**4. Contemporary multimodality management**

While chronic conditions such as heart failure and malignancy are responsible for most of the late deaths in acute PE, early 30-day mortality results primarily from right ventricular failure [31]. Contemporary diagnostic modalities such as computed tomography and echo‐ cardiography allow for improved risk stratification and patient selection for pulmonary em‐ bolectomy, while evolution of surgical techniques has prompted a renewed enthusiasm for surgical pulmonary embolectomy as part of a multimodality approach to massive acute PE (Figure 5). The indications for open surgical embolectomy have traditionally been for clearly documented acute massive pulmonary embolism with persistent hypotension refractory to maximal pharmacological support.

**Figure 5.** Contemporary multimodality approach to treatment of acute massive PE

Multimodality treatment begins with immediate systemic heparinization at diagnosis, car‐ diogenic support with inotropic agents and vasopressors as indicated, and correction of hy‐ poxemia with supplemental oxygen or ventilatory support with pulmonary arterial vasodilation using inhaled nitric oxide. The underlying critical pathology is acutely elevated pulmonary vascular resistance (PVR) leading to pressure overload of the right ventricle and acute RV distention. Through ventricular interdependence, LV filling is reduced, compro‐ mising cardiac output and oxygen delivery. (Figure 6). The initial goals of medical manage‐ ment are optimization of RV preload and systolic function, reduction of pulmonary vascular resistance, and maintenance of right coronary perfusion pressure by adequate aortic root pressure [35]. Acute massive pulmonary embolism is initially a pressure overload problem of the RV. Higher filling pressures may be required; however an altered Frank-Starling curve in the setting of RV dysfunction may lead to volume overload as well. For patients with low cardiac output and normal blood pressure, modest fluid challenges may be benefi‐ cial, and the use of dobutamine and dopamine is a class IIa recommendation. Class I recom‐ mendations include correction of systemic hypotension and use of vasopressors, although the use of norepinephrine lacks clinical data, while the beneficial use of epinephrine in PE with shock has been reported [36].

**Figure 6.** Hemodynamic effects of acute massive PE

therapy [32]. Echocardiography may demonstrate the McConnell sign of acute pulmonary embolism, a characteristic pattern of akinesis of the mid free wall and normal motion of the apex [33]. Other signs include right ventricular hypokinesis, right ventricle dilation, and signs of pulmonary hypertension. In normotensive patients, RV dilation is present in 30-40% and predicts in-hospital mortality as well higher non-resolution and recurrence of pulmona‐

While chronic conditions such as heart failure and malignancy are responsible for most of the late deaths in acute PE, early 30-day mortality results primarily from right ventricular failure [31]. Contemporary diagnostic modalities such as computed tomography and echo‐ cardiography allow for improved risk stratification and patient selection for pulmonary em‐ bolectomy, while evolution of surgical techniques has prompted a renewed enthusiasm for surgical pulmonary embolectomy as part of a multimodality approach to massive acute PE (Figure 5). The indications for open surgical embolectomy have traditionally been for clearly documented acute massive pulmonary embolism with persistent hypotension refractory to

Systemic heparin

ventilatory support with iNO

Multimodality treatment begins with immediate systemic heparinization at diagnosis, car‐ diogenic support with inotropic agents and vasopressors as indicated, and correction of hy‐ poxemia with supplemental oxygen or ventilatory support with pulmonary arterial vasodilation using inhaled nitric oxide. The underlying critical pathology is acutely elevated pulmonary vascular resistance (PVR) leading to pressure overload of the right ventricle and acute RV distention. Through ventricular interdependence, LV filling is reduced, compro‐ mising cardiac output and oxygen delivery. (Figure 6). The initial goals of medical manage‐

Surgical pulmonary embolectomy

Aggressive pharmacological cardiac support and

Prevention of re-embolization with IVC filter

ry thrombus burden [34].

402 Principles and Practice of Cardiothoracic Surgery

maximal pharmacological support.

Anticoagulation

Pharmacological Support

Surgical Therapy

Prevention of Re-Embolization

**Figure 5.** Contemporary multimodality approach to treatment of acute massive PE

**4. Contemporary multimodality management**

RV function is coupled to pulmonary vascular resistance. Agents to reverse elevated PVR may be intravenous, inhaled, or oral. All intravenous forms (prostacyclin, iloprost, sildena‐ fil, milrinone, and adenosine) carry the risk of systemic hypotension and should be institut‐ ed only after resuscitation and adequate perfusion of the RV. These agents may worsen the ventilation/perfusion ratio, increasing the degree of pulmonary shunt. Inhalational agents target the therapy to well-ventilated regions of the pulmonary bed, improving V/Q ratio and decreasing shunt fraction. Inhaled nitric oxide (iNO) has been studied in ARDS, pulmonary hypertension, and post mitral valve surgery, while evidence of its use in pulmonary embo‐ lism is limited to case reports and small case series. [37, 38, 39, 40]. While controlled studies supporting its routine use as an adjunct are lacking, anecdotal evidence based on timing of the institution of iNO seems to point to reductions in mean pulmonary artery pressures, in‐ creases in arterial oxygenation, and improvement in hemodynamics [38].

monary vein and attached to the arterial line through a Y connector [44]. Finally, adequate visualization of the distal arterial tree can be extended with use of an arterioscope. Postoper‐ ative mortality in these patients is felt to be due to eventual right ventricular failure from residual thrombus causing persistent pulmonary hypertension and interstitial pulmonary edema [41]. However, data concerning which of the above techniques is best to remove thrombus burden in the lungs, reduce RV strain, or improve outcomes is lacking. Intraoper‐ ative use of TEE during pulmonary embolectomy is recommended and can identify intra‐ thoracic extrapulmonary thromboemboli which may alter planned surgical maneuvers [45]. Reflecting back towards the original Trendelenburg procedure, inflow occlusion pulmonary embolectomy is an option where CPB is not immediately available. This technique consists of caval occlusion for 3-minute maximal periods, beyond which there is great risk of cardiac

Contemporary Surgical Management of Acute Massive Pulmonary Embolism

http://dx.doi.org/10.5772/53969

405

**Figure 7.** Technique of cardiopulmonary bypass with bicaval cannulation, arrows indicating direction of blood flow. Randall stone forceps are inserted through the main pulmonary arteriotomy to extract a portion of embolus from the left pulmonary artery. Inset: The three arteriotomy sites: main pulmonary artery, left and right pulmonary arteries

A systematic review of pulmonary embolectomies in the period from 1961 to 2006 showed the average mortality to be 30%. Several important factors in mortality included the time pe‐ riod, with higher mortality reported in studies before 1985 (32% vs 20%) and in patients

**4.2. Contemporary surgical outcomes and expanded indications**

and neurologic complications [46].

#### **4.1. Surgical pulmonary embolectomy**

The Trendelenburg operation was performed through a second transthoracic incision with resection of the second rib, occlusion of the aorta and pulmonary artery with an encircling rubber tube, and rapid removal of the embolism through a limited arteriotomy. Occlusion was limited to "forty-five seconds to two minutes, beyond that, death occurs" [7]. Modern surgical approach is by median sternotomy. After systemic heparinization, normothermic CPB is instituted via aortic and bicaval cannulation. The vena cavae are encircled with um‐ bilical tapes. The operation is performed either with a beating heart and vacuum-assisted venous drainage or with the heart arrested. Deep hypothermic circulatory arrest has also been used in cases to optimize visualization for complete embolectomy [41]. The cavae are snared to isolate right heart inflow. A longitudinal incision of the pulmonary trunk is made two cm above the pulmonary valve. The extent of pulmonary arteriotomy is tailored to the location of thrombus. The incision can be carried in a hockey-stick fashion onto the left main pulmonary artery (Figure 7). For right-sided embolectomy, the right pulmonary artery is in‐ cised between the superior vena cava and the aorta. A variety of techniques of thrombus ex‐ traction have been described. Large clot can be retrieved with Randall stone forceps, vigorous suction, and Fogarty embolectomy catheters passed into branch arteries. Opening of the bilateral pleura and manual compression of the lungs to extrude peripheral clot has been described but has the drawbacks of mechanical injury to the arterial walls and lung pa‐ renchyma, as well as possibly causing endobronchial bleeding [42].

Retrograde flushing via direct cannulation of the pulmonary veins from the left atrium has been described to remove not only residual thrombotic material but air embolism as well. As described by Zarrabi et al, if the right atrium is opened to look for suspected clot, a septal incision through the fossa is then made, the left atrium entered, and the pulmonary veins identified. A cannula is attached to the pump oxygenator, inserted into each pulmonary vein sequentially, and flushed for 60-80 seconds with a mean pressure of 15-17 mm Hg. Clot and debris thus flushed retrograde through the pulmonary veins is extracted through the pulmonary arteriotomy [43]. If the right atrium is not entered, retrograde flushing of the left atrium can be performed via a 20 Fr cannula. This is inserted through the right superior pul‐ monary vein and attached to the arterial line through a Y connector [44]. Finally, adequate visualization of the distal arterial tree can be extended with use of an arterioscope. Postoper‐ ative mortality in these patients is felt to be due to eventual right ventricular failure from residual thrombus causing persistent pulmonary hypertension and interstitial pulmonary edema [41]. However, data concerning which of the above techniques is best to remove thrombus burden in the lungs, reduce RV strain, or improve outcomes is lacking. Intraoper‐ ative use of TEE during pulmonary embolectomy is recommended and can identify intra‐ thoracic extrapulmonary thromboemboli which may alter planned surgical maneuvers [45]. Reflecting back towards the original Trendelenburg procedure, inflow occlusion pulmonary embolectomy is an option where CPB is not immediately available. This technique consists of caval occlusion for 3-minute maximal periods, beyond which there is great risk of cardiac and neurologic complications [46].

RV function is coupled to pulmonary vascular resistance. Agents to reverse elevated PVR may be intravenous, inhaled, or oral. All intravenous forms (prostacyclin, iloprost, sildena‐ fil, milrinone, and adenosine) carry the risk of systemic hypotension and should be institut‐ ed only after resuscitation and adequate perfusion of the RV. These agents may worsen the ventilation/perfusion ratio, increasing the degree of pulmonary shunt. Inhalational agents target the therapy to well-ventilated regions of the pulmonary bed, improving V/Q ratio and decreasing shunt fraction. Inhaled nitric oxide (iNO) has been studied in ARDS, pulmonary hypertension, and post mitral valve surgery, while evidence of its use in pulmonary embo‐ lism is limited to case reports and small case series. [37, 38, 39, 40]. While controlled studies supporting its routine use as an adjunct are lacking, anecdotal evidence based on timing of the institution of iNO seems to point to reductions in mean pulmonary artery pressures, in‐

The Trendelenburg operation was performed through a second transthoracic incision with resection of the second rib, occlusion of the aorta and pulmonary artery with an encircling rubber tube, and rapid removal of the embolism through a limited arteriotomy. Occlusion was limited to "forty-five seconds to two minutes, beyond that, death occurs" [7]. Modern surgical approach is by median sternotomy. After systemic heparinization, normothermic CPB is instituted via aortic and bicaval cannulation. The vena cavae are encircled with um‐ bilical tapes. The operation is performed either with a beating heart and vacuum-assisted venous drainage or with the heart arrested. Deep hypothermic circulatory arrest has also been used in cases to optimize visualization for complete embolectomy [41]. The cavae are snared to isolate right heart inflow. A longitudinal incision of the pulmonary trunk is made two cm above the pulmonary valve. The extent of pulmonary arteriotomy is tailored to the location of thrombus. The incision can be carried in a hockey-stick fashion onto the left main pulmonary artery (Figure 7). For right-sided embolectomy, the right pulmonary artery is in‐ cised between the superior vena cava and the aorta. A variety of techniques of thrombus ex‐ traction have been described. Large clot can be retrieved with Randall stone forceps, vigorous suction, and Fogarty embolectomy catheters passed into branch arteries. Opening of the bilateral pleura and manual compression of the lungs to extrude peripheral clot has been described but has the drawbacks of mechanical injury to the arterial walls and lung pa‐

Retrograde flushing via direct cannulation of the pulmonary veins from the left atrium has been described to remove not only residual thrombotic material but air embolism as well. As described by Zarrabi et al, if the right atrium is opened to look for suspected clot, a septal incision through the fossa is then made, the left atrium entered, and the pulmonary veins identified. A cannula is attached to the pump oxygenator, inserted into each pulmonary vein sequentially, and flushed for 60-80 seconds with a mean pressure of 15-17 mm Hg. Clot and debris thus flushed retrograde through the pulmonary veins is extracted through the pulmonary arteriotomy [43]. If the right atrium is not entered, retrograde flushing of the left atrium can be performed via a 20 Fr cannula. This is inserted through the right superior pul‐

creases in arterial oxygenation, and improvement in hemodynamics [38].

renchyma, as well as possibly causing endobronchial bleeding [42].

**4.1. Surgical pulmonary embolectomy**

404 Principles and Practice of Cardiothoracic Surgery

**Figure 7.** Technique of cardiopulmonary bypass with bicaval cannulation, arrows indicating direction of blood flow. Randall stone forceps are inserted through the main pulmonary arteriotomy to extract a portion of embolus from the left pulmonary artery. Inset: The three arteriotomy sites: main pulmonary artery, left and right pulmonary arteries

#### **4.2. Contemporary surgical outcomes and expanded indications**

A systematic review of pulmonary embolectomies in the period from 1961 to 2006 showed the average mortality to be 30%. Several important factors in mortality included the time pe‐ riod, with higher mortality reported in studies before 1985 (32% vs 20%) and in patients with preoperative cardiac arrest (59% vs 29%) [47]. Prospectively studied patients that have failed an initial course of thrombolytics have lower mortality with embolectomy than with a second course of thrombolysis (7% vs. 38%) [48]. More recent studies have begun to examine results in patients not meeting strict criteria of sustained hypotension or cardiogenic shock, but rather using evidence of RV dysfunction as an expanded criteria for pulmonary embo‐ lectomy, with operative mortality in contemporary series being 6-8% [49-53]. Expediency of operation has also found to have improved outcomes, particularly with surgical therapy oc‐ curring within 24 hours of diagnosis [54]. The improvement in operative mortality in the modern era may be due to several factors: improved patient selection, early identification of RV dysfunction with contemporary diagnostic modalities, extent of pulmonary thrombecto‐ my to prevent residual thrombus and thus pulmonary hypertension, the prophylactic use of IVC filters, and early operation before the development of cardiogenic shock or the need for cardiopulmonary resuscitation, both of which confer a significantly increased in-hospital mortality (25% and 65%, respectively vs 8.1%) [55]. By instituting a criteria of RV dysfunc‐ tion as an indication for pulmonary embolectomy, the population to be considered expands to include patients with submassive PE.

Trauma guidelines [60]. Increased risk of both thromboembolic disease and intracranial hemorrhage is seen also in patients with brain tumors. Successful pulmonary embolectomy has been reported in a patient with advanced glioblastoma multiforme, suggesting that this clinical scenario may represent an extended indication for surgery [61]. In patients with sig‐ nificant cardiac disease, pulmonary symptoms are often ascribed to cardiac etiology, but rarely concomitant PE may be discovered [62], in which case surgical pulmonary embolecto‐

Contemporary Surgical Management of Acute Massive Pulmonary Embolism

http://dx.doi.org/10.5772/53969

407

Catheter-based techniques include aspiration thrombectomy, fragmentation, and rheolytic thrombectomy. Rheolytic thrombectomy using the AngioJet and Rotarex devices has been shown to be technically feasible with success rates of 92.2% to 100%, with significant im‐ provements in both angiographic indices and clinical indices (i.e, Miller Index, obstruction index, perfusion index, mean pulmonary artery pressures, partial arterial pressures) [63, 64]. Data is limited to small series, and this therapy requires experienced laboratories. Its role as primary therapy is for patients with contraindications to thrombolysis, failed thrombolysis, or impending death from shock prior to thrombolysis when no other inter‐

The placement of IVC filters is prudent even after treatment with pulmonary embolectomy to prevent recurrent embolism from lower extremity sources. In several series, this has re‐ sulted in a zero recurrence rate [53, 65], while a 23% recurrence rate was noted in a series of

Acute massive pulmonary embolism is a disease best treated by multimodality therapy, be‐ ginning with systemic heparinization and IVC filter placement. A multitude of diagnostic modalities, including transesophageal echocardiography and computed chest tomography, are available in the contemporary setting to guide risk-stratification and to assess RV dys‐ function. Contemporary series of pulmonary embolectomy have demonstrated low opera‐ tive mortality with improved surgical techniques, and survival is increased when operative therapy occurs before the development of hemodynamic collapse. Thus, the modified Tren‐ delenburg procedure with extended distal pulmonary embolectomy should be part of an ag‐

Department of Cardiothoracic Surgery, University of Southern California Keck School of

my may be combined with the operation to treat the primary cardiac disease.

patients without IVC filter placement after embolectomy [48].

gressive approach to an otherwise lethal problem in the current age.

vention is available [58].

**5. Conclusion**

**Author details**

Dawn S. Hui and P. Michael McFadden

Medicine, Los Angeles, California, USA

#### **4.3. Thrombolytics, special populations, catheter-based therapy, and IVC filters**

The benefit of thrombolytic therapy in the treatment of acute PE has been controversial. A meta-analysis showed that overall, there was no significant reduction in PE or death when comparing thrombolysis with heparin; neither was the risk of major bleeding significantly increased. Subgroup analysis showed a significant reduction in PE and death in the trials that included patients with major (i.e. hemodynamically unstable) PE and no benefit in those trials that excluded those patients [56]. A review of current evidence concluded that, "Despite the lack of a verifiable mortality benefit associated with thrombolytic therapy in patients with massive PE resulting in hemodynamic instability, most clinicians accept this clinical scenario as indication for thrombolytics and it is guideline based" [57]. In the most recent guidelines (2012), The American College of Chest Physicians evidence for thrombo‐ lytic administration is graded 2C for unstable patients without high bleeding risk; recom‐ mendations are against thrombolytics in stable patients (Grade 1C) [58].

Because the effects are systemic, thrombolytics poses a risk of serious perioperative bleeding and should be approached with caution in patients with acute massive PE that may be con‐ sidered for surgical embolectomy.

This decision is of particular interest in populations whose underlying disease places them at increased risk of bleeding elsewhere. Trauma patients with immobility and/or traumatic brain injury are prone to DVT and PE; sites of bleeding risk include concomitant solid organ injury and intracranial hemorrhage. Reluctance to place prophylactic IVC filters has been due to filter-related complications and inconsistent follow-up; this has been tempered by more recent studies showing low complication rates and safe retrievability at greater inter‐ vals. Limited data consisting of matched-control trials have shown reduced PE and PE-relat‐ ed mortality rates with prophylactic filters [59]. Yet, prophylactic IVC filter placement in atrisk patients remains a Level III recommendation by the Eastern Association for the Surgery Trauma guidelines [60]. Increased risk of both thromboembolic disease and intracranial hemorrhage is seen also in patients with brain tumors. Successful pulmonary embolectomy has been reported in a patient with advanced glioblastoma multiforme, suggesting that this clinical scenario may represent an extended indication for surgery [61]. In patients with sig‐ nificant cardiac disease, pulmonary symptoms are often ascribed to cardiac etiology, but rarely concomitant PE may be discovered [62], in which case surgical pulmonary embolecto‐ my may be combined with the operation to treat the primary cardiac disease.

Catheter-based techniques include aspiration thrombectomy, fragmentation, and rheolytic thrombectomy. Rheolytic thrombectomy using the AngioJet and Rotarex devices has been shown to be technically feasible with success rates of 92.2% to 100%, with significant im‐ provements in both angiographic indices and clinical indices (i.e, Miller Index, obstruction index, perfusion index, mean pulmonary artery pressures, partial arterial pressures) [63, 64]. Data is limited to small series, and this therapy requires experienced laboratories. Its role as primary therapy is for patients with contraindications to thrombolysis, failed thrombolysis, or impending death from shock prior to thrombolysis when no other inter‐ vention is available [58].

The placement of IVC filters is prudent even after treatment with pulmonary embolectomy to prevent recurrent embolism from lower extremity sources. In several series, this has re‐ sulted in a zero recurrence rate [53, 65], while a 23% recurrence rate was noted in a series of patients without IVC filter placement after embolectomy [48].
