= 53%
UFH 45%
OR 0.69 (0.59 to 0.81)


LMWH = 41/3500 (1.2%)
UFH 73/3624 (2.0%)
OR 0.57 (0.39 to 0.83)
LMWH 187/4193 (4.5%)
UFH 233/3861 (6.0%)
OR 0.76 (0.62 to 0.92)
BID dosing ? Better

CI for OR crossed 0
Aric 2005
Case 1 Continued


Pt started on Enoxaparin
Arranged to see her oncologist and a hematologist
as out-patient 2 days later
Discharge
Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.


Outpatient treatment is safe and effective in a wide
variety of patients
Admission may be required if:
 Co-morbidities:
 Renal
failure, high bleeding risk
 Extensive DVT (painful blue leg)
 Necessity for parenteral narcotics
 Inability to have injections at home
Special Circumstances
Superficial Thrombophlebitis



Uncommonly evolves into a thromboemboic event
BUT, many patients have synchronous DVT (~8%)
Consider treatment with ASA or LMWH
 Then
symptomatic treatment with:
 NSAIDS
 Heat
 Graded
compression stocking (30-40 mmHg)
 Ambulation
Case 2


44♂, painful swollen right calf
Hx/PE:
3/7 days ago – dull ache
 No trauma/previous DVT
 Calf swollen 4cm, generally tender
 No other risk factors


U/S:

Isolated calf DVT
How do you want to manage this?
Isolated Calf or Saphenous DVT
Canadian Medical Associan Journal. 2003; 168(2)




Rarely causes leg symptoms (80% of symptomatic DVT involve
proximal veins)
Rarely cause clinical significant PE
~25% of untreated calf DVTs will extend to involve the proximal
veins
Vast majority of those that will progress do so within a week of
presentation
Clinically this means that you can re-U/S them
and hold the LMWH (+/- ASA)
Phlegmasia Cerulea Dolens
(Painful Blue Leg)

Massive iliofemoral occlusion results in swelling of
the entire leg with extensive vascular congestion and
associated venous ischemia

Leg is extremely painful and cyanotic

Vascular surgery consult

If timely consult not available, early thrombolytic
therapy maybe limb-salvaging
Upper Limb Venous Thromboses
Bernardi, E., et al. 2001. Semin Vasc Med. 1;105-10.


Catheter related vs non
ALL require treatment
 High
embolization rate
 If present, central venous catheters should be removed
What’s new and exciting?
Fondaparinux
Matisse Investigators. Ann Intern Med. 2004;140:867-73.

Synthetic polysaccharide

Anti Factor Xa

DBRCT Fondaparinux vs Enoxaparin in symptomatic DVT



2205 pts with symptomatic DVT from 154 centres worldwide
Fondaparinux 7.5mg*sc od vs Enoxaparin 1mg/kg sc bid
Outcomes:



Symptomatic recurrent VTE
Bleeding
Death
Fondaparinux
Matisse Investigators. Ann Intern Med. 2004;140:867-73.

At least as safe and effective as LMH

To date: no reported heparin-induced thrombocytopenia

However, not available in Canada at this time
Other topics for you to think about



Superficial Thrombophlebitis
Thrombolysis
IVC filters
Pulmonary Embolus (PE)
Background
Rosen’s Emergency Medicine: 6th Edition

PE results from a clot that formed hours, days, or weeks earlier in the
deep veins which has traveled to the lungs

Presentation is highly variable

EP’s probably correctly identify about half of pts with PE

~10% of ED pts die within 30 days even with prompt diagnosis

If no cardiopulmonary disease, 30% obstruction can be tolerated with
minor symptoms only
Case 3

61♀ presents to ED complaining of mild pleuritic chest
pain
 Total

knee arthroplasty 5/12 ago. Healthy otherwise
Tell me about:
 History
 Physical
 Investigations
Risk Assessment
Emergency Medicine Reports. 2004;25(11)


History and Physical do not confirm the diagnosis, they merely raise the
suspicion of the diagnosis, triggering further investigation
Hx:



Have to consider PE: dyspnea, tachypnea Pleuritic CP, syncope, hypotension
& hemoptysis
Non-specific
PE:

Tachypnea and tachycardia are most common
Risk Assessment
Emergency Medicine Reports. 2004;25(11)

CXR:




Often AbN (Pleural effusion, atelectasis, elevated hemidiaphragm)
N CXR with dyspnea & hypoxemia = PE
Know Hampton’s and Westermark for exams
EKG:

Non-specific ST, Twave changes, Tachy



Signs of R heart strain (Anterior/Inferior T-wave inversions)
Know SIQIIITIII for exams
ABG:



Hypoxemia common, but not always present
AAD02 >20 suggests PE (PIOPED)
25-35% of pts with PE have normal blood gasses, pulse ox, and A-A gradient
Bottom Line


By themselves, H&P can help to stratify patients
But like w/ DVT, we now have standardized criteria
Pretest Probability
Emergency Medicine Reports. 2004;25(11)

All decision trees start here

Several exist

Wells and Geneva validated

Wells NPV: 99.5%

Others more cumbersome to use

Geneva (Wicki): add ABG, CXR

PISA-PED: Add ECG
Case 3 Continued

HR: 104
Nil else

She gets 1.5 points



Now what?
Do you even start to work her up for PE?
Pretest Probability
Rosen’s Emergency Medicine. 6th Edition

One approach is to compare pretest prob with the “test threshold”




Theoretical cutoff is pretest prob above which some workup should be
initiated and below which the pt would be harmed by further testing
Test Threshold for PE is ~1.8-2%
Canadian (Wells) score <2 had probability of 1.3% but not
repeated
How then?


Unstructured  variable
PE Rule Out Criteria  Developed and validated in two populations
PE Rule-Out Criteria (PERC Rule)
Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55


Based on the premise that overuse of D-dimer to screen for PE can have
negative consequences
Derivation phase:



3148 patients evaluated for PE in 10 US EDs
Data collected on 21 variables
Logistic regression and interobserver agreement used to narrow to rule of 8.
PE Rule-Out Criteria (PERC Rule)
Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55








Age <50
Pulse rate <100 beats/min
Oxygen saturation >94%
No hemoptysis
No unilateral leg swelling
No recent major surgery or trauma
No prior pulmonary embolism or deep venous
thrombosis
No hormone use
PE Rule-Out Criteria (PERC Rule)
Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Validation Phase:
2
Groups
 Low
risk (board certified EP believed D-dimer warranted
but good enough to r/o PE)

n = 1427, 114 (8%) had VTE diagnosed within 90d
 Very

low risk (chief complain dyspnea – PE not suspected)
n = 382, 9 (2.4%) had VTE diagnosed within 90d
PE Rule-Out Criteria (PERC Rule)
Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Endpoint: VTE before 90 days. Good follow-up

Both Wells score and PERC rule functioned relatively well


Wells better with very low risk population and included more patients in
both groups
Both had very wide confidence intervals
PERC Rule – Bottom Line

Compliments clinical judgement
 DOESN’T
REPLACE IT!
Pause before ordering a D-dimer in a patient
who does not have any of the eight criteria
Then order it if you still think it’s indicated
Case 3 Continued



Age > 50
HR >100
Does not meet PERC criteria. Wells 1.5

Send the D-dimer
 Result: 0.59 mg/L (↑)
 Does this mean anything? What if it was 1.9 mg/L?
D-dimer in PE
Does D-dimer level correspond to clot burden in PE?
 What about mortality?
D-dimer in PE
Grau, E. et al. Crit Care Med. 2007; 35:1937-41


Observational study of 588 pts with symptomatic PE
Quantitative D-dimer performed on admission (Automated Latex
agglutination test) and clinical follow up for 90 days
D-dimer in PE
Grau, E. et al. Crit Care Med. 2007; 35:1937-41
= 0.5-2.49 mg/L

Compared to pts with D-dimer 500-2499 ng/mL, OR of 90d mortality:



1.91 (0.91 – 4.09) in pts with D-dimer 2500-4999 = 2.5-4.999 mg/L
2.94 (1.42 – 6.45) in pts with D-dimer ≥ 5000
= ≥ 5 mg/L
Pts with D-Dimer ≥ 5000 ng/mL:



Higher risk of death from fatal pulmonary embolism OR 4.4 (0.5-33) than
from other causes OR 2.1 (0.7-6.0)
95% CIs for odds ratios cross 1
More of a point of interest
Confirmatory Testing



Evaluation divided between screening and
confirmatory testing
“Screening” is H&P, D-dimer
Confirmatory:
 Gold
Standard ?still Angiography
 Landmark Articles used:



V/Q [Pioped I]
CTPA [Pioped II]
MRA [Pioped III]
PIOPED I – V/Q Scanning
PIOPED Investigators. JAMA. 1990;263:2753

Multicentre study

Sens/Spec of V/Q in setting of pre-test prob

Reference standard was Angio/autopsy
PIOPED I – V/Q Scanning
PIOPED Investigators. JAMA. 1990;263:2753
PIOPED I – V/Q Scanning
PIOPED Investigators. JAMA. 1990;263:2753


Most important finding was that PE often present in
non-diagnostic scans w/ high clinical probability
Except in low probability pts, low probability scans
require additional testing
 CT
or repeated Dupplex U/S (Rosen’s)
PIOPED II – CTA / CTV
Stien, P. NEJM. 2006. 354; 22, pp 2317-2327


Prospective multicentre study, N = 824
Looking at the accuracy of CTA/CTV in setting of clinical prediction tool
(Wells)

Composite reference standard (incl V/Q, Angio neg U/S)

CTA Report 51/824 inconclusive (6%)

CTA Sens 83%, Spec 96%

CTA-CTV inconclusive 87/824

CTA-CTV 90% and 95%

Mostly 4-slice CT (didn’t have enough 8 & 16 slice to comment)
PIOPED II – CTA / CTV
Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
PIOPED II – Bottom Line
Lalani, N. Don’t Feed Me BS and Call it Candy. 2006





Didn’t really give us the answers that we wanted
Didn’t enroll 2/3 of eligible pts
CT Scanners have evolved since
Compared with V/Q, reports are far more ‘binary’
CT is probably better than this 




Dutch study 510 pts all got spiral CT +/- U/S
Gold standard: 90d follow-up
False Neg Rate 0.4%, Sens 99.6%
8/510 scans indeterminate  angio
Multi-detector Row CT
Stork, A. Knows Too Much for Own Good. 2005


4,8,16, 64 row scanners
Resolution <1mm


Visualization to 6th order vessels
Entire chest scanned in <10seconds

Reduce number of non-diagnostic scans

Less intravenous contrast
Can be formatted to 2D and 3D images

Result


Increased sensitivity for subsegmental PE
8-bit vs 64-bit resolution
CT vs Angiography
Wlner-Muram, HT. et al. Radiology. 2004; 233(3):806-15




Prospective study of 93 pts (emerg and ward) in
whom PE was suspected
4-slice CT and pulmonary angiography within 48h
SN: 100%
SP: 89%
Outcomes: Multi-detector Row CT
Moores, L., et al. Ann Intern Med. 2004; 141:866-874



Meta-analysis of 23 studies
 Negative CT PE who didn’t receive AC
 4657 patients
Results (3 month follow up)
 VTE: 1.4% (1.1-1.8%)
 Fatal PE: 0.51% (0.33-0.76%)
Conclusions
 CTPA has similar rates of recurrence as angiography
 Appears safe to withhold anticoagulation based on negative CTPA
Outcomes: Multi-detector Row CT
Quiroz, R., et al. JAMA. 2005; 293:2012-7

15 Studies Reviewed, N=3500

Studies excluded:

D-Dimer used as initial triage tool

Insufficient F/U (needed at least 3 months)

Poor quality study (objective criteria)

NPV: 99.1% (98.7 - 99.5)

NLR: 0.07 (0.05 – 0.11)
CTPE






Quick
Widely available
Relatively non-invasive
Performs similarly to angiography
Provides a “binary” outcome (interpreter dependent)
Can offer alternative diagnosis when PE is absent
CTPE - Weaknesses

Poor ability to detect small, peripheral PE’s
 ?Clinically





relavence
Protocol variability (slices, legs, venogram included)
Interpretation variability (day/night, staff/resident)
Radiation
Contrast (anaphylactoid reactions, nephropathy)
Pts may have contraindications
CT Scanning: Bottom Line
CTPA should be considered as good as the gold standard
When used with DD and U/S, NPV of >95%
Magnetic Resonance Angiography
Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

Advantages:
 Eliminates
radiation
 Probably safer in pregnancy
 Decreased nephrotoxicity

Disadvantages:
 Cost
 Availability
 Failure
studies
to demonstrate adequate SN in preliminary
PIOPED III – MR-A

Purpose

Determine accuracy of Gd-MRA of pulmonary arteries with
MRV of the thigh veins in pts with clinically suspected PE

Rationale: In PIOPED II, 25% had contraindications to
CTPA/Angio such patients could benefit from safer MR

Expect 1250 pts (lots of exclusions incl Pregnant)

Calgary is one of the Centres
Real-Life Aproach
Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83
CHR Approach


Again, the next 4 slides describe the current Calgary
Health Region approach
Even fewer people use this than the DVT model:
 Released
before PIOPED II (CTPE not included)
 V/Q results don’t tend to be this straightforward
Wells Criteria for Probability of PE
Clinical Hx/Sign
1.
Criteria
Points
leg swelling – objectively measured
S/S of DVT
3.0
AND pain with palpation in the deep vein region
2.
Pulse>100/min
3.
Immobilization
1.5
bedrest (except access to BR) > 3 days
1.5
OR surgery in previous 4 weeks
4.
Previous DVT or PE
5.
Hemoptysis
6.
Malignancy
Must have been objectively diagnosed
1.5
1.0
receiving active treatment for cancer
1.0
OR have received treatment for cancer in past 6 mo.
OR are receiving palliative care for cancer
7.
PE as likely or more
likely than an alternative
Dx.
No specific criteria – use Hx, Physical, CXR, EKG, and
labs to decide
Total Points
<2
2-6
>6
Probability
LOW
MODERATE
HIGH
LR
0.12
1.90
6.00
3.0
LOW PROBABILITY PE:
D-Dimer
Neg
STOP
Positive
VQ Scan
Normal
Non-high
High
STOP
CUS legs
Pulm Angio
DVT
Normal Positive
TREAT
STOP TREAT
Normal
CUS
In 1 week
MODERATE PROBABILITY PE:
D-Dimer
Neg
STOP
Normal
Pulm Angio
Positive
VQ Scan
Non-high
High
CUS legs
TREAT
Normal
DVT
CUS
TREAT
OR
In 1 week
HIGH PROBABILITY PE:
VQ Scan
Normal
Non-high
Pulm Angio OR CUS legsOR Pulm Angio
Normal
Pulm Angio OR CUS
In 1 week
DVT
TREAT
High
TREAT
What does the expert say?
Wells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50

Divide pts into PE likely (Wells >4) or unlikely (≤4)
Case 3 Continued




Recall…
Low probability (Wells 1.5)
D-Dimer: Positive
Therefore...
 CTPE
 Positive
Treatment
Emergency Medicine Reports. 2004;25(12)
1.
First decide primary therapy
 Significant
 Chemical
clot burden  immediate removal
- thrombolysis
 Mechanical
 Less
Significant Anticoagulation
 UFH,
2.
– embolectomy
LMWH, Coumadin
Next decide prevention against future emboli
 Anticoagulation
 IVC
filters
Fibrinolysis
Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and
meta-analysis. Crit Care Resusc 2007; 9(4)

Massive PE:
 PE
with systemic arterial hypotension, cardiogenic shock,
severe dyspnea or respiratory failure
 Multiple
case reports/series of improved outcomes and ROSC
 Kucher et al. 2006: no change in mortality or recurrence of PE

Submassive PE:
 PE
occurring in hemodynamically stable patients with
evidence of right ventricular heart strain, as seen on
ECG or echocardiography
 NEJM
2002; 347(15) –100mg alteplase in addition to heparin
improves clinical course (ARR = 13.6%, P=0.006)
Fibrinolysis in sub-massive PE
Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and metaanalysis. Crit Care Resusc 2007; 9(4)
Results of randomized trials comparing the addition of thrombolytic therapy to standard
heparin therapy for treatment of submassive pulmonary embolism fail to show any significant
differences in clinically important outcomes. [Ann Emerg Med. 2007;50:78-84.]
Fibrinolytics – Bottom Line
Consider in PE with hypotension or systemic
hypoperfusion or in the rapidly
deteriorating patient
Out-Patient Treatment of PE
Merli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res.
2008; doi:10.1016
1.
Is it technically possible?

Newer treatments allow out-pt treatment of VTE


2.
LMWH
SC UFH
Is it safe?

Pts at high risk of “badness” shouldn’t go home
Massive & Submassive PE – no brainers
 Risk stratify the rest:



Geneva Risk Score
Pulmonary Embolism Severity Index (PESI)
V. Low Risk = 1.1% 30d Mortality 
Out-Patient Treatment of PE
Merli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb
Res. 2008; doi:10.1016
3.
Is outpatient treatment appropriate in THIS patient?

Medical and Social Issues:


Bleeding risk, underlying malignancy, renal status, obesity, heart failure,
thrombophilia, and concomitant medications that interact with anticoagulants
(aspirin, clopidogrel, NSAID etc)
Medication compliance, availability of home-care, living situation, logistics of
bloodwork
Out-Pt Treatment of PE

Bottom Line:
There is no consensus on who can safely be treated at home
If the patient is hemodynamically stable, with no signs of R
heart strain and otherwise completely healthy, consideration
of out-pt treatment is reasonable.
Would make this decision in discussion with pulmonary or the
patient’s FP.
Wait, is she just a little hefty or…?

Common – VTE most frequent cause of death in pregnancy

0.5-3.0 / 1000 pregnancies

Most trials exclude pregnant pts

D-Dimer is less specific!


More false positives  more work-up
US is great…if there’s a DVT

+ in 13-15% with suspected PE

What about CTPE? V/Q?

MRI/A not studied yet
PE in Pregnancy
Winer-Muram HT, et al. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT.
Radiology 2002;224(2):487–92.





Historically, V/Q recommended  less radiation
Newer scanners supposed to be better?
V/Q still gives indeterminate results
Study used US to determine fetal geometry
Monte Carlo method for measuring radiation dose
of helical CT 2.5mm cuts to 4cm below xiphoid
Average fetal radiation dose with helical CT is less than that with
V/Q lung scanning during all trimesters. Pregnancy should not
preclude use of helical CT for the diagnosis of PE.
PE in Pregnancy
Cook JV, Kyriou J. Radiation from CT and perfusion scanning in pregnancy. BMJ. 2005;331:350.

Compared maternal and fetal-absorbed doses (16-slice)

Maternal whole body effective dose:



CTPE: 2 mSv

V/Q: 0.6 mSv
Fetal absorbed doses:

CTPE: 0.01mGy (1/1 000 000 risk of Ca by age 15)

V/Q: 0.12 mGy (1/280 000)
Breast absorbed doses:

CTPE: 10 mGy

V/Q: 0.28 mGy
CTPE: less risk to fetus,
more to mom’s breasts
PE in Pregnancy - Treatment

Same as other populations except Warfarin
 Known
Teratogen  don’t use.
Bottom Lines

History and Physical are insensitive and non-specific


Use them to determine pretest probability
D-dimer is a sensitive screening test

But not benign – use your head

Remember PERC “rule” – only a guideline

All upper limb DVT require treatment

CTPE is very powerful when combined with DD, U/S

If neg – safe to withhold treatment