Pulmonary embolism management options

1. Kav Senasinghe October 2016
Pulmonary
Embolism Management Options

2. Why follow the guidelines?
• Yield of CT Pulmonary Angiography in the Emergency Department When Providers
Override Evidence-based Clinical Decision Support.
• Compared CTPA yield for PE in clinicians who overrode CDS (Clinical Decision Support)
vs. those adherent to CDS
• Wells Score </= 4 and normal D-dimer or no D-dimer (override group) vs Adherent group
• 2993 CTPAs in 2655 patients.
• 563 had Wells </= 4 and did not undergo D-Dimer testing
• 26 had Wells </= 4 and a normal D-Dimer
• i.e. most overrides due to lack of D-Dimer testing
• Positive for PE 4.2% in override group vs. 11.2%
• After adjustment, the odds of an acute PE finding were 51.3% lower in the override group

3. Definitions
Massive PE
Acute PE with sustained hypotension
(SBP<90mmHg for at least 15 mins or
requiring inotropic support, not due to a
cause other than PE), pulselessness, or
persistent profound bradycardia
(HR<40bpm with signs or symptoms of
shock)

4. Definitions
Submassive PE
Acute PE without systemic hypotension
(SBP >90mmHg) but with either RV
dysfunction or myocardial necrosis
RV Dysfunction:
• RV dysfunction or dilatation on echo
• RV dilatation on CT
• elevated BNP
• ECG changes
Myocardial Necrosis:
• elevated Troponin T
• elevated Troponin I

5. PE Relevance
• It is estimated that there are approximately 17 000 new cases of
venous thromboembolism (VTE) in Australia per year.
Pulmonary embolism (PE) accounts for about 40% of these
events
• 151,923 North-East Metropolitan Perth residents from
01/10/2003 - 31/10/2004
• 87 DVT, 53 PE
• 0.31 per 1000 residents per year
• WHO age-adjusted incidence of 0.21 per 1000

6. PE relevance
• ~20% of all PE are submassive PE
(numbers vary as we get better at
detecting PE)
• a meta-analysis by Cho et al, 2014
found increased short-term mortality
for haemodynamically stable patients
with RV dysfunction (OR 2.29; 13.7%
vs 6.5% without RV dysfunction)
• there may be selection bias, as those
patients that get an echo are more
likely to be sick
• Leads to long term morbidity -
pulmonary hypertension and reduced
functional outcome

7. Treatments
• Anticoagulation
• NOACs
• Warfarin
• Heparin/LMWH
• Thrombolysis
• Intra-arterial Thrombolysis
• Interventional Clot Disruption
• Surgical Embolectomy
• ECMO?

8. Anticoagulation
• Parenteral anticoagulants (Heparin/LMWH) overlapping the start of Warfarin Therapy
• RivaroXaban (Factor Xa inhibitor)
• PBS: Initial and continuing treatment of confirmed, acute symptomatic pulmonary embolism
• Rivaroxaban is no worse than enoxaparin plus warfarin for preventing VTE recurrence in initial treatment of
acute DVT or PE
• Contraindicated in severe renal impairment
• Currently no antidote
• Associated with more GI bleeding compared to Warfarin - 3.61/100 patient years vs 2.60, but no significant
difference in Severe or Fatal GI bleeding (ROCKET AF Trial)
• ApiXaban
• Also on the PBS for PE
• Similar in efficacy to Rivaroxaban
• Appears to be associated with a lower bleeding risk - indirect comparisons. More studies required
• DabigaTran - not on PBS for treatment of acute PE. Does have antidote.

9. Thrombolysis
• Pros:
• Less long-term pulmonary hypertension
(MOPETT trial)
• Clots resolve faster
• Patients appear to improve faster clinically
• Decreased death or haemodynamic
instability (PEITHO trial)
• Cons:
• Risk of ICH (2% in >75yo in PEITHO)
• Risk of other haemorrhage (~6% in PEITHO)
• similar improvement at 7 days overall
(~65% reduction in size of total defect
regardless of whether thrombolysed or anti
coagulated)

10. PEITHO Trial (Pulmonary EmbolIsm THrOmbolysis)
• Tenecteplase vs. Placebo for intermediate risk PE
• 1005 patients
• Death or haemodynamic compromise in 2.6% vs 5.6% in
placebo
• Major extra cranial bleeding in 6.3% vs 1.2 % in placebo
• <75yo 4.1% vs 1.5% - not significant
• >75yo 11.1% vs 0.6%
• Intracranial Bleeding in 2% vs 0.2% in placebo

11. MOPETT Trial (Moderate Pulmonary Embolism treated with
Thrombolysis)
• “In patients with submassive PE does low-dose tPA reduce the incidence of
pulmonary hypertension recurrent PE when compared to anticoagulation
alone?”
• 121 patients. single center. unblinded.
• low-dose tPA vs control
• All patients received anticoagulation with LMWH or UFH and warfarin
• Thrombolysis associated with reduction in Pulm. HTN 16% vs 57% in
control - mean follow-up 2.3 years
• No significant difference in rates of recurrent PE
• tPA did not confer a survival benefit

12. Thrombolysis: how to give it
• Tenecteplase - weight-based calculation
• Alteplase
• >65kg given 100mg total
• 10mg bolus, 90mg over next 2 hours
• <65kg adjust total dose not to exceed 1.5mg/kg
• Start heparin infusion
• LMWH efficacy is unknown

13. Thrombolysis: Contraindications
• Absolute contraindications include
• any prior intracranial haemorrhage
• known structural intracranial cerebrovascular disease (eg, arteriovenous malformation)
• known malignant intracranial neoplasm
• ischaemic stroke within 3 months
• suspected aortic dissection
• active bleeding or bleeding diathesis
• recent surgery encroaching on the spinal canal or brain, and
• recent significant closed-head or facial trauma with radiographic evidence of bony fracture or brain injury
• Relative contraindications include
• age >75 years
• current use of anticoagulation
• pregnancy
• non-compressible vascular punctures
• traumatic or prolonged cardiopulmonary resuscitation (>10 minutes)
• recent internal bleeding (within 2 to 4 weeks)
• history of chronic, severe, and poorly controlled hypertension
• severe uncontrolled hypertension on presentation (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)
• dementia
• remote (>3 months) ischaemic stroke; and
• major surgery within 3 weeks

14. Intra-Arterial Thrombolysis
• Potential for same benefits as systemic
thrombolysis with lower bleeding risk
• Wire passed through embolus followed by
an infusion catheter with multiple
openings - thrombolytic is then infused to
the clot
• Evidence is lacking - SEATTLE-II trial 2015

15. Endovascular Procedures
• An option when thrombolysis
is contraindicated or the
condition is refractory to
thrombolysis
• Patient preference, institute
and operator preference and
availability
• case-by-case basis
• https://www.youtube.com/
watch?v=cWh1ovlJg24

16. Surgical Embolectomy
• An option when thrombolysis is
contraindicated or the condition is
refractory to thrombolysis
• Pt on CPB
• Usually limited to directly
visualised clot
• Patient preference, institute and
operator preference and availability
• case-by-case basis
• https://www.youtube.com/
watch?v=SzsQWIMYbN8

17. Sir Charles Gairdner Hospital
Pulmonary Embolism Advanced Care Pathway
Non massive &
Low risk submassive PE
• Not clinically compromised
A senior clinician should be involved in the assessment of patients with pulmonary embolism, and discussion between
Emergency medicine, respiratory medicine, cardiothoracic surgery and interventional radiology is encouraged.
These are only guidelines, patients are unique, there is a broad and complex spectrum of presentation, and definitive evidence is limited.
High bleeding
risk
Low bleeding
risk
Accessible PE
(≥ lobar PA involved)
• Surgical
embolectomy
Peripheral PE
• Full dose tPA
Options include:
• Standard anticoagulation
• Catheter directed lysis
• Surgical embolectomy
• ½ dose systemic thrombolysis
Discuss with appropriate specialty:
• Central clot - Respiratory Medicine plus
Cardiothoracic surgery if clinical compromise
• Peripheral clot – Respiratory Medicine
plus Interventional radiology if clinical
compromise
• Plus make ICU aware
•Decision based on:
• Clot burden and location
• High versus low bleeding risk
• Clinical state and comorbidities
• Resource availability
• Patient preference
Accessible PE
(≥ lobar PA involved)
• Surgical
embolectomy
Peripheral PE
• Catheter
directed lysis
Low molecular
weight heparin /
anticoagulation
ICU or HDU / Resp HDUHDU / Resp HDU
Consider discharge if noconcerning features
(see list under high risk submassive PE)
Ensure appropriate follow up – anticoag nurse /
resp / +/- haematology
Otherwise generally admit respiratory medicine
Massive Pulmonary
Embolism
•Ongoing hypotension with significant
clinical compromise
(<90mmHg or > 40 mmHg drop in
systolic BP)
High risk submassive PE
Features from at least 2 of the below categories:
1. Clinical: looks unwell or compromised,
deteriorating, severe hypoxia, syncope hx
2. Imaging: large clot burden, concerning echo
3. Laboratory: Elevated lactate, BNP, troponin
Designed in collaboration and with agreement from Emergency Medicine, Respiratory Medicine, Interventional Radiology and Cardiothoracic Surgery For Review 2017
Reference: Modified from the EMCrit.org website May 2015. http://i2.wp.com/emcrit.org/wp-content/uploads/2014/07/Orens-PE-Algo.jpg James Rippey

18. Sir Charles Gairdner Hospital
Pulmonary Embolism Advanced Care Pathway – additional information
Absolute
• Known allergy / hypersensitivity / adverse reaction to thrombolytics or allergy to
Gentamicin ( a trace residue from the manufacturing process)
• Active or recent internal bleeding within 14 days (excludes menstruation)
• Significant closed head, facial or other severe trauma within past 3 months
• Suspected aortic dissection or pericarditis
• Prior intracranial haemorrhage within past 6 months
• Ischaemic stroke within 3 months or previous haemorrhagic stroke
• Known structural cerebral vascular lesion (AVM or aneurysm)
• Known malignant intracranial or intraspinal neoplasm
• Known severe bleeding disorder
• Recent (within past 2 months) intracranial or intraspinal surgery)
Relative
• Age more than 75 years
• Current anticoagulant use (if on warfarin
only thrombolyse if INR <2.0)
• Non compressible vascular puncture within
past 10 days
• Recent major surgery (within 3 weeks)
• Traumatic or prolonged CPR (for more than
10 minutes)
• Recent internal bleeding (within 2-4 weeks)
• History severe chronic poorly controlled
• Hypertension
• Uncontrolled hypertension on presentation
(Systolic >180 or diastolic >110mmHg)
• Ischaemic stroke over 3 months ago
• Dementia or known intracranial pathology
• Pregnancy or recent delivery
• Reduced GCS
• Haemorrhagic ophthalmic conditions
• Active peptic ulcer or other ulcerative
conditions (i.e. Crohn’s disease)
• Advanced kidney or liver disease
• Prior Streptokinase / Alteplase / Reteplase
High bleeding risk and contraindications to thrombolysis
Consideration of imaging for source of PE and need for IVC filter
• In patients with suspected massive or high risk submassive PE, CTPA with concurrent CTV down to popliteal veins is recommended.
• Where CTV is not prospectively performed ultrasound of the lower limbs is an alternative and strongly recommended if considering major Rx (lysis, cath, embolectomy).
• IVC filter is placed in patients who have undergone surgical pulmonary embolectomy and in whom there remains significant lower limb thrombus.
• IVC filter is considered in patients with submassive PE, in whom there remains significant lower limb thrombus, particularly if it appears unstable.
• Advice on the use of TED stockings is available on the SCGH ED DVT pathway
Administration of thrombolysis for pulmonary embolism
Full dose thrombolysis
Alteplase (tPA)
> 65kg 10mg IV bolus, followed by 90mg IV infusion over 2 hours
< 65kg adjust dose so it does not exceed 1.5mg/kg; give 10mg IV bolus then the remainder of the dose over 2 hours
Half dose thrombolysis
Alteplase (tPA)
> 65kg 10mg IV bolus, followed by 40mg IV infusion over 2 hours
< 65kg adjust dose so it does not exceed 0.75mg/kg; give 10mg IV bolus then the remainder of the dose over 2 hours
Follow the Alteplase 2 hour infusion with anticoagulation with unfractionated heparin via IV infusion as per anticoagulation chart protocol.
Catheter directed thrombolysis
Alteplase (tPA) as directed by interventional radiology

19. References
1.Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic
Pulmonary Hypertension Circulation. AHA. 2011;123:1788-1830
2.Ho WK, Hankey GJ, Eikelboom JW. The incidence of venous thromboembolism: a prospective, community-based study in Perth,
Western Australia. Med J Aust 2008;189:144–47
3.Yan Z et al. Yield of CT Pulmonary Angiography in the Emergency Department When Providers Override Evidence-based Clinical
Decision Support. Radiology 2016 Sep30:151985
4.Cho JHet al. Right ventricular dysfunction as an echocardiographic prognostic factor in haemodynamically stable patients with acute
pulmonary embolism: a meta-analysis. BMC Cardiovascular Disorders 2014, 14:64 dos: 10.1186/1471-2261-14-64
5.Pharmaceutical Benefits Scheme. http://www.pbs.gov.au/pbs/home
6.http://www.nps.org.au/medicines/heart-blood-and-blood-vessels/anti-clotting-medicines/for-individuals/anticoagulant-
medicines/for-health-professionals/evidence-summary/venous-thromboembolism
7.Sherwood et al. Gastrointestinal Bleeding in Patients with Atrial Fibrillation Treated with Rivaroxaban or Warfarin. J Am Coll Cardiol.
2015 Dec 1;66(21):2271-81. doi: 10.1016/j.jacc.2015.09.024
8.Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism. https://
www.ncbi.nlm.nih.gov/pubmed/24989022
9.Sharif M et al. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). J Cardio 2013; 111:273
10.Meyer et al, Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism N Engl J Med 2014;370:1402-11. DOI: 10.1056/
NEJMoa1302097
11.Piazza G, et al. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for
Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-92. doi:
10.1016/j.jcin.2015.04.020
12.Life in the Fast Lane www.lifeinthefastlane.com
13.Charlie’s ED www.scghed.com