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