Dose-Finding Methodology for Peripheral Nerve Blocks

Abstract

Dose-finding studies enable the successful conduct of peripheral nerve blocks by ensuring the administration of appropriate doses of local anesthetic. However, the optimal dose-finding methodology remains ambiguous. In this research methodology article, we set out to review the basic aspects pertaining to dose-response curves (graded vs quantal), the pharmacodynamic indices required by dose-finding studies, the properties of different dose-finding methods (sigmoidal dose-response curve analysis, Dixon-Mood method, Biased Coin Design, and Bayesian analysis), as well as strategies and recommendations for future research.

Minimum Effective Volume of Lidocaine for Ultrasound-Guided Costoclavicular Block

“…Volume assignment was carried out using a BCD up-and-down sequential method, where the total volume administered to each patient depended on the response of the previous one. 4,7,8 The first subject recruited received 20 mL. This initial volume was derived from the initial recommendation of Karmakar et al 1,3 Subsequently, volume assignment was based on the response of the previous patient.…”

“…Biased coin design constitutes a relatively new method to approximate the MEV for US-guided peripheral nerve blocks. 5,8 To date, most dose-finding studies have focused exclusively on MEV50 and relied on the Dixon and Massey up-and-down sequential method. 7 Maximum likelihood logistic or probit regression is then used to extrapolate to higher quantiles (eg, MEV95).…”

“…Unfortunately, such extrapolation can be notoriously imprecise. 8 In contrast, BCD allows the direct investigation of MEV at any quantile. 8 In the costoclavicular space, the 3 cords of the brachial plexus are situated closer together than in the lateral infraclavicular fossa, where the paracoracoid ICB is commonly performed.…”

Cardiac Arrest and Seizures Caused by Local Anesthetic Systemic Toxicity After Peripheral Nerve Blocks

“…The use of ultrasound guidance has led to a reduction in recommended dose, and several studies have tried to establish the minimum effective doses for different PNBs. 17 However, exact individual dose requirements vary despite population estimates, 18 and our study suggests that there is a safety margin in the dose of local anesthetic tolerated by patients without developing major LAST after PNBs. Pharmacokinetics of absorption of local anesthetic after PNBs may also serve as a safety margin.…”

“…As noted, the ASA NACOR database analyzed nearly 1.5 million cases to determine the incidence and risk factors for perioperative cardiac arrest after a variety of cases, anesthetic techniques, and perioperative settings. 18 A similar accumulation of sufficient cases specifically pertaining to LAST after PNBs would be a formidable challenge. Alternatively, the rarity of cardiac arrest caused by LAST after PNBs may suggest that the evolution of the safety steps of our current practice for performing PNBs has reduced this once-feared bogeyman to a ghost.…”