Regional anaesthesia has come a full circle from time of its inception, when Halstead performed first brachial plexus block by injecting cocaine under vision to one where drug is delivered with the help of visual cues. However, it wasn’t a smooth one as it took several decades and various innovations.
Most important aspect of regional anaesthesia is to ensure complete blockade of the nerve/plexus with least possible amount of local anaesthetic at reasonably little discomfort to the patient and quickest onset time. The ultimate goal, therefore, is to inject a certain amount of local anaesthetic in close proximity to the nerve to block nerve conduction and provide a sensory and motor block for surgery and/or, eventually, analgesia for pain management, also, to avoid an intraneural, intrafascicular injection and consequently, nerve injury. Not to forget, limiting the amount of drug injected is vital to prevent local anaesthetic toxicity. Thus, it is mandatory to locate the target tissue prior to execution of injection. The sure shot technique is to expose the nerve under vision and deposit the local anaesthetic drug directly on it, as was practiced by Halstead. This is not practicable most often, compelling the physician to look for alternative means to precisely locate the neural tissue and ensure drug delivery in close proximity. Knowledge of anatomy and relationship of target neural tissue to the landmarks in juxtaposition, can help to a great extent in delivering the drug accurately. However, anatomical variation are far too common, for example, relationship between scalene muscles and the roots of brachial plexus is different as frequently as 40% of the times, which may account for most of the block failures1.  Therefore, there is a great need for ascertaining the presence of target neural tissue at the tip of the needle before local anaesthetic injection. Following methods are available to guide the operator in doing so:

1. Paraesthesia technique
2. Peripheral nerve stimulation
3. Transcutaneous nerve localization
4. Ultrasound guidance

Till recently, most widely practiced technique of testing the correct location of needle tip was eliciting paraesthesia. Here, we presume certain things. For example, the target neural tissue should have sensory component at the site of contact with needle to produce paraesthesia. As patient’s feedback forms the basis of successful block, it cannot be performed in a patient who is sedated or anaesthetized. For example, this technique is unsuitable for paediatric patients, who are not in a position to cooperate and express occurrence of paraesthesia precisely. If there is branching, it takes place only distal to the point of drug delivery. It also presumes that any paraesthesia in the corresponding area is due to the contact with desired part of nerve/neural tissue, as it is very difficult to verify where exactly the patient experiences paraesthesia and which nerve is responsible for that, especially when working on plexus. Last but not the least, justifiable fear of permanent damage to the neural tissue due to the physical trauma caused by the direct contact with needle and injection of local anaesthetic solution within the perineurium, which may produce undue high pressures, when nerve is encased in a sheath or compactly packed with  surrounding tissues. Not to forget the possibility ischaemia caused by the vasopressor contained in the solution. Thus, there was a need for better guide to locate the neural tissue ahead of drug delivery.
Meanwhile, nerve stimulation, known to scientific community ever since Galvani’s demonstration of peripheral nerve stimulation in 1780, did not make it in to anaesthesia practice till mid-90s.  With better understanding of electronics and introduction of insulated needles, peripheral nerve stimulation gained popularity and became standard of care in clinical practice. Unfortunately, peripheral nerve stimulation has its own limitations. They were understood very lately as there no means to verify these facts clinically.
Disadvantages of nerve stimulation:

1. Anatomical variations in the relationship with landmarks may cause some difficulty in localizing the neural tissue, though easier than with paraesthesia.
2. Response may vary for reasons not related to the anatomical placement of needle.
1. Current output may vary from instrument to instrument depending on the manufacturer.
2. Poor anode connection may result in excessive voltage.
3. Variation in the electrical impedance of human tissues may influence the current delivered.
3. Causes uncomfortable sensation in the area of nerve stimulated. This is a very highly variable phenomenon and difficult to predict. Recent advances in the knowledge and technology has reduced such possibilities by selecting strength and duration of current just suitable to stimulate only motor fibres, sparing sensory component (Aδ and C).
4. Certain diseases may increase the threshold for stimulus, rendering standard settings ineffective. For example, diabetic neuropathy, settings less than 0.5mA may not elicit any response2.
5. In case of paralyzed patients it cannot be used as motor response is difficult elicit
6. Expensive insulated needles are required.
7. Extraneural placement of local anaesthetic is still possible if response is obtained at minimum current more than 0.5 mA.
8. Motor twitches can be very painful among some patients. This is specifically true in cases of trauma.
9. It does not indicate/prevent injury to other structures, for example vascular puncture.

Some of these draw backs can be overcome by transcutaneous nerve location. For example,

1. Anatomical variations can be identified by mapping the course of the nerve/plexus, without causing much discomfort/multiple pricks.
2. Uncomfortable sensation is reduced due to less number of punctures and number of stimulations.

Thus, there was a need for alternative technology to guide the operator, especially in difficult anatomy or clinical settings unsuitable for nerve stimulation. Advent of ultrasound machine with high frequency linear probes and understanding of sono-anatomy, encouraged application of the same in regional anaesthesia. Then came the portable ultrasound machines, heralding the era of ultrasound guided (USG) regional anaesthesia.
Ultrasound guidance has certain advantages:

1. A fairly accurate idea of nerve/plexus location can be obtained by preliminary examination, in 3D. In fact, with some modern machines 3D reconstruction of the image is possible for reference prior to the actual procedure, thereby preparing for anatomical variations, improving the end result.
2. With adequate experience, number of needle punctures and redirections can be minimized, reducing the patient discomfort. Presence of local anaesthetic in the area may not alter the end result unlike in case of paraesthesia or nerve stimulation technique.
3. There is no direct contact with the target neural tissue as whole procedure is carried under real time visual guidance. This obviates possibility of paraesthesia and nerve injury.
4. Multiple injections are possible as no response is required to be elicited, thus ensuring complete coverage of neural tissue as there is no need for feedback, on which other techniques depend on. The feedback is lost as soon as small amount of local anaesthetic is injected.
5. Unlike either paraesthesia or nerve stimulation technique, nerve blocks can be performed at different locations than classical. Once the nerve is traced from its better known/more constant/superficial location, more convenient site may be selected.
6. Possibility of intravascular injection is very much reduced as presence of vessels in the near vicinity can be confirmed with Doppler.

These features of ultrasound guidance made the technique very popular despite its steep costs involved.

Having said that, ultrasound guidance too has its limitations. Some are:

1. First and foremost is need for training in use of ultrasound, which is relatively new in the field of anaesthesia.
2. Cost and availability of the equipment.
3. Variations in the image produced (hypo/hyper echoic) by the neural tissue at different locations in the body confusing the novices.
4. Gross anatomical variations leading to doubt about exact location of the neural tissue (femoral nerve).
5. Conditions like obesity, surgical emphysema, oedema of the overlying tissues, leading to difficulty in ensuring correct placement of drug.
6. Catheter placement, requires three dimensional image to understand exact positioning unlike needle tip location for single injection technique.
7. Image is subjective in interpretation.
8. Limited by ability to optimize the image.
9. Awareness of physics of sonography influences image obtained.
10. Overall experience and skill of the operator matters most.
11. Safety of ultrasound as claimed by the enthusiast need not translate in to safe clinical practice.

Thus, there is a need for additional confirmation for the final position of the needle tip/catheter before injection of local anaesthetic which ever technique is used to guide the performance of the nerve block. By then, many anaesthesiologists were familiar with peripheral nerve stimulation (PNS), there was a thought to combine PNS with ultrasound guidance, which is a newer technology to enter the field.
It was postulated that by combining two techniques it is possible to overcome the drawbacks of each of the above technique. Then new set of doubts creped in. Is it really true? Does dual guidance has reduced the incidence of complications? Has it increased success rate? What about the time taken for the performance of the block? What is the slope of the learning curve for the novice and that for the consultant, to use both methods together?

Several authors have tried to answer these questions. However, there is no concrete data to say that dual/multiple guidance is better than single and combination of peripheral nerve stimulation and ultrasound guidance is better than each one individually. Let us examine each indication for dual guidance:

Injury to the neural tissue: It has been proved that eliciting motor response at a currant < 0.2mA is indicative of intraneuaral needle placement. Voelkel et al demonstrated that eliciting twitch at currents less than 0.2mA caused inflammatory changes in the neural tissue. However, such changes were absent when response was obtained at higher currents (0.3 to 0.5mA)3.  Bigeleisen and co-workers reported high specificity for intraneural placement of needle tip when a twitch was present at stimulating currents less than 0.2mA.No motor response could be elicited at a current of 0.2mA or less unless needle tip was intraneural4.  Thus, absence of motor response at currents less than 0.2mA while it could be elicited at higher currents is a definitive indication of non intraneural placement of the needle tip. Thereby avoiding injury to the neural tissue.
In contrast, proponents of ultrasound only for nerve block technique argue that intraneural placement of needle can be visualized prior to the drug injection so that there is no need for confirmation with nerve stimulation. Moreover, the nerve swelling and histopatholoical evidences suggest that such event not to cause clinically detectable deficits in pigs5. Novices are known to lose the track of needle during advancement.    This may end up in severe complications such as nerve injury or vascular injury. Sonological observation of nerve swelling to realize intraneural injection of LA (local anaesthetic) may not protect against nerve damage as by the time it is noticed nerve damage would have happened. PNS provides complimentary anatomical information for confirming location of needle tip. Vassiliou et al reported that dual guidance of ultrasound with PNS approach combines the benefits of the US and the NS techniques in terms of a higher rate of close needle tip placements and a lower incidence of haematoma formation6.
Training: To acquire mastery over use of ultrasound guidance for nerve blocks, some skill and knowledge gathering is needed along with ability to process and integrate the information obtained in real time.  It can be broken down into several components. For example, 1. Anatomical knowledge, 2. Ultrasound physics, 3. Three dimensional special processing, 4. Bilateral hand –eye coordination. For a beginner it may intimidating and not very encouraging.  If PNS is added to it, the scenario gets even more complicated. However, if one is already familiar with PNS, they can seek specific motor response after placing the needle under ultrasound guidance to confirm before injection. This boosts the confidence, especially when multiple nerve elements are visualized or anatomy is uncertain. For example, axillary-brachial plexus block performed by seeking individual nerve. This reinforces anatomical knowledge.
Difficult visualization: Sometimes, seeking deeply located nerves like sciatic via anterior or subglutial approach, confirmation of needle placement is required. Similarly, blocks within facial planes or when more than one hyper echoic structures are seen as in obturator nerve block, nerve stimulation is of great help.
There is significant amount of evidence against the use of dual guidance:
Reliability of nerve stimulation: Basic tenet of employing PNS as a supplementary guide is to prevent damage to neural tissue. In other words, ‘closer the needle to the nerve, stronger the twitch’ is the slogan taught since PNS was being used in clinic practice. Several studies have debunked this myth, after locating the nerve with ultrasound or paraesthesia, increasing current strengths where used to elicit motor response. Whether brachial plexus or sciatic or other nerves, the investigators found that sometimes current more than 0.5mA failed to elicit response in good percentage of individuals, in spite of obvious intimacy of the needle and nerve. Moreover, in some cases, currant as high as 1.5mA could not elicit any response. The explanations for this suboptimal sensitivity may relate to non-uniform distribution of motor and sensory fascicles within a compound nerve; alternatively, it may be due to the varying patterns of impedance and conductance in perineural tissue that results in little current stimulating the motor axons7,8,9,10,11. The operator can be in a great confusion if there is no motor response in spite of good evidence on ultrasound screen. He may attempt at repositioning the needle to obtain motor response which may result in several needle passes predisposing to nerve damage.
Additional cost: If PNS is not going to improve the success of the nerve block, then the cost savings can be considerable, when a non-insulated ordinary needle is substituted for insulated needle meant for use with nerve stimulator.
Block time: Studies have shown that ultrasound guidance significantly decreases block times in expert hands12, 13, 14, 15. Additional use of nerve stimulator, not only increased the time required for seeking the motor response, but also decreased the success rate15!
Discomfort: A practical concern is the potential for discomfort in those patients who are subjected to a 1-2 Hz repetitive motor response. While this is usually insignificant, in certain populations (e.g. trauma, fractures) any further movement can result in pain for the patient. This may appear unjustified if the success and safety rates are similar with and without NS.
Clinical evidence: The evidence is inadequate to categorically state the benefits of one over the other. However, with the current literature, it is evident that ultrasound not only increases the success rate and speed of block, but also can reduce incidence of complications in case of supraclavicular and interscalene approaches. However, addition of nerve stimulation may simply delay the block without increasing the success rate16. Similarly, in the infraclavicular approach to brachial plexus, overall patient comfort and satisfaction seem to be greater in patients receiving ultrasound-guided axillary blocks simply because nerve stimulation in this area is uncomfortable, requires more time, and use of ultrasound may be associated with a higher success rate. In terms of success rate, there is no evidence that dual guidance is superior to ultrasound alone in this region.
In case of lumbar plexus block, as both techniques in question do not have very high efficiency in terms of success rate, a combination of the two may improve the success and analgesia. Femoral nerve anatomy is known to vary greatly especially regarding its branching and relation to the femoral artery, which is a major landmark guide for its approach. Whether guidance is based on ultrasound or PNS, these variations are going to affect the outcome of the procedure. Nader and colleagues demonstrated need for dual guidance on anatomical basis17.  However, clinical evidence has failed to demonstrate any advantage of dual guidance. Moreover, there was increased discomfort and delay in onset of block when nerve stimulation was involved. Based on anatomical study, in in-plane technique directed toward the lateral, rather than the medial, aspect of the nerve may have a higher likelihood of success with the femoral block when single or dual guidance is used.
Sciatic nerve is located very deep at subgluteal level and not many studies are available to establish supremacy of one over the other. However, ultrasound has shown to decrease the amount of local anaethetic require for successful block. Meanwhile, inability of the ultrasound penetration at high frequencies, makes land mark based PNS technique more suitable for the block18.  Approach to sciatic nerve at popliteal region appears to be preferred method for many due its easy visibility. Multiple studies have favoured use of ultrasound over PNS for this approach citing improved success as well as decreased patient discomfort (needle passes)19. However, dual guidance may improve the outcome as variation in the division of sciatic nerve is common at this level19.  
There not enough studies to support the positive effect of ultrasound on central neuraxial blocks. Available data is pertaining to only obstetrics and is from a single centre, thus not generalizable.
Comparison of complications of regional blocks between guidance methods: It is intuitive to assume that ultrasound would reduce the complications associated, especially related to intravascular injections and toxicity as needle tip advancement can be visualized and controlled to prevent vessel puncture, which are very well made out with sonography. There are several case reports and some studies contradicting this assumption20,21. Although the incidence of paresthesia was higher in the ultrasound group (20.5 vs 10.8 per 1000 patients), the late or long-term neurologic deficits were higher in the nerve stimulation group20. As noted previously, ultrasound-guided supraclavicular and interscalene blocks are associated with an extremely low incidence of vascular punctures and permanent nerve injury22 .
Recommendations for dual guidance of regional anesthesia:
Dual guidance of peripheral nerve blockade procedures with both nerve stimulation and ultrasound is definitely warranted under certain specific circumstances. Abnormal location of nerves, for example, femoral nerve, makes it difficult to identify them reliably in all cases with ultrasound alone. Therefore, the combination of ultra sound and nerve stimulation is recommended in these cases. Based on the lack of concordance between the current output and the needle tip to nerve, it may be more useful and appropriate to use PNS (in conjunction with ultrasound) as a qualitative tool (‘‘yes or no’’) to confirm the location of peripheral nerve rather than attempting to achieve a predefined minimum current output.
Recommended indications for dual guidance methods:

1. Nerves with common anatomic variability or abnormal anatomy: a combination helps to identify peripheral neural structures
2. Deep blocks such as sciatic and lumbar plexus: poor ultrasound visualization
3. Obesity/morbid obesity: poor ultrasound visualization
4. Lymphedema, subcutaneous emphysema: poor ultrasound visualization
5. Unsure of anatomy or structures: burns, scarring
6. Novice sonologist/regional anaesthesiologist
7. Need to perform an additional block after a failed or partial initial block
8. Catheter techniques: initial localization with ultrasound followed by insertion of stimulating catheter may improve the perineural placement, as catheters may be difficult to visualize with ultrasound23.

Conclusion: The newer mode of guidance for peripheral nerve blocks, ultrasound is just finding its place in routine clinical practice. Thus, there is not enough data to prove the benefits of multiple/dual guidance for improved outcomes. Considering that dual guidance does not produce consistently better results, adding another modality (ultrasound to PNS) will simply impose additional cost. However, it all depends on the expertise of the operator in developing or adjusting to new skill, or relearning to manage dual guidance by integrating the information in real time to obtain best possible outcome for the patient. Further, there are certain clinical situations where a single techniques is simply inadequate, for example, obesity, multiple guidance may help in verifying the anatomy to ensure 100% success rate. Nevertheless, in cases of doubt combinations of various techniques (e.g., ultrasound or nerve stimulation) will help to avoid serious—although rare—complications. Future developments, including reduced costs and improvements in image quality available with ultrasound machines, as well as formal training in ultra sound-guided techniques, seem likely to turn the tide toward ultrasound-based techniques as an integral part of regional anaesthesia practice.

References:

1. Harry WG, Bennett JD, Guha SC. Scalene muscles and the brachial plexus: anatomical variations and their clinical significance. Clin Anat. 1997;10(4):250-2.
2. www.dvcipm.org/files/maraa-book/chapt4.pdf.
3. Voelckel WG, Klima G, Krismer AC, et al. Signs of inflammation after sciatic nerve block in pigs. Anesth. Analg. 2005;101(6):1844-1846.
4. Bigeleisen PE, Moayeri N, Groen GJ. Extraneural versus intraneural stimulation thresholds during ultrasound-guided supraclavicular block. Anesthesiology. 2009;110(6):1235-1243.
5. Sites BD, Spence BC, Gallagher JD, et al. characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia. Reg Anesth Pain Med. 2007;32(2):107-115.
6. Vassiliou T, Eider J, Nimphius W, Wiesmann T, de Andres J, Müller HH, Wulf H, Steinfeldt T. Dual guidance improves needle tip placement for peripheral nerve blocks in a porcine model. Acta Anaesthesiol Scand. 2012 Oct;56(9):1156-62. doi: 10.1111/j.1399-6576.2012.02740.x. Epub 2012 Jul 26.
7. Robards C, Hadzic A, Somasundaram L, et al. Intraneural injection with low-current stimulation during popliteal sciatic nerve block. Anesth. Analg. 2009;109(2):673-677.
8. Altermatt FR, Corvetto MA, Venegas C, et al. Brief report: The sensitivity of motor responses for detecting catheter-nerve contact during ultrasound-guided femoral nerve blocks with stimulating catheters. Anesth. Analg.2011;113(5):1276.
9. Urmey WF, Stanton J. Inability to consistently elicit a motor response following sensory paresthesia during interscalene block administration. Anesthesiology. 2002;96(3):552-554.
10. Perlas A, Niazi A, McCartney CJ, et al. The sensitivity of motor response to nerve stimulation and paraesthesia for nerve localization as evaluated by ultrasound. Regional Anesthesia and Pain Medicine. 2006;33:245-50.
11.  Perlas A, Brull R, Chan VW, et al. Ultrasound guidance improves the success of sciatic nerve block at the popliteal fossa. Regional Anesthesia and Pain Medicine. 2008;33:259-65.
12. Dingemans E, Williams SR, Arcand G, et al. Neurostimulation in ultrasound-guided infraclavicular block: a prospective randomized trial. Anesth. Analg.2007;104(5):1275-1280.
13. Gürkan Y, Tekin M, Acar S, Solak M, Toker K. Is nerve stimulation needed during an ultrasound-guided lateral sagittal infraclavicular block? Acta Anaesthesiol Scand. 2010;54(4):403-407.
14. Chan VWS, Brull R, McCartney CJL, et al. An ultrasonographic and histological study of intraneural injection and electrical stimulation in pigs. Anesth. Analg. 2007;104(5):1281-1284.
15. Sites BD, Beach ML, Chinn CD, Redborg KE, Gallagher JD. A comparison of sensory and motor loss after a femoral nerve block conducted with ultrasound versus ultrasound and nerve stimulation. Reg Anesth Pain Med. 2009;34(5):508-513.
16. Williams SR, Chouinard P, Arcand G, et al. Ultrasound guidance speeds execution and improves the quality of supraclavicular block. Anesth Analg 2003;97(5):1518–23.
17. Nader A, Malik K, Kendall MC, et al. Relationship between ultrasound imaging and eliciting motor response during femoral nerve stimulation. J Ultrasound Med 2009;28(3): 345–50.
18. Bruhn J, Moayeri N, Groen GJ, et al. Soft tissue landmark for ultrasound identification of the sciatic nerve in the infragluteal region: the tendon of the long head of the biceps femoris muscle. Acta Anaesthesiol Scand 2009;53(7):921–5.
19. Wadhwa A, Kandadai SK, Tongpresert S, Obal D, Gebhard RE. Ultrasound guidance for deep peripheral nerve blocks: a brief review. Anesthesiol Res Pract. 2011; 2011: 262070. doi:  10.1155/2011/262070
20. 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(6):534–41.
21. Gnaho A, Eyrieux S, Gentili M. Cardiac arrest during an ultrasound-guided sciatic nerve block combined with nerve stimulation. Reg Anesth Pain Med 2009;34(3):278)
22. Liu SS, Gordon MA, Shaw PM, et al. A prospective clinical registry of ultrasound-guided regional anesthesia for ambulatory shoulder surgery. Anesth Analg 2010;111(3):617–23.
23. Wadhwa A, Gebhard RE, Obal D. Single or Multiple Guidance Methods for Peripheral Nerve Blockade in Modern-Day Practice of Regional Anesthesia. Advances in Anesthesia 05/2011; 28(1):187-210. DOI: 10.1016/j.aan.2010.08.002

Further reading:

1. Principles and Practice of Regional Anaesthesia edited by McLeod G, McCartney C, Wildsmith JAW, Wildsmith T Oxford University Press accessed at http://www.oup.com/localecatalogue/google/?i=9780199586691.

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