ARDS Mechanical Ventilation Strategies

• A pulmonary embolism (PE) is when one or more branches of the pulmonary artery (PA) is obstructed by particulate matter originating elsewhere in the body.
• Pulmonary emboli are most commonly caused by thrombi but can also be caused by tumor, amniotic fluid, air, or fat, in which case they are referred to as nonthrombotic pulmonary emboli (NTPE).
• NTPEs are very dangerous; amniotic fluid emboli (AFE) have a 17% rate of failure to rescue the mother from death, and this increases to over 30% when there are concurrent complications.
• The greatest risk factor for PE is the presence of deep vein thrombosis (DVT).
• Virchow's triad, consisting of venous stasis, vessel wall damage, and hypercoagulability is the major predisposing factor for DVT. Prolonged immobility is the most common cause of DVT.

Sources of Pulmonary Emboli

• Deep vein thrombi are formed when a clot breaks free from its site of origin, and travels from the deep veins of the leg or pelvis to the pulmonary vasculature.
• Fat emboli are caused by long bone fractures or liposuction.
• Air emboli come from central venous catheter (CVC) insertion, where negative intrathoracic pressure allows air to enter a CVC on insertion or if disconnected from a fluid source, as well as cardiopulmonary bypass.
• Amniotic fluid emboli occur when amniotic fluid moves into the vascular space during delivery through placental vessels.
• Tumor emboli occur when tumor sloughs off, and tumor particles travel to the pulmonary vasculature.

Virchow's Triad

• Hypercoagulability can be caused by cancer, oral contraceptives, dehydration/hemoconcentration, sickle cell anemia, polycythemia vera, or abrupt discontinuation of anticoagulants.
• Venous Stasis can be caused by prolonged bedrest/immobility, obesity, burns, or pregnancy.
• Intimal damage of vessels can be caused by vasculitis/thrombophlebitis, bacterial endocarditis, any postoperative state, trauma, or IV drug use.

Other Risk Factors for DVT

• Atherosclerosis
• Obesity
• Smoking
• Chronic heart or vascular disease
• Fracture (hip or leg)
• Hip or knee replacement
• Major surgery
• Major trauma
• Spinal cord injury
• History of previous venous thromboembolism
• Malignancy
• Age >50 years
• Estrogen use (i.e., oral contraceptives)
• Pregnancy
• Prior to 2020, the incidence of PE was approximately 1 to 2 per 1,000 persons in the United States, with 50,000 to 100,000 patients dying from PE.
• PE was a common complication of SARS-CoV-2, with more than 15% of patients affected.
• Over 40% of patients diagnosed with PE also have DVT.
• Venous thromboembolism (VTE) occurs 30 days post-COVID-19 infection in 50.99 per 1,000 persons, compared to 2.37 per 1,000 persons in noninfected individuals.
• PE is the third most common cause of death in hospitalized patients.
• Older adult patients are the most likely recipients of knee or hip replacement surgery and are thus at high risk for PE due to limited mobility and aging changes.

Pathophysiology

• When a blood clot or other particulate matter travels to the lungs, it lodges in the PA and blocks blood flow.
• This obstruction results in an impaired ventilation-to-perfusion ratio (V/Q ratio) described as decreased or blocked blood flow or perfusion to functioning alveoli and is referred to as a V/Q mismatch where there is decreased blood flow to functioning alveoli or areas of the lung where adequate gas exchange can take place.
• PE results in a high-ventilation/low-perfusion scenario-a high V/Q mismatch that prevents gas exchange at the alveolar level, leading to hypoxemia (low blood oxygen levels) and local vasoconstriction in the affected pulmonary vascular bed.
• PE also results in an increase in pulmonary vascular resistance (PVR) because blood flow cannot move past the venous obstruction. If the right ventricle cannot overcome increased PVR, left ventricular preload (blood flow to the left ventricle) is reduced, leading to decreased oxygenation, cardiac output, and hypotension.
• Inadequate tissue perfusion and hypoxia from decreased oxygenation and cardiac output results in inadequate oxygenation at the cellular level.
• Increased PVR leads to pulmonary hypertension (high pressures in the pulmonary vasculature), causing a backflow of blood into the right ventricle and right heart failure, exacerbating growing vascular obstruction. Acute pulmonary emboli are classified as massive (high risk), submassive (intermediate risk), or low risk.
• Massive pulmonary emboli are abrupt, and onset of symptoms follows obstruction. They can rapidly cause right ventricular heart failure and death.
• A massive PE is present if more than 50% of the blood flow through the PA is obstructed.
• A submassive PE is present when an echocardiogram shows right heart dysfunction but no hemodynamic instability, while a low-risk PE has either no indications of heart dysfunction, elevated biomarkers, or hypotension.
• PEs are further categorized by the placement of the embolus, as a saddle PE, which straddles the bifurcation of the PA, either fully or partially obstructing both branches that often results in sudden death.
• A central PE is an embolus/emboli found in the main branch of the PA or in either the right or left branch, while a peripheral PE is an embolism/emboli found in the peripheral or smaller branches of the pulmonary arteries.

Clinical Manifestations

• Sudden onset of intense dyspnea, pleuritic chest pain, and tachypnea are a first indication of PE. It should be suspected in any postoperative, and especially long-bone surgery patients with new onset of shortness of breath.
• Pain is attributed to inflammatory mediators that have been released.
• In cases of massive PE, acute right ventricular failure may present with jugular venous distention (JVD). Decreased cardiac output may cause hypotension and tachycardia and increased dead-space ventilation may cause tachycardia. Cerebral perfusion may be compromised, causing anxiety, restlessness, and/or confusion.
• If pulmonary infarction has occurred because of hypoxia of pulmonary tissue, the patient may have hemoptysis (bloody sputum).

Pulmonary Embolism Classifications

For a massive or high-risk acute pulmonary embolism:

• Prolonged hypotension requiring pharmacological support is common
• Right and left ventricular dysfunction is likely
• Shock and/or cardiac arrest is possible

For a submassive/intermediate risk acute pulmonary embolism:

• Normal blood pressure is maintained
• Right ventricular dysfunction which is evidenced by echocardiogram
• Myocardial necrosis which is indicated by elevated troponin I and elevated brain natriuretic peptide (BNP)

For a low-risk acute pulmonary embolism:

• Normal blood pressure is maintained
• No right ventricular dysfunction is present
• No elevated biomarkers (troponin or BNP)

Common Signs and Symptoms of Pulmonary Embolism

• Dyspnea
• Accessory muscle use
• Pleuritic chest pain
• Tachycardia
• Tachypnea
• Crackles upon auscultation
• Cough
• Hemoptysis
• Unilateral lower extremity edema due to the presence of a deep vein thrombus (DVT), pain in extremity, with redness and warmth

Diagnosis

• The diagnosis of PE is done through imaging and laboratory studies. If a patient presents with chest pain, an electrocardiogram (ECG) is performed to rule out myocardial infarction (MI), and can also show ischemic changes like inverted T waves and ST changes as well as new Q waves and right bundle branch blocks to represent damage to the myocardium.
• An initial chest x-ray may be done to rule out other causes of respiratory distress, such as atelectatic changes similar to pneumonia and infiltrates at the area of the embolism. A chest x-ray alone is not sufficient to diagnose a PE.
• Spiral computed tomography (CT) with intravenous contrast is the most commonly ordered test to diagnose a PE and can effectively identify central and peripheral emboli.
• A nuclear medicine ventilation-perfusion scan (V/Q scan) can be utilized if a CT scan is not available.
• A V/Q scan can identify areas of ventilated lungs that are not effectively perfused, indicating pulmonary vasculature obstruction or PE.
• The phrase "high probability" indicates a V/Q mismatch, however a CT scan is still preferred due to the VQ scan’s lower sensitivity and specificity and significantly longer time of around 60 minutes.
• Pulmonary angiography is the most definitive study for the diagnosis of PE, visualizing pulmonary vasculature and detecting any obstruction. Use is limited to stable patients due to its invasive nature and more patient radiation than CT.
• Once the patient is stabilized, a lower extremity venous ultrasound is often conducted to determine the extent of any DVT since recurrent PE is a major cause of mortality for patients who have had an acute PE.
• The discovery of a DVT helps guide inpatient and post-discharge therapy and education.

Laboratory Testing

• A plasma D-dimer level increases as clots are dissolved, is a very specific indicator of the possibility of a thrombus being present in the body, in which case further testing is required, but a negative D-dimer rules out the possibility of a clot. An initial blood test done when a PE is suspected.
• Arterial blood gas (ABG) evaluation is used to reveal hypoxemia (PaO2 less than 80 mm Hg) and respiratory alkalosis (PaCO2 less than 35) due to the patient's increased respiratory rate. More profound hypoxemia that is directly related to the amount of pulmonary vessel obstruction the patient is experiencing and may later reveal metabolic acidosis in the body due to it switching to anaerobic metabolism in the face of later stage hypoxemia of PE.
• B-type natriuretic peptide (BNP) may be elevated due to strain on the ventricles, where levels above 100 pg/mL indicate heart failure. Troponin I and troponin T may also rise, but this elevation is transient when compared with MI.

Treatment

• Treatment for symptomatic PE includes supportive care to ensure oxygenation, curative care to remove or reduce the clot, and prevent clot growth and formation. Medication therapy when treating acute PE is primarily anticoagulation (does not reduce clot size), which keeps the clot from getting larger and helps to reduce the formation of other clots.
• Asymptomatic patients with low-risk clots may undergo anticoagulation with an oral factor Xa inhibitor to inhibit the conversion of prothrombin to thrombin, without requiring hospitalization.
• Symptomatic PE patients must be hospitalized and undergo intravenous heparin therapy, no matter the type of PE, as platelets will aggregate and blood clots will adhere to the substance, making the obstruction larger.
• Heparin therapy involves an IV bolus followed by a continuous drip, with dosages based on the patient's weight that is monitored via activated partial thromboplastin time (aPTT) which is drawn before initiation of therapy and then every 4 to 6 hours to monitor therapy.
• The therapeutic goal is 1.5 to 2.5 times the normal value, or 40 to 90 seconds. An additional heparin bolus may be given along with an increase in the rate of the infusion if the initial aPTT is below the designated therapeutic level, and vice versa.
• If the aPTT is very high, the infusion should be held for a specified time before restarting at a lower rate. Facilities have protocols for aPTT for patients receiving heparin, but reaching a therapeutic aPTT level within 24 hours has better outcomes.
• Protamine sulfate is the reversal agent to heparin and should be readily available in case of bleeding.
• Low-molecular-weight heparin, fondaparinux, or unfractionated heparin may be prescribed in lieu of a weight-based heparin protocol.
• Patients need to be on anticoagulation for at least 3 months post-discharge, using subcutaneous low-molecular-weight heparin, factor Xa inhibitors, or warfarin (Coumadin), which is monitored using the international normalized ratio (INR) lab value (therapeutic anticoagulation goal is an INR of 2.0 to 3.0).
• Because it takes 3 to 5 days to reach a therapeutic warfarin level, heparin and warfarin are often prescribed concurrently.
• If a patient is hemodynamically compromised, alteplase via thrombolytic therapy is considered, where systemic thrombolysis removes clots from the PA, in contrast to anticoagulation. However, thrombolytic agents may cause bleeding, a particular concern in older adults, who risk cerebral hemorrhage.
• Heparin is typically discontinued during alteplase infusion but is restarted afterwards. Both absolute and relative contraindications in patients must be considered before the treatment starts.
• Patients who are hemodynamically unstable may be candidates for catheter-directed thrombolysis (CDT) using a low-dose hourly infusion of tissue plasminogen activator (tPA) or urokinase, where medication will administer directly to the clot site, lysing the clot and reducing bleeding risk, which is safe and beneficial for those with massive and submassive PEs.
• Isotonic IV fluid decreases blood viscosity, but caution must be used to maintain a safe fluid balance, where IV fluid may be held during right ventricular compromise. In such cases, an inotropic pharmacological agent like dobutamine, can increase cardiac contractility to overcome PVR and afterload and maximize cardiac output. Additionally, hypotension can be managed by vasopressors if needed.
• Surgical management is considered during acute massive PE resulting in hemodynamic instability where thrombolytic agents are contraindicated, and involves embolectomy. Types include catheter or surgical, as well as rheolytic or rotational catheter embolectomy.
• Rheolytic catheter embolectomy uses pressurized saline to erode the clot, but a large venous catheter/sheath is required and thus can cause bleeding. Rotational embolectomy is another type of catheter embolectomy that uses a rotating toll to break down the clot; it uses a standard cardiac catheter and poses less risk to the patient.
• Catheter embolectomy is used for clots found in main, segmented, or lobar PA branches. However, the method only has a mortality rate of around 20%.

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