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Peripheral nerve blocks (PNBs) provide numerous advantages for surgical patients when used either as an analgesic supplement or as an alternative to general anesthesia. These advantages include superior pain control and avoidance of adverse effects associated with volatile anesthetics and opioids.1 However, the benefits of PNBs are limited by the pharmacodynamics of the local anesthetic agents injected. Analgesia provided by PNBs lasts only as long as the duration of action of the local anesthetic at specific tissue sites. Typically, local anesthetics are characterized according to their latency (“onset time”) and duration of action. For practical clinical purposes, local anesthetics can be grouped into one of three categories: (1) rapid onset and short duration (eg, chloroprocaine, procaine); (2) rapid onset and intermediate duration (eg, lidocaine, mepivacaine); and (3) slower onset and long duration (eg, bupivacaine, ropivacaine, tetracaine).2

An ideal local anesthetic for a PNB would have a fast onset coupled with a long duration and low toxicity.3 At present, no such drug exists. In an attempt to achieve a single-injection PNB with characteristics close to ideal, mixtures of local anesthetics (most commonly, faster-onset, intermediate-duration local anesthetic and slower-onset, long-duration local anesthetic) for PNBs have been used clinically and have remained a common practice for over a century.3,4,5,6 While compounding two drugs to obtain the “best” features of each is compelling, few studies have objectively examined the pharmacodynamics of mixtures of local anesthetics. Moreover, because many of the existing studies were conducted before the era of ultrasound guidance, it is difficult to extrapolate those data to current practice given the reduced volumes and doses of local anesthetic ultrasound guidance affords. This chapter examines the evidence base for utilizing local anesthetic mixtures for PNBs and summarizes the advantages and disadvantages of mixing local anesthetics. This chapter does not address the eutectic mixture of lidocaine and prilocaine used for topical analgesia.


In clinical practice, local anesthetics are described according to their clinical properties: potency, duration, latency, and toxicity. These clinical properties are not independent and are determined by each local anesthetic’s structural, stereochemical, and physicochemical properties, such as pKa, lipid solubility, and molecular weight (Table 10–1).

Table 10–1.Physicochemical properties of commonly used local anesthetics.

Latency is largely determined by pKa and lipid solubility. The more ...

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