Mechanism of action





Introduction


Radiofrequency ablation (RFA) is a unique modality used to treat many different conditions in a variety of clinical scenarios. The principles of RFA were first described in 1891 by French physician and physicist Jacques-Arsene D’Arsonval (1851–1940). His research included work on alternating currents and their physiological effects. He demonstrated, among other things, that alternating currents with a frequency greater than 5000 Hz do not cause muscular contractions or nerve stimulation, unlike other electric shocks applied to neuromuscular tissues. This constituted the beginning of the field of electrotherapy and later the development of therapeutic diathermy. By the early 1900s, applications of radiofrequency (RF) waves included treatment of bladder neoplasms using cauterization through a cystoscope and the use of oscillatory desiccation in the treatment of malignant tumors accessible for minor surgical procedures. , Perhaps the most well-known application of RF from the early 20th century is the Bovie knife, which was introduced in 1928 by William T. Bovie (1882–1958) and Harvey Cushing (1869–1939). Bovie was an American scientist and inventor, and Cushing is frequently cited as the father of modern neurosurgery. The first-generation Bovie knife was a monopolar electrode similar to modern electrodes used for percutaneous RF techniques. The device produces an alternating current from a small knife-like electrode and a large grounding pad. Continuous current produces the cutting effect of the Bovie knife, while cauterization is an effect of a pulsed or damped current.


In 1931, a German surgeon, Martin Kirschner (1879–1942), was investigating a novel treatment for trigeminal neuralgia utilizing a head frame and thermocoagulation of the gasserian ganglion. This is perhaps the first application of RFA for the treatment of chronic pain as well as the first stereotactic surgery performed in humans. Kirschner’s body of work was expanded upon by B.J. Cosman, S. Aronow, and O.A. Wyss in the 1950s and 1960s, eventually leading to the first commercial availability of RFA machines.


Mechanism of action


Radiofrequency waves are part of the electromagnetic (EM) spectrum and range in frequencies from 3 Hz to 300 GHz, with further subdivisions ranging from extremely low frequency to extremely high frequency. RF waves in the human body can generate heat. The amount of heat generated by RF waves depends on the duration of the radiation, the frequencies used (which correspond to energy of the waves), the shape of the RF emitting device, and the constitution of the surrounding tissue. For example, the small size of typical modern RF probes creates a high degree of energy flux at the site of the probe. Conversely, the grounding pad used in modern RF procedures has a large surface area exposed to tissue, leading to a small amount of energy flux across the adjacent tissue, and thus there is typically no burning at the site of the grounding pad. This circuit ( Fig. 2.1 ), from probe tip to grounding pad, is essential to a functional RFA.




Fig. 2.1


Schematic diagram of the RF circuit. Note the difference in flux, or line density, at the needle tip compared to the grounding pad.

(From: Hong K, Georgiades C. Radiofrequency ablation: Mechanism of action and devices. J Vasc Interv Radiol . 2010;21(suppl 8). doi:10.1016/j.jvir.2010.04.008 )


In general all RFA systems are designed to impart a necrotic effect on the local tissue at the site of the probe. This process begins with the molecules, predominantly water, directly adjacent to the probe. The EM field, with a focal point at the tip of the probe, causes nearby water molecules to orient in the direction of the field. As the field’s orientation is flipped rapidly, the molecules vibrate. Friction between adjacent vibrating molecules results in heat and ultimately an increase in local temperature. An important point is that the probe itself does not become hot or generate heat.


As the temperature approaches 50˚C, human tissue burns rapidly. Tissue death in mammals occurs in 2 seconds at 55˚C, whereas at 100˚C tissue death is instantaneous and results in charring of tissue adjacent to the electrode tip. The longer the duration of the RF ablation, the larger the volume of the burnt tissue. As demonstrated in Figs. 2.2 and 2.3 , both temperature and duration of the ablation are important considerations when performing an RFA procedure.




Fig. 2.2


Representation of the ablation size in relation to temperature and timing.

(From: Hong K, Georgiades C. Radiofrequency ablation: Mechanism of action and devices. J Vasc Interv Radiol . 2010;21(suppl 8). doi:10.1016/j.jvir.2010.04.008 )



Fig. 2.3


Effects of ablation size and temperature on biological tissue. From: Zhang B, Moser MAJ, Zhang EM, Luo Y, Liu C, Zhang W. A review of radiofrequency ablation: Large target tissue necrosis and mathematical modelling. Physica Medica . 2016;32(8):961-971. doi:10.1016/j.ejmp.2016.07.092 .

(Adapted from Chu KF, Dupuy DE. Thermal ablation of tumours: Biological mechanisms and advances in therapy. Nat Rev Cancer . 2014;14:199-208.)


Modern continuous RF devices apply energy at a frequency of 0.1–1 MHz to produce an RF heat lesion. Sensory stimulation at 50 Hz at less than 0.5 V is utilized to produce pain or paresthesia in the area involved. Motor stimulation, usually at 2 Hz, is utilized to ensure proper placement and to avoid lesioning of motor nerves. The RFA lesion is then maintained at a temperature of 60–90˚C for 60–90 seconds.


One of the limitations of traditional RFA is the radius of the ablation. Larger ablations using traditional RFA require either longer duration of applied RF energy or higher amounts of energy, both of which cause increasing impedance in the core of the ablation, thereby limiting their feasibility. Larger ablations are possible using probes perfused with liquid that circulates to cool the tissue at the core of the ablation ( Fig. 2.4 ). This is termed cooled RFA . For example, in one 2017 study of ex vivo bovine livers, the mean dimensions of cooled RFA ablations (5.5 cm × 5.3 cm) were significantly larger than ablations achieved using traditional RFA (3.6 cm × 2.7 cm). These lesions are composed of cooled tissue adjacent to the electrode, followed by isotherms of increasing tissue temperature surrounded by lower-temperature isotherms. The active lesion size depends on the size of the probe, electrode temperature, and duration of current applied like continuous RFA. Cooled RFA was originally used in cardiac electrophysiology and tumor ablation; its use in pain management is more recent.




Fig. 2.4


Diagram of the catheter tip in a cooled RFA device. Blue arrows indicate the direction of moving fluid. This technique is similar to continuous RFA where the thermal lesion is created by the electrode near the target tissue; however, a multichannel electrode is actively cooled by the continuous flow of liquid.

(From: Zhang B, Moser MAJ, Zhang EM, Luo Y, Liu C, Zhang W. A review of radiofrequency ablation: Large target tissue necrosis and mathematical modelling. Physica Medica . 2016;32(8), 961–971. doi: 10.1016/j.ejmp.2016.07.092 )


In contrast to traditional and cooled RFA, pulsed radiofrequency ablation (PRF) catheter tips heat adjacent tissue to temperatures at or below 42˚C. The mechanism by which PRF achieves pain relief is still being elucidated. One possible mechanism is similar to that of traditional RF, that is in causing a destructive lesion. One 2009 study demonstrated via electron microscopy that PRF causes microscopic lesions, which may preferentially affect the small pain-related peripheral nerve fibers—the A-delta and C fibers. Another study showed that PRF stimulates noradrenergic and serotonergic descending pain inhibitory fibers and inhibits excitatory nociception. Similarly, Vallejo et al. demonstrated a reduction of multiple cytokines after PRF (tumor necrosis factor-alpha and interleukin-6). Finally, another proposed mechanism is the downregulation of microglial activity in the dorsal horn of the spinal cord (particularly after PRF of the dorsal root ganglia).


PRF signals have pulse durations ranging from 10 to 30 ms and pulse repetition rates ranging from 1 to 8 Hz. As in traditional RFA, lesions to nerve tissue are applied by transmission of a high-voltage current through a thermocouple probe. Currents are cycled for 20 ms, at 2 Hz, for 120 s. The voltage is controlled so that the highest temperature remains below 42˚C.


RFA machines


Machine history


The original machines of Cosman, Aronow, and Wyss used continuous wave RF power sources in the 0.1–1 MHz frequency to produce the RF heat lesions. Since then, several variables have been modified to optimize the burn, for instance, the electrode tip shape/diameter, exposed tip length, temperature of the burn, and duration of the burn. As these factors are modified, unique burn patterns result ( Fig. 2.5 ). ,


Aug 6, 2023 | Posted by in ANESTHESIA | Comments Off on Mechanism of action

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