Pulmonary Embolism - case series & literature review

1. PULMONARY EMBOLISM:
MASSIVE VS SUB-MASSIVE
- TREATMENT DILEMMA
DR. MISBAH
EMERGENCY REGISTRAR
QUEEN ELIZABETH HOSPITAL, WOOLWICH

2. OBJECTIVE
• Review cases of PE thrombolysed in our ED
• Massive vs Submassive PE
• Optimal treatment – an ongoing debate
• Thrombolysis in Submassive PE - Pros & Cons
• Evidence

3. CASE NUMBER 1
• 68 yrs old man suspected PE
• Hemodynamically stable
• Desaturating but able to maintain > 94% sat on high flow
Oxygen
• D-dimer & Trop positive
• RSI done & patient thrombolysed within 4 hrs
• CTPA confirmed PE

4. CASE NUMBER 2
• 36 yrs old with suspected PE
• Hemodynamically stable
• Maintaining saturation on high flow
• Tachypnea & marked dyspnea present
• Bedside Echo s/o RV strain
• Thrombolysis done by AM Consultant

5. CASE NUMBER 3
• 41 yrs old lady with suspected PE
• Hemodynamically stable
• Desaturating on high flow oxygen
• Bedside Echo
• Thrombolysis done after Cardiac Arrest
• CTPA confirmed PE

6. DEFINITIONS – MASSIVE PE
• Anatomical criteria: >50% obstruction of pulmonary vasculature
or occlusion of 2 or more lobar arteries
• Now more commonly defined by hemodynamic instability
• Acute PE as per Jaff et al (Circulation 2011) — sustained
hypotension (SBP <90 mm Hg for at least 15 min or requiring
inotropic support, not due to a cause other than PE, such as
arrhythmia, hypovolemia, sepsis, or LV dysfunction)
— pulselessness
— or persistent profound bradycardia (HR <40 bpm with signs
or symptoms of shock)

7. DEFINITIONS – SUB-MASSIVE PE
• As per Jaff et al (Circulation 2011)
• Acute PE without systemic hypotension (SBP ≥90 mm Hg)
• with either RV dysfunction
• or myocardial necrosis (positive Trop)

8. RV DYSFUNCTION:
• RV dilation or RV systolic dysfunction on Echo or CT
• Elevation of BNP (>90 pg/mL)
• Elevation of N-terminal pro-BNP (>500 pg/mL); or
• ECG changes (NEW complete or incomplete RBBB, anteroseptal
ST elevation or depression, or anteroseptal T-wave inversion)

9. PROS OF SYSTEMIC THROMBOLYSIS FOR
SUBMASSIVE PE
• Patients appear to feel better quicker – symptomatic relief
• Clots resolve faster (30% to 35% reduction in total perfusion defect at
24h, with minimal improvement if just anticoagulated) early
reduction in PAP and RV strain
• Decreased recurrence of PE
• Decreased death or hemodynamic instability (composite endpoint) at
7 days (PEITHO trial)
• Improved functional outcome (unproven, TOPCOAT trial)
• less long-term pulmonary hypertension (MOPETT trial)

10. CONS OF SYSTEMIC THROMBOLYSIS FOR
SUBMASSIVE PE
• risk of intracerebral haemorrhage (2% in >75y group in PEITHO)
• risk of other haemorrhage (major bleeding, i.e. transfusion needed, ~6% in PEITHO)
• similar improvement at 7 days overall (≈65% to 70% reduction in total defect regardless of
whether thrombolysed or anticoagulated)
• Increased cost
• No mortality benefit proven (improved composite of mortality and haemodynamic stability
in PEITHO, as yet unpublished)
• Catheter-directed thrombolysis, if available, may be safer and equally effective
• RV dysfunction can markedly improve over 24 to 48h with systemic anticoagulation (e.g.
heparin) in some patients

11. ADMINISTRATION OF SYSTEMIC
THROMBOLYTICS
• Alteplase (patients 65 kg or more) 10 mg IV bolus, followed by
90 mg IV infusion over 2 hours (the MOPPET trial used half-
dose, i.e. total of 50 mg)
• For patients weighing less than 65 kg (dose = 1.5 mg/kg)
includes 10 mg IV bolus loading dose
• Alternatives - Streptokinase or Tenecteplase
• Use the peripheral IV route – no benefit to ‘targeted’
thrombolysis via CVC or PAC

12. ANTICOAGULATION
• Unfractionated heparin (UFH) infusion
• UFH 80 units/kg loading dose IV f/b 18 units/kg/hr IVI
• Check APTT after 4-6 hours, then daily when stable
• Efficacy of LMWH - unknown

13. CONTRA-INDICATIONS (A) TO
THROMBOLYSIS
• Intracranial hemorrhage
• known structural intracranial cerebrovascular disease (eg, AVM)
• known malignant intracranial neoplasm
• ischemic stroke within 3 months
• suspected aortic dissection
• active bleeding or bleeding diathesis
• recent surgery of spinal canal or brain
• recent significant closed-head or facial trauma with
radiographic evidence of bony fracture or brain injury

14. CONTRA-INDICATIONS (R) TO
THROMBOLYSIS
• Age >75 years
• Current use of anticoagulation
• Pregnancy
• Noncompressible vascular punctures
• Traumatic or prolonged CPR(>10 minutes)
• Recent internal bleeding (within 2 to 4 weeks)
• H/o chronic, severe, & poorly controlled HTN - severe uncontrolled
HTN on presentation (SBP >180 mm Hg or DBP >110 mm Hg)
• Dementia
• Remote (>3 months) ischemic stroke;
• Major surgery within 3 weeks

15. EVIDENCE FOR SYSTEMIC THROMBOLYSIS
• Chaterjee et al, 2014
• meta-analysis of 16 RCTs (n=2115) comparing thrombolysis
with anticoagulant therapy in patients with PE
• NNT 59 for all cause mortality benefit, with mortality ARR of
1.12%
• NNH 18 for major bleeding (not significant if <65 yrs of age)

16. CATHETER-DIRECTED THROMBOLYSIS
• Catheter-directed thrombolysis has the potential to achieve the
same benefits as systemic thrombolysis with a lower risk of
haemorrhage
• Typically a wire passed through the embolus followed by a
multi-holed infusion catheter, through which a thrombolytic is
infused over 12-24 hours
• Other approaches (e.g. mechanical fragmentation and clot
aspiration; sonographic disruption) may also be used,
particularly in more unstable patients
• Not available universally & yet to be in regular practice

17. RISK-ADJUSTED MANAGEMENT STRATEGIES
IN ACUTE PULMONARY EMBOLISM (PE) – ERS

18. RECOMMENDATIONS
• Assess for significant RV dysfunction (ECHO, BNP) & myocardial
necrosis (Trop), if both are present or the patient ‘looks sick’
the patient will probably benefit from thrombolysis (age <75
yrs)
• If the patient does not improve over the first few hours (e.g. 4
hours) or the patient deteriorates then consider thrombolysis
• Consider using ‘half-dose’ thrombolysis & monitor effect (e.g.
improvement in RV function on Echo)
• Thrombolysis can be performed as late as 14 days after the
onset of the first symptoms

19. SUMMARY
• Difficult decision – involve seniors/Consultants
• Involve stakeholders (patients & relatives) in discussion
• Multi-disciplinary discussion and decision making (if time
permits)
• RISK VS BENEFIT – it’s CLINICAL GESTALT
•TIME is LIFE !!!

20. REFERENCES
• http://lifeinthefastlane.com/ccc/thrombolysis-submassive-
pulmonary-embolus
• http://erj.ersjournals.com/content/44/6/1385
• http://jamanetwork.com/journals/jama/fullarticle/1881311:
Chatterjee et al: Meta-Analysis

21. THANK YOU