Irreversible electroporation (IRE) is an emerging non-thermal ablative technique with recent studies demonstrating its efficacy in destroying solid organ malignancies (Figure). The principle underlying IRE is applying sufficient electrical pulses to permanently increase cell membrane permeability. Subsequent formation of pores allows ionic and molecular transport into and out of the cell. Variables such as electric field, number of pulses, pulse duration and pulse interval affect the degree of disruption to the cell membrane, with multiple studies outlining the ideal parameters for specific cancer models, as efficacy depends on the size, shape, and electric charge of the cell. Increased permeability of the cell leads to an influx of Ca2+ and Na+ and efflux of K+ and ATP; the high concentration of intracellular Ca2+ leads to cell necrosis or apoptosis.

Figure:

Three IRE Electrodes Placed Percutaneously Under CT Guidance

Figure:

Three IRE Electrodes Placed Percutaneously Under CT Guidance

As a non-thermal ablation method, it is differentiated from other ablation techniques such as microwave ablation or radiofrequency ablation by the decreased risk of damage to surrounding structures such as blood vessels, bile ducts, and bowel. Two examples where IRE has shown efficacy include the treatment of inoperable hepatocellular carcinoma and locally advanced pancreatic cancer.

IRE is primarily performed via the percutaneous approach in the CT suite by interventional radiologists. The importance of open and effective communication between the interventional radiologist and anesthesiologist cannot be overemphasized. For liver or lung ablation requiring artificial pneumothorax and one lung ventilation, communication and optimal preparation are vital. Communication before each pulse stimulation to ensure adequate time for a bolus of opioid or muscle relaxant to exert their effects is also needed.

Preprocedure considerations

  1. In addition to a focused history and physical examination that would otherwise be standard for any general anesthetic, special attention must be given to a history of cardiac arrhythmias, implanted pacemakers or ICDs, and the use of antiarrhythmic drugs. Since IRE uses a direct current to apply an external electric field to the ablation site, this technique is proarrhythmic, and patients with known arrhythmias are likely at higher risk. Hence it is a relative contraindication.

  2. Patients with congestive heart failure or coronary artery disease may be at increased risk for acute exacerbation because of their limited reserve to handle intraoperative arrhythmias and bouts of hypertension.

  3. A history of seizures is a contraindication listed by the IRE manufacturer, as electrical discharge at the catheter tip can theoretically trigger seizure activity. However, a recent study showed the absence of seizures or any evidence of reactive cerebral response to IRE stimulation on EEG (Br J Anaesth 2014;113:985-92).

  4. Metal near the tumor site is an absolute contraindication as it can cause significant deflection of energy, resulting in incomplete ablation and higher risk of thermal injury. This is especially relevant for biliary stents placed for pancreatic head cancers, and these should be removed or replaced with a plastic stent prior to IRE.

Intraprocedure considerations

Martin et al. (Anesth Pain Med 2015;5:e22786) recommended general anesthesia with two large-bore peripheral I.V.s and arterial catheterization as well as epidural analgesia combined with remifentanil infusion. Of note, their study examined all IRE approaches: open, laparoscopic, and percutaneous. For open procedures, thoracic epidural is offered as it provides superior analgesia and minimizes opioids and their undesired side effects.

In our practice, we typically secure one peripheral I.V. and monitor blood pressure via a non-invasive cuff; defibrillator pads should also be placed on the patient as a precautionary measure. We use general anesthesia and manage blood pressure spikes using remifentanil infusion. IRE pulses may induce hypertension despite adequate depth of anesthesia; analgesics have been shown to be superior to antihypertensive drugs for treatment (Anesth Pain Med 2015;5:e22786). Deep neuromuscular blockade to achieve a train-of-four (TOF) ratio of 0 is recommended because IRE stimulation results in local muscle contractions and involuntary movements, particularly if the patient is not deeply anesthetized. Both can compromise the accuracy of ablation on the target and exacerbate needle trauma with potential surgical complication.

Considerations specific to IRE are related to the episodes of electrical discharge at the catheter tip. To minimize the incidence of arrhythmias, these procedures are performed with cardiac synchronization and thus require that an accurately placed five-lead ECG is connected to the IRE control unit. This allows for IRE pulses to synchronize with the refractory period and avoid the R-on-T phenomenon known to trigger arrhythmias.

Postprocedure considerations

Recovery of patients after IRE can be straightforward and swift after a percutaneous approach. IREs done with laparotomy can have a lengthier recovery, mostly related to pain control.

Potential complications

  1. Arrhythmias: The most common complication intraoperatively is IRE-induced arrhythmia. Cardiac synchronization during intra-abdominal solid tumor IRE greatly decreased incidence of arrhythmias, from 22% to 1.2% (J Surg Oncol 2020;122:407-11). It was shown that without synchronized pulsing, occasional ventricular tachycardia can be triggered, whereas only atrial arrhythmias were seen with synchronized pulsing.

  2. Hypertension: IRE-induced hypertension can have adverse effects in patients with limited cardiopulmonary reserve, but it is transient and easily treated.

  3. Muscle contractions: IRE causes severe reflex contractions, but the use of deep neuromuscular blockade has ameliorated this concern. With a TOF ratio of 0, generalized skeletal muscle contractions are fully blunted, but mild localized contractions can still be seen, especially if electrodes pass through large musculature (Br J Anaesth 2014;113:985-92). Even so, dislocation of electrodes and subsequent overt injury of nearby structures have not been reported.

  4. Tissue trauma around the local site

    • Hepatobiliary cancer: Transient elevation in liver function tests is common. Biliary and portal vein injury can occur but is rare, according to a systematic review documenting such complications in three out of 221 patients (J Vasc Interv Radiol 2014;25:997-1011). In a study of percutaneous IRE of hepatic tumors, post-ablation CT imaging revealed an 8% incidence of abscess formation, likely related to the presence of a bilioenteric anastomosis in these patients (J Vasc Interv Radiol 2016;27:480-6).

    • Pancreatic cancer: One study noted a 4% rate of complications after 90-day follow-up, including pancreatitis or pancreatic failure. However, these only occurred in patients who underwent a combination of surgical resection and IRE. Risks of pancreatic fistula and abscess secondary to percutaneous IRE occurred 1% of the time. By contrast, these complications occurred in 12% of thermal ablations (Br J Surg 2010;97:220-5).

  5. Other complications: Pneumothorax, intraperitoneal hemorrhage, and self-contained hematomas have also been documented (Br J Anaesth 2014;113:985-92; J Vasc Interv Radiol 2016;27:480-6).

IRE is an ablative technique with an effective regional tissue damage profile and proven efficacy, especially in solid hepatobiliary tumors. Arrhythmias, hypertension, and muscle contractions induced by IRE pulses are important considerations for the anesthesiologist. As with other percutaneous ablative procedures, postoperative complications related to local injury have been reported but are not common. Based on our experience at Brigham and Women's Hospital, most IREs are performed percutaneously under CT-guidance and may be managed with a standard general endotracheal anesthetic, cardiac cycle synchronization, and muscle relaxation.

Ken Lee, MD, Resident, Brigham and Women's Hospital, Boston.

Ken Lee, MD, Resident, Brigham and Women's Hospital, Boston.

Darshan Vora, MD, Resident Physician in Interventional Radiology, Brigham and Women's Hospital, Boston.

Darshan Vora, MD, Resident Physician in Interventional Radiology, Brigham and Women's Hospital, Boston.

Paul B. Shyn, MD, Associate Professor of Radiology, Harvard Medical School, Boston.

Paul B. Shyn, MD, Associate Professor of Radiology, Harvard Medical School, Boston.

Lalitha Sundararaman, MD, Clinical Instructor, Department of Anesthesiology and Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.

Lalitha Sundararaman, MD, Clinical Instructor, Department of Anesthesiology and Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.