Local Anesthetic Systemic Toxicity

Abstract

Archimedes would have been frustrated as a clinical scientist. Eureka moments in this business are rare: Few of us find the answer to our question when water overflows the bathtub after we gain a few extra pounds, and, contrary to Isaac Newton, we seldom discover grand theories when an apple falls on our head. By and large, progress in the clinical sciences is a slow, plodding extension of the work performed by others before us. And so it is with the outstanding work published in this issue of Regional Anesthesia and Pain Medicine by Australian anesthesiologist Michael Barrington and statistician Roman Kluger. 1 Based on their efforts, we now have expanded our knowledge regarding the role of ultrasound guidance in reducing the risk of local anesthetic systemic toxicity (LAST). Barrington and Kluger’s laudable contribution builds upon previous work (some their own) to slowly but surely further our understanding of LAST prevention; their efforts should incrementally improve patient safety. Yet complete avoidance of LAST must await another day and further evolution of knowledge. Until then we remain at a familiar crossroads—ultrasound guidance improves selected portions of our practice but does not completely eliminate complications. Thus, one would be ill- advised to place total faith in this remarkable instrument of nerve localization at the risk of ignoring other principles of LAST prevention. 2 There is every reason to expect that ultrasound guidance might reduce the incidence of LAST; it allows us to see and hopefully avoid vascular structures, to note the unexpected absence of local anesthetic spread at the moment of injection, and to confidently inject smaller volumes, which should attenuate the effects of both direct intravascular injection and delayed tissue uptake by limiting total local anesthetic dose. Confirmation of these touted benefits has been realized in a remarkably short period of time. In 2009, Abrahams and colleagues 3 published a meta-analysis in which ultrasound guidance was clearly linked to a reduction of unintended vascular punctures during performance of peripheral nerve blocks. Unfortunately, it remained uncertain whether reduction in the surrogate outcome of vascular puncture correlated with likewise reduction in the true outcome of actual LAST—as might be defined by fewer episodes of subjective central nervous system excitatory changes coincident with wayward local anesthetic administration or, more significantly, by reduction in major central nervous system toxicity (seizures) and/or cardiac arrest. 4 On the heels of this meta-analysis, 2 clinical reports that same year described conflicting results. Barrington et al, 5 in a preliminary report from the same clinical registry used to generate their current study, found no difference in the rate of seizure (overall 95% confidence interval [CI], 0.42:1000–1.9:1000) in more than 7000 peripheral nerve blocks as a function of ultrasound guidance or peripheral nerve stimulation (PNS). In a somewhat smaller quality assurance study, Orebaugh and colleagues 6 reported fewer seizures associated with upper-extremity blocks performed using PNS alone versus ultrasound guidance with or without adjunctive PNS (P = 0.044), but they found no statistical difference if all blocks were included. Subsequent case reports of LAST occurring despite the use of ultrasound continued to surface and the American Society of Regional Anesthesia and Pain Medicine’s 2010 evidence-based analysis of ultrasound-guided regional anesthesia therefore concluded that the effect of ultrasound guidance on reducing LASTwas essentially too close to call. 7 Then in late 2012, 2 major studies demonstrated that ultrasound guidance might meaningfully affect the incidence of LAST. The Dartmouth Registry reported by Sites and colleagues 8 noted only 1 LAST event in 12,668 ultrasound-guided blocks (95% CI, 0.0:1000–0.4:1000). Shortly thereafter, Orebaugh et al 9 in a further iteration of the University of Pittsburgh’s quality assurance work, reported their 6-year frequency of LAST as 6 per 5436 using landmark-PNS localization versus 0 per 9238 using ultrasoundPNS (P = 0.006). Slowly but surely, emerging data have proven that ultrasound guidance reduces the rate of not only unintended vascular puncture, but LAST events as well—that is, ultrasound-guidance affects the true outcome.