Management of Pulmonary Embolism in Emergency Department

Dr. A. Barai MBBS, MRCS Ed, MSc (Critical acre)

Registrar in Emergency Medicine

• 26 years old male• Otherwise fit and healthy

HOPC:• Collapsed inside the house while standing• Unresponsive for 5 minutes• Diaphoretic and tachypnoeic• Computer engineer by profession• Has been in front of the computer for 18 hours a day for a

month without any break

Case 1Case 1

O/E:• Pulse 128/min, regular• BP: 126/72 mmHg• RR 32/min• Sats: 90% RA• ECG: Sinus tachycardia. S1Q3T3 pattern• ABG: PO2= 56 mmHg• CXR: Normal• Doppler USS: DVT in left leg.• VQ scan: Perfusion defect in right lower lobe.

Treatment:• Unfractionated heparin IV followed by• Oral Warfarin

Introduction• Pulmonary embolism (PE) is a medical emergency

where pulmonary artery or its branches are blocked with embolic substances most commonly blood clots

• Most cases are not life threatening.

• Incidence: 600,000/year in USA

• Mortality rate: 50,000 to 200,000/yr in US

Types of PE• Massive PE: Acute PE with obstructive shock or SBP

<90 mmHg for > 15 minutes or shock

• Sub-massive PE: Acute PE without systemic hypotension (SBP ≥90 mm Hg) but with either RV dysfunction or myocardial necrosis

• Non-massive or low risk PE: None of the above severe features.

Jaff MR, et al. (2011)

Diagnosis• Risk stratification

• Clinical examination

• Bed side tests

• Laboratory tests

• Imaging techniques

Risk factors• Alteration of blood flow:

– Prolonged immobilisation, – Obesity, – Pregnancy, – Cancer

• Factors in blood vessel wall: – Surgery, – Catheterisation.– Trauma

• Hypercoagulable states: – Estrogen containing OCP, – Genetic thrombophilia (Factor V Leiden deficiency, Protein C and

Protein S deficiency, antithrombin III deficiency etc.), – Acquired thrombophilia (antiphospholipid syndrome, nephrotic

syndrome, paroxysmal nocturnal hemoglobinuria)

Risk stratification

• PERC Rule

• Wells score for PE

• Modified Geneva score for PE

PERC

PERC

Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost 2004;2:1247–55.

Wells score for PE

Investigations• Bed side tests: ECG, ABG

• Blood tests: D-dimer, FBC, Troponin, UEC

• Imaging techniques: Ultrasound/ Doppler scan, Chest xray, CTPA, V/Q scan, Echocardiogram

ABG findings in PE

• pH= ↑ • PaO2= ↓• PaCO2= ↓• HCO3= Normal• Aa gradient= Large

Aa gradient= PAO2- PaO2

Chest xray• Mostly normal findings

• Done to exclude other pathology

• Plural effusion

• Specific signs:- Hampton’s hump- Westermark sign

Hampton’s hump

Westermark sign

ECG findings in PE• Normal sinus rhythm

• Sinus tachycardia

• Tall peaked T waves in V1- V4

• S1Q3T3 pattern: Not specific. Can be seen in any Cor pulmonale syndrome

• RBBB

S1Q3T3 pattern ECG

D-dimer in PE• D-dimer is a type of Fibrin degradation product

• Can be raised due to a number of reasons

• Negative D-dimer rules out PE/DVT in 98% cases

• False positive D-dimer: infection, pregnancy, renal failure, post-operative

Echocardiogram in PE

Doppler USS

CTPAIndications:

- Suspected PE

Contra-indications:- Renal failure- Pregnancy- Allergy to radio-contrast

Procedure:- Radioactive iodine administered IV- CT scan performed

Ventilation-perfusion scanIndications:

- Renal failure- Pregnancy

Procedure:- Ventilation scan with Xenon inhalation- Perfusion scan with Tc99m labelled radioactive dye infusion- Scan V/Q- Result: unmatched V/Q

Pitfalls of CTPA• Average radiation exposure is 12.4-31.8 mSV.

• This was estimated to increase the risk of breast cancer by 1.004 to 1.042 and lung cancer from 1.005 to 1.076.

• The excess risk of cancer for individuals over 55 would be less than 1%;

• In a young 20-year-old woman this would be estimated to increase the relative lifetime risk of breast or lung cancer by 1.7 to 5.5%.

(Hurwitz et al. 2007)

Treatment options• Symptomatic treatment:

– ABCD approach– Oxygen– Analgesia

• Anticoagulation:– IV Heparin– S/C LMWH eg Enoxaparine, Dalteparine– Oral Warfarin

• IVC filter: If there is contra-indications for anti-coagulation

• Thrombolysis: tPA eg Alteplase, Tenectaplase

• Surgical procedures: Pulmonary embolectomy

Treatment options

• Massive PE: Thrombolysis/embolectomy

• Sub-massive PE: Strongly consider thrombolysis/embolectomy but need to balance risk of bleeding

• Non-massive PE: Anticoagulation

Thrombolysis• Indications:

– Massive PE– Sub-massive PE where risk of bleeding low

• Contraindications:– Bleeding, recent stroke, HI, current GI bleeding, bleeding

PUD, surgery within 7 day, prolonged CPR

• Drugs:– Alteplase 100mg IV: 15mg IV stat followed by 85mg over

2 hours– Followed by Heparin infusion

Anticoagulation

• IV Heparin: – 80 units/kg bolus followed by – 18 units/kg infusion

• Monitor APTT 60-90 sec

• Side effects: – HITS (Heparin induced thrombocytopenia syndrome):

paradoxical hypercoagulable state leads to clots– Bleeding

Dilemma

• Thrombolysis in normotensive patients with acute PE was associated with increased mortality (Riera-Mestre, A.et al. 2012).

• European Society of Cardiology (ESC) guidelines suggest assessing for RV dysfunction (using echocardiography, CT or B-type natriuretic peptide) or ischaemia (troponin) to aid risk stratification.(Torbicki A, 2008).

• Use of tenecteplase in submassive PE (PEITHO) observed rates of major bleeding of 6.3% and Intracranial haemorrhage of 2%.

Dilemma1:Dilemma1: Submassive PE

• Major bleeding occurred in >50% of patients receiving thrombolysis within 1 week of surgery and in 20% of patients thrombolysed 1–2 weeks postoperatively. (Condliffe, R. et al. 2014).

• Thrmbolysis is a relative contraindication in these patient groups. (American College of Chest Physicians Guidelines)

Dilemma2:Dilemma2: Recent surgery

• Thrombolytic agents for PE should be administered peripherally.

• Alteplase: 10mg IV bolus followed by 90mg over 1-2 hours.

• Alternative drugs: tenecteplase, streptokinase, urokinase

• If already on LMWH: Start IV Heparin 18 hours after last dose of LMWH

Dilemma3Dilemma3::Patient on LMWH

• Echocardiogram to confirm right heart strain

• Thrombolysis: Alteplase 50mg IV bolus (Kadner et al. 2008)

• Emergency pulmonary embolectomy

• If cause of arrest unclear: No thrombolysis

Dilemma4:Dilemma4: Arrest or periarrest

• If a patient with acute PE fails to respond to initial anticoagulation, with worsening cardiovascular instability and/or respiratory failure, then thrombolysis should be considered.

• In the MAPPET-3 study of submassive PE, delayed thrombolysis was performed in 23% of patients treated initially with heparin, with no difference in mortality compared with patients receiving up-front thrombolysis.

(Konstantinides et al 2002)

Dilemma5:Dilemma5: Recent PE failed Rx

AnticoagulationLow molecular weight Heparin (LMWH)

Enoxaprin (Clexane): S/C- 1.5mg/kg/24 hours Or 1mg/kg/12 hours- 1 mg/kg/24 hours in renal impairment

Duration: 6 to 9 months

Side effect: Low HITS

Anticoagulation• Vitamin K antagonist

• Warfarin: – 5mg PO initial dose– Check regular INR 2-3

• Side effects:– Bleeding– Unusual bruises– Headache

IVC filter

Indications:- DVT with massive pulmonary embolus- Recurrent PE not treatable with anticoagulation- Absolute contra-indications for anti-coagulation- Trauma patients

PE in Pregnancy• All three components of Virchow’s triad are affected during

pregnancy

• D-dimer has high negative predictive value. False positive result is common

• V/Q scan is preferred technique

• CTPA can be done if VQ is inconclusive

• Preferred treatment option: LMWH

• Warfarin is contraindicated

Prevention of PE• Control of obesity

• Stop smoking

• Stockings

• Heparin: 5000 units/day IV

• Enoxaprin: 40 mg/day S/C

And finally…

PE is often over-diagnosed;

PE is often under-diagnosed;

Both conditions result in increased cost, morbidity, mortality and medico-legal issues.

References• Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med. 2010 Jul 15;363(3):266-74. doi:

10.1056/NEJMra0907731. Epub 2010 Jun 30

• Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy.Lancet. 2010;375:500-512

• Hofman, M. S.; Beauregard, J. -M.; Barber, T. W. et al.(2011). 68Ga PET/CT Ventilation-Perfusion Imaging for Pulmonary Embolism: A Pilot Study with Comparison to Conventional Scintigraphy. Journal of Nuclear Medicine 52 (10): 1513–1519.

• Jaff MR, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21. Erratum in: Circulation. 2012 Mar 20;125(11):e495. Circulation. 2012 Aug 14;126(7):e104.

• Mattu, A. PE in pregnancy: A complicated diagnosis. Medscape. August 9, 2010 (Online) URL: http://www.medscape.com/viewarticle/726318

• Pulmonary embolism. Life in the fast lane. (Online). http://lifeinthefastlane.com/education/ccc/pulmonary-embolism/

• Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost 2004;2:1247–55.

• Riera-Mestre A, Jimenez D, Muriel A, et al. Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary embolism. J Thromb Haemost 2012;10:751–9.

• Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276–315.

• Condliffe R, Elliot CA, Hughes RJ, et al. Management dilemmas in acute pulmonary embolism. Thorax 2014;69:174–180.

References

• Hurwitz LM, Reiman RE, Yoshizumi TT, et al. Radiation dose from contemporary cardiothoracic multidetector CT protocols with anthropomorphic female phantom: implications for cancer induction. Radiology 2007; 245:742-750.

• Kadner A, Schmidli J, Schonhoff F, et al. Excellent outcome after surgical treatment of massive pulmonary embolism in critically ill patients. J Thorac Cardiovasc Surg 2008;136:448–51.

• Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002;347:1143–50.

References

Thank you!