Safety of intraneural injection of local anesthetic.

There is conflicting information in the literature regarding nerve damage following regional anesthesia. Intraneural injection of local anesthetic was described as a safe practice in regional anesthesia. This review focuses on the histopathological and functional assessment of peripheral nerve function following intraneural injection of local anesthetics.

INTRODUCTION

There is conflicting information in the literature regarding nerve damage following regional anesthesia. Intraneural injection of local anesthetic was described as a safe practice in regional anesthesia. However, in one study it was concluded that a small volume of local anesthetic injected intraneurally may not invariably result in nerve injury.[1] In a prospective study on the neurological complications of 1000 ultrasound (US) guided peripheral nerve blocks (PNB), a low-rate of neurological complications was described.[2] Despite the fact that, in the field of PNB there was a transition from eliciting paresthesia to the use of electric nerve stimulation and most recently the use of US technology, the reported incidence of new neurological deficits after orthopedic surgery conducted under PNB may be as high as 15% at less than 2 weeks post-operatively, but it doesn't mean they were all due to PNB.[3] For ethical reasons studies, on histologic changes associated with nerve damage are limited to animal experimental studies. Correctly administered local anesthetics of clinical concentration are safe, but animal data indicate that all local anesthetics are potentially neurotoxic.[4-7] The limitation of the previous animal experiments using a rat model and removal of the sciatic nerve for histologic assessment was the inability to assess the neurobehavioral consequences of the neurotoxic effects of local anesthetics.

RESULTS

In an unpublished results on five male beagle dogs under general anesthesia, bilateral posterior tibial nerves (PTN) were dissected and exposed to bupivacaine local anesthetic for up to 48 h at different concentrations 0.25 and 0.5%. Longitudinal nerve specimens were taken from the PTN and sent for histologic analysis. Nerve inflammation was defined by the presence of perineural or intraneural macrophages, lymphocytes, neutrophils, granulation tissue, or reactive fibroblasts. The presence of each inflammatory marker was graded as “none” (if no inflammatory reaction was seen), “mild” (if the inflammatory infiltrate was seen in one high-power microscopic field), or “moderate” (if the inflammatory infiltrate was seen in two high-power microscopic fields). Mild to moderate perineural inflammation at 48 h of 0.25% bupivacaine exposure was noticed [Figure 1]. Also the same reaction with fat necrosis was seen 48 h of 0.5% bupivacaine exposure [Figure 2]. These unpublished data demonstrated varying degrees of mild to moderate inflammatory changes in the dog nerve specimens exposed to bupivacaine at 24 h, which became more evident at 48 h. These findings are in keeping with other studies where prolonged exposure of rat sciatic nerve with either bupivacaine or ropivacaine induced significant nerve demyelination and infiltration with inflammatory cells.[89] Intraneural needle placement, without injection, was described to cause non-specific mechanical disruption and marked cellular infiltration.[1011] In another study, intraneural needle placement without local anesthetic injection was described to cause pathophysiologic changes in the form of inflammatory cells infiltration and axonal degeneration.[12] A functional consequence of intraneural injection of local anesthetic was described in one.[13] In a previous study on gel-nerve contact, we have reported limping as well as a consequence of nerve trauma.[14] Histologic changes of the spinal cord following intrathecal injection in the form of axonal degeneration was observed in an experiment on rats treated with greater than 16% prilocaine or mepivacaine or with greater than 4% bupivacaine.[15] In another similar animal study on electrophysiologic histopathologic and behavioral changes; bupivacaine was described as safer local anesthetic compared to lidocaine.[16-18] The neurotoxicity of local anesthetics can be demonstrated in vitro by the collapse of growth cones isolated from chick embryo and neurites in cultured neurons. In that regard, it was found that lidocaine was more toxic than bupivacaine and ropivacaine. Furthermore, it was found that mepivacaine, which is pharmacologically similar to lidocaine, has the least-adverse effects on cone growth among the clinically used local anesthetics.[1920] Since the use of US guidance in regional anesthesia became more popular it seemed that intraneural puncture and injection of local anesthetics was much more common than previously thought. Various studies demonstrated that if intraneural puncture occurred the needle usually took a path away from the fascicles, while intraneural trans-fascicular puncture seemed relatively rare and intraneural intra-fascicular placement of the needle even more uncommon. As long as the needle is placed intraneurally but in an extra-fascicular fashion a safe injection and the absence of neurologic damage can be assumed. However, if nerve fascicles are affected neurologic dysfunction can occur.[21] In a recent study conducted to determine the incidence of US-guided intraneural injection of local anesthetics, it was found to be as high of 16.3% for the US-guided subgluteal approach to the sciatic nerve.[22]

Figure 1

Nerve specimen showing mild to moderate perineural inflammatory reaction. Note the presence of chronic inflammatory cells (arrow head)

Figure 2

Nerve specimen showing perineural inflammation (arrow head) with fat necrosis. Note the presence of distorted fat cells

Sciatic nerve function as a method of functional evaluation was used in some animal studies. Sciatic function index (SFI) was used for such purpose and found that in a rat model following ropivacaine toxicity, 0.2 and 0.75% ropivacaine had no deleterious effect.[23] There are significant concerns with overreliance on the SFI as an outcome measure. Traditional SFI data lack resolving power and are prone to fail to detect a difference, even when significant differences are demonstrated by other methods of evaluation. Although, the SFI is useful for detecting severe injuries, such as a complete nerve transaction, it has low-sensitivity for partial loss of nerve function.

CONCLUSION

Histologic changes following needle-nerve trauma either with or without local anesthetic are non-specific. However, intraneural injection of local anesthetics should be discouraged because the functional neurobehavioral consequences are not fully understood. Furthermore, the histopathological perineural changes following bupivacaine injection are not certain and further studies are needed in that field.