Pulmonary Thromboendarterectomy

What the Anesthesiologist Should Know before the Operative Procedure

Pulmonary thromboendarterectomy (PTE) is the surgical therapy for chronic thromboembolic pulmonary hypertension (CTEPH), which is defined as pulmonary hypertension (mean pulmonary artery pressure >25 mmHg) that persists for at least 6 months after an episode of pulmonary embolism. At experienced centers, PTE has a perioperative mortality of less than 10%. The elective procedure of PTE must be distinguished from the emergency procedure of pulmonary embolectomy, which is the surgical removal of fresh thrombus in patients presenting with life-threatening acute pulmonary embolism.

What are the critical issues?

The first critical issue in the patient presenting for PTE is whether the clot burden is proximal in the pulmonary tree, and hence easily accessible to the surgeon. Patients presenting with a large proximal clot burden experience the greatest acute reductions in pulmonary vascular resistance after PTE, and typically have excellent outcomes as a result.

The second critical issue in the patient presenting for PTE is the degree of right ventricular dysfunction, as this frequently determines mortality. Patients with severe right ventricular dysfunction have the highest risk for severe hemodynamic instability in the perioperative period at critical times, such as during anesthetic induction and during weaning from cardiopulmonary bypass.

The third critical issue in PTE is the level of experience of the entire perioperative team in these complex procedures. Clinical outcomes after PTE are highly dependent on experienced and skillful management, both in the operating room and the intensive care unit. As a result, these procedures tend to cluster in specialized centers.

What are the typical comorbidities?

Patients are typically in their 5th decade, the most common age for clinical presentation of CTEPH. Patients will typically have right ventricular hypertrophy and tricuspid regurgitation due to advanced chronic pulmonary hypertension. Most patients will have a degree of right ventricular dysfunction that frequently presents clinically as dypsnea, poor effort tolerance, and edema.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

PTE is an elective surgical procedure that entails removal of chronic organized thrombus from the pulmonary vasculature in patients with CTEPH, most typically involving cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).

PTE is distinct from pulmonary embolectomy, which is the emergency surgical removal of fresh thromboemboli from the pulmonary vasculature in patients with acute massive or submassive pulmonary embolism who are hemodynamically unstable and/or who have right ventricular dysfunction. Current guidelines from the American Heart Association (AHA) recommend pulmonary embolectomy in these patient subgroups, especially in those who have contraindications to thrombolysis with a tissue plasmonogen activator, such as alteplase.

Because PTE at an experienced medical center is the definitive therapy for CTEPTH, there should be minimal delay once the diagnosis of CTEPH has been established. The AHA guidelines recommend that patients with CTEPH be promptly referred for PTE, regardless of symptom levels (Class I Recommendation; Level of Evidence B).

Although pulmonary vasodilator therapy may be indicated in CTEPH, it should not delay prompt evaluation for PTE (Class III Recommendation; Level of Evidence B). Chronic pulmonary vasodilator therapy is indicated in patients with CTEPH who refuse PTE, who have excessive operative risk due to severe comorbidities, or who have residual pulmonary hypertension after PTE at an experienced center (Class IIb; Level of Evidence B). The risk of excessive delay in PTE for patients with CTEPH is worsening of pulmonary hypertension and right ventricular dysfunction, both of which significantly increase interim mortality and perioperative risk.

Considerations for emergency surgery: PTE is typically an elective procedure, as explained earlier. The typical considerations for patients undergoing pulmonary embolectomy as an emergency are discussed in the recent AHA guidelines.

Considerations for urgent surgery: PTE is typically an elective procedure, as explained earlier. The typical considerations for patients undergoing pulmonary embolectomy as an urgent procedure are discussed in the recent AHA guidelines.

Considerations for elective surgery: PTE is an elective procedure. The typical considerations for PTE and their perioperative management are more fully explained in the rest of this module.

2. Preoperative evaluation

The preoperative evaluation of a patient with CTEPH for PTE should focus on the following aspects, since they significantly determine perioperative risk.

Extent of the clot burden in CTEPH as staged by the Jamieson Classification

The Jamieson Classification of CTEPH divides the clot burden in CTEPH into four types. Type I disease is characterized by proximal thrombus in the main or lobar pulmonary arteries. This pattern occurs in about 25% of cases. Type 2 disease is characterized by intimal thickening and fibrosis, with or without thrombus proximal to the pulmonary segmental arteries. This pattern accounts for about 40% of cases.

Type 3 disease is characterized by intimal webbing and thickening, with or without organized thrombus within distal segmental and subsegmental vessels. The type 3 pattern accounts for approximately 30% of cases and may represent advanced chronic disease, in which the proximal thromboembolic material has been reabsorbed.

Type 4 disease is characterized by distal arteriolar vasculopathy without visible thromboembolic disease. This distal pattern does not represent classic CTEPH and is typically inoperable.

Patients with distal disease (type 3 and type 4 patterns) have a less dramatic response to CTEPH. Compared to patients with proximal disease (type 1 and type 2 patterns), they have a higher postoperative mortality, longer stays in the intensive care unit and hospital, and greater dependence on postoperative inotropic support.

Severity of pulmonary hypertension

In the majority of patients, echocardiography serves as a useful screening test for the noninvasive detection of pulmonary hypertension, based on spectral Doppler pressure assessment of tricuspid regurgitation. Right heart catheterization is indicated for definitive measurement of pulmonary pressures and calculation of pulmonary vascular resistance. Typical values in CTEPH are as follow: systolic pulmonary arterial pressure >40 mmHg; mean pulmonary artery pressure >25 mmHg; and pulmonary vascular resistance >3 Wood units.

In CTEPH, the severity of the pulmonary vascular resistance is an important perioperative prognostic determinant, especially when considered in conjunction with the Jamieson Classification. Patients with severe pulmonary hypertension and proximal disease (Jamieson types 1 and 2) are very likely to have a major decrease in pulmonary vascular resistance after PTE, as the proximal clot is within easy reach of the surgeon. In contrast, the worst prognosis after PTE is in patients with CTEPH characterized by severe pulmonary hypertension and distal disease (Jamieson types 3 and 4).

Right ventricular function

In CTEPH, right ventricular afterload is always increased due to chronic pulmonary hypertension. Consequently, the right ventricle is hypertrophied. As the right ventricle begins to fail, it becomes dilated and hypokinetic. Tricuspid regurgitation is typical in this setting. Severe right ventricular dysfunction significantly affects the anesthetic plan (see later discussion). Furthermore, even though the failing right ventricle complicates perioperative management, the prognosis is favorable, especially when there is significant reduction in pulmonary vascular resistance after PTE.

Associated parenchymal lung disease (type and severity)

In CTEPH, associated significant parenchymal disease complicates the clinical outcome after PTE. This remains true whether the lung disease is restrictive, obstructive, or mixed. This associated chronic pulmonary disease significantly decreases perioperative respiratory reserve.

Reperfusion pulmonary edema is common after PTE. Thus, in the patient subgroup with chronic lung disease, this acute lung injury can precipitate severe refractory respiratory failure that may prevent separation from CPB and require extracorporeal membrane oxygenation as a bridge to recovery.

Consider the following options in the preoperative assessment of patients with CTEPH for PTE:

Medically unstable conditions warrant further evaluation: Right ventricular dysfunction, lung disease, liver dysfunction, and renal failure.
Delaying surgery may be indicated if: The patient exhibits decompensated organ dysfunction (e.g., congestive heart failure).

It is important in the setting of significant organ dysfunction to obtain adequate diagnostic evaluation and institute appropriate preoperative interventions as indicated before proceeding with PTE. The first goal is to diagnose the cause and severity of each organ dysfunction. The second goal is to intervene appropriately to maximize organ recovery prior to PTE.

3. What are the implications of co-existing disease on perioperative care?

Significant co-existing diseases will frequently and significantly impact the perioperative plan of care.

Significant concomitantdiseases may be causes of CTEPH (e.g., cancer or hypercoagulable states)or may result from advanced CTEPH (e.g., right ventriculardysfunction).

b. Cardiovascular system

The central perioperative cardiovascular consideration in patients with CTEPH for PTE is right ventricular function, given the increased afterload due to elevated pulmonary vascular resistance. In the setting of right ventricular dysfunction, perioperative management should be designed to optimize right ventricular performance with adequate volume loading, inotropic support, and pulmonary vasodilation.

c. Pulmonary

Concomitant lung disease may be obstructive or restrictive. Common obstructive lung diseases include emphysema, chronic bronchitis, and asthma. Restrictive lung diseases include primary lung infiltrations (e.g., interstitial pulmonary fibrosis and collagen vascular diseases) or secondary extrapulmonary restriction (e.g., morbid obesity). In severe lung disease, pulmonary function testing is useful to document severity and test for reversibility of airway constriction with bronchodilators. Furthermore, a baseline arterial blood gas serves as a useful guide to perioperative management of ventilation.

The implications of significant lung disease in PTE include appropriate mechanical ventilation based on the type of lung pathology and the understanding of the degree of respiratory reserve. Since reperfusion pulmonary edema is common in PTE, it is important to integrate the management of this acute lung injury with the background, concomitant chronic lung disease. This acute lung injury can precipitate severe refractory respiratory failure that may prevent separation from CPB and extracorporeal membrane oxygenation as a bridge to recovery.

d. Renal-GI:

Hepatic considerations

Liver function tests and coagulation indices may be abnormal, secondary to hepatic congestion from right heart failure. Hepatic congestion causing abnormal LFTs and coagulation may predispose the patient to an increased risk of bleeding and transfusion in the perioperative period. Furthermore, if there is significant hepatic compromise, the risk of perioperative acute liver failure is significant, given the exposure to CPB and DHCA that often accompanies PTE.

An important pharmacokinetic consideration is that perioperative drugs that are hepatically metabolized (e.g., vecuronium) will have prolonged clinical effects in this setting.

Renal considerations

Renal dysfunction may develop as part of the natural history of CTEPH, due to decreased cardiac output from advanced right ventricular dysfunction. This complication would be reflected by an increased serum creatinine and urea. Advanced compromise of renal reserve in CTEPH is a significant risk factor for perioperative renal failure, renal replacement therapy, and increased mortality risk after PTE.

An important pharmacokinetic consideration is that perioperative drugs that are renally eliminated (e.g., pancuroninium) will have prolonged clinical effects in this setting.

e. Neurologic:

Baseline neurologic function should be assessed, as surgery involves CPB and DHCA. Both have been associated with neurologic complications, such as delirium and stroke. The risks of perioperative delirium and stroke are increased when the duration of deep hypothermic circulatory arrest is more than 30 minutes.

The spectrum of acuteneurological disorders after DHCA includes delirium, seizures, focalstroke, and coma. Although recovery from delirium and seizures istypical, the patient with stroke is most often left with permanentneurological deficits. Global neurological deficits, such as coma,have a grave perioperative prognosis.

f. Endocrine:

The most common endocrine disorder that accompanies CTEPH is hypothyroidism. The patient is typically receiving thyroid hormone replacement therapy and is clinically euthyroid at the time of surgical intervention. In these cases, recent thyroid function testing is useful to confirm adequate baseline thyroid function before PTE.

Furthermore, an additional perioperative endocrine consideration is that steroid therapy is often utilized for neuroprotection during DHCA. The resulting perioperative hyperglycemia often requires insulin infusion to restore euglycemia in the perioperative period.

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

Hematologic considerations

CTEPH may be accompanied by polycythemia secondary to chronic hypoxia. Furthermore, there may be underlying hypercoagulable syndromes that may require specialized hematological investigation. In the setting of a hypercoagulable syndrome, perioperative administration of an antifibrinolytic agent during PTE should be conducted with caution, given the prothrombotic milieu.

4. What are the patient's medications and how should they be managed in the perioperative period?

Patients with CTEPH are commonly managed medically with pulmonary vasodilators, which may have specific perioperative considerations.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

Pulmonary vasodilators are commonly part of the medical regimen for patients with CTEPH.

Bosentan is an oral pulmonary vasodilator. It affects pulmonary vasodilation through nonselective endothelin receptor antagonism. Bosentan is a liver enzyme inducer that may increase the hepatic metabolism of certain drugs, such as rocuronium. Because bosentan has also been associated with hepatic injury, it has been recommended that hepatic transaminase levels be monitored on a regular basis for prompt detection of this serious complication. If this complication is detected prior to PTE, bosentan therapy should be discontinued to allow recovery of liver function prior to PTE.

Sildenafil is an oral inhibitor of type 5 phosphodiesterase, an enzyme that degrades cyclic guanosine monophosphate. As a consequence, sildenafil causes pulmonary vasodilation by increasing levels of cyclic guanosine monophosphate, which is a secondary messenger for pulmonary vascular smooth muscle relaxation. On the other hand, nitric oxide causes vasodilation by increasing production of cyclic guanosine monophosphate.

Type 5 phosphodiesterase is also found in the systemic vascular smooth muscle. Consequently, in patients taking sildenafil, an exaggerated hypotensive effect may be seen with agents that mediate vasodilation through nitric oxide, such as nitroglycerin and sodium nitroprusside. Therefore, nitroglycerin and sodium nitroprusside should be cautiously utilized in patients on sildenafil, who are undergoing PTE for CTEPH.

Epoprostenol is a potent direct pulmonary and systemic vasodilator that is utilized intravenously as a bridge to PTE. It is typically administered centrally by infusion because its half-life is only 6 minutes. It is important to continue this agent perioperatively because its rapid withdrawal can precipitate catastrophic rebound pulmonary hypertension and acute right ventricular failure.

i. What should be recommended with regard to continuation of medications taken chronically?

Chronic medications in patients for PTE should be managed in the standard fashion for patients undergoing cardiac surgery with CPB and DHCA. In general, pulmonary vasodilators should be continued throughout the perioperative period to facilitate pulmonary vasodilation for optimal right ventricular performance.

j. How To modify care for patients with known allergies –

In general, if the allergy is serious, the trigger should be avoided (e.g., anaphylaxis to latex). In the case of medications such as antibiotics, clinical alternatives should be prescribed.

Because PTE involves heparinization for CPB and DHCA, active or very recent heparin-induced thrombocytopenia is a reason to postpone heparin exposure for PTE until the relevant antibodies are no longer detectable in the patient’s serum. This typically takes about 3 months. PTE is typically an elective procedure, so this surgical delay is generally feasible.

In the unusual circumstance when PTE cannot be delayed for this time period, such as in the case of life-threatening diseases, PTE should proceed with nonheparin anticoagulation, such as bivalirudin, a short-acting direct thrombin inhibitor.

k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

In general, latex allergy is best managed by avoiding exposure to latex in the perioperative period. This includes the operating room environment.

l. Does the patient have any antibiotic allergies? (common antibiotic allergies and alternative antibiotics)

The typical incision for PTE involves a midline sternotomy. Typical perioperative antibiotic therapy for this surgical approach includes a vancomycin and a cephalosporin, such as cefazolin. Antibiotic therapy will often be specific for a given institution, depending on recent patterns of microbial infection and antibiotic resistance.

For patients with serious penicillin allergies, alternatives to cephalosporins include aminoglycosides, such as gentamicin, or quinolones, such as levofloxacin.

m. Does the patient have a history of allergy to anesthesia?

Malignant hyperthermia

The main consideration here is malignant hyperthermia. In patients with previous episodes or a family history of malignant hyperthermia, general anesthesia should be provided in the standard fashion. A trigger-free anesthetic technique should be employed, with avoidance of trigger agents, such as succinylcholine, and inhalational anesthetics, such as total intravenous anesthesia with infusions of propofol and remifentanil.

It is important during CPB to maintain anesthesia in a trigger-free fashion. Furthermore, a management plan and sufficient dantrolnene should be immediately available should a malignant hyperthermia episode occur.

5. What laboratory tests should be obtained and has everything been reviewed?

Laboratory tests should include the following:

Complete blood count with hemoglobin, hematocrit, white blood cell count, and platelet count.
Electrolyte and renal function panel.
Liver function tests.
Coagulation panel with prothrombin time, international normalized ratio, and partial thromboplastin time.
Cardiovascular assessment, including echocardiography and right heart catheterization.
Pulmonary assessment, including chest radiograph, pulmonary function tests, ventilation-perfusion scanning, pulmonary angiography, and computed axial tomography.

This comprehensive preoperative assessment is typically completed on an outpatient basis in a multidisciplinary fashion at a specialized center for the management of CTEPH. Advanced testing may be indicated in the diagnosis and management of associated medical conditions and underlying hypercoagulable states.

The anesthesia team should review the entire preoperative assessment, including the specialized testing. This review, together with the clinical assessment of the patient, will facilitate the development of a sound and individualized anesthetic plan. It will allow appreciation of the CTEPH clot burden, the severity of the pulmonary hypertension, the degree of right ventricular dysfunction, and the severity of concomitant pulmonary parenchymal disease.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

Patients with CTEPH for PTE typically undergo median sternotomy. Surgical exposure of the pulmonary vascular tree is facilitated by CPB with periods of DHCA. The procedure is long, with the patient in the supine position. The upper extremities are padded and tucked at the patient’s sides.

The anesthetic technique for PTE is general anesthesia with endotracheal intubation. Although a concomitant neuraxial anesthetic technique is possible to enhance perioperative analgesia, it is not sufficient as a primary anesthetic technique. Due to systemic heparinization for CPB and the coagulopathy associated with DHCA, neuraxial techniques in this setting carry an enhanced risk of neuraxial hematoma. The role of neuraxial anesthesia in PTE has been very limited.

a. Neuraxial anesthesia

Neuraxial anesthetic techniques for PTE are combined with general anesthesia. Due to risks such as neuraxial hematoma and unproven outcome advantages over general anesthesia alone, the role of concomitant neuraxial anesthetic techniques has been restricted in PTE.

The feasibility of epidural anesthesia was demonstrated in a recent small randomized trial (N = 32: 2005 – 2006) at a European university medical center. In this pilot study, thoracic epidural analgesia was associated with hemodynamic stability and significantly decreased postoperative pain and time to tracheal extubation. The study was underpowered to assess effects on mortality, organ-based complications, and hospital length of stay.

Although spinal anesthesia is an option in PTE, a thorough literature search has failed to find any recently published study on this anesthetic technique in PTE.

b. General anesthesia

The gold-standard anesthetic technique for PTE is general anesthesia with endotracheal intubation. This technique provides a secure airway, allows precise control of ventilation, permits transesophageal echocardiography, and facilitates hemodynamic stability during PTE.

c. Monitored anesthesia care

Monitored anesthesia care is not a realistic option for patients undergoing PTE, given its duration, surgical exposure, degree of hypothermia, and the precise control of ventilation required.

6. What is the author's preferred method of anesthesia technique and why?

The recommended anesthetic technique for PTE is general endotracheal anesthesia. It is the anesthetic technique that addresses all the requirements of PTE.

The recommended prophylactic antibiotics are vancomycin and cefazolin. Antibiotic selection will vary by institution, depending on patterns of local microbial infection and the prevalence of antibiotic resistance. It is important to administer the antibiotics prior to skin incision to ensure adequate tissue levels prior to surgical incision.

Premedication

Premedication is typically minimized or avoided, as it can lead to hypoxia and hypercarbia, which could potentially worsen pulmonary artery hypertension.

Induction

The goals of anesthetic induction include maintenance of hemodynamic stability and avoidance of hypoxia and hypercarbia while securing the airway. A balanced anesthetic technique involving midazolam, fentanyl, and a long-acting muscle relaxant is a common drug combination for the induction of anesthesia.

Etomidate is a preferred anesthetic induction agent in this setting due to its hemodynamic stability. Inotropic support may be necessary during induction, given the prevalence of significant right ventricular dysfunction in this setting. Consider low-dose epinephrine/dopamine/dobutamine infusion to provide positive inotropy and chronotropy.

Maintenance of anesthesia

Anesthetic maintenance may be volatile (e.g., isoflurane and/or intravenous propofol). Analgesia should be maintained with a titrated narcotic, such as fentanyl. Narcotic infusions with opioids such as sufentanil, fentanyl, or remifentanil also provide excellent analgesic maintenance.

Monitors

Invasive arterial blood pressure monitoring

Preinduction placement is encouraged, so that hemodynamics can be monitored with induction. Preference is for the right radial arterial line, as it may be useful if antegrade cerebral perfusion is used during DHCA. Femoral artery cannulation may be useful as well, if radial artery over-damping occurs from peripheral vasoconstriction after prolonged CPB and DHCA.

Central venous and pulmonary artery catheters

Postinduction line placement is encouraged because laying supine may not be tolerated by the patient, particularly if the patient has compromised cardiac function. Avoid steep Trendelenberg position for line placement, as an acute increase in venous return can precipitate right heart failure. Avoid wedging the pulmonary arterial catheter because of increased risk of pulmonary artery rupture.

Intraoperative transesophageal echocardiography (TEE)

TEE can be used to visualize clots in the main pulmonary artery and proximal right and left pulmonary arteries. A full comprehensive exam should be performed in order to:

Rule out the presence of thrombus in the heart
Evaluate ventricular function, with a particular focus on the right ventricle
Assess valvular function, especially the tricuspid valve
Detect other cardiac abnormalities, such as patient foramen ovale.

TEE provides online assessment of cardiac function to guide the diagnostic evaluation of intraoperative shock and to provide immediate feedback on the efficacy of instituted management. These capabilities are very useful in the management of hemodynamics at critical times, such as during anesthetic induction, surgical incision, and cannulation for CPB, as well as during and after separation from CPB.

Cerebral oximetry

Its perioperative application remains controversial. This monitor is sensitive to acute changes in cerebral oxygenation. A fall in cerebral oxygenation can assist in the early detection of cerebral hypoxia due to factors such as hypotension, acute anemia, inadequate blood oxygenation, and impaired cerebral perfusion during CPB (e.g., kinked caval cannula) or during DHCA (e.g., cannula occlusion during antegrade cerebral perfusion).

Surgical approach

Incision

Median sternotomy. Full CPB with bicaval and aortic cannulation.

Cerebral perfusion

Cerebral perfusion is a common perfusion adjunct during deep hypothermic circulatory arrest. During antegrade cerebral perfusion, a cannula is generally placed in the right axillary/subclavian artery and the head is perfused directly. During retrograde cerebral perfusion, a cannula is placed in the superior vena cava and perfusion is with cold blood at low flows.

Deep hypothermic circulatory arrest (DHCA)

Allows for cessation of circulation and collateral flow so that proper identification of tissue planes can occur. If dissection is too deep, pulmonary artery perforation may result. If dissection is too shallow, there may be incomplete removal of thromboembolic material, resulting in persistent pulmonary hypertension after PTE.

Systemic cooling occurs to a clinical end-point, such as a set temperature or an isoelectric encephalogram. Core body temperature is generally 15ºC to 20ºC. The aim is to limit the period of deep hypothermic circulatory arrest to less than 30 minutes to minimize the risk of neurological complications.

Anesthetic considerations for CPB and DHCA

Antifibrinolytic use

Lysine analogues are frequently utilized, including tranexamic acid or aminocaproic acid. There use is controversial, as an underlying hypercoagulable state is common.

Systemic heparinization for CPB

Heparinization follows the institutional protocol for cardiopulmonary bypass. Generally, the ACT is maintained above 400 seconds.

Neuroprotective agents

Multiple agents have been studied. Evidence base for all agents is weak. A steroid is commonly given before DHCA for neuroprotection, such as 1000 mg methylprednisolone. Common additional agents include propofol, lidocaine, and magnesium.

Separation from CPB

Patient should be rewarmed until the core temperature is euthermic. During rewarming, it is useful to ventilate the lungs and apply positive-end expiratory pressure to minimize atelectasis and edema during reperfusion.

Depending on ventricular function, inotropes may be indicated. Right ventricular dysfunction is common. Inotropes, such as epinephrine, dopamine, or dobutamine, and phosphodiesterase inhibitors, such as milronone, are useful. Consider intra-aortic balloon pump insertion if ventricular failure persists despite inotropic support.

Selective pulmonary vasodilation with inhaled nitric oxide or prostacyclin can be employed if elevated pulmonary arterial pressures persist and right ventricular function is compromised.

Significant coagulopathy is common after heparin reversal with protamine due to multiple factors, such as preoperative warfarin therapy, chronic liver dysfunction secondary to right heart failure, prolonged cardiopulmonary bypass, and deep hypothermic circulatory arrest. Titrated transfusion of platelets and/or fresh frozen plasma and/or cryoprecipitate is often indicated to restore normal coagulation. This transfusion may be guided by point-of-care coagulation testing (e.g., thromboelastography).

Surgical outcome measures

Successful surgery for PTE is associated with a significant reduction in pulmonary artery pressures and pulmonary vascular resistance. It is also associated with improved right ventricular geometry and performance. There is also frequently a dramatic improvement in the degree of tricuspid regurgitation. The response of the right heart to PTE is often longitudinally followed by serial transthoracic echocardiography.

Cardiac complications

Right ventricular failure

This is the most common cardiac complication. A degree of right ventricular dysfunction is frequent, given the decreased preoperative right ventricular reserve, the prolonged hypothermic CPB, and the myocardial ischemia from the aortic cross-clamp period.

In severe cases, multiple inotropes are required in high doses. A common synergistic inotrope combination is epinephrine and milrinone, given their different mechanisms of action. Epinephrine directly increases levels of cyclic adenosine monophopshate (cAMP), whereas milrinone increases cAMP indirectly by preventing its breakdown due to inhibition of type 3 phosphodiesterase. Milrinone is a potent pulmonary vasodilator, which further augments right ventricular function due to decreased afterload.

In severe cases, selective pulmonary vasodilation with inhaled nitric oxide or inhaled prostacyclin is indicated. This intervention selectively unloads the right ventricle with no systemic vasodilation. Both inhaled nitric oxide and prostacyclin are cleared in the pulmonary circulation and have minimal effect on the systemic circulation.

In refractory cases, mechanical circulatory support with a right ventricular assist device or extracorporeal membrane oxygenation may be required as a bridge to clinical recovery.

Pulmonary complications

Persistent pulmonary hypertension

The incidence of significant residual pulmonary hypertension after PTE is about 10%. The common causes for this syndrome include surgically inaccessible thromboembolic disease and/or small vessel arteriopathy from chronic pulmonary hypertension.

The management priorities include support of right ventricular function and pharmacologic pulmonary vasodilation. Chronic pulmonary vasodilator therapy is indicated in this patient subgroup (AHA Class IIb recommendation; Level of Evidence B). Surgical interventions for this patient subgroup include repeat evaluation for PTE at an experienced center and/or lung transplantation.

Pulmonary reperfusion injury

The postoperative incidence is about 10% to 15%. This syndrome typically occurs in areas of lung, where proximal vascular obstructions were relieved (Jamieson type 1 and type 2). The relative hyperperfusion results in pulmonary edema.

The alveolar-arterial gradient generally peaks in the first postoperative week. Management is supportive. Refractory cases require extracorporeal membrane oxygenation as a bridge to recovery.

a. Neurologic:

The main neurologic complications after PTE are delirium, seizures, and stroke.

Delirium

This syndrome represents a form of transient neurologic dysfunction, which is primarily in response to the period of DHCA that accompanies the surgical conduct of PTE. It has the same diagnostic features common to all postoperative deliriums, including loss of orientation and inability to focus. The associated disordered motor activity may be hypoactive or hyperactive.

It is typically self-limited to the first postoperative week. The management is supportive.

Seizures

Seizures may be focal or generalized. Confirmation of the diagnosis may require intermittent or continuous electroencephalography. Common causes include drug exposure (e.g., high-dose tranexamic acid) or structural brain injury (e.g., new stroke).

Conventional anticonvulsants may be indicated for prophylaxis. Prognosis depends on the underlying etiology.

Stoke, including coma

These syndromes represent forms of permanent neurologic dysfunction as a consequence of neuronal damage. These neuronal lesions result primarily from the ischemic deficit due to DHCA during which time the brain has an interrupted blood supply.

The ischemia may result in focal deficits, such as hemiplegia, or global deficits, including coma. The risk of stroke increases with the duration of DHCA, especially when longer than 30 minutes. Management is supportive. Global deficits with coma have a grave prognosis.

b. If the patient is intubated, are there any special criteria for extubation?

The criteria for endotracheal extubation after PTE include:

An awake patient who is able to follow simple commands
Normal body temperature
Hemodynamic stability
Absence of major mediastinal bleeding
Adequate muscle strength, as reflected by sustained head lift and/or sustained tetanus on neuromuscular testing
Adequate spontaneous respiration on minimal ventilator settings
The absence of a severe alveolar-arterial gradient (e.g., oxygen saturation >92% on FiO2 <0.50)

c. Postoperative management

Management after PTE usually takes place in an intensive care unit setting, as the patient typically requires active rewarming, mechanical ventilation, close hemodynamic monitoring, titration of vasoactive infusions, and intravascular volume management with crystalloid and/or colloid. These postoperative issues usually require a cardiothoracic surgical intensive care unit. Furthermore, a subgroup of patients will require more advanced postoperative care because they will be supported with intra-aortic balloon counterpulsation or extracorporeal membrane oxygenation.

The initial analgesic requirements are satisfied with titrated opioids such as morphine or hydromorphone. When the patient is awake, opioid patient-controlled analgesia can also be commenced for those patients with a significant analgesic requirement. In the subset of patients with an epidural catheter, epidural infusions of dilute local anesthetic and opioid result in potent postoperative analgesia. When the patient is awake, patient-controlled epidural analgesia can also be commenced.

The postoperative course of patients after PTE generally follows one of the following courses:

Track A

This is an essentially uncomplicated course. The length of stay in the intensive care unit is generally less than 7 days. Patients have no major complications and recover rapidly from surgery. The risk of mortality is low.

Track B

This track is characterized by at least one major organ complication (see sections on complications). The length of stay in the intensive care unit is generally less than 21 days. Patients experience a gradual but steady recovery from surgery and their organ based injury. The risk of mortality rises.

Track C

This track is characterized by multiple organ complications (see sections on complications). The length of stay in the intensive care unit is generally more than 21 days. Patients may experience a prolonged recovery from surgery and their organ-based injury. The risk of mortality is high.

What's the Evidence?

Jaff, MR, McMurry, MS, Archer, SL. “on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Peripheral Vascular Disease, and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association”. Circulation. vol. 123. 2011. pp. 1788-1830. (Venous thromboembolism (VTE) is a condition that carries a significant morbidity and mortality; the aim of this article is to provide the clinician with a reference for management of patients with VTE and its sequelae.)

Thistlethwaite, PA, Mo, M, Madani, MM. “Operative classification of thromboembolic disease determines outcome after pulmonary endarterectomy”. J Thorac Cardiovasc Surg. vol. 124. 2002. pp. 1203-11. (Classification of pulmonary embolism is important in understanding the pathophysiology associated with CTEPH and is a useful predictor of postoperative outcomes after pulmonary thromboembolectomy.)

Stein, E, Ramakrishna, H, Augoustides, JG. “Recent advances in chronic thromboembolic pulmonary hypertension”. J Cardiothorac Vasc Anesth. vol. 25. 2011. pp. 744-8. (This is a review article describing the predictors of outcome after PTE, role of medical therapy before and after PTE, and possible postoperative complications of management.)

Piazza, G, Goldhaber, SZ. “Chronic thromboembolic pulmonary hypertension”. N Engl J Med. vol. 364. 2011. pp. 351-60. (This article summarizes the clinical presentation, diagnosis, and treatment of patients with chronic thromboembolic pulmonary hypertension.)

Guerrero, E, Banks, DA, Auger, WR. “Case 1-2011: the challenges posed by a complicated pulmonary thromboendarterectomy”. J Cardiothorac Vasc Anesth. vol. 25. 2011. pp. 183-91. (The article highlights the immediate postoperative management of patients undergoing PTE and the implications of severe pulmonary hypertension after PTE.)

Auger, WR, Kim, NH. “Chronic thromboembolic pulmonary hypertension”. Clin Chest Med. vol. 28. 2007. pp. 255-69. (This reference describes the epidemiology, risk factors, natural history, and preoperative evaluation of patients with CTEPH. It also describes the technical aspects of PTE and the role of medical therapy.)

Jamieson, SW. “Pulmonary endarterectomy: experience and lessons learned in 1500 cases”. Ann Thorac Surg. vol. 76. 2003. pp. 1457-62. (This article describes the technical aspects and perioperative management of patients undergoing PTE from a center that has the most clinical experience with PTE.)

Augoustides, JG. “Update in hematology: heparin-induced thrombocytopenia and bivalirudin”. J Cardiothorac Vasc Anesth. vol. 25. 2011. pp. 371-5. (Heparin-induced thrombocytopenia (HIT) is common and carries a significant increase in mortality after cardiac surgery. This article addresses the use of a bivalrudin, a thrombin inhibitor, as an alternative to heparin during cardiac surgery.)

Roscoe, A, Klein, A. “Pulmonary endarterectomy”. Curr Opin Anesth. vol. 21. 2008. pp. 16-20. (This review article highlights the pathophysiology of CTEPH and the perioperative implications of pulmonary endarterectomy.)

Kunstyr, J, Klein, A, Lindner, J. “Use of high-thoracic epidural analgesia in pulmonary endarterectomy: a randomized feasibility study”. Heart Surg Forum. vol. 11. 2008. pp. E202-8. (The use of thoracic epidural analgesia in cardiac surgery is controversial. This is a prospective randomized trial in which patients received a thoracic epidural combined with general anesthesia for pulmonary endarterectomy. It showed that these patients were hemodynamically stable, had reduced time to tracheal extubation, and had decreased postoperative pain.)

Berman, M, Tsui, S, Vuylsteke, A. “Successful extracorporeal membrane oxygenation support after pulmonary thromboendarterectomy”. Ann Thorac Surg. vol. 86. 2008. pp. 1261-7. (The use of extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy after PTE in the setting of severe cardiac and/or pulmonary compromise.)

Pepke-Zaba, J. “Diagnostic testing to guide the management of chronic pulmonary thromboembolic pulmonary hypertension: state of the art”. Eur Respir Rev. vol. 19. 2010. pp. 55-8. (This article provides an up-to-date review of diagnostic testing used to assess the severity of CTEPH and to determine its effects on other organs.)

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This article originally appeared on Clinical Pain Advisor