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How local anesthetics work
How local anesthetics work Rudolph H de Jong, MD
Local anesthetics are among the most frequently used drugs in the operating room. It is, perhaps, no wonder that an aura of mystery often surrounds their use. It is almost magical to see how a few drops of solution can render portions of the human body insensitive to pain without producing unconsciousness.
I would like to share my fascination with local anesthetics and try to lift that curtain of mystery a bit. Knowing more about local anesthetics will make operating room nursing profesRudolph H de Jong, MD, i s professor o f anesthesiology and pharmacology at the University of Washington School of Medicine, Seattle. H e received his M D degree from the Stanford School o f Medicine. During surgical training he became aware that anesthesia, poorly administered, was a major cause o f postoperative morbidity. H e turned ta anesthesiology. A f t e r four years as chief o f operative and anesthesia services i n the Army, he obtained research training in neurophysiology and neuropharmacology. This two-part article resulted from research supported by a Research Career Development Award.
286
sionally more rewarding, and may avert potential mishaps in case of a toxic reaction.
Nerve. Local anesthetics block pain and other sensations by stabilizing the nerve membrane. To understand these events, let us quickly review pertinent essentials of neurophysiology. A nerve fiber, also called axon, is basically a long filament of protein (the axoplasm) encased in a membrane which separates it from the tissue fluids. While the axon actually is the long threadlike outgrowth of a centrally located nerve cell, we need only to discuss the axonal portion in connection with local anesthesia. Functionally, the membrane is the most important part of the nerve fiber. This was shown ingeniously by an experiment where axoplasm was replaced with ionic solution, like a sausage casing filled with water (Hodgkins, 1965). This weird ghost of a nerve still conducted impulses in
AORN Journal, August 1973, Vol 18, N o 2
normal fashion for many hours. From this, and many other studies, it became clear that the membrane is essential to the conduction of impulses to and from the central nervous system, while the axoplasm serves merely as an energy reservoir. Much of what we know about nerves is derived from a very distant cousin, the squid. The squid propels himself rocket-like through the ocean by squeezing the powerful muscles in the mantle surrounding his body. The mantle muscles are innervated by a single huge nerve fiber, so large that for many years it was thought to be a blood vessel. This giant axon is 20 times thicker than the thickest human nerve. Because it is so big, it is much more easily studied and analyzed. Membrane potential. A fine electrode inserted through the axon’s membrane registers a voltage of about -70 mv. This voltage across the membrane of the resting axon is called the membrane potential, and the nerve is said to be poZarixed. Polarization is analogous to a loaded pistol ready to be fired by a light pull on the trigger. How the membrane potential is generated is important to this discussion. If we squeeze the axoplasm from a giant axon and analyze its contents, we find a high concentration of potassium ions, a fair amount of negatively charged chloride and protein ions but, importantly, barely any sodium ions. If we also analyze the tissue fluid outside the membrane, we find a high concentration of sodium and chloride ions, but hardly any potassium ions. Ionic gradients. We see that the nerve membrane separates two solutions quite different in their composi-
tion. One is rich in positively charged sodium ions, the other in positively charged potassium ions. If we remove the membrane, or inactivate i t with a neurotoxic substance, the ionic differences between the inside and the outside of the nerve membrane would soon be eliminated. Normally, however, the living membrane maintains ionic segregation, keeping potassium inside and sodium outside. Such a membrane is semipermeable to ions. On examining the situation more closely we find that the small potassium and chloride ions can move freely back and forth through the membrane, but the thicker sodium ions cannot. The much larger protein anions in the axoplasm are held back completely by the membrane. Because the potassium ions can travel freely through the membrane, they tend to move down the concentration gradient to equalize the transmembrane concentration difference from axoplasm to extracellular fluid. However, their larger and oppositely charged “mates,” the p o t e i n anions, cannot penetrate the membrane and are left behind. When the potassium ions, which are positively charged, leave the nerve interior, they carry their positive charge with them into the extracellular fluid, leaving an excess of negatively charged protein anions behind. The result is that the membrane exterior is positively charged while the interior is negatively charged. Membrane structure. The semipermeable properties of the membrane reside in its unique skeleton of a double-thickness layer of columnar lipid molecules. Each side of the bimolecular lipid layer is coated with a thin sheet of protein, like a buttered
AORN Journal, August 1973,Vol18,N o 2
287
sandwich turned inside out. (The protein, rather than being a continuous sheet, may also exist as large globules interspersed between the lipid molecules.) The columnar skeletal structure creates channels that run parallel to the framework. These channels, or pores, provide the avenues for ions to travel between nerve interior and exterior. While this is a considerable oversimplification, the principle remains the same. The pore width allows ready passage of potassium ions but, in the resting state, is too small to let sodium ions pass through.
Depobrixation. S o far we have looked only at a resting, inactive nerve fiber. Most nerves, of course, are hard at work carrying impulses from one part of the body to another. Let us go back to the squid’s giant axon and again insert a fine electrode through the membrane, recalling that in the resting state a -70 mv resting potential registers across the membrane. Now let us apply a stimulus some distance away from the electrode. We usually use electrical pulses in the laboratory because they are easily controlled, but impulses in the human body are generated by a variety of stimuli. Whatever the stimulus, a weak one will cause only a slight change in the membrane, decreasing the transmembrane potential from perhaps -70 to -55 mv a t most. If we remove the stimulus, the needle of the recording voltmeter immediately returns to the resting level of -70 mv. A brief or weak stimulus thus merely causes a transient voltage change without anything exciting happening. However, if we apply a slightly stronger stimulus, some major chang-
288
es take place with lightning speed. Slowing down events, we would see, on applying the stimulus, a rather slow initial movement of the voltmeter to -55 mv. This voltage level is called the firing threshoZd. Once the threshold is reached, the voltage suddenly swings violently from the negative side of the meter, then, much more slowly, returns to normal again. We have just witnessed a very quick and brief reversal of membrane voltage, the total excursion of the needle being some 100 to 120 mv. This rapid change in membrane voltage is called depoZarixation, and the large voltage so generated is called the action po-
tential. Membrane events. What happened? Let us go back to the resting membrane which excluded sodium ions (concentrated in the extraneural fluid) from the nerve interior. The nerve interior, the axoplasm, barely has any sodium ions in it, creating a large transmembrane sodium concentration gradient. The membrane interior is negatively charged and the sodium ions are positively charged. Hence, there is not only a sodium concentration gradient, but also an electrostatic sodium gradient, both trying t o pull sodium ions inward. Through mechanisms not altogether clear yet, the membrane changes its configuration under the influence of an electric field such as the stimulus we applied. This configurational change causes the pores to widen sufficiently to accommodate sodium ions. Pulled by powerful forces, sodium ions now rush through the membrane down their concentration and electrostatic gradients. So many sodium ions enter so fast that it briefly causes an excess of positively charged sodium
AORN Journal, August 1973, Vol 18, N o 2
ions a t the nerve membrane interior. This explains the brief overshoot of the membrane potential during depolarization. As soon as the stimulus is turned off, the membrane reverts to its original sodium-excluding state, potassium ions start moving out and the resting potential is restored. Note that each depolarization cycle traps some sodium ions inside the membrane, so that the transmembrane sodium gradient will be erased eventually. Sodium trapping, and consequent rundown of the action potential, is prevented in living nerve by the sodium pump mechanism that actively returns sodium ions to the external fluid.
Impulse spread. The story is now almost complete. We initiated depolarization with a stimulus that caused changes in the membrane. The enormous and fast voltage changes in the membrane during depolarization reverses the polarity of the membrane. The negatively charged membrane interior acquires a brief positive charge during depolarization. The membrane exterior changes briefly from a positive to a negative charge. The depolarized membrane is charged oppositely from neighboring membrane sites. To restore equilibrium, electrical charges begin to flow along the membrane, just as in a battery. These current flows in turn lower the membrane potential in areas adjacent to the initial site of depolarization. Lowering of the transmembrane potential is initiated a t a new site. Depolarization o f contiguous membrane areas is self-regenerating; once initiated it proceeds from one end of the axon to the other. This process of the impulse traveling along the nerve is like a spark in
a powder fuse. To detonate a stick of dynamite, you roll out a long fuse and light the end with a match. A portion of the fuse starts to burn, thereby heating the adjacent portion to its burning point so that i t starts to burn. Once lit a t one end, the fuse transmits the spark to the dynamite stick. Recall my earlier comparison of a nerve fiber with a loaded pistol. It takes only a light and brief pull on the trigger to set off tremendous forces.
Local anesthesia. What has all this to do with local anesthesia? Local anesthetics, in a way not yet clear, “freeze” the nerve membrane in its resting or stable configuration and prevent the membrane from changing when an impulse arrives. In physiologic terms, local anesthetics maintain the membrane in its resting, sodium-excluding, polarized state. With the membrane incapable of depolarizing, an action potential is not generated a t the anesthetized site. Let us go back to the analogy of a lighted powder fuse. If a portion of the fuse is wet, when the spark reaches the damp site it will not be able to heat that part to the burning point. The spark soon fizzles out and the dynamite stick never explodes. If you think of anesthetized nerve in similar fashion, you will see that the membrane, being unable to depolarize, cannot set up currents in adjacent membranes. The process of impulse transmission is halted a t the anesthetized site and the nerve is said to be blocked. Impulse transmission is blocked in either direction. Neither signals arriving from the skin such as a painful stimulus, nor impulses originating from the central nervous system such
AORN Journal, August 1973, V ol18, No 2
289
as a command to a muscle, can proceed. Thus the area innervated by the blocked nerve is numb and insensitive to other modalities such as heat and pressure. In the case of a blocked motor nerve, the patient is unable to move the innervated muscle groups. DiffewntiaZ Mock. The situation is actually more complicated. A peripheral nerve contains many nerve fibers of many different sizes. Size is an important characteristic of a nerve fiber which determines many physiologic properties including sensitivity to local anesthetics and function. The thicker a nerve fiber, the less readily it is blocked by local anesthetic. A certain concentration of local anesthetic may block a thin fiber but may be too low to block a thicker fiber. A strong local anesthetic solution, having a concentration sufficient to block thick fibers, will also block thinner nerve fibers. A division of labor exists among nerve fibers. In man, thin fibers transmit impulses related to pain and temperature while thick nerve fibers transmit impulses such as touch, pressure and stretch impulses to skeletal muscles. Pain impulses, traveling over thin nerve fibers, are more readily anesthetized than motor impulses which traverse thick nerve fibers. When a mixed peripheral nerve is blocked, the patient may be completely free of pain yet still be able to move muscles and perceive touch and pressure. This type of nerve block, where some functions are interrupted and others are not, is called a differentiaz Mock. A differential block may exist after local anesthesia, and the patient, who feels no pain, may still feel the touch of the surgeon’s knife. Patients are unde rs t a n d a bl y apprehensive about this experience. A few soothing
290
words from the nurse will often work wonders in allowing successful completion of the operation.
The blocking process. Nearly all anesthetics in current use are amines. The amine, often called the base because it is weakly basic, is insoluble in water (though very lipid soluble). The drug for injection should be in a water-soluble stable form. This is accomplished by forming the local anesthetic salt from the base and a strong acid, commonly hydrochloric acid. In water, the local anesthetic salt dissociates into two molecular forms. One is the original local anesthetic base which is electrically uncharged. The other is the quarternary amine form, the positively charged cation. The proportion of base and cation in solution varies with the pH; the more acid the solution, the more cation is present and the less base. The reverse holds in an alkaline environment. The two forms, base and cation, each important to the blocking process, have distinctly different properties. The cation, the charged quarternary species, binds to receptor sites in the nerve membrane, stabilizing it and preventing depolarization. The cation is the actual nerve-blocking molecular form. The local anesthetic base, lipid soluble and carrying no electrical charge, readily diffuses into tissues and traverses diffusion barriers such as fibrous tissue. The base delivers the drug from the site of injection to the site of cation. Once at the nerve membrane, the cation takes over to cause the actual transmission block. The proportion of base and cation thus is important for a smooth block. If the solution is too acid, not enough base dissociates to move the drug to the nerve mem-
AORN Journal, August 1973, Vol 18, N o 2
brane. If the solution is too alkaline, it diffuses rapidly but inhibits release of sufficient cations to block the nerve. Disease states such as infection affect tissue pH, and can also affect the course of local anesthesia.
Summary. Resting nerve is polarized, with the inside of the nerve membrane negatively charged with respect to the outside. This is because the resting membrane is impermeable to sodium ions. A stimulus disturbs this state and briefly reverses membrane polarity; the nerve interior now being positively charged with respect to the exterior. The explosive changes associated with depolarization are attributable to a change in membrane permeability which briefly permits sodium ion passage. The polarity reversal brought about by depolarization sets up currents in adjacent parts of the nerve, in turn depolarizing them. A single brief membrane change a t one end of the
nerve fiber thus initiates an advancing electrical wave, the action potential or impulse, which travels from one end of the nerve to the other. Local anesthetics, by retaining membrane integrity and sodium impermeability, prevent depolarization. Hence an impulse traveling along a nerve by spreading depolarization is halted a t the anesthetized site. The nerve is blocked and impulses can travel neither to, nor from, the central nervous system. The innervated body area is numb and the muscles
El
paralyzed. REFERENCES
A d r i a n i , J. The Pharmacology of Anesthetic Drugs,
4th ed. Springfield: Thomas, 1968. Hodgkin, A L. The Conduction of t h e Nervous Impulse. Liverpool: University Press, 1965. d e Jong,
R
H . Physiology and Pharmacology of
Local Anesthesia.
Springfield: Thomas, 1970.
Katz, 8. Nerve, Muscle ond Synapse. New York: M c G r a w - H i l l , 1966.
Infecfion sfudy reporfed Medical researchers a t a symposium held a t the New York Academy of Medicine on “Hospital Infections and Hand Washing” heard that a routine hand washing lasting only 20 seconds with a potent non-hexachlorophene microbicide may b e the keystone to the control of hospital infection. Other soaps were included in the research reported at the symposium held under the auspices of the Department of Environmental Sciences of the University of Massachusetts. Warren Litsky, commonwealth professor of microbiology a t the University of Massachusetts, reported that his tests showed that hexachlorophene and other soap preparations are relatively ineffective against gram-negative microorganisms. He said the soaps inhibited the growth of bacteria but did not destroy them, and the preparations all had a slow onset of action and cumulative effect. However, the microbicidal preparation killed gram negative and gram positive germs on 20 second contact and did not depend on repeated use. Peter Dineen, MD, clinical professor a t the New York Hospital-Cornell Medical Center, conducted a study which essentially confirmed Dr Litsky’s findings.
AORN Journal, August 1973, V o l 1 8 , N o 2
291
Local anesthetics are among the most frequently used drugs in the operating room. It is, perhaps, no wonder that an aura of mystery often surrounds their use. It is almost magical to see how a few drops of solution can render portions of the human body insensitive to pain without producing unconsciousness.
I would like to share my fascination with local anesthetics and try to lift that curtain of mystery a bit. Knowing more about local anesthetics will make operating room nursing profesRudolph H de Jong, MD, i s professor o f anesthesiology and pharmacology at the University of Washington School of Medicine, Seattle. H e received his M D degree from the Stanford School o f Medicine. During surgical training he became aware that anesthesia, poorly administered, was a major cause o f postoperative morbidity. H e turned ta anesthesiology. A f t e r four years as chief o f operative and anesthesia services i n the Army, he obtained research training in neurophysiology and neuropharmacology. This two-part article resulted from research supported by a Research Career Development Award.
286
sionally more rewarding, and may avert potential mishaps in case of a toxic reaction.
Nerve. Local anesthetics block pain and other sensations by stabilizing the nerve membrane. To understand these events, let us quickly review pertinent essentials of neurophysiology. A nerve fiber, also called axon, is basically a long filament of protein (the axoplasm) encased in a membrane which separates it from the tissue fluids. While the axon actually is the long threadlike outgrowth of a centrally located nerve cell, we need only to discuss the axonal portion in connection with local anesthesia. Functionally, the membrane is the most important part of the nerve fiber. This was shown ingeniously by an experiment where axoplasm was replaced with ionic solution, like a sausage casing filled with water (Hodgkins, 1965). This weird ghost of a nerve still conducted impulses in
AORN Journal, August 1973, Vol 18, N o 2
normal fashion for many hours. From this, and many other studies, it became clear that the membrane is essential to the conduction of impulses to and from the central nervous system, while the axoplasm serves merely as an energy reservoir. Much of what we know about nerves is derived from a very distant cousin, the squid. The squid propels himself rocket-like through the ocean by squeezing the powerful muscles in the mantle surrounding his body. The mantle muscles are innervated by a single huge nerve fiber, so large that for many years it was thought to be a blood vessel. This giant axon is 20 times thicker than the thickest human nerve. Because it is so big, it is much more easily studied and analyzed. Membrane potential. A fine electrode inserted through the axon’s membrane registers a voltage of about -70 mv. This voltage across the membrane of the resting axon is called the membrane potential, and the nerve is said to be poZarixed. Polarization is analogous to a loaded pistol ready to be fired by a light pull on the trigger. How the membrane potential is generated is important to this discussion. If we squeeze the axoplasm from a giant axon and analyze its contents, we find a high concentration of potassium ions, a fair amount of negatively charged chloride and protein ions but, importantly, barely any sodium ions. If we also analyze the tissue fluid outside the membrane, we find a high concentration of sodium and chloride ions, but hardly any potassium ions. Ionic gradients. We see that the nerve membrane separates two solutions quite different in their composi-
tion. One is rich in positively charged sodium ions, the other in positively charged potassium ions. If we remove the membrane, or inactivate i t with a neurotoxic substance, the ionic differences between the inside and the outside of the nerve membrane would soon be eliminated. Normally, however, the living membrane maintains ionic segregation, keeping potassium inside and sodium outside. Such a membrane is semipermeable to ions. On examining the situation more closely we find that the small potassium and chloride ions can move freely back and forth through the membrane, but the thicker sodium ions cannot. The much larger protein anions in the axoplasm are held back completely by the membrane. Because the potassium ions can travel freely through the membrane, they tend to move down the concentration gradient to equalize the transmembrane concentration difference from axoplasm to extracellular fluid. However, their larger and oppositely charged “mates,” the p o t e i n anions, cannot penetrate the membrane and are left behind. When the potassium ions, which are positively charged, leave the nerve interior, they carry their positive charge with them into the extracellular fluid, leaving an excess of negatively charged protein anions behind. The result is that the membrane exterior is positively charged while the interior is negatively charged. Membrane structure. The semipermeable properties of the membrane reside in its unique skeleton of a double-thickness layer of columnar lipid molecules. Each side of the bimolecular lipid layer is coated with a thin sheet of protein, like a buttered
AORN Journal, August 1973,Vol18,N o 2
287
sandwich turned inside out. (The protein, rather than being a continuous sheet, may also exist as large globules interspersed between the lipid molecules.) The columnar skeletal structure creates channels that run parallel to the framework. These channels, or pores, provide the avenues for ions to travel between nerve interior and exterior. While this is a considerable oversimplification, the principle remains the same. The pore width allows ready passage of potassium ions but, in the resting state, is too small to let sodium ions pass through.
Depobrixation. S o far we have looked only at a resting, inactive nerve fiber. Most nerves, of course, are hard at work carrying impulses from one part of the body to another. Let us go back to the squid’s giant axon and again insert a fine electrode through the membrane, recalling that in the resting state a -70 mv resting potential registers across the membrane. Now let us apply a stimulus some distance away from the electrode. We usually use electrical pulses in the laboratory because they are easily controlled, but impulses in the human body are generated by a variety of stimuli. Whatever the stimulus, a weak one will cause only a slight change in the membrane, decreasing the transmembrane potential from perhaps -70 to -55 mv a t most. If we remove the stimulus, the needle of the recording voltmeter immediately returns to the resting level of -70 mv. A brief or weak stimulus thus merely causes a transient voltage change without anything exciting happening. However, if we apply a slightly stronger stimulus, some major chang-
288
es take place with lightning speed. Slowing down events, we would see, on applying the stimulus, a rather slow initial movement of the voltmeter to -55 mv. This voltage level is called the firing threshoZd. Once the threshold is reached, the voltage suddenly swings violently from the negative side of the meter, then, much more slowly, returns to normal again. We have just witnessed a very quick and brief reversal of membrane voltage, the total excursion of the needle being some 100 to 120 mv. This rapid change in membrane voltage is called depoZarixation, and the large voltage so generated is called the action po-
tential. Membrane events. What happened? Let us go back to the resting membrane which excluded sodium ions (concentrated in the extraneural fluid) from the nerve interior. The nerve interior, the axoplasm, barely has any sodium ions in it, creating a large transmembrane sodium concentration gradient. The membrane interior is negatively charged and the sodium ions are positively charged. Hence, there is not only a sodium concentration gradient, but also an electrostatic sodium gradient, both trying t o pull sodium ions inward. Through mechanisms not altogether clear yet, the membrane changes its configuration under the influence of an electric field such as the stimulus we applied. This configurational change causes the pores to widen sufficiently to accommodate sodium ions. Pulled by powerful forces, sodium ions now rush through the membrane down their concentration and electrostatic gradients. So many sodium ions enter so fast that it briefly causes an excess of positively charged sodium
AORN Journal, August 1973, Vol 18, N o 2
ions a t the nerve membrane interior. This explains the brief overshoot of the membrane potential during depolarization. As soon as the stimulus is turned off, the membrane reverts to its original sodium-excluding state, potassium ions start moving out and the resting potential is restored. Note that each depolarization cycle traps some sodium ions inside the membrane, so that the transmembrane sodium gradient will be erased eventually. Sodium trapping, and consequent rundown of the action potential, is prevented in living nerve by the sodium pump mechanism that actively returns sodium ions to the external fluid.
Impulse spread. The story is now almost complete. We initiated depolarization with a stimulus that caused changes in the membrane. The enormous and fast voltage changes in the membrane during depolarization reverses the polarity of the membrane. The negatively charged membrane interior acquires a brief positive charge during depolarization. The membrane exterior changes briefly from a positive to a negative charge. The depolarized membrane is charged oppositely from neighboring membrane sites. To restore equilibrium, electrical charges begin to flow along the membrane, just as in a battery. These current flows in turn lower the membrane potential in areas adjacent to the initial site of depolarization. Lowering of the transmembrane potential is initiated a t a new site. Depolarization o f contiguous membrane areas is self-regenerating; once initiated it proceeds from one end of the axon to the other. This process of the impulse traveling along the nerve is like a spark in
a powder fuse. To detonate a stick of dynamite, you roll out a long fuse and light the end with a match. A portion of the fuse starts to burn, thereby heating the adjacent portion to its burning point so that i t starts to burn. Once lit a t one end, the fuse transmits the spark to the dynamite stick. Recall my earlier comparison of a nerve fiber with a loaded pistol. It takes only a light and brief pull on the trigger to set off tremendous forces.
Local anesthesia. What has all this to do with local anesthesia? Local anesthetics, in a way not yet clear, “freeze” the nerve membrane in its resting or stable configuration and prevent the membrane from changing when an impulse arrives. In physiologic terms, local anesthetics maintain the membrane in its resting, sodium-excluding, polarized state. With the membrane incapable of depolarizing, an action potential is not generated a t the anesthetized site. Let us go back to the analogy of a lighted powder fuse. If a portion of the fuse is wet, when the spark reaches the damp site it will not be able to heat that part to the burning point. The spark soon fizzles out and the dynamite stick never explodes. If you think of anesthetized nerve in similar fashion, you will see that the membrane, being unable to depolarize, cannot set up currents in adjacent membranes. The process of impulse transmission is halted a t the anesthetized site and the nerve is said to be blocked. Impulse transmission is blocked in either direction. Neither signals arriving from the skin such as a painful stimulus, nor impulses originating from the central nervous system such
AORN Journal, August 1973, V ol18, No 2
289
as a command to a muscle, can proceed. Thus the area innervated by the blocked nerve is numb and insensitive to other modalities such as heat and pressure. In the case of a blocked motor nerve, the patient is unable to move the innervated muscle groups. DiffewntiaZ Mock. The situation is actually more complicated. A peripheral nerve contains many nerve fibers of many different sizes. Size is an important characteristic of a nerve fiber which determines many physiologic properties including sensitivity to local anesthetics and function. The thicker a nerve fiber, the less readily it is blocked by local anesthetic. A certain concentration of local anesthetic may block a thin fiber but may be too low to block a thicker fiber. A strong local anesthetic solution, having a concentration sufficient to block thick fibers, will also block thinner nerve fibers. A division of labor exists among nerve fibers. In man, thin fibers transmit impulses related to pain and temperature while thick nerve fibers transmit impulses such as touch, pressure and stretch impulses to skeletal muscles. Pain impulses, traveling over thin nerve fibers, are more readily anesthetized than motor impulses which traverse thick nerve fibers. When a mixed peripheral nerve is blocked, the patient may be completely free of pain yet still be able to move muscles and perceive touch and pressure. This type of nerve block, where some functions are interrupted and others are not, is called a differentiaz Mock. A differential block may exist after local anesthesia, and the patient, who feels no pain, may still feel the touch of the surgeon’s knife. Patients are unde rs t a n d a bl y apprehensive about this experience. A few soothing
290
words from the nurse will often work wonders in allowing successful completion of the operation.
The blocking process. Nearly all anesthetics in current use are amines. The amine, often called the base because it is weakly basic, is insoluble in water (though very lipid soluble). The drug for injection should be in a water-soluble stable form. This is accomplished by forming the local anesthetic salt from the base and a strong acid, commonly hydrochloric acid. In water, the local anesthetic salt dissociates into two molecular forms. One is the original local anesthetic base which is electrically uncharged. The other is the quarternary amine form, the positively charged cation. The proportion of base and cation in solution varies with the pH; the more acid the solution, the more cation is present and the less base. The reverse holds in an alkaline environment. The two forms, base and cation, each important to the blocking process, have distinctly different properties. The cation, the charged quarternary species, binds to receptor sites in the nerve membrane, stabilizing it and preventing depolarization. The cation is the actual nerve-blocking molecular form. The local anesthetic base, lipid soluble and carrying no electrical charge, readily diffuses into tissues and traverses diffusion barriers such as fibrous tissue. The base delivers the drug from the site of injection to the site of cation. Once at the nerve membrane, the cation takes over to cause the actual transmission block. The proportion of base and cation thus is important for a smooth block. If the solution is too acid, not enough base dissociates to move the drug to the nerve mem-
AORN Journal, August 1973, Vol 18, N o 2
brane. If the solution is too alkaline, it diffuses rapidly but inhibits release of sufficient cations to block the nerve. Disease states such as infection affect tissue pH, and can also affect the course of local anesthesia.
Summary. Resting nerve is polarized, with the inside of the nerve membrane negatively charged with respect to the outside. This is because the resting membrane is impermeable to sodium ions. A stimulus disturbs this state and briefly reverses membrane polarity; the nerve interior now being positively charged with respect to the exterior. The explosive changes associated with depolarization are attributable to a change in membrane permeability which briefly permits sodium ion passage. The polarity reversal brought about by depolarization sets up currents in adjacent parts of the nerve, in turn depolarizing them. A single brief membrane change a t one end of the
nerve fiber thus initiates an advancing electrical wave, the action potential or impulse, which travels from one end of the nerve to the other. Local anesthetics, by retaining membrane integrity and sodium impermeability, prevent depolarization. Hence an impulse traveling along a nerve by spreading depolarization is halted a t the anesthetized site. The nerve is blocked and impulses can travel neither to, nor from, the central nervous system. The innervated body area is numb and the muscles
El
paralyzed. REFERENCES
A d r i a n i , J. The Pharmacology of Anesthetic Drugs,
4th ed. Springfield: Thomas, 1968. Hodgkin, A L. The Conduction of t h e Nervous Impulse. Liverpool: University Press, 1965. d e Jong,
R
H . Physiology and Pharmacology of
Local Anesthesia.
Springfield: Thomas, 1970.
Katz, 8. Nerve, Muscle ond Synapse. New York: M c G r a w - H i l l , 1966.
Infecfion sfudy reporfed Medical researchers a t a symposium held a t the New York Academy of Medicine on “Hospital Infections and Hand Washing” heard that a routine hand washing lasting only 20 seconds with a potent non-hexachlorophene microbicide may b e the keystone to the control of hospital infection. Other soaps were included in the research reported at the symposium held under the auspices of the Department of Environmental Sciences of the University of Massachusetts. Warren Litsky, commonwealth professor of microbiology a t the University of Massachusetts, reported that his tests showed that hexachlorophene and other soap preparations are relatively ineffective against gram-negative microorganisms. He said the soaps inhibited the growth of bacteria but did not destroy them, and the preparations all had a slow onset of action and cumulative effect. However, the microbicidal preparation killed gram negative and gram positive germs on 20 second contact and did not depend on repeated use. Peter Dineen, MD, clinical professor a t the New York Hospital-Cornell Medical Center, conducted a study which essentially confirmed Dr Litsky’s findings.
AORN Journal, August 1973, V o l 1 8 , N o 2
291