1. Introduction
Primary lung malignancies are the leading cause of cancer mortality. The majority of newly diagnosed patients already suffer from an advanced disease stage. The peak incidence of lung cancer is between the ages 55 and 65. Annually, primary carcinoma of the lungs affects about 93,000 men and 80,000 women in the US with 15% five year survival rate [1].
Percutaneous cryoablation treatment (PCT) is a viable, minimally invasive treatment option for patients with non-small cell lung cancer (NSCLC) or pulmonary metastases [2-4]. Based on our experience, PCT for NSCLC is an excellent palliative alternative for patients who are considered inoperable. An advantage of PCT is that the procedure can be repeated if a patient has a recurrence or a new malignancy. Indications for PCT include patients with lung tumors < 3 cm in size and patients requiring palliation for inoperable lung tumors [4]. PCT has been used with varying degrees of success for treatment of hepatic and renal lesions [5-9]. Interesting applications of this technique have also been described for treatment of endobronchial lesions [2] and neurolysis for chronic post-thoracotomy pain syndromes [10].
PCT has been applied for treatment of pulmonary lesions. Maiwand and Asimakopoulos (2004) [3] reviewed the use of cryotherapy in a group of 15 patients that underwent direct intrathoracic cryosurgery. In their experience there were no post-operative complications resulting from the direct tumor ablation; in fact, dyspnea symptoms improved in 66.7% of patients. In a retrospective report, Zemlyak, Moore & Bilfinger (2010) [4] compared survival after sublobar resection, radiofrequency therapy and percutaneous cryoablation in 64 patients with stage 1 NSCLC. Patients were not randomly assigned to groups; instead, the treatment for each patient was chosen on a case by case basis. Survival after PCT was comparable to outcomes with the other therapies, without serious complications or longterm loss of pulmonary function. In a larger series Wang and colleagues [11] reported 200 procedures performed under local anesthesia with sedation with a 12% incidence of pneumothorax PTX, a 62% incidence of hemoptysis, and a small number of major complications. Unlike other reports, this group used inclusion criteria which did not follow the American College of Surgeons Oncology Group (ACOSOG). This allowed them to include patients with lesions greater than 4 cm in size as well worse pulmonary status, who had previously failed chemotherapy and/or radiation therapy.
Surgical resection is not an option due to poor performance status, comorbidities, and disease status common to patients that qualify for PCT under the American College of Surgery (ACOS) guidelines [4]. Consequently, the anesthesiologist should anticipate significant pulmonary disease and a heightened potential for airway compromise. Better understanding of PCT, the anesthetic management, and potential complications will facilitate a more effective relationship between the anesthesiologist, the thoracic surgeon, and interventional radiologist for improved patient care.
2. Technical Aspects of Cryoablation
Cryoablation, also called cryosurgery, cryotherapy, or percutaneous cryoablation (PCT) is a minimally invasive, localized treatment that uses extreme cold to destroy tumor cells by intracellular and extracellular ice crystal formation. These direct and indirect effects on tumor cells and vasculature result in membrane rupture and cell dehydration [12]. The concept of using cold for tissue destruction of malignant tumors is not novel, as it was attempted in the 19th century [12]. PCT utility has recently increased for a wide range of applications, including the treatment of renal masses, prostate carcinoma, hepatic malignancy, lung cancer, and nerve ablation for pain syndromes, amongst other indications [6-10].
For non-operable lung cancer or metastases, PCT involves inserting a cryoprobe into the lesion of the lung with the goal of local tissue destruction. PCT is most effective for patients with tumors < 3 cm because this is the approximate diameter of cryoablation probes. In our center, cryoablation is performed under CT guidance by an interventional radiologist and thoracic surgeon. An anesthesiologist is present and the patient remains under general anesthesia for the duration of the procedure.
The PCT procedural protocol includes placing a Percryo 17 or Percryo 24 (1.7 mm or 2.4 mm diameter) cryoablation probe (Endocare Cryocare CS, Irvine, CA, USA) into the targeted lesion under CT guidance (see Figure 1). When the probe is in the optimal position as confirmed by CT imaging the ablation is performed (see Figure 2). The standard protocol used for all procedures is a ten minute active freeze cycle with typical temperatures of −160 degrees Celsius, an eight minute “stick” cycle which is an inactive freeze cycle with typical temperatures of −10 degrees Celsius to be followed by a final ten minute active freeze cycle.
The cryoprobe uses high-pressure argon and helium gas for freezing and thawing, respectively, on the basis of the Joule-Thomson principle. During the active freeze cycle argon enters the distal aspect of the probe and passes through a valve. This results in rapid change in the temperature. Close to the probe there is intracellular ice formation. During the 10 minute freeze cycle re-crystallization occurs, which causes super-cooling of the intra-cellular cytoplasm and results in cell death by destruction of the intra-cellular structures. Several millimeters away from the tip of the probe there is a more gradual cooling of the tissues which results in extracellular ice formation. This results in an osmotic gradation and intra-cellular dehydration. During the active warming cycle, when helium is introduced to the tip of the probe there is heating of the probe to +40 degrees C. This results in shifts of fluid into the cell and cellular lysis.
At the cellular level, the fast freezing cycle creates ice crystals inside and outside the cells. During the fast thawing phase, helium gas is introduced and cracks the lethal ice. As a result, the cell mitochondria disappear, and the membranes are split causing cell death. PCT also causes transcellular electrolytes and osmotic pressure imbalance furthering local cell destruction.
Figure 1. Percutaneous cryoprobe creating an ice ball. Probe manufactured by Endocare Cryocare CS, Irvine, CA, USA.
Figure 2. Image of thoracic cavity with cryoprobes inserted under CT guidance. (a) Lung lesion; (b) Cryoprobe inserted into lesion.
Air in the lung can interfere with the creation of the ice ball. Positioning of the probe into the lesion is critical for the freezing process as the air in the lung will act as an insulator, thus limiting the extent of the freeze. Cellular reperfusion injury, which takes place during the thawing phase may also account for more tumor tissue destruction and necrosis [12].
3. Anesthesia Management
The anesthetic management of a patient presenting for PCT is similar to the common guidelines and principles applied for patients undergoing a surgical procedure. Understanding of the patient’s basic pathology, comorbidities, their expected impact on the anesthesia care, and the procedure itself is essential for patient safety. All patients at our institution visit Pre-Anesthesia Testing prior to the procedure. A comprehensive medical history and physical assessments are obtained, with specific attention to coexisting illness and cardiopulmonary reserve. Required laboratory evaluations include: electrocardiogram, chest X-ray, and laboratory tests, including complete blood cell count and chemistry profile. If additional information is needed, it is ordered at this time. At this visit, the patient is counseled regarding the anesthesia risk, fasting guidelines, and anticipated anesthetic technique.
In our institution, almost all of our patients are admitted on the same day of the procedure. After placement of a peripheral intravenous line, premedication in the form of intravenous midazolam is typically given. Attention should be directed towards the patient’s pulmonary status and the potential risk for airway obstruction and hypoventilation. The patient is brought to the interventional radiology suite and positioned on a stretcher. Monitoring includes standard ASA monitors: ECG, pulse oximeter, noninvasive automated blood pressure cuff, temperature probe and capnography.
General anesthesia induction with endotracheal intubation is performed prior to the final positioning on the CT imaging bed. The method of securing an airway in this patient population requires multiple considerations. In special circumstances such as when difficult intubation or lung separation is indicated, it is essential to coordinate availability of advanced airway equipment and support as most of these procedures are taking place at a remote location in the hospital. At the discretion of the anesthesiologist additional access lines and monitors may include extra-large bore intravenous access, invasive arterial blood pressure monitoring, and central venous pressure monitoring.
Patient positioning is an important part of PCT cases. Depending on the target area of the lesion, patients may be positioned prone, supine, or laterally. Attention should be directed towards the fall risk as the radiology suite’s procedure beds are generally narrower than the standard operative beds increasing the risk for fall injuries. It is important to protect the patient’s body, specifically the upper extremities, from potential injury caused by the scanner bore while the bed is moving the patient in and out of position. Greater emphasis on this particular consideration should be given for obese patients with a BMI greater than 40. Appropriate padding and support should be available for positioning patients in the prone or lateral position (see Figure 3).
Anesthesia maintenance can be achieved using a balanced technique combining volatile agents, muscle relaxants, and narcotic analgesics. Volatile agents such as sevoflurane or desflurane have a relatively fast onset and offset, function as bronchodilators, and allow for better hemodynamic control appropriate for this type of procedure. Short or intermediate-acting muscle relaxants (e.g. rocuronium, vecuronium) are appropriate to facilitate patient positioning and mechanical ventilation. Narcotics should be carefully administered maintaining a balance between appropriate analgesia management and the risk for post-procedure hypoventilation.
Due to the minimally invasive nature of this procedure, the expected heat loss is minor. Some heat loss is expected due to vasodilation caused by anesthetics and exposure to cool room air. The risk of hypothermia is minimized by the short duration of anesthesia for the PCT procedure. Furthermore, there is no documentation regarding major heat loss from the cryoprobe during the procedure. Active warming devices, such as convective heating blankets, warm IV fluids, or circuit moisture devices, are not used routinely but may be considered for cases longer in duration. Use of a convective heating system presents a potential concern while moving the bed into the scanner bore.
Figure 3. Patient positioned prone for PCT.
4. Post-Procedure Phase
Immediate post-operative complications are strongly related to intraoperative airway thermo-trauma and bleeding. After meeting standard extubation criteria, ETT and lower airway suctioning followed by early extubation in the procedure room is strongly recommended. More extensive procedures may result in a more complicated clinical course in the immediate post-procedure period, such as PTX, severe hemoptysis, and severe airway irritation. These complications may require temporary ventilatory support (typically < 6 hours) and insertion of a chest tube. All patients typically recover in the main post anesthesia care unit (PACU). Regardless of the intraoperative course, these patients should be provided with intensive postoperative follow up due to the inconsistent nature of post-procedural complications associated with PCT. Acute post-procedural pain is expected from the probe insertion site and chest tube placement. Almost all patients will require pain management in the form of narcotics. The anesthesiologist should be aware of the high risk for post-procedure hypoventilation associated with narcotic use. Most patients will require 24 hours admission post-procedurally for pain management and monitoring for PTX.
5. Our Experience
Our retrospective review included 53 patients with lung cancer who underwent 69 PCT treatments under anesthesia at Stony Brook University Hospital between January 2006 and January 2011. These patients are substantially the same cohort previously reported on by Zemlyak, Moore & Bilfinger (2010) [4]. All these patients met at least one major or two minor criteria of the American College of Surgeons Oncology Group (ACOSOG) for inoperability (www.acosog.org) and had been reviewed by a tumor board. After obtaining IRB approval, we extracted information from the electronic medical records and reviewed anesthesia records. The following data were recorded: gender, age, ASA status, co-morbidities, medications, diagnosis, treatment area, positioning, use of invasive monitoring, airway management, complications, fluid management, anesthetic technique, and length of stay.
The patients’ mean age at time of treatment was 69 years, 58% of patients were female, 75.4% of patients were ASA III and the remainder were ASA IV. The majority of the patients were diagnosed with non-small cell lung cancer, with 24.6% of patients having metastases at the time of treatment (Table 1).
Table 2 gives the information on the anesthetic management of our cases. Advanced airway techniques were utilized in 10% of cases. These techniques included a Bougie guide, fiberoptic guided intubation, and retrograde bronchoscopy; a double lumen endotracheal tube was used in two cases. In our population patients were positioned for the procedure most often in the lateral position, followed by the supine and prone positions. Cen-