Surgery for pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive disease, is often diagnosed at an advanced stage, and has a 5-year survival rate of only 5 to 10%. The most important risk factor for its development is exposure to asbestos; the transformation of work practices worldwide has led to a modest decline in incidence. The three primary histologic types are epithelioid, sarcomatoid, and biphasic or mixed histology, with epithelioid resulting in more favorable outcomes than sarcomatoid or mixed histology.

One of two operations is performed: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). EPP is the radical en bloc resection of the lung, pleura, diaphragm, and pericardium. P/D is a lung-sparing but still radical procedure in which the diseased pleural envelope that encases and constricts the lung is dissected from the chest wall, mediastinum, diaphram, and pericardium, and then is stripped from the surface of the lung.P/D is the more frequently used approach as of this writing as EPP has shown no survival advantage and patients experience improved quality of life when the lung remains intact.

Currently a multi-center trial, MARS 2, is ongoing in the UK to test the hypothesis that P/D and chemotherapy is superior to chemotherapy alone with respect to overall survival for patients with pleural mesothelioma. The trial will also examine a range of secondary outcomes including adverse health events and cost-effectiveness. If the results of this trial are negative, there will be reason to question if radical surgery, as opposed to palliative procedures such as PleurX catheter insertion, should continue to have a role in the treatment of mesothelioma.

This article will focus on the anesthetic management of radical pleurectomy/decortication, which is done via open thoracotomy with one-lung ventilation by double-lumen endotracheal tube. These procedures may last for eight hours or more, and typically involve substantial blood and fluid loss. Most centers send patients directly to ICU whether or not extubation is possible at the conclusion of surgery.

Preoperative management

Patients may present for P/D with substantial disease burden including decreased lung function on the affected side, pleural or pericardial effusion, anemia, poor nutritional status, and effects of neoadjuvant chemotherapy. Whenever possible, prehabilitation in preparation for surgery should be considered to correct anemia, improve nutritional status, and improve functional capacity.

• Patient evaluation

System	Considerations
Cardiovascular	Consider stress testing, echocardiography; look for evidence of ventricular dysfunction, pulmonary hypertension, right heart strain from tumor involvement of pericardium
Hematologic	Hypercoagulability due to underlying malignancy
Respiratory	Pulmonary function testing; CT scan to evaluate extent of lung compression on the operative side, extent of pleural effusion
Neurologic	Peripheral neuropathy due to chemotherapy; assess appropriateness for epidural analgesia
Renal	Preexisting renal disease may worsen under stress of fluid shifts, blood loss, potential hypotension

Operating room setup

The operating room setup will be for open thoracotomy with an operating room table that can be flexed. A checklist for equipment and supplies typically will include:

1. Double-lumen endotracheal tube
2. Fiberoptic bronchoscope
3. Video laryngoscope
4. Arterial line setup and transducer
5. Consider flow parameter monitoring (e.g. FloTrac system, Edwards Lifesciences)
6. IV fluid warming device
7. Infusion pumps for vasoactive infusion
8. Availability of cross-matched blood, albumin
9. CPAP equipment with airflow and PEEP control

Patient preparation and premedication

Patients should fast per institutional guidelines. Premedication is at the choice of the anesthesiologist depending on the patient's age and other relevant factors.

Regional and neuraxial techniques

Thoracic epidural analgesia is highly recommended as it will benefit the patient's ability to breathe comfortably and resume mobility after the extensive thoracotomy required for radical mesothelioma resection.

The epidural catheter should be inserted at a high enough level that the patient will not have any lumbar motor block and can safely ambulate. Insertion prior to surgery offers the advantage of beginning epidural infusion before the patient emerges from anesthesia.

As there will be continuous blood and fluid loss throughout surgery, it may be preferred not to give any bolus dose or epidural infusion until near the end of surgery to avoid the hypotensive effect of sympathectomy. This decision must be weighed against the potential analgesic value of preemptive dosing.

If the patient has a contraindication to epidural catheter placement, other regional techniques may be considered: lumbar spinal opioid analgesia, erector spinae plane block , intercostal or paravertebral blocks.

Intraoperative management

Monitoring and access

1. Arterial monitoring is highly recommended for continuous blood pressure monitoring and blood gas measurement. Consider use of a flow parameter monitoring transducer (e.g. FloTrac, Edwards Lifesciences).
2. Large-bore IV access is indicated; central venous access is not mandatory unless peripheral veins are inadequate.

Induction and airway management

1. Induction medications and muscle relaxant choice per anesthesiologist preference. Ketamine may be a useful adjunct, especially for patients with chronic pain or a history of preoperative opioid use.
2. A double-lumen endotracheal tube (typically 37-39 Fr) is inserted and position confirmed with fiberoptic bronchoscopy

Positioning

The patient is placed in the lateral decubitus position with the table flexed. No position changes are usually necessary during the operation.

Maintenance and surgical considerations

The choice of maintenance anesthetic is per anesthesiologist preference; inhaled agents offer the advantage of bronchodilation. Muscle relaxation is continued throughout the procedure.

Lung protective ventilation strategies are recommended:

• Tidal volume 4-6 ml/kg on one-lung ventilation

• Permissive hypercapnia if necessary
• PEEP to the nonoperative lung

Regular blood gas measurement helps in the assessment of blood loss, volume status, and electrolyte balance. The development of metabolic acidosis may be a valuable indicator of volume deficit. For diabetic patients, insulin infusion may be helpful. The surgeon may use intermittent irrigation of the plane of dissection with sterile water to aid in lysis of adhesions, so careful attention must be paid to distinguish irrigation fluid from accumulated blood loss.

During dissection and decortication of the visceral pleura from the lung surface, the surgeon may request reinflation of the lung and maintenance of partial inflation with continuous CPAP at a range of 5-20 cm H20. A CPAP/PEEP valve connected to an auxiliary oxygen source is used at the flow rate requested by the surgeon. Avoid attaching oxygen tubing directly to a double-lumen tube without a CPAP valve as this can lead to over-inflation and barotrauma to the lung.

During dissection, venous return may be impeded by compression from retractors and by blunt dissection pressure. It may be tempting to correct preload with crystalloid volume expansion. However, albumin, vasopressors, and blood products may be more helpful in optimizing volume status until the specimen is removed.

Blood loss may not be obvious as it pools in the chest cavity.

Coagulation parameters (PT/PTT/INR), platelet count, and fibrinogen should be assessed as surgery progresses, typically after transfusion of 2-4 units of PRBC. The use of FFP and platelets may be necessary. Cryoprecipitate, recombinant clotting factors, and Factor VII have been required in some cases.

It is not uncommon to see vasoplegia or the apparent development of a systemic inflammatory response during mesothelioma resection, resulting in refractory hypotension despite adequate volume replacement. Blood pressure support with phenylephrine or norepinephrine frequently is needed.

Emergence

If the operative lung has a large air leak, it may be necessary to maintain positive pressure ventilation on the dependent lung until the patient begins to breathe spontaneously.

As air leaks are common, it is preferable to extubate at the conclusion of surgery in order to avoid worsening the air leaks in the operative lung.

As the level of general anesthesia is lightened, the epidural catheter may be activated either by bolus or continuous infusion, per clinician preference.

If the pericardium was involved with tumor and pericardiectomy was performed, herniation of the heart with torsion of the great vessels and circulatory arrest may abruptly occur upon turning the patient to the supine position at the end of surgery. This is more common in right-sided cases. The immediate return to the lateral position is the appropriate response.

Procedure variants

	Variant 1	Variant 2
Unique considerations
Position
Surgical time
EBL
Postoperative disposition
Pain management
Potential complications