Neurovascular Bundle Anatomy

The neurovascular bundle consists of peripheral nerve fibers wrapped in connective tissue, intermingled by a capillary plexus (Fig. 23-1). Three types of connective tissue are present within the peripheral nerve: endoneurium, perineurium, and epineurium. The endoneurium is a delicate, supporting structure located adjacent to individual axons within a fascicle. This layer covers the entire individual nerve fiber. Individual fascicles are bound by the perineurium.^4,5 The perineurial barrier is formed by adjacent perineurial cells via tight junctions, which help manage the axonal microenvironment, in addition to the blood-nerve barrier and nerve-cerebrospinal fluid (CSF) barrier.⁶ The fascicles are bound in groups by the outermost layer, the epineurium (Fig. 23-2), which encloses the nerve as a whole. This layer contains the vasa nervorum, which divides into arterioles that penetrate the perineurium (Fig. 23-3). Ultimately, a network of capillaries reaches each fascicle to supply individual axons. More specifically, the vasa nervorum forms the endoneurial capillaries. The endoneurial capillary endothelium contains tight junctional connections, which create the blood-nerve barrier. Cells that compose the distal layer of the arachnoid membrane are connected by tight junctions as well, which form the boundary of the nerve-CSF barrier. As nerve roots leave the subarachnoid space, the perineurium fuses with the cells of the distal layer of the arachnoid membrane. Anterior and posterior nerve roots, which are motor and sensory, respectively, initially leave the spinal cord separately, but merge via the connective tissue architecture, to become mixed sensorimotor nerves exiting the spinal canal.⁶

Figure 23-1 Under magnification, the neurovascular bundle with extrinsic blood vessels and a segmental supplying artery are apparent (EV). The linear extrinsic vessels parallel grooves created by adjacent fascicles (F).

(From Beek AV, Kleinert HE: Peripheral nerve injuries and repair. In Rand R [ed]: Microneurosurgery, 3rd ed. St. Louis, Mosby, 1985, p 742, with permission.)

Figure 23-2 Under magnification, a cross-section of the median nerve demonstrates individual and groups of fascicles (FASC). Note the connective tissue between each fascicle and surrounding the entire nerve.

(From Beek AV, Kleinert HE: Peripheral nerve injuries and repair. In Rand R [ed]: Microneurosurgery, 3rd ed. St. Louis, Mosby, 1985, p 742, with permission.)

Figure 23-3 Neurovascular bundle demonstrating the entrance of the arterial supply into the epineurium with surrounding connective tissue.

(From Zancolli EA, Cozzi EP: Nerves of the upper limb. In Zancolli EA, Cozzi EP [eds]: Atlas of Surgical Anatomy of the Hand. New York, Churchill Livingstone, 1992, p 685, with permission.)

The neurovascular bundle usually lies well protected between muscle or bone. At its most proximal location—the spinal root level—the neurovascular bundle contains motor, sensory, and autonomic fibers. These roots divide into dorsal and ventral rami, the latter of which reconnect to form a plexus of nerves. Ultimately, terminal nerve branches of isolated fiber types—sensory or motor branches—are formed.

Local Anesthetic Pharmacology

Local anesthetic agents are categorized by their chemical composition—esters and amides (Table 23-3). Ester and amide anesthetics are weak bases—their pKa is near physiologic pH. Each is comprised of a lipophilic group, such as a benzene ring, and a hydrophilic group, such as a tertiary amine. These groups are either connected by an ester or amide linkage. This linkage is what imparts their categorization as an ester or amide. Esters are readily metabolized by plasma cholinesterase, thus their half-life is very short, on the order of minutes. Para-aminobenzoic acid (PABA) is one of the break-down products of this reaction. Amides undergo hepatic metabolism through N-dealkylation and hydrolysis. This is a slower process, imparting a longer half-life (2 to 3 hours), assuming the patient has normal liver function. Some patients with local anesthetic allergy may be sensitive to PABA, and a detailed history and chart review may be necessary to delineate if a ester local anesthetic was really the causative agent responsible for an earlier allergic reaction. Some local anesthetics, esters and amides alike, are stored in multi-use vials with the preservative methylparaben. Methylparaben may also cause an allergic reaction in patients with a PABA allergy.⁸

Table 23-3 Categorization of Local Anesthetic Agents

All local anesthetics are weak bases, and their pKa is near physiologic pH. This allows for these agents to be present in both the ionized (charged) and nonionized (uncharged) forms when administered. The lower the agent’s pKa and higher the pH, the more that will be uncharged in-vivo. The uncharged local anesthetics are lipophilic and readily cross cell membranes, namely neuronal axons. Thus, the more uncharged local anesthetic that exists in vivo for a given agent, the more potent and faster onset that agent is rendered. For this reason, clinicians will elect to add sodium bicarbonate to their local anesthetics, to raise the pH and thereby increase the amount of nonionic local anesthetic.

Local anesthetics act on neuronal axons. These agents, when uncharged, passively diffuse to the sodium channels of axons. These sodium channels allow Na⁺ to enter the axon, depolarize, and propagate an action potential to allow for communication between neurons. Local anesthetics inhibit this process by binding to these sodium channels, ceasing depolarization as well as action potential propagation, and thus neuronal signaling and transmission of pain signals (Tables 23-4 and 23-5).

Local anesthetics block in a sequential order, which is related to the diameter of the axon (see Tables 23-4 and Table 23-5). C-fibers, which carry pain and temperature information, are blocked first, as their diameter is small. A-α and A-β fibers have the largest axonal diameter, and are the last to become blocked. These fibers are primarily motor and proprioceptive. However, nerves with myelin may only require pharmacologic sodium channel blockade at the nodes of Ranvier, leaving these nerves susceptible to local anesthetic action.⁸

Mechanical or chemical vasoconstriction is sometimes beneficial for local anesthesia. It allows for a block of longer duration and stronger intensity by decreasing systemic uptake. This also imparts protection against systemic local anesthetic toxicity. Dilute epinephrine is the most common agent added to local anesthetics for this purpose, although phenylephrine and norepinephrine may also suffice, with lesser results.⁹ Epinephrine dilutions of 1:200,000 (5 mcg/mL) and 1:400,000 (2.5 mcg/mL) are typically prepared with the local anesthetic. An added benefit of adding epinephrine is that it may serve as an early indicator of unintentional vascular injection. This is sometimes referred to as a “test dose”, whereby a small dose of local anesthetic with epinephrine is injected while the patient’s heart rate is monitored. An increase in heart rate above 20% of the baseline heart rate would confer a positive test dose, indicating an intravascular injection may have occurred. There are potential contraindications to the addition of a chemical vasoconstrictor to local anesthetics, although the evidence for these may be weak¹⁰ (Table 23-6). Furthermore, chemical tourniquets should not be used when anesthetizing digits, ears, noses, genitals, or other areas with a poor collateral blood supply because this could lead to tissue necrosis. However, several recent large trials and literature reviews failed to demonstrate consistent tissue injury from the use of chemical vasoconstriction in some of these areas.^12–14

Table 23-6 Relative Contradictions to the Addition of Chemical Vasoconstrictors to Local Anesthetics

What is the maximum allowable dose of local anesthetic that can be administered to the patient? This is a common question asked of clinicians, and it can be a source of confusion. The answer varies, and can depend on factors such as the local anesthetic used, to even the country in which the clinician is practicing. First, it is recommended that the package insert for the local anesthetics used be reviewed as a basis for dosing guidelines. However, a recent review of the maximum allowable dose of common local anesthetics found grade C evidence for dose adjustments depending on several factors (Table 23-7).¹⁵ Within the United States, 300 mg of lidocaine is considered the maximum allowable dose. Interestingly, the source for this cannot be found in the scientific literature.¹⁵

Table 23-7 Grade C Evidence for Adjusting the Maximum Allowable Dose of Local Anesthetics

Adapted from Rosenberg PH, Veering BT, Urmey WF: Maximum recommended doses of local anesthetics: A multifactorial concept. Reg Anesth Pain Med. 29(6):564-575, 2004.

Neural Block Technique: General Considerations

Peripheral nerve blockade can be obtained through a variety of techniques. However, to accomplish a successful block, the clinician must have a detailed understanding of the relevant anatomy, as well as technical skill. When selective motor nerves are blocked, knowledge of kinesiology is useful. To safely block a nerve of choice, local anesthetic must be deposited into the nerve sheath, or epineural space, and not intraneurally. The following techniques will describe the basic principles of approaching the nerve, such that local anesthetic can be safely given, without resulting in an intraneural injection.

In preparation for these procedures, neural blocks should always be performed under sterile conditions. An antiseptic skin preparation, sterile equipment, sterile gloves, as well as masks and caps being worn are essential elements in reducing the risk of inoculating the patient with an infectious agent. A short-acting premedication may be given to the patient to reduce anxiety and pain, such as midazolam or fentanyl. However, the clinician must not give so much sedation that communication breaks down, and paresthesias cannot be appreciated during the block procedure.

Needles used for neural blockade are often stiff; to allow for deep penetration, 23- and 22-gauge needles ranging from 25 to 150 mm in length are commonly used, depending on the type of block and procedure to be carried out. Needle trauma (discussed subsequently) is always a concern during neural blockade, and several needle bevel types are available. Sprotte and Whitacre tips, as well as short-bevel needles, are associated with less nerve trauma when compared with standard A-bevel needles.¹⁶

The two common approaches used to block nerves are the paresthesia technique (PT) and nonparesthesia technique (NPT), also known as a field block. PT attempts to purposefully provoke paresthesias of the nerve before injection. These paresthesias indicate that the needle is in contact with the nerve and serve as a warning of potential nerve injury. This technique assumes that the patient’s sensory pathways are intact and that the patient is able to cooperate with the procedure. However, this method can be uncomfortable, and can potentially damage the nerve of interest.^17–19 To help avoid neural injury, the clinician should make every effort to stop, reposition, and refrain from injecting whenever a serious or persistent paresthesia occurs. The second approach, NPT, avoids this deliberate probing for paresthesias and relies on anatomic landmarks, but generally requires greater volumes of local anesthetic. NPT is best suited for superficial nerves, and often helps supplement a prior regional anesthetic which may be inadequate over certain areas. NPT uses dilute, high volumes of local anesthetic, with the addition of epinephrine, to reduce the risk of local anesthetic toxicity.²⁰ With NPT, the needle tip may not approximate the nerve as closely as with PT. However, to provide the safest regional anesthetic, PT should be avoided when possible.

Electrical stimulation (Fig. 23-4) can be used to locate and block peripheral nerves. These stimulators are available commercially, although office electrodiagnostic equipment often will suffice. An electrical impulse generated by the stimulator and controlled by a rheostat is transmitted through the needle. A ground electrode is placed on the patient and connected to the positive lead, while the negative lead is connected to the needle. Insulated needles are available, many of which are covered with materials such as polytetrafluoroethylene (Teflon). In general, insulated needles are preferred over noninsulated needles. As the needle approaches the nerve, either a motor, sensory, or mixed response can be elicited, depending on the fiber types contained within the nerve. Typically, the clinician looks for a twitch in the expected muscle group associated with the nerve. This twitching is not typically uncomfortable for the patient; however, if it is painful in anyway, the needle should be redirected. The neural response should increase as the needle tip approaches the nerve. It is desirable to obtain a strong neural response with a low stimulus output, thereby ensuring needle placement is sufficiently distant from the nerve to provide anesthesia, yet prevent an intraneural injection. This technique is preferred when injecting neurolytic agents for the treatment of spasticity. One can quickly identify selective motor responses and quickly determine the effect of chemical neurolysis after injection.

Figure 23-4 As the physician holds the syringe in his right hand, the rheostat is adjusted on the block stimulator with the left hand. The syringe is attached to a Teflon-coated hypodermic needle, which is attached to the stimulator. Note the surface ground pad on the patient’s inner thigh.

The use of ultrasound guidance for peripheral nerve blockade has become popular in recent years, allowing the clinician to incorporate real-time, two-dimensional, visual data, in conjunction with electrical nerve stimulation data, to facilitate block procedures.

Continuous neural blockade can be achieved through the use of perineural infusion indwelling catheters (Fig. 23-5). These catheters are most commonly placed perioperatively for postoperative pain from ambulatory orthopedic surgery. These catheters can be used in the hospital or at home by the patient in recovery for several days by way of infusion pumps. There are even case reports of portable pumps, which allow the patient to ambulate and regain independence.²¹ Both continuous infusions, as well as patient-controlled regional anesthesia systems have been described.²² These catheters must be placed under strict sterile conditions because these are indwelling devices that remain in the patient for days. Potential complications include nerve injury and transient neurologic damage, infection, associated unwanted nerve blockade, and local anesthetic side effects and toxicity.²²

Figure 23-5 Longitudinal approach to the continuous interscalene block. A 17- to 18-gauge insulated Touhy needle is placed on the superior root of the brachial plexus with the aid of a nerve stimulator. Once placed, the nerve stimulator is attached to the proximal end of a 19- to 20-gauge stimulating catheter, which conducts electricity to the tip of the catheter. The catheter is advanced 3 to 5 cm beyond the needle tip, while maintaining an unchanged motor response.

(From Boezaart AP: Perineural infusion of local anesthetics. Anesthesiology 104(4):872-880, 2006.)

Computed tomography (CT) guidance for peripheral nerve blockade has also been described as an effective means to provide regional anesthesia, especially in patients where the relevant anatomy is difficult to identify (Fig. 23-6).²³ This form of image guidance for neural blockade allows for excellent visualization of the anatomy and appropriate spread of local anesthetic. CT-guided nerve blocks are not commonly used because they require expensive equipment and trained radiology technicians. Radiation exposure to the patient and care providers is a concern in performing CT-guided blocks.

Figure 23-6 Brachial plexus block to treat a left C7 mononeuropathy. A, Transverse contrast-enhanced CT scan, obtained after the skin over the brachial plexus was marked with barium paste (arrows), was acquired to help identify the locations of the common carotid artery (C), internal jugular vein (J), and vertebral artery (V). A, anterior scalene muscle, M, middle scalene muscle. B, Transverse CT scan demonstrates the tip of the needle inserted within the plane separating the anterior and middle scalene muscles.

(From Mukherji SK, Wagle A, Armao DM, Dogra S: Brachial plexus nerve block with CT guidance for regional pain management: initial results. Radiology 216:886-890, 2000.)

Regardless of the technique, the needle tip should always remain in the epineural space during an injection (Fig. 23-7). Intraneural injections have a high association with fascicular damage.^24,25 If paresthesias are elicited, the needle should be repositioned before local anesthetic solution is injected. Forceful injection is never recommended because it may be a sign of injecting into a fixed space, such as tendon or adjacent to bone. Repeat anesthetic injections close to the same nerve in a single patient encounter should be avoided because warning paresthesias may be suppressed and occult iatrogenic nerve injury may occur.

Figure 23-7 Needle placement in the intrafascicular space (A) compared to the extrafascicular space (B).

(Adapted from Gentili F, Hudson A, Kline D, et al: Peripheral nerve injection injury: An experimental injury. Neurosurgery 4:244-253, 1979, © Congress of Neurological Surgeons.)

Accidental intravascular injection of local anesthetic is an unintentional event with potentially life-threatening results. To avoid this, slow administration of local anesthetic is advisable to allow detection of early side effects, such as tinnitus, perioral numbness, or tachycardia. Intravascular injection can usually be avoided by frequently aspirating for blood in several planes prior to, and during, a slow injection, by pulling back on the syringe plunger. Most importantly, an understanding of the relevant anatomy, clinician diligence, as well as a plan to treat and resuscitate the patient from an inadvertent intravascular injection, will maximize the chance for a positive patient outcome.

Nerve Injuries

Trauma, toxicity, and ischemia are the major causes of nerve injury during neural blockade. Nerve injection injuries are almost always due to one or more of these factors.¹⁸ The incidence of neural injury during block procedures is about 1% to 2%, most of which are minor in nature.²⁶

Trauma to the nerve during neural blockade occurs with aggressive probing during needle insertion. This can directly injure the nerve fascicles. Additives, such as epinephrine, increase the toxicity of the anesthetics when injected intrafascicularly.^26a,27,28 Selander and colleagues showed a reduction in the incidence of nerve trauma and fascicle injury when short, beveled needles were used. They also demonstrated that nerve fascicles rolled or slid with needle contact.¹⁸ Most traumatic nerve injury symptoms self-resolve in 4 to 6 weeks, and essentially all reach resolution within 12 months.²⁷

Intraneural injections of solution not only directly injure nerve fibers, but also cause damage to the blood-nerve barrier function.^24,25 The spread of anesthesia with intraneural injections has been demonstrated and, when near the spine, may cause unexpected spinal anesthesia.²⁹ Neural compression or stretching also may result from large volumes of solution injected into a fixed space, thereby traumatizing the nerve.

Neurotoxicity can be caused by direct injection of anesthetics into nervous tissue—intrafascicular injections can cause profound or permanent nerve damage. The degree of damage depends on the type and amount of drug injected, as well as the kind of preservative used for the anesthetic medication.^24,25 Ester anesthetics generally demonstrate greater toxicity than amides when injected into the intrafascicular space.^30,31 Extrafascicular injections of anesthetics in routine concentrations rarely cause significant histologic nerve damage or disruption of the blood-nerve barrier, but can alter the permeability of the perineurium, leading to endoneurial edema.^30,31 The epineurium provides some neuroprotective function during injection, thereby reducing toxicity from anesthetic medication.

Mackinnon and colleagues found that corticosteroid injections into the epineural tissue did not cause nerve damage.³² When injected into the intrafascicular space, corticosteroids exerted a direct neurotoxic effect with disruption of the blood-nerve barrier, similar to anesthetics. Severe nerve fiber damage was noted with hydrocortisone (Solu-Cortef) and triamcinolone hexacetonide (Aristospan), moderate damage with triamcinolone acetonide (Kenalog) and methylprednisolone (Depo-Medrol), and the least damage with dexamethasone (Decadron) (Fig. 23-8).

Figure 23-8 A, Cross-section of a normal myelinated nerve fiber population within a sciatic nerve (×585). B, Cross-section 12 days after intrafascicular injection of dexamethasone (Decadron), demonstrating relatively normal appearance with minimal evidence of nerve injury (×585). C, Cross-section 12 days after intrafascicular injection of triamcinolone hexacetonide (Aristospan), demonstrating severe widespread axonal and myelin degeneration (×585).

(From Mackinnon SE, Hudson AR, Gentili F, et al: Peripheral nerve injection injury with steroid agents. Plast Reconstr Surg 69:482-489, 1982, with permission.)

Ischemia is typically thought to be the result of the application of a tourniquet for a prolonged time period, or improper positioning of the patient. However, a nerve block itself, if the injection is given into the intrafascicular space, may also cause ischemic damage. The ischemia results from increased intraneural compartment pressure by the injectate volume, which reduces neural perfusion. This intraneural pressure has been shown experimentally to remain above the blood perfusion pressure for 15 minutes without damage.²⁹ A rare potential cause of ischemic nerve injury is the result of a local hematoma formed during the block procedure from inadvertent arterial puncture.

To diagnose a neural injury, a combination of radiologic imaging and electrophysiologic tests can be performed in conjunction with the patient’s history and physical examination. Obtaining input from other specialty consultants, such as neurologists and radiologists, often hastens appropriate testing and diagnosis of a potential nerve injury. Magnetic resonance imaging (MRI) can be useful in revealing nerve compressions secondary to fluid accumulation from blood, edema, or local anesthetic injectate.²⁶ Conduction tests can be used to assess the amount of damage to large diameter sensory and motor axons. Electromyography (EMG) can evaluate and quantify damage to smaller motor units²⁶ as well as help with locating the site of neuronal injury.

Patients with an underlying peripheral neuropathy, either known or subclinical, may be more susceptible to nerve injury during neural blockade, a phenomenon known as the “double crush” syndrome (Fig. 23-9). The double crush syndrome hypothesis claims that damaged axons may be more prone to damage at a more distal location.³³ Furthermore, two relatively small lesions along a single axon are worse than a single larger lesion—the damage of two axonal stressors “far exceeds the expected additive damage caused by each isolated compression”.³³ For example, a case report in 2001 of a young female undergoing chemotherapy with cisplatin, an agent known to cause peripheral neuropathies, developed a brachial plexopathy after an interscalene block.³³ Bearing this in mind, patients with a potential initial axonal insult from any cause, may be susceptible to nerve damage from subsequent neural blockade.

Figure 23-9 Neural lesions resulting in denervation. Axoplasmic flow is indicated by the density of shading. Complete loss of axoplasmic flow results in denervation (C, D, E). A, Normal neuron. B, Mild neuronal injury at a single site (X) is insufficient to cause denervation. C, Mild neuronal injury at two separate sites (X₁ and X₂) may cause distal denervation. D, Severe neuronal injury at a single site (X) may also cause distal denervation. E, Diffuse underlying disease process (toxic, metabolic, ischemic) impairs axonal flow throughout the neuron that predisposes the axon to distal denervation after a single minor neural insult at X.

(From Hebl JR, Horlocker TT, Pritchard DJ: Diffuse brachial plexopathy after interscalene blockade in a patient receiving cisplatin chemotherapy: The pharmacologic double crush syndrome. Anesth Analg 92:249-251, 2001.)

General Principles of Neural Blockade

A number of agents, and combinations, are often used to provide a nerve block. The most common mixtures include local anesthetics with corticosteroids. When chemical neurolysis is desired, such as with hypertonicity or chronic intractable pain, neurolytic drugs (e.g., phenol), may be administered. A brief discussion of the principles of anesthetic, motor, sensory, and neurolytic blocks follows.

Education, Training, and Simulation

Teaching clinical fellows, residents and medical students not only the informational and academic aspects of neural blockade, but also the technical procedures and associated ergonomics is important. However, it is not always possible to expose trainees to enough procedures to allow them to perform these blocks individually in a safe and efficient fashion. High-fidelity simulators have become increasingly popular for trainees to gain these valuable skills. Likewise, simulation can allow trainees, and the practicing clinician alike, to manage rare complications and crisis situations as they relate to neural blockade (e.g., anaphylaxis). A recent case report describes how the use of simulation facilitated the management of a patient in cardiac arrest from bupivacaine toxicity.³⁶ High-fidelity simulation for educating trainees to perform a variety procedures and managing critical events will likely become an essential component of medical education.

Conclusion

Clinicians and patients alike have long shared the desire to achieve a safe and effective means to anesthetize regions of the body stricken by pain. The available techniques for neural blockade require the clinician to be familiar with, and understand, regional anatomy, indications, side effects, and local anesthetic pharmacology. With this knowledge and mastery of the technical aspects of these procedures, the patient can expect relief from the application of neural blockade.

Acknowledgment

The author would like to extend a special thank you to Ted Lennard, MD, for his original work on this chapter.