pulmonary embolism management options
TRANSCRIPT
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Kav Senasinghe October 2016
Pulmonary Embolism
Management Options
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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
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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)
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Definitions
Submassive PEAcute 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
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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
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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
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Treatments• Anticoagulation
• NOACs
• Warfarin
• Heparin/LMWH
• Thrombolysis
• Intra-arterial Thrombolysis
• Interventional Clot Disruption
• Surgical Embolectomy
• ECMO?
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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.
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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)
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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
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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
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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
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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
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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
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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
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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
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SirCharlesGairdnerHospitalPulmonaryEmbolismAdvancedCarePathway
Nonmassive&Lowrisksubmassive PE
• Notclinicallycompromised
Aseniorclinician should beinvolvedintheassessmentofpatientswith pulmonaryembolism, anddiscussion betweenEmergencymedicine, respiratory medicine, cardiothoracic surgeryandinterventional radiologyisencouraged.
Theseareonlyguidelines,patientsareunique,thereisabroadandcomplexspectrumofpresentation,anddefinitiveevidence islimited.
Highbleedingrisk
Lowbleedingrisk
AccessiblePE(≥lobar PAinvolved)• Surgical
embolectomy
PeripheralPE• FulldosetPA
Options include:• Standardanticoagulation• Catheterdirectedlysis• Surgicalembolectomy• ½dosesystemicthrombolysisDiscuss with appropriate specialty: • Central clot - Respiratory Medicine plus Cardiothoracic surgery if clinical compromise• Peripheral clot – Respiratory Medicineplus Interventional radiology if clinicalcompromise• Plus make ICU aware
•Decision basedon:• Clotburdenandlocation• Highversuslowbleedingrisk• Clinicalstateandcomorbidities• Resourceavailability• Patientpreference
AccessiblePE(≥lobar PAinvolved)• Surgical
embolectomy
PeripheralPE• Catheter
directedlysis
Lowmolecularweightheparin/anticoagulation
ICUorHDU/Resp HDUHDU/Resp HDU
Considerdischargeifnoconcerningfeatures(seelistunder highrisksubmassive PE)
Ensureappropriatefollowup– anticoag nurse/resp /+/- haematology
Otherwisegenerallyadmitrespiratorymedicine
MassivePulmonaryEmbolism
•Ongoinghypotensionwithsignificantclinicalcompromise
(<90mmHgor>40mmHgdropinsystolicBP)
High risksubmassive PEFeaturesfromatleast2ofthebelowcategories:1. Clinical: looksunwellorcompromised,
deteriorating, severehypoxia, syncopehx2. Imaging:largeclotburden,concerning echo3. Laboratory: Elevatedlactate, BNP, troponin
Designedincollaborationandwithagreement fromEmergency Medicine,RespiratoryMedicine,InterventionalRadiologyandCardiothoracicSurgery ForReview 2017Reference: ModifiedfromtheEMCrit.orgwebsiteMay2015.http://i2.wp.com/emcrit.org/wp-content/uploads/2014/07/Orens-PE-Algo.jpg JamesRippey
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SirCharlesGairdnerHospitalPulmonaryEmbolismAdvancedCarePathway– additionalinformation
Absolute• Knownallergy /hypersensitivity/adverse reactiontothrombolytics orallergyto
Gentamicin(atrace residuefromthemanufacturingprocess)• Activeorrecentinternalbleedingwithin14days(excludesmenstruation)• Significantclosedhead,facialorothersevere traumawithinpast3months• Suspectedaorticdissectionorpericarditis• Priorintracranialhaemorrhage withinpast6months• Ischaemic strokewithin3monthsorprevioushaemorrhagic stroke• Knownstructuralcerebralvascularlesion(AVMoraneurysm)• Knownmalignantintracranialorintraspinal neoplasm• Knownseverebleedingdisorder• Recent(withinpast2months)intracranialorintraspinal surgery)
Relative• Agemore than75years• Currentanticoagulantuse(ifonwarfarin
onlythrombolyse ifINR<2.0)• Noncompressiblevascularpuncturewithin
past10days• Recentmajor surgery(within3weeks)• TraumaticorprolongedCPR(formorethan
10minutes)• Recentinternalbleeding (within2-4weeks)• Historyseverechronicpoorlycontrolled• Hypertension
• Uncontrolledhypertensiononpresentation(Systolic>180ordiastolic>110mmHg)
• Ischaemic strokeover3monthsago• Dementiaorknownintracranialpathology• Pregnancyorrecentdelivery• ReducedGCS• Haemorrhagic ophthalmicconditions• Activepepticulcerorotherulcerative
conditions(i.e.Crohn’s disease)• Advancedkidneyorliverdisease• PriorStreptokinase/Alteplase /Reteplase
Highbleedingriskandcontraindicationstothrombolysis
ConsiderationofimagingforsourceofPEandneedforIVCfilter• InpatientswithsuspectedmassiveorhighrisksubmassivePE,CTPAwithconcurrentCTVdowntopoplitealveinsisrecommended.• WhereCTVisnotprospectivelyperformedultrasoundofthelowerlimbsisanalternativeandstronglyrecommended ifconsidering majorRx(lysis,cath,embolectomy).• IVCfilter isplacedinpatientswhohaveundergonesurgicalpulmonaryembolectomyandinwhomthere remainssignificantlowerlimbthrombus.• IVCfilter isconsideredinpatientswithsubmassivePE,inwhomthereremainssignificantlowerlimbthrombus,particularlyifitappearsunstable.• AdviceontheuseofTEDstockingsisavailableontheSCGHEDDVTpathway
AdministrationofthrombolysisforpulmonaryembolismFulldosethrombolysis
Alteplase(tPA)>65kg 10mgIVbolus,followed by90mgIVinfusionover2hours<65kg adjustdosesoitdoesnotexceed1.5mg/kg;give10mgIVbolusthentheremainder ofthedoseover2hours
HalfdosethrombolysisAlteplase(tPA)>65kg 10mgIVbolus,followed by40mgIVinfusionover2hours<65kg adjustdosesoitdoesnotexceed0.75mg/kg;give10mgIVbolusthentheremainder ofthedoseover2hours
Follow theAlteplase2hour infusionwithanticoagulation withunfractionated heparinviaIVinfusionasperanticoagulation chartprotocol.Catheterdirected thrombolysis
Alteplase(tPA)asdirected byinterventional radiology
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References1.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