July 1, 2007
An examination to gain understanding of the peripheral nervous system axon
by Jack Vander Beek
With this article we begin a series aimed at exploring a singularly unique and mostly overlooked part of vertebrate anatomy. This area is the domain of the regional nerve block and its characteristics determine the success or failure of your regional nerve block. This is also the region where conditions occasionally align to create the worst outcome of the regional nerve block, permanent nerve injury. It has no observable moving parts. It uses energy silently but efficiently. It is tolerant of most abuses but seems very slow to repair even the slightest damage. Its work is done on the molecular level and our understanding of this domain is crude and limited, but we impose on its hospitality everyday. We inject our drugs around it to purposefully stop it from doing its job, then sit back and expect it to clean up the mess and go back to business as usual, on our schedule, AND most of the time it does just that, so we are surprised when it doesn't.
It is the axon of the peripheral nervous system. It is small in diameter, around a 10th of the diameter of the human hair but in some cases it can be a meter long. The axon carries the messages to and from the muscles and skin, the subcutaneous tissue and the periosteum, and the ligaments and the arteries. It is a marvel of biological engineering, constantly renewing itself, never being replaced, with, in most cases, a duty cycle of 16+ hours a day, 365 days a year, with a MTBF (mean time between failures) of more than 70 years. For all we know it is the only component of our bodies which, in most cases, is completely intact at the time of our deaths.
At the end of this series of articles we hope to have a little better understanding of how this part of us works and what occasionally goes wrong with the way we treat it and subsequently damage it.
What inspired this series
"Primum non nocere", First do no harm. But what if you're not really sure what causes harm in a given situation? Is it then best to do nothing? Understanding will let us move ahead with confidence to create safe regional block techniques.
A recurrent topic in the world of regional anesthesia is the appearance of nerve injury following what appears to be a normal and uneventful regional nerve block. To date, peripheral nerve injuries associated with block have been blamed on such factors as intraneuronal needlestick or injection, the addition of vasoconstrictive adjuncts to local anesthetic solution, or hypertonic or chemically irritating local anesthetic solutions.
Remedies to the situations or practical tips on how to avoid dangerous situations include such nostrums as: never accept nerve stimulator needle placements with stimulating currents below 0.5 milliamps, never inject when "excessive" resistance to injection is felt, avoid the addition of vasoconstrictive agents such as epinephrine which may lead to ischemic damage of the nerve, and others. These admonitions may or may not be worthwhile specifically to avoid nerve injury during regional block, however each of these, and any other common prohibitions that you may add, lack usefulness and "the ring of truth" because they are not practical or even possible in most situations where you intend to end your procedure with a working block.
The uncomfortable truth is that the nerve injuries don’t just occur in the practices of novice anesthesiologists. If it did we could expect that experience alone would protect us from the danger. In most cases the disaster seems as likely to occur on your 10,000th block as your first. When it happens we are left wondering why, searching for the difference between that block and all the others, wondering what to change in the technique.
We will start by examining what are commonly thought to be risk factors in techniques. We will move on then to examining the structure of axons and how they are thought to work. After that we will look at the effects of local anesthetics on axons, on different injury types on axons, and how and when they heal. We can hope at the end of the series to understand the entire system of nerves and nerve blocks better and use that understanding to create safer techniques for performing them.
Werewolves and Nerve Injuries
What do these 2 things have in common? Both of these are to be avoided and traditional thinking has it that avoidance is best accomplished by observing some common proscriptions. Just as garlic, silver objects, and crucifixes will keep one safe from vampires and werewolves, so it is "known" that by following a few specific recommendations you will remain safe from the nerve injuries that lurk by night. So what follows in this article may appear to some to be blasphemy or tempting fate. Unsettling as it may seem let us take a closer look at some of these common beliefs.
First Common Belief: Nerve Stimulators will Keep You Safe
Hopefully, it is by now fairly apparent that not all nerves twitch. By this I mean, while observing with ultrasound it is very common to see nerve stimulator needles touch, and even penetrate nerves multiple times without creating a motor response or a parasthesia. This is extremely common in patients with neuropathies, diabetic or other. But it is also seen in a limited sense on any nerve. Here's a common scenario, you are performing a sciatic nerve block using a nerve stimulator needle under ultrasound guidance. You watch the needle approach the sciatic nerve and touch it. No twitch is produced. You check your return electrode connection, check your connection to the needle, and make sure that the nerve stimulator box is turned on and adjusted correctly. Everything is technically correct but still the nerve does not twitch. You withdraw the needle, reposition it, and the typical motor response is elicited. What just happened? Healthy patient, no history of neuropathy, no comorbid conditions that might explain the reaction. Perhaps the answer is much simpler than this, perhaps the tip of the stimulating needle did not touch near a motor axon.
Since you can place a nerve stimulator needle in, around, and through nerves without creating a motor response, and since there is no naturally occurring calibration between milliamps of stimulation and proximity to a working motor nerve, nerve stimulators are misleading and unreliable when information about position of the needle tip in relation to the nerve substance is sought. In other words, if you're trying to get close to a nerve but not inside of it and you have better tools (such as the ultrasound) then nerve stimulators should not be used. They are ultimately inaccurate and even dangerous if you believe you should not stick needles in nerves.
Second Common Belief: You Should Not Stick Needles into Nerves
Most people agree with this one, although there are a few who deliberately stick needles in nerves and inject slowly to get blocks. In general, it's indisputable that physical damage to nerves created by sharp objects such as needles can cause nerve injury. It is probably only the amount of injury which determines whether there would be a perceptible or detectable degree of dysfunction resulting. I think everyone knows that needles get stuck into and through nerves frequently. Anyone who has observed residents attempting to perform a femoral artery or vein stick can surmise how this might happen. But in addition while using ultrasound guidance for nerve blocks it is not uncommon to view penetration of the nerve with needles, nerve stimulating and other, and even partial injections into nerves. Indeed, recently major anesthesia journals have contained articles and letters discussing the overall lack of untoward outcomes following inadvertent or even intentional penetration of nerve bundles with needles and injections.
Some thinking that is related to this topic may go like this for a motor unit, that is, an axon leading to one or more individual muscle groups. Axons within nerve bundles are very small (on the order of a few microns). A single axon may branch and innervate more than one muscle unit, a muscle unit may receive synaptic connections from more than one motor axon, the muscle unit is one of many that makes up a muscle group, damage to one or more associated axons may or may not produce a detectable deficit in a motor response. In other words, there is a certain amount of redundancy which is built into the system allowing for some loss of innervation a motor units, and presumably sensory units.
So if you can say that sticking a needle into a nerve only sometimes creates detectable nerve injury, and that injecting local anesthetic solution into a nerve bundle only sometimes creates detectable nerve injury (implying that many times needle sticks and intraneuronal injections do not create detectable nerve injury), then it follows that sticking needles into nerves or injecting into nerves, in and of themselves, do not create detectable nerve injury. In the cases in which nerve injury occurs concurrently with needles being stuck in the nerves or injections be made in the nerves, and there is some special characteristic of those sticks and injections which creates the injury, or there are other conditions, which are not yet apparent, which facilitate the occurrence of the injury under those special circumstances.
Third Common Belief: You Should Not Inject If an "Excessive" Amount of Resistance to Injection is Encountered (because it could lead to the next topic)
This commonly heard warning assumes that you know approximately where the tip of your needle is and this is not a foregone conclusion. “Excessive resistance” can only be felt if you are trying to inject and if you are using a nerve stimulator to place the needle, you will only try to inject after you have received a motor response to stimulation, and that usually means that you've ready to accept the current output setting as indicating you could be in the right place. As discussed above, the absence of a motor response to stimulation should not be interpreted to mean your needle is not within the substance of the nerve. Therefore when using a nerve stimulator, you generally just keep passing the needle until you get a motor response, potentially puncturing the nerve multiple times. Then you can test resistance to injection.
Unless you are sure your needle tip is within the nerve, you must rule out other causes of increased resistance to injection, such as, clot or tissue in the needle tip, or the tip positioned within an anatomical layer of some kind.
Under ultrasound guidance with even a reasonably good indication of where the needle tip is you should be able to tell what is causing increased resistance, and this information will dictate what your next maneuver is. Many times it is clear that an increase in resistance to injection pressure is caused by a fascial plane outside of the nerve bundle. In this circumstance it would be necessary to further advance the needle to pass the tip through the tissue plane and closer to the nerve. On the other hand if you see that you're close to the nerve on ultrasound and you encounter what you consider to be excessive resistance to injection, it would seem prudent to withdraw the needle a millimeter or two and try to inject again.
What constitutes an "excessive" resistance is subjective unless you're measuring, and if you're measuring then you must make a decision (based on some kind of information) as to how much pressure is excessive. In this case you've taken that fatal step that says this much resistance pressure is safe and more is not. I think this is "whistling past the graveyard", a false sense of security based on an arbitrary belief that all nerve substance regardless of tissue age and condition will produce the same resistance to injection from all needles, syringes and speeds of injection.
In most cases, injecting through a short bevel needle tip which has been inserted a small distance into the substance of the nerve would most likely push the nerve off of the needle tip with little of the solution ending up intraneuronally. Again, I say this not to advocate placing the needle into nerves and injecting, but to propose that there is a pre-existing safety factor in the scenario that could likely prevent inadvertent injection into the nerve substance.
Fourth Common Belief: You Should Not Inject Into the Substance of the Nerve Bundle (again, because it could lead to the next topic)
This topic is covered in part in the section about so only the more specific characteristics will be discussed here. There are at least three qualities which could be considered regarding injection into a nerve bundles; the creation of a fluid occupying space within the bundle and the blunt dissection along planes that creates this space, the pressure contained within the space and transmission of the pressure to adjacent tissues, any physical or chemical effects to it the tissues contacted by the solution are subjected (such as hyper/hypotonicity, pH, reactivity to side chains, etc.).
One can easily imagine circumstances for each of these characteristics which could create conditions conducive to nerve injury. For example, large volumes such as 100 mL injected into the sciatic nerve, extremely fast injections creating high-pressure areas within the nerve bundle, hypertonic solutions, exceedingly alkalotic solutions, and so on. Common sense could be used to avoid most of the problems associated with these extremes.
Consider for a moment the effects of pressure on nerve bundles, and think of that pressure across a continuum of magnitude. When we sit we put pressure on the sciatic nerves. The amount of pressure we place on the sciatic nerves is a function of how much we weigh, how much intervening tissue there is to spread our weight, and what we are sitting on (a recliner chair versus a fence rail). Still the pressure is on our sciatic nerves and occasionally we do have a foot "fall asleep" after staying in one position too long. Everyone has felt the "pins and needles" of an extremity "waking up", how many have gone to the ER to have it checked. Consider the common phenomenon of waking up in the night with an anesthetic hand caused by "sleeping funny". Rhabdomyolysis sometimes can occur during extreme interruptions in blood supply to extremities, or crush injuries, but the offending forces in these instances are much larger and usually contain circumstances that lead to a spiral of increasing pressure with little or no outlet. It seems that if pressure alone caused permanent nerve injury we would see many more debilitating injuries arising from the ubiquitous use of barstools and epidemics in the ranks of our legislators.
Again I am not advocating injecting into nerve bundles, I am only pointing out that people do and have injected either inadvertently or intentionally into nerve bundles without consistent evidence of nerve injury. And because of this it is reasonable to assume that simply injecting in the nerve bundles is not an absolute cause of nerve injury.
Fifth Common Belief: If You Inject Into a Nerve, Excessive Pressure Within The Nerve Could Cause Ischemic Damage
This sounds true and I have no reason to doubt it when considered in the light of some imaginable circumstances. For example placing a needle dead center into the sciatic nerve open (preferably a very small needle such as a 25 gauge, so that there would be a minimum of leakage back out of the nerve substance around the track of the needle) and then purposely injecting a relatively large volume (on the order of more than 20 mL) into the substance of the nerve bundle. The circumstance above is not unimaginable given some of the common techniques used for nerve blocks. As a matter of fact I'm certain that some variant of this exact situation occurs in some small percentage of sciatic nerve blocks performed every day the United States (and the world). I have even seen this very situation published on websites (probably unknown to the author) but nonetheless clearly evident in the ultrasound movie and apparently resulting in no harm.
But there is the thought; that the nerve bundle may act as a charged pressure vessel, with internal pressure reversing a pressure gradient which would ordinarily allow nutrients from the blood supply, the vasa vasorum, to move into the axons and sustain it. This is the picture created by the warning about ischemic damage from intraneuronal injection, that raises the question, Just how does the axon receive its nutrients?
This question, it turns out, is not so simply answered, and if that is so, then there are many other related concerns (like how do blocks work, or what causes nerve damage) that cannot be completely understood without addressing the simpler issues first.
So Where Do We Begin To Understand and Explain Blocks That Work and Blocks that Don't and the Occasional Nerve Injury
It occurred to me that the majority of our concern and attention in performing regional nerve blocks whether using nerve stimulator or with ultrasound guidance is centered on the axon of the peripheral nervous system. It is in the environment of the axon where the effects of the local anesthetic solution are made manifest. Whether this be a failed block, a poor block, a perfect block, or some degree of nerve injury. It would seem prudent therefore, if one hopes to have consistent success in creating nerve blocks, one should understand the environment in which either occur. Without this understanding we are left with little hope of correcting problems or capitalizing on successes because we cannot know how they occur. This leaves us in the same situation as the pundits struggling to explain the movements of public stockmarkets.
So we start at the very basics of the axon and seek as much detail as is understandable and necessary to form a model of their function, and dysfunction. It will be useful to simplify what is known about the structure and function of neuron in general and the axon in particular where possible and concentrate on creating a usable model based on what is known and what is probable (when we reach a gap in the knowledge). If at the end of this series of articles all that we have accomplished is a review of the theories associated with the propagation of action potentials and the proposed action of local anesthetics, then it will be worthwhile. But, it is possible that by applying reason to existing information we will arrive at a different model of the axon and its place in the regional nerve block, a new picture of those factors which can lead to nerve injury, and maybe even ways to improve existing techniques based on reasons that we have explored and found worthy.
Or else we too risk being inexorably drawn into the maelstrom of the “madness of detail” which lies in wait for the unsuspecting researcher, ruining their taste in clothes and making them fit company for only the 2 or 3 other people who share their “interest” in the subject. The desire to avoid such a fate is, of course, one of the reasons you became anesthesiologists, so we will consider the subject of avoiding arcanum closed, for good, sufficient and self-evident reasons.
We will start by describing the axon, in as much detail as it takes to form a working picture in our mind. We'll look at what is known and possibly what is missing from the picture. I once worked with a builder who said that after looking at blueprints for a few minutes he could “walk through the house” in his mind and explore it. That is the view we will try to create, a view of a living axon that you walk through.
This is where we will begin in the next installment of this article.