I. General treatment: bed rest, oxygen, dulcolax, morphine, codeine, etc. for severe pain
Respiratory and circulatory support
Hypoxia and hypocarbia are most common in patients with pulmonary embolism. If PaO2<60--65mmHG (1mmHG=0.133KPa) and cardiac output is reduced, oxygen should be administered by mask or tracheal intubation, and mechanical ventilation is required. Care should be taken to avoid hemodynamic side effects. Positive intrathoracic pressure due to mechanical ventilation may reduce venous return and worsen right heart failure in patients with massive pulmonary embolism. Some authors recommend a low tidal volume and advocate a low fluid load.
Patients with acute massive pulmonary embolism are often hemodynamically unstable, mainly due to a reduction in the cross-sectional area of the pulmonary vascular bed and preexisting cardiopulmonary disease. In acute massive pulmonary embolism, right ventricular ischemia and left ventricular diastolic dysfunction are present, leading to left heart failure. Many patients with massive pulmonary embolism die within a few hours of the onset of symptoms. Therefore, supportive therapy is very important in hemodynamically unstable patients. For hypotension and shock, intravenous dobutamine and alamine can be administered to maintain the systolic blood pressure above 90 mmHG.
III. Thrombolytic therapy
ⅠBenefits of thrombolytic therapy
Thrombolytic therapy directly or indirectly transforms plasma fibrinogen into fibrinolytic enzyme, which rapidly degrades fibrin and dissolves the blood clot; it also has part of anticoagulation effect,
The increase of right ventricular afterload in patients with massive pulmonary embolism can lead to right ventricular failure, hypotension and shock, all of which suggest a poor prognosis. Thrombolytic therapy can improve the above-mentioned hemodynamic instability. Thrombolytic therapy, compared with heparin treatment alone, has the following advantages: it can rapidly dissolve the thrombus and restore pulmonary tissue reperfusion, resulting in rapid improvement of hemodynamic parameters; it facilitates the dissolution of venous emboli, potentially reducing the recurrence rate of pulmonary embolism; 3. it can prevent the occurrence and development of chronic pulmonary vascular obstruction, thus reducing the incidence of pulmonary hypertension. Patients with massive and non-massive pulmonary embolism benefit differently from receiving thrombolytic therapy. Most scholars believe that thrombolytic therapy is indicated for patients with massive PTE with shock and hypotension, and it is controversial whether to perform thrombolytic therapy in patients with submassive PTE with normal blood pressure and right ventricular insufficiency. However, the results of a study (719 cases) reported by Konstantinides et al [17] showed that tolerant combined with anticoagulation therapy resulted in lower rates of morbidity and mortality and embolic recurrence in acute PTE compared with anticoagulation alone, suggesting that thrombolytic therapy may be more beneficial in patients with submassive acute PTE without absolute contraindications to thrombolysis.
Indications and contraindications for II thrombolytic therapy
In the absence of an absolute contraindication, all patients with massive pulmonary embolism receive thrombolytic therapy. In patients with normal blood pressure and normal tissue perfusion and clinical and echocardiographic evidence of right ventricular insufficiency (e.g., submassive pulmonary embolism), thrombolysis may be performed if there are no contraindications. Patients with neither massive nor submassive pulmonary embolism should not receive thrombolytic therapy. PE has been reported to cause 50% of the 10% of patients admitted for non-traumatic sudden death with electrocardiograms showing electro-mechanical separation and cardiac arrest.
The thrombolysis process closely detects patients for signs of bleeding such as vascular puncture sites, skin, and other areas. Observe whether there is carnal hematuria and microscopic hematuria, and closely observe whether there are new neurological symptoms and signs. Serious hemorrhage should terminate thrombolysis and blood transfusion. Intracranial hemorrhage should be treated as an emergency, and contact with neurology or surgery quickly to decide the treatment.
IV. Anticoagulation therapy
Anticoagulation therapy can prevent the development and recurrence of pulmonary embolism, commonly used anticoagulant drugs common heparin, low molecular heparin and warfarin therapy, mainly applied after thrombolysis of pulmonary embolism; those who do not have the indication of thrombolysis of pulmonary embolism, anticoagulation alone.
Contraindications to anticoagulation therapy
Thrombocytopenia, active bleeding, coagulopathy, severe uncontrolled hypertension, and recent surgery, but these are all relative contraindications for patients with confirmed pulmonary embolism.
Normal heparin should be applied intravenously after thrombolysis of massive pulmonary embolism. The European Society of Cardiology recommends the following dose: a loading dose of 5000 – 10000u intravenously, followed by 800-1250u/h or 15-20u/kg/h continuous intravenous drip. The rate of administration is adjusted according to body weight and the target APTT is 1-5 times to 2-5 times the control value, corresponding to a factor Xa activity in the range of 0.3 – 0.6 U. APTT is measured for the first time 4–6 hours after intravenous administration of normal heparin. pulmonary embolism without hypotension, shock, or right heart insufficiency can be replaced with low molecular heparin instead of normal heparin, but not in large pulmonary embolisms because these patients were not included in trials of low molecular heparin for pulmonary embolism.
If the pulmonary embolism occurs postoperatively, heparin should not be used for 12 – 24 hours after major surgery, and treatment should be further delayed if bleeding is still present at the surgical site. Heparin is safe for use in pregnancy because it does not pass through the placenta. However, heparin resistance should be increased at this time and the dose adjusted according to APTT or Xa activity. Patients with cancer have an increased rate of recurrent venous embolism and require long-term anticoagulation therapy.
Oral anticoagulant agents are currently commonly used as warfarin sodium. The oral anticoagulant is started on the first or second day of heparin application. Its starting dose is 2 – 3 mg, and the dose is adjusted according to the INR. The loading dose does not achieve the target INR (2–3) any faster than the maintenance dose, but is detrimental and therefore must be combined with heparin for 4–5 d until the iNR reaches therapeutic levels for at least 2 days. the INR should be tested daily until it reaches therapeutic levels, twice a week for the first 2 weeks of treatment, and then once a week or less depending on how well the INR reaches stability. For long-term treatment, monitoring should be done every 4 weeks. Effective treatment should result in an INR of 2–3. The duration of anticoagulation depends on the type of clinical event and the coexisting risk factors. Therefore, for patients with a low recurrence rate in the presence of transient risk factors, 3–6 months of treatment is appropriate. For patients with no predicted risk factors after the first episode, long-term anticoagulation should be administered for 6 months. Indefinite anticoagulation (>2 years) for malignancy or recurrent venous embolism
Bleeding is the most common complication of oral anticoagulants and the risk is related to the degree of anticoagulation, with sufficient evidence that bleeding is common at INR >3. , can be discontinued if clinically indicated and counteracted by oral or injectable vitamin K (1 – 2 mg), if the patient bleeds severely, vitamin K and fresh plasma or prothrombin complex should be administered intravenously. The most important non-bleeding side effect of oral anticoagulants is skin necrosis, occurring in the first week of treatment, a complication associated with protein C and protein S and malignancy
Oral anticoagulants can pass through the placenta during pregnancy and can cause miscarriage and embryopathy during the first trimester of pregnancy. Therefore oral anticoagulants during the first trimester and 6 weeks before delivery should be changed to heparin therapy, either subcutaneous heparin or low molecular heparin as long-term treatment. Postpartum breastfeeding oral anticoagulants, because even with the application of warfarin, no drug component was found in the breast milk.
V. Interventional treatment
Interventional treatment includes: intracatheter thrombolysis, catheter thrombus mashing, local mechanical dissipation, balloon angiogenesis, vena cava filter placement, in addition to some interventional treatment methods, such as electrolyte embolization, negative pressure suction embolization, etc. However, when there is an absolute contraindication to thrombolysis, or when thrombolysis fails and the patient’s life is in danger, the right heart catheter mechanical technique can be applied to successfully break up the large thrombus or perform embolus removal.
Indications: Acute massive pulmonary embolism with progressive hypotension, severe respiratory distress, shock, syncope, cardiac arrest; contraindication to thrombolysis, contraindication to open chest/ or intervention with extremely easy to dislodge inferior vena cava and lower extremity venous thrombosis, with high safety and little technical difficulty, is an effective method with broad research prospect, but still needs further improvement.
Pulmonary embolism is a common cardiopulmonary disease with high mortality rate and easy to be misdiagnosed and missed in clinical practice. We believe that with the improvement of diagnostic technology and level, clinicians will improve the treatment method. We believe that with the improvement of diagnostic techniques and treatment methods, clinicians will further improve their understanding of pulmonary embolism, reduce the rate of underdiagnosis and misdiagnosis, and enable more patients to receive timely diagnosis and correct treatment to reduce the death and disability rates.