PE & DVT

BASIC Instructor & Provider Course, October 2008, Sydney. Registration deadline 27th September.
Click here for details

Thromboembolic disease

Mechanism of risk	Risk factors	Pathophysiology
Clinical features	Differential diagnosis	Investigations
Management	Prognosis	Pregnancy
Further reading

70% of patients with confirmed PE have DVT
40% of patients with DVT have silent PE
DVT limited to calf veins (distal DVT) seldom results in clinically obvious PE
similarity in clinical outcome of patients with DVT or with PE during long-term follow up
PE and DVT should probably be regarded as a single clinicopathological entity

Risk

~6.5% of patients have DVT on admission to ICU
further 20-30% develop DVT during ICU stay
risk highest amongst patients who have suffered major trauma (40-70%) and spinal cord injury (60-80%)

Mechanism of risk

Changes in blood flow

venous stasis
- immobilization
- raised CVP
- valvular damage due to previous thromboembolic disease

Changes in properties of blood

increased coagulation and/or platelet activity eg lupus anticoagulant
decrease in physiological anticoagulants and/or fibrinolytic activity common in critically ill patients
- antithrombin III, protein S and protein C deficiencies
- acquired activated protein C resistance
- high levels plasminogen activator inhibitor I

Changes in vessel wall

endothelial damage triggers coagulation
- trauma
- central venous catheters

Risk factors

prolonged immobilization
increased age
surgery & trauma
coagulation abnormalities:
- polycythaemia
- platelet abnormalities
- antithrombin III deficiency
- protein C & S deficiencies
- inherited abnormalities of fibrinogen and plasminogen
- previous venous thrombosis
- smoking
medical conditions, especially those associated with low cardiac output or prolonged bed rest:
- CCF, MI
- shock syndromes
- CVA
- obesity
- malignancy, especially pancreas, stomach, lung, GU tract, breast
- vasculitis
- dysproteinaemias
- hyperlipidaemia
- inflammatory bowel disease
- paroxysmal nocturnal haemoglobinuria
- Behcets
- sickle cell anaemia
drugs, eg oral contraceptive/oestrogen
pregnancy

Pathophysiology

massive PE increases RV afterload, enlarges RV and deviates septum to left thus decreasing LV volume and compliance
cardiac output and coronary blood flow (especially to right heart) are diminished resulting in decreased ventricular contractility and a cycle of cardiac decompensation. Death is usually due to right heart failure not refractory hypoxia.
neurogenic and humoral influences may result in catastrophic pulmonary hypertension with occlusion of as little as 30% of the pulmonary vascular bed
critically ill patients often have reduced cardiorespiratory reserve and small pulmonary emboli which would be well tolerated by less sick patients may be poorly tolerated by ICU patients

Clinical features

Small "heraldic" emboli commonly precede a major embolus and 90% of fatal emboli are recurrent emboli

Symptoms

dyspnoea or tachypnoea in 91% of patients; dyspnoea, tachypnoea or pleuritic pain present in 97% of patients with acute PE
non-productive cough
haemoptysis only occurs if infarction has occurred
syncope (suggests massive PE though may occur following minor PE)

Physical signs

RS

tachypnoea common
cyanosis usually only occurs after massive PE
pleural effusion and rub
wheeze and crackles

CVS

HR: usually increased, bradycardia ominous
+/- signs of pulmonary hypertension, especially following massive PE
+/- raised JVP with prominent "a" waves
+/- shock after massive PE. Small sharp peripheral pulse may be palpated

Lower limbs

clinical evidence of DVT found in only 30%. DVT found in "normal" leg in 36%

Others

sweating and fever infrequent

Differential diagnosis

MI
LVF
aspiration pneumonitis
pleural effusion
pneumonia
fat embolism
pneumothorax
aortic dissection

Investigations

Most screening tests have not been adequately validated for use in ICU patients and comments on sensitivity and specificity are based on studies in other groups of patients

To diagnose DVT

US. Doppler US notoriously insensitive in detecting proximal vein thrombi in asymptomatic patients (even those at high risk) although sensitivity in symptomatic patients is 91%. High specificity in both groups of patients. Examination of common femoral and popliteal vessels only appears to be adequate
impedence plethysmography: low sensitivity and specificity
contrast venography: visualization of external and common iliac veins is inadequate. Complications include pain, hypersensitivity reactions, phlebitis, DVT
MRI: accuracy of 96% in detecting pelvic thromboses

To diagnose PE

blood tests: raised WCC, raised D-dimer (non specific but very sensitive; D-dimer <500 mg/L virtually excludes PE)
CXR
- changes neither sensitive nor specific.
- localized infiltrates, consolidation, atelectasis in 2/3
- pleural effusion in 1/2
- classical "plump" pulmonary arteries with peripheral pruning relatively rare and non-specific. Tends to be associated with massive PE
ECG
- normal in 30%.
- changes of R heart strain most common
- S1Q3T3 pattern infrequent
- LAD > RAD
- P pulmonale, RBBB, atrial arrhythmias occasionally present. Persistent if PE massive
ABG
- hypoxaemia frequent but PaO2 >10.6 in 1/4 and A-a gradient may be normal
- metabolic acidosis in shocked patients
VQ scan
- probability of PE based on clinical suspicion and results of VQ scan. High clinical suspicion based on presence of one or more predisposing factors, appropriate clinical presentation and absence of other diseases to account for presentation while low suspicion based on absence of underlying risk factors and the presence of other diseases to account for presentation.

Clinical suspicion	Low	Intermediate	High
Normal/very low probability scan	2	6	0
Low probability scan	4	16	40
Intermediate probability scan	16	28	66
High probability scan	56	88	96

pulmonary angiography
- "gold standard". Indicated in those patients in whom probability of PE based on clinical suspicion and VQ scan does not allow confident diagnosis or exclusion of PE. Contrast may cause catastrophic vasodilatation and resuscitation facilities should be available
- if pulmonary angiography is not available:- patients with low or intermediate probability scans in whom clinical suspicion of PE is intermediate or high should have Doppler US of legs. If this is normal the probability of a thromboembolic event is < 5%. In patients without cardiorespiratory disease it is probably reasonable not to treat at this level of risk. However patients with underlying cardiorespiratory disease require a more aggressive approach as PE appears to be more dangerous in this group.
echocardiographic features associated with PE:
- decreased mitral valve opening
- thromboemboli in R heart or PA
- RV dilatation
- RV hypokinesis
- abnormal septal position/paradoxical systolic movement
- reduced LV size
- increased RV:LV diameter ratio
- PA dilatation
- tricuspid or pulmonary regurgitation
CT angiography

Prevention of DVT

low molecular weight heparin or low dose unfractionated heparin
graduated compression stockings ±intermittent pneumatic compression device for those in whom anticoagulation is contra-indicated. (Note that the efficacy of mechanical prophylaxis has never been tested in ICU patients).

Risk of DVT or PE	Risk of bleeding	Recommendations
++	+	Heparin 5000U subcutaneously twice daily
+++	+	Low molecular weight heparin
++	++	Mechanical prophylaxis initially. Heparin 5000U SC bd when bleeding risk decreases
+++	++	Mechanical prophylaxis initially. LMW heparin when bleeding risk decreases

Management of pulmonary embolus

Supportive

Cautious fluid loading – marked rise in RVEDP will result in a marked decrease in right sided coronary perfusion pressure and a shift of the interventricular septum to the left, reducing LV preload
Norepinephrine ± dobutamine may be best combination of vasoactive drugs.
- Isoproterenol is arrhythmogenic and a systemic vasodilator and is detrimental.
- Nitroprusside decreases RV coronary perfusion.
Anticoagulation with heparin and then warfarin.
- Heparin should be started as soon as the diagnosis is suspected in the absence of specific contraindications
- Heparin should be continued for 5 days after the start of warfarin even if INR is in therapeutic range. This is because warfarin not only inhibits vitamin K dependent clotting factors, it also reduces protein C levels. Thus a hypercoagulable state may exist during early stages of warfarin therapy, before the longer half-life factors (II, IX, X) are inhibited. There is a wide discrepancy in recommended heparin dosage regimes. The American College of Chest Physicians recommend an initial bolus of 80 U/kg followed by 18 U/kg/h. Subsequent changes in infusion rate are based on APTT (see table 1).

APTT (sec)	APTT (x control)	Adjustment
<35	<1.2	80 U/kg bolus & infusion by 4 U/kg/h
35-45	1.2-1.5	40 U/kg bolus & infusion by 2 U/kg/h
46-70	1.5-2.3	No change
71-90	2.3-3	¯ infusion by 2 U/kg
>90	>3	Stop infusion for 1 h then ¯ infusion by 3 U/kg/h

Table 1. Heparin dose adjustment

Definitive therapy

Thrombolytic therapy

improves outcome in patients with massive PE although when given to all patients with PE no evidence of benefit in terms of outcome has been demonstrated. Should probably be reserved for those patients with diagnosis proven by a well established imaging method (ie pulmonary angiography or CT angiography).
may also be used for patients with significant swelling associated with proximal DVT in absence of contraindications (rare in ICU patients).
contraindicated in pregnancy
recommended regimes:
- streptokinase: 250000 U over 30 min then 100000 U/h for 24 h
- urokinase: 900U/kg over 10 min then 900U/kg/h for 24 h
- rtPA: 100 mg over 2 h

rtPA may produce more rapid improvement than streptokinase and is probably the agent of choice as deaths from massive pulmonary embolus tend to occur early and result from acute right heart failure

check APTT after infusion of thrombolytic is complete. Start heparin without loading dose when APTT <2 times upper limit of normal. If APTT is above this level repeat measurement every 4 h until safe to start heparin.

Catheter extraction of clot

requires technical expertise
limited case series suggest that this is a useful technique in those in whom thrombolysis is contraindicated

Surgical embolectomy

Rarely indicated
Mortality approaches 40%
Consider if thrombolysis contraindicated or unsuccessful and there is persistent hypotension, oliguria, hypoxia and metabolic acidosis with radiological confirmation of >50% occlusion

Secondary prevention

IVC filter

Indications:

recurrent PE despite adequate anticoagulation
anticoagulant intolerance
large free-floating thrombus in ileo-femoral veins
immediately following embolectomy

Prognosis

initial mortality following PE is 2.5%, mostly due to recurrent PE
in 399 patients with well-documented PE, 1 year mortality was 24% (19.2% of those treated with heparin followed by oral anticoagulation). Cardiac disease, recurrent PE and cancer caused 3/4 of deaths (cancer 1/3 of them). Recurrences of PE were usually seen in first 2 weeks of follow-up and accounted for only about 10% of deaths
mortality of in-hospital DVT 5%

Thromboembolic disease and pregnancy

PE causes 15-25% of maternal deaths
pregnancy associated with 6-fold increase in thromboembolism as a result of venous stasis, a hypercoagulable state and vascular injury associated with delivery
venography after the first trimester and ventilation perfusion scans should not be avoided if indicated
warfarin should not be used before delivery
heparin continued until labour begins and is restarted in postpartum period when bleeding has stopped