Pulmonary Embolism

Approach to suspected PE:

a) Formulation of pre-test probability is CRITICAL in interpretation of subsequent diagnostic studies

b) There are multiple ways to do this, most widely studied is the Wells criteria

c) Wells critieria:

- Signs and symptoms of DVT: 3 pts

- PE most likely diagnosis: 3

- Tachycardia: 1.5

- Hx PE/DVT: 1.5

- Immobilization for at least 3 days, or surgery within 4 weeks: 1.5

- Hemoptysis: 1

- Malignancy treated within 6 months, or palliative: 1

d) Wells score:

- 0-2 pts: Low probability

- 2-6 pts: Moderate probability

- >6 pts: High probability

e) Modified Wells score:

- 0-4 pts: Unlikely

- >4 pts: Likely

Diagnostic modalities to evaluate for PE:

a) CT angio: If no contraindications (e.g. AKI), diagnostic modality of choice, given strong PPV and NPV

b) V/Q scan: Helpful if normal or highly probable for PE, but often non-diagnostic

c) LE ultrasound: Can provide indirect evidence of PE if LE DVT is visualized

d) Both CT angio and V/Q scan must be interpreted in the context of your pre-test probability, as the accuracy of diagnosis is highly influenced by this (PIOPED I and PIOPED II data)

Algorithm to PE diagnosis (see attached Christopher study):

a) First, determine pre-test probability with modified Wells score

b) If Wells score 0-4, check D-dimer

- If negative, then no need for further studies (0.5% risk of PE in this group)

- If positive, proceed to CTA

- If positive, treat; if negative, PE excluded

c) If Wells score >4, proceed straight to CTA

- If positive, treat; if negative, must consider overall clinical picture (5% risk of PE in this group)

d) V/Q scan can substitute for CTA as imaging

- If V/Q is indeterminate, one strategy is to perform serial LE u/s, and if they are negative over 2 weeks, PE may be excluded

VQ Scan-what, why, limits
V/Q scan is a 2 step, low risk study that requires little pt preparation
step 1: inject technetium tagged albumin which gets trapped in lung circulation, images obtained in many positions. If ruling out PTE and this step is normal, step 2 not necessary
step 2: pt inhales aerosolized solution of diethylenetriaminepentaacetic acid (DTPA) which is trapped in proportion to alveolar aeration
PTE is suggested with mismatch in V and Q whereby perfusion is limited but aeration is not. Matched defects are suggestive of parenchymal disease. V/Q scans are compared simultaneously to CXR to correlate lung fields

Indications to use VA Scan:
PTE in case of renal failure, contrast allergy, facility without CT capabilities
Burn Inhalation injuries
Preoperative eval for chronic obstructive pulmonary disease and candidates for pneumonectomy.
Limits: Can be false positive in Pneumonia, mass, prior PTE, radiation may affect fetus so not recommended in pregnancy

Pulmonary Embolism Severity Index:

a. Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute PE

i. The PESI uses objective clinical items to create a risk stratification score: age, h/o cancer, h/o COPD, HR ≥ 110, SPB<100, O2 sat <90%, RR>30, AMS, T<36

ii. PESI does not involve imaging or laboratory biomarkers (facilitates quick risk stratification)

iii. Based on the total score, patients can be stratified into one of 5 risk classes (I–V), where the mortality increases with increasing class stratification (30-day mortality is ~ 1.1% for class I, but 24.5% for class V)

iv. PESI is a reproducible and reliable scoring tool to predict both 30- and 90-day mortality (see article link for )

v. PESI has excellent negative predictive value for short-term mortality

vi. PESI can be used to identify patients who may be candidates for outpatient management

b. Simplified PESI (Jimenez et al, Arch Intern Med 8/2010): http://sfx.stanford.edu.laneproxy.stanford.edu/local?sid=Entrez:PubMed&id=pmid:20696966

i. Simplified PESI: based on age >80, h/o cancer, h/o COPD, HR ≥ 110, SPB<100, O2 sat <90% (1 pt for each, 0 pts is low risk, ≥1 pt is high risk)

ii. The simplified PESI has similar prognostic accuracy and clinical compared with the original PESI and was easier to use

c. Other risk factors for high mortality: RV dysfunction, elevated BNP (nt-BNP>600), elevated troponins, concomitant DVT or RV thrombus

Treatment of PE:

Initial therapy is with unfractionated or low-molecular weight heparin
- LMWH:

Advantages: Lower risk of recurrent DVT/PE compared to UFH, possible mortality benefit, lack of monitoring given predictable pharmacokinetics
Disadvantages: Renally-cleared, so use in kidney disease less predictable, cannot be reversed, subcutaneous absorption variable in obese pts

UFH:
- Advantages: Can be turned off quickly or reversed

Disadvantages: Requires monitoring, higher incidence of heparin-induced thrombocytopenia

LMWH should be drug of choice, unless there is a high risk of bleed, impending procedure, renal insufficiency, or potential need for thrombolysis
Ultimate therapy is typically vitamin K antagonist (e.g. warfarin)

Must overlap therapy with 4-5 days of UFH/LMWH, even if INR becomes therapeutic earlier
Initial rise in INR is from inhibition of factor VII, which has the shortest half-life, and inhibition of intrinsic pathway takes more time
One exception to warfarin is in patients with malignancy, where LMWH is superior in preventing recurrent VTE (CLOT trial)

Massive v. submassive PE: definition, treatment

a. massive PE: defined as a hemodynamically significant PE causing SBP to drop >40 pts from baseline or <90mmHg

b. All acute PE not meeting the definition of massive PE are considered submassive PE (can have evidence of RV dysfunction)

c. A saddle PE is a PE that lodges at the bifurcation of the main pulmonary artery into the right and left pulmonary arteries. Most saddle PE are actually sub-massive (retrospective study of 546 patients with PE, 14 (2.6 percent) had a saddle PE, 2 patients with saddle PE had hypotension). Arguably, this doesn’t include pts who may have died before reaching the hospital…

d. Treatment of massive PE:

i. First line tx is hemodynamic support: initially w IVF, cautiously (assess neck veins, start w/ 500cc-1L) as volume overload can worsen RV failure

ii. If no improvement, vasopressors should be started (no RCTs show benefit of one vasopressor over others in PE-related shock). Have to manage effects of inotropy (ie. afib).

iii. Anticoagulation should be started during the resuscitative period if no major contraindications (ie. recent head bleed); does not affect mortality in the first few hours; risk for recurrent PE is as high as 25% if the PTT is not therapeutic w/in 24 hrs

iv. Untreated PEs (submassive + massive) have a 30% mortality rate, 5% with treatment

v. Thrombolysis?

1. Thrombolytic therapy accelerates the lysis of acute PE and improves important physiologic parameters, such as RV function and pulmonary perfusion. However, no clinical trial has been large enough to conclusively demonstrate a mortality benefit **

2. Thrombolytic therapy is associated with an increased risk of major hemorrhage (intracranial hemorrhage, retroperitoneal hemorrhage, or bleeding leading directly to death, hospitalization, or transfusion)

Risk of intracranial hemorrhage is 1-3%, with major bleeding 20%

No mortality benefit (MAPPET-3), but may accelerate lysis and hemodynamic improvement

Catheter-directed has not been shown to be superior to systemic therapy

Most recent guidelines recommend consideration in patients who are high risk, with low bleed risk

3. Persistent hypotension due to PE (ie, massive PE) is the most widely accepted indication for thrombolytic therapy.

4. thrombolysis may be considered in submassive PE under certain clinical circumstances (such as severe hypoxemia, large perfusion defects, RV dysfunction,etc.)

vi. Embolectomy?

1. Embolectomy can be performed by IR (catheter-directed) or surgically

2. can be considered when a patient's presentation is severe enough to warrant thrombolysis, but this approach either fails or is contraindicated

vii. IVC filter

Indications:

Contraindication to anticoagulation

Recurrent PE on therapy

hemodynamic compromise such that subsequent PE would not be tolerated

Effectiveness (PREPIC): only studied with concomitant anticoagulation on board

Do not reduce risk of recurrent VTE or mortality

Reduces risk of PE, but increases risk of DVT

** The NEJM review of Acute PE last month mentions a mortality benefit for thrombolysis in massive PE, based on a 2004 meta-analysis in Circulation. The main issue with this meta-analysis is the relatively small cohort of patients with hemodynamically stable PE. The authors of this meta-analysis conclude: “Currently available data provide no evidence for a benefit of thrombolytic therapy compared with heparin for the initial treatment of unselected patients with acute pulmonary embolism. A benefit is suggested in those at highest risk of recurrence or death. The number of patients enrolled in randomized trials to date is modest, and further evaluation of the efficacy and safety of thrombolytic therapy for the treatment of high-risk patients with acute pulmonary embolism appears warranted.”

http://circ.ahajournals.org.laneproxy.stanford.edu/cgi/content/full/110/6/744

** Cochrane review for thrombolytic therapy in acute PE 2009: concludes “based on the limited evidence found we cannot conclude whether thrombolytic therapy is better than heparin for pulmonary embolism. More double-blind RCTs, with subgroup analysis of patients presenting with haemodynamically stable acute pulmonary embolism compared to those patients with a haemodynamic unstable condition, are required” http://sfx.stanford.edu.laneproxy.stanford.edu/local?sid=Entrez:PubMed&id=pmid:19588357

Thrombophilia workup:

a) Controversial, as risk of recurrent VTE does not appear to be higher in those with inherited thrombophilia (see attached JAMA paper)

b) Protein C/S and antithrombin levels can be decreased in setting of acute clot, and thus low levels may not represent true deficiency

- However, if levels are normal, deficiency is effectively ruled out

c) Prothrombin gene mutation and factor V Leiden can be evaluted at any time

d) Duration of anticoagulation is typically not influenced by this, as most significant prognostic factor is recurrent clot

(Ellen Eaton MD, 9/21/10)

(Christopher Woo MD, 8/5/10, 4/19/11)

(Victoria Kelly MD, 7/17/10, 9/2/10)