(BQ) Part 2 book The protocol book for intensive care presents the following contents: Vascular emergencies, acute cardiac care in pediatric practice, hypertensive crisis, electrolyte imbalance, management of adult severe acute asthma, mechanical ventilation, acute kidney injury,...
chapter Vascular Emergencies 11 Shuvanan Ray, Aniket Niyogi, Soumitra Kumar Venous Thromboembolic Disorders Average annual incidence in developed countries is in 1000 Commonly occurs in legs but also occurs in other veins, such as cerebral sinus, retina, arms and mesentery Etiology i Clinical risk factors: Age (higher risk in older patients, obesity, surgery, pregnancy and drugs, e.g oral contraceptive pills, tamoxifen), long haul flights ii Thrombophilias: a Inherited (genetic) b Acquired a Inherited thrombophilias Prevalence in first VTE episode Elevated factor VIII levels 25% Factor V Leiden: Heterozygous 18.8% Homozygous Rare Hyperhomocysteinemia (>18.5 mcmol/l) 10% Prothrombin G 20210A Allele 7.1% Protein C deficiency 3.7% Protein S deficiency 2.3% Antithrombin III deficiency 1.9% b Acquired thrombophilia • Mucin secreting carcinomas • Antiphospholipid antibody syndrome • Myeloproliferative disorders • Paroxysmal nocturnal hemoglobinuria Clinical Diagnosis of Deep Venous Thrombosis of Lower Limb Clinical diagnosis of deep venous thrombosis (DVT) of lower limb is unreliable Individual signs and symptoms are of limited value Homan’s sign is of no value 256 The Protocol Book for Intensive Care Clinical Model for Predicting Pretest Probability of DVT Clinical Feature Score • Active cancer (Rx ongoing or within previous months or palliative) • Paralysis, paresis or recent plaster immobilization of legs • Recently bedridden for > days or major surgery within weeks • Localized tenderness along distribution of deep venous system • Entire leg swollen • Calf swelling > cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity) • Pitting edema (greater in asymptomatic leg) • Collateral superficial veins (non-varicose) • Alternative diagnosis as likely or wider than that of DVT –2 • Low probability or less • Moderate probability 1-2 • High probability or more Differential Diagnosis of Deep Venous Thrombosis • • • • • • • • Superficial thrombophlebitis Muscle or tendon tear, muscle cramps Popliteal inflammatory cysts (Baker’s cysts) Cellulitis (without lymphangitis) Internal derangement of the knee Postphlebitic syndrome Cutaneous vasculitis Lymphedema Investigations for DVT A Screening investigations: • D-dimer tests: Sensitive but nonspecific; has high negative predictive value i Laboratory tests ELISA Latex agglutination tests ii Bedside tests Simpli-RED (agglutination) Simplify (immunochromatography) • P lesthysmography: Recording of changes in the size of the limb due to tissue fluid or pooled blood in the veins B Definitive investigations (directly visualize the thrombus) • Venography: Gold standard • Ultrasonography i Compression ultrasound Vascular Emergencies ii Duplex ultrasonography iii Color coded Doppler ultrasonography • Computed tomography • Magnetic resonance imaging [D-dimer > 400 ng/ml : positive; ≤ 400 ng/ml; negative] Treatment of DVT The main goals in the treatment of venous thromboembolism (VTE), which comprises DVT and pulmonary embolism (PE), are to restore perfusion of the occluded vessel, to inhibit progression and embolization of the thrombus, and to prevent recurrence Initial Treatment a Antithrombotics: i Unfractionated heparin (UFH) • Remains the drug of choice in symptomatic DVT • Aim for APTT within 1.5 to 2.5 times upper limit of normal • Therapeutic APTT to be achieved within 24 hours ii Low molecular weight heparin (LMWH) 257 258 The Protocol Book for Intensive Care • S table patients may benefit from LMWH and it may even be superior to UFH • No monitoring required • Likely to replace UFH in near future iii T he mainstay of initial treatment for DVT is anticoagulation Nonetheless, anticoagulation therapy does not actually treat DVT by dissolution of thrombus but instead prevents the propagation of the existing acute DVT In selected patients with extensive acute proximal DVT (e.g those with iliofemoral DVT, upper extremity DVT, symptoms of less than 14 days’ duration, good functional status, of a life expectancy exceeding year whose bleeding risk is low, catheterdirected thrombolysis (CDT) may be used to reduce symptoms and post-thrombotic morbidity if appropriate resources are available The CDT is performed under imaging guidance; the procedure delivers the thrombolytic agent directly to the clot through a catheter inserted in the vein Intraclot injection of the thrombus with a fibrinspecific thrombolytic agent, such as alteplase is an alternative to continuous infusion and minimizes the duration of systemic exposure to thrombolytic agents Efficacy and safety of urokinase, alteplase and reteplase in CDT for the treatment of symptomatic DVT concluded that the three thrombolytic agents had similar success and complication rates Tenecteplase was reported to achieve significant or complete lysis in 83.3 percent of cases Despite the known effectiveness of thrombolysis, widespread use of thrombolytics in the treatment of DVT is limited by the long infusion times required and the substantial risk of hemorrhagic complications associated with large doses of these agents Pharmacomechanical CDT (PCDT) refers to combination of CDT and mechanical thrombectomy to fragment, macerate or aspirate the thrombus With use of such devices, thrombus removal can be performed with reduced dose of thrombolytic drug and in a single procedure session However, there are no rigorously performed prospective studies to validate this finding and there may be risks associated with greater mechanical manipulation of thrombus and vein The CDT or PCDT should be given to patients with IFDVT associated with limb-threatening circulatory compromise (i.e phlegmasia cerulea dolens) Thrombolytic Regimens lteplase: For lysis of venous thrombus, catheter-directed infusion of alteplase A 1-1.5 mg/hr for 12 to 24 hours has been used; regimens may vary, depending on local expertise Vascular Emergencies Urokinase: The usual systemic urokinase regimen for DVT consists of 4400 U/kg as an IV bolus followed by a maintenance drip of 4400 U/ kg/h The drip is continued for to days, until clinical or laboratory investigations demonstrate thrombus resolution When available, intrathrombus delivery of urokinase can avoid a systemic lytic state; via this route, the drug is given in a loading dose of 250,000 U IV followed by infusion of 500 U/kg/h If clot lysis is inadequate, the infusion rate can be gradually increased up to 2000 U/kg/h Streptokinase: The usual streptokinase regimen for DVT consists of an IV bolus of 250,000 U followed by a maintenance drip at 100,000 U/h The drip is continued for to days, until clinical or laboratory investigation shows thrombus resolution Reteplase: Reteplase is not approved by the US Food and Drug Administration (FDA) for lysis of venous thrombus in DVT but is often used off label Catheter-directed infusion of U/h is maintained for 18 to 36 hours iv IVC interruption by the insertion of an IVC filter (Greenfield filter) is only indicated in the following settings: Patients with acute venous thromboembolism who have an absolute contraindication to anticoagulant therapy (e.g recent surgery, hemorrhagic stroke, significant active or recent bleeding) Patients with massive pulmonary embolism who survived but in whom recurrent embolism invariably will be fatal Patients who have objectively documented recurrent venous thromboembolism, adequate anticoagulant therapy notwithstanding In patients with a time-limited indication for IVC filter placement (e.g a short-term contraindication to anticoagulation), it is reasonable to select a retrievable IVC filter and evaluate the patient periodically for filter retrieval After placement of an IVC filter, AHA guidelines recommend that anticoagulation be resumed once contraindications to anticoagulation or active bleeding complications have resolved v New antithrombotic agents for initial treatment of DVT a Fondaparinux - synthetic selective antifactor Xa: mg for body weight < 50 kg 7.5 mg for body weight 50-100 kg 10 mg for body weight > 100 kg b Ximelagatran - oral direct thrombin inhibitor: Ximelagatran- not marketed due to liver damage c Oral factor Xa inhibitor: Rivaroxaban has been approved for acute treatment of DVT and PE at dosage of 15 mg twice daily with food for the first 21 days; 22nd day onward, it is to be given at 20 mg once daily with food at same time every day for remaining/extended period of treatment Avoid its use in patients with creatinine 259 260 The Protocol Book for Intensive Care clearance < 30 ml/min, patients with moderate and severe hepatic impairment (Child Pugh B & C), inhibitors or inducers of P-gp and CYP3A4 In pregnant women, rivaroxaban should be used only if potential benefit justifies the potential risk to mother and fetus (It has not been studied in pregnancy) Another upcoming oral, reversible and selective factor Xa inhibitor is Apixaban It is being evaluated for treatment in these conditions Long-term Treatment of Acute-DVT The patients with acute DVT require long-term treatment (Tables 11.1 and 11.2) to prevent high frequency of symptomatic extension (15-50%) of thrombosis and/or recurrent venous thromboembolic events in patients of proximal vein thrombosis (popliteal, femoral, iliac veins) and also deep veins of the calf Treatment with oral vitamin K antagonists (VKA) is the preferred approach in long-term anticoagulation except in pregnancy, where VKAs are contraindicated Dose of VKA has to be adjusted to maintain a target INR of 2.0 to 3.0 Dabigatran is an oral direct thrombin inhibitor with a dose of 150 mg bid, is superior to warfarin with similar bleeding rate but with a 110 mg bid, is noninferior to warfarin with significantly less major bleeding No need to monitor PT regularly Ecarin clotting time is best indicator of efficacy It has an approximate lesser risk of bleeds (major and minor) than warfarin but GI upset and dyspepsia seen in many Complications of Anticoagulant Therapy • • • • Bleeding Failure of anticoagulation: Recurrent VTE may occur despite adequate anticoagulation in patients with overt or occult cancer and possibly APLA syndrome Heparin-induced thrombocytopenia (HIT): Frequency is < percent when UFH or LMWH is given no more than to days Recombinant hirudin (lepirudin) has been specifically approved for HIT accompanied by thrombosis Post-phlebitic syndrome: occurs in 20 to 50 percent of patients after a documented episode of DVT Prevention: Use of elastic compression stockings with pressure of 30 to 40 mm Hg for years after a DVT episode Treatment: Physical: Severe edema leg—intermittent pneumatic compression; Mild edema leg—elastic compression stocking Drugs: Rotusides may be tried Vascular Emergencies Table 11.1 Duration of anticoagulation after a venous thromboembolism episode Groups Duration of anticoagulation a Transient major or risk factor (i.e surgery, hospitalization, trauma, general anesthesia) a 3-6 months of conventional intensity anticoagulation (INR 2-3) b Unprovoked events (with or without common thrombophilia risk factor V Leiden, prothrombin mutation, etc.) b 2-4 years with either: INR 1.5-2 (better than placebo) or INR 2-3 (better than low-intensity anticoagulation) c Recurrent unprovoked events or severe underlying prothrombotic factor • Active cancer • Antiphospholipid antibodies • Protein C or S deficiency – Antithrombin deficiency – Homozygous factor V Leiden – G20210A Prothrombin gene mutation – Combined thrombophilic abnormalities – Pulmonary hypertension c Long-term therapy • At least one year but, likely indefinitely (risk-benefit to be reassessed, depending on patient preference and/or if risk of bleeding increases) • Most experts recommend life long therapy in active cancer or at least until cancer is cured Therapy with low molecular weight heparin might be superior to coumadin in this group Table 11.2 Prevention of venous thromboembolism in medical patients Groups Recommendations AMI Prophylactic or therapeutic anticoagulant therapy with SC UFH or LMWH Ischemic stroke (and impaired mobility) SC UFH or LMWH or a heparinoid (danaparoid) Other medical conditions (cancer, bedrest, heart failure, severe lung disease) SC UFH or LMWH If anticoagulant prophylaxis is contraindicated, elastic stockings or IPC are recommended SC = Subcutaneous, IPC = Intermittent pneumatic compression Oral rivaroxaban is approved for surgical prophylaxis of DVT which may lead to PE after knee or hip replacement surgery at 10 mg once daily (12 days for knee replacement and 35 days for hip replacement) Use of Compression Therapy Patients with ileofemoral DVT (IFDVT) should wear 30 to 40 mm Hg knee-high graduated external compression stocking (ECS) on a daily basis for at least years In patients with prior IFDVT and severe edema, intermittent sequential pneumatic compression followed by daily use of ECS is recommended 261 262 The Protocol Book for Intensive Care Pulmonary Embolism The deep veins of the lower extremities and pelvis are the most common sources of pulmonary emboli Thrombi dislodge from these veins and embolize to the pulmonary arterial tree where they trigger pathophysiologic changes in hemodynamic and gas exchange Clinical Features • • • • Dyspnea is the most frequent symptom and tachypnea is the most common sign Pleuritic chest pain, cough or hemoptysis most often indicates a small peripherally located pulmonary embolism (PE) Massive PE may present with hypotension, syncope, cardiogenic shock or cardiac arrest Classic signs, e.g tachycardia, fever, neck vein distension, tricuspid regurgitation and an accentuated pulmonic valve closure sound are often conspicuous by their absence Investigations i Cardiac biomarkers: These include troponin and BNP and are not specific for the diagnosis of acute PE D-dimer assay (ELISA) has a high sensitivity and high negative predictive value Hence , D-dimer ELISA alone can exclude PE in patients with low to moderate clinical suspicion without the need for further costly imaging tests ii Electrocardiography (ECG): Findings in PE are: • Sinus tachycardia • T-wave inversions in lead III and aVF or in leads VI-V4 • Incomplete or complete RBBB • QRS axis greater than 90º or indeterminate axis • Concurrent deep S wave in lead I with Q wave and T wave inversion in lead III (S1 Q3 T3) • S waves in lead I and aVL greater than 1.5 mm • Q waves in leads III and aVF but not in lead II • Transition zone shift to V5 • Low limb lead voltage • AF iii Chest radiography: Classically described radiographic findings in PE include: a Focal oligemia (Westermark sign) b Peripheral wedge-shaped density above diaphragm (Hampton’s hump) c An enlarged right descending pulmonary artery Vascular Emergencies iv Echocardiography: Findings in patients with pulmonary embolism are: • RV dilatation and hypokinesis In acute PE, severe RV wall hypokinesis is seen sparing the apex (McConnell’s sign) • Interventricular septal flattening and paradoxical motion • Tricuspid regurgitation • Pulmonary hypertension as identified by a tricuspid regurgitant jet velocity greater than 2.6 m/sec • Loss of respiratory phasic collapse of the inferior vena cava with inspiration • Decrease in the difference between LV area during diastole and systole (indicates low cardiac output state) • Patent foramen ovale v Chest CT: Spiral or helical chest CT scanning with contrast has become the initial imaging test of choice in the evaluation of patients with suspected PE Sensitivity of chest CT is highest in detecting PE in proximal pulmonary arteries; newer generation multidetector CT scanners may diagnose segmental or subsequental PEs but also have increased frequency of indeterminate studies vi Ventilation-Perfusion (V/Q) lung scanning: While a high probablity scan in the setting of moderate to high clinical suspicion virtually ensures the diagnosis of PE and a normal scan excludes it; the majority of patients have non-diagnostic scan Lung scanning is still used for patients with renal failure, anaphylaxis to IV contrast or pregnancy vii MR Angiography: MR angiography avoids the risk of iodinated contrast and ionizing radiation MR angiography holds promise for imaging proximal pulmonary arteries viii Contrast pulmonary angiography is indicated when chest V/Q scanning, lower extremity ultrasonography for DVT and echocardio graphy are non-diagnostic in setting of high clinical suspicion for PE Immediate bedside clinical assessment for the presence or absence of clinical hemodynamic compromise allows for stratification into ‘highrisk’ and ‘non-high-risk’ PE Principal Markers Useful for Risk Stratification Clinical markers: Shock, hypotension [SBP < 90 mm Hg or a pressure drop of > 40 mmHg for > 15 minutes if not caused by new-onset arrhythmia, hypovolemia or sepsis] Markers of RV dysfunction: RV dilatation (4-chamber RV diameter divided by LV diameter > 0.9 on echo), hypokinesia or pressure overload on echocardiography RV dilatation on spiral computed tomography (same as echo with 4-chamber slice) 263 264 The Protocol Book for Intensive Care BNP or NT-proBNP elevation (BNP > 90 pg/ml or NT pro BNP > 500 pg/ ml Elevated right heart pressures at right heart catheterization Markers of myocardial injury: Cardiac troponin T or I positive (Hearttype fatty-acids binding protein is an emerging marker) (Troponin I > 0.4 ng/ml, Troponin T > 0.1 ng/ml) Risk Stratification in Pulmonary Embolism Independent predictors of increased mortality at three months after pulmonary embolism • Age greater than 70 years • Cancer • Clinical CHF • Chronic obstructive pulmonary disease • Systolic BP less than 90 mm Hg ... recommended 26 1 26 2 The Protocol Book for Intensive Care Pulmonary Embolism The deep veins of the lower extremities and pelvis are the most common sources of pulmonary emboli Thrombi dislodge from these... may be used Other options are IV esmolol or IV verapamil or Diltiazem IV Enalaprilat 0. 625 mg or 1 .25 mg over minute every hours up to maximum of mg qid 27 1 27 2 The Protocol Book for Intensive Care... left shunt either by decreasing the venous return or by increasing the systemic vascular resistance Step • Moist O2 inhalation • Knee-chest position 27 9 28 0 The Protocol Book for Intensive Care