PULMONARYPULMONARY EMBOLISMEMBOLISM

--EDHEDH-- SEPTEMBERSEPTEMBER 20072007 DRDR SS CC COKACOKA CASECASE PRESENTATIONPRESENTATION

Mrs.Mrs. N.N. MkhizeMkhize 5151 yryr oldold presentedpresented with:with: -- ShortnessShortness ofof breathbreath forfor oneone daysdays durationduration RiskRisk factors:factors: -- RaisedRaised BMIBMI -- StrongStrong familyfamily hxhx ofof MIMI-- fatherfather andand sistersister bothboth dieddied ofof MIMI inin theirtheir 5050’’ss NoNo otherother traditionaltraditional riskrisk factorsfactors OnOn EnquiryEnquiry:: -- GradeGrade 33 dyspnoeadyspnoea (NYHAC)(NYHAC) ƒƒ associatedassociated chestchest painpain underunder leftleft breastbreast radiatingradiating toto thethe backback describeddescribed asas stabbingstabbing inin naturenature ƒƒ NoNo nausea,nausea, vomittingvomitting nornor sweating.sweating. ƒƒ painpain waswas ofof suddensudden onsetonset atat restrest notnot relatedrelated toto mealsmeals nono identifiableidentifiable relievingrelieving nornor exacerbatingexacerbating factorsfactors --NoNo historyhistory ofof orthopnea/orthopnea/ PND/pedalPND/pedal oedemaoedema --NoNo historyhistory ofof coughcough nornor haempotysishaempotysis PMHPMH:: NoneNone ofof notenote

PSH:PSH: varicosevaricose veinvein strippingstripping inin leftleft legleg inin 19931993 PreviousPrevious C/SC/S inin 19851985 SHSH:: SheShe isis ofof sobersober habitshabits FH:FH: FatherFather dieddied ofof MIMI atat ageage 56,56, sistersister alsoalso dieddied ofof MIMI atat ageage 5454 andand brotherbrother hashas unstableunstable anginaangina PHYSICALPHYSICAL EXAMINATIONEXAMINATION::

GeneralGeneral Exam:Exam:

PatientPatient waswas stablestable withwith goodgood generalgeneral conditioncondition IncreasedIncreased BMIBMI waswas notednoted ApyrexialApyrexial Hgt=6Hgt=6 mmoles/lmmoles/l BPBP 139/98139/98 P82P82 b/mb/m-- normalnormal volumevolume andand character,character, allall presentpresent andand =.=. RR=20RR=20 NoNo pedalpedal oedemaoedema NoNo signssigns ofof hyperlipidaemiahyperlipidaemia NoNo thyroidthyroid massmass BilateralBilateral varicosevaricose veinsveins werewere notednoted RespiratoryRespiratory system:system: NotNot inin respiratoryrespiratory failurefailure ChestChest movementsmovements werewere symmetricalsymmetrical ChestChest expansionexpansion waswas normalnormal PercussionPercussion notenote waswas normalnormal BreathBreath soundssounds == bilaterallybilaterally NoNo pleuralpleural rubrub CardiovascularCardiovascular system:system: NotNot inin heartheart failurefailure NoNo signssigns ofof pulmonarypulmonary hypertensionhypertension S1S1 S2S2 normalnormal NoNo murmursmurmurs oror addedadded soundssounds AbdominalAbdominal System:System: SNTSNT NoNo visceromegalyvisceromegaly NoNo pelvicpelvic massesmasses NoNo ascitesascites BSBS presentpresent CentralCentral nervousnervous system:system: FullyFully orientatedorientated NoNo meningismmeningism NoNo focalfocal signssigns Assessment:Assessment: 5151 yearyear oldold Mrs.Mrs. MkhizeMkhize withwith aa strongstrong familyfamily historyhistory ofof ischaemicischaemic heartheart disease,disease, varicosevaricose veinsveins andand increasedincreased BMIBMI presentedpresented withwith acuteacute dyspnoeadyspnoea andand chestchest painpain withwith nono signssigns ofof heartheart failurefailure nornor respiratoryrespiratory abnormality.abnormality. DifferentialDifferential Diagnosis:Diagnosis: 1.1. AcuteAcute coronarycoronary syndromesyndrome -- ?? UnstableUnstable anginaangina 2.2. PulmonaryPulmonary embolusembolus Investigations:Investigations: 1.1. ECGECG 2. Blood Investigations ƒ FBC: Hb : 15.0 Plt 208 WCC 13.27 ƒ U + E: Normal ƒ LFT: Normal ƒ INR: 1.2 LDH 876 ƒ Bloodgas: PH 7.39 CO2 4.8 kPa O2 18.9 kPa HCOз 21.8 mmol/l SO2 99%

ƒ Cardiac enzymes: Myoglobin 40.2 Trop. I 0,02 ƒ D-dimers: › 20000mg ChestChest XX--rayray CTCT Angiogram:Angiogram: PulmonaryPulmonary EmbolismEmbolism

Incidence ƒ Common, potentially lethal disease ƒ Diagnosis often missed as most patients present with non specific signs and symptoms. ƒ In US: PE is present in 60-80% of patients with DVT, even though more than half are asymptomatic. ƒ Third most common cause of death in hospitalised patients. ± 650 000 cases annually. ƒ Autopsy studies have shown ± 60% of patients who died in hospital had PE and diagnosis was missed in 70% of cases.

Mortality/Morbidity ƒ Massive PE is second only to sudden cardiac death as cause of unexpected death. ƒ ± 10% of patients with PE die within first hour and 30% die from recurrent embolism. Anticoagulant treatment decreases mortality rate to less than 5%. SexSex:: ƒƒ RiskRisk ofof PEPE isis increasedincreased inin pregnancypregnancy andand duringduring postpartumpostpartum period;period; otherwiseotherwise sexsex isis notnot aa significantsignificant riskrisk factorfactor ofof PE.PE.

AgeAge:: ƒƒ InIn hospitalisedhospitalised elderlyelderly patientspatients PEPE isis commonlycommonly missedmissed andand oftenoften isis thethe causecause ofof death.death. PathophysiologyPathophysiology 1.1. NaturalNatural historyhistory ofof pulmonarypulmonary embolismembolism

¾ Usually arise from thrombi in deep venous system of lower extremities, however rarely from pelvic, renal or upper extremity veins and right heart chambers.

¾ In the lung thrombi lodge at bifurcation of main pulmonary artery or lobar branches and cause haemodynamic compromise.

¾ Smaller thrombi travel distally, occluding a smaller vessel in the lung periphery. This produces an inflammatory response adjacent to the parietal pleura.

¾ Most emboli are multiple and lower lobes are commonly involved. 2.2. RespiratoryRespiratory consequencesconsequences

¾ IncreasedIncreased alveolaralveolar deaddead space,space, pneumoconstriction,pneumoconstriction, hypoxaemiahypoxaemia andand hyperventilation.hyperventilation.

¾ LaterLater regionalregional lossloss ofof surfactantsurfactant andand pulmonarypulmonary infarction.infarction.

¾ TheThe mechanismsmechanisms ofof hypoxaemiahypoxaemia includeinclude ventilationventilation –– perfusion,perfusion, mismatch,mismatch, intrapulmonaryintrapulmonary shunts,shunts, reducedreduced cardiaccardiac outputoutput andand intracardiacintracardiac shuntshunt viavia patentpatent foramenforamen ovale.ovale.

¾ InfarctionInfarction isis uncommonuncommon becausebecause ofof thethe bronchialbronchial collateralcollateral arterialarterial circulation.circulation. 3.3. HaemodynamicHaemodynamic consequencesconsequences

¾ Reduction of cross-sectional area of pulmonary vascular bed, resulting in increased pulmonary vascular resistance, which in turn increases the right ventricular after load. This may result in right ventricular failure.

¾ Humoral and reflex mechanisms can contribute to the pulmonary arterial constriction.

¾ Prior poor cardiopulmonary status in an important factor leading to haemodynamic collapse.

¾ Anticoagulant therapy decreases these consequences. Causes: ƒ Are multifactorial and not readily apparent in many cases. The following have been described in literature: 1. Venous stasis

¾ Leads to accumulation of platelets and thrombin veins.

¾ Increased viscosity may occur due to polycythemia and dehydration, immobility, raised venous pressure in cardiac failure or compression of vein by tumour. 2. Hypercoagulable states

¾ May be acquired or congenital. Factor V Leiden mutation causing resistance to activated protein C is the most common risk factor. Factor V mutation is present in up to 5% of the normal population is the most common cause of familial thromboembolism.

¾ Protein C, S, and antithrombin III deficiencies are other risk factors. Accounts for 10% of thrombosis in younger people. 3. Immobilisation ¾ Leads to local venous stasis by accumulation of clotting factors and fibrin, and thrombus is formed. ¾ Increase risk of PE occurs with prolonged bed rest or immobilisation of a limb. ¾ Paralysis increases the risk. 4. Surgery and Trauma

¾ Fractures of femur and tibia are associated with highest risk followed by pelvic and spinal fractures. ¾ Severe burns carry a higher risk of DVT and PE. ¾ Study by Greets in 1994 indicated major trauma was associated with 58% incidence of DVT. ¾ PE may account for 15% of all postoperative deaths. Leg amputations and hip, pelvic and spinal surgery have highest risks. 5. Pregnancy

¾ Risk is 1 in 200 deliveries to 1 in 1400 deliveries. ¾ Fatal cases may occur in 1 – 2 cases per 100 000 pregnancies. 6. Oral contraceptives and Eostrogen replacement

¾ Increased risk which is proportional to eostrogen content in HRT. ¾ Relative risk in threefold, but absolute risk is 20-30 cases per 100 000 per year. 7.7. MalignancyMalignancy

¾ IdentifiedIdentified inin 17%17% ofof patientspatients withwith thromboembolism.thromboembolism.

¾ CommonestCommonest withwith pancreaticpancreatic carcinomacarcinoma 8.8. OthersOthers

¾ StrokeStroke

¾ ObesityObesity

¾ VaricoseVaricose veinsveins

¾ PreviousPrevious historyhistory ofof thrombosisthrombosis

¾ CongestiveCongestive cardiaccardiac failurefailure

¾ InflammatoryInflammatory bowelbowel diseasedisease

¾ IndwellingIndwelling venousvenous catheterscatheters Clinical Presentation Presentation can be categorised in to 4 classes based on the acuity and severity of pulmonary arterial occlusion. 1. Massive pulmonary embolism

¾ Produce circulatory collapse and shock.

¾ Patient has hypotension, appears pale, weak, sweaty and oliguric and develops impaired mentation. 2. Acute pulmonary infarction

¾ Patients present with acute onset of pleuritic chest pain, beathlessness and haemoptysis.

¾ Chest pain may be indistinguishable from ischaemic myocardial pain. Pain does not respond to TNT. 3. Acute embolism without infarction

¾ Patients have non specific symptoms of unexplained dyspnoea and or substernal discomfort. 4. Multiple pulmonary emboli

¾ Repeated episodes over years present with signs and symptoms of pulmonary hypertension and cor pulmonale. The most common symptoms of PE in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study were: 1. Dyspnoea - 73% 2. Pleuritic chest pain - 66% 3. Cough – 37% 4. Haemoptysis – 13% The most common physical signs in the PIOPED study were: 1. Tachypnoea – 70% 2. Crackles – 51% 3. Tachycardia – 30% 4. Fourth heart sound – 24% 5. Loud P2 – 23% Atypical symptoms in a high risk patient include: 1. Seizures 2. Syncope 3. Fever (of less than 39ºC) 4. Wheezing 5. New onset atrial fibrillation 6. Chest wall tenderness Investigations 1. Lab studies a) Arterial bloodgas ¾ May reveal hypoxaemia, hypocapnia and respiratory alkalosis, however predictive value of hypoxaemia is low. ¾ Low PaO2 in conjunction with dyspnoea in high risk settings may have a strong predictive value. b) D-dimer ¾ Degradation product produced by plasmin – mediated proteases is measured via ELISA or latex agglutination tests. Latex agglutination is unreliable and has a sensitivity of 50-60%. ELISA is more sensitive but does not carry a highly negative predictive value. ¾ D-dimer test misses 10% of patients with PE while only 30% of patients with positive D-dimer have a confirmatory diagnosis of PE. ¾ Test alone is not recommended for definitive diagnosis or initiating treatment. 2.2. ImagingImaging StudiesStudies a)a) ChestChest radiographradiograph ¾ May initially be normal ¾ In later stages may show Westermark sign (dilatation of pulmonary vessels and a sharp cutoff), atelectasis, a small pleural effusion, and an elevated diaphragm. b)b) VentilationVentilation –– perfusionperfusion scanscan (V/Q)(V/Q) ¾ Important diagnostic tool. ¾ Scans should be interpreted either as having a diagnostic or non diagnostic pattern, indicating whether the patient has a high likelihood or does not have a high likelihood of having PE. DiagnosticDiagnostic pattern:pattern: I.I. NormalNormal V/QV/Q scanscan indicatesindicates anan absenceabsence ofof anyany perfusionperfusion defects.defects. 4%4% ofof thesethese patientspatients maymay stillstill havehave aa PE.PE. II.II. HighHigh probabilityprobability scanscan findingsfindings areare 22 oror moremore segmentalsegmental oror 11 largerlarger perfusionperfusion defectsdefects inin thethe presencepresence ofof normalnormal chestchest radiographyradiography findingsfindings andand ventilationventilation scanscan findings.findings. ±± 87%87% ofof thesethese patientspatients werewere foundfound toto havehave PE.PE. HighHigh probabilityprobability perfusionperfusion lunglung scanscan showingshowing segmentalsegmental perfusionperfusion defectsdefects inin rightright upperupper lobelobe andand subsub segmentalsegmental perfusionperfusion defectsdefects inin rightright lowerlower lobe.lobe. 3.3. PulmonaryPulmonary angiographyangiography

¾ Gold standard

¾ Safe procedure

¾ Negative pulmonary angiogram findings even if false negative exclude clinically relevant PE.

Angiogram showing abrupt termination of ascending branch of right upper lobe artery, confirming diagnosis of Pulmonary embolism 4.4. ECGECG

¾ MostMost commoncommon findingsfindings areare tachycardiatachycardia andand nonnon specificspecific STST--TT wavewave abnormalities.abnormalities.

¾ ClassicClassic findingfinding ofof rightright heartheart strainstrain demonstrateddemonstrated byby anan S1Q3T3S1Q3T3 patternpattern isis observedobserved inin onlyonly 20%20% ofof patientspatients withwith provenproven PE.PE. 5.5. DopplerDoppler ultraultra soundsound

¾ UsedUsed inin assessingassessing DVTDVT 6.6. OtherOther

¾ SpiralSpiral CTCT

¾ MRIMRI TreatmentTreatment ¾¾ImmediateImmediate fullfull anticoagulationanticoagulation isis mandatory.mandatory. ¾¾DiagnosticDiagnostic investigationsinvestigations shouldshould notnot delaydelay anticoagulantanticoagulant therapy.therapy. ¾¾InitialInitial anticoagulationanticoagulation isis performedperformed withwith heparinheparin toto slowslow oror preventprevent progressionprogression ofof embolus.embolus. PatientPatient shouldshould bebe startedstarted simultaneouslysimultaneously onon oraloral warfarin.warfarin. ¾¾AfterAfter aa therapeutictherapeutic dosedose ofof warfarinwarfarin isis established,established, heparinheparin isis discontinueddiscontinued andand warfarinwarfarin isis continued.continued. 1. Thrombolytic Therapy

¾ Should be considered for patients who are haemodynamically unstable, patients who have right heart strain, and high risk patients with underlying poor cardiopulmonary reserve.

¾ Dramatically improves acute cor pulmonale.

¾ Has replaced surgical embolectomy as a treatment for unstable patients.

¾ Treatments in use are metalase, urokinase and streptokinase. 2. Anticoagulants

¾ LMWH should be initiated at first suspicion of PE.

¾ Does not dissolve existing clot but prevents clot propagation and embolisation.

¾ Warfarin is used to maintain an INR of 2-3

¾ Duration of anticoagulation is for 3-6 months in the presence of a reversible risk factor.

¾ In the absence of a risk factor treatment is for minimum of 6 months and 3 months anticoagulation is insufficient.

¾ Treatment for longer than 6 months is indicated in patients with recurrent embolism or with continuing risk factor. 3.3. SurgicalSurgical TreatmentTreatment

¾ IVCIVC interruptioninterruption byby insertioninsertion ofof anan IVCIVC filterfilter (Greenfield)(Greenfield) isis indicatedindicated inin thethe following:following: a) Those patients who have an absolute contra indication to anticoagulant therapy b) Patients with massive PE who survived but in whom recurrent embolism would be fatal. c) Patients who have objectively documented recurrent thromboembolism adequate anticoagulant therapy not with standing. ComplicationsComplications 1.1. SuddenSudden cardiaccardiac deathdeath 2.2. ObstructiveObstructive shockshock 3.3. PulselessPulseless electricalelectrical activityactivity 4.4. AtrialAtrial oror ventricularventricular arrhythmiasarrhythmias 5.5. SecondarySecondary pulmonarypulmonary arterialarterial hypertensionhypertension 6.6. CorCor pulmonalepulmonale 7.7. RightRight toto leftleft intraintra cardiaccardiac shuntshunt 8.8. LungLung infarctioninfarction 9.9. PleuralPleural effusioneffusion 10.10. ParadoxicalParadoxical embolismembolism PrognosisPrognosis ¾¾DependsDepends onon twotwo factors:(1)factors:(1) underlyingunderlying diseasedisease andand (2)(2) appropriateappropriate diagnosisdiagnosis andand treatmenttreatment ¾¾AtAt 55 daysdays ofof therapy,therapy, 36%36% ofof lunglung scanscan defectsdefects resolved,resolved, atat 22 weeksweeks 52%52% areare resolved,resolved, atat 33 monthsmonths 73%73% resolved.resolved. ¾¾TheThe mortalitymortality raterate inin patientpatient withwith undiagnosedundiagnosed PEPE isis 30%.30%. ¾¾InIn thethe PIOPEDPIOPED studystudy thethe 11 yearyear mortalitymortality raterate waswas 24%.24%. DeathsDeaths occurredoccurred duedue toto cardiaccardiac diseases,diseases, recurrentrecurrent PE,PE, infectioninfection andand cancer.cancer. ¾¾RiskRisk ofof recurrencerecurrence ofof PEPE duedue toto recurrencerecurrence ofof proximalproximal venousvenous thrombosisthrombosis isis ±± 17%.17%.