A 52-year-old man with a history of hypertension presents for an elective subtotal colectomy for colon cancer. A recent workup identified a partially obstructing mass at the patient's splenic flexure. As an outpatient, he underwent a colonoscopy with a biopsy of the mass which revealed a moderately differentiated adenocarcinoma. At the time of admission, he denied any symptoms of constipation, diarrhea, abdominal pain, weight loss, or hematochezia. He has no history of heavy alcohol intake, tobacco use, or illicit drug use. He does not have a family history of malignancy. He undergoes a successful subtotal colectomy and ileocolic anastomosis, without any signs of complication. His immediate postoperative state is stable, but on postoperative day 5 he develops sudden-onset shortness of breath. He denies having any chest pain, palpitations, nausea, or diaphoresis.
On physical examination, his blood pressure is 132/74 mm Hg; his pulse is regular, with a rate of 105beats/min, and his respiratory rate is 30 breaths/min. His temperature is 98.7°F and his oxygen saturation is 90% on room air, which improves to 96% on 3 L of oxygen via nasal cannula. He is in mild respiratory distress but is able to speak in full sentences. He is not using the accessory muscles of respiration. The examination of his head and neck is normal. He has mildly decreased breath sounds at his right lung base. His heart examination demonstrates a normal S1 and S2 without murmurs or gallops. His abdomen is soft, nontender, and mildly distended with good bowel sounds; a midline incision scar is clean and nontender. He has palpable peripheral arterial pulses in his upper and lower extremities. The patient did not have edema or tenderness in the lower extremities.
The laboratory analyses, including a complete blood cell count and basic metabolic panel, are normal. An arterial blood gas on room air demonstrates a pH of 7.45, a pCO2 of 32 mm Hg, and a pO2 of 62 mm Hg, with an oxygen saturation of 93%. A chest x-ray reveals bibasilar subsegmental atelectasis. He is encouraged to perform incentive spirometry; however, his oxygen saturation deteriorates progressively and rapidly. On postoperative day 6 his hypoxemia is refractory to oxygen via a non-rebreather mask and he is intubated for hypoxemic respiratory distress and impending respiratory arrest. He is transferred to the ICU. His ECG shows an S1Q3T3 pattern and sinus tachycardia.
A presumptive diagnosis of massive pulmonary embolism was made on the basis of the patient's medical history, current physical findings, and the ECG findings. The radiographic finding of mild subsegmental atelectasis is not adequate to explain the significant and refractory hypoxemia. A diagnosis of malignant pericardial effusion was entertained, but an echocardiogram showed no effusion, a normal left ventricular ejection fraction, and a normal diastolic function. Furthermore, the right ventricle was dilated and had severe systolic dysfunction. A CT angiogram of the chest showed saddle pulmonary embolism and right ventricular strain.
Pulmonary embolism is a relatively common condition that can be potentially lethal. It affects all age groups. Prompt diagnosis and treatment can reduce the morbidity and mortality associated with pulmonary embolism; however, the diagnosis is often missed because the symptoms are frequently vague and nonspecific.
Thrombi responsible for pulmonary emboli usually arise in the deep venous system of the lower extremities; however, they may rarely originate in veins in the pelvis, kidneys, upper extremities, or the right heart chambers. After traveling to the lung, large thrombi can lodge at the bifurcation of the main pulmonary artery or the lobar branches and cause hemodynamic compromise. Typically, smaller thrombi occlude smaller vessels in the lung periphery. These are more likely to produce pleuritic chest pain by initiating an inflammatory response adjacent to the parietal pleura. Most pulmonary emboli are associated with multiple embolic events, and the lower lobes are more commonly involved.
The incidence of pulmonary embolism in the United States is estimated at 1 case per 1000 persons per year. Males and females seem to be equally affected; however, recurrent thromboembolic events are more common in men than in women. Venous thromboembolism and pulmonary embolism are diseases associated with advancing age. This may well be the result of a cumulative effect of risk factors that patients acquire with aging.
The presentation of pulmonary embolism may vary from gradually progressive dyspnea to sudden catastrophic hemodynamic collapse with sudden death or syncope. The diagnosis of pulmonary embolism should be considered in patients with respiratory symptoms unexplained by an alternate diagnosis. The symptoms of pulmonary embolism are nonspecific; therefore, a high index of suspicion is required, particularly when a patient has risk factors for the condition. The presentation of patients with pulmonary embolism can be categorized into multiple classes on the basis of the acuity and severity of pulmonary arterial occlusion:
Massive pulmonary embolism:
- Large emboli compromise sufficient pulmonary circulation to produce circulatory collapse and shock.
- Symptoms include hypotension, tachycardia, weakness, pallor, diaphoresis, oliguria, and altered mentation.
Acute pulmonary infarction:
- Approximately 10% of patients have occlusion of a pulmonary artery, causing parenchymal infarction.
- Symptoms include acute-onset pleuritic chest pain, breathlessness, and hemoptysis; the chest pain may be indistinguishable from acute ischemic coronary syndrome.
Acute embolism without infarction:
- Patients may have nonspecific symptoms of unexplained dyspnea and/or substernal discomfort or atypical/pleuritic chest pain.
The most common symptoms of pulmonary embolism in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study were dyspnea (73%), pleuritic chest pain (66%), cough (37%), and hemoptysis (13%).
An observational subgroup of the PIOPED study that included 117 patients with pulmonary embolism concluded that the ECG was abnormal in as much as 70% of patients with pulmonary embolism. Nonspecific ST segment or T-wave abnormalities occurred in 49% of the patients, while the aforementioned signs of right ventricular overload were present in only 6% of the patients. It is important to emphasize that tachyarrhythmia (be it sinus tachycardia, atrial flutter, atrial fibrillation, or another supraventricular tachycardia) is the rhythm most commonly associated with pulmonary embolism. Unexplained, new-onset tachycardia in any patient with risk factors should prompt suspicion for pulmonary embolus.
Both the postoperative state and the presence of malignancy are associated with pulmonary embolus. A study performed by Kakkar and colleagues compared the incidence of autopsy-confirmed fatal pulmonary embolism, death, and bleeding in cancer patients (n = 6124) with that in noncancer patients (n = 16, 954). Fatal pulmonary embolism was significantly more frequent in cancer patients than in noncancer patients (relative risk [RR], 3.7; 95% confidence interval [CI], 1.80-7.77; P = .0001). Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (RR, 4.54; 95% CI, 3.59-5.76; P = .0001).
Other classic risk factors for the development of venous thromboembolism include the use of oral contraceptives (especially in young females), immobilization, prolonged travel, and pregnancy. Congenital hypercoagulable states have also been described in this setting, most commonly resulting from a mutation in factor V Leiden, and also acquired deficiencies in protein C, protein S, and antithrombin III.
Different diagnostic modalities can be used to diagnose pulmonary embolism. When clinical prediction rule results indicate that the patient has a low pretest probability of pulmonary embolism, D-dimer testing is the usual next step because negative results reliably exclude pulmonary embolism. CT angiography is the initial imaging modality of choice for stable patients with suspected pulmonary embolism. In centers inexperienced in interpreting CT angiography, or in patients who cannot undergo the study, ventilation-perfusion scanning is a reasonable option. Doppler ultrasound of the lower extremities has excellent sensitivity and specificity to diagnose deep venous thrombosis (DVT) but its sensitivity to diagnose pulmonary embolism is much lower, especially in patients without symptoms of DVT.
Treatment includes immediate, full anticoagulation for all patients suspected to have DVT or pulmonary embolism. In fact, diagnostic investigations should not delay empirical anticoagulant therapy. Current guidelines recommend starting unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux (all grade 1A recommendations)in addition to an oral anticoagulant (warfarin) at the time of diagnosis, and to discontinue UFH, LMWH, or fondaparinux only after the international normalized ratio is 2.0 for at least 24 hours, but no sooner than 5 days after warfarin therapy has been started (grade 1C recommendation). The recommended duration of UFH, LMWH, and fondaparinux concomitant to warfarin therapy is based on evidence suggesting that early monotherapy with warfarin may provoke a paradoxical hypercoagulable state. The current grade 1A recommendation is that patients with acute pulmonary embolism should not routinely receive vena cava filters in addition to anticoagulants. Inferior vena cava (IVC) filter (Greenfield filter) is only indicated in patients with acute venous thromboembolism who have an absolute contraindication to anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, significant active or recent bleeding), those with massive pulmonary embolism who survived but in whom recurrent embolism invariably will be fatal, and in those who have objectively documented recurrent venous thromboembolism, adequate anticoagulant therapy notwithstanding.
A patient with a first thromboembolic event occurring in the setting of reversible risk factors such as immobilization, surgery, or trauma should receive warfarin therapy for at least 3 months. Among patients with an idiopathic (or unprovoked) thromboembolic event, the current recommendation is anticoagulation for at least 3 months, and the need for extending the duration of anticoagulation should be reevaluated at that time.
Warfarin treatment for longer than 6 months is indicated in patients with recurrent venous thromboembolism or in those in whom a continuing risk factor for venous thromboembolism exists, including malignancy, immobilization, or morbid obesity.
A meta-analysis published in 2008 addressed the question of UFH vs LMWH for thromboprophylaxis. No differences in mortality in patients receiving LMWH compared with UFH (RR, 0.89; 95% CI, 0.61-1.28) or in the incidence of clinically suspected DVT (RR, 0.73; 95% CI, 0.23- 2.28) were noted.
Thrombolysis is indicated for hemodynamically unstable patients with pulmonary embolism. Current recommendations based on the ACCP guidelines limit the use of thrombolysis for patients with hemodynamic compromise and occasionally for high-risk patients with a low risk for bleeding. In regard to the case described above, the patient was not a candidate for intravenous tissue plasminogen activator (tPA) due to recent abdominal surgery. The interventional radiology team attempted mechanical thrombectomy and local tPA infusion and achieved a partial radiologic response. An inferior vena cava filter was inserted. There are no randomized controlled trials to evaluate interventional techniques to treat massive pulmonary embolism. There are, however, case series confirming the safety and potential benefits of these methods. The most recent study included 18 patients with massive pulmonary embolism and failed thrombolysis who underwent thrombus fragmentation and aspiration. There were significant improvements in the hemodynamic parameters, including systolic systemic blood pressure, mean pulmonary arterial pressure, and oxygen saturation. This modality has yet to undergo stricter scrutiny via a randomized controlled trial.
The patient remained hypotensive despite the treatment described above and was taken emergently to the operating room to undergo pulmonary embolectomy. The surgical technique used for acute pulmonary embolectomy is a variation of the modified Trendelenburg procedure used by many surgeons. Historical literature emphasized a near prohibitive mortality rate (57%-85%) in patients undergoing pulmonary embolectomy during or after cardiopulmonary arrest for salvage. In view of its use as a last resort, a systematic review from 2007 analyzed historic case series and included data from 1300 patients. In patients operated on before 1985, the average mortality was 32%, compared with 20% of patients from 1985 to 2005. In patients who experienced cardiac arrest before pulmonary embolectomy, the operative mortality was 59% compared with 29% in patients who did not have preoperative cardiac arrest. A recent report from the Mayo Clinic showed 30-day survival rates of 83%. ACCP guidelines suggest that pulmonary embolectomy may be used in highly compromised patients who are unable to receive thrombolytics because of a bleeding risk or whose critical status does not allow time for systemic thrombolytics to be effective.
Despite undergoing pulmonary embolectomy, the patient in this case remained hypotensive and was started on extracorporeal membrane oxygenation (ECMO). ECMO is a modality that provides respiratory and cardiac support in patients who are unresponsive to conventional therapeutic interventions. In summary, blood is removed from the venous system via cannulation of a femoral vein or centrally via cannulation of the right atrium, the carbon dioxide is extracted and the blood is oxygenated, and then it is returned to the arterial circulation either via a femoral artery or centrally via the ascending aorta. Alternatively, the oxygenated blood can be returned to the venous circulation in situations in which only respiratory support is required (ie, acute respiratory distress syndrome). The most common indication for ECMO as a cardiac support device is failure to wean from cardiopulmonary bypass. The Extracorporeal Life Support Organization maintains a registry of all known cases in which ECMO was used. The most recent data show that cardiac support cases accounted for less than 1% of the total cases in which ECMO was used.
Unfortunately, the patient in this case developed multiorgan failure, including acute kidney injury requiring hemodialysis and an ischemic bowel, and died 24 hours after the institution of ECMO.
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