Kenneth R. Thomson

Irreversible Electroporation: A New Challenge in "Out of Operating Theater" Anesthesia

BACKGROUND: Bioelectrics, an interesting new area of medicine, combines pulsed high-voltage engineering with cell biology and has many potential applications. Pulsed electric current can be used to produce irreversible electroporation (IRE) of cell membranes with resulting cell death. This process has been shown to ablate tumors in animal studies. METHODS: A clinical trial of IRE as a tumor ablation therapy was performed at our institution. A pulsating direct current of 20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors in the liver, kidney, or lung via needle electrodes inserted under computed tomography (CT) or ultrasound guidance. Patients required a relaxant general anesthetic. We describe some challenges presented to anesthesiologists. Guidelines for anesthesia were produced and modified as issues became apparent. The patients charts were audited throughout. RESULTS: We noted a number of issues. The electrical discharge produced generalized upper body muscular contractions requiring neuromuscular blockade. Two patients developed positional neuropraxia because of the extended arm position requested for CT scanning. After experimentation, we have developed a modified arm position. Some patients developed self-limiting ventricular tachycardias that are now minimized by using an electrocardiogram synchronizer. Three patients developed pneumothoraces as a result of the needle electrode insertion. CONCLUSIONS: Relaxant general anesthesia is required for IRE of the liver, lung, and kidney. An electrocardiogram synchronizer should be used to minimize the risk of arrhythmias. Attention to the position of the arms is required to maximize CT scan quality but minimize brachial plexus strain. Simple postoperative analgesia is all that is required in most patients.

In Vivo Irreversible Electroporation Kidney Ablation: Experimentally Correlated Numerical Models

Irreversible electroporation (IRE) ablation uses brief electric pulses to kill a volume of tissue without damaging the structures contraindicated for surgical resection or thermal ablation, including blood vessels and ureters. IRE offers a targeted nephron-sparing approach for treating kidney tumors, but the relevant organ-specific electrical properties and cellular susceptibility to IRE electric pulses remain to be characterized. Here, a pulse protocol of 100 electric pulses, each 100 μs long, is delivered at 1 pulse/s to canine kidneys at three different voltage-to-distance ratios while measuring intrapulse current, completed 6 h before humane euthanasia. Numerical models were correlated with lesions and electrical measurements to determine electrical conductivity behavior and lethal electric field threshold. Three methods for modeling tissue response to the pulses were investigated (static, linear dynamic, and asymmetrical sigmoid dynamic), where the asymmetrical sigmoid dynamic conductivity function most accurately and precisely matched lesion dimensions, with a lethal electric field threshold of 575 ± 67 V/cm for the protocols used. The linear dynamic model also attains accurate predictions with a simpler function. These findings can aid renal IRE treatment planning under varying electrode geometries and pulse strengths. Histology showed a wholly necrotic core lesion at the highest electric fields, surrounded by a transitional perimeter of differential tissue viability dependent on renal structure.

A Positive Response to a Recruitment Maneuver With PEEP Titration in Patients With ARDS, Regardless of Transient Oxygen Desaturation During the Maneuver:

Recruitment maneuvers (RMs) can expand collapsed alveoli in ventilated patients. The optimal method for delivering RMs is unknown. Purpose: To evaluate the safety and the respiratory and hemodynamic effects of a staircase recruitment maneuver (SRM) with decremental positive end expiratory pressure (PEEP) titration and the consequences of desaturation during the SRM in patients with early acute lung injury (ALI). Methods: In total, 20 consecutive patients with early ALI were enrolled and received an SRM. Patients were given 15 ± 3 cm H2O pressure-controlled ventilation. Positive end expiratory pressure was increased from baseline (range 10-18) to 20, 30, and 40 cm H2O every 2 minutes to achieve maximum alveolar pressure of 55 ± 3 cm H2O, then decreased at 3-minute intervals to 25, 22.5, 20, 17.5, and 15 cm H2O until a decrease of 1% to 2% oxygen saturation from maximum was detected. Positive end expiratory pressure was left at the level where the fall in oxygen saturation occurred. Standard respiratory and circulatory variables, arterial and central venous gases were measured before, during, and after the SRM. Results: There were significant improvements in shunt fraction (36.3% ± 10% to 26.4% ± 14%, P < .001), oxygen saturation (93.4% ± 2% to 96.8% ± 3%, P = .007), partial pressure of oxygen, arterial (PaO2)/fraction of inspired oxygen ([FIO2]; 150 ± 42 to 227 ± 100, P = .004), lung compliance (33.9 ± 9.1 to 40.1 ± 11.4 mL/cm H2O, P < .01), and chest x-ray (CXR) after the SRM. Briefly, 80% of the patients responded and the response was maintained at 1 hour. In total, 8 patients desaturated 6.1% ± 2.8% in SaO2 during the SRM but 5 of those improved SaO2 relative to baseline by the end of the SRM. Conclusions: In all, 80% of the patients with early ALI responded to the SRM with decremental PEEP titration. Desaturation during the SRM did not indicate a failed response 1 hour later.

Initial experience in 115 patients with the retrievable Cook Celect vena cava filter

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97u2003years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9u2003days (range 14–267u2003days). Failed retrievals were due to a thrombosed vena cava (nu2003=u20031) and endothelialisation of the filter (nu2003=u20033). In the failed retrieval group the mean implantation time was 142u2003days (range 78–211u2003days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14–267u2003days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow‐up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

Retrievable Gunther Tulip inferior vena cava filter: Experience in 317 patients

The aim of our study was to assess our experience with the retrievable Gunther Tulip (GT) inferior vena cava (IVC) filter, with regard to its insertion, efficacy, ease of placement and retrieval, and associated complications. Between November 2001 and October 2005, 322 GT filters were placed in 317 patients. Insertion indications included the following: pulmonary embolus (PE) prophylaxis in trauma patients (nu2003=u2003232), PE prophylaxis in perioperative patients (nu2003=u200327), PE prophylaxis in moribund intensive care unit patients (nu2003=u200322), recent PE (nu2003=u200348), extensive deep venous thrombosis (nu2003=u200366), contraindication to anticoagulation (nu2003=u200363), anticoagulation complication (nu2003=u20038) and deep venous thrombosis with failed anticoagulation (nu2003=u20038). Some patients had more than one indication for caval filter placement. Two hundred and five attempted retrievals have been carried out, with 15 failures. Our successful retrieval rate is 92%. Nineteen filters were originally inserted permanently. There have been three minor complications associated with insertion and five with retrieval. The mean time from filter insertion to attempted retrieval was 76.95u2003days. The ideal filter implantation time gives the patient the benefit of PE protection, while avoiding the long‐term risks associated with caval filters. Although GT retrieval times have lengthened considerably, our data suggest that this is at the expense of successful retrieval rates.

Human Experience with Irreversible Electroporation

Considering the remarkable opportunities and safety profile demonstrated in the animal studies using irreversible electroporation, it would seem intuitive that this method would provide a safer, more effective and more widely applicable treatment for solid tumours in humans.

Catheter-Directed Thrombolysis of Lower Limb Thrombosis

Late complications of thrombosis of the deep veins in the region between the popliteal vein termination and the confluence of the common iliac veins and inferior vena cava (suprapopliteal deep-vein thrombosis) are common and often unrecognized by those responsible for the initial management. Pharmacomechanical-assisted clearance of the thrombus at the time of first presentation provides the best opportunity for complete recovery with preservation of normal venous valve function and avoidance of recurrent deep-vein thrombosis and postthrombotic syndrome. Recent interventional radiology methods provide for rapid and complete thrombolysis even in some patients in whom thrombolysis was previously considered contraindicated. This review describes the methods, safety, and efficacy of acute interventional treatment of suprapopliteal deep-vein thrombosis.

Transjugular liver biopsy is a safe and effective intervention to guide management for patients with a congenital bleeding disorder infected with hepatitis C

Abstract

The Effects of Metallic Implants on Electroporation Therapies: Feasibility of Irreversible Electroporation for Brachytherapy Salvage

AbstractPurposenElectroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments.Materials and MethodsThis study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions werexa0examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions.ResultsThere was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all pxa0>xa00.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all pxa0>xa00.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins.ConclusionThis study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

Radiation exposure and the justification of computed tomography scanning in an Australian hospital emergency department.

In an emergency department (ED), computed tomography (CT) is particularly beneficial in the investigation of high‐speed trauma patients. With the advent of multidetector CT (MDCT) scanners, it is becoming faster and easier to conduct scans. In recent years, this has become evident with an increasing number of CT requests. Patients who have multiple CT scans during their hospital stay can receive radiation doses that have an increased theoretical risk of induction of cancer. It is essential that the clinical justification for each CT scan be considered on an individual basis and that due consideration is given to the radiation risk and possible diagnostic benefit. The current lack of a central State or Commonwealth data repository for medical images is a contributing factor to excessive radiation dosage to the population. The principles of justification and radiation risks are discussed in this study.