Vous êtes sur la page 1sur 20

1

Local Anesthetics Etidocaine 0.5-1.5% (Duranest) 4 Rap 7.7 94 141


Prilocaine 1 7.9 55 0.9
Ropivacaine 0.75% (Naropin) 4 Mod 8.1 94 2.9
Mechanism of Action

Local anesthetics block the generation and conduction of nerve impulses at the level of the cell membrane by
preventing the transient increase in permeability of excitable membranes. Local anesthetics bind directly within the
intracellular portion of voltage-gated sodium channels. The degree of block produced by local anesthetics is Local Anesthetic Time Line (minutes)
Infiltration plain sol'nSpinal plain WithEpidural plain sol'n
dependent upon how the nerve has been stimulated and on its resting membrane potential. Local anesthetics are
With Epinephrine Epinephrine With Epinephrine
only able to bind to sodium channels in their charged form and when the sodium channels are open. In this situation, 30-45
the local anesthetic is able to bind more tightly to and stabilize the sodium channel. Differences in pKa, lipid solubility, Chloroprocaine
45-60
and molecular size influence the binding of local anesthetics to to the sodium channels. Hyperbaric
60-120 80-120
Lidocaine 60
90-180 120-180
60-90
In general, small nerve fibers are more sensitive to local anesthetics than large nerve fibers. However, myelinated
90-140
fibers are blocked before non-myelinated fibers of the same diameter. Autonomic fibers, small unmyelinated C fibers Mepivacaine
140-200
(mediating pain) and small myelinated A-delta fibers (mediating pain and temperature sensation) are blocked before Hyperbaric
larger myelinated A-gamma, A-beta, or A-alpha fibers (mediating touch, pressure, muscle and postural inputs). Small, Tetracaine 120-180
sensory fibers are preferentially blocked since nerve conduction is more easily blocked over shorter distances and 180-400
these fibers have longer action potentials allowing more of the local anesthetic to bind. Clinically, the loss of nerve 140-200
Ropivacaine
function proceeds as loss of pain, temperature, touch, proprioception, and then skeletal muscle tone. 160-220
Hyperbaric
180-360 180-360
Bupivacaine 120-360
300-480 120-240
120-360
Lidocaine

Properties of Local Anesthetic Agents


Lidocaine is the most widely used local anesthetic agent because of inherent potency, rapid onset, tissue penetration
and effectiveness. This agent is available as an ointment, jelly, patch, or aerosol for topical use, as an oral solution,
Properties Amino esters Amino amides and as an injection for local infiltration, peripheral nerve block, epidural block and Bier's block. The absorption of
Metabolism rapid by plasma cholinesterase slow, hepatic
lidocaine after subcutaneous injection is relatively small, however repeated dosing may result in detectable lidocaine
Systemic toxicity less likely more likely
Allergic reaction possible - PABA derivatives form very rare blood levels due to gradual accumulation of the drug or its metabolites. The duration of action of subcutaneously
Stability in solution breaks down in ampules (heat,sun) very stable chemically administered lidocaine is 1-3 hours. The addition of epinephrine 1:200,000 to 1:100,000 to lidocaine slows the
Onset of action slow as a general rule moderate to fast vascular absorption of lidocaine and prolongs its effects.
pKa's higher than PH = 7.4 (8.5-8.9) close to PH = 7.4 (7.6-8.1)
Clinical Pharmacology

The potency of Local Anesthetics, their onset and duration of action are primary determined by physicochemical
properties of various agents and their inherent vasodilator activity of same local anesthetics.

Lipid solubility is the primary determinant of anesthetic potency and it is expressed as lipid: water
Partition Coefficient
Protein binding influences the duration of action Bupivacaine
pKa of Local anesthetics determinates the onset of action
The addition of vasoconstrictors, such as epinephrine or phenylephrine can prolong duration of action of
Bupivacaine is a long-acting local anesthetic of the amide type recommended for infiltration, peripheral nerve block,
local anesthetics, decrease their absorption (and the peak plasma level) and enhance the blockade
epidural and spinal anesthesia. Its onset of action is rapid (1-5 minutes) if used for spinal anesthesia but slower when
Agent Pot. Onset pKa %PB P. coef
Procaine 0.5-1% (Novocain) 1 Rap 8.9 5.8 0.02 used for peripheral nerve block. Its duration is significantly longer than that of other commonly used local anesthetics.
Chloroprocaine 2-3% (Nesacain) 4 Rap 8.7 ? 0.14 Useful concentration of the drug range from 0.125% to 0.75%. Lower concentration may provide differential sensory
Tetracaine 0.1-0.5% (Pontocain) Slow 8.5 75.6 4.1 motor block. Bupivacaine is available in multiple forms including sterile isotonic solutions with or without the
Lidocaine 1-5% (Xylocaine) 1 Rap 7.9 64.3 2.9 preservative methyl paraben, and hyperbaric solutions consisting of bupivacaine hydrochloride in dextran. All forms
Mepivacaine 1.5% (Carbocaine) 1 Mod 7.6 77.5 0.8 are available with epinephrine. The main disadvantage of bupivacaine is the severe cardiotoxicity which may occur
Bupivacaine 0.25-0.75% (Marcainesensorcaine) 4 Slow 8.1 95.6 27.5 with high plasma levels.
2

Benzocaine

Ropivacaine Benzocaine is a short-acting local anesthetic of the ester type. It is used for topical anesthesia in a wide variety of
clinical situations including mucous membrane anesthesia prior to endoscopic examination or instrumentation, gag
Ropivacaine is a long-acting, amide-type local anesthetic. Its structure and pharmacokinetics are similar to those of reflex suppression, and anorectal disorders and various pain syndromes. It is available in many dosage forms
bupivacaine, however, ropivacaine exhibits significantly better cardiotoxicity profile compared to bupivacaine. Duration including gels, creams, ointments, lotions, aerosols, and lozenges. Many nonprescription products are available for
of action for ropivacaine ranges 2.5-5.9 hours for epidural block to 8-13 hours for peripheral nerve block. Ropivacaine the temporary relief of dental or oral pain. Benzocaine and tetracaine are more likely to cause contact sensitization
is also less lipid soluble and cleared via the liver more rapidly than bupivacaine. Some studies have shown less motor than are other local anesthetics.
blocking effects of ropivacaine than that of bupivacaine. Due to its better safety profile and significantly better
sensory-motor differentiation, Ropivacaine is currently the long-acting anesthetic of choice in our practice. Benzocaine is minimally absorbed and therefore relatively free from systemic side effects or adverse drug
interactions. Onset of action is rapid, with initial effects obtained in about 1 minute and action lasting about 15-20
minutes. It is metabolized hepatically. Metabolites are renally excreted.

Levobupivacaine

Etidocaine
Levobupivacaine is an amino amide type of local anesthetic. Levobupivacaine is the S (-)-enantiomer of bupivacaine.
Levobupivacaine produces sensory and motor blockade that is similar to bupivacaine. Its onset time, maximum
spread of sensory block, or intensity of motor block in patients receiving lumbar epidural anesthesia with Etidocaine is a long-acting local anesthetic of the amide type. It is used for epidural, local, and retrobulbar anesthesia
levobupivacaine is comparable to that of bupivacaine. Levobupivacaine exhibits less cardiotoxicity than bupivacaine. in surgical and dental procedures. Like lidocaine, it has a rapid onset of sensory and motor blockade, but duration of
The threshold for CNS effects of levobupivacaine is also higher than that of bupivacaine. Its primary use is in epidural analgesia is 1.5-2 times longer than lidocaine when given epidurally. This difference is greater following peripheral
anesthesia. The data on its efficacy in peripheral nerve blockade is sparse; however it should be quite similar if not nerve block. Etidocaine produces profound motor blockade and muscle relaxation when used for epidural analgesia.
identical to that of bupivacaine. Etidocaine is rapidly absorbed from parenteral injection sites, and epidural injections of 1% solutions result in
anesthesia within 2-8 minutes, with complete sensory and motor blockade occurring in less than 20 minutes. Duration
of action varies between 4.5-13 hours. Etidocaine passively diffuses across blood-brain and placental barriers, and
Mepivacaine fetal plasma levels are usually 20-30% of maternal plasma concentrations.

Mepivacaine is a local anesthetic of the amide type with an intermediate duration of action. Mepivacaine is used for
Procaine
infiltration and transtracheal anesthesia, and peripheral, sympathetic, regional (Bier block), and epidural nerve blocks.
Compared with lidocaine, mepivacaine produces less vasodilatation and has a more rapid onset and longer duration
of action. In our practice, this is the #1 intermediate-acting local anesthetic to use for peripheral nerve blocks. Procaine hydrochloride is a short-acting, slow onset, low potency local anesthetic of the ester type used for local,
regional and short acting spinal anesthesia. It lacks topical anesthetic activity. Its toxicity is the standard against which
others are compared.
Prilocaine

Systemic absorption of procaine depends on the dose, concentration, route of administration, local tissue vascularity,
Prilocaine is a local anesthetic of the amide class used primarily for dental anesthesia. It has an intermediate duration
and degree of vasodilation. A vasoconstrictor such as epinephrine may be necessary to counteract the vasodilation
of action and is longer acting than lidocaine. Lidocaine and prilocaine are combined in a topical formulation for use on
produced by procaine. Chemical Structure will slow the rate of absorption, prolong the duration of action, and
intact skin for local analgesia. An example is EMLA cream, which provides dermal analgesia by the release of
maintain hemostasis. Anesthesia is obtained within 2-5 minutes and lasts approximately 1 hour.
lidocaine and prilocaine into the epidermal and dermal layers of the skin and accumulation of drug near dermal pain
receptors. However, there have been reports of significant methemoglobinemia (20-30%) in infants and children
following excessive applications of EMLA cream. These cases involved the use of large dosages, larger than Chloroprocaine
recommended areas of application, or occurred in infants <3 months.
Chloroprocaine is a short-acting local anesthetic of the ester type, similar in structure to procaine. Chloroprocaine is
used for infiltration anesthesia, peripheral, sympathetic, epidural, caudal, and intravenous regional (Bier block) blocks.
Chloroprocaine is not effective as a topical anesthetic, and it is not available for subarachnoid use.
3

Absorption depends on the dose, concentration, route of administration, tissue vascularity, and degree of vasodilation. and its requirement for immediate relief, which dictate the development of suitable management protocols.
However, due to its rapid hydrolysis in the blood, toxic levels are rare even with high doses. The addition of Preemptive and preventive analgesia also represent concepts that only apply to acute postoperative pain. Finally, it is
epinephrine slows the rate of absorption, prolong the duration of action. Anesthesia is obtained within 6-12 minutes important to recognize the role of acute pain in the development of chronic pain syndrome.
Irrespective of its nature, pain is not an objective but rather a subjective symptom. In the surgical as well as medical
and lasts approximately 30-60 minutes (60-90 minutes when epinephrine is added).
environment, intrinsic and extrinsic factors affect individual pain thresholds. Accordingly, the clinician must be always
aware that pain treatment must be approached using a multimodal and multipharmacologic approach; no one single
technique by itself, including the use of continuous peripheral nerve block, provides adequate pain relief in all patients
and in all circumstances. The first description of continuous peripheral nerve block was reported in 1946 by Paul
Ansbro,[1] who described the placement at the supraclavicular level of a blunt needle secured to the patients skin
using a cork, through which the needle was inserted before block placement. This cumbersome apparatus allowed
the incremental injection of local anesthetic in order to prolong the duration of anesthesia in patients undergoing
upper extremity surgery. In their report the authors used a short-onset/intermediate duration local anesthetic, like 1%
procaine. After an initial 40-mL bolus the authors injected incremental doses based on the duration of surgery, up to a
final volume ranging between 120 mL for 1.5-h surgery and 220 mL for 4-h surgery. During the following 3 years
Tetracaine continuous perineural infusion techniques continued to be developed, and their indications extended; initially they
were mainly used for upper extremity blocks, afterward they were also employed for lower limb blocks.
In 1977 Selander[2] reported on the injection of 30 to 50 mL of mepivacaine to conduct a continuous axillary block in
Tetracaine is an ester-type local anesthetic with an intermediate to long duration of action. Relative to other local 137 patients undergoing hand surgery, and in 1979 Manriquez and Pallares[3] reported on the repeated injection of
anesthetics, tetracaine is significantly more toxic. Tetracaine is available in various injectable forms for spinal 20 mL of 0.25% bupivacaine every 6 h to prolong the sympathetic block and pain control for 4 days.
anesthesia, as well as preparations for topical use. These preparations are typically used prior to examination of the In 1982 Matsuda and colleagues[4] reported on the use of either 30 mL of 1% lidocaine with epinephrine followed by
larynx, trachea, or esophagus, to abolish laryngeal and esophageal reflexes and provide local analgesia. 15 mL intermittently (1.52.75 h) or 40 mL of a 0.5% bupivacaine and 1% lidocaine mixture followed by intermittent
injection of 20 mL (1.254.3 h) in 50 patients undergoing upper extremity reimplantation. Subsequently most of the
groups have focused their clinical protocols on the use of low concentrations (0.1250.25%) of bupivacaine.57
Systemic absorption of tetracaine depends on the dose, concentration, route of administration, tissue vascularity and More recently, with the introduction of newlong-acting aminoamide local anesthetics, such as ropivacaine or
degree of vasodilatation. Systemic absorption from topical preparations is minimal, but application to broken or levobupivacaine, the attention of clinicians has shifted to the evaluation of these new agents, often with interesting
bruised skin greatly increases absorption. When used for spinal anesthesia the onset of action can be delayed, with a findings. Borgeat and coworkers[8] compared 0.2% ropivacaine and 0.15% bupivacaine (to account for the difference
duration of 1.5-3 hours. The addition of a vasoconstrictor can substantially prolong the duration of spinal anesthesia in potency between the two agents) in terms of their effects on motor function and demonstrated that they provided
similar postoperative pain control, but 0.2% ropivacaine allowed for better preservation of motor function than
achieved with tetracaine. For topical and aerosol solutions, the onset of action is 3-10 minutes and the duration of
bupivacaine. On the other hand, levobupivacaine at 0.125% concentration seems to provide the same level of motor
action is 30-60 minutes. For ophthalmic preparations, the onset of action is about 15 seconds, with a duration of 15 preservation as 0.2% ropivacaine.9
minutes. Due to its potential for toxicity, tetracaine is infrequently used for neuronal blockade. The advantages of continuous block techniques have been largely demonstrated for major orthopedic surgery,
implementing the rehabilitation of these patients after total arthroplasty allowing early, pain-free mobilization of the
operated limb. Finally, the indication of this technique of pain control has also been expanded to outpatient
Cocaine
procedures. In fact it is known that over 40% of ambulatory patients experience moderate to severe pain within the
first 48 h after ambulatory orthopedic surgery. Although different therapeutic approaches have been advocated, none
Cocaine is a naturally occurring alkaloid present in the leaves of Erythroxylon coca. Cocaine is commercially available provide reliable pain control, and pain remains a major concern. Most frequently patients are discharged with oral
in a variety of forms and it is applied to mucous membranes of the oral, laryngeal, and nasal cavities for use as a medication that has limited effects on pain relief. Intraarticular injections of narcotic analgesics or local anesthetics
topical anesthetic. Cocaine causes significant euphoria, and abuse and it can lead to physical dependence. Despite have also been used, but these techniques have been shown to provide only limited and short-lasting pain relief. In
recent years several groups have evaluated the use of continuous nerve blocks in outpatients. Most of these
being an excellent local anesthetic, the risk of abuse and the intense local vasoconstriction it produces prevent
investigators used solutions of 0.125% bupivacaine or 0.2% ropivacaine infused through either elastomeric or
cocaine from being more widely used clinically. electronic patient-controlled (PCA) pumps, with relevant benefits not only in terms of quality of postoperative
analgesia, but also in improved quality of life during the first postoperative days.1012
Cocaine is well absorbed from all mucous membranes, especially from damaged or inflamed tissue. Although topical Nerve Roots Anatomy & Classification of Nerve Fibers
The nerve roots are divided into three types according to their anatomic and functional properties: A, B, and C fibers.
vasoconstriction can limit the absorption rate, significant systemic absorption can occur. When used for topical
The A fibers are responsible for motor efferent conduction and are divided in A, A, and A fibers. They are all
anesthesia, the onset of action occurs within 1 minute, and maximum effect is within 5 minutes. The duration of action myelinated, like the A fibers, which are sensory fibers carrying pressure and distension information. The B fibers are
is about 30 minutes. constituted of the autonomic pregangliar fibers, and the C fibers include all the amyelinic fibers of the posterior spinal
roots as well as the postgangliar autonomic fibers.
Clinical Pearls
Local Anesthetic Solutions For Continuous Nerve Blocks Generally, the bigger the sizeof the nerve fibers the greater the amount of
Introduction local anesthetic solution required to block conduction. Thus, fibers of small
In the past few years progress has been made in understanding the mechanisms and pathways involved in the size are blocked sooner than those of larger diameter.
modulation of pain, as well as in developing new therapeutic tools to provide satisfactory pain relief after surgery. The The B fibers of the autonomic systemconstitute an exception of this rule:
relationship between the intensity of acute postoperative pain and the duration of the patients recovery and functional even though they are myelinated fibers a minimum concentration of local
outcome has been well established. For these reasons, the prevention and treatment of acute pain had become the anesthetic solution is required to produce an effective blockade.
focus of great interest for perioperative specialists. Postoperative pain differs from chronic pain by its shorter duration This explains why the sympathetic blockade is observed before the onset of
4

sensory or motor blockade. current by 50% within 5 min. The potency of local anesthetics is strictly related to their lipid-solubility; the more lipid-
In the myelinated nerve roots, the action potential conduction proceeds from one Ranvier node to the next (jumping, soluble a local anesthetic is, the greater its potency and consequently the lower its Cm.
or saltatory, conduction). Because the size of the fibers is proportional to the length between one Ranvier node and The Cm of a local anesthetic also changes according to the size of the nerve fiber. Although the total amount of local
the next, the speed of conduction of the action potential increases with the size of the fibers. Generally, the bigger the anesthetic affects the onset, degree, and duration of the nerve block, its concentration primarily influences the
size of the nerve fibers, the greater the amount of local anesthetic solution required to block the conduction. Thus, the intensity of the blockade. The smallest fibers (A-, , and C), with a slower conduction speed, are more sensitive to
fibers of small size are blocked sooner than those of larger diameter. The B fibers of the autonomic system constitute the blocking activity of the local anesthetic solution than are those with a larger diameter (A- and A-) and fast
an exception of this rule: even though they are myelinated fibers, a minimum concentration of local anesthetic solution conduction. In otherwords, the smallest fibers need a lower Cm than those of larger size. This aspect is related to the
is required to produce an effective blockade. This property of B fibers explains why the sympathetic blockade is number of anesthetic molecules available to block the conduction; when using low concentrations the small number of
observed before the block of the other fibers (Table 1). The difference in sensitivity to neural blockade allows local anesthetic molecules available will block only the small fibers. A possible explanation is the need for blocking
determination of the minimum concentration of local anesthetic that blocks only the small fibers, mainly responsible three consecutive Ranvier nodes in order to produce a complete nerve block. Since the distance between
for nociception, with minimum or no block of the lager fibers. This in turn, allows neural blockade to accomplish consecutive Ranvier nodes increases as the size of the nerve fiber increases, low concentrations of local anesthetics
analgesia with no or minimum motor block; the basis of the differential sensorymotor blockade. blocks three consecutive nodes only in the small nerve fibers and not in the large ones. This is the basis for the
Table 1: Onset and Recovery of Nerve Blockade in the differential sensory motor blockade, which is more evident with the lipophilic agents with high pKa, such as
Different Types of Nerve Fibers bupivacaine, ropivacaine, and levobupivacaine.
Nerve Block Onset Nerve Block Recovery Clinical Pearl
B A- The duration of the action of local anesthetic solutions depends on the
C; A- A- protein binding as well as the clearance from the injection site
A- A- The duration of the action of local anesthetic solutions depends on the protein binding as well as the clearance from
A- C; A- the injection site.13 Table 2 shows the main chemical/physical properties of the considered local anesthetics, as well
A- B as their reported equipotent concentrations.
Table 2: Chemical and Physical Properties of the Main Local Anesthetic Drugs,
Clinical Properties Of Local Anesthetic Solutions Including the Reported Equipotent Concentrations
The choice for a local anesthetic solution for peripheral nerve blocks is based on: Lidocaine Mepivacaine Bupivacaine Ropivacaine Levobupivacaine
1. Onset time Molecular
2. Duration of blockade 234 246 288 274 288
weight
3. Ability to produce a differential sensorymotor block pKa 7.7 7.6 8.1 8.1 8.1
4. Potential for toxicity Liposolubility 4 1 30 2.8 30
The onset time of local anesthetics is influenced by the molecules pKa (the higher the pKa the slower the onset time Partition
of the nerve block in a physiologic environment) and diffusibility.13 On the other hand, the ability to cross the cell 2.9 0.8 28 9 28
coefficient
membrane depends on the molecular weight and the liposolubility of the molecule. All local anesthetics have nearly Protein binding65% 75% 95% 94% 95%
the same molecular weight, but the diffusibility of the local anesthetic molecules from the injection site depends on its Equipotent
hydrophilicity. The nonionized form of the molecule is more lipid-soluble than the ionized one, so it and can cross the 2% 1.5% 0.5% 0.75% 0.5%
concentration
cell membrane easier but diffuses less easily. The commercial solutions of local anesthetics have an acid pH, and the Clinical Pearls
pKa of the different local anesthetics range from 7.9 to 8.1. Accordingly, the ionized form, which is less lipophilic, is The closer the pKa of a local anesthetic is to physiologic pH, the shorter the
more represented than the nonionized one. onset time of the nerve block.
Clinical Pearls Increasing the lipophilicity of a local anesthetic increases its potency and
The onset time of local anesthetics is influenced by the molecules pKa (the toxicity, whereas protein binding is proportional to the duration of action of
higher the pKa, the slower the onset time of the nerve block in a physiologic the local anesthetic.
environment) and diffusibility. Sensorymotor differentiation is based on the different size and
The ability to cross the cell membrane depends on the molecular weight myelinization of the nerve fibers involved in pain conduction (A and C) as
and the liposolubility of the molecule. compared with those involved in motor function (A)
All local anesthetics have nearly the same molecular weight, but the
diffusibility of the local anesthetic molecules from the injection site depends General Principles
on its hydrophilicity. Different local anesthetic solutions, including lidocaine, bupivacaine, ropivacaine,andmore recently levobupivacaine,
The nonionized form of the molecule is more lipid soluble than the ionized have been used for continuous peripheral nerve blocks. When choosing a local anesthetic solution for continuous
one, therefore, it can more readily crosses the cell membrane but diffuses peripheral nerve blocks two main aspects are considered:
less easily. 1. The need for the surgical anesthesia and
As onset time decreases, the dose, volume, or concentration of a given local anesthetic can be increased. Other 2. Maintenance of the block through a perineural catheter
strategies include the modification of the pKa of the anesthetic solution by warming it or adding sodium bicarbonate to Ideally, the local anesthetic would provide a fast and reliable onset time for surgery; long duration, good differentiation
increase the number of nonionized local anesthetic molecules, especially with lidocaine and mepivacaine. The in sensorymotor block during postoperative continuous infusion; and a safe toxicity profile without a risk of
alkalinization of ropivacaine, bupivacaine, or levobupivacaine is much more difficult, because of their very high pKa. accumulation in the postoperative period.
Another important aspect deserving consideration is the pH of tissues; for example, the local tissue acidosis related to
inflammation can increase the ionized form of local anesthetic, thereby reducing its efficacy. The potency of a local Selecting A Local Anesthetic For Surgical Anesthesia
anesthetic is usually expressed as the minimum effective concentration (Cm): the minimum anesthetic concentration The choice of the best anesthetic solution to induce the nerve block should be tailored to patient characteristics as
that reduces the action potential of a nerve fiber bathed in a solution with a 7.27.4 pH and stimulated with a 30-Hz well as the safe dose according to the type of block and effect desired (anesthesia versus analgesia). Local
anesthetics with a short onset have the disadvantage of short duration that usually reduces their usefulness for
5

painful procedures where prolonged postoperative analgesia is desirable. However, placing a catheter close to the provide a postoperative analgesia with minimal impairment of motor function. Concentrations as low as 0.1250.25%
nerve(s) allows for prolongation of the block with the same or another agent. Therefore, a shortonset/intermediate- bupivacaine, 0.1250.2% levobupivacaine, or 0.2% ropivacaine are usually used.
duration anesthetic solution (eg, mepivacaine or lidocaine at concentrations ranging between 1.5% and 2%) can be The infusion rate is usually adjusted according to the block technique selected. Several infusion regimens have been
used to initiate the block and accomplish surgical anesthesia. The block can then be extended with another agent as suggested, ranging from an intermittent bolus technique to a patient-controlled continuous perineural infusion. In
desired. Some authors use combinations of anesthetic solutions with different kinetic properties; the most frequent general, continuous infusion combined with patient-controlled bolus doses optimizes analgesia and decreases the
mixture is a combination of a short-onset anesthetic, like mepivacaine, with a long-duration one, such as bupivacaine, need for oral analgesic use compared with basal- or bolus-only dosing regimens.1820
ropivacaine, or levobupivacaine. Theoretically, the advantage of mixing different anesthetics is that the risk of toxicity
decreases with long-acting, more a toxic local anesthetic mixture. However, injection of two anesthetic drugs results in Using Additives For Continuous Peripheral Nerve Blocks
competitive binding to the protein carriers and the free concentration of the more toxic local anesthetic is similar to Addition of various additives to local anesthetics has been suggested to hasten the onset, decrease systemic
that produced by using it alone in a volume similar to the total injected volume of the mixture. Consequently, it absorption, and prolong neural blockade or analgesia. The most commonly used additives for peripheral nerve blocks
questionable whether these mixtures reduce the overall toxicity. are vasoactive agents, alkalinizing agents, clonidine, and opioids. Unfortunately, few properly conducted studies have
The volumes and doses of local anesthetics depend on the type of surgery (eg, single block or combination of focused on the specifically proposed advantages for continuous peripheral nerve blocks.
different blocks, such as for lower limb procedures), as well as on the use of additional anesthetic agents (eg, light Vasoconstrictors
general anesthesia) for intraoperative maintenance. Accordingly, the maximum doses suggested for each anesthetic The duration of a local anesthetic agent depends on the duration of the contact between the anesthetic agent and the
drug should always kept in mind (Table 3). It should be noted, however, that significantly larger doses of local nerve fibers as well as on the number of local anesthetic molecules bound to the sodium channels. A more intense
anesthetics than those recommended for intravenous administration may be safely used for peripheral nerve blocks. and longer lasting block can be achieved by increasing the concentration and dose of the local anesthetic solution or
Table 3: Block Characteristics, Concentrations and Doses Suggested to Induce a pharmacologically reducing the removal of local anesthetic from the nerve target. Epinephrine, in a dose range of 5
Peripheral Nerve Block With the Considered Local Anesthetic Agents mcg/mL (1:200.000), reduces the absorption of local anesthetics, increasing their concentration at the intended target
Maximum Dose nerves or plexuses. In general, addition of epinephrine to solutions of lidocaine, mepivacaine, or bupivacaine used for
Agent Concentration (%) Onset Duration (h) pH
(mg) peripheral nerve blocks increases the duration and intensity of the block. However, a vasoconstrictor reduces the
300 perfusion of the vasa nervorum, which potentially increases the risk of an ischemic nerve injury. For these reasons the
Lidocaine 1.52 Fast 12 500 + epinephrine6.5 extensive use of epinephrine as an adjuvant to local anesthetic solutions for continuous peripheral nerve blocks is not
500 recommended, especially if continuous infusion rather than an intermittent bolus technique is used to manage
600 + epinephrine postoperative pain. In addition, it is probably prudent to limit the concentration of epinephrine to 1:300,000 in
Mepivacaine 1.52 Fast 2-3 4.5
150 peripheral nerve blockade.
225 + epinephrine Alkalinization
Bupivacaine 0.5 Slow 48 4.56
300 The pH of commercially available solutions of local anesthetic ranges from 3 to 6, 5, whereas their pKa ranges from
Ropivacaine 0.751 Slow 46 7.6 to 8.9. The alkalinization of local anesthetic solutions, usually obtained by adding 1 mEq of sodium bicarbonate to
Levobupivacaine0.50.75 Slow 48 150 46 10 mL of lidocaine, mepivacaine, and chloroprocaine reduces the onset time of a nerve block induced with these
agents. This, however, does not occur when sodium bicarbonate is added to bupivacaine or ropivacaine.21,22
Postoperative Maintenance Of Nerve Block However, even though changing the pH of the anesthetic solution may shorten the onset time of the block, there are
In several fields of anesthesia the pharmaceutical research is focused on the development of very short acting agents not clinically relevant advantages when a continuous peripheral nerve block is used. Importantly, the stability of
to be used through continuous infusion in order to allow rapid titration of the effects and easy handling of the anesthetic solutions with added bicarbonate is not well studied. Therefore, because the local anesthetic mixtures in
anesthesia plan, but peripheral nerve blocks are mainly conducted using longer acting agents. the infusion are used for 24 h or longer, the use of sodium bicarbonate for continuous peripheral nerve blocks is not
Capdevilla and colleagues[14,15] reported on the use of 1%lidocaine solution for continuous peripheral nerve blocks recommended.
after major orthopedic surgery and demonstrated similar benefits to those obtained with bupivacaine and ropivacaine Clonidine
perineural infusions. Moreover, lidocaine also has the advantage of a reduced toxicity compared with bupivacaine, The analgesic effects of 2-agonists have been well documented. For instance, the addition of clonidine to local
levobupivacaine, and even ropivacaine.13 In addition, using short-acting agents to maintain continuous peripheral anesthetic solutions is known to improve the duration and quality of analgesia with peripheral nerve blocks. Clonidine
nerve block also has the theoretical advantage of allowing a faster recovery of normal neurologic function (when reduces the onset time, prolongs postoperative analgesia, and improves the efficacy of nerve block during surgery.
indicated) after the infusion is stopped. Unfortunately, shorter acting anesthetic agents have been demonstrated to be Several authors have reported on the use of low doses of clonidine for continuous peripheral nerve blocks using a
less effective in providing a good differentiation between sensory and motor blocks. For instance, patient-controlled concentration as low as 1 mcg/mL. The rationale for adding clonidine is to minimize the doses of local anesthetic
interscalene analgesia with 0.2% ropivacaine or 1% lidocaine after open shoulder surgery both result in a similar solution required to produce an effective postoperative analgesia and thus reduce the risks of local anesthetic-related
quality of pain relief.16 However, a more efficient recovery of motor function occurs in patients receiving 0.2% side effects; nonetheless, only few controlled studies have investigated the efficacy of this practice to improve
ropivacaine than in those receiving 1% lidocaine. This finding is similar to a previous report with epidural analgesia analgesia for continuous perineural local anesthetic.
and can be explained by the different physical-chemical properties of the two agents: lidocaine penetrates nerve roots Ilfeld and coworkers[23] evaluated the usefulness of adding 1 mcg/mL clonidine to 0.2% ropivacaine for a continuous
easier than ropivacaine, because of the different pKa and lipophilicity of the two agents.15 This property can explain infraclavicular brachial plexus block in 34 outpatients undergoing moderately painful upper extremity orthopedic
the less effective differentiation between sensory and motor blocks with lidocaine than occur with ropivacaine. Even surgery. The authors reported that adding clonidine resulted in a statistically significant decrease in the number of
though the mild sparing effect on motor block can be considered as a minor problem, it is of clinical interest because self-administered bolus doses on the first two postoperative days, but this decreased actual local anesthetic
a differentiation in sensory and motor blocks is an important endpoint in improving postoperative patient rehabilitation. consumptionby only 27 mL/day. In addition, no differences in any other investigated variable were reported,
It is for this reason that most authors prefer to use long acting agents for continuous peripheral block techniques (eg, including sleep quality or oral analgesic requirements. Therefore, the clinical significance of this finding is
bupivacaine, ropivacaine, or levobupivacaine). questionable.
For the last 20 years, bupivacaine (0.1250.25%) has been generally used for upper limb continuous peripheral nerve When clonidine is added to the initial bolus of local anesthetic (1 mcg/kg), or to both the initial bolus (1 mcg/kg) and
block; however, 0.2% ropivacaine provides a similarly effective analgesia with better preservation of motor function the continuous infusion solution (1 mcg/mL) for continuous femoral nerve block after total knee arthroplasty, no
than an equipotent concentration of 0.15% bupivacaine.8 Levobupivacaine at 0.125% concentration has been differences were found among the groups in the degree of pain, total consumption of local anesthetic solution,
reported to be similarly effective in pain relief to 0.2% ropivacaine,with a comparable preservation of motor function, sedation, and hemodynamic parameters during the first 48 h of infusion.24 However, persistent motor function
whereas the use of 0.2% levobupivacaine resulted in deeper motor block than both 0.2% ropivacaine and 0.125% impairment after 48 h of infusion was observed in 27% of patients receiving clonidine in the infusion solution, but only
levobupivacaine.9,17 It is for these reasons that clinicians prefer to use low concentrations of long-acting agents to 6% of cases in patients not receiving clonidine at all, or receiving it only with the initial bolus (p = 0.05). This finding
6

may be of clinical significance because it could potentially delay the recovery of normal motor function, which is instance, ultrasound scanning has been suggested to locate the nerve structures and more precisely place the
important in orthopedic patients undergoing early rehabilitation. Similar results have been also reported during perineural catheter.32,33 Such technology may allow both a real-time monitoring of the catheter placement and
continuous epidural infusion of clonidine containing solutions of local anesthetics.25 reduction in the dose required to accomplish a successful nerve block.34 Another important issue in decreasing the
Peripheral Opioids risk of intraneural injection is avoidance of high injection pressures during local anesthetic administration.
Opioid agents are known to exert their analgesic activity directly in the neuraxis; the addition of opioids to local Unintentional intraneural injection of local anesthetics is associated with resistance to injection and high injection
anesthetic solution improves the quality of anesthesia and postoperative analgesia during epidural and spinal block. pressures (>20 psi) and may result in mechanical injury and pressure ischemia of the nerve fascicles.35 Perineural
Various biochemical and electrophysiologic studies have suggested and supported the existence and functional injections result in a seamless injection; consequently, the injection pressures are low (<5 psi). In contrast, most
significance of opioid receptors on primary afferent neurons.26 The existence of such peripheral receptors has been intraneural injections are associated with a resistance to injection and high injection pressures exceeding 20 psi at the
demonstrated both immunocytochemically[27] and functionally.28 Occupation of these receptors has been suggested beginning of the injection. Such injections are followed by persistent motor deficitswith destruction of neural
to result in the inhibition of either the propagation of action potentials or release of excitatory transmitters in primary architecture and degeneration of axons at the histologic examination.35 Accordingly, to minimize the risk of this type
afferent fibers. Adding small doses of opioids to local anesthetic solutions for peripheral nerve blocks has been of local anesthetic-related toxicity we should avoid injection if high injection pressures are encountered.
suggested to result in an improvement in the onset time, quality, and duration of nerve block.29 Small concentrations Systemic toxicity of local anesthetics can occur in cases of overdose or in cases of inadvertent intravascular injection.
of either fentanyl (12 mcg/mL), sufentanil (0.1 mcg/mL), or morphine (0.03 mg/mL) have been suggested for The severity of these systemic reactions is related to the maximum concentration achieved in the blood and may vary
continuous peripheral nerve blocks. However, there is no evidence that addition of opioids to local anesthetics in from simple reports of agitation, drowsiness, and metallic taste, to seizures, coma, and cardiac arrest with increasing
peripheral nerve blocks results in any clinically significant benefit. plasma levels.
Tramadol is a weak opioid receptor agonist and an interesting opioid agent for use as an additive to local anesthetic Theoretically, continuing infusion of a local anesthetic solution after surgery may be associated with a risk for drug
due to its inhibitory effects on the reuptake of serotonin and norepinephrine. Tramadol has a local anesthetic-like accumulation. This can be especially troublesome in patients discharged home after surgery with an infusion of local
effect on peripheral nerves,[30,31] and this could potentially provide a synergistic effect during continuous peripheral anesthetic solution still running. Fortunately, however, pharmacokinetic studies during continuous peripheral nerve
infusion of local anesthetic solutions. However, its clinical use has not be reported. blocks reported on the safety of this technique, with unbound plasma concentrations of local anesthetic remaining
Table 4 shows the concentration and regimens suggested for maintenance of continuous peripheral nerve blocks with well below threshold levels for systemic central nervous toxicity,[3638] provided the catheter is located in the right
the main anesthetic solutions used in the literature and in our clinical experience, as well as the concentrations of position.39
additives. Clinical Pearls
Table 4: Concentrations and Infusion Rates Suggested for the Maintenance of Allergic reactions are rare and are associated with aminoester type local
Continuous Peripheral Nerve BlocksWith the Considered Anesthetic Solutions anesthetics.
Infusion Rate Local toxicitywith neurotoxicity primarily occur in cases of intraneural
Concentration (%) Additives
(mL/h) injection, rather than normal application of clinically relevant concentrations
Lidocaine 1 510 Clonidine, 1 g/mL of local anesthetics.
Bupivacaine 0.1250.25 510 Fentanyl, 12 g/mL To decrease the risk of nerve injury, utmost care should be taken during
Ropivacaine 0.200.30 510 Sufentanil, 0.1 g/mL nerve localization; excessively high concentrations of local anesthetic and
Morphine sulfate, 0.03 high injection pressures should be avoided.
Levobupivacaine 0.1250.25 510
mg/mL
Systemic toxicity can be associated with unwanted intravascular injection
(early-onset) or systemic reabsorption with overdosing (late-onset). To
Clinical Pearls
minimize these complications the planned volume of local anesthetic should
When a catheter is placed for postoperative analgesia, the induction of
be injected only with frequent aspiration to reduce the risk of intravascular
nerve block can be performed with a shortacting agent (mepivacaine 1.5%) injection.
or a combination of short-acting (mepivacaine 1.5%) and a long-acting one
(ropivacaine 0.75% or levobupivacaine 0.5%). Nerve Localization: Paresthesia or Nerve Stimulation
Postoperative maintenance is best performed with low concentrations of a
long-acting agent, like 0.2% ropivacaine, 0.1250.2% levobupivacaine.
The addition of vasoconstrictors or sodium bicarbonate is not The debate over which technique, paresthesia or nerve stimulation, is safer and more effica-cious is moot. The
recommended for postoperative continuous infusion. debate must be limited only to brachial plexus blockade, as the use of paresthesia techniques in infraclavicular,
Always remember that postoperative analgesia must be a multimodal and lumbar plexus, femoral, sciatic, popliteal, and other "deep" blocks is both unreliable and unacceptable in modern
multipharmacologic treatment. Thus always implement analgesia with practice. Consequently, modern regional anesthesia practice is nearly impossible without nerve stimulators. Most
NSAIDs at fixed times and oral or parenteral opioids at request for recent published reports in the field describe the use of nerve stimulators in their methods.
breakthrough
pain.
The question of whether eliciting paresthesia or nerve stimulation is safer in brachial plexus blockade though, still
Complications Related To The Injection & Infusion Of Local Anesthetic Solutions continue to be debated by some researchers. Selander and Plevak suggest that the paresthesia technique increases
Although rare, administration of local anesthetic drugs can results in allergic reaction. These are however, primarily the risk of postblock neuropathies. Indeed, the frequency of postanesthesia neuropathy was significantly greater
related to the use of aminoester drugs, such as procaine and chloroprocaine. The allergic reaction is related to the when paresthesia techniques were utilized, as compared with "nonparesthesia" techniques. On the other hand,
paraaminobenzoic acid, a preservative commonly found in cosmetic preparations. However, even when using amide- careful use of the paresthesia technique to localize the brachial plexus is successfully used at many centers without a
type local anesthetic solutions, allergies can occur when solutions contain preservatives (multidose preparations) or
significant increase in the risk of nerve injury. The major drawback of the paresthesia technique is that it is associated
antibacterial additives.
Local tissue toxicity reactions are rare when clinically relevant concentrations of the anesthetic solution are used. with greater patient discomfort. It is much more difficult to teach, as compared to nerve stimulator technique.
However, local anesthetics can result in neurotoxicity in cases of intraneural injection. To minimize the risk of incorrect
needle placement, much work on imaging-assisted nerve block placement and injection monitoring is underway. For
7

Nerve fibers can be myelinated or unmyelinated; sensory and motor nerves contain both in a ratio of 4:1, respectively.
Unmyelinated fibers are composed of several axons, wrapped by a single Schwann cell. The axons of myelinated
Neurologic Complications of PNBs: Mechanisms and Management nerve fibers are enveloped individually by a single Schwann cell. A thin layer of collagen fibers, the endoneurium,
surrounds the individually myelinated or groups of unmyelinated fibers.
Introduction
Nerve fibers depend on a specific endoneurial environment for their function. Peripheral nerves are richly supplied by
Although there are relatively few published reports of anesthesia-related nerve injury associated with the use of an extensive vascular network in which the endoneurial capillaries have endothelial tight junctions, a peripheral
peripheral nerve blocks (PNBs), it is likely that the commonly cited incidence (0.4%) of severe injury is analogy to the blood-brain barrier. The neurovascular bed is regulated by the sympathetic nervous system, and its
underestimated owing to underreporting.1-3 Most complications of peripheral nerve blocks were reported with upper blood flow can be as high as 30-40 mL/100 g/minute.7 In addition to conducting nerve impulses, nerve fibers also
extremity blocks. The less frequent clinical application of lower-extremity nerve blocks may be the main reason that maintain axonal transport of various functionally important substances, such as proteins, and precursors for receptors
there are even fewer reports of anesthesia-related nerve injury associated with lower-extremity PNBs as compared and transmitters. This process is highly dependent on oxidative metabolism. Any of these structures and functions
with upper-extremity PNBs.4 While neurologic complications after PNBs can be related to a variety of factors related can be deranged during a traumatic nerve injury, with the possible result of temporary or permanent impairment or
to the block (e.g., needle trauma, intraneuronal injection, neuronal ischemia, and toxicity of local anesthetics), a loss of neural function.
search for other common causes should also include positional and surgical factors (eg, positioning, stretching,
retractor injury, ischemia, and hematoma formation). In some instances, the neurologic injury may be a result of a The size and the number of the fascicles greatly in a peripheral nerve substantially vary from one peripheral nerve to
combination of these factors. another. In general, the larger the nerve, the greater the number and the size of the fascicles. Additionally, the larger
the fascicle, the greater is the risk of intraneural injection as large fascicles can accommodate the tip of the needle.8
In this chapter, mechanisms and consequences of acute neurologic injury related to the nerve block procedure are Of note, the fascicular bundles are not continuous throughout the peripheral nerve. They divide and anastomose with
discussed and where appropriate, methods and techniques to reduce the risk of complications are suggested. one another as frequently, as every few millimeters.9 However, the axons within a small set of adjacent bundles
Specific nerve injuries with upper and lower nerve block techniques, neuraxial anesthesia, and local anesthetic redistribute themselves so that the axons remain in approximately the same quadrant of the nerve for several
toxicity elsewhere in this volume. centimeters. This arrangement is of practical concern to the surgeons trying to repair a severed nerve. If the cut is
clean, it may be possible to suture individual fascicular bundles together. In such a scenario, there is a good
probability that the distal segment of nerves synapsing with the muscles will be sutured to the central stump of motor
axons and the same for sensory axons. In such cases, good functional recovery is possible. If a short segment of the
nerve is missing, however, the fascicles in the various quadrants of the stump may no longer correspond with one
Functional Histology of the Peripheral Nerves another, good axial alignment may not be possible and functional recovery is greatly compromised or improbable.9
This arrangement of the peripheral nerve helps explain why intraneural injections result in disastrous consequences
The functional histology of the peripheral nerve is important to understand the as opposed to clean needle nerve cuts which tend to heal much more readily.
mechanisms of peripheral nerve injury. Here we will only briefly review salient features
of the organization of the peripheral nerves. A peripheral nerve is a complex structure The connective tissue of a nerve is tough, compared to the nerve fibers themselves. The connective tissue of a nerve
consisting of fascicles held together by the epineuriuman enveloping, external permits a certain amount of stretch without damage to the nerve fibers. The nerve fibers are somewhat wavy, and
connective sheath, Figure 1. Each fascicle contains many nerve fibers and capillary when they are stretched, the connective tissue around them is also stretched giving it some protection.5 This
blood vessels embedded in a loose connective tissue, the endoneurium.5 The feature, perhaps, plays a safety role in nerve blockade by allowing the nerves to be pushed rather than pierced by
perineurium is a multilayered epithelial sheath that surrounds individual fascicles and the advancing needle during nerve localization. For this reason, it is prudent to avoid stretching the nerves and nerve
Table 1. Mechanism of peripheral nerve injury related to peripheral nerve consists of several layers of plexii during nerve blockade (such as in axillary brachial plexus block and some approaches to sciatic block).
Figureblocks
1. Histology of the perineural cells. Therefore, in Nerves receive blood from the adjacent blood vessels running along their course. These feeding branches to larger
peripheral nerve. Shown are essence, a fascicle is a group of nerves are of macroscopic size and irregularly arranged, forming anastomoses to become longitudinally running
a large fascicle of the nerve fibers or a bundle of vessel(s) that supply the nerve and give off subsidiary branches. Although the connective tissue sheath enveloping
Mechanical-acute
peripheral nerve with its nerves surrounded by nerves serves to protect the nerves from stretching, it also believed that neuronal injury after nerve blockade may be
Laceration
axons,Stretch
surrounded by perineurium. Of note, fascicles due, at least partly, to the pressure or stretch within poorly stretchable connective sheaths and the consequent
perineurium, epineurium and can be organized in 1 of 3 interference with the vascular supply to the nerve.
Intraneural injection
nourishing blood vessels. common arrangements:
Vascular
monofascicular (single, large
Acute ischemia
fascicle); oligofascicular (few
Hemorrhage
fascicles of various sizes); and
Pressure
polyfascicular (many few
Extraneural
fascicles of various sizes) 6.
Intraneural
Compartment syndrome
Chemical
Injection of neurotoxic solutions
8

conceivable, for instance, in a patient who positions the anesthetized arm (e.g., long-acting or continuous brachial
plexus block) in a nonphysiologic position for a few hours. Another example of pressure-related nerve injury is
prolonged use of a high-pressure tourniquet. Finally, an intraneural injection may lead to sustained high intraneural
pressure, which exceeds capillary occlusion pressure, and leads to nerve ischemia 10. Vascular nerve damage after
nerve blocks can occur when there is acute occlusion of the arteries from which the vasa nervora are derived or from
Clinical Pearls a hemorrhage within a nerve sheath. With injection injuries, the nerve may be directly impaled and the drug injected
The larger the nerve, the greater the number and the size of the fascicles.
directly into the nerve, or the drug may be injected into adjacent tissues, causing an acute inflammatory reaction or
Additionally, the larger the fascicle, the greater is the risk of intraneural
chronic fibrosis, both indirectly involving the nerve. Chemical nerve injury is the result of tissue toxicity of injected
injection as large fascicles can accommodate the tip of the needle.
The delicate arrangement of the peripheral nerve offers an explanation as solutions (e.g., local anesthetic toxicity, neurolysis with alcohol or phenol, etc.)
to why intraneural injections result in disastrous consequences as opposed
to clean needle injuries which heal much more readily. Clinical Classification of Acute Nerve Injuries

Classification of acute nerve injuries is useful when considering the physical and functional state of damaged nerves.
Mechanisms of Peripheral Nerve Injury In his classification, Seddon 11 introduced the terms neurapraxia, axonotmesis, and neurotmesis (Table 2);
Sunderland 12 subsequently proposed a 5-grade classification system.

The etiology of peripheral nerve injury related to the use of PNBs falls in 1 of 4 categories, Table 1. Laceration results
when the nerve is cut partially or completely, such as by a scalpel or a large-gauge cutting needle. Stretch injuries to Neuropraxia refers to nerve dysfunction lasting several hours to 6 months after a blunt injury to the nerve. In
the nerves may result when nerves or plexuses are stretched in a nonphysiologic or exaggerated physiologic position, neuropraxia, the nerve axons and connective tissue structures remain intact. The nerve dysfunction probably results
such as during shoulder manipulation under an interscalene block. Pressure, as a mechanism of nerve injury, is from several factors, of which focal demyelination is the most important abnormality. Intraneural hemorrhage,
relatively common. Typical example of this mechanism is chronic compression of the nerves by neighboring changes in the vasa nervora, disruption of the blood-nerve barrier and axon membranes, and electrolyte disturbances
structures, such as fibrous bands, scar tissue, or abnormal muscles where they pass through fibro-osseous spaces if all may add to the impairment of nerve function. Because the nerve dysfunction is rarely complete, clinical deficits are
the space is too small, such as the carpal tunnel. Such chronic compression syndromes are called entrapment partial and recovery usually occurs within a few weeks, although some neurapraxic lesions (with minimal or no axonal
neuropathies. Examples of pressure injuries applicable to PNBs include external pressure over a period of hours degeneration) may take several months to recover.
(e.g., a saturday night palsy resulting from pressure of a chair back on the radial nerve of the insensate arm). The
pressure may be repeated and Axonotmesis consists of physical interruption of the axons but within intact Schwann cell tubes and intact connective
have a cumulative effect (e.g., an ulnar neuropathy resulting from habitually leaning on the elbow). Such a scenario is tissue structures of the nerve (ie, the endoneurium, perineurium, and epineurium). Sunderland subdivided this group,
Table 2. Classification of nerve injuries* depending on which of the 3 structures were involved, Table 2. With axonotmesis, the nerve sheath remains intact,
enabling regenerating nerve fibers to find their way into the distal segment. Consequently, efficient axonal
Seddon Sunderland Structural and functional processes regeneration can eventually take place.

Neurotmesis refers to a complete interruption of the entire nerve including the axons and all connective tissue
structures (epineurium included). Clinically, there is total nerve dysfunction. With both axonotmesis and neurotmesis,
Neurapraxia 1 Myelin damage, conduction slowing, and blocking
axonal disruption leads to wallerian degeneration, from which recovery occurs through the slow process of axonal
regeneration. However, with neurotmesis, the 2 nerve ends may be completely separated, and the regenerating
axons may not be able to find the distal stump. For these reasons, effective recovery does not occur unless the
Axonotmesis 2 Loss of axonal continuity, endoneurium intact, no conduction severed ends are sutured or joined by a nerve graft. With closed injuries the only way to distinguish clearly between
axonotmesis and neurotmesis is surgical exploration and intraoperative inspection of the nerve.

3 Loss of axonal and endoneurial continuity, perineurium intact, no conduction It should be noted that most acute nerve injuries are mixed lesions.11 Different fascicles and nerve fibers typically
sustain different degrees of injury, which may make it difficult to assess the type of injury and predict outcome even by
electrophysiologic means. Recovery from a mixed lesion is characteristically biphasic; it is relatively rapid for fibers
with neurapraxic damage, but much slower for axons that have been totally interrupted and have undergone wallerian
Neurotmesis 4 Loss of axonal, endoneurial, and perineurial continuity; epineurium intact; no conduction degeneration.

5 Entire nerve trunk separated; no conduction

Based on data from Seddon11, Sunderland12, and Lundborg13


9

needle-nerve relationship, agent injected and dose of the drug used.16,17,18,19 In general, subperineural changes
tend to be more prominent, compared with the central area of the fascicle.20 Additionally injury to primary sensory
neurons which is not detectable hsitologically, causes a shift in membrane channel expression, sensitivity to
algogenic substances, neuropeptide production, and intracellular signal transduction, both at the injury site and in the
cell body in the dorsal root ganglion. All of this leads to increased excitability and the occurrence of acute or chronic
pain often experienced by patients with neurologic injury. It should be noted that intraneural injection and its resultant
mechanical injury are merely the inciting mechanisms; a host of additional changes occur involving inflammatory
reactions, chemical neuritis, intraneural hemorrhage, all of which eventually leading to nerve scaring and chronic
neuropathic pain.

Prevention of Intraneural Injection


Pain on injection
Figure 2. An Figure 3. Fascicular injury after an intraneural
example of Little is known about how to avoid an intraneuronal injection. injection. Shown is loss axonal degeneration,
mechanical injection Pain with injection has long been thought of as the cardinal sign extravasation of erythrocytes and inflammatory cell
injury to the of intraneuronal injection; consequently, it is commonly infiltration.
peripheral nerve. suggested that blocks be avoided in heavily premedicated or
Shown is a large anesthetized patients. However, numerous case reports have
fascicle, with a suggested that pain may not be reliable as a sole warning sign of impending nerve injury, and it may present in only a
needle track, syrinx minority of cases.21-25 Fanelli and colleagues have reported unintended paresthesia in 14% of patients in their
created by study; however, univariate analysis of potential risk factors for postoperative neurologic dysfunction failed to
hydrostatic pressure demonstrate paresthesia as a risk factor.3 In addition, the sensory nature of the pain-paresthesia can be difficult to
of the injectate, as interpret in clinical practice.26 For instance, a certain degree of discomfort on injection (pressure paresthesia) is
well as the needle considered normal and affirmative of impending successful blockade because it is thought that this symptoms
track into the indicates that injection of local anesthetic has been made in the vicinity of the targeted nerve.26 In clinical practice
fascicle. however, it can be difficult to discern when pain-paresthesia on injection is normal and when it is the ominous sign of
Perineurium is seen an intraneural injection.27 Moreover, it is unclear how pain or paresthesia on injection, even when present, can be
bulging off the used clinically to prevent development of neurologic injury. For instance, in a prospective study on neurologic
surface of the complications of regional anesthesia by Auroy and colleagues,2 neurologic injuries after paresthesia ensued,
fascicle. although the participating anesthesiologists stopped the injection when pain on injection was reported by the patients.
Mechanical nerve injury
Intraneural Injection
Intensity of the stimulating current
As opposed to a relatively clear injury caused by a sharp needle cut, intraneural injection has the potential to create
structural damage to the fascicle(s) that is more extensive and less likely to heal, Figure 2. Indeed, the devastating The optimal current intensity resulting in accurate localization of a nerve has been a topic of controversy.28-32 For
sequelae of sensory and motor loss after injection of various agents into peripheral nerves has been well instance, stimulation at currents higher than 0.5 mA may result in block failure because the needle tip is distant from
documented.14 Nearly all experimental studies on this subject have demonstrated that the site of injection is critical in the nerve, whereas stimulation at currents lower than 0.2 mA theoretically may pose a risk of intraneuronal
determining the degree and nature of injury. More specifically, to induce neurologic injury, the injectate must be injection.33 Other authors suggest that a motor response with a current intensity between 1.0 and 0.5 mA is sufficient
injected intrafascicularly; extrafascicular injections of the same substance typically do not cause nerve injury.15 Thus, for accurate placement of the block needle,28 while some advise using a current of much lower intensity (0.5 to 0.1
the main factor leading to a substantial peripheral nerve damage associated with injection techniques is injection of mA).29,31 Others simply suggest stimulating with currents less than 0.75 mA, 32,34 or progressively reducing the
local anesthetic into a fascicle. This causes mechanical destruction of the fascicular architecture and sets into motion current to as low a level as possible while still maintaining a motor response.30
a cascade of pathophysiologic changes including inflammation, cellular infiltration, axonal degeneration, and others,
all possibly leading to nerve scaring.
Clinical Pearls
Most authors suggest that nerve stimulation with current intenisity 0.2-0.5
Histologic features of injury after intraneural injection are rather nonspecific and range from simple mechanical mA (0.1 msec) indicates intimate needle-nerve placement
disruption and delamination, to fragmentation of the myelin sheath and marked cellular infiltration, Figure 3. Using a Stimulation with current intensity 0.2mA my be associated with intraneural
variety of animal models of nerve injury, a vast array of cellular changes following peripheral nerve trauma have been needle placement
documented.15 The extent of actual neurologic damage after an intrafascicular injection can range from neuropraxia Motor response to nerve stimulation may be absent even when the needle
with minimal structural damage to neurotmesis with severe axonal and myelin degeneration, depending upon the is inserted intraneurally.
10

Assessing resistance to injection is a common practice, similar to loss of resistance to injection of air or saline using a
syringe feel during administration of epidural, paravertebral, or lumbar plexus blocks. Similarly, assessing tissue
resistance and injection compliance is another means of estimating the anatomic location of the needle tip during the
practice of PNBs. For this, clinicians use a "syringe feel" to estimate what may be an abnormal resistance to nerve
Figure 4. Intensity of the electrical current required to obtain a motor response in a block injection and thus, reduce the risk of intraneural injection. 10,31,38 However, this practice has significant
sciatic nerve block model in pigs. As the distance of the needle to the nerve inherent limitations.20 For instance, the resistance to injection is greater with smaller needles, introducing additional
decreases from 0.1 mm to the intraneural location of the needle, stimulation can be confusion as to what constitutes normal or abnormal resistance. Secondly, as opposed to loss of resistance in an
obtained with a current of progressively lesser intensity (minimum 0.08 mA (0.1 epidural injection, there is no baseline pressure information or a change in tissue compliance during nerve block
msec) with needle intraneurally). However, in 5 (25%) of the attempts to stimulate injection. In other words, with nerve block injection there is no change in pressure that can be relied upon. For
with needle intraneurally motor response could not be obtained with currents of instance, in a study by Claudio and colleagues, all anesthesiologists detected a change in pressure of as little as 0.5
0.5mA-1.7mA.* psi during a simulated nerve block injection.20 However, when gauging the absolute pressure, clinicians substantially
varied (by as much as 40 psi) in their perception of what constituted an abnormal resistance to injection. Finally, no
* Kapur E, et al. 2006 Unpublished data. information has been available on what constitutes normal and abnormal injection pressure during nerve block
performance. For these reasons, subjective estimation of resistance to injection is at least as inaccurate as perhaps
estimating blood pressure by palpating radial artery pulse; objective means of assessing resistance to injection should
be far superior in standardizing injection force and pressure.

Clinical Pearls
Normal injections into epineurium of the nerves should not result in
significant resistance to injection
When injection proves to be difficult (injection pressures >20 psi using
clinically relevant injection speed), the injection is best aborted and the
needle flashed to assure patency before trying to re-inject
Manual assessment of the resistance to injection using a hand-feel method
is highly subjective and depends on the speed of injection, needle size, and
ability of the person injecting to consistently discern the "normal" from
"abnormal" resistance.

To explain the mechanisms responsible for development of neuraxial anesthesia after an interscalene block, 39,40
Most recently published reports on nerve blocks have suggested obtaining nerve stimulation with currents of 0.2-0.5
Selander and coworkers, injected solutions of local anesthetic into rabbit sciatic nerves and traced the spread of the
mA (100 msec) before injecting local anesthetics, believing that motor response with current intensities lower than 0.2
anesthetic along the nerve sheet.41 They postulated that an intraneural injection results in significant intraneural
mA may be associated with intraneural needle placement. However logical these beliefs might sound, there are no
spread of local anesthetic. In their model, these investigators incidentally noticed that intraneural injections often
published clinical reports substantiating these concerns.
resulted in higher pressures (up to 9 psi) than those required for perineural injections (< 4 psi). Injection into a nerve
fascicle resulted in rupture of the perineurium and histologic evidence of disruption of the fascicular anatomy. This
Consequently, in current clinical practice, development of nerve localization and injection monitoring techniques to study, however, used a small-animal model, microinjections (10-200 mcl), miniature needles, clinically irrelevant
reliably prevent intraneural injection remains elusive.22 Nerve stimulators are very useful for nerve localization; injection rates (100-300 mcl/min), and did not study neurologic consequences after intraneural injections. It is perhaps
however, the needle-nerve relationship cannot be adequately precisely and reliably ascertained as early literature for these reasons that their foretelling results on the possible association of injection pressure with intrafascicular
suggests.28 Response to nerve stimulation with a commonly used current intensity (1 mA) may be absent even when injection did not change the clinical practice.
the needle makes physical contact with or is inserted into a nerve, Figure 4.35-37 Occurrence of nerve injuries
despite using nerve stimulation to localize nerves further suggests that nerve stimulators can at best provide only a
More recent studies, however, have used clinically more-applicable injection speeds and volumes of local anesthetic
rough approximation of the needle-nerve relationship.1 One fundamental problem with the nerve stimulation is that
in a canine model of nerve injury.4 The results of these studies suggest that intrafascicular injection is associated with
the current flows in all directions following the path of the least resistance and not necessarily only towards the nerve.
high-injection pressures (> 20 psi) and carry a risk of neurologic injury, Figures 5 and 6.4 Only intraneural injections
Miniscule changes at the needle tip-tissue interface can make a substantial difference on the preferential flow of
resulting in pressures greater than 20 psi have been associated with clinically detectable neurologic deficits (Figure
current away from the nerve. This may results in cessation of the motor response even when needle is in intimate
7) as well as histologic evidence of injury to nerve fascicles.
relationship with the nerve or even intraneurally. The current interest for ultrasound-assisted nerve localization holds
promise for facilitating nerve localization and administration of nerve blocks; however, the image resolution of this
technology is insufficient to visualize nerve fascicles and prevent intrafascicular injection.

Resistance to injection
11

the sciatic nerve with 12- to 27-beveled needles, with short-beveled needles resulted in the greatest degree of
neural trauma. Their work suggests that sharp needles produce clean, more-likely-to-heal cuts, whereas blunt
needles produced noncongruent cuts and more extensive damage on the microscopic images. In addition, the cuts
produced by the sharper needles were more likely to recover faster and more completely than were the irregular,
more traumatic injuries caused by the blunter, short-beveled needles.44 Although the data on needle design and
nerve injury have not been clinically substantiated, the theoretical advantage of short-beveled needles in reducing the
risk of nerve penetration has influenced both practitioners and needle manufacturers. Consequently, whenever
practical, most clinicians today prefer to use short-beveled needles for major conduction blocks of the peripheral
Figure 5. Injection pressures recorded during perineural Figure 6. Injection pressures recorded during intraneural nerves and plexuses. Sharp bevel, small-gauge needles however, continue to be used routinely for many nerve block
injection of 2% lidocaine in a sciatic nerve block model in injection of 2% lidocaine in a sciatic nerve block model in procedures, such as axillary transarterial brachial plexus block, wrist and ankle blocks, cutaneous nerve block, and
pigs. Using an injection speed of 15 ml/min and 25 gauge pigs. Using an injection speed of 15 ml/min and 25 gauge others.
insulated nerve block needle injections pressures were at insulated nerve block needle injections pressures were at
or bellow 20 psi in all but one injection.* significantly above 20 psi in all but two injections.*
Regardless of the considerations related to the needle design and risk of nerve injury, the actual clinical significance
of isolated, direct needle trauma remains unclear. For instance, it is possible that both paresthesia and nerve
* Kapur E, et al. 2006 Unpublished data. * Kapur E, et al. 2006 Unpublished data. stimulation techniques of nerve localization may often result in unrecognized intraneural needle placement, yet the
risk of neurologic injury remains relatively low. Similarly, during femoral arterial cannulation (arterial line insertion), it is
likely that the needle is often inadvertently inserted into the femoral nerve, yet injuries to the femoral nerve are rare,
and when they occur, they are usually attributed to hematoma formation rather than needle injury.45 It is possible that
a needle-related trauma without accompanying intraneural injection results in injury of a relatively minor magnitude,
which readily heals and may go clinically undetected. In contrast, needle trauma coupled with injection of local
anesthetic into the nerve fascicles carry a risk of much more severe injury.20

Toxicity of injected solution

Nerves can be injured by direct contact with a needle, injection of a drug into or around the nerve, pressure from a
Figure 7. Twenty four hours after perineural or intraneural application of hematoma, or scarring around the nerve 8,46-48. Experimental studies have shown that the degree of nerve damage
2% lidocaine in a sciatic nerve block model in pigs, the intraneural group continues to exhibit following an injection depends on the exact site of the injection and the type and quantity of the drug used 49. The
signs of paresis in the sciatic nerve distribution. most severe damage is produced by intrafascicular injections, although extrafascicular (subepineurial) injections of
some particularly noxious drugs can also produce nerve damage.17,18 Benzylpenicillin, diazepam, and paraldehyde
are the most damaging; however, a number of other medications such as, antibiotics, analgesics, sedatives, and
The current evidence suggests that neurologic injury does not always develop after an intraneural injection. 42 In fact, antiemetic medications are also capable of damaging peripheral nerves when injected experimentally or
injection after an intraneural needle placement is more likely to result in deposition of the local anesthetic between accidentally49.
and not into the fascicles.4 Intraneural, but extrafascicular (interfascicular) injection probably occurs more commonly
than thought in clinical practice.37 Such an injection results in a block of unusually fast onset and long duration rather Local anesthetics produce a variety of cytotoxic effects in cell cultures, including inhibition of cell growth, motility, and
than in a neurologic injury. This is because an intraneural but extrafascicular injection leads to intimate exposure of survival, as well as morphologic changes. The extent of these effects is proportionate to the length of time the cells
nerve fascicles to high concentration and doses of local anesthetics. However, permanent neurologic injury does not are exposed to the local anesthetic solution and occur using local anesthetic at normal clinical concentrations. Within
develop since the local anesthetic is deposited outside the fascicles and the blocks slowly resolve after the injection normal ranges, the cytotoxic changes are greater as concentrations increase. In the clinical setting, the exact site of
without evidence of histologic derangement. local anesthetic deposition plays a critical role in determining the pathogenic potential.50 After applying local
anesthetics outside a fascicle, the regulatory function of the perineural and endothelial blood-nerve barrier is only
Needle design and direct needle trauma minimally compromised. High concentrations of extrafascicular anesthetics may produce axonal injury independent of
edema formation and elevated endoneural fluid pressure.51 As with the effects of local anesthetics in cell cultures,
the duration of exposure and concentration of local anesthetic determine the degree and incidence of local-
Needle tip design and risk of neurologic injury have been matters of considerable debate for more than 3 decades.
anestheticinduced residual paralysis. Neurotoxicity of local anesthetics will be dealt with in greater detail elsewhere
Nearly 30 years ago, Selander and colleagues,43 suggested that the risk of perforating a nerve fascicle was
in this text.
significantly lower when a short-bevel (e.g., 45) needle was used as opposed to a long-bevel (12-15) needle.43
The results of their work is largely responsible for the currently prevalent trend of using short-bevel needles (i.e.,
angles 30- 45) for the majority of major peripheral nerve conduction blocks. However, the more recent work of Rice Neurologic complications following regional anesthesia may also be caused by the direct effects of local anesthetics
and McMahon44 suggested that when placed intraneurally, short-beveled needles cause more mechanical damage on the nervous tissue. Toxicity has been reported primarily with the intrathecal use of local anesthetics, but with the
than the long-beveled needles.44 In their experiment in a rat model, deliberate penetration of the largest fascicle of increasing popularity of peripheral nerve block anesthesia, reports are surfacing about the direct toxic effects of local
12

anesthetics on peripheral nerves.2 Several theories regarding the mechanism of injury have been suggested. typically higher baricity, more concentrated dose of local anesthetic bathing the spinal cord for a prolonged period of
Prolonged exposure, high doses, high concentrations, body positioning and the specific agent used may cause time as compared to a large volume, less concentrated solution typically used in epidural and peripheral nerve
transient or permanent neurologic injury by a number of intracellular mechanisms. Once the neurologic injury has anesthesia.
occurred, it has been suggested that additives such as epinephrine, or the existence of a pre-existing neurologic
condition may predispose the patient to neurotoxic effects of local anesthetics (the double-crush concept). Neuronal ischemia

Experimental models of neurotoxicity of local anesthetics have included application of local anesthetic to the sciatic Lack of blood flow to the primary afferent neuron results in metabolic stress. The earliest response of the peripheral
nerve in animals, desheathed nerve preparations, and dorsal root ganglion cells in culture using concentration of local sensory neuron to ischemia is depolarization and generation of spontaneous activity, symptomatically perceived as
anesthetic comparable to those used clinically.52 These studies have revealed considerable information about the paresthesias. This is followed by blockade of slow-conducting myelinated fibers and eventually all neurons, possibly
mechanism of injury. Sakura and colleagues discovered that the mechanism did not involve voltage dependent through accumulation of excess intracellular calcium, which accounts for the loss of sensation with initiation of limb
sodium channels. They substituted tetrodotoxin for lidocaine and found that tetrodotoxin blocked these channels as ischemia. Nerve function returns within 6 hours if ischemic times are less than 2 hours. Ischemic periods of up to 6
effectively as lidocaine without producing the toxicity associated with lidocaine.53 Johnson and colleagues discovered hours may not produce permanent structural changes in nerves. However, detailed pathological examination after
that cell toxicity may be related to mitochondrial degradation. Local anesthetics caused the mitochondria to depolarize ischemia initially shows minimal changes, but with 3 hours or more of reperfusion, there develops edema and fiber
and stop producing ATP. With the loss of ATP, energy-dependent mechanisms are compromised, leading to the degeneration that last for 1 to 2 weeks, followed by a phase of regeneration lasting 6 weeks. In addition to neuronal
accumulation of calcium intracellularly and activation of enzymes that cause cell degredation.54 He found that this damage, oxidative injury associated with ischemia and reperfusion also affects the Schwann cells, initiating apoptosis.
was unrelated to hypoxia, because lidocaine actually reduced oxygen demand.52 Cell death or apoptosis was related
to the concentration and/or the length of exposure. 1% lidocaine at an exposure for more than 90 minutes was
required to kill 50% of the cells. Exposures of less than an hour were completely reversible, but exposure to lidocaine The perineurium is a tough and resistant tissue layer. An injection into this compartment or a fascicle can cause a
at 5% concentration caused immediate cell death or necrosis.52 prolonged increase in endoneurial pressure, exceeding the capillary perfusion pressure. This pressure, in turn, can
result in endoneural ischemia.10,41 The addition of vasoconstricting agents theoretically can enhance ischemia
In addition to electrolyte imbalance (leading to cell death), the loss of ATP has been found to cause failure of axonal because of the resultant vasoconstriction and reduction in blood flow. The addition of epinephrine has been shown in
transport compromising the ability of the neuron to transport materials synthesized in the perikaryon to the axon vitro to decrease the blood supply to intact nerves in the rabbit.66 However, in patients undergoing lower-extremity
terminal.55 Fast axonal transport moves neurotransmitters from the cell body to the nerve terminal. Lidocaine has surgery, addition of epinephrine to the local anesthetic solution used in combined femoral and sciatic nerve blocks
been shown to produce a reversible blockade of rapid axonal transport. Recovery is dependent on the concentration has not been shown to be a risk factor for developing postblock nerve dysfunction.3
and the exposure time of the local anesthetic on the nerve tissue. High concentrations and/or prolonged exposure has
been postulated to cause prolonged or permanent nerve injury.56 Furthermore, the loss of ATP leads to the failure of Tourniquet Neuropathy
the sequestration of neurotransmitters within the cells, leading to an increase in the extracellular concentration of
glutamate. Excessive glutamate in the extracellular space through NMDA receptors can exacerbate the elevation of
Tourniquet-induced neuropathy is well documented in the orthopedic literature and ranges from mild neuropraxia to
calcium within the cells ultimately leading to further cell degredation.55,57 This effect is noted only in the central
permanent neurologic injury.67-70 The incidence of tourniquet paralysis has been reported as 1 in 8000
neuraxis where glutamate is found.
operations.71 A prospective study of lower-extremity nerve blockade suggests that higher tourniquet inflation pressure
(> 400 mm Hg) was associated with an increased risk of transient nerve injury.3 Current recommendations for
Local anesthetics have been shown to cause membrane solubilization at high concentrations. At clinical appropriate use of the tourniquet include the maintenance of a pressure of no more than 150 mm Hg greater than the
concentrations, they can form micelles that may act as detergents to disrupt the cell membrane, although this has not systolic blood pressure and deflation of the tourniquet every 90 to 120 minutes.70 Even with these recommendations,
been proven in nerve cell membranes.58-61 Oda and colleagues demonstrated that 5% lidocaine and 0.5% dibucaine posttourniquet-application neuropraxia may occur, particularly in the setting of preexisting neuropathy.72,73
were minimum concentrations causing irreversible neurologic damage. No neurologic damage was seen with 2%
lidocaine or 0.2% dibucaine.62
Compressive Hematoma

Neurotoxicity varies with the local anesthetic solution. In histopathologic, electrophysiologic, and neuronal cell Little data exists regarding the safety of PNB in patients treated with anticoagulants. Compressive hematoma
models, lidocaine and tetracaine have been shown to have a greater potential for neurotoxicity than bupivacaine.63 formation leading to neuropathy has been associated with needle misadventures when performing lower extremity
Additives, i.e. epinephrine, can increase the toxicity of both lidocaine and bupivacaine.64 A preexisting neurologic PNB, particulary with concomitant treatment with anticoagulants.74,75 However, as opposed to spinal or epidural
condition, i.e. peripheral neuropathy, injury, surgery, may predispose the patient to nerve injury from toxicity at clinical hematoma, peripheral neuropathy from this etiology typically resolves completely.72,76-78 Regardless, these reports
doses (i.e. double crush concept).65 emphasize the important differences in the risk-benefit ratio of PNBs compared with neuraxial blocks in patients
receiving anticoagulant therapy.
In summary, local anesthetics have potentially cytotoxic effects. The mechanisms appear to involve disruption of
mitochondrial function, electrolyte imbalance leading to detrimental intracellular calcium accumulation, loss of axonal
transport and release of glutamate. The toxicity and ultimate damage to nerve tissue is related to concentration of the
agent, site of action, time of exposure and the specific local anesthetic agent used. Most studies have demonstrated a
Peripheral Nerve Blocks In Anesthetized Patients
greater effect on the intrathecal use compared to epidural or peripheral nerve exposure. This may be reflect the
13

Regional anesthesia-associated nerve injury is a significant source of concern for patients, surgeons, and become injured at the very onset of the injection and with injection of very small volume of local anesthetic (as little as
anesthesiologists alike. In addition nerve injury is a potential medico-legal liability for anesthesiologists.32 Peripheral 0.5-1 ml).79,88 Thereafter, as injection continues, the fascicle ruptures and the injectate simply leaks out through the
nerve blocks (PNBs), in particular, are of significant concern because the typical technique involves placing the ruptured perineurium into the epineurial sheath. At this stage however, the damage to the fascicle(s) may already
needle tip in the immediate vicinity of the nerve or plexus. Consequently, any postoperative neurological impairment is have been done.
automatically, and often unjustly, attributed to the PNB procedure.
(iii) Third, pain is notoriously difficult to assess in terms of quality and intensity. Therefore, distinguishing between the
Few issues in regional anesthesia have been the subject of as intense controversy as to whether peripheral nerve discomfort that is commonly seen during local anesthetic injection (which is considered normal) and that of intraneural
blocks (PNBs) carry a higher risk of neurological complications when performed in anesthetized patients versus injection can be difficult. As an example, in the study by Borgeat et al, 21% of patients undergoing interscalene block
awake patients. Opinions vary from heavy premedication being essential to the success of regional anesthesia63 to reported transient, burning pain, yet none of these patients went on to develop neurologic complication.
its being equated with negligence. Unfortunately, no large-scale controlled studies of the safety of PNBs in awake
versus anesthetized patients exists, nor are such studies likely to be available in the future. In the absence of Table 3. Reports of peripheral nerve injury with major conduction blocks
randomized, controlled studies, experts are left to draw conclusions and make logical recommendations solely on
their interpretation of the few available case reports, and anecdotal experiences. However, any such
recommendations regarding the use of sedation or general anesthesia in patients receiving PNBs could have Normal Versus Abnormal Discomfort/Pain On Injection
significant medicolegal repercussions. Therefore, the purpose of this article is to review the available literature that
supports or refutes the practice of administering nerve blocks in anesthetized patients, discuss the current Injection of LA in the close proximity to the nerves is often associated with discomfort on injection.81,93 This is
controversies, and provide insight into the future of the subspecialty with regard to this issue. Specific concerns thought to result from spraying of the LA in the vicinity of the components of the brachial plexus. Based on his
regarding performance of PNBs in anesthetized patients are presented and addressed below. Although the scientific studies of brachial plexus anesthesia, Winnie coined the term pressure paresthesia to describe the discomfort
value of case reports are often discounted, they may actually be more informative than large epidemiological studies patients feel during local anesthetic injection and implied that this was a desirable sign of impending successful
because they include a detailed account of peri-block events, which is often lacking in epidemiologic studies. blockade.81 In actual clinical practice however, the variability of patients pain thresholds, their ability to verbalize a
sensation pain during a procedure, and an anesthesiologists subjective interpretation of any such response make it
very difficult to recommend where a line could be drawn between normal and abnormal pain or paresthesia on
Symptoms of Intraneural Injections
injection. In fact, a number of published case reports demonstrate that patients complaints of pain during PNB may
not be helpful in preventing the development of the neurological complication. For instance, Barutell et al published a
The premise behind the common recommendation that PNB should only be performed in awake patients is that an report where a patient communicated discomfort on injection which was perceived as normal pressure paresthesia
awake patient can provide information that will prevent intraneural injection and therefore avoid neurological injury. by the anesthesia team and when the injection was carried out; the patient went on to develop permanent neurologic
This is because it is believed that intraneural injections are excruciatingly painful, and an awake protesting patient is damage.26 Similarly, in the report by Kaufman et al,26 all 7 patients had discomfort at some point during block
the best available monitor. However, there are three significant problems with this logic. injection; however this information could not be used to prevent the development of permanent neurologic injury
which occurred in all patients. This however may be an example of case-report bias. In other words, it is possible that
(i) The first is that the literature does not support the widespread notion that relying on an a fully awake patient's patients reports of pain may have prevented injuries but such events are unlikely to get reported.
report of pain on injection is reliable method to prevent nerve injury. In fact, most neurologic complications reported in
the literature have not been associated with pain on injection.1-3,20,23-25,27,79-83 For instance, of 49 cases of Dogmas On Complications Of Regional Anesthesia
nerve injury found in the literature search (TABLE 3), 48 patients (98%) were awake. Of these, 42 cases included
specific information about the patients response to the injection; only 4 (10%) patients reported pain on injection.
Blanket statements and dogmas are common in the field of medicine and regional anesthesia in particular. Much too
Some reports specifically state that the patient did not have pain, whereas in most others the authors commented that
often, a wide range of recommendations based on a single observation are inappropriately extrapolated. As an
the block performance was uneventful. Interestingly, the pain on administration of local anesthetic (LA) into nerve
example, Walton et al. reported the occurrence of brachial plexus palsy after total shoulder arthroplasty under an
tissue may be absent even in the central neuraxial area. For instance Kao et al. reported a case of neural injury that
otherwise uneventful interscalene block.27 However, the authors went on to suggest that, to minimize the risk of
was clearly related to spinal cord trauma from a thoracic catheter that had been inserted while the patient was
brachial plexus injury with interscalene block PNBs should not be performed in anesthetized patients, and if
anesthetized; the patient did not have pain during administration of LA postoperatively.84 More recently, Tripathi et al
paresthesia of unusual severity occurs, the injection should be immediately stopped. Ironically, their patient was
reported a case report of paraplegia after an intracordal injection during attempted steroid injection85, whereas Tsui
neither anesthetized prior to the block injection, nor did he have paresthesia or pain on injection!
and Armstrong reported a case of direct spinal cord injury after epidural injection86. Both complications occurred in
awake patients who did not report pain on needle placement and consequent injection. These report clearly indicate
that reliance on pain as a symptom of injection into neurologic tissue is unreliable. Benumof reported 4 cases of severe neurological injury that resulted in cervical paraplegia in patients receiving
interscalene brachial plexus blocks under GA.91 The discussions that followed however, often recommended that
sedation and GA be abandoned to decrease the risk of nerve injury. Such recommendations are based on this case
(ii) The second problem refers to the value of the pain (if present) as monitor in preventing nerve injury, because in
report are inappropriate because none of the patients in this report suffered a peripheral nerve injury. Rather, these
cases in which the pain does accompany an intraneural injection it may already be too late to prevent neurologic
patients received an intracordal injection, a complication entirely avoidable with restriction of the needle insertion
injury. For example, in the ASA closed-claims study, Cheney and coworkers indicate that on those occasions where
depth and/or use of more lateral approach to interscalene block.4,92,94
pain did occur during injection, the anesthesiologist stopped the injection, however, the patients still went on to
develop nerve injury.87 Similarly, studies utilizing animal models of intraneural injection suggest that nerve fascicles
14

Those who base their criticism of "heavy" premedication or GA prior to performing peripheral nerve blocks on the be inserted or injection be made into an anesthetized nerve.81 Common examples of rescue blocks after failed
cases reported by Benumof95 forget that interscalene block is a superficial procedure, devoid of significant discomfort axillary or interscalene brachial plexus blocks include elbow and wrist blocks.100,101
where excessive sedation and analgesia are usually unnecessary except in children who otherwise would not hold
still during the procedure. In contrast, many other PNB procedures involve deeper placement of the needle and Multiple injection techniques
several attempts at nerve localization that result in significant patient discomfort.94,96,97 Therefore, generalized
recommendations to avoid premedication during PNBs carry the risk of limiting the use of PNBs because of an
inevitable decrease in patient acceptance. In our practice at St. Luke's-Roosevelt Hospital Center in New York, Multiple injection techniques for both upper and lower limb blockade have been introduced relatively recently in
patients are sent an anesthesia satisfaction survey after their discharge home. Analyses of more than 5,000 of patient clinical practice with the suggestion that they decrease onset time, increase the success rate, and decreases the
responses clearly indicate that the most satisfied patients are those with no recollection of any anesthetic procedure required dose of LA.102-109 The withdrawal and redirection of the needle to elicit multiple motor responses however,
being performed on them. Therefore, if PNBs are to be accepted by patients, adequate premedication is necessary to carry a greater risk of direct needle trauma and intraneural injection into already anesthetized nerves. Regardless,
avoid patient discomfort during needle placement. this technique has been uniformly accepted by most experts in the field.

Literature Review Double blocks and repeat blocks after failed blocks

No study has compared the risk of neurologic complications in awake versus Regional anesthesia for elbow surgery has traditionally been a challenge. The most commonly used brachial plexus
anesthetized patients, and it is unlikely that such studies will ever be done. A review of blocks--the classical approach to interscalene block and the axillary block--are not ideal because they either do not
published reports of injury after PNBs indicates that significant neurologic injury after result in reliable block of the ulnar nerve or do not result in adequate analgesia for the tourniquet, respectively. For
PNBs in awake patients occurs at a rate of 0.2%-0.4%.97 Most of these reports that reason, in patients undergoing elbow surgery successful regional anesthesia requires the concomitant use of two
included brachial plexus blocks only, probably because these techniques are used separate approaches, an interscalene and an axillary approach.110 Obviously, performance of brachial plexus block
more frequently than lower extremity nerve blocks.20 In a recent similar prospective at either level precludes the sensory or motor feedback information during performance of the block at the second
evaluation by Bogdanov and Loveland, none of 548 patients who received an level.
interscalene brachial plexus block after induction of GA developed permanent or long- Figure 8. Injection of local
term neurologic complications.81 Similarly, in a report presented at the 2005 Annual anesthetic in lateral Awake Patients Will Have Signs Of Cns Toxicity As A Monitor Before Cvs Toxicity Ensues
ASRA Spring Meeting, Tsai et al presented the data on 226 PNBs of both upper and approach to popliteal block
lower extremities, all performed in heavily sedated or anesthetized patients, none of with in-line monitoring of the Practice of PNBs involves administering large volumes and doses of LAs. A typical clinical presentation of LA toxicity
whom developed neurologic complications. Bogdanov et al. used a modified classical injection pressure to avoid is in an awake or sedated patient during or immediately after injection of LA, followed by sudden onset of confusion,
approach to interscalene block proposed to reduce complications whereas Tsai et al. pressures >20 psi which seizure, arrhythmias or cardiac arrest.111,112 It has been suggested that heavy sedation or GA increases the risk of
used objective assessment of injection pressures to reduce the risk of intraneural may be associated with severe systemic toxicity of LAs because it diminishes the patients ability to report early signs and symptoms of rising
injection during PNBs of both upper and lower extremity, Figure 8.98 While the intraneural injection. LA serum levels. However, there are no reports of LA toxicity in adult patients under GA; essentially all reports of
relatively small number of patients in these reports do not allow accurate comparison, toxicity were in awake patients.23,91,113,114 For example, Edde and Deutsch reported an occurrence of cardiac
these studies at least indicate that the risk of complications of PNBs after GA may not arrest after interscalene brachial plexus block in an awake patient who had no symptoms of toxicity until the entire
be substantially more common than complications reported in other similarly powered studies in awake patients.99 In dose (20 mL of 0.5% bupivacaine) was administered.115,116 Conversely, others may argue that premedication offers
fact, performance of PNBs in heavily premedicated patients or after induction of GA is undoubtedly a common protection because of its anticonvulsive effects. Moreover, since the critical steps in treating patients with severe
practice, and a routine in the pediatric anesthesia practice. A recent informal poll conducted during the ASRA 2005 toxicity is establishment of patent airway, hyperventilation, administration of oxygen, and hemodynamic support, one
session on complications of PNBs indicated that approximately half of the present attendees performed blocks in can argue that anesthetized and ventilated patients who develop systemic toxicity may actually be better off because
heavily sedated or anesthetized patients. they already have a secured airway, they are receiving a high concentration of oxygen and they are typically in, an
environment that is ideally suited for aggressive resuscitation.
Rescue Blocks, Multiple Injection Techniques, And Reverse Axis Blocks
Bernards et al. reported that pigs given an intravenous infusion of bupivacaine failed to demonstrate signs of CNS
Several PNB techniques that are equivalent of a PNBs in anesthetized patients are accepted as sound practice. toxicity prior to cardiovascular collapse if they had been pre-medicated with benzodiazepines.23 Indeed, in clinical
These include rescue blocks, multiple injection techniques and reverse axis blocks; they are all similar to the studies of local anesthetic toxicity, volunteers clearly report an escalating series of symptoms as plasma
practice of PNBs in anesthetized patients because the PNB is performed in a partially or fully anesthetized limb. concentration of local anesthetic rises during continuous, slow intravenous infusion. However, the occurrence of
symptoms of local anesthetic toxicity depends on the rate at which drug is injected. The difficulty in extrapolating this
Rescue blocks into clinical practice is that local anesthetic for the purpose of neuronal blockade is given as a relatively rapid bolus,
rather than a slow, escalating continuous infusion as is the case in animal models.

Missed nerve blocks may occur from 3% to30% of the time and usually involve only one or two of the terminal
nerves.20 Several well established and universally accepted techniques of PNBs, such as repetition of the block, For these reason, any suggestion that GA predisposes to a greater risk of severe systemic toxicity of LA is purely
peripheral injection of the nerve and others are often used to rescue failed blocks despite the risk that the needle may theoretical, as there are no data to firmly support this belief. Finally, LA toxicity is of potentially greater concern in the
15

pediatric patient due to lower dose requirements and need for stringent adherence to mg/kg dosage rather than a on the practice of regional anesthesia. Many patients and PNB techniques require appropriate sedation for block
volume dosage as is the common practice in adult anesthesia. Regardless, the practice of regional anesthesia in performance and patient acceptance, however, clinicians may be reluctant to use them due to the medico-legal
anesthetized patients is universally accepted in this patient population. concerns engendered by admonitions against performing blocks in sedated or anesthetized patients. Future efforts
must be directed toward developing more objective and exacting nerve localization and injection monitoring
Nerve Blocks In Anesthetized Children Versus Adults techniques to more reliably detect and prevent intraneural injection. The results of these efforts will inevitably be of far
greater importance to the future of PNBs and their role in practice of modern anesthesiology than over-reaching,
unsubstantiated opinions and statements.
As opposed to PNBs in adults, performing blocks in anesthetized pediatric patients is a universally accepted practice.
This is by necessity, because pediatric patients are unlikely to be cooperative during needle insertion, nerve
stimulation and manipulation necessary to accomplish PNB. In addition, most pediatric patients require concomitant
administration of GA to allow for immobility during the surgical procedure. However, from the standpoint of risk of
complications, this divergence in consensus on PNBs after GA between adults and pediatric patients does not make Methods And Means To Decrease The Risk Of Neurologic Complications Associated With Nerve Block
much sense. In other words, with perhaps the exception of infants, there are no sufficient anatomical, or neuro-
physiological differences to justify this divergence in recommendations. While one can argue that complications of
The published data suggests that neurologic complications of PNBs are relatively rare. However, their the severity of
PNBs in children are rare, PNBs are not routinely used in the pediatric population and there are simply no series
consequences and lack of prevention strategies continue to present a source of significant concern for both clinicians
comparable to those in adults to allow one to draw a clear conclusion regarding the risk of nerve injury in children.
and patients. The main inciting mechanism of neurologic injury with PNBs appears to be an intrafascicular or
However, a large prospective study performed in France in children demonstrated a small risk of complications with
intraneural injection. It is fortunate that peripheral nerves possess an inherent natural protection; intraneural injections
peripheral nerve blocks.117
often do not result in intrafascicular needle placement and therefore, do not necessarily lead to nerve injury. It is
commonly suggested that the use of short-beveled needles and avoidance of excessive sedation and general
Monitoring Possibilities During PNBs anesthesia should be employed to decrease the risk of nerve injury. However, these commonly voiced
recommendations have been recently challenged. In addition, avoidance of adequate premedication may have a
Since this discussion focuses on the impact of heavy sedation or GA on the risk of neurologic complications, it is significant negative impact by decreasing the patients acceptance and satisfaction with PNBs. The relatively low
important to discuss the monitoring that is available to reduce the risk of nerve injury during PNBs. In general, there incidence rate of complications with PNBs, coupled with the lack of objective documentation and means to more
are two phases amenable to monitoring during placement of PNBs. These include needle placement guidance precisely monitor administration of nerve blocks make retrospective analyses of cases of nerve injury largely
(percutaneous stimulation, ultrasound) and avoidance of intraneural injection (report of pain on injection by the patient speculative with regard to the actual mechanism of nerve injury in clinical practice.
(when present), nerve stimulation, and assessment of resistance to injection).118 With regards to intraneural
injection, neither percutaneous stimulation or ultrasound guidance are helpful. Percutaneous stimulation may be The following recommendations are suggested to decrease the risk of complications with PNBs:
helpful with approximating the needle insertion site but it is useless in estimating the needle-nerve relationship.
Ultrasound on the other hand, offers real-time needle guidance below the skin level. However, in addition to the
required skill, expense and inconvenience of the equipment, the image resolution is simply insufficient to rule out Aseptic technique
Most nerve block techniques are merely percutaneous injections. However, infections are known to occur
intraneural needle placement.119 Nerve stimulator-assisted PNBs entered the practice of regional anesthesia with the
and can result in significant disability. Since this complication is almost entirely preventable, every effort
promise of decreasing the risk of neurologic complications associated with paresthesia technique.120 However, it should be made to adhere to strictly aseptic technique.
soon became apparent that nerve stimulators could not prevent neurologic injury.37 More recently, it has been Short bevel insulated needles
suggested that in many circumstances, the motor response to nerve stimulation may be absent at the point at which Insulated needles are now widely available and result in much more precise needle placement. The short
the needle makes contact with the nerve,121 and that intraneural needle placement is possible despite the use of bevel design helps prevent nerve penetration.
nerve stimulators, Figure 4.1 Needles of appropriate length for each block technique
Excessively long needles should not be used for nerve blockade. For instance, never use needles longer
than 50 mm for an interscalene block. In addition to the safety reasons, needles of appropriate length are
In summary, few issues in the practice of regional anesthesia have evoked such strong and divergent opinion among also advanced with far greater precision than excessively long needles.
clinicians as performance of PNBs in anesthetized or deeply sedated patients. This is because administration of Surface localization
PNBs has traditionally been based on individual preferences, clinical impressions, and other subjective criteria, rather In patients with difficult anatomy, surface localization of superficially seated nerves or plexuses can help
then on established practice standards. Avoidance of deep sedation and GA is often suggested to decrease the risk of reduce the number of needle passes.
peripheral nerve injury with PNBs, however, there is no evidence in the literature to suggest that either practice is Needle advancement
safer with regards to the risk of nerve injury. Regardless, the serious nature of complications resulting from During needle localization, advance and withdraw the needle slowly. Keep in mind that nerve stimulators
inadvertent injections into the spinal cord suggests that regional anesthesia techniques close to the centroneuraxis deliver current of very short duration once (1 Hz) or twice (2 Hz) a second and that no current is delivered
should be practiced with extreme caution and insight into the appropriate depth of the needle insertion whether the between the pulses. Thus, fast insertions and withdrawal of the needle passages may result in failure to
stimulate the nerve because the needle may pass near by, or even through, the nerve between the
patient is awake, sedated or anesthetized. It is the opinion of these authors that proper training, and use of proper
stimuli without eliciting nerve stimulation.
techniques and nerve block/monitoring equipment are more likely to decrease the risk of complication than are Fractionated injections
unfounded blanket statements as to the advisability of performing peripheral nerve blocks in anesthetized patients. Inject smaller doses and volumes of local anesthetics (3-5 mL) with intermittent aspiration to avoid
This is because such statements are unfounded by the relevant literature and can have a potentially negative impact inadvertent intravascular injection. Always observe the patient during the injection of local anesthetic
16

because negative aspiration of blood is not always present with an intravenous injection. This approach Peripheral Nerve Injury After Peripheral Nerve Blocks: Diagnosis, Prognosis, And Treatment
may allow detection of the signs of local anesthetic toxicity before the entire dose is injected.
Accuracy of the nerve stimulator
Nerve injury is recognized as a potential complication of peripheral nerve block anesthesia, but fortunately, severe or
Always make sure that the nerve stimulator is operational, delivering the specified current, and that the
disabling injuries are rare. When they do occur, they can be a frightening complication for the patient, the surgeon,
leads are properly connected to the patient and the needle.
Avoidance of forceful, fast injections and the anesthesiologist. Fortunately, most symptoms of nerve injury usually resolve in four to six weeks in over 95%
Forceful, fast injections are more likely to result in channeling of local anesthetic to the unwanted tissue of patients, and in 99% of the patients by one year.35 Early intervention may help prevent the long-term sequelae that
layers, lymphatic vessels, or small veins that may have been cut during needle advancement. Such can occur with unrecognized, and therefore improperly treated nerve injuries. With the resurgence of interest and
injections may result in massive channeling of the local anesthetic in the systemic circulation, with utilization of peripheral nerve block anesthesia, it is important to develop a coinciding plan for management of
consequent risk of severe CNS and cardiac toxicity. Finally, forceful, fast injections under excessive postoperative nerve injuries. The plan should include recognition, diagnosis, and treatment of the nerve injury. A
pressure are more likely to result in an unrecognized intraneuronal injection. Limit the injection speed to working knowledge of the long-term prognosis, understanding the importance of appropriate neurology consultations
15-20 mL/minute. and familiarity with available diagnostic tests and treatment options is essential for the proper management of patients
Avoidance of injection against abnormal resistance
with neurologic injury.
Intraneuronal needle placement may result in high resistance (pressure) to injection due to the compact
nature of the neuronal tissue and its connective tissue sheaths. Always use the same syringe and needle
size to develop a feel during the injection. As a rule, when injection of the first 1 mL of local anesthetic With any peripheral nerve block, inclusive documentation of the block is of utmost importance for diagnostic,
proves difficult, the needle should be slightly withdrawn and the injection attempted again. If the therapeutic and medicolegal purposes. Documentation that includes the nerve(s) stimulated, the minimum current
resistance persists, the needle should be completely withdrawn and flushed before repeating the used, the number of attempts, the appearance of pain or paresthesia during the procedure and measures taken,
insertion. Ultimately, objective injection pressure monitoring will likely become a standard monitor to
resistance to injection and injection pressure if pressure monitoring is used, type/dose of local anesthetic agent, and
standardize nerve block injections, reduce the risk of intraneural injection and for medico-legal
documentation, Figure 8. patient condition during the block is essential in understanding the mechanism of the injury. This documentation can
Abort injection if pain is reported by the patient help the anesthesiologist and/or consulting specialist determine the possibly etiology of the injury, any associated
Severe pain or discomfort on injection may signify intraneuronal placement of the needle and should be conditions, and guide treatment modalities.
avoided. When this occurs, the injection should be abandoned, although the chances are that a damage
may have already been caused at the time when the pain occurs. Lancinating, "shooting" pain on
Mechanisms of Injury/Symptoms
injection should not be confused with a mild paresthesia-like report by the patient when the needle is
placed in the immediate vicinity to the nerve or plexus. In this case, local anesthetic can be injected
slowly, provided that the resistance to injection is normal (<20 psi). Resuming the injection after waiting to Following peripheral nerve anesthesia, if sensory and/or motor function remains depressed beyond the expected
see whether the pain will go away should not be done under any circumstances. duration of action of the local anesthetic, potential causes for the neurologic deficits should be investigated.
Choose your local anesthetic solution wisely Neurologic deficits may be related to vascular injuries, compression injuries, local anesthetic action, or traumatic
Always choose a shorter acting (and less toxic) local anesthetic for short procedures where long-lasting nerve injury with fascicular disruption. When faced with a neurologic deficit, especially in a patient in whom a
postoperative analgesia is not required. Local anesthetic toxicity is the most common complication with
peripheral nerve block has been placed, it is important to remember that there are many causes of nerve injury
neuronal blockade; The risk of sever toxicity is substantially lower with chloroprocaine or lidocaine than
with bupivacaine. unrelated to the performance of the regional anesthetic.
Blocks in anesthetized patients
In the absence of reliable monitoring, blocks in anesthetized patients should still not be a common Other factors, i.e. tourniquet use, improper positioning, postoperative swelling, surgical trauma, and pre-existing
practice. When it is necessary to place blocks in anesthetized patients, this should be done by neurologic deficits may be contributing or causative influences. Proper and objective documentation of the nerve
practitioners with experience and pro-cons documented in the chart. The introduction of ultrasound-
block procedures can go a long way in deciphering whether the injury was caused by a nerve block, surgery or other
guided nerve blocks and injection pressure monitoring will likely change the practice and allow more
routine performance of nerve blocks in anesthetized patients. factors.
Repeating blocks after a failed block
Repeating a block after a failed block should be avoided whenever possible. When indicated, it should be a. Vascular Injuries - When symptoms occur early in the postoperative period (i.e. within minutes to hours), the
done only by those with substantial experience in the planned technique. Avoidance of abnormal anesthesiologist should suspect a vascular or compression-type injury due to disruption of the blood supply from an
resistance to injection or objective injection pressure monitoring is of utmost importance here as the insult to the vascular structures, from hematoma at the surgical or block site, or from deep venous thrombosis. This is
clinician can no longer count on pain on injection as a sign of intraneural injection.
particularly true should a neurologic deficit appear after apparent resolution of the block.

b. Compression Injuries - Compression neuropathies usually present as a focal mononeuropathy at sites where
nerves pass through tissue tunnels, i.e. median through carpal tunnel, spinal nerve through vertebral foramina. Acute
Management Of Patients With Neurologic Injury compression injuries can develop secondary to limb tourniquet paralysis, retractors used for surgical procedures, from
expanding hematomas, or from improper intraoperative positioning, i.e. stretching of the cords of the brachial plexus
during sternal retraction, or extending/pronating the forearm causing ulnar nerve compression.37,122 A compression
injury can also occur with peripheral nerve block anesthesia from increased endoneural fluid pressure. This can occur
with injection into a tight tissue compartment or when high injection pressures are used during nerve block
17

administration.77 Metabolic diseases such as diabetes mellitus may make nerves more susceptible to compression Patient Evaluation/Physical Examination
injuries.123 Symptoms Of Nerve Injury

c. Local Anesthetic Action- It is important to remember that neurologic deficits may be related to the residual The symptoms of a nerve lesion after peripheral nerve block manifest after the block has receded; usually within 48
neurologic blockade. Long-acting local anesthetics such as ropivacaine or bupivacaine have been reported to last up hours. The perception of symptoms is influenced by the origin of the nerve lesion and other confounding factors, such
to twenty-four hours. It is nowadays well recognized that intraneural injections can and do occur without obligatory as postoperative pain, immobility, effects of surgery, position, application of casts, dressing, bandaging, and so forth.
neurologic injury.124 Most such injections result in intraneural, but perifascicular injection of local anesthetic and their The intensity and duration of symptoms may also vary with the severity of the injury, from a light, intermittent tingling
hallmark is a block of much longer duration than expected.125 When additives are included in the local anesthetic and numbness lasting a few weeks to a persistent, painful paresthesia, neuropathic pain, sensory loss, and/or motor
mixture, particularly in the setting of an intraneural injection, the block can be prolonged up to forty-eight hours.37 In weakness lasting for several months or years. Some nerve injuries may even evolve into a severe causalgia or reflex
the elderly and in those with pre-existing neurologic diseases, local anesthetic action can be prolonged secondary to sympathetic dystrophy. It should be kept in mind that although dermatomes can provide clues to the location of
abnormal uptake or reduced perfusion to the nervous tissue.126 The site of the block may have an effect on the injuries, the loss of sensation at the skin does not provide precise information concerning the site of injury because
duration of action of the local anesthetic.127 Therefore, in patients with known or occult preexisting neurologic the boundaries of dermatomes are not precise, clearly defined lines. More useful information can be obtained from
diseases, the elderly, and in those treated with long-acting local anesthetics, sufficient time should be allowed for the the loss of motor function on the basis of the origin and assessment of motor performance.
local anesthetic to be thoroughly metabolized. Physical examination of these patients will usually reveal a slowly
receding block. Once the return of motor function occurs, the block will usually recede in an accelerated fashion. If The symptoms of neurological injury may range from mild to severe. Typical symptoms include dyesthesia,
motor function returns with persistent sensory deficits, or motor dysfunction persists, further evaluation is necessary. paresthesia, numbness, weakness, and pain. Symptoms of nerve injury may be acute or may not become clinically
apparent for several days to several weeks. The approach to patient evaluation should be indistinguishable
d. Traumatic/Toxic Nerve Injury - Nerve injury following peripheral nerve blocks may be caused by direct needle regardless of the timing of the suspected injury. Physical examination should include an assessment of vascular
trauma, intraneural injection or local anesthetic neurotoxicity. Several animal studies have demonstrated that the integrity, sensory/motor function, and reflexes.
frequency of nerve injury is greater with long beveled needles, but the duration and severity of the injury is greater
with short beveled needles. When the bevel orientation is perpendicular instead of parallel to the nerve fibers, studies a. Vascular Mediated
have shown that nerve injury can be more severe.128 Intraneural intrafascicular injection is characterized by high
injection pressures at the onset of injection.129 Such injections are characterized by a prolong blockade followed by
Vascular-mediated injuries include injury to arteries, veins, the formation of deep vein thrombosis, or a combination of
incomplete resolution and residual neurologic deficit. Because miniscule amount of local anesthetic (as little as 0.5
any of these, creating vascular compromise.
ml) is required to rupture the fascicle, intraneural injection should be suspected whenever there is resistance to
injection or when the patient experiences severe pain on injection.
Vascular injury with associated ischemia should be immediately. The examination should include an assessment of
both venous and arterial circulation, skin color changes, the presence of engorgement or edema, hematoma or pain
All of the local anesthetics are potentially neurotoxic. Neurotoxicity is dependent on the dose, concentration, and
at the surgical or block site. If a vascular injury is suspected, the surgical team should be consulted immediately to
length of exposure to the nerve tissue. Vasoconstrictive additives such as epinephrine that can affect neural blood
manage and treat the problem. For example, patients with lower extremity joint replacement surgeries are prone to
flow may potentiate nerve injuries.130,131 Local anesthetic neurotoxicity is more prevalent in patients with pre-
the development of deep venous thrombosis. Patients may be completely asymptomatic, or they may complain of
existing neurologic deficits, especially those with demyelinating diseases. In several studies of patients with occult or
limb pain, limb swelling, or leg pain on dorsiflexion of the foot. If the patient is receiving a continuous femoral nerve
diagnosed multiple sclerosis, local anesthetic action was prolonged. The prolonged duration was thought to be related
block, (typical after this type of surgery), and complains of pain behind the knee (sciatic distribution), the
to an abnormal uptake of local anesthetic in demyelinated nerves.132
anesthesiologist must be cognizant of the possibility of a deep venous thrombosis vs incisional pain not covered by
the femoral block. Occlusive dressing should be evaluated to make sure that they are not contributing to the vascular
Magnitude of Neural Injury insult. With arterial compromise, the patient will complain of intense pain, paresthesia, and cold. The onset is usually
rapid. A doppler/vascular study is the most common diagnostic test used to aid in the diagnosis. Arterial occlusion or
The degree of neural insult can be defined by the the terms neurapraxia, axonotmesis, and neurotmesis. The mildest compromise will usually require emergent surgical exploration.
form, neurapraxia, denotes a mild degree of neural insult with failure of impulse conduction across the affected
segment. The electromyogram (EMG) is normal, but conduction velocity as demonstrated by a nerve conduction b. Neurologically Mediated
study (NCS) is decreased. Usually when the offending cause has been removed, recovery occurs over a variable
amount of time that may be as long as several weeks. Complete recovery can usually be anticipated. Axonotmesis,
If the physical examination demonstrates intact circulation, then a more thorough neurologic examination should be
an intermediate injury, occurs when there is axonal disruption with preservation of the endoneurium. Recovery is
initiated. This includes a comprehensive motor and sensory examination as well as assessment of the reflexes. In
dependent on the rate of axonal regeneration (1-3 mm/day). If recovery occurs, it is most likely to be prolonged and
multiple studies evaluating the incidence and prognosis of nerve injury after peripheral nerve block anesthesia, the
incomplete. The prognosis is better for young, healthy patients with distal lesions. The most severe form of neural
majority of mild symptoms such as dyesthesia, mild paresthesia or numbness, or mild pain resolved within the first
injury is neurotmesis; a complete transection or crushing of the nerve with disruption of the endoneurium. Surgical
few days or weeks of the insult. Further diagnostic testing was not indicated.2,32,35,133,134
repair is usually indicated, but even then, recovery is usually incomplete. Prognosis for full recovery is poor.
18

If the neurologic deficit is persistent or more severe (i.e. moderate to severe numbness, weakness and/or pain) then brachial plexus. Although some authors promote early EMG testing with repeat EMGs at intervals, in reality, most
an evaluation by a neurologist may be indicated. For the hospitalized patient, the neurology consultation and patients will not agree to repeat testing. The major disadvantage of EMGs are that they are painful procedures
subsequent examination should take place during the hospitalization. If the patient has already been discharged, a performed on awake patients. This test should be utilized when the highest probability of capturing signs of de-
neurologist can be contacted for an outpatient evaluation. The magnitude or the rate of progression of symptoms will innervation are present, i.e. two to four weeks after the initial injury. If the test is delayed beyond that time interval,
influence the urgency of the neurology consultation. Temporizing measures for pain control may be initiated until the signs of re-innervation, i.e. long-duration, high-amplitude, polyphasic motor unit potentials, become present.
patient can be evaluated. The neurology assessment will involve a more meticulous clinical examination to try to
evaluate the degree of deficit and to determine what further diagnostic tests are indicated. b. Doppler Ultrasound/High Frequency Ultrasound

Diagnostic Tests Doppler ultrasound provides both functional and structural information about the image being scanned. Most
commonly it is used to study the carotid arteries and major arteries and veins of the lower extremities. It can be also
There is a variety of diagnostic tests available for the detection of nerve injury. Each test has specific indications, be used to examine the arteries at the wrist, in the palms, and in the digits. It is the most common diagnostic test for
advantages and disadvantages depending on the injury, the patient characteristics, the availability of the diagnostic deep venous thrombosis.
equipment, and the expertise of the operator. The diagnostic tests currently available include electrophysiology, high-
resolution ultrasound, and magnetic resonance imaging.
A newer type of ultrasound, high frequency ultrasound, is an effective imaging modality for identifying morphologic
changes in the peripheral nerves. It is being used to evaluate nerve rupture, inflammatory processes, and
a. Electrophysiology Testing compressive syndromes in peripheral nerves. It is an excellent test to localize the lesion, possibly providing an
alternative to EMG. But because is does not test for the functional capacity of the nerve, it should probably be
Electrophysiology testing is important for defining the neurogenic basis of weakness, for localizing the site of the combined with a nerve conduction study. It may be a useful tool for initial imaging of a suspected peripheral nerve
lesion, and to aid in determining the site of the lesion. Nerve conduction studies evaluate the sensory and motor injury or for follow-up imaging. It is faster and more cost-effective than magnetic resonance imaging, and avoids the
signal amplitude and conduction velocity in myelinated nerves. In sensory nerves, changes in amplitude relate to the problems associated with claustrophobia. But it has limitations in that the test is operator dependent, requires an
degree of axonal damage, while changes in conduction velocity relate to myelin damage. In motor nerves, changes in extended learning curve to obtain and interpret images, and is limited to nerves within 2 cm of the skin surface.3 At
amplitude and conduction velocity are more difficult to localize because the signal involves the entire motor unit (i.e. greater depths, coarser quality ultrasound nerve images can be obtained but they are difficult to distinguish from other
the motor axon, neuromuscular junction, muscle fibers). If an isolated motor deficit is elicited, then the presence of tissues such as tendons.122
disease involving the neuromuscular junction or muscle itself may need to be evaluated.
c. Magnetic Resonance Imaging/Magnetic Resonance Neurography
The indication for a nerve conduction study is weakness, numbness, or paresthesia. If nerve injury has occurred,
changes in the nerve conduction study can be seen within days. If the complaint is strictly pain, a nerve conduction Magnetic resonance imaging, specifically magnetic resonance neurography, is a relatively new imaging technique that
study is unlikely to detect any injury because only the signals transmitted via myelinated fibers are evaluated by this can reliably and selectively image peripheral nerves.135 By manipulating MRI parameters, nerves can be made to
test; the function of unmyelinated axons. i.e. those responsible for pain transmission, is not evaluated. Therefore, the show up as three-dimensional neurographic images, comparable to angiograms. When it is properly implemented,
patient can have a normal nerve conduction study and still suffer from pain. MR neurography is capable of providing high-quality information about nerve compression, nerve inflammation, nerve
trauma, systemic neuropathies, and recovery of nerves from pathologic states.136 Direct nerve imaging has been
If the initial study is normal, there is a strong probability that the patient has neuropraxia which should resolve over shown to demonstrate nerve continuity, distinguish intraneural from perineural masses, and localize nerve
time. Therefore, the patient should be followed clinically for improvement of symptoms. If symptoms persist or compressions prior to surgical exploration.137 Like ultrasound, its indication for acute peripheral nerve injury is in
worsen, the study may be repeated in four to six weeks. If the initial study is abnormal, the contralateral limb should localizing the lesion. In some studies, MR signal alterations were shown to occur as early as twenty-four hours after
be evaluated to rule out systemic neurological disease such as diabetic neuropathy. If the study in the contralateral an axonal nerve lesion, possibly making it the earliest form of detection of nerve injury.138 MR studies are limited by
limb is normal, then electromyography may be considered. access to the patient, cost, longer scanning times and equipment availability.

Electromyography involves recording of the electrical activity in muscle via a needle electrode inserted within the Treatment Options For Peripheral Nerve Injury
muscle. When an EMG needle is placed in a normal muscle at rest, there is no electrical activity. When nerve injury
occurs, spontaneous muscle fasciculation appear in a resting muscle within two to three weeks of the insult. As Once a nerve injury has occurred, treatment of the patient depends on the severity of the injury. It is prudent to
muscle is released from control by the nerve and contractions begin to occur spontaneously, the specific changes remember that the majority of these injuries resolve with time. The care of the patient with a nerve injury can be
seen on the electromyography are positive waves and fibrillations. A positive nerve conduction study detects the divided into two groups, those with minor deficits and those with major deficits. Regardless of the type of injury, the
presence of a lesion, whereas the EMG can further localize the lesion to a specific site of injury on the nerve. For patient should be evaluated clinically to ascertain that a more serious or occult injury or correctable contributing
example, a patient develops weakness in the hand grip after an open reduction, internal fixation of the distal radius condition is not overlooked.
under infraclavicular brachial plexus block. A nerve conduction study demonstrates altered conduction in the
distribution of the median nerve. An EMG may be able to localize the lesion to the surgical site or to the block site by Minor Deficits
evaluating groups of muscles innervated by the median nerve. If the intrinsic muscles of the hand are affected, but the
intrinsic muscles of the forearm are unaffected, then the site of injury would appear to be at the wrist and not at the
19

If the examination reveals minor deficits, reassurance is key to relieving the patients anxiety. Further diagnostic Commonly prescribed anticonvulsants in the treatment of minor neural changes, i.e. pain and paresthesia, are
testing or therapy is usually not indicated. Weekly to bi-weekly telephone follow-up to assess resolution of the injury gabapentin and carbamazepine. Gabapentin is an amino acid derivative of GABA (gamma-amino butyric acid). The
by the pain management team will provide reassurance, allow early detection of more serious problems, and instill proposed mechanism of analgesic action is related to its effect on sensitized neurons. It is thought to directly or
confidence in the patient. It is important to remember that one bad experience with regional anesthesia will often indirectly inhibit excitatory neurotransmitters, block neuronal calcium channels, and augment central nervous system
create a negative attitude toward future application for the patient, his family, and possibly the surgical team. inhibitory pathways by increasing GABA transmission.141 Gabapentin is usually started at 300 mg daily with
Providing the patient with consistent, caring follow-up, despite the injury, will help to rebuild patient confidence in increasing doses to 1300 to 1800 mg per day in divided doses. Side effects of gabapentin include drowsiness,
future anesthetic experiences. anxiety, visual disturbances, hypertension, and ataxia. Other anticonvulsants that have been used in the treatment of
neurally-mediated pain are carbamazepine, topiramate, levetiracetam, and oxcarbazepine.
Major Deficits
Opioids
If the clinical examination of the patient reveals a major neurologic deficit, early neurologic and/or neurosurgery
consultation is advisable. In addition to a complete neurologic examination, the neurologist will determine the most Opioid therapy is controversial, but may to be effective in alleviating pain of peripheral nerve injury origin. In five
appropriate diagnostic test for the patient. For example, if a compression injury is suspected, ultrasonography or MRI randomized, controlled trials of opioid therapy used for neuropathic pain, all demonstrated benefits of opioids in
of the involved plexus may be performed. In patients with pain, medication for pain should be started early to prevent controlling pain.142,143 Commonly prescribed opiods for short-term therapy include oxycodone, oxycontin, or
nerve sensitization. Physical and occupational therapy consults will be obtained by neurology with arrangements fentanyl patches. To prevent opioid dependence or tolerance, other therapeutic agents, i.e. amitriptyline, gabapentin,
made for treatment after the patient is discharged. A consultation for social services may be necessary if the injury will should be titrated up while titrating off the opioids.
impact the patients ability to perform activities of daily living. Similarly, early consultation with physical therapy is a
must to reduce the risk of contractures, muscle atrophy and prolonged disability. Close follow-up by neurology should Tramadol
be arranged, and well as continued follow-up by anesthesiology until the injury is completely resolved or is stable.

Tramadol is approved for use in the United States for moderate to severe pain. It binds to mu opioid receptors
Drug Therapy contributing to its analgesic properties. It inhibits the reuptake of serotonin and norepinephrine the the central nervous
system. In recent literature, tramadol has been shown to be effective in the treatment of arthrosic and neuropathic
Multiple drugs are effective to treat neurally-mediated pain. The more commonly prescribed medications include pain, and in mixed nociceptive-neuropathic pain.144 It is tolerated by elderly patients, has a low incidence of
tricyclic antidepressants, serotonin reuptake inhibitors, anticonvulsants, opiods, and capsaicin cream. These drugs constipation, is devoid of immunosuppressive activity, and has a low tendency toward tolerance. It has a minimum
should be administered under the direction of a chronic pain specialist or a neurologist who has evaluated the patient risk of addiction and abuse.
and has the capacity to do follow-up evaluations.
Capsacion Ointment
a. Tricylic Antidepressants
Capsaicin is a vanniloid compound most commonly found in hot peppers. Many of the neuropathies with pain as the
Amitriptyline is among the more efficacious drugs. It has multiple effects including blocking the reuptake of serotonin predominant symptom involve small afferent fibers resistant to the analgesic action of the more commonly prescribed
and norepinephrine, blocking the NMDA receptor, and blocking voltage dependent sodium channels. A more recent medications. Capsaicin can deplete the transmitter contents of these small afferent fibers leading to their
study demonstrated that amitriptyline has an ability to maintain spinal cord GABA(B) receptor activity.139 The drug degeneration and subsequent pain-generating ability. Its application is primarily for cutaneous hyperalgesia states
can be started at 10mg to 25mg daily, and escalated by 25 mg every week to an effected level. Doses should be such as postherpetic neuralgia. It is probably not effective for most painful neuropathies of deeper origin.
limited to 100mg daily. Side effects include decreased salivation, constipation, urinary hesitancy, blurred vision,
orthostatic hypotension, sedation and cognitive impairment. One very serious side effect in cardiac patients is After starting medication therapy, consultant follow-up should be scheduled for two weeks after the injury to determine
torsade-de-point from prolongation of the Q-T interval, but this has been shown to occur only in higher doses. if the deficit has resolved, persisted, or worsened. If the deficit has resolved, the medication will most likely be
discontinued. The patient should be instructed to notify the consultant if any neurologic changes develop within the
b. Selective Serotonin Reuptake Inhibitors: next month. If the deficit persists, the dose of medication will be adjusted as described. During follow-up visits, the
patient should be ask
Paroxetine is the only selective serotonin reuptake inhibitor that might be effective in the treatment of neurally-derived
pain. In a study comparing paroxetine to imipramine (another TCA), paroxetine was as effective in 60-70% of the ed about any side effects associated with the prescribed medication. Subsequent follow-up depends on the nature of
patients receiving the drug.140 Because of its marginal effectiveness, it is reserved only for those patients unable to the deficit. If it is stable but persistant, consultant follow-up should be arranged for three to six months. If it has
tolerate other classes of medications. worsened, adjustments will be made in the drug therapy to try to alleviate symptoms. Follow-up will be determined by
the consultant based on the patients condition and symptoms.
c. Anticonvulsants
Summary
20

Despite meticulous care, patient selection, and experience, neurologic deficits after regional anesthesia may occur. In closing, few publications have had a greater impact on the clinical practice of anesthesiology then the American
The debate over performing blocks in awake or sedated/asleep patients is inconsequential since nerve injuries have Society of Anesthesiologists (ASA) practice guidelines.145 These practice guidelines have been designed to enhance
occurred in both groups. Understanding the mechanism of injury, the typical clinical course following injury, the and promote the safety of anesthetic practice and have made the practice of general anesthesia much safer. Such
prognosis, and obtaining appropriate consults is essential knowledge for the regional anesthesiologist. A basic guidelines are much needed but currently do not exist with regards to the practice of PNBs. This is most likely
understanding of diagnostic tests and treatment modalities will provide the clinician with information necessary to because administration of PNBs has been traditionally based on individual preferences, clinical impressions and other
participate in meaningful discussions with the patient and other specialists involved in the patients care. Regardless subjective methods. Future efforts should be directed toward developing more objective and exacting nerve
of the consults obtained, the importance of follow-up by anesthesiology cannot be over-emphasized. Complete localization and injection monitoring techniques to more reliably detect and prevent intraneural intrafascicular
documentation of the initial consult, the block procedure, the post-operative care and follow-up will be extremely injection. The results of these efforts will inevitably be of crucial importance to the future of PNBs and their role in
important in the event of any legal action as well as in the professional care of the patient. practice of modern anesthesiology.