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Minimal Current Intensity to Elicit an Evoked Motor Response Cannot Discern Between Needle-Nerve Contact and Intraneural Needle Insertion

Wiesmann, Thomas MD*; Bornträger, Andreas MD*; Vassiliou, Timon MD*; Hadzic, Admir MD, PhD; Wulf, Hinnerk MD*; Müller, Hans-Helge MD; Steinfeldt, Thorsten MD*

doi: 10.1213/ANE.0b013e3182a94454
Regional Anesthesia: Research Report
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BACKGROUND: The ability of an evoked motor response (EMR) with nerve stimulation to detect intraneural needle placement reliably at low current intensity has recently been challenged. In this study, we hypothesized that current intensity is higher in needle-nerve contact than in intraneural needle placement.

METHODS: Brachial plexus nerves were exposed surgically in 6 anesthetized pigs. An insulated needle connected to a nerve stimulator was placed either with 1 mm distance to the nerve (control position), adjacent to nerve epineurium (needle-nerve contact position), or inside the nerve (intraneural position). Three pulse duration settings were applied in random fashion (0.1, 0.3, or 1.0 milliseconds) at each needle position. Starting at 0.0 mA, electrical current was increased until a minimal threshold current resulting in a specific EMR was observed. Fifty threshold current measurements were scheduled for each needle position-pulse duration setting.

RESULTS: Four hundred-fifty threshold currents in 50 peripheral nerves were measured. Threshold current intensities (mA) to elicit EMR showed small differences between the needle-nerve contact position [median (25th–75th percentiles); 0.1 milliseconds: 0.12 (0.08–0.18) mA; 0.3 milliseconds: 0.10 (0.06–0.12) mA; 1.0 milliseconds: 0.06 (0.04–0.10) mA] and the intraneural position (0.1 milliseconds: 0.12 [0.10–0.16] mA; 0.3 milliseconds: 0.08 [0.06–0.10] mA; 1.0 milliseconds: 0.06 [0.06–0.08] mA) that are neither statistically significant nor clinically relevant. Regardless of the pulse duration that was applied, the 98.33% confidence interval revealed a difference of at most 0.02 mA. However, threshold current intensities to elicit EMR were lower for the needle-nerve contact position than for the control position (0.1 milliseconds: 0.28 [0.26–0.32] mA; 0.3 milliseconds: 0.20 [0.16–0.22] mA; 1.0 milliseconds: 0.12 [0.10–0.14] mA).

CONCLUSIONS: The confidence interval for differences suggests minimal current intensity to elicit a motor response that cannot reliably discern between a needle-nerve contact from intraneural needle placement. In addition, an EMR at threshold currents <0.2 mA (irrespective of the applied pulse duration) indicates intraneural needle placement or needle-nerve contact.

Published ahead of print November 27, 2013

From the *Faculty of Medicine, Department of Anesthesiology and Critical Care Therapy, Philipps University Marburg, Marburg, Germany; St. Luke’s and Roosevelt Hospital Center, University Hospital of Columbia University, College of Physicians and Surgeons, New York City, New York; and Institute of Medical Informatics, Biostatistics and Epidemiology (IBE), Ludwig-Maximilians-University (LMU), Munich, Germany.

Accepted for publication August 7, 2013.

Published ahead of print November 27, 2013

Funding: Institutional grants.

Conflict of Interest: See Disclosures at the end of the article.

This report was previously presented, in part, at the ESRA 2011, Dresden, Germany.

Reprints will not be available from the authors.

Address correspondence to Thomas Wiesmann, MD, Department of Anesthesiology and Intensive Care Therapy, Philipps University Marburg, University Hospital Giessen-Marburg, Campus Marburg, Baldingerstrasse, 35032 Marburg, Germany. Address e-mail to t.wiesmann@web.de.

Electrical nerve stimulation is commonly used during nerve localization for peripheral nerve blocks.1 An evoked motor response (EMR) that occurs at a low current intensity is thought to indicate close proximity of the needle to a target nerve. Therefore, it is commonly held that an EMR elicited at a minimal stimulation current (MSC) <0.3 mA (0.1 milliseconds) likely indicates intraneural needletip localization and should be avoided.2–5 However, few studies have examined the role of an EMR at a low current intensity as an indicator of intraneural needle position. Moreover, there are little data on the ability of different pulse durations to detect intraneural needle placement.6 The aims of this study were to determine the MSC indicative of intraneural needletip position or direct needle-nerve contact and to test the effects of different pulse durations on current intensities required for EMR in different needle positions. We hypothesized that MSCs between the needle-nerve contact position as well as the intraneural needle tip position are lower compared with needle placement 1 mm distant from the nerve (control position).

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METHODS

Experimental Set-Up

Experiments were approved by local authorities (Study No 5. 06/2010 MR 20/13; Regional Board of Animal Welfare, Giessen, Germany), and the study was performed in compliance with the Helsinki convention for the use and care of animals. General anesthesia and euthanasia after the experiments were conducted as described previously.7 Animals with neurological deficits (i.e., paresis) were excluded due to observation of animal behavior on the day before the experiment. Six female pigs (Deutsche Landrasse) weighing 28 to 37 kg were placed in supine position, and both brachial regions were exposed surgically (TS, TW). Porcine nerves in the brachial region (median, ulnar, musculocutaneous, radial, and caudal pectoral nerves; Fig. 1) were kept moist during the study period. The neutral electrode and the stimulation needle (Stimuplex A 22G, 50 mm; B. Braun, Melsungen, Germany) were connected to a nerve stimulator (Stimuplex HNS 11; B. Braun, Melsungen, Germany, margin of error ± 0.02 mA).

Figure 1

Figure 1

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Experimental Protocol

The needletip was placed under direct vision at 1 site per nerve (Figs. 1–3) in 3 different positions by Investigator A (TW) in a predefined order: First, 1 mm distant to the target nerve (control position, Fig. 1) mimicking a close needle-nerve placement without needle-nerve contact. The needletip was positioned on nerve surrounding tissue, thereby maintaining a closed electrical circuit. Second, the needle was placed in needle-nerve contact (contact position, Fig. 2). Third, the needle was advanced intraneurally (intraneural position, Fig. 3).

Figure 2

Figure 2

Figure 3

Figure 3

For each nerve, measurements were performed for each pulse duration (0.1, 0.3, 1.0 milliseconds) and for each needletip position (control, needle-nerve contact, intraneural) (Table 1), resulting in 450 measurements (50 exposed nerves × 3-pulse durations × 3 needletip positions).

Table 1

Table 1

Investigator A was blinded to the pulse duration that the nerve stimulator applied. The sequence of pulse durations was predefined in a random order using an Internet–based randomization tool (www.randomizer.org). The display of the nerve stimulator was only visible to a second investigator who investigated who generated the pulse duration sequence for each position of needle placement. Investigator B increased the stimulating current intensity from 0.0 mA in increments of 0.02 mA until Investigator C (TS), blinded to needle position, pulse duration, and current intensity, was able to detect the specific neuromuscular response of the stimulated nerve. Differentiation of the nerves corresponded to anatomy and specific motor responses triggered by electrical nerve stimulation.

In brief:

  • radial nerve stimulation → extension of the cloven hoof
  • median nerve stimulation → flexion of the cloven hoof
  • ulnar nerve stimulation → twitch of the lateral cloven hoof/dew claw, corresponding to a human ulnar deviation response
  • musculocutaneous nerve stimulation → flexion of the limb due to porcine biceps muscle activation
  • caudal pectoral nerve stimulation → stimulation of the lateral aspect of upper thorax

After each MSC measurement, nerve stimulation was stopped for 60 seconds to avoid possible confounding by hyperpolarization.8

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Criteria for Study Termination

In the event of accidental vascular and/or nerve tissue dissection by surgical exposure of the brachial plexus, further needle placements in the corresponding region were not performed due to the potential interference of nerve trauma or bleeding with MSC measurements.

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Statistical Analysis

The primary end point was the MSC with the 3 differences among the control, needle-nerve contact, and intraneural needletip positions as primary outcome measures.

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Sample Size Calculation

A difference of MSC intensities of at least 0.1 mA between 2 needle locations was considered relevant for clinical practice. A difference of MSC intensities of 0.05 mA between 2 needle locations may have clinical relevance in a diagnostic setting, if stimulating current can be certainly set up in steps of 0.02 mA and the standard deviation (SD) of MSC intensities are about 0.05 mA. Assuming a SD of 0.05 mA in each group (based on a pilot study data set) and accounting for multiplicity with 6 tests in the first step, a sample size of 32 needle placements for each condition (i.e., needle location by pulse duration) was estimated to have a power of 80% to detect a difference of 0.05 mA among the 3 needle location groups. Considering a dropout rate of 20% (criteria for study termination) for single stimulations, a loss rate of 20% of nerves and perhaps loss of 1 pig, a maximum of 10 nerves per pig for needle placement was calculated per pig. Thus, 6 pigs were required for the total experiment.

Data are presented as median (interquartile range [IQR]). Due to nonnormality of the MSC distributions within the needle location by pulse duration conditions, pairwise comparisons of MSCs in groups were performed with the Wilcoxon-Mann-Whitney test, and differences were estimated (point estimates and confidence intervals [CIs]) using the method of Hodges and Lehmann. Jonckheere-Terpstra analysis was used to confirm the influence of pulse duration (P < 0.0001 overall and in each needle position group).

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Kruskal-Wallis Analysis was Performed to Identify Potential Individual Interferences by the Animals

Closed testing accounts for multiplicity with strong control of the multiple significance level of 0.05 when testing the primary end point applying 2-sided tests. Bonferroni adjustment was applied for 3-pulse durations. Within each pulse duration, 3 pairwise comparisons of the needle position groups were performed. These 3 comparisons were structured as Dunnett-type tests versus the control group first (2 tests), enhanced by the main test between the experimental needle positions of interest with no further adjustment despite closed testing. Raw P-values and P-values adjusted for closed testing are presented. To simplify in sample size calculation, the Dunnett-type tests were slightly conservative replaced by Bonferroni adjustment. Thus, sample size calculation considers Bonferroni adjustment of 6 (3 times 2) tests. Since this closed testing procedure is not a single step procedure, we accounted only for simultaneously testing the 3-pulse durations and present 98.33% CIs.

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RESULTS

Number of Animals and Needle Placements

Fifty peripheral nerves (median, musculocutaneous, radial, ulnar, and caudal pectoral nerves at the axillary plexus level, each n = 10) were exposed in 6 pigs. For each nerve, measurements were performed for each pulse duration group (0.1, 0.3, 1.0 milliseconds) and for each needletip position (control, needle-nerve contact, intraneural) (Table 1), resulting in 450 measurements (50 exposed nerves × 3-pulse durations × 3 needletip positions). Ten peripheral nerves were excluded from needle placement due to the occurrence of bleeding and hematoma during surgical exposure of the axillary region in 2 pigs.

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Minimal Stimulation Currents in the Needle-Nerve Contact and the Intraneural Needletip Positions

After nerve contact and intraneural needle placement, MSC intensities ≤0.2 mA were observed (Table 1) irrespective of the pulse duration applied. There was no significant difference in MSC between needle-nerve contact and intraneural needletip positions (Table 1). Regardless of the applied pulse duration, the 98.33% CI revealed a difference of at most 0.02 mA, suggesting no clinically relevant potential of nerve stimulation for discrimination of intraneural and direct epineural needletip position (Table 2). However, control nerve stimulation (in 1 mm distance) required significantly higher MSC intensities than the needle-nerve contact position irrespective of the applied pulse duration. The estimated increase with 98.33% CI was for 0.1 milliseconds: 0.16 (0.14–0.18) mA; for 0.3 milliseconds: 0.10 (0.08–0.14) mA; and for 1.0 milliseconds: 0.06 (0.04–0.06) mA, suggesting a discriminatory utility of nerve stimulation when a short pulse duration is applied (Table 2).

Table 2

Table 2

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Threshold Currents with Different Pulse Durations

In each needle location, MSC was higher for the 0.1-milliseconds pulse duration compared with 0.3- or 1.0-milliseconds pulse durations (Table 1). Jonckheere-Terpstra analysis showed a significant influence of pulse duration (P < 0.0001 overall and in each needle position group).

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Statistical Independency Between Animals

Data sets of each animal with pairwise differences of MSCs between intraneural and epineural contact needletip position were compared using Kruskal-Wallis testing. Comparing these differences for each respective pulse duration group, no significant effects could be obtained among the animals (0.1 milliseconds, P = 0.818; 0.3 milliseconds, P = 0.865; 1.0 milliseconds, P = 0.972). No interindividual influences were found.

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DISCUSSION

Our study found no significant difference between the current intensity required to elicit a motor response between a needle placed intraneurally versus the needle-nerve contact position. However, current thresholds were significantly lower during needle-nerve contact compared with control needle placement at 1 mm distance without nerve contact. These effects were reproducible for the range of pulse durations studied. Longer pulse durations resulted in significantly lower threshold currents at each needletip position.

Tsai et al8 applied threshold current measurements in the sciatic nerves in pigs. In contrast to our observations, higher intraneural, epineural, and extraneural output currents were observed. This can be explained by differences in experimental protocols. Tsai et al.8 started electrical stimulation with 2.0 mA close to the target nerve and then decreased current intensity, whereas an increasing approach was followed in our protocol. Johnson et al.9 and Bhadra and Kilgore10 have shown that high energy amounts during needle-nerve contact or close needle-nerve proximity may induce a hyperpolarization within the nerve, resulting in a “stimulation block.” The findings of Tsai et al.8 support this idea because stimulation blocks occur in approximately 30% of extraneural and 5% of intraneural needle positioning. We did not find any stimulation block during needle placement despite repetitive stimulation attempts for our study purposes (3-pulse durations × 3 needletip positions for each nerve).

However, our data show that a motor response at <0.2 mA might be a predictor for intraneural needle placement. Li et al.11 observed similar threshold currents during intraneural stimulation (0.12 mA) of the sciatic nerve in rats; however, they measured electrical action potentials distal to the insertion site of the electrode delivering current, not evoked motor responses.

Regarding clinical correlates, Bigeleisen et al.2 found higher threshold currents than in our study. However, their observations were based on a percutaneous approach, and needle positioning was provided by ultrasound guidance.2 A precise evaluation of needletip localization and different layers of the nerve12 with sonography might be overly ambitious.2,13 Particularly regarding the intraneural position, a needletip location between the epineurium and paraneural tissue should be excluded for intraneural threshold current measurement. Thus, residual connective or paraneural tissue2,14 between the needletip and the epineurium, which was unlikely visualized by ultrasound, could have conferred resistance that resulted in higher stimulating currents. Nevertheless, our results are consistent with that of Bigeleisen et al.2 In that study, they did not observe output currents <0.2 mA in the extraneural needletip position, whereas intraneural currents <0.2 mA were noted in 44% of patients. Our results are also in agreement with previous studies15–18 showing decreasing current threshold for triggering motor response when longer pulse durations are applied.

Our study has several limitations. First, an “open approach” might interfere with tissue impedance or conductive properties around the needletip. However, the selected experimental setting was necessary for precise and reproducible needle placement on the nerve epineurium or within the intraneural space.11,13,15 For intraneural needle stimulation, we do not assume interference to threshold current intensities; however, resulting threshold currents for needle-nerve contact or distant control measurements might be affected by the experimental setting. We showed in a previous study7 with a “closed animal model” that low stimulation currents <0.3 mA (and 0.1-milliseconds pulse duration) result in a needletip position close to the target nerve. Second, variations between human and pig anatomy of nerve and surrounding connective tissue may result in divergent stimulation threshold currents.19 Third, we did not focus on potential differences between nerves (e.g., median versus radial nerve) and resulting differences in muscular response (measured with electromyography). Limited data are available for variable electrophysiological characteristics in different nerves. However, SDs were small in our experiments, suggesting limited interference between different peripheral nerves and corresponding threshold currents in the present study. Nerves were kept moist with saline-soaked swabs to avoid local dehydration. However, the effects of this topical application of saline solution on electrophysiology of peripheral nerves are unknown and therefore another potential bias.

Future clinical trials in patients should clarify whether an evoked motor response elicited by a “preadjusted current” (i.e., 0.2 mA) during needle guidance with ultrasound could prevent intraneural needle placement, intraneural injection of local anesthetics, or triggering of paresthesia compared with ultrasound-guided needle placement without a preadjusted current threshold.

In conclusion, under the conditions of our study, minimal current intensity at which a motor response occurs cannot reliably discern between needle-nerve contact from intraneural needle placement with any of the 3 tested electrical pulse durations. However, an evoked motor response at threshold currents <0.2 mA (at 0.1-milliseconds pulse duration) occurred only with intraneural needle placement or needle-nerve contact.

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DISCLOSURES

Name: Thomas Wiesmann, MD.

Contribution: This author helped design and conduct the study, analyze the data, and write the manuscript.

Attestation: Thomas Wiesmann has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Andreas Bornträger, MD.

Contribution: This author helped analyze the data and write the manuscript.

Attestation: Andreas Bornträger has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Timon Vassiliou, MD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Timon Vassiliou has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Admir Hadzic, MD, PhD.

Contribution: This author helped analyze the data and write the manuscript.

Attestation: Admir Hadzic reviewed the analysis of the data and approved the final manuscript.

Conflicts of Interest: Admir Hadzic is a major equity holder of Macosta Medical USA. Macosta Medical USA is a patent assignee for BSmart, injection pressure monitor. Royalties; LifeTech, Inc.

Name: Hinnerk Wulf, MD, PhD.

Contribution: This author helped design the study and write the manuscript.

Attestation: Hinnerk Wulf has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: Hinnerk Wulf reported a conflict of interest with Sonosite, received research funding from B.Braun, reported a conflict of interest with B.Braun, received research funding from Teleflex medical, and reported a conflict of interest with Teleflex medical. Hinnerk Wulf has received speaker fees and/or research funding by Sonosite, B. Braun, and Teleflex medical (Arrow).

Name: Hans-Helge Müller, MD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Hans-Helge Müller has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Thorsten Steinfeldt, MD.

Contribution: This author helped design and conduct the study, analyze the data, and write the manuscript.

Attestation: Thorsten Steinfeldt has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: Thorsten Steinfeldt reported a conflict of interest with B.Braun and reported a conflict of interest with Teleflex medical Speaker Fees.

This manuscript was handled by: Terese T. Horlocker, MD.

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ACKNOWLEDGMENTS

We gratefully thank Andreas Gockel, Laura Ehrhardt, and Carina Korte for their support during the performance of the experiments.

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