Local Anesthetic Solutions for Continuous Infusion

Ovid: Peripheral Nerve Blocks: A Color Atlas

Editors: Chelly, Jacques E.
Title: Peripheral Nerve Blocks: A Color Atlas, 3rd Edition
> Table of Contents > Section III – Continuous Nerve Blocks > 25 – Local Anesthetic Solutions for Continuous Infusion

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


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.


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


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 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.
Suggested Readings
A, Kalberer F, Jacob H, et al. Patient-controlled interscalene
analgesia with ropivacaine 0.2% versus bupivacaine 0.15% after major
open shoulder surgery: the effects on hand and motor function. Anesth Analg 2001;92:218–223.
A, Perschak H, Bird P, et al. Patient-controlled interscalene analgesia
with ropivacaine 0.2% versus patient-controlled intravenous analgesia
after major shoulder surgery: effects on diaphragmatic and respiratory
function. Anesthesiology 2000;92:102–108.
X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic
technique on the surgical outcome and duration of rehabilitation after
major knee surgery. Anesthesiology 1999;91:8–15.
A, Borghi B, Fanelli G, et al. Interscalene brachial plexus anesthesia
and analgesia for open shoulder surgery: a randomized, double-blinded
comparison between levobupivacaine and ropivacaine. Anesth Analg 2003;96:253–259.
A, Vinciguerra F, Cappelleri G, et al. Adding clonidine to the
induction bolus and postoperative infusion during continuous femoral
nerve block delays recovery of motor function after total knee
arthroplasty. Anesth Analg 2005;100:866–872.
A, Vinciguerra F, Cappelleri G, et al. Levobupivacaine 0.2% or 0.125%
for continuous sciatic nerve block: a prospective, randomized,
double-blind comparison with 0.2% ropivacaine. Anesth Analg 2004;99:919–923.


A, Vinciguerra F, Scarioni M, et al. Lidocaine versus ropivacaine for
continuous interscalene brachial plexus block after open shoulder
surgery. Acta Anaesthesiol Scand 2003;47:355–360.
Covino BG, Bush DF. Clinical evaluation of local anaesthetic agents. Br J Anaesth 1975;47:289–296.
Benedetto P, Casati A, Bertini L. Continuous subgluteus sciatic nerve
block for after orthopedic foot surgery: comparison of two infusion
techniques. Reg Anesth Pain Med 2002;27:168–172.
Benedetto P, Casati A, Bertini L, et al. Postoperative analgesia with
continuous sciatic nerve block after foot surgery: a prospective,
randomized comparison between the popliteal and subgluteal approaches. Anesth Analg 2002;94:996–1000.
T, Gunes Y, Guven M, et al. Differential effects of lidocaine and
tramadol on modified nerve impulse by 4-aminopyridine in rats. Pharmacology 2003;69:68–73.
Murphy DB, McCartney CI, Chan VW. Novel analgesic adjuncts for brachial plexus block: a systematic review. Anesth Analg 2000;90:1122–1128.
FJ, Vanderelst PE, Gouverneur JM. Extended femoral nerve sheath block
after total hip arthroplasty: continuous versus patient-controlled
techniques. Anesth Analg 2001;92:455–459.

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