Objectives:
1.) Name the two chemical classes of local anesthetics.
2.) Describe the metabolism of the ester local anesthetics and how
the metabolic product relates to their allergenic potential.
3.) Give the advantages of amide local anesthetics.
4.) Name an intermediate and a long acting local anesthetic and generally
accepted dose limits for each to avoid systemic toxicity.
5.) List the reasons epinephrine is added to local anesthetic solutions.
6.) Give the signs and symptoms of local anesthetic systemic toxicity.
7.) Describe the equipment and supplies that should be available where
nerve blocks are performed.
8.) Explain why local anesthetics will not cause numbness if injected
into an abscess.
9.) Identify which nerves transmit pain sensation.
10.) Describe the function of an electric nerve stimulator.
11.) Explain how to perform an intravenous or Bier block.
12.) Compare and contrast spinal and epidural anesthesia in terms
of anatomy, drug doses required, rapidity of onset.
13.) Describe the symptoms, pathophysiology and treatment of a post
dural puncture headache.
14.) List absolute and relative contraindications to regional anesthesia.
The first local anesthetic was cocaine, a naturally occurring substance,
isolated from cocoa leaves by a German chemist (Gaedcke) in 1855.
In 1884, Koller, an Austrian, used this substance to produce topical
anesthesia of the eye. Later that year, two Americans, Halsted and
Hall administered cocaine to each other to produce neural blockade,
presumably of peripheral nerves.
Corning described spinal anesthesia in 1885, but his meticulous description
did not mention the efflux of cerebral spinal fluid. It is thought
he performed an epidural anesthetic. Interestingly, the technique
for lumbar puncture was reported six years later by Quincke. One type
of cutting bevel spinal needle is known to this day as a "Quincke"
needle.
The first spinal anesthetic was performed in 1898 and is generally
attributed to August Bier, a German physician (1861-1949). Bier was
the subject. His graduate student placed the needle and CSF poured
out. It was only then that they discovered that the syringe did not
mate to the needle. This experiment preceded the universal use of
standardized needles and hubs that we refer to as Luer locks. Luer,
a German instrument maker, died in 1883.
Bier suffered from one of the sequelae of spinal anesthesia that we
warn our patients of today, the post dural puncture headache. Impressively,
he attributed the headache to the loss of CSF and advocated the use
of small gauge needles.
Following his recovery, Bier performed the procedure on his assistant.
They were ecstatic when after the injection of cocaine the young man's
legs became numb and proceeded to celebrate with wine and cigars.
The insensibility of his legs was demonstrated with repeated blows
and kicks. As you can imagine, his recovery was complicated both by
a headache and very sore shins.
Another German chemist, Einhorn produced the first synthesized local
anesthetic, in 1904. Procaine (Novocaine) is the first in the class
of "ester" local anesthetics and is short acting. Other esters still
in use in our operating rooms are the long acting tetracaine and 2-chloro
procaine (Nesacaine) which is ultrashort acting. All of the ester
local anesthetics are metabolized in the plasma by the enzyme commonly
referred to as plasma pseudocholinesterase. You may recall this is
the same enzyme that acts on succinylcholine.
The metabolic product of the degradation of procaine is para-aminobenzoic
acid (PABA) which was a common ingredient in topical sunscreens. Modern
sunscreens use alternate UV light blockers and are frequently advertised
as "PABA free" because PABA provokes an allergic reaction. While allergy
to local anesthesia is not a major problem, when it does occur, it
is most likely due to the ester local anesthetics because of this
metabolite.
The other chemical class of local anesthetics is the amides. The most
commonly recognized drug in this class, lidocaine (Xylocaine), was
synthesized in 1943. Torsten Gordh, a Swedish anesthesiologist, who
received his anesthesia training at the University of Wisconsin under
our first chairman, Ralph Waters, introduced it into clinical practice.
The amides have several advantages over the esters. They are far less
likely to produce allergic reaction, and they can undergo repeated
high temperature sterilization without losing potency. Most of the
local anesthetics in common use today belong to the amide class. These
include, in addition to lidocaine, bupivacaine (Marcaine or Sensorcaine),
mepivacaine, etidocaine, prilocaine, and the most recent, ropivacaine.
If you choose two local anesthetics to learn to use, I suggest the
intermediate acting lidocaine and the long acting bupivacaine. Lidocaine
is supplied in many formulations, for example, for topical use in
an ointment, a water soluble jell and a 4% solution, as a 5% solution
with dextrose for spinal administration, and for injection as 0.5%,
1%, 1.5% and 2% solutions. It is also widely available in a 1% multi-dose
vial, and pre-prepared with epinephrine. A word of caution: the multi-dose
vials contain a preservative, methylparaben, which should not be given
in a spinal or epidural anesthetic because of concerns about neuro
toxicty. Interestingly, the metabolite of methylparaben is PABA and
may be the real culprit in many cases of lidocaine allergy. Also,
there have been recent reports of cauda equina syndrome and mono-radiculopathies
due to spinally administered lidocaine. Lidocaine dose limits to avoid
systemic toxicity with nerve block or infiltration are 5 mg/Kg of
plain solution or 7 mg/Kg if the solution contains epinephrine.
Commercially available solutions of local anesthetic containing epinephrine
are prepared at a low pH to prevent degradation of the epinephrine.
This has implications for the onset time of the drug, as we will discuss
later. Most anesthesiologists will prepare local anesthetics containing
epinephrine at a concentration of 1:200,000 or 5 mcg of epinephrine/ml
just before use. The addition of epi to local anesthetic solutions
can serve several purposes: 1.) prolongs the action of the local anesthetic,
2.) blunts systemic uptake and thereby limits systemic toxicity, 3.)
decreases bleeding at the site of injection, 4.) serves as a marker
of intravascular injection and 5) improves the quality of spinal blockade,
probably on the basis of spinal alpha receptors.
Bupivacaine is a long acting local anesthetic. It has an interesting
characteristic in that it tends to cause a longer sensory block than
motor block. This makes it ideal for post-operative analgesia. Bupivacaine
is available as 0.25%, 0.5% and 0.75%. The higher concentrations will
lead to increased motor block. Bupivacaine is highly tissue bound
and its action is not prolonged by the addition of epinephrine. If
it is injected systemically it may result in cardiac asystole. CPR
should be carried on for a prolonged period in this situation. The
general recommendation for dose limits for bupivacaine is 2 mg/Kg
plain and 3 mg/Kg with epinephrine.
Systemic toxicity of local anesthetics will be seen after intravascular
injection or systemic absorption of drug used for a nerve block. Some
nerve block sites have higher rates of absorption than others. Sites
are generally ranked intercostal>epidural>brachial plexus>spinal.
The signs of systemic toxicity are peri-oral numbness, metallic taste
in the mouth, tinnitus, dizziness, respiratory depression, coma, seizure,
cardiovascular system depression. The important thing about this list
is to notice that cardiovascular depression occurs only at very high
blood concentrations. Thus, if the other symptoms occur, ask the patient
to hyperventilate, provide oxygen and prepare to secure the airway
and treat a seizure. If you prevent hypercarbia, hypoxia, and aspiration
of stomach contents, then it is likely the patient will weather the
insult without sequelae.
Consider what equipment and supplies you would provide in a location
where nerve blocks are to be performed. Certainly you would want oxygen
and a way to deliver it, laryngoscope, endotrachial tubes, ventilation
bag and mask, suction, drugs to treat hypotension, bradycardia, seizure,
anxiety, and pain, local anesthetics, monitors, IV starting equipment,
a bed that can be adjusted into various positions, and an assistant.
As a general rule, particularly when using a "stationary needle technique,"
that is, when the local anesthetic is injected at one site, always
aspirate before injecting and aspirate repeatedly during the injection.
An exception to this rule is if the amount of local anesthetic well
below the level of systemic toxicity.
Local anesthetics are weak bases with pKa in the range of 7.9. This
of course means that at a pH of 7.9 a population of local anesthetic
molecules is equally divided between a charged and uncharged state.
In order to keep the local anesthetic molecules in solution, hydrogen
ions are added (that is, the solution is made acidic) or said another
way, the pH of the solution is lowered. If the local anesthetic solution
is made with epinephrine, the pH is made even lower.
Lets turn our discussion now to a consideration of nerves. As most
junior high school students know, nerve membranes are a lipid bilayer
with protein channels. Local anesthetics act in the sodium channel,
entering from the internal aspect. Now you may have noticed a bit
of a problem. Positively charged local anesthetic molecules soluble
in an aqueous solution will have trouble passing through a lipid membrane.
This problem is overcome when the tissue surrounding the nerve accepts
(or buffers) the hydrogen ion and the uncharged molecules are then
free to pass through the axonal membrane. Once in the cell, the molecules
must be recharged before they can effect a block of the sodium channel.
OK, so what? What difference does this make clinically? Local anesthetics
will not work in tissue that is unable to buffer the excess hydrogen
ions. This is why local anesthetics injected into the acidic environment
of an abscess will not cause numbness. Occasionally anesthesiologists
will add NaHCO3 to local anesthetic to speed the onset of the drug
effect. This additive is not a powerful enough base to overcome the
acidity in abscessed tissue, however.
Nerves are classified in several ways. There are motor, sensory and
autonomic nerves. Nerves are myelinated and unmyelinated. A common
system categorizes nerves into A, B, and C; A is further divided into
alpha, beta, gamma and delta. Only the C fibers are unmyelinated.
A delta and C fibers carry pain sensation. A delta fibers, being myelinated,
conduct at a very rapid rate and carry "first pain" or discriminative
pain. C fibers are slower and carry "second pain" which is dull, aching
and boring in nature. Local anesthetics will act all along C fibers,
but only at the breaks in the myelin or the Nodes of Ranvier (French
pathologist, 1835-1922) on the A delta fibers. Typically, three or
more Nodes of Ranvier must be blocked to stop transmission along the
nerve.
Nerves may be blocked wherever they can be found. Certainly, there
are some locations where it may be unwise to attempt a block. Examples
of this are bony or fascial tunnels where the pressure of the injected
agent may cause pressure related nerve damage. Textbooks describe
nerve blocks in relation to anatomic landmarks. Thus, for example,
the median nerve may be blocked at the wrist or elbow. If you are
able to locate the median nerve in the forearm, it could be blocked
there.
Strategies to find nerves include looking for the accompanying artery,
seeking a paresthesia (recall the old saying, "No paresthesia, no
anesthesia") or using an "electric nerve stimulator." This is a device
that gives a short pulse of electrical current and is attached to
an insulated needle and a grounding pad on the patient. As a mixed
function or motor nerve is approached with the needle the nerve will
be stimulated and a muscle twitch will result. The closer the needle
is to the nerve, the less current it takes to cause a brisk muscle
twitch. Generally, I start seeking the nerve with a current of 2 mA
and inject when I am able to dial down to 0.5 mA. Twitches at very
low current may indicate the needle is resting in the nerve. Injection
at that position will be very painful, may result in nerve damage
and should be avoided.
The simplest sort of local anesthetic block is infiltration or field
block. Specific nerves are not sought, the local anesthetic is just
injected into the skin and tissue where the painful procedure will
be done. Placing a skin wheal prior to starting an IV is an example
of this sort of infiltration.
Peripheral nerve blocks seek to block individual nerves and include,
for example, median, ulnar and radial nerves at the wrist or elbow,
the superficial and deep peroneal, saphenous, sural and tibial nerves
at the ankle, or even the intercostal nerves. Frequently the anesthesiologist
would like to block the entire arm or a large portion of the leg with
a single injection or an injection at a single site. In this situation
a plexus block is ideal. A single injection of local anesthetic onto
the brachial plexus will result in a block of arm tissue innervated
by several peripheral nerves. Several approaches to the brachial plexus
have been described: the axillary, infraclavicular, supraclavicular,
and intrascalene approaches each have advantages in certain situations.
Another way to block an extremity is the Intravenous Block first described
by August Bier. An IV is inserted into a distal vein in the extremity
and capped. A wide rubber band (Esmarch bandage, Esmarch 1823-1908
was a friend of Bier) is tightly wrapped starting distally and working
proximally to exsanguinate the limb. A pneumatic tourniquet is inflated
to prevent arterial inflow to the extremity and the Esmarch is removed.
Fifty to 60 ml of lidocaine 0.5% is injected through the distal IV
and held in the arm or leg by the tourniquet. The tourniquet may remain
inflated for up to two hours, but the ischemic pain beneath the tourniquet
make this a better technique for shorter cases. At the end of the
case the tourniquet is dropped and re-inflated over several minutes
to gradually wash out the local anesthetic and lessen the risk of
systemic toxicity. The block resolves within minutes of releasing
the tourniquet.
Neuraxial nerve blocks include spinal, epidural and caudal blocks.
A spinal is more precisely called a subarachnoid block (SAB). The
local anesthetic is injected into the cerebral spinal fluid (CSF).
As the nerves are unprotected here, a very small amount of anesthetic
will cause the rapid onset of a dense block. The injectate may be
hyperbaric, hypobaric or isobaric relative to CSF. By having a different
baricity from CSF the anesthetic solution spread and the extent of
the block may be controlled by positioning the patient. Spinal anesthesia
is widely thought by non-anesthesiologists to be a safer form of anesthesia
for ill patients. This is probably because patients don't necessarily
have to be intubated or "put to sleep" when under spinal anesthesia.
In reality, the physiologic changes due to blockade of sympathetic
fibers and the resultant decreased afterload, hypotension, bradycardia,
and respiratory depression (depending on spinal segments blocked)
may be more of a risk and less controllable than a well monitored
general anesthetic. Note that respiratory depression most often follows
hypotension and ischemia of the brain stem respiratory centers and
is rarely if ever due to paralysis of the spinal roots supplying the
phrenic nerve.
Many patients worry about back pain, paralysis or other nerve damage,
and infection following SAB. Back pain is about as common after a
general anesthetic as a spinal. It is probably due to stretch on the
ligaments in the back with flattening of the lumbar curve against
the OR table. Nerve damage and infection occur very rarely. The most
common adverse sequelae following spinal anesthesia is a post dural
puncture headache (PDPHA). This is related to low CSF pressure due
to leak of the fluid from the puncture hole in the dura made with
the spinal needle. A very powerful diagnostic feature of the headache
is its positional nature. It is worse when the patient is sitting
or standing and better when the patient is lying flat. Patients in
the second and third decade and larger needles with cutting bevels
are associated with a higher incidence of PDPHA. Our standard is to
use 25 gauge pencil point (Whitacre) needle with a reported headache
incidence of less than 1% in the high risk age group. PDPHA is treated
with recumbency, hydration, caffeine, or more aggressively with an
epidural blood patch of the leaking dural hole.
A needle headed for the epidural space takes a similar path to a spinal
needle, but is stopped before piercing the dura. This is usually accomplished
by using the loss of resistance technique. A needle is placed into
the rather dense interspinous ligament between two spinous processes.
Then a syringe containing saline or air (saline is preferred) is attached
to the hub of the needle and an attempt to inject is made. Resistance
is noted. The needle is advanced with repeated testing of resistance
to injection. As the bevel passes into the ligamentum flavum increased
resistance may be noted. Often a pop is felt or heard as the needle
is advanced through the ligamentum flavum and then there is a loss
of resistance to injection. If the needle is advanced too far, the
dura will be punctured and CSF will pour out when the syringe is removed.
A Tuohy (20th century American anesthesiologist) needle is most commonly
used for epidural anesthesia. It has a curved bevel that will direct
a catheter threaded through it into the epidural space. If a Tuohy
needle punctures the dura, both its large gauge and bevel design will
result in a large hole and a high risk (70%) of PDPHA. In well trained
hands the risk is between 0.1 to 1% or less.
Caudal blocks are an approach to the epidural space through the sacrococcygeal
ligament, just above the coccyx. Caudal blocks are useful for perineal
operations and may be used in children to thread a catheter up the
epidural space to thoracic levels.
Epidural anesthesia requires about ten times the dose of local anesthetic
to achieve a block as compared to a spinal. This raises the potential
for systemic toxicity. The blocks set up more slowly than spinal blocks.
This is maddening if you are trying to get a case underway, but is
good in terms of controlling blood pressure with fluid resuscitation.
It is far more common to perform a continuous epidural block by placing
a catheter than a continuous spinal. A continuous epidural allows
prolonged operative anesthesia (generally with IV sedation or as an
"over-under technique" with light general anesthesia) or postoperative
epidural analgesia using dilute local anesthetics and opiates. Epidurals
are a frequent method of labor analgesia for pregnant women because
they produce good analgesia with little neuropsychiatric depression
of the newborn as compared to IV opioid analgesics. There is an ongoing
debate as to the effect of epidural labor analgesia on the progress
of labor and the incidence of forceps delivery.
Not all patients are appropriate for regional anesthesia. Those who
refuse or have an infection at the injection site are considered to
have absolute contraindications. The requirements are even more stringent
for neuraxial blockade. Coagulopathy whether therapeutic or part of
the patient's pathology and increased ICP are added to the list of
generally accepted absolute contraindications when epidural or spinal
is considered. Relative contraindications include sepsis, hypovolemia,
neurologic disease, psychologic instability, antiplatelet drugs, prolonged
surgery, certain cardiac diseases (idiopathic hypertrophic subaortic
stenosis, aortic stenosis), and uncooperative patient or surgeon.
Regional anesthesia is undergoing a renaissance. This is fueled by
exciting new concepts in pre-emptive analgesia which promise to decrease
the postoperative pain experience and inhibit actual physical changes
in the spinal cord due to pain. New drugs and adjuvant analgesics
and a growing knowledge about how to use them will allow us to tailor
our anesthetic approaches to specific patients. Anatomy is an old
science, but surprisingly, new approaches to nerve blocks continue
to be described. The recurrent challenge is to help an individual
patient do better than they expected, to allay their anxiety and to
have less pain.
