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Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 80-82

Safety of intraneural injection of local anesthetic

1 Department of Anesthesia, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Histopathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 Department of Anesthesia, King Khaled University Hospital, King Saud University, Riyadh, Saudi Arabia

Correspondence Address:
Abdelazeem Eldawlatly
King Saud University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-354X.109821

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Date of Web Publication30-Mar-2013


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.

Keywords: Intraneural injection, local anesthetics, neurobehavior

How to cite this article:
Eldawlatly A, Rikabi AA, Elmasry S. Safety of intraneural injection of local anesthetic. Saudi J Anaesth 2013;7:80-2

How to cite this URL:
Eldawlatly A, Rikabi AA, Elmasry S. Safety of intraneural injection of local anesthetic. Saudi J Anaesth [serial online] 2013 [cited 2020 Aug 11];7:80-2. Available from:

  Introduction Top

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],[5],[6],[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 Top

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. [8],[9] Intraneural needle placement, without injection, was described to cause non-specific mechanical disruption and marked cellular infiltration. [10],[11] 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],[17],[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. [19],[20] 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)

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Figure 2: Nerve specimen showing perineural inflammation (arrow head) with fat necrosis. Note the presence of distorted fat cells

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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 Top

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.

  References Top

1.Fredrickson MJ, Kilfoyle DH. Neurological complication analysis of 1000 ultrasound guided peripheral nerve blocks for elective orthopaedic surgery: A prospective study. Anaesthesia 2009;64:836-44.  Back to cited text no. 1
2.Bigeleisen PE. Nerve puncture and apparent intraneural injection during ultrasound-guided axillary block does not invariably result in neurologic injury. Anesthesiology 2006;105:779-83.  Back to cited text no. 2
3.Jeng CL, Rosenblatt MA. Intraneural injections and regional anesthesia: The known and the unknown. Minerva Anestesiol 2011;77:54-8.  Back to cited text no. 3
4.Selander D. Neurotoxicity of local anesthetics: Animal data. Reg Anesth 1993;18:461-8.  Back to cited text no. 4
5.Myers RR, Kalichman MW, Reisner LS, Powell HC. Neurotoxicity of local anesthetics: Altered perineurial permeability, edema, and nerve fiber injury. Anesthesiology 1986;64:29-35.  Back to cited text no. 5
6.Kalichman MW, Powell HC, Myers RR. Quantitative histologic analysis of local anesthetic-induced injury to rat sciatic nerve. J Pharmacol Exp Ther 1989;250:406-13.  Back to cited text no. 6
7.Kalichman MW, Moorhouse DF, Powell HC, Myers RR. Relative neural toxicity of local anesthetics. J Neuropathol Exp Neurol 1993;52:234-40.  Back to cited text no. 7
8.Yang S, Abrahams MS, Hurn PD, Grafe MR, Kirsch JR. Local anesthetic Schwann cell toxicity is time and concentration dependent. Reg Anesth Pain Med 2011;36:444-51.  Back to cited text no. 8
9.Whitlock EL, Brenner MJ, Fox IK, Moradzadeh A, Hunter DA, Mackinnon SE. Ropivacaine-induced peripheral nerve injection injury in the rodent model. Anesth Analg 2010;111:214-20.  Back to cited text no. 9
10.Mackinson S, Dellon A. Classification of nerve injuries as the basis of treatment. In: Mackinson SE, editor. Surgery of the Peripheral Nerve. New York: Thieme Medical Publisher, Inc.; 1988. p. 35-63.  Back to cited text no. 10
11.Sakura S, Bollen AW, Ciriales R, Drasner K. Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels. Anesth Analg 1995;81:338-46.  Back to cited text no. 11
12.Hadzic A, Dilberovic F, Shah S, Kulenovic A, Kapur E, Zaciragic A, et al. Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs. Reg Anesth Pain Med 2004;29:417-23.  Back to cited text no. 12
13.Fredrickson MJ. Case report: Neurological deficit associated with intraneural needle placement without injection. Can J Anaesth 2009;56:935-8.  Back to cited text no. 13
14.El-Dawlatly A, Kathiry K, Al Rikabi A, Hajjar W, Al Obaid O, Alzahrani T. Ultrasound gel-nerve contact: An experimental animal histologic study. Anesth Analg 2011;113:657-9.  Back to cited text no. 14
15.Takenami T, Yagishita S, Nara Y, Tsai YH, Hiruma H, Kawakami T, et al. Spinal procaine is less neurotoxic than mepivacaine, prilocaine and bupivacaine in rats. Reg Anesth Pain Med 2009;34:189-95.  Back to cited text no. 15
16.Kanai Y, Katsuki H, Takasaki M. Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro. Anesth Analg 1998;86:569-73.  Back to cited text no. 16
17.Gentili F, Hudson AR, Hunter D, Kline DG. Nerve injection injury with local anesthetic agents: A light and electron microscopic, fluorescent microscopic, and horseradish peroxidase study. Neurosurgery 1980;6:263-72.  Back to cited text no. 17
18.Drasner K, Sakura S, Chan VW, Bollen AW, Ciriales R. Persistent sacral sensory deficit induced by intrathecal local anesthetic infusion in the rat. Anesthesiology 1994;80:847-52.  Back to cited text no. 18
19.Kasaba T, Onizuka S, Takasaki M. Procaine and mepivacaine have less toxicity in vitro than other clinically used local anesthetics. Anesth Analg 2003;97:85-90.  Back to cited text no. 19
20.Radwan IA, Saito S, Goto F. The neurotoxicity of local anesthetics on growing neurons: A comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg 2002;94:319-24.  Back to cited text no. 20
21.Gorsewski G, Dinse-Lambracht A, Tugtekin I, Gauss A. Ultrasound-guided peripheral regional anesthesia: Placement and dosage of local anesthetics. Anaesthesist 2012;61:711-21.  Back to cited text no. 21
22.Hara K, Sakura S, Yokokawa N, Tadenuma S. Incidence and effects of unintentional intraneural injection during ultrasound-guided subgluteal sciatic nerve block. Reg Anesth Pain Med 2012;37:289-93.  Back to cited text no. 22
23.Iohom G, Lan GB, Diarra DP, Grignon Y, Kinirons BP, Girard F, et al. Long-term evaluation of motor function following intraneural injection of ropivacaine using walking track analysis in rats. Br J Anaesth 2005;94:524-9  Back to cited text no. 23


  [Figure 1], [Figure 2]


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