Ovid: Peripheral Nerve Blocks: A Color Atlas

Local Anesthetic Solutions for Continuous Infusion

Andrea Casati

Different local anesthetic solutions, including lidocaine, bupivacaine, ropivacaine, and more recently levobupivacaine, have been used for continuous peripheral nerve blocks. When considering local anesthetics, their concentrations, and their mode of administration for continuous peripheral nerve block techniques, it is important to differentiate between the need for surgical anesthesia and maintenance of the block through a perineural catheter. The ideal local anesthetic for clinicians should provide a fast and reliable onset time of both sensory and motor blocks, a long duration of analgesia with maximum differentiation between sensory and motor block in the postoperative period through a continuous or patient-controlled perineural infusion, and the safest profile from a toxicological point of view due to the large infusions for long periods of time leading to a consistent risk of accumulation. Although such an “ideal” local anesthetic is not available on the market, we usually obtain good results with using different local anesthetic solutions used at different concentrations for surgery and postoperative analgesia.

Anesthetic Blocks

The choice of the anesthetic solution, its concentration, and total dose administered must be tailored to the individual patient's requirement to minimize the onset time and the risk for overdosage. When a catheter is placed close to the nerve, we do not have the problem of prolonging the effects of initial injection, thus we can select a short-onset, intermediate-duration anesthetic solution, such as mepivacaine or lidocaine in concentrations ranging between 1.5% and 2.0%, for the initial bolus. Some authors recommend the use of a combination of anesthetic solutions with different pharmacokinetic properties. The most frequent of these mixtures is a combination of two local anesthetics, one with a short onset and one with a long onset, such as a combination of mepivacaine with either bupivacaine, ropivacaine, or levobupivacaine. The rationale for using these mixtures is to achieve a compromise between the onset of the shorter-acting drug and the duration of the longer-acting agent. However, it must be considered that diluting the two local anesthetics actually reduces the drive of diffusion of each agent into the nerves by reducing the final concentration of each agent. Moreover, it has been reported that when two different local anesthetics are mixed, there is a competitive binding of the two different agents to the

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protein carriers, and the free concentration of the more toxic local anesthetic is similar to that produced by using it alone in a volume similar to the volume actually injected.

Table 25-1. Concentrations, Suggested Doses, and Block Characteristics for Peripheral Nerve Blocks with the Local Anesthetic Agents Discussed

	Concentration (%)	Onset	Duration (h)	Maximum Dose (mg)	pH
Lidocaine	1.5–2	Fast	1–2	300–500 + epinephrine	6.5
Mepivacaine	1.5–2	Fast	2–3	500–600 + epinephrine	4.5
Bupivacaine	0.5	Slow	4–12	150–225 + epinephrine	4.5–6
Ropivacaine	0.5–0.75	Slow	2–6	225–300	4–6
Levobupivacaine	0.5	Slow	4–12	150	4–6

The volumes and doses of local anesthetics will depend on the type of surgery (e.g., single block or a combination of different blocks, such as for the lower limb) as well as on whether light general anesthesia is used during surgery. Accordingly, the maximum doses suggested for each anesthetic drug must always be considered (Table 25-1).

Analgesic Blocks

From a theoretical standpoint, it is possible to use either a short-onset and short-duration local anesthetic or a long-acting one also for continuous postoperative infusion. The use of a short-acting anesthetic, such as lidocaine or mepivacaine, is mainly based on the reduced toxicity potential as compared with more potent and lipid-soluble agents. Moreover, short-acting agents also have the theoretical potential for allowing a fast recovery of sensory and motor function after the infusion is stopped, to enable quick and easy neurologic evaluation. The main disadvantage of shorter-acting agents is that they have been demonstrated to be less effective in providing a good differentiation between sensory and motor blocks. Evaluating the use of either 0.2% ropivacaine or 1% lidocaine for continuous interscalene analgesia after open shoulder surgery, it has been reported that both agents provide a similarly adequate analgesia, but a more efficient recovery of motor function was observed in patients receiving 0.2% ropivacaine. This finding is similar to that previously reported with epidural blockade, and can be explained with the different pKa of the two drugs. For this reason, most authors prefer to use long-acting local anesthetics (e.g., bupivacaine, ropivacaine, or levobupivacaine) for continuous perineural infusions.

Bupivacaine 0.125% or 0.25% had been the most widely used agent for peripheral nerve blocks and continuous perineural infusion during the last 20 years; however, it is associated with a higher toxic potential as compared with new pure left isomers introduced into the market in the last 8 years—ropivacaine and levobupivacaine. Moreover, it has also been demonstrated that 0.2% ropivacaine provides a similarly effective postoperative analgesia with better preservation of motor function when compared with an equipotent concentration of 0.15% bupivacaine. The differentiation between sensory and motor blocks reported with levobupivacaine 0.125% is similar to that obtained with 0.2% ropivacaine; while increasing the concentration of levobupivacaine to 0.2% may result in more frequent motor block after surgery. For these reasons concentrations as low as 0.125% to 0.25% bupivacaine, 0.125% to 0.2% levobupivacaine, or 0.2% ropivacaine are usually used.

The use of a patient-controlled intermittent bolus technique, with or without a basal rate ranging between 5 and 10 mL/hour, allows optimization of the analgesic efficacy and minimizes the total amount of anesthetic drug used.

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Table 25-2. Concentrations and Infusion Rates Suggested for the Maintenance of Continuous Peripheral Nerve Blocks with the Anesthetic Solutions Discussed

	Concentration (%)	Infusion Rate (mL/h)
Lidocaine	1	5–10
Bupivacaine	0.125–0.25	5–10
Ropivacaine	0.20	5–10
Levobupivacaine	0.125–0.25	5–10

Additives for continuous peripheral nerve blocks

Several additives have also been suggested as a part of the local anesthetic mixture, to modify the pharmacokinetic/pharmacodynamic profile of the local anesthetic solutions. The most commonly used additives for peripheral nerve blocks include vasoactive agents, alkalinizing agents, clonidine, and opioids. However, only few properly conducted studies have specifically evaluated the usefulness of this mixture for continuous peripheral nerve blocks, and little evidence is present in the literature supporting their introduction in standard protocols of our Acute Pain Services. Table 25-2 shows the concentration and regimens suggested for maintenance of continuous peripheral nerve blocks with the main anesthetic solutions used in the literature and in our clinical experience, as well as the concentrations of additives.

Vasoconstrictors

The duration of a local anesthetic agent depends on the duration of the contact between the anesthetic agent and the nerve fibers, as well as on the number of local anesthetic molecules able to interact with the sodium channels in the nerve fibers. To produce a more intense and longer-lasting block, we can either increase the dose of local anesthetic solution injected, or decrease the amount of local anesthetic removed from the target in the unit time. Epinephrine, at concentrations ranging between 1/200,000 and 1/300,000, reduces the vascular absorption of local anesthetics, increasing their concentration at the target. The addition of epinephrine to solutions of lidocaine, mepivacaine, or bupivacaine used for peripheral nerve blocks increases the duration and the intensity of the block. Nonetheless, it must be also considered that infusing a vasoconstrictor close to a nerve can reduce the perfusion of the vasa nervorum, potentially increasing the risk for an ischemic nerve injury. For these reasons, the extensive use of epinephrine as an adjuvant to local anesthetic solutions for continuous peripheral nerve blocks is not recommended—especially if continuous infusion rather than an intermittent bolus technique is used to manage postoperative pain.

Alkalinization

The pH of commercially available solutions of local anesthetic ranges from 3.0 to 6.5, whereas the pKa of local anesthetics ranges from 7.6 to 8.9. The alkalinization of local anesthetic solutions, usually obtained by adding 1 mEq of sodium bicarbonate to 10 mL of 2% lidocaine, 2% mepivacaine, or 3% chloroprocaine, can reduce the onset time of a nerve block induced with these agents—though this does not occur when sodium bicarbonate is added to bupivacaine or ropivacaine. However, even though changing the pH of the anesthetic solution may shorten the onset time of the block, there are no clinically relevant advantages when a continuous peripheral nerve block is used. On the contrary, the stability of anesthetic solutions with added sodium bicarbonate is not well known. Accordingly, since the solution must remain in the infusion bag for up to 24 hours before being renewed, the use of sodium bicarbonate for continuous peripheral nerve blocks is not recommended.

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Clonidine

The analgesic effects of α2-agonists are well known, and clonidine is widely used for chronic and acute pain management. The addition of clonidine to local anesthetic solutions is known to improve single nerve blocks: it reduces the onset time, prolongs postoperative analgesia, and improves the efficacy of nerve blocks during surgery. Although several authors have reported on the use of low doses of clonidine for continuous peripheral nerve blocks at a concentration as low as 1 µg/mL, there is little evidence in the literature supporting this practice. Moreover, when clonidine was added to the initial bolus of local anesthetic (1 µg/kg), or both to the initial bolus (1 µg/kg) and the continuous infusion solution (1 µg/mL) for continuous femoral nerve block after total knee arthroplasty, no differences were found among the groups in the degree of pain, total consumption of local anesthetic solution, sedation, and hemodynamic parameters during the first 48 hours of infusion. However, persistent motor function impairment after 48 hours of infusion was observed in 27% of patients receiving clonidine in the infusion solution as compared with only 6% of cases in patients not receiving clonidine at all, or receiving it only in the initial bolus (P = 0.05).

Opioids

Opioids are known to exert their analgesic activity directly on the central nervous system, and the addition of opioids to local anesthetic solutions improves the quality of anesthesia and postoperative analgesia during epidural and spinal blocks. Basic science studies in vitro or in animals have also suggested the possibility for expression of opioid receptors at the peripheral sites with inflammation. Adding small doses of opioids to local anesthetics for peripheral nerve blocks has been suggested to result in an improvement in the onset time, and quality and duration of the nerve block. Some authors have also reported on the use of small concentrations of sufentanil (0.1 µg/mL), fentanyl (1–2 µg/mL), or morphine (30 µg/mL) for continuous peripheral nerve blocks. However, there is no evidence supporting the usefulness of adding opioids to local anesthetics in peripheral nerve blocks.

The only minor opioid agonist with potential interest for synergistic action with local anesthetic at a peripheral nerve site is tramadol. In fact, it has been demonstrated that tramadol has a local anesthetic-like effect on peripheral nerves, and this could potentially provide a potentiation of local anesthetic solutions during continuous peripheral nerve infusion. However, there are no clinical reports on its use for this indication.