Deep Vein Thrombosis and Pulmonary Embolism in the Operating Room

Colloquially known as blood clots, deep vein thrombosis (DVT) and pulmonary embolism (PE) are forms of venous thromboembolism (VTE). VTE events are common both inside and outside the operating room (OR) and are associated with increased morbidity and mortality.[1, 2]  With approximately 600,000 total cases diagnosed and as many as 100,000 deaths per year, VTE is a significant factor in all-cause disability, morbidity, and mortality in the general population.[1, 3]

In population-based studies, the incidence of DVT has been reported as ranging from 43.7 to 145 per 100,000, whereas that of PE has ranged from 20.8 to 65.8 per 100,000. Overall, VTE is more common in older males and females than in their younger counterparts; in particular, VTE rates are higher in males older than 45 years. A notable exception to this is the slightly higher incidence of VTE noted in females in their reproductive years, a large part of which is attributable to oral contraceptive use.[1]

In an effort to reduce VTE-associated morbidity and mortality, considerable emphasis is now being placed on primary prevention. Efforts by The Joint Commission have been aimed at developing standardized approaches to VTE prophylaxis, with the institution of the Surgical Care Improvement Project (SCIP) measures. Preventive measures include requiring hospitals to institute VTE prophylaxis 24 hours before and after surgery in appropriate patient populations.[4]

The pathophysiology of VTE can be multifactorial. In the simplest terms, it involves the following three factors (Virchow's triad)[5] :

• Hypercoagulability
• Stasis
• Endothelial injury

Examples of hypercoagulable states are the following:

• High levels of plasma homocysteine
• Antiphospholipid antibody syndrome
• Deficiencies of antithrombin, protein C, or protein S

Some hypercoagulable states are unique to certain patient populations. For instance, factor V Leiden mutation (resistance to activated protein C [APC]) and the prothrombin G20210A mutation (increased prothrombin activity) are more prevalent in white populations.[6]

Population-based and multicenter case-control studies have identified acquired risk factors that may contribute to the development of VTE.[6, 7, 8] Patients at increased risk for VTE include those who have had one or more of the following withn the preceding 3 months:

• Surgical procedure
• Malignancy
• Hospital admission

Also at higher risk for VTE are patients with any of the following:

• Decreased mobility for more than 48 hours in the preceding month
• Obesity
• Recent trauma
• Venous insufficiency
• Chronic heart failure
• Infection
• Pregnancy
• Oral contraceptive use

Recurrence is a risk in patients who have had VTE episodes. Those with a history of previous VTE are at greater risk for VTE than those who do not have such a history. One study assigned an odds ratio of 15.6 for DVT to aptients who had had a prior DVT.[8]

In the perioperative period, there are several characteristic risk factors that contribute to an increase in VTE. In accordance with Virchow’s triad, tissue trauma and endothelial injury from surgery cause an acute inflammatory reaction. Hypercoagulability arises from increased activity in the coagulation cascade that leads to the formation of clot. Prolonged immobilization on the OR table or in the hospital bed directly contributes to venous stasis.[9]

With regard to specific surgical specialties, it has long been known that orthopedic surgery and abdominal surgery are associated with an increased risk of development of VTE.[8, 10] Overall, surgery and the perioperative period cause as much as a fivefold increase in the incidence of PE; thus, the time surrounding an operation is a highly critical one not only for primary prevention but also for expeditious diagnosis and treatment.[9]

PE can be classified according to the time pattern of presentation—that is, as acute, subacute, or chronic. It can also be classified according to its severity, which is determined on the basis of the presence or absence of hemodynamic instability, the presence or absence of respiratory symptoms, and the anatomic location of the embolism in the pulmonary vasculature.

In 2011, the American Heart Association (AHA) developed guidelines for identifying specific clinical conditions associated with the formation of PE, which used the terms massive, submassive, and low-risk to classify PE.[11] These terms were defined as follows:

• Massive PE - Acute PE with sustained hypotension (systolic blood pressure [BP] ≤90 mm Hg for at least 15 minutes) or requiring inotropic support
• Submassive PE - Acute PE without systemic hypotension (systolic BP ≥90 mm Hg) but with either right ventricular (RV) dysfunction or signs of myocardial necrosis
• Low-risk PE - Acute PE without any of the clinical markers of adverse prognosis that define massive or submassive PE

After a PE has formed, the patient's overall clinical condition depends on a variety of factors, including the following[12] :

• Degree of pulmonary vascular resistance (PVR) caused by the PE
• Robustness of the patient’s cardiovascular status
• Other systemic conditions

All of these factors can contribute to outcome.

The pathophysiology of a massive PE in the pulmonary vasculature is a cascade of events (see the image below). The PE in the pulmonary vasculature leads to increased RV afterload. With the increased PVR, the RV begins to dilate. With RV dilation, RV wall tension increases, leading to increased oxygen demand and inflammation.

Pathophysiology and common ultrasonographic findings of pulmonary embolism.

In this setting, RV ischemia can begin if right coronary perfusion pressure drops. If RV output decreases, this decrease will lead to a drop in left ventricular (LV) preload and a subsequent fall in cardiac output.[10]  Hypotension may develop and, if sufficiently severe, may necessitate the use of vasopressors or inotropes to maintain an adequate systemic systolic BP.[10]

Depending on the size and location of the PE, it may create an alveolar ventilation/perfusion (VA/Q) mismatch through a series of events. The embolic occlusion prevents blood flow to the vascular beds of the alveoli, thereby creating areas that are ventilated but not perfused. After being diverted from these blocked areas, blood flows to perfuse regions that are already ventilated, leading to the development of a low VA/Q state in these regions. Hypoxemia may ensue secondary to the VA/Q mismatch.[12, 13]

In the OR, hypocapnia can result from a reduction in the total systemic carbon dioxide delivered to the lungs. This reduction is secondary to decreased arterial perfusion. Waveform capnography will show a gradual decrease in end-tidal carbon dioxide secondary to this hypocapnia.[13]

Addressing the problem

Generally speaking, in the perioperative period, most of the management and diagnosis of VTE takes place outside the OR. There are, however, notable exceptions to this general rule. For example, in vascular surgery, there are cases where DVT is found in the surgical field. If this finding is confirmed intraoperatively, anticoagulation should be started in patients with proximal DVT (eg, DVT in the popliteal, femoral, or iliac vein), as well as in patients who have symptoms in association with distal DVT (eg, DVT below the knee).

In making the decision to initiate anticoagulation, it is necessary first to confirm that the benefit to the patient outweighs the risk of bleeding.[11] After initial anticoagulation, careful thought must be given to whether continued anticoagulation will be needed to prevent further thromboses.

PE in the OR has its own unique challenges. Identification of PE necessitates a high level of suspicion in the differential diagnosis. Echocardiographic imaging is often helpful for diagnosis of massive PE but may be less helpful for detecting smaller embolic events. On either transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE), RV dysfunction can be evaluated by calculating the RV ejection fraction (EF). The elevated PVR and subsequent RV dilation described above (see Problem) result in a lower RVEF.

Echocardiography may reveal an interventricular septum that bulges toward the LV during systole. Other signs seen on TTE or TEE are RV enlargement and RV hypokinesis. Direct visualization of PE via TTE or TEE is also possible when the embolus is located either proximal to or at the bifurcation of the pulmonary artery.[14, 15] On echocardiographic images, the McConnell sign (normal RV apex motion with the rest of the RV showing wall-motion abnormalities) is strongly associated with PE.[14]

Ultrasonography (US) of the lung can be used in the OR as a noninvasive diagnostic tool for identifying PE. The bedside lung ultrasound in emergency (BLUE) protocol is used for the diagnosis of acute respiratory failure and has had success in identifying patients with PE. However, with an accuracy of roughly 90.5%, it should not be used as the sole diagnostic tool when PE is suspected.[16]

Initial management of PE is determined by the presence or absence of hemodynamic instability. The majority of patients who have PE are, in fact, hemodynamically stable.[10] Initial steps in management are aimed at supportive measures. Although each situation is different and treatment must be tailored to the specific hemodynamics of each patient, initial managemetn is most likely to start with peripheral intravenous (IV) access, along with, possibly, IV fluids and anticoagulation.

In the less common scenario where a patient is hemodynamically unstable from a PE event, the provider must address the state of systemic perfusion, support the patient's respiratory status, and determine the need for treatment (eg, anticoagulation, thrombolysis, or additional mechanical support).[12, 10]

If hypotension occurs, initial support should focus upon restoring perfusion with IV fluid resuscitation and, if needed, vasopressor support. Reasonable fluid resuscitation (~500 mL at a time) is suggested; more aggressive fluid administration is not advised if signs of RV failure are present.

European guidelines recommend norepinephrine in hypotensive patients.[10]  As a beta and alpha agonist, ths agent increases blood pressure through vasoconstriction and works in part as an inotrope, thus improving coronary perfusion. If a patient has a low cardiac index with a normal BP, either dobutamine or dopamine can be used as an inotrope. Some consider epinephrine the best vasopressor/inotrope overall in this setting. This agent has more inotropic effects than norepinephrine does and lacks the systemic vasodilation associated with dobutamine.

Anticoagulation is the predominant treatment for PE and DVT; studies have reported it to be used in as many as 69% of patients with a confirmed diagnosis of PE (see Evidence-Based Recommendations below).[11]  If contraindications for anticoagulation are present, placement of an inferior vena cava (IVC) filter is an option for either PE or DVT.[17]  Additional treatments for PE and DVT are catheter-directed thrombolysis and thrombectomy.  

Thrombolysis, though often an effective option for the treatment of VTE, is not without its own risks. In patients who are at risk for bleeding complications, the benefits to be expected with thrombolytic treatment must be carefully evaluated against the potential adverse effects, especially in the setting of low-risk PE. Usually, therefore, thrombolysis is reserved for PE patients who are hemodynamically unstable (see Evidence-Based Recommendations below).[11]

In the OR, diagnosis and management of DVT and PE can be challenging. With ongoing technologic advances and the availability of a variety of treatment options, it is to be hoped that significant decreases in the overall morbidity and mortality associated with VTE, especially in the perioperative period, can be achieved.

Evidence-based recommendations

The 2011 AHA Scientific Statement listed the following recommendations for anticoagulation[11] :

• Therapeutic anticoagulation with subcutaneous low-molecular-weight heparin (LMWH), IV or subcutaneous unfractionated heparin (UFH) with monitoring, unmonitored weight-based subcutaneous UFH, or subcutaneous fondaparinux should be given to patients with objectively confirmed PE and no contraindications for anticoagulation (class I recommendation; evidence level A)
• Therapeutic anticoagulation during the diagnostic workup should be given to patients with intermediate or high clinical probability of PE and no contraindications for anticoagulation (class I recommendation; evidence level C)

The 2011 AHA Scientific Statement listed the following recommendations for fibrinolysis[11] :

• Fibrinolysis is reasonable for patients with massive acute PE and an acceptable risk of bleeding complications (class IIa recommendation; evidence level B)
• Fibrinolysis may be considered for patients with submassive acute PE who are judged to have clinical evidence of an adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and a low risk of bleeding complications (class IIb recommendation; evidence level C)
• Fibrinolysis is not recommended for patients with low-risk PE (class III recommendation; evidence level B) or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (class III recommendation; evidence level B)

Clinical scenario

A 58-year-old man is admitted from an outside hospital after initial onset shortness of breath, dizziness, and Clostridium difficile diarrhea. He has a medical history of inflammatory bowel disease (IBD), is receiving long-term oral steroid therapy, and has undergone IVC filter placement for DVT. Physical examination is positive only for tachycardia with audible S1/S2, diffuse abdominal tenderness, and bilateral +1 lower-extremity edema.

Lower-extremity US is positive for acute thrombosis of the left common femoral, popliteal, and tibial veins. At this time, a high level of suspicion for PE prompts the performance of computed tomography (CT) angiography (CTA). (See the image below.) A diagnosis of bilateral PE is established. TTE is ordered to assess RV function and shows an LV ejection fraction (LVEF) of 60% (LVEF), an enlarged RV, and mild tricuspid regurgitation. 

CT scan shows filling defect in left and main pulmonary arteries.

Because of the high level of suspicion for bowel perforation and likely sepsis, the patient is taken to the OR for emergency exploratory laparotomy approximately 7 hours after admission. His initial vital signs include a BP of 103/73 mm Hg and a heart rate (HR) of 94 beats/min.

Approximately 20 minutes after induction of general anesthesia, the anesthesiologist performs intraoperative TEE, which shows a large embolus in the pulmonary trunk (pulmonary artery) and in both the right and the left pulmonary artery (see the image below), an LVEF of 55%, a markedly dilated RV with abnormal septal-wall motion, a dilated IVC, and poor visualization of the pulmonary vasculature.

Intraoperative transesophageal echocardiogram demonstrates pulmonary embolism.

A cardiothoracic surgery consult is obtained intraoperatively, and a cardiac surgical team is mobilized preemptively in case an emergency thrombectomy proves necessary. The planned surgery proceeds, and surgical exploration determines that the patient has a perforated sigmoid colon with colonic ischemia necessitating total colectomy and ileostomy.

Approximately 100 minutes after the surgical incision is made and after the total colectomy is performed, the patient’s HR falls from 110 to 54 beats/min during adjustment of the nasogastric tube. The patient then develops ventricular fibrillation (VF).

Resolution

After VF was noted, advanced cardiovascular life support (ACLS) was begun. The patient was defibrillated twice and also was given epinephrine 4 mg IV, atropine 2 mg IV, calcium 1 g IV, and one ampoule of sodium bicarbonate. Emergency TEE was performed and showed a large pulmonary embolus in the pulmonary trunk and the right and left pulmonary arteries, with severely worsened distention of the RV (see the image below). Temporary closure of the abdomen was carried out.

Emergency transesophageal echocardiogram shows dilated right ventricle and underfilled left ventricle.

Within 16 minutes of initiation of ACLS, the patient was placed on cardiopulmonary bypass (CPB) for immediate pulmonary thrombectomy; the total CPB time was 70 minutes. The patient successfully came off CPB, supported by norepinephrine, phenylephrine, and milrinone IV infusions. Postoperative TEE showed moderate RV function with mild dilation and an ejection fraction of 45-50% on inotropic and vasopressor support.

Approximately 48 hours after the initial surgical procedure, the patient was returned to the OR for abdominal washout and closure. Intraoperative TEE revealed postthrombectomy changes and showed an RV that was still moderately dilated (see the image below).

Second intraoperative transesophageal echocardiogram (midesophageal view) demonstrates postoperative changes.

The patient was extubated on postoperative day 4 with intact neurologic function. He was eventually discharged from the hospital to an outpatient rehabilitation facility.