3 How common is venous thromboembolism in critically ill patients?

DVT and PE are common and often underdiagnosed in critically ill patients. In prospective studies, 33% of medical patients in the intensive care unit (ICU) had DVTs on routine clinical screening, and 18% of trauma patients had proximal DVTs. In a retrospective series of respiratory ICU patients, 27% had PE on autopsy.

4 How reliable is the physical examination for diagnosing DVT?

When patients complain of unilateral calf pain and swelling, a DVT is nearly always possible, and it is difficult to rule in or rule out its presence with physical examination alone. Furthermore, asymptomatic DVT may occur 5% to 10% of the time. Specific physical examination maneuvers aimed at improving diagnostic accuracy include palpation for cords in the greater saphenous vein and its branches, detection of dilation of superficial tibial veins, checking for increased temperature in the lower extremity, squeezing specific parts of the leg to elicit tenderness, measuring the diameter of each leg, and checking for pain on passive ankle dorsiflexion (referred to as Homans sign). Unfortunately these maneuvers have limited sensitivity and specificity. Simplified clinical prediction models that combine many signs, symptoms, and historical features with serum D-dimer testing have been validated in outpatients. In these patients the combination of a low clinical probability of DVT and a low serum D-dimer level may effectively exclude DVT without ultrasonography. Importantly, these clinical prediction models have not been validated in critically ill patients.

5 What are the signs and symptoms of an acute PE?

The symptoms of an acute PE depend on the thromboembolic burden, the degree of underlying pulmonary parenchymal disease, and the ability of the right ventricle to accommodate acute pressure changes. Patients can present with syncope, shock, tachycardia, acute right ventricular failure, increased dead space, or refractory hypoxemia. However, patients may also be relatively asymptomatic. In patients with underlying cardiac or pulmonary disease, significant hemodynamic compromise may occur with less occlusion of the pulmonary vasculature. Common signs and symptoms of PE are listed in Box 26-2.

6 What are some specific findings of PE visible on chest radiography?

Chest radiography can neither be used to make nor to exclude the diagnosis of PE. However, the chest radiograph does assist in ruling out alternative diagnoses, determining the severity of the patient’s illness, and identifying abnormalities that may require further evaluation. Contrary to common belief, the chest radiograph is frequently abnormal in patients with proven PE. Focal atelectasis, seen as linear streaks that run parallel above an elevated hemidiaphragm, may be seen (Fleischner lines). Small to moderate unilateral, exudative pleural effusions occur in approximately one third of patients. Although not specific for the diagnosis, patients with a pulmonary infarct may occasionally have a wedge-shaped opacity that abuts the pleura (Hampton hump). In addition, focal oligemia may be visible (Westermark sign) and when present should prompt further evaluation for PE.

7 What are the electrocardiographic (ECG) findings associated with PE?

ECG findings are also variable and relatively nonspecific. Sinus tachycardia and nonspecific ST-segment and T-wave changes occur frequently. The classic ECG findings of S₁, Q₃, T₃, or right bundle branch block occur in fewer than 15% of patients. The development of ECG findings of acute right ventricular strain (i.e., rightward shift of the QRS axis or peaked P waves in the inferior leads) in a critically ill patient should raise concern about potential PE.

8 Are any laboratory test result abnormalities helpful in diagnosing PE?

No arterial blood gas values have adequate operating characteristics to exclude PE. Elevated serum D-dimer levels are highly sensitive but have low specificity. Although primarily validated in outpatients, when clinical suspicion for PE is low, the additional information of a serum D-dimer level below 500 ng/mL may be helpful to exclude the presence of PE without the need for further chest imaging.

9 When should a ventilation-perfusion (V/Q) scan be ordered in the diagnostic work-up of PE?

V/Q scans can be particularly useful:

Eighty-seven percent of patients with a high-probability V/Q scan have a PE, whereas the diagnosis can essentially be excluded in patients with a normal V/Q scan. Unfortunately, more than 50% of V/Q scans are nondiagnostic (i.e., intermediate or low probability), and further testing is needed. Importantly, V/Q scans are more difficult to interpret in patients with preexisting lung disease.

10 What about CTA for the diagnosis of PE?

The sensitivity and specificity of CTA exceed 90%. Higher imaging resolution and more experienced radiologists have contributed to this increase in CTA sensitivity and specificity. The sensitivity of CTA for small, subsegmental emboli is lower. However, several studies have demonstrated that subsequent DVT will develop in fewer than 1% of patients with a negative CTA for the diagnosis of PE over the next 3 months. Three additional advantages of CTA are the following:

A potential disadvantage of increased CTA sensitivity is the initiation of anticoagulation and an increased bleeding risk for patients with potentially insignificant emboli. Utility of CTA in the ICU is limited in patients with impaired renal function, the inability to lie flat, or illnesses that prohibit transportation.

11 What is the role of echocardiography in the evaluation of PE?

Echocardiography is useful for risk stratification, and for those patients whose condition is too unstable for them to be transported for further imaging procedures. As many as 40% of patients with PE exhibit abnormalities of the right ventricle (RV). Findings of RV volume and pressure overload include abnormal motion of the intraventricular septum, RV dilation, and RV hypokinesis. Patients with signs of RV dysfunction by echocardiography may be at increased risk of death because of PE. Echocardiography also may diagnose conditions that simulate PE, such as aortic aneurysm, myocardial infarction, and pericardial tamponade.

12 What is the recommended algorithm for the diagnosis of PE in the ICU for a patient who is hemodynamically stable?

In hemodynamically stable patients in whom PE is suspected the initial diagnostic test should be either a CTA or a V/Q scan. If these tests are nondiagnostic, a Doppler ultrasound scan of the legs should be performed. If the diagnosis is still not confirmed and the clinical suspicion for PE is high, pulmonary angiography should be performed.

13 What is the recommended algorithm for the diagnosis of PE in the ICU for a patient who is hemodynamically unstable?

Anticoagulation should be started (if not contraindicated) as soon as PE is suspected. Because moving an unstable patient is difficult and potentially unsafe, the initial tests should be a Doppler ultrasound scan of the legs and cardiac echocardiography to look for signs of right ventricular dilatation, dysfunction, or thrombosis. A portable chest radiograph should be obtained to evaluate for alternative diagnoses.

14 What are the goals of treatment for PE and DVT, and how are they achieved?

The major goals of PE and DVT therapy are to prevent further thrombotic and embolic complications and to promote resolution of the existing thrombosis. In the short term, unfractionated (UF) or low-molecular-weight (LMW) heparin should be administered. Oral anticoagulation therapy can be started when the patient’s condition is stable and no invasive procedures are planned. If warfarin is used, in the absence of a mechanical heart valve or severe antiphospholipid antibody syndrome, the target international normalized ratio (INR) is 2.0 to 3.0. It is important to continue the heparin until the INR has been therapeutic for at least 2 days. The benefits of anticoagulation therapy need to be weighed against its risks. The most important complications include bleeding and thrombocytopenia. An often discussed but rare complication of warfarin therapy is skin necrosis caused by preexisting protein C or protein S deficiency.

15 How long should a patient with PE or DVT be treated with anticoagulation?

Patients with their first episode of PE or DVT due to a transient (reversible) risk factor (e.g., surgery, trauma, immobilization, pregnancy, venous catheter, hip fracture) should receive anticoagulation for 3 months.

Patients with their first episode of an unprovoked PE or DVT should be treated for at least 3 months, followed by an assessment and a discussion of the risks and benefits of long-term treatment.

Lifelong anticoagulation is recommended in those patients without contraindications who have the following:

A second episode of PE or DVT

An underlying hypercoagulable state

An especially large thrombosis

A thrombosis in an unusual site (i.e., cerebral vein)

16 When should LMW heparin be used?

Patients with their first episode of an unprovoked PE or DVT should be treated for at least 3 months, followed by an assessment and a discussion of the risks and benefits of long-term treatment. Many patients and physicians opt for lifelong treatment in this situation.

17 What is the role for newer oral anticoagulant agents in the treatment of DVT or PE?

In several clinical trials, patients taking warfarin have an INR within a therapeutic range only 60% of the time. In 2006, more than a half century after warfarin’s initial approval, the Food and Drug Administration issued a black box warning for its bleeding risk. The bleeding risk, combined with warfarin’s narrow therapeutic window, slow onset and offset, food and drug interactions, and monitoring requirements have prompted continued searches for an alternative oral anticoagulant. Although not approved for the treatment of venous thromboembolism, two new classes of oral anticoagulants, direct thrombin inhibitors and factor Xa inhibitors, are currently being studied in this disease. Early trials suggest that these agents may be effective and safe in patients with near-normal renal function who are seen with acute DVT. A trial of these agents in acute symptomatic PE is ongoing.

18 Which patients with PE should be treated with thrombolytic therapy?

On the basis of limited clinical evidence, systemic thrombolytic therapy is recommended for patients with PE associated with significant hemodynamic compromise who lack contraindications related to bleeding risk (Box 26-3). Patients with significant hemodynamic compromise (systolic blood pressure < 90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE) are often referred as having a massive PE. In contrast, submassive PE is often defined as PE with systolic blood pressure > 90 mm Hg but with either right ventricular dysfunction or evidence supporting cardiac ischemia. The use of systemic thrombolytic therapy in submassive PE is debated, and no strong guidelines exist.

BP, Blood pressure.

19 When should the placement of an inferior vena cava (IVC) filter be considered?

The most common and agreed-on indications for IVC filter placement are as follows:

Patients with a large acute PE and poor cardiopulmonary reserve are often considered for IVC filter placement, although data to guide this decision are virtually absent, and decisions are often made on a case-by-case basis. Finally, in patients without an existing DVT or PE, but who have significant trauma (severe closed head injury, spinal cord injury, complex pelvic fracture, multiple long bone fractures) and high bleeding risk, some data suggest that prophylactic IVC filters may have a favorable risk/benefit ratio. Given the greatly increased risk for subsequent DVT (21%) and IVC thrombosis (2%-10%) in patients with IVC filters, resumption of anticoagulation is recommended when bleeding risk decreases, as long as the filter remains in place. The need for continued anticoagulation, combined with a finite window of time for safe filter removal, necessitates a clinician’s attention for the potential to remove the filter when appropriate. Other complications of IVC filter placement include device malposition (1.3%), pneumothorax (0.02%), hematoma (0.6%), IVC penetration (0.3%), filter migration or fracture (0.3%), and air embolism (0.2%).

20 Are there important long-term sequelae of a PE?

Symptomatic pulmonary hypertension occurs in approximately 4% of patients within 2 years after their first episode of PE.

21 What is the recommended prophylactic therapy for patients at risk for the development of DVT or PE?

Pharmacologic prophylaxis is recommended in all high-risk patients who lack contraindications and has been reported to decrease the incidence of DVT by 67%. Although mechanical methods of thromboprophylaxis (graduated compression stockings, intermittent pneumatic compression devices) are generally less efficacious, they are recommended in patients for whom anticoagulants are contraindicated. Importantly, the use of computerized electronic alert programs increased the use of prophylactic therapy and reduced the rate of DVT and PE in hospitalized patients.

The most common recommended medications for DVT or PE prophylaxis are as follows:

A recent multicenter, randomized, double-blinded, placebo-controlled trial in 3746 ICU patients compared dalteparin (5000 units once daily) with UF heparin (5000 units twice daily). No difference was seen in the primary outcome of proximal leg DVT. Secondary outcomes included any DVT, PE, death, major bleeding, and HIT. No significant between-group difference was seen in the rates of major bleeding or death; however, significantly fewer PEs occurred in the dalteparin group. These results suggest that either UF or LMW heparin can be used, with similar risks for proximal DVT, major bleeding, and HIT.

22 What is the fat embolism syndrome (FES)? Who is at risk for development of it?

Embolism of fat occurs in nearly all patients with traumatic bone fractures and during orthopedic procedures. It can also occur in patients with pancreatitis or sickle cell crises and during liposuction. Most cases are asymptomatic. FES occurs in the minority of these patients who have signs and symptoms, usually affecting the respiratory, neurologic, and hematologic systems and the skin. Symptoms typically occur 12 to 72 hours after the initial injury. The presentation may be catastrophic with RV failure and cardiovascular collapse.

23 How is FES diagnosed?

Fat embolism is a clinical diagnosis. The use of bronchoscopy or pulmonary artery catheterization to detect fat particles in alveolar macrophages or blood from the pulmonary artery lacks both sensitivity and specificity for the diagnosis of FES. The Gurd criteria are the most widely used method of diagnosis (Box 26-4).

24 What is the recommended treatment for FES?

Treatment of FES is primarily supportive. Although it has been studied extensively, no compelling evidence exists that the use of corticosteroids is indicated for FES. Some studies have suggested that early stabilization of long bone fractures can minimize bone marrow embolization into the venous system.