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Risks and Benefits of Ultrasound, Nerve Stimulation, and Their Combination for Guiding Peripheral Nerve Blocks: A Retrospective Registry Analysis

Bomberg, Hagen MD*; Wetjen, Laura MS*; Wagenpfeil, Stefan PhD; Schöpe, Jakob MS; Kessler, Paul MD; Wulf, Hinnerk MD§; Wiesmann, Thomas MD§; Standl, Thomas MD; Gottschalk, André MD; Döffert, Jens MD#; Hering, Werner MD**; Birnbaum, Jürgen MD††; Kutter, Bernd MD‡‡; Winckelmann, Jörg MD‡‡; Liebl-Biereige, Simone MD§§; Meissner, Winfried MD‖‖; Vicent, Oliver MD¶¶; Koch, Thea MD¶¶; Bürkle, Hartmut MD, PhD##; Sessler, Daniel I. MD***; Volk, Thomas MD*

doi: 10.1213/ANE.0000000000003480
Regional Anesthesia and Acute Pain Medicine: Original Clinical Research Report
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BACKGROUND: Ultrasound, nerve stimulation, and their combination are all considered acceptable ways to guide peripheral nerve blocks. Which approach is most effective and associated with the fewest complications is unknown. We therefore used a large registry to analyze whether there are differences in vascular punctures, multiple skin punctures, and unintended paresthesia.

METHODS: Twenty-six thousand seven hundred and thirty-three cases were extracted from the 25-center German Network for Regional Anesthesia registry between 2007 and 2016 and grouped into ultrasound-guided puncture (n = 10,380), ultrasound combined with nerve stimulation (n=8173), and nerve stimulation alone (n = 8180). The primary outcomes of vascular puncture, multiple skin punctures, and unintended paresthesia during insertion were compared with conditional logistic regression after 1:1:1 propensity score matching. Results are presented as odds ratios and 95% CIs.

RESULTS: Propensity matching successfully paired 2508 patients with ultrasound alone (24% of 10,380 patients), 2508 patients with a combination of ultrasound/nerve stimulation (31% of 8173 patients), and 2508 patients with nerve stimulation alone (31% of 8180 patients). After matching, no variable was imbalanced (standardized differences <0.1). Compared with ultrasound guidance alone, the odds of multiple skin punctures (2.2 [1.7–2.8]; P < .001) and vascular puncture (2.7 [1.6–4.5]; P < .001) were higher with nerve stimulation alone, and the odds for unintended paresthesia were lower with nerve stimulation alone (0.3 [0.1–0.7]; P = .03). The combined use of ultrasound/nerve stimulation showed higher odds of multiple skin punctures (1.5 [1.2–1.9]; P = .001) and lower odds of unintended paresthesia (0.4 [0.2–0.8]; P = .007) compared with ultrasound alone. Comparing the combined use of ultrasound/nerve stimulation with ultrasound alone, the odds for vascular puncture (1.3 [0.7–2.2]; P = .4) did not differ significantly. Systemic toxicity of local anesthetics was not observed in any patient with ultrasound guidance alone, in 1 patient with the combined use of ultrasound and nerve stimulation, and in 1 patient with nerve stimulation alone.

CONCLUSIONS: Use of ultrasound alone reduced the odds of vascular and multiple skin punctures. However, the sole use of ultrasound increases the odds of paresthesia.

From the *Department of Anesthesiology, Intensive Care Medicine and Pain Medicine

Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, University Medical Center, Homburg/Saar, Germany

Department of Anesthesiology, Intensive Care and Pain Medicine, Orthopedic University Hospital, Frankfurt, Germany

§Department of Anesthesiology and Intensive Care Therapy, Philipps University Marburg, Marburg, Germany

Department of Anesthesia, Intensive and Palliative Care Medicine, Academic Hospital Solingen, Solingen, Germany

Department of Anesthesiology, Intensive Care and Pain Medicine, Friederikenstift Hannover, Hannover, Germany

#Department of Anesthesiology and Intensive Care Medicine, Hospital Calw-Nagold, Nagold, Germany

**Department of Anesthesiology, St Marien-Hospital, Siegen, Germany

††Department of Anesthesiology and Operative Intensive Care Medicine, Charité Campus Virchow Klinikum and Campus Mitte, Charité University Medicine Berlin, Berlin, Germany

‡‡Department of Anesthesiology, Intensive Care and Pain Therapy, University and Rehabilitation Clinics, Ulm, Germany

§§Department of Anesthesiology, Intensive Care and Pain Therapy, HELIOS Hospital Erfurt, Erfurt, Germany

‖‖Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

¶¶Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

##Department of Anesthesiology and Critical Care, Medical Center, University of Freiburg, Medical Faculty University Freiburg, Freiburg, Germany

***Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio.

Published ahead of print May 31, 2018.

Accepted for publication April 3, 2018.

Funding: This analysis was supported by institutional funds from the German Network for Regional Anesthesia which was supported by the German Society of Anesthesiology and Intensive Care Medicine (DGAI), the Association of German Anesthesiologists (BDA), and the German Research Foundation (DFG).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Hagen Bomberg, MD, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, Saarland University Medical Center, Kirrbergerstrasse 1, 66421 Homburg/Saar, Germany. Address e-mail to Hagen.Bomberg@uniklinikum-saarland.de.

Various techniques are used to identify suitable approximation of needles to nerves. Peripheral nerve stimulation, for example, has been used to indicate needle and nerve proximity for more than half a century.1 But with the introduction of ultrasound, it became possible to visualize the desired target. There is already evidence that blocks performed with ultrasound guidance are more likely to be successful than with nerve stimulation, and that inadvertent puncture of vessels is less likely to occur.2,3

The combination of ultrasound and nerve stimulation has been advocated, particularly in areas where ultrasound image tends to be poor.4 However, the combination may lead to contradictory information such as good needle visualization with poor stimulation or that image quality may decline by stimulation-induced muscular activity. In particular, there is no general recommendation for the combination of nerve stimulation with ultrasound.

Which approach is superior and whether combining both methods provides additional benefit remains unknown.5,6 We hypothesized that the use of ultrasound decreases the odds of complications. We therefore compared the effects of ultrasound guidance, the combination of ultrasound guidance and nerve stimulation, and nerve stimulation alone on our primary outcomes which were vascular puncture, multiple skin punctures, and unintended paresthesia. The secondary outcomes were local anesthetic systemic toxicity (LAST).

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METHODS

Ethical approval for this study (Saarland Medical Chamber number Ha50/11) was provided by the Ethical Committee of the Saarland Medical Chamber, 66111 Saarbrücken, Germany (Chairperson San.-Rat Professor Dr Hermann Schieffer) on March 22, 2011. Written consent was waived as the data were anonymous (regulatory proof of protection of data privacy, Saarland commissioner, 12-MAR-2014).

In 2007, the German Society for Anesthesiology and Intensive Care Medicine established a network for safety in regional anesthesia. The German Network for Regional Anesthesia database collects preoperative, intraoperative, and postoperative data from practicing physicians at 25 German centers who were requested to complete a standard form (Supplemental Digital Content 1, Appendix 1, http://links.lww.com/AA/C415).7 Data which are collected during patient care include detailed information about the medical conditions of patients undergoing regional anesthesia and details regarding the procedure and postoperative course.

Data collection has 2 phases: placement and maintenance. Both have the equivalent of a typical case report form. The case report form can either be used as a commercially available machine-readable paper document, an online version of the web application, or within an adapted patient data management system. Every 3 months, locally stored data are transferred in an anonymous SSL encrypted standard. This process has been approved by data safety protection officials. The current XML-scheme can be seen at http://www.nra-dgai.de/schema/nra-2.0.xsd.

The registry included 136,699 cases in the period extending from September 2007 to April 2016. The study protocol is reported in Supplemental Digital Content 2, Appendix 2, http://links.lww.com/AA/C416. Data integrity was evaluated according to specific rules to delete erroneously entered data and cases with missing information (proof of plausibility, Supplemental Digital Content 6, Appendix 2, http://links.lww.com/AA/C416). The relation between height and weight were verified. The body mass index (BMI) was calculated and defined from 16 to 70 kg/m2.

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Case Selection

Inclusion criteria for the analysis before data validation include all cases with peripheral block (catheter or single injection) and information about the use of ultrasound or nerve stimulation during block insertion. Exclusion criteria for the study population were implausible data, and missing information about: sex, BMI, American Society of Anesthesiologists physical status, block site, surgical specialty, year of surgery, hospital center, vascular puncture, multiple skin punctures, unintended paresthesia, and LAST.

Prospectively defined block-related complications included:

The primary outcomes were:

  1. Vascular puncture: aspiration of blood through the puncture needle or catheter
  2. Multiple skin puncture: more than 1 skin puncture for 1 particular block procedure
  3. Unintended paresthesia during insertion: an unintended and unexpected painful, unpleasant, or electrifying sensation within the area supplied by the nerve(s) affected by the regional anesthesia.

The secondary outcome was systemic local anesthetic toxicity: symptoms of intoxication (neurologic and/or cardiovascular) after the injection of the local anesthetic.

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Data Analysis

Our main analysis was based on propensity score-matched groups, adjusted for variables that remained unbalanced. Furthermore, multivariable regression as sensitivity analysis was used. Population characteristics are reported as standardized differences (STDs; value of means or proportions [ultrasound alone minus combination of ultrasound/nerve stimulation; ultrasound alone minus nerve stimulation alone] divided by the pooled standard deviation).

We developed a propensity score for each patient using 2 logistic regressions based on potential confounding factors. Potential confounders included sex, age, BMI, American Society of Anesthesiologists physical status, surgical specialty, block site, type of block, year of surgery, and hospital. Age and BMI were included as continuous variables; all other covariates were included as categorical variables. Patients with ultrasound alone were matched to patients with a combination of ultrasound/nerve stimulation and patients with nerve stimulation alone in a 1:1:1 ratio with the closest propensity score. Triplets of propensity-matched patients were obtained by a 3-step procedure. First, each patient who had ultrasound alone was matched to a patient with a combination of ultrasound/nerve stimulation. Then, each patient who had ultrasound alone was again matched, this time to a patient with nerve stimulation alone. Finally, a filter was applied to include only patients with ultrasound who were successfully matched with both combination of ultrasound/nerve stimulation and nerve stimulation alone, thus resulting in the matched triplets. The maximum difference in propensity score was <0.02. The matching algorithm used was nearest neighbor matching without replacement. After matching, the 3 groups were compared with conditional logistic regression analysis reported as odds ratios (ORs) and 95% CI.

As a sensitivity analysis, unconditional multivariable logistic regression was used to calculate ORs with 95% CIs. The analysis was adjusted for the same confounders that were used for the propensity score approach. Vascular puncture was additionally adjusted for multiple skin puncture and paresthesia was additionally adjusted for multiple skin puncture and vascular puncture. We calculated pairwise correlation coefficients for the set of confounder variables before inclusion in multiple regression analysis to determine whether there was much multicollinearity. We prospectively considered correlation coefficients exceeding +0.5 or less than −0.5 to be problematic. The following correlation coefficients were calculated: Pearson or Spearman (quantitative versus quantitative variables), Eta (quantitative versus binary variables), or Cramer-V (binary versus binary variables). Goodness of fit for logistic regression analysis was assessed by Hosmer-Lemeshow tests.

Data analysis was performed using IBM SPSS Statistics 19 (IBM Corp, Armonk, NY) and R 2.10.1 for Windows. Continuous variables are expressed as means and standard deviations. Categorical variables are presented as absolute and relative frequencies, respectively. Statistical significance was accepted at 2-sided P ≤ .05. To avoid overestimating α by multiple testing, we adjusted 2-sided significance levels according to Holm-Bonferroni correction for our 6 primary hypotheses. Among the 6 P values, the lowest was compared with the global significance level divided by 6. If significant (that is the lowest P value was lower than the global significance level divided by 6), we continued and compared the second highest P value with the global significance level divided by 5, and so on, until the highest P value of the 6 was compared with the original prespecified global significance level (.05). The 6 primary hypotheses were based on the primary outcomes: multiple skin punctures, vascular puncture, and unintended paresthesia during insertion. Each was compared twice: ultrasound guidance versus the combination of ultrasound guidance, and nerve stimulation and ultrasound guidance versus nerve stimulation alone.

The global 2-sided significance level was set to .05.

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RESULTS

The initial study population consisted of 26,733 cases, all with continuous catheters or single-shot blocks, and information about ultrasound use (Figure 1). This cohort was subdivided into the following groups: ultrasound guidance alone (n = 10,380), the combination of ultrasound guidance/nerve stimulation (n = 8173), and nerve stimulation alone (n = 8180).

Figure 1.

Figure 1.

Characteristics of the patients, who were mainly treated for orthopedics and trauma, are presented in Table 1 (left columns). Patients with ultrasound guidance alone compared with nerve stimulation alone were typically male, older, had other types of surgery, upper limb blocks, and had fewer single-shot blocks. The same was found in patients with ultrasound guidance alone compared with the combination of ultrasound guidance/nerve stimulation.

Table 1.

Table 1.

Propensity matching successfully paired 2508 patients with ultrasound alone (24% of 10,380 patients), 2508 patients with a combination of ultrasound/nerve stimulation (31% of 8173 patients), and 2508 patients with nerve stimulation alone (31% of 8180 patients). As seen in Table 1 (right columns), patients were much better balanced on covariables as a result of propensity matching, and all variables were balanced (STDs <0.1).

Block-related complications are shown in Figure 2 and Table 2. We used the Holm-Bonferroni correction for multiple comparisons because we had 6 primary hypotheses. The outcomes were multiple skin punctures, vascular puncture, and unintended paresthesia during insertion; each compared across 2 different comparisons: ultrasound guidance versus the combination of ultrasound guidance, and nerve stimulation and ultrasound guidance versus nerve stimulation alone. Matched patients with nerve stimulation alone compared with ultrasound guidance alone had higher odds for multiple skin punctures (OR [95% CI] of 2.2 [1.7–2.8]; P < .001) and vascular puncture (2.7 [1.6–4.5]; P < .001). In contrast, the odds were lower for unintended paresthesia (0.3 [0.1–0.7]; P = .03). Compared with ultrasound guidance alone, the odds were higher with ultrasound/nerve stimulation for multiple skin punctures (1.5 [1.2–1.9]; P = .001) and lower for unintended paresthesia (0.4 [0.2–0.8]; P = .007); however, the odds were not different for vascular puncture (1.3 [0.7–2.2]; P = .4). Systemic toxicity of local anesthetics was not observed in any patient with ultrasound guidance alone but was observed in 1 patient with combined ultrasound and nerve stimulation and in 1 patient with nerve stimulation alone.

Table 2.

Table 2.

Figure 2.

Figure 2.

As a sensitivity analysis, multivariable regression to estimate treatment effects was used. After adjustment for confounders, the sensitivity analyses did not show different results (Table 2). Multicollinearity was not an issue, because the absolute value of any correlation coefficient was <0.5. The goodness of fit for each adjusted model was assessed by Hosmer-Lemeshow tests. The P values for all the regression models were .25.

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DISCUSSION

In our multicenter registry analysis of 26,733 patients, use of ultrasound was strongly associated with fewer vascular punctures and multiple skin punctures, whereas the rate of unintended paresthesia during insertion increased. After propensity score matching and adjustment for imbalanced covariables, the use of ultrasound was still associated with fewer vascular puncture and reduced need for multiple skin punctures. The combination of ultrasound and nerve stimulation increased the odds of multiple punctures and did not influence the rate of vascular punctures. Multivariable regression sensitivity analysis strengthened the impression that nerve stimulation increases multiple skin punctures and vascular punctures, whereas the rate of unintended paresthesia was significantly decreased.

Our findings are almost identical with a previous registry report.3 For example, with ultrasound, vascular puncture in 0.4% of patients was observed, whereas it was 0.5% in Barrington et al.3 Similarly, with nerve stimulation alone, vascular puncture in 1.7% of cases was observed, whereas it was 1.4% of cases for Barrington et al.3 Systematic reviews and meta-analysis of randomized controlled trials also conclude that the odds of vascular puncture decrease when ultrasound is used instead of nerve stimulation.5,8 However, each of these meta-analyses included fewer than 1000 patients compared with our analysis of more than 26,000 patients. Meta-analysis also concluded that it takes less time to perform the block when ultrasound guidance alone is used instead of nerve stimulation alone.5 Our registry does not include procedural time, but it seems likely that more time was required with nerve stimulation alone as more attempts were necessary.

Lewis et al9 also found in a meta-analysis that performance time decreases when ultrasound guidance alone is used, but it was unclear whether this result reflects performance in experienced hands. As our registry mainly includes data from unselected practitioners and patients not included in randomized trials, our data support the generalization of this conclusion assuming that fewer multiple skin punctures decreases performance time.

The incidence of LAST was low in our study with 0.1 per 1000, yet still within the range known from previous studies (0.06–0.87 per 1000).2,10,11 The large range is related to the reporting of milder (0.87 per 1000)2 compared to severe (0.06 to 0.07 per 1000) signs of LAST.10,11 Barrington et al3 reported in a retrospective analysis of a multicenter database a decreased incidence of LAST when ultrasound guidance was applied. However, a comparison of ultrasound guidance with nerve stimulation in our study population was not possible due to the low incidence of LAST.2 Nevertheless, in 10,380 patients with ultrasound guidance alone, no cases of LAST were observed.

The combination of ultrasound and nerve stimulation has been termed “protective nerve stimulation” or “dual-guidance,” but whether this combination is associated with fewer acute complications is unknown in a large population. In a randomized trial of 109 patients, interscalene blocks were less successful with the combination of ultrasound guidance and nerve stimulation than with ultrasound alone—and superior to nerve stimulation alone.12 However, the incidence of paresthesia and vascular puncture was not reported. In our large population, vascular puncture was not decreased by the combination of ultrasound and nerve stimulation, whereas multiple punctures were more often required than with ultrasound alone. However, the increased odds of multiple punctures could be related to more difficult anatomic condition, because in this case, the combination of ultrasound guidance and nerve stimulation is routinely used in the hospital centers of the registry.

Data from an Australasian registry indicated that unintended paresthesia during insertion doubled when ultrasound guidance alone was used instead of nerve stimulation alone (2% vs 1%).3 The increased incidence of paresthesia during use of ultrasound was not associated with an increased incidence of late or long-term neurologic deficits.3 Further studies confirmed that ultrasound guidance is not associated with more long-term neurologic deficits.13,14 Accordingly, the American Society of Regional Anesthesia and Pain Medicine found in 2015 that paresthesia during needle advancement is not entirely predictive of peripheral nerve injury.15

We also observed that paresthesia is more common with ultrasound guidance alone than nerve stimulation or the combination of both. We can only speculate about the difference in paresthesia between the groups. In a previous randomized observer-blinded study of 60 patients with interscalene block, the incidence of transient paresthesia increased significantly when the block was performed inside the brachial plexus sheath compared with outside.16 Other studies reported that the inability of ultrasound guidance to reduce paresthesia compared with nerve stimulation may stem from technical or training limitations in discerning nerve from surrounding tissues, resulting in an unintended nerve contact.15,17 A further possibility could be that unintended paresthesia during nerve stimulation is underreported, because twitches may subjectively be confused with paresthesia.18

We could not determine whether the minor complications recorded were linked to more serious outcomes because duration of hospitalization, long-term outcomes, and long-term mortality were not recorded. However, given the minor nature of the observed complications, it seems unlikely that substantive clinical outcomes were much affected.

Bias was likely because we retrospectively analyzed 3 nonrandomized groups. To minimize confounder bias, we thus used propensity score matching in our main analysis and multivariable logistic regression as a sensitivity analysis. The results in our main analysis cannot be generalized to the entire population because we were only able to match about 25% of the primary cohort across the 3 conditions. But after triple matching, variables were well balanced with STDs <0.1.

Our results were adjusted for the year of surgery under the assumption that there were improvements in knowledge, skills, and techniques during the 8-year observation period. Clinical site was also considered a potential confounder in our statistical model under the assumption that skills with various methods vary from center to center. In large registry studies, it is common to identify differences that are statistically significant but not clinically important; however, the magnitude of our primary associations was clearly clinically meaningful. Participation bias is possible; therefore, hospital centers were included in the propensity score matching with residual poorly matched factors included in a multivariable logistic regression. Although our analysis was retrospective, complications data in our registry were specifically collected concurrent with patient care and were defined a priori.

In summary, ultrasound guidance thus appears to be the best approach for peripheral nerve blocks in regard to inadvertent vascular puncture and multiple attempts for block placement. Whether nerve stimulation reduces postblock nerve dysfunction remain unclear.

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ACKNOWLEDGMENTS

Network for Regional Anesthesia investigators are all 23 participating hospital centers that collected data for the present study: Berlin: Charité CCM/CVK, University Professor Dr Claudia Spies; Berlin: DRK Kliniken Westend, Professor Dr med. Arnd Timmermann; Bochum: Knappschaftskrankenhaus, Professor Dr Michael Adamzik; Bad Saarow: HELIOS Klinikum, Dr med. Stefan Wirtz; Bad Wildbad-Sana Klinik, Dr med. Edgar Bauderer; Dresden: Uniklinikum, Professor Dr med. Thea Koch; Erfurt: HELIOS Klinikum, Professor Dr med. Andreas Meier-Hellmann and Dr med. Simone Liebl-Biereige; Frankfurt: Orthopädische Uniklinik, Professor Dr med. Paul Kessler; Frankfurt: BGU, Dr med. Rolf Teßmann; Freiburg: Uniklinikum, Professor Dr med. Hartmut Bürkle; Hamburg: UKE, University Professor Dr med. Alwin E. Goetz; Hannover: Diakoniekrankenhaus Friederikenstift gGmbH, PD. Dr med. André Gottschalk; Hannover: Ambulatory surgery centers; Homburg: UKS, University Professor Dr med. Thomas Volk; Jena: Uniklinikum, Professor Dr med. Winfried Meissner, MD; Lengerich: HELIOS Klinikum, Dr med. Albrecht Pfeiff; Ludwigsburg: Klinikum, Professor Dr med. Götz Geldner; Marburg: Uniklinikum, Professor Dr med. Hinnerk F. W. Wulf; Markgröningen: Dr med. Reimund Stögbauer; Memmingen: Klinikum, Professor Dr med. Lars Fischer; Siegen: St Marien-Krankenhaus, Professor Dr med. Werner Hering; Städtisches Klinikum Solingen gGmbH, Professor Dr med. Thomas Standl; Ulm: Rehabilitationskrankenhaus, Dr med. Jörg Winckelmann.

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DISCLOSURES

Name: Hagen Bomberg, MD.

Contribution: This author had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. He also made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Laura Wetjen, MS.

Contribution: This author had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis.

Name: Stefan Wagenpfeil, PhD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Jakob Schöpe, MS.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Paul Kessler, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Hinnerk Wulf, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Thomas Wiesmann, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Thomas Standl, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: André Gottschalk, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Jens Döffert, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Werner Hering, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Jürgen Birnbaum, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Bernd Kutter, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Jörg Winckelmann, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Simone Liebl-Biereige, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Winfried Meissner, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Oliver Vicent, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Thea Koch, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Hartmut Bürkle, MD, PhD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Daniel I. Sessler, MD.

Contribution: This author made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

Name: Thomas Volk, MD.

Contribution: This author had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. He also made substantial contributions to the concept and the design of the study, the acquisition, the analysis, and the interpretation of data, drafting the article, and revising it critically for important intellectual content.

This manuscript was handled by: Richard Brull, MD, FRCPC.

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REFERENCES

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3. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications. Reg Anesth Pain Med. 2009;34:534–541.
4. Steinfeldt T, Schwemmer U, Volk T, et al.; German Society of Anaesthesiology and Intensive Care Medicine. Nerve localization for peripheral regional anesthesia. Recommendations of the German Society of Anaesthesiology and Intensive Care Medicine. Anaesthesist. 2014;63:597–602.
5. Abrahams MS, Aziz MF, Fu RF, Horn JL. Ultrasound guidance compared with electrical neurostimulation for peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth. 2009;102:408–417.
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9. Lewis SR, Price A, Walker KJ, McGrattan K, Smith AF. Ultrasound guidance for upper and lower limb blocks. Cochrane Database Syst Rev. 2015:CD006459.
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12. Kolny M, Stasiowski MJ, Zuber M, et al. Randomized, comparative study of the effectiveness of three different techniques of interscalene brachial plexus block using 0.5% ropivacaine for shoulder arthroscopy. Anaesthesiol Intensive Ther. 2017;49:47–52.
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14. Sites BD, Taenzer AH, Herrick MD, et al. Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Reg Anesth Pain Med. 2012;37:478–482.
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16. Maga J, Missair A, Visan A, et al. Comparison of outside versus inside brachial plexus sheath injection for ultrasound-guided interscalene nerve blocks. J Ultrasound Med. 2016;35:279–285.
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