I would like to thank Dr. Shankar for his response regarding my concerns about ultrasound-guided regional anesthesia and for clarifying some of the ultrasound parameters. However, my main reason for writing was that we do not understand the interaction of ultrasound and local anesthetics. No literature exists, that I could locate, addressing the combination effects that have the potential to be significant. The literature also does not support a reduced nerve injury rate when ultrasound guidance is used. In the cases of nerve injury unrelated to positioning, especially pan-plexopathies, when the needle tip was visualized away from the nerve during injection, something other than direct trauma must be playing a role, and assumptions that direct trauma, nerve ischemia, or injection trauma were primarily responsible may be too simplistic.

As I pointed out in my original letter, ultrasound is demonstratively cytotoxic in vitro  at intensities used for regional anesthesia, and comparison dosimetry with ionizing radiation has been performed.1,2Also, local anesthetics have long been known to be neurotoxic above critical concentrations. Furthermore, the mechanisms of toxicity are different for the two agents. Although both ultrasound and ionizing radiation work primarily by free radical formation, activation of the mitogen-induced protein kinase system is likely responsible for local anesthetic neurotoxicity.3The mechanism for an ultrasound-related nerve injury may be the formation of hydrogen peroxide from hydroxyl ion and subsequent membrane lipid peroxidation.4This may be offset by the observation that local anesthetics have been shown capable of free radical scavenging, especially hydroxyl ions.5The observations suggest that the combination may actually protect from any ultrasound-related toxicity. If another ultrasound neurotoxic effect is at play, the combination of the two agents may have additive or even synergistic effects. We simply do not know. When a chemotherapeutic agent, that is, cisplatin or methotrexate, is added to the mix, the effects on neurotoxicity may be dramatic.6,7 

Regarding the references given by Dr. Shankar and myself to other neurologic effects in animals and humans, I do not read the literature as showing decades of animal research demonstrating clear safety. Rather, there seems to be a fair amount of noise in the literature with some compelling data showing adverse effects on fetal neuronal migration, opening of the blood brain barrier, and adult locomotor abnormalities in mice exposed in utero  to diagnostic ultrasound levels.8–10The study he quotes in humans has a problem in that the control group also received antenatal ultrasound.11The mouse locomotor study indicates that any exposure in utero  may be significant, suggesting that only a control group with no history of ultrasound exposure would be suitable—a very difficult study to arrange today.

I appreciate the observations of Drs. Gray and Drasner regarding the bioeffects of ultrasound, including the ability of high-intensity ultrasound to promote nerve regeneration. I remain unsure how to relate the Food and Drug Administration imposed limit of 720 mW/cm2for diagnostic imaging to the Ipa.3@MImaxratings listed in the M-Turbo manual that are well into the hundreds of Watts per square centimeters range.12 

I am pleased that Drs. Gray and Drasner agree that more work is needed to address the interactions between ultrasound and local anesthetics. In referencing Orebaugh et al.  13regarding complication rates, I am reminded of the question of who was performing the block. I suspect these data come from resident-performed regional anesthesia, and if so, likely reflect the steep learning curve for safely performing blocks with anatomic landmarks and nerve stimulation as the only guide. It is very clear that ultrasound shortens the steep learning curve substantially but at the steep price of making practitioners ultrasound dependent.

St. James Healthcare, Butte, Montana. pcory@littleappletech.com

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