Peripheral Nerve Blockade and the Effects of Paraesthesiae

Home , Endoneurium, Epineurium, Nerve fascicle, Perineurium

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MA Reina1, JA De Andrés2, A López1, V Badorrey1

1Department of Anaesthesiology and Critical Care, Hospital de Móstoles, Hospital Madrid Montepríncipe, Madrid & 2Department of Anaesthesiology, Critical Care and Pain Therapy, Consorcio Hospital General Universitario, Valencia, Spain

A peripheral nerve consists of bundles of parallel axons, called fas- nucleus. The number of layers depends on the size of the cicles, which are enveloped by a connective tissue sheath. The ensheathed nerve fascicle and is greater around large fascicles of axon distribution within the nerve comprises a plexus in which the nerve fibres. axons are positioned along the path of the fascicles, allowing a close relationship between adjoining axons and their specific The endoneurium location along the nerve [1]. On repeated cuts of a nerve, the The endoneurium is a delicate tubular structure that surrounds topography of the fascicles changes. Generally, the number of the Schwann cells and each capillary within the fascicles [1]. It fascicles increases and the bundle surface area decreases in areas is composed of longitudinally oriented collagen fibres. The where the nerve branches and on the areas next to joints. In con- inner fibres and the ones closest to the Schwann cells have a trast, the number of fascicles decreases and their surface area more disorganised distribution [1]. A basal lamina separates the increases in the areas located between the appearance of the sub- endoneurium from the Schwann and endothelial cells [1]. divisions of the nerve and on the areas between joints. The different components surrounding the axons are called the The blood–nerve barrier endoneurium, perineurium and epineurium. They are found The nature of the epineurium, perineurium and endoneurium along the whole extension of the nerve and become progres- helps us to interpret the function of the blood–nerve barrier. At sively thinner as the nerve divides into its branches [1]. their margins, contiguous perineurial cells are linked by extensive zonulae occludents (tight junctions) constituting the mor- The epineurium phological basis of the perineurial diffusion barrier. In contrast, Outside the nerve, the epineurium is the connective tissue that the epineurial cells are not joined by zonulae occludentes or surrounds the entire nerve trunk. Its thickness varies according other specialised junctions and the endoneurium is not made by to the nerve and to the specific location. The epineurium con- cells, but by a condensation of collagen fibres. Both layers may tains mainly collagen fibrils (oriented longitudinally along the allow the free passage of substances across them. nerve axis) as well as a few elastin fibres, adipose tissue, some When a peripheral nerve is blocked, only a small amount of fibroblasts, mast cells, blood vessels (vasa nervorum), lymphatic local anaesthetic agent can diffuse through the epineurium, per- capillaries and small nerve endings that supply the vessels (nervi ineurium and endoneurium to reach the site of action on the nervorum) [1]. In general, the more numerous the fascicles, the axonal membrane. Local diffusion is influenced mainly by the greater the quantity of epineurium. integrity of the perineurium, the presence of myelinated or unmyelinated axons and the size and location of axons along the The perineurium nerve. However, we know very little about the actual amount of The next sheath of connective tissue, which is denser and anaesthetic solution injected that reaches the axons as very few encloses individual nerve fascicles, is called the perineurium. It studies have been done on this topic. Popitz and colleagues [3] is made of between eight and 15 concentric layers of cell measured a maximum intraneural concentration of nearly 1.6% processes that surround each bundle and alternate with layers of of the injected dose when a total block was given. When the collagen fibrils [2]. Perineurial cells are flattened, joined response was limited to deep painful stimulus, the concentration together by tight junctions (zonulae occludentes) and was near to 0.3% and when the recovery from the block was hemidesmosomes which, together, make up a diffusion barrier. complete the concentration was close to 0.065%. The thickness of the perineurium is the result of the number of With regard to the nerve vascular supply, 92% of the vessels layers and varies between 10 to 25 µm [2]. Each perineurial cell have a diameter of less than 10 µm. Capillaries are the most is 1 µm thick at the core and 0.1 µm in the area outside the abundant vessels with a diameter of between 6 and 10 µm and a 3

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them. These groups of bundles are the origin of the distal branches of the nerve. The fat tissue does not increase the whole diameter of the nerve, but only in the areas that separate the group of fascicles [4]. This tissue overgrowth can be found at a variable dis- tance from the macroscopic split of the nerve branch [4,5].

Nerve damage related to peripheral nerve blocks When performing a nerve block, the needle tip can induce paraesthesiae due either to direct contact or mechanical stimulus of the nerve fibre. These paraesthesiae can occur at any time and are not closely related to either the intentional use of a previous paraesthe- sia as a landmark for locating the nerve, perivascular location tech- niques or nerve electrical stimulation procedures. In the last two cases, unintentional paraesthesiae can occur in up to 40% of patients. Once paraesthesiae have been established, their clinical variations do not depend on the anaesthetic technique employed and are more related to specific features of the nerve (size and prox- imal or distal location), the needle type and the depth of intraneural penetration of the needle tip. Fig. 1. Transmission electron microscopy of a capillary vessel Paraesthesiae can be caused by fascicular compression when the within a nerve fascicle showing the specialised junction. needle is inserted to a depth of 0.1–0.2 mm, resulting in a superfi- (From reference 3, with permission.) cial lesion that will affect only the epineurium and will not compromise the nerve [5]. When the needle reaches a depth of 0.3–0.4 vascular barrier is formed by the tight junctions between adja- mm, the needle tip can transverse a fascicle and cause a paraesthe- cent endothelial cells (Figure 1). sia from direct contact [5] (Figure 2). Selander et al [6–10] looked The blood–nerve barrier in the peripheral nerve is very similar to at what happened to the perineurium of the damaged fascicles the blood–brain barrier. The selective solute permeability on the when long-bevel needles with a bevel cut at 14º or short-bevel nee- perineurium internal lamina and the endothelium of the endoneur- dles at 45º were used. The perineurium became damaged in 47% ial vessels allows an adequate endoneural environment to be main- and 10% of the samples, respectively. Selander’s team also found tained to preserve axonal function [2]. However, the blood–nerve barrier can be altered in different neuropathies — such as diabetic neuropathy — which then predisposes to a greater passage of substances when an injection is given in its proximity. Another aspect to consider when performing nerve blocks is the amount and distribution of fat cells within the epineurium. The fat tissue thickness is variable: 0.5 mm for the central areas and 0.2 mm for the peripheral areas [4]. Very rarely fat is located inside the fascicles. The fat tissue is organised so that it forms a cover around the fascicles, either in an isolated way or around a group of fascicles [4]. This could interfere with injected solution, alter- ing the duration of a nerve block. Local anaesthetic agents of high lipid solubility could accumulate within the intraneural fat tissue modifying the duration of block, as there is a slow and sustained release of the drug towards the nearest fascicles. We studied a selected area from sciatic nerve sections 10 cm above the knee fold. At this level the nerve length was about 7 mm × 3.8 mm and had 45 to 62 bundles according to the sample [5]. The diameter of the fascicles varied between 0.25 mm and 0.80 mm. At 1 mm deep, we found one or two fascicles, depending on their size, distributed along the transverse section of the nerve Fig. 2. Scanning electron microscopy showing representation of and therefore occupying its periphery [5]. the orientation of a long and short bevel needle, on the same In general, at 0.1–0.2 mm deep, a contact with the fascicle can measurement scale for all the structures. At 0.4 mm deep the be made. In the areas close to the macroscopic nerve branching, needle tip makes contact with the fascicles. (From references 2 4 the fascicles form groups with plentiful fat tissue in between and 4, with permission.)

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2 1

Fig. 3. Arrangement of a transverse section of the sciatic nerve and the orientation of a long- and short-bevel needle, on the same scale for all structures. At 1.0 mm deep the structures in contact with the needle tip are shown. (From reference 2, with permission.)

that if the needle penetrated the fascicle, the lesion was more References severe with a short-bevel needle. 1. Reina MA, López A, Villanueva MC et al. Morfología de los Rice et al [11–12] believed that the histological changes of a nervios periféricos, de sus cubiertas y de su vascularización. Rev Esp Anestesiol Reanim 2000; 47: 464Ð475. lesion occur over time. They studied needle damage from 23 G 2. Reina MA, López A, De Andrés et al. Posibilidad de lesiones long-bevel needles at an angle of 12º and from 22 G short-bevel nerviosas relacionadas con los bloqueos nerviosos periféricos. needles at 27º. They examined the recently produced lesion and Un estudio en nervio ciático humano con diferentes agujas. Rev the same lesion at the 7th and the 28th day, after introducing the Esp Anestesiol Reanim 2003; 50: 274Ð283. needle bevel parallel, or perpendicular, to the nerve axis. They 3. Reina MA, López A, De Andrés JA. La barrera hemato-nerviosa en los nervios periféricos. Rev Esp Anestesiol Reanim 2003; 50: found that the fascicular changes were more frequent, severe and 80Ð86. extensive when short-bevel needles were used. In the early stages 4. Reina MA, López A, De Andrés JA. Tejido adiposo dentro de los the lesion produced was greater with the bevel oriented perpen- nervios periféricos. Rev Esp Anestesiol Reanim 2002; 49: 397Ð402. dicularly; however, at the 28th day, there was no statistical differ- 5. Popitz-Bergez S, Lee-Soon S, Strichartz GR et al. Relation between ence between the needle alignments. functional deficit and intraneural local anesthetic during peripheral nerve block. A study in the rat sciatic nerve. Anesthesiology 1995; The studies of Selander et al and Rice et al do not contradict each 83: 583Ð592. other as they used different methods. Selander’s team looked at how 6. Selander D, Brattsand R, Lundborg G et al. Local anesthetics: often the lesion of the perineurial membrane surrounding the importance of mode of application, concentration and adrenaline for bundles occurred and Rice et al studied the frequency and severity the appearance of nerve lesions. Acta Anaesthesiol Scand 1979; 23: of the lesion within the fascicle. When the depth of penetration of the 127Ð136. 7. Selander D, Dhunér KG, Lundborg G. Peripheral nerve injury needle is 0.2 to 0.3 mm, the chance of overcoming the elasticity and due to injection needles used for regional anesthesia. Acta of breaking and penetrating the perineurial laminae is greater with Anaesthesiol Scand 1977; 21: 182Ð188. long-bevel needles [5]. At a depth of 0.4 to 1 mm, the lesion is more 8. Selander D, Sjöstrand J. Longitudinal spread of intraneurally injec- extensive with short-bevel needles and it will compromise the per- ted local anaesthetics. Acta Anaesthesiol Scand 1978; 22: 622Ð634. ineurium and the axons of some fascicles [5] (Figure 3). 9. Selander D, Marisson LG, Karlsson L et al. Adrenergic vasoconstric- Due to its detrimental effect, it is strongly recommended not to tion in peripheral nerves of the rabbit. Anesthesiology 1985; 62: 6Ð10. 10. Selander D, Edshage S, Wolff T. Paresthesiae or no paresthesiae? perform an anaesthetic block over nerve branches that are under Nerve lesions after axillary blocks. Acta Anaesthesiol Scand intraoperative ischaemia. If paraesthesiae occur on these ischaemic 1979; 23: 27Ð33. nerves, the trauma lesion will evolve in a more unpredictable and 11. Rice ASC, McMahon SB. Peripheral nerve injury caused by slow manner. It is also not recommended to top up a block distally injection needles used in regional anaesthesia: influence of over a previously blocked nerve. In this case, the needle tip could bevel configuration, studied in a rat model. Br J Anaesth 1992; 69: 433Ð438. inadvertently be introduced to a depth of 1 mm or more. It is then 12. Rice ASC, Andreev NY, McMahon SB. The consequences of quite probable that the needle would penetrate a fascicle causing microneurography electrode-induced injury of peripheral greater damage, especially if a short-bevel needle is used. nerves observed in the rat and man. Pain 1994; 59: 385Ð393. 5