see also: EMedicine.com - PE

• Mx of PE (Pulmonary Embolism)
• Mx of suspected or actual DVT (Deep Vein Thrombosis)
• investigation of suspected pulmonary embolism
• historical perspectives of PE
• anticoagulants
• pulmonary vein thrombosis (PVT)

• deep venous thrombosis (DVT) & PE are much more common than is usually realised
• without anticoagulant prophylaxis, acute DVT's are found in (50% of these will have PE):
  • 10-13% of all general medical pts admitted for bedrest > 1wk
  • 29-33% of medical ICU pts
  • 20-26% of pulm. disease pts kept in bed >= 3 days
  • 27-33% of CCU pts post-AMI
  • 48% of asymptomatic pts post-CAG surgery
• prophylactic heparin given to medical pts admitted via ED reduced overall mortality by 31%
• having an autopsy tends to double the likelihood that PE will be listed on death certificate
• PE was found in 18.5% of consecutive autopsies & were responsible for 11% of all deaths
• PE is 2nd only to AMI as a cause of sudden unexpected natural death at any age & the Dx is especially likely to be missed in older pts:
  • in pts dying of massive PE, correct Dx made in 30% overall, but only 10% in those aged > 70yrs
• PE is the single most common unsuspected cause of death in pts who die while on ventilator
• Bedell found a major missed diagnosis in 14% of pts who die in hospital & had autopsy after CPR:
  • 90% of these major missed diagnoses were PE's or bowel ischaemia
• at autopsy of pts clinically diagnosed with primary pulm. HT, 57% will have chronic pulm. thromboembolism rather than primary pulm. HT (the Mx is different for each of these diseases!!)
• The bad news about thromboembolism:
  • most DVTs are asymptomatic
  • most DVTs produce PE
  • most PEs are asymptomatic
  • many PEs are not detectable by current imaging techniques
  • many DVTs are not detectable by current imaging techniques
  • many non-detectable DVTs & PEs will progress, with recurrences that can cause sudden death and chronic morbidity

• systolic BP < 90mmHg or less than 40mmHg below usual BP for more than 15 minutes requiring high dose vasopressor support, or,
• persistent bradycardia HR < 40 with clinical features of shock, or,
• patient in extremis (diaphoretic, mottled, confused, sensation of dying)

• systolic BP < 90mmHg or less than 40mmHg below usual BP for more than 15 minutes but not requiring high dose vasopressor support, or,
• persistent bradycardia HR < 40

• no features of massive but either:
  • raised troponin,
  • RV dysfunction on echo,
  • large clot seen in RV,
  • raised lactate,
  • diaphoresis, mottled, severe tachypnoea, or,
  • shock index (HR/SBP) > 1, or,
  • Neutrophil to lymphocyte ratio >9.2 in patients with no other cause for a raised neutrophil count (suggests high mortality risk of around ~26%)

• no features of higher severity as above, but:
  • large clot burden on CT scan, and,
  • definite RV dilatation, and,
  • euvolaemic (no other cause for any haemodynamic instability such as dehydration or blood loss)

• not really useful in an ED setting as we need more acute mortality risk scoring, and those with high-risk submassive PE may have a low PESI score

• interpretation:
  • ≤ 65 = class I (very low risk)
  • 66-85 = class II (low risk)
  • 86-105 = class III (intermediate risk)
  • 106-125 = class IV (high risk)
  • ≥ 126 = class V (very high risk)

• 10% of pts with acute PE will die in 1st 60min
  • presence of shock increases mortality 3-7x, with most deaths occurring within 1hr presentation¹⁾
• mortality rates in the 1st 3 days following diagnosis depends upon severity of presentation²⁾:
  • cardiac arrest on arrival = ~95%
  • requiring mechanical ventilation or CPR = ~80%
  • syncope = ~40%
  • haemodynamically stable patients who have echocardiographic evidence of right ventricular dysfunction = 15% (and a further 8% mortality within 1 yr if survive to discharge from hospital)³⁾
  • all “stable” patients who had CT-PA or V/Q = 1-2%
• massive PE
  • 90 day mortality: 58% (International Cooperative Pulmonary Embolism Registry (ICOPER) )
• sub-massive PE with abnormal RV function and raised troponin levels:
  • hemodynamically stable PE, with an RV/LV transverse ratio on CTPA ≥ 0.9 was associated with increased death or clinical deterioration (HR 3.8, 95% CI 1.3–10.9, p = 0.007) ⁴⁾
  • elevated troponins were associated with increased short-term death (OR 5.24; 95% CI 3.28–8.38) ⁵⁾
  • raised high-sensitive cardiac troponin T (hsTnT) also showed increased death (OR 3.80, 95% CI 2.74–5.27) ⁶⁾
  • in normotensive PE patients, hsTnT levels ≥ 14 pg/mL had a PPV and NPV for adverse 30 day outcomes of 8% and 100%, respectively ⁷⁾
  • ? 5% mortality in 1st 48hrs with early anticoagulation
  • 30 day mortality with anticoagulation: PEITHO study: 1.2% Becattini et al study: 7.7% I-COPER registry: 16% ⁸⁾
  • 90 day mortality of all “sub-massive” cases: 15% (International Cooperative Pulmonary Embolism Registry (ICOPER) )
• of those patients who do not present with massive PE:
  • 1/3rd will be eventually diagnosed & Rx:
    • of these 1 in 12 will die from massive PE or complications of PE
  • 2/3rds will remain undiagnosed (ie. 400,000 cases /yr in USA):
    • of these, 1/3rd will die
• survivors will be at risk of:
  • recurrent PE's
    • risk is dependent upon:
      • persisting underlying cause for thrombosis (eg. cancer, thrombophilia)
      • “unprovoked” PE
      • elevated D-Dimer after cessation of anticoagulant Rx
      • compliance with anticoagulation Rx
  • chronic thromboembolic pulmonary hypertension (CTEPH)
    • 4% of treated patients by 2 yrs after PE
    • risk depends upon:
      • more than one episode of PE (odds ratio, 19.0)
      • younger age (odds ratio, 1.79 per decade)
      • a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion)
      • idiopathic pulmonary embolism at presentation (odds ratio, 5.70)⁹⁾

• apart from gynae. surgery pts & major trauma pts, lower extremity venous thrombosis virtually always starts in the calf veins, and propagates above the knee in 87% of cases with symptomatic DVT
• in pts with PE, 70% have DVT evident on venograms (?50% on US) although up to 90% of all PEs arise from pelvic or lower DVTs
• risk of embolisation from DVTs:
  • ileofemoral: ~100%
  • popliteal-femoral: 60-80% (half of these PEs will be asymptomatic) - degree of proximity not important
  • calf veins: 33-46%
    • 35% of pts with PE
    • 25% of lethal PEs
    • 33% of “serious” PEs (NB. all PE's are clinically significant as minor ones may just be sentinal events!)
• see Deep venous thrombosis

• amniotic fluid embolism:
  • most commonly occurs near end of 1st stage of labour, but also in abortion or immediate post-partum period
  • Mx:
    • empty the uterus
    • Rx DIC which contributes to the 80% mortality rate
• fat embolism:
  • most commonly occur after fractures of long bones
  • fat globules pass through pulm. circulation to enter systemic circulation where end-organs are affected via obstruction of end-capillaries causing petechiae, CNS symptoms (headache, irritability, convulsions, coma), ARDS, thrombocytopenia
  • Mx:
    • high-dose steroid Rx
    • heparin is C/I as theoretical risk of increasing production of toxic fatty acids in the lungs.
• air embolism:
  • generally iatrogenic, but may be from pressurised underwater breathing apparatus, air-powered drills, vaginal insufflation (in orogenital sex, esp. in pregnancy)
  • often venous (causing circulatory collapse) and arterial (causing CNS impairment)
  • clinical syndrome:
    • loud churning murmur over precordium
    • air bubbles within heart may be seen on echo
    • circulatory collapse may result from as little as 5ml/kg of air forming an air lock in RV or pulm. circulation
  • Mx:
    • left lateral position in an attempt to trap air within RA
• other embolism:
  • bile:
    • post-percutaneous transhepatic drainage for Ca pancreas
  • tumour:
    • ~20% of embolism deaths in pts with solid cancers
  • bone marrow:
    • assoc. with # long bones or sternum/ribs in CPR
  • IV drug preparations
  • broken catheters
  • parasites
  • bullets
  • cardiac vegetations

• blockage of one portion of pulm. vasculature causes increased pulm. vasc. resistance
  • ⇒ increased pulm. arterial pressures (if > 25% pulm. vasculature blocked)
    • ⇒ increased RV pressures
    • ⇒ if > 50% blocked then:
      • signif. pulm. HT results with cor pulmonale
        • in extreme cases, with PABP > 40mmHg, TI results
      • haemodynamic collapse may occur ⇒ death
  • ⇒ V/Q mismatches ⇒ nonperfused lung converted into physiologic dead space
    • ⇒ increased minute ventilation (~1% increase per 1% decrease in perfused alveoli)
      • eg. 15% increase via RR 14to16/min or 150ml increase in tidal volume ⇒ subtle!
  • pain/anxiety ⇒ further hyperventilation
  • after 24hrs, localised alveolar oedema may occur ⇒ rales
  • release of neurohumoral factors may ⇒ pulm. vasoconstriction & bronchoconstriction ⇒ rhonchi
• small recurrent PE's:
  • pulm. arterial endothelium is relatively incapable of lysing thrombus so most emboli remain there permanently!!
    • V/Q & angio. abn. often resolve but this is by organisation & recanalisation
      • decreased pulm. vascular distensibility, thus any attempt to increase cardiac output results in increased pulm. vasc. resistance
        • ⇒ cardiac output can only increase if PABP increases enough to overcome this additional resistance
          • ⇒ pulmonary HT ⇒ chronic cor pulmonale

• clinically apparent factor(s) present in 90% of pts with PEs:
  • past DVT/PE - single strongest risk factor for recurrence (RR 15-30x)
  • immobilisation
  • malignancy
  • stroke
  • recent surgery
  • pregnancy & post partum:
    • recognised thromboembolism occurs in 3-4/1000 births
    • accounts for 20-50% of maternal mortality
    • 75% of clinically recognised PEs occur antepartum, > 50% in 1st 15wks gestation, HOWEVER, it is likely that incidence is equal in each of the trimesters, it just gets harder to diagnose later in pregnancy
    • gradient compression stockings are strongly recommended for all pregnant pts
    • NB. post-partum endometritis:
      • risk of septic pelvic vein thrombophlebitis ⇒ septic pulmonary emboli in 40% if untreated
      • thus consider anticoagulant Rx in pts with significant post-partum endometritis
    • NB. ovarian vein thrombosis:
      • diagnosis is rarely clinically apparent & usually made laparoscopically or at C.S. or on CT
      • thrombus may extend into vena cava in which case a vena caval filter is indicated
• cardiac failure, AMI
• haematological factors (usually not clinically apparent)
• obesity (> 20% more than ideal)
• see also: haemostasis pathophysiology

• PE is known as “the great masquerader”
• pleuritic chest pain
• “pneumonia”
• “asthma”
  • “All that wheezes is not asthma” (Chevallier Jackson). PE may appear as asthma when diffuse wheezing results from the release of vasoactive and bronchoactive mediators. 10-20% of PE patients present with wheezing.
• “pleurisy”
• “angina” (4-30% present & misdiagnosed as angina)
• “AMI” (PE is 10% of deaths in pts Dx with AMI)
  • conversely, AMI is the most common cause of death when clinical Dx of PE is incorrect!
• paradoxical embolism (usually from calf DVTs which tend have smaller emboli):
  • 27% adults have patent foramen ovale
• pulmonary infarction mimicking “bronchogenic carcinoma” or if cavitates, a “lung abscess” on CXR or V/Q
• “psychosomatic hyperventilation” or “anxiety disorder”
• collapse, cardiac arrest with PEA and death - within 2 hrs of onset of massive PE

• dyspnoea (73%)
• pleuritic pain (66%)
• cough (37%)
• leg oedema (28%)
• leg pain (26%)
• haemoptysis (13%)
• palpitations (10%)
• wheeze (9%)

• tachypnoea (70%)
• rales (51%)
• tachycardia (30-44%)
• elevated neck veins (31%)
• S4 (24%)
• loud S2 (23%)
• cyanosis (11%)
• sweating (11%)
• rhonchi (5%)
• pleural rub (3%)

• increased A-a gradient (75-90%):
  • see under hypoxia
  • normal A-a gradient:
    • in air:
      • < 10mmHg in young adults
      • < 20mmHg in elderly
      • < 4+ age/4 on air (Skorodin)
    • < 10% pIO2
  • A-a gradient = alveolar pO2 - arterial pO2
    • alveolar pO2 = (760-47)xFiO2 - arterial PCO2/R, where R usually = 0.8
    • may be normal in 23% of pts with PE
    • if abnormal, is more likely to be due to other pulmonary pathology rather than PE
    • thus although better than pO2 or pCO2, it has poor predictive value
• pO2:
  • has zero predictive value (as does SaO2)
  • 20% have pO2 > 80mmHg in air & 5% have pO2 > 100mmHg in air
  • in pts with suspected PE (ie. probability of PE ~50%):
    • the incidence of PE is higher in the group with pO2 higher rather than lower than an arbitrary pO2 cutoff value (whether 65, 70 or 80mmHg)
• low pCO2:
  • poor marker - 35% PE's vs 33% no PE!

• abnormal in 70% but non-specific abnormalities due to right heart strain:
• acute PE:
  • ST/T changes (esp. III, V1-2) (49%)
    • see https://lifeinthefastlane.com/ecg-library/100-ecgs/quiz-ecg-007/
  • sinus tachycardia (44%)
  • RBBB (15%)
  • S1Q3T3 (12%)
  • P pulmonale (6%)
  • atrial arrhythmias (2%)
• chronic PE:
  • RAH (7%)
  • RVH (6%)
  • T wave inversion (esp. III, V1-2) (40%) - if T inv. in both ant. & inf. leads this is highly specific for PE (75%) - Marriott
  • pseudoinfarction (11%)

• usually abnormal (84%) but mostly subtle abnormalities:
  • atelectasis or parenchymal abnormality (68%) - may take 3 days to develop
  • pleural effusion (48%)
  • pleural based opacity (35%)
    • eg. Hampton's hump (rare):
      • pleural based density/lung consolidation with a rounded border pointing to hilum
  • elevated hemidiaphragm (30%)
  • reduced pulmonary vasculature (21%)
  • prominent central pulmonary arteries (14%)
    • Westermark's sign (7%)
      • dilated pulmonary outflow tract on side of embolism with area of decreased perfusion distal to it
  • pulmonary oedema (4%, BUT 13% pts without PE had it!!)
• useful in diagnosis of other conditions (eg. pneumonia, APO, pneumothorax)
• if “normal” in setting of hypoxaemia then suggestive of PE

• PIOPED II study: sens 83% and spec 96% for PE thus positive likelihood ratio (LR) = 0.83/(1-0.96) = 21