PULMONARY PULMONARY EMBOLISM EMBOLISM

--EDHEDH--SEPTEMBER 2007SEPTEMBER 2007

DR S C COKADR S C COKA

CASE PRESENTATIONCASE PRESENTATION

Mrs. N. Mkhize 51 yr old presented with:Mrs. N. Mkhize 51 yr old presented with:-- Shortness of breath for one days durationShortness of breath for one days durationRisk factors:Risk factors:-- Raised BMIRaised BMI-- Strong family hx of MIStrong family hx of MI-- father and sister father and sister

both died of MI in their 50both died of MI in their 50’’ssNo other traditional risk factorsNo other traditional risk factors

On EnquiryOn Enquiry::-- Grade 3 dyspnoea (NYHAC)Grade 3 dyspnoea (NYHAC)

associated chest pain under left breastassociated chest pain under left breastradiating to the back described as stabbing in radiating to the back described as stabbing in naturenatureNo nausea, vomitting nor sweating.No nausea, vomitting nor sweating.pain was of sudden onset at rest pain was of sudden onset at rest not related to meals not related to meals no identifiable relieving nor exacerbating factorsno identifiable relieving nor exacerbating factors

--No history of orthopnea/ PND/pedal oedemaNo history of orthopnea/ PND/pedal oedema--No history of cough nor haempotysisNo history of cough nor haempotysis

PMHPMH: None of note: None of note

PSH:PSH: varicose vein stripping in left leg in varicose vein stripping in left leg in 19931993

Previous C/S in 1985Previous C/S in 1985SHSH: She is of sober habits: She is of sober habitsFH:FH: Father died of MI at age 56, sister also died Father died of MI at age 56, sister also died

of MI at age 54 and brother has unstable of MI at age 54 and brother has unstable anginaangina

PHYSICAL EXAMINATIONPHYSICAL EXAMINATION: :

General Exam:General Exam:

Patient was stable with good general condition Patient was stable with good general condition Increased BMI was notedIncreased BMI was notedApyrexialApyrexialHgt=6 mmoles/l BP 139/98 P82 b/mHgt=6 mmoles/l BP 139/98 P82 b/m-- normal volume normal volume

and character, all present and =. RR=20and character, all present and =. RR=20No pedal oedemaNo pedal oedemaNo signs of hyperlipidaemiaNo signs of hyperlipidaemiaNo thyroid massNo thyroid massBilateral varicose veins were notedBilateral varicose veins were noted

Respiratory system:Respiratory system:Not in respiratory failure Not in respiratory failure Chest movements were symmetrical Chest movements were symmetrical Chest expansion was normal Chest expansion was normal Percussion note was normal Percussion note was normal Breath sounds = bilaterally Breath sounds = bilaterally No pleural rub No pleural rub

Cardiovascular system: Cardiovascular system: Not in heart failure Not in heart failure No signs of pulmonary hypertension No signs of pulmonary hypertension S1 S2 normal S1 S2 normal No murmurs or added sounds No murmurs or added sounds

Abdominal System: Abdominal System: SNT SNT No visceromegaly No visceromegaly No pelvic masses No pelvic masses No ascites No ascites BS present BS present

Central nervous system:Central nervous system:Fully orientated Fully orientated No meningismNo meningismNo focal signs No focal signs

Assessment:Assessment:51 year old Mrs. Mkhize with a strong family 51 year old Mrs. Mkhize with a strong family

history of ischaemic heart disease, history of ischaemic heart disease, varicose veins and increased BMI varicose veins and increased BMI presented with acute dyspnoea and presented with acute dyspnoea and chest pain with no signs of heart failure chest pain with no signs of heart failure nor respiratory abnormality. nor respiratory abnormality.

Differential Diagnosis:Differential Diagnosis:1.1. Acute coronary syndrome Acute coronary syndrome -- ? Unstable ? Unstable

anginaangina2.2. Pulmonary embolus Pulmonary embolus

Investigations:Investigations:1.1. ECG ECG

2. 2. Blood Investigations Blood Investigations FBCFBC: :

Hb : 15.0Hb : 15.0 Plt 208 Plt 208 WCC 13.27WCC 13.27U + EU + E: Normal : Normal

LFT: Normal LFT: Normal INRINR: 1.2 : 1.2 LDH 876 LDH 876

Bloodgas:Bloodgas:PH 7.39PH 7.39 CO2 4.8 kPa CO2 4.8 kPa O2 18.9 kPaO2 18.9 kPa

HCOHCOзз 21.8 mmol/l21.8 mmol/l SO2 99%SO2 99%

Cardiac enzymes: Cardiac enzymes: MyoglobinMyoglobin 40.240.2

Trop. I Trop. I 0,02 0,02 DD--dimersdimers::

›› 20000mg 20000mg

Chest XChest X--rayray

CT Angiogram: CT Angiogram:

Pulmonary EmbolismPulmonary EmbolismIncidence Incidence

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

Mortality/Morbidity Mortality/Morbidity Massive PE is second only to sudden cardiac death as cause of unMassive PE is second only to sudden cardiac death as cause of unexpected expected death.death.±± 10% of patients with PE die within first hour and 30% die from10% of patients with PE die within first hour and 30% die from recurrent recurrent embolism. Anticoagulant treatment decreases mortality rate to leembolism. Anticoagulant treatment decreases mortality rate to less than ss than 5%.5%.

SexSex: : Risk of PE is increased in pregnancy and Risk of PE is increased in pregnancy and during postpartum period; otherwise sex is during postpartum period; otherwise sex is not a significant risk factor of PE.not a significant risk factor of PE.

AgeAge::In hospitalisedIn hospitalised elderly patients PE is elderly patients PE is commonly missed and often is the cause commonly missed and often is the cause of death.of death.

PathophysiologyPathophysiology1.1. Natural history of pulmonary embolism Natural history of pulmonary embolism

Usually arise from thrombi in deep venous system Usually arise from thrombi in deep venous system of lower extremities, however rarely from pelvic, of lower extremities, however rarely from pelvic, renal or upper extremity veins and right heart renal or upper extremity veins and right heart chambers.chambers.In the lung thrombi lodge at bifurcation of main In the lung thrombi lodge at bifurcation of main pulmonary artery or lobar branches and cause pulmonary artery or lobar branches and cause haemodynamichaemodynamic compromise.compromise.Smaller thrombi travel distally, occluding a smaller Smaller thrombi travel distally, occluding a smaller vessel in the lung periphery. This produces an vessel in the lung periphery. This produces an inflammatory response adjacent to the parietal inflammatory response adjacent to the parietal pleura.pleura.Most emboli are multiple and lower lobes are Most emboli are multiple and lower lobes are commonly involved. commonly involved.

2.2. Respiratory consequencesRespiratory consequencesIncreased alveolar dead space, Increased alveolar dead space, pneumoconstriction, hypoxaemia and pneumoconstriction, hypoxaemia and hyperventilation.hyperventilation.Later regional loss of surfactant and Later regional loss of surfactant and pulmonary infarction.pulmonary infarction.The mechanisms of hypoxaemia include The mechanisms of hypoxaemia include ventilation ventilation –– perfusion, mismatch, perfusion, mismatch, intrapulmonary shunts, reduced cardiac intrapulmonary shunts, reduced cardiac output and intracardiac shunt via patent output and intracardiac shunt via patent foramen ovale.foramen ovale.Infarction is uncommon because of the Infarction is uncommon because of the bronchial collateral arterial circulation. bronchial collateral arterial circulation.

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

HumoralHumoral and reflex mechanisms can contribute to and reflex mechanisms can contribute to the pulmonary arterial constriction.the pulmonary arterial constriction.

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

Anticoagulant therapy decreases these Anticoagulant therapy decreases these consequences. consequences.

Causes:Causes:Are multifactorial and not readily apparent in many cases. The Are multifactorial and not readily apparent in many cases. The following have been described in literature:following have been described in literature:

1.1. Venous stasis Venous stasis Leads to accumulation of platelets and thrombin veins.Leads to accumulation of platelets and thrombin veins.

Increased viscosity may occur due to polycythemia and dehydratioIncreased viscosity may occur due to polycythemia and dehydration, n, immobility, raised venous pressure in cardiac failure or compresimmobility, raised venous pressure in cardiac failure or compression sion of vein by tumour. of vein by tumour.

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

Protein C, S, and antithrombin III deficiencies are other risk fProtein C, S, and antithrombin III deficiencies are other risk factors. actors. Accounts for 10% of thrombosis in younger people.Accounts for 10% of thrombosis in younger people.

3.3. ImmobilisationImmobilisationLeads to local venous stasis by accumulation of clotting factorsLeads to local venous stasis by accumulation of clotting factors and and fibrin, and thrombus is formed.fibrin, and thrombus is formed.Increase risk of PE occurs with prolonged bed rest or Increase risk of PE occurs with prolonged bed rest or immobilisationimmobilisationof a limb.of a limb.Paralysis increases the risk.Paralysis increases the risk.

4.4. Surgery and TraumaSurgery and TraumaFractures of femur and tibia are associated with highest risk foFractures of femur and tibia are associated with highest risk followed llowed by pelvic and spinal fractures.by pelvic and spinal fractures.Severe burns carry a higher risk of DVT and PE.Severe burns carry a higher risk of DVT and PE.Study by Greets in 1994 indicated major trauma was associated wiStudy by Greets in 1994 indicated major trauma was associated with th 58% incidence of DVT.58% incidence of DVT.PE may account for 15% of all postoperative deaths. Leg PE may account for 15% of all postoperative deaths. Leg amputations and hip, pelvic and spinal surgery have highest riskamputations and hip, pelvic and spinal surgery have highest risks.s.

5.5. Pregnancy Pregnancy Risk is 1 in 200 deliveries to 1 in 1400 deliveries.Risk is 1 in 200 deliveries to 1 in 1400 deliveries.Fatal cases may occur in 1 Fatal cases may occur in 1 –– 2 cases per 100 000 pregnancies.2 cases per 100 000 pregnancies.

6.6. Oral contraceptives and Eostrogen replacementOral contraceptives and Eostrogen replacementIncreased risk which is proportional to eostrogen content in HRTIncreased risk which is proportional to eostrogen content in HRT..Relative risk in threefold, but absolute risk is 20Relative risk in threefold, but absolute risk is 20--30 cases per 100 000 30 cases per 100 000 per year. per year.

7.7. Malignancy Malignancy Identified in 17% of patients with Identified in 17% of patients with thromboembolism.thromboembolism.Commonest with pancreatic carcinoma Commonest with pancreatic carcinoma

8.8. Others Others Stroke Stroke Obesity Obesity Varicose veins Varicose veins Previous history of thrombosis Previous history of thrombosis Congestive cardiac failure Congestive cardiac failure Inflammatory bowel diseaseInflammatory bowel diseaseIndwelling venous catheters Indwelling venous catheters

Clinical Presentation Clinical Presentation Presentation can be categorised in to 4 classes based on Presentation can be categorised in to 4 classes based on the acuity and severity of pulmonary arterial occlusion.the acuity and severity of pulmonary arterial occlusion.

1.1. Massive pulmonary embolism Massive pulmonary embolism Produce circulatory collapse and shock.Produce circulatory collapse and shock.Patient has hypotension, appears pale, weak, sweaty and Patient has hypotension, appears pale, weak, sweaty and oliguricoliguricand develops impaired mentation. and develops impaired mentation.

2.2. Acute pulmonary infarction Acute pulmonary infarction Patients present with acute onset of Patients present with acute onset of pleuriticpleuritic chest pain, chest pain, beathlessnessbeathlessness and and haemoptysishaemoptysis..Chest pain may be indistinguishable from Chest pain may be indistinguishable from ischaemicischaemic myocardial myocardial pain. Pain does not respond to TNT.pain. Pain does not respond to TNT.

3.3. Acute embolism without infarctionAcute embolism without infarctionPatients have non specific symptoms of unexplained dyspnoea Patients have non specific symptoms of unexplained dyspnoea and or and or substernalsubsternal discomfort.discomfort.

4.4. Multiple pulmonary emboli Multiple pulmonary emboli Repeated episodes over years present with signs and symptoms Repeated episodes over years present with signs and symptoms of pulmonary hypertension and of pulmonary hypertension and corcor pulmonalepulmonale. .

The most common symptoms of PE in the Prospective Investigation The most common symptoms of PE in the Prospective Investigation of of Pulmonary Embolism Diagnosis (PIOPED) study were:Pulmonary Embolism Diagnosis (PIOPED) study were:

1.1. Dyspnoea Dyspnoea -- 73% 73% 2.2. Pleuritic chest pain Pleuritic chest pain -- 66%66%3.3. Cough Cough –– 37%37%4.4. Haemoptysis Haemoptysis –– 13%13%The most common physical signs in the PIOPED study were:The most common physical signs in the PIOPED study were:1.1. Tachypnoea Tachypnoea –– 70%70%2.2. Crackles Crackles –– 51%51%3.3. Tachycardia Tachycardia –– 30%30%4.4. Fourth heart sound Fourth heart sound –– 24% 24% 5.5. Loud P2 Loud P2 –– 23%23%Atypical symptoms in a high risk patient include:Atypical symptoms in a high risk patient include:1.1. Seizures Seizures 2.2. SyncopeSyncope3.3. Fever (of less than 39Fever (of less than 39ººC)C)4.4. WheezingWheezing5.5. New onset atrial fibrillation New onset atrial fibrillation 6.6. Chest wall tenderness Chest wall tenderness

Investigations Investigations 1.1. Lab studies Lab studies

a) Arterial a) Arterial bloodgasbloodgasMay reveal hypoxaemia, May reveal hypoxaemia, hypocapniahypocapnia and respiratory alkalosis, and respiratory alkalosis, however predictive value of hypoxaemia is low.however predictive value of hypoxaemia is low.Low PaO2 in conjunction with dyspnoea in high risk settings may Low PaO2 in conjunction with dyspnoea in high risk settings may have a strong predictive value.have a strong predictive value.

b) Db) D--dimerdimerDegradation product produced by Degradation product produced by plasminplasmin –– mediated proteases mediated proteases is measured via ELISA or latex agglutination tests. Latex is measured via ELISA or latex agglutination tests. Latex agglutination is unreliable and has a sensitivity of 50agglutination is unreliable and has a sensitivity of 50--60%. ELISA 60%. ELISA is more sensitive but does not carry a highly negative predictivis more sensitive but does not carry a highly negative predictive e value.value.DD--dimerdimer test misses 10% of patients with PE while only 30% of test misses 10% of patients with PE while only 30% of patients with positive Dpatients with positive D--dimerdimer have a confirmatory diagnosis of have a confirmatory diagnosis of PE. PE. Test alone is not recommended for definitive diagnosis or Test alone is not recommended for definitive diagnosis or initiating treatment. initiating treatment.

2.2. Imaging Studies Imaging Studies a) Chest radiographa) Chest radiograph

May initially be normal May initially be normal In later stages may show In later stages may show WestermarkWestermark sign sign (dilatation of pulmonary vessels and a sharp (dilatation of pulmonary vessels and a sharp cutoff), cutoff), atelectasisatelectasis, a small pleural effusion, and , a small pleural effusion, and an elevated diaphragm.an elevated diaphragm.

b) Ventilation b) Ventilation –– perfusion scan (V/Q)perfusion scan (V/Q)Important diagnostic tool.Important diagnostic tool.Scans should be interpreted either as having a Scans should be interpreted either as having a diagnostic or non diagnostic pattern, indicating diagnostic or non diagnostic pattern, indicating whether the patient has a high likelihood or does whether the patient has a high likelihood or does not have a high likelihood of having PE. not have a high likelihood of having PE.

Diagnostic pattern:Diagnostic pattern:I.I. Normal V/Q scan indicates an absence Normal V/Q scan indicates an absence

of any perfusion defects. 4% of these of any perfusion defects. 4% of these patients may still have a PE.patients may still have a PE.

II.II. High probability scan findings are 2 or High probability scan findings are 2 or more segmental or 1 larger perfusion more segmental or 1 larger perfusion defects in the presence of normal chest defects in the presence of normal chest radiography findings and ventilation radiography findings and ventilation scan findings. scan findings. ±± 87% of these patients 87% of these patients were found to have PE.were found to have PE.

High probability perfusion High probability perfusion lung scan showing lung scan showing segmental perfusion segmental perfusion defects in right upper lobe defects in right upper lobe and sub segmental and sub segmental perfusion defects in right perfusion defects in right lower lobe. lower lobe.

3.3. Pulmonary angiography Pulmonary angiography Gold standard Gold standard Safe procedure Safe procedure Negative pulmonary Negative pulmonary angiogram findings even angiogram findings even if false negative exclude if false negative exclude clinically relevant PE.clinically relevant PE.

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

4.4. ECGECGMost common findings are tachycardia and Most common findings are tachycardia and non specific STnon specific ST--T wave abnormalities.T wave abnormalities.Classic finding of right heart strain Classic finding of right heart strain demonstrated by an S1Q3T3 pattern is demonstrated by an S1Q3T3 pattern is observed in only 20% of patients with observed in only 20% of patients with proven PE.proven PE.

5.5. Doppler ultra sound Doppler ultra sound Used in assessing DVTUsed in assessing DVT

6.6. Other Other Spiral CT Spiral CT MRI MRI

Treatment Treatment Immediate full anticoagulation is Immediate full anticoagulation is mandatory.mandatory.Diagnostic investigations should not delay Diagnostic investigations should not delay anticoagulant therapy.anticoagulant therapy.Initial anticoagulation is performed with Initial anticoagulation is performed with heparin to slow or prevent progression of heparin to slow or prevent progression of embolus. Patient should be started embolus. Patient should be started simultaneously on oral warfarin. simultaneously on oral warfarin. After a therapeutic dose of warfarin is After a therapeutic dose of warfarin is established, heparin is discontinued and established, heparin is discontinued and warfarin is continued.warfarin is continued.

1.1. ThrombolyticThrombolytic Therapy Therapy Should be considered for patients who are Should be considered for patients who are haemodynamicallyhaemodynamicallyunstable, patients who have right heart strain, and high risk unstable, patients who have right heart strain, and high risk patients with underlying poor cardiopulmonary reserve.patients with underlying poor cardiopulmonary reserve.Dramatically improves acute Dramatically improves acute corcor pulmonalepulmonale..Has replaced surgical Has replaced surgical embolectomyembolectomy as a treatment for as a treatment for unstable patients.unstable patients.Treatments in use are Treatments in use are metalasemetalase, , urokinaseurokinase and streptokinase.and streptokinase.

2.2. Anticoagulants Anticoagulants LMWH should be initiated at first suspicion of PE.LMWH should be initiated at first suspicion of PE.Does not dissolve existing clot but prevents clot propagation Does not dissolve existing clot but prevents clot propagation and and embolisationembolisation. . Warfarin is used to maintain an INR of 2Warfarin is used to maintain an INR of 2--3 3 Duration of anticoagulation is for 3Duration of anticoagulation is for 3--6 months in the presence 6 months in the presence of a reversible risk factor.of a reversible risk factor.In the absence of a risk factor treatment is for minimum of 6 In the absence of a risk factor treatment is for minimum of 6 months and 3 months anticoagulation is insufficient.months and 3 months anticoagulation is insufficient.Treatment for longer than 6 months is indicated in patients Treatment for longer than 6 months is indicated in patients with recurrent embolism or with continuing risk factor.with recurrent embolism or with continuing risk factor.

3.3. Surgical Treatment Surgical Treatment IVC interruption by insertion of an IVC filter IVC interruption by insertion of an IVC filter (Greenfield) is indicated in the following:(Greenfield) is indicated in the following:a)a) Those patients who have an absolute contra Those patients who have an absolute contra

indication to anticoagulant therapy indication to anticoagulant therapy

b)b) Patients with massive PE who survived but in Patients with massive PE who survived but in whom recurrent embolism would be fatal.whom recurrent embolism would be fatal.

c)c) Patients who have objectively documented Patients who have objectively documented recurrent thromboembolism adequate recurrent thromboembolism adequate anticoagulant therapy not with standing. anticoagulant therapy not with standing.

Complications Complications 1.1. Sudden cardiac deathSudden cardiac death2.2. Obstructive shockObstructive shock3.3. PulselessPulseless electrical activity electrical activity 4.4. Atrial or ventricular arrhythmias Atrial or ventricular arrhythmias 5.5. Secondary pulmonary arterial hypertension Secondary pulmonary arterial hypertension 6.6. CorCor pulmonalepulmonale7.7. Right to left intra cardiac shunt Right to left intra cardiac shunt 8.8. Lung infarction Lung infarction 9.9. Pleural effusion Pleural effusion 10.10. Paradoxical embolism Paradoxical embolism

Prognosis Prognosis Depends on two factors:(1) underlying disease Depends on two factors:(1) underlying disease and (2) appropriate diagnosis and treatment and (2) appropriate diagnosis and treatment At 5 days of therapy, 36% of lung scan defects At 5 days of therapy, 36% of lung scan defects resolved, at 2 weeks 52% are resolved, at 3 resolved, at 2 weeks 52% are resolved, at 3 months 73% resolved.months 73% resolved.The mortality rate in patient with undiagnosed The mortality rate in patient with undiagnosed PE is 30%.PE is 30%.In the PIOPED study the 1 year mortality rate In the PIOPED study the 1 year mortality rate was 24%. Deaths occurred due to cardiac was 24%. Deaths occurred due to cardiac diseases, recurrent PE, infection and cancer.diseases, recurrent PE, infection and cancer.Risk of recurrence of PE due to recurrence of Risk of recurrence of PE due to recurrence of proximal venous thrombosis is proximal venous thrombosis is ±± 17%. 17%.