Needle to Nerve Proximity What Do the Animal Studies Tell Us? Alan James Robert Macfarlane, MBChB, MRCP, FRCA,* Anuj Bhatia, MBBS, MD, FRCA,Þ and Richard Brull, MD, FRCPCÞ Abstract: Recent animal studies have provided insight and under- standing, as well as promising clinical tools, to help identify needle- to-nerve contact and potentially hazardous intraneural injection. This narrative review describes and summarizes the contemporary animal studies primarily relating to indicators of needle-to-nerve contact and in- traneural injection. Resultant nerve injury, whenever sought, is discussed. (Reg Anesth Pain Med 2011;36: 290Y302) I t has long been believed that intraneural, particularly intra- fascicular, injection is a significant cause of nerve injury. 1,2 Unfortunately, our ability in clinical practice to reliably detect needle-to-nerve contact and, importantly, unintentional intra- neural injection remains limited. Recently, a number of animal studies have provided insight and understanding, as well as promising clinical tools, to help identify needle-to-nerve contact and potentially hazardous intraneural injection. These studies have challenged many traditional tenets of needle-to-nerve proximity and may ultimately reshape the practice of regional anesthesia. This narrative review describes and summarizes the contemporary animal studies primarily relating to indicators of needle-to-nerve contact and intraneural injection. Resultant nerve injury, whenever reported, is discussed. METHODS We (A.B. and A.J.R.M.) searched the electronic databases MEDLINE and EMBASE (from January 1995 to December 2010) using the following search terms: ‘‘needle-nerve’’ OR ‘‘needle to nerve’’ OR ‘‘nerve AND contact’’ OR ‘‘nerve AND distance’’ OR ‘‘intraneural.’’ These search results then were combined with ‘‘anesthesia’’ OR ‘‘peripheral nerve block’’ using the Boolean search operator ‘‘AND.’’ All study formats or re- ports were included, and there were no language restrictions. After excluding nonregional anesthesia citations, the remaining abstracts were screened for studies that examined indicators of needle-to-nerve contact or intraneural injection. The search was subsequently limited to animal studies only. Finally, the refer- ences of the resulting studies were reviewed to capture any additional relevant publications. The definitions of ‘‘intraneural’’vary between studies. For the purposes of the present review, ‘‘intraneural’’ refers to a needle tip located within the epineurium, either extrafascicular or intrafascicular. ‘‘Extrafascicular’’ refers to outside the peri- neurium but inside the epineurium, whereas ‘‘intrafascicular’’ indicates an injection within the perineurium. Wherever possi- ble, the location of the needle tip for all studies included in this review has been described in this manner, even if alternative descriptions were used in the original work. RESULTS We identified 12 studies suitable for the present review (Fig. 1 and Table 1), which are broadly grouped below accord- ing to measurement toolVelectrical current (Table 2) 3Y9 and electrical impedance, 10 injection pressure (Table 3), 9,11Y14 and ultrasound (US) (Table 4). 4,9,13 Between and within each of these groups, there was considerable methodological hetero- geneity regarding the animals studied, experimental technique, and/or definition(s) of nerve injury (Table 1). Electrical Stimulation Background The motor response to nerve stimulation is governed by Coulomb’s law, which implies that the threshold current required to elicit a response (the minimum stimulating current [MSC]) exponentially decreases as the insulated needle tip advances closer to the nerve. The absolute MSC, however, is influenced by a variety of factors such as pulse width, bore size of the insulated needle tip, and the constitution of the needle-tissue interface (eg, dextrose vs saline). 15 Furthermore, the MSC may vary depending on the specific peripheral nerve being stimu- lated. 16 Nevertheless, it has been conventionally accepted that an MSC greater than 0.5 mA is more likely to be associated with block failure, whereas that less than 0.2 mA may increase the risk of intraneural injection. 15 However, the reliability of the re- lationship between needle tip location relative to the target nerve and MSC has been questioned, 17 and recent animal studies have addressed this issue (Table 2). Animal Literature The association between a very low MSC and subsequent nerve injury in animals was proposed in 2005 by Voelckel et al 3 who performed sciatic nerve blocks in pigs. Histological nerve injury was evident in 50% of the pigs when an MSC of less than 0.2 mA was used compared with no histological changes at an MSC between 0.3 and 0.5 mA. More recent animal studies, however, have suggested that an MSC less than 0.2 mA may be a specific but not a sensitive indicator of intraneural needle place- ment. With the tip of a stimulating needle intentionally placed within the nerves of the brachial plexus in pigs, Chan et al 4 demonstrated that the MSC required to achieve a distal motor REVIEW ARTICLE 290 Regional Anesthesia and Pain Medicine & Volume 36, Number 3, May-June 2011 From the *Departments of Anaesthesia, Glasgow Royal Infirmary, Scotland, United Kingdom; and †Anesthesia and Pain Management, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada. Accepted for publication January 19, 2011. Address correspondence to: Richard Brull, MD, FRCPC, Toronto Western Hospital, Department of Anesthesia, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8 (e-mail: richard.brull@uhn.on.ca). The authors did not receive funding for this study. The authors have no conflicts of interest to declare. This review was presented in part at the American Society of Regional Anesthesia and Pain Medicine Annual Spring Meeting and Workshops; April 22Y25, 2010; Toronto, Ontario. Copyright * 2011 by American Society of Regional Anesthesia and Pain Medicine ISSN: 1098-7339 DOI: 10.1097/AAP.0b013e318217a9ed Copyright © 2011 American Society of Regional Anesthesia and Pain Medicine. Unauthorized reproduction of this article is prohibited.