The use of a nerve stimulator provides the anesthesiologist with the huge advantage of a clear and objective endpoint to look for when placing peripheral nerve blocks: the contraction of the muscle innervated by the stimulated nerve. This represents a crucial feedback about the appropriateness of needle position (1), minimizing the discomfort for the patient and improving the reliability and ease of peripheral nerve blocks (2,3).

When using a single injection technique several studies failed to demonstrate clinically relevant differences between the use of nerve stimulation or paresthesia techniques (4,5). However, we must remember that, contrary to the illustrations made by medical artists, peripheral nerves and plexuses are included in compartments containing connective tissue and fat; while terminal branches of plexuses and nerves divide and separate very frequently, and the different branches may run at some distance one from each other. Also big terminal nerves are often constituted by different branches: the sciatic nerve, in example, is constituted by the tibial and common peroneal branches, which are often separated at the level of the pelvis (each of them with its own perineural fascia) (Figure 1). Similar consideration can be made also for the femoral nerve, which divides in 6 7 terminal branches just below the inguinal ligament (and the needle is usually inserted at the level of the inguinal crease, below the inguinal ligament) (Figure 2). Accordingly, once injected at one single site the local anesthetic molecules have to diffuse through several barriers before reaching the nerves, the first barrier being represented by the distance between the injection site and each branch.

Using a nerve stimulator easily allows to identify different muscular twitches during block placement by simply redirecting the stimulating needle using the "so called" multiple injection technique (6). The rationale of the multiple injection technique is to block each branch involved in surgery with a small volume of local anesthetic solution. The nerve stimulator is set at 1 1.5 mA intensity to get the first twitch. Afterwards, the intensity of stimulating current is progressively reduced to less than 0.5 mA maintaining the proper twitch; then 5 7 ml of local anesthetic solution is injected. When the first branch is blocked, the nerve stimulator is set again at 1 1.5 mA and the needle redirected to elicit the second twitch and the manoeuvre repeated for all the main branches (Table 1).

Searching for multiple muscular responses and injecting a small volume of local anesthetic solution at each twitch provides effective peripheral nerve blocks for both upper and lower extremity, with volumes of local anesthetic solution markedly lower than those usually reported (6). When injecting the same amount of local anesthetic solution at single branch, at two branches or at all four branches innervating the upper arm, Lavoie et al (7) demonstrated that blocking selectively all the four branches of the upper limb, or at least two of them, gives a higher success rate of axillary block than the stimulation of only one nerve. Koscielniak-Nielsen and co-workers (8,9) reported similar results when comparing a transarterial or a multiple injection technique with nerve stimulator for the same nerve block, while other authors demonstrated similar results with other different nerve blocks, including the interscalene (10) or midhumeral (11) approach to brachial plexus anesthesia, the sciatic block (12,13) or the femoral nerve block (14). The use of this new philosophy for peripheral nerve block placement can also be used to produce a "super-selective" analgesia according to surgery (15,16).

Most anesthesiologists claim that looking for multiple muscular twitches requires too much time for block placement. However, different studies in different clinical setting, including axillary, interscalene or femoral nerve blocks, demonstrated that, although the time required to place the block is slightly longer with the multiple injection technique, the latency of the surgical block is so much shorter with the multiple injection that total preoperative time (from skin disinfection to readiness to surgery) is significantly shorter with the multiple than single injection technique (8-10,13,14).

Looking for multiple twitches also minimizes the dose of local anesthetic required to produce a successful nerve block. Using an up-and-down method, we recently demonstrated that the volume of local anesthetic solution required to produce complete sensory and motor block of the femoral nerve in 95% of patients within 20 min after the injection is reduced by nearly 30% when the three main branches of the femoral nerve are blocked separately (Figure 2) as compared with injecting all anesthetic volume at the contraction of the vastus intermedious muscle (17). Reducing the volume of local anesthetic become especially important for lower limb surgery, which requires a combination of different nerve blocks with increased risk for local anesthetic overdosing.

Another important advantage of the multiple injection technique concerns the occurrence of accidental intravascular injection. In fact, it is well known that a negative blood aspiration before the injection does not prevent the risk for unwanted intravascular injection (18,19). If a single injection technique is used we can theoretically inject up to 30 40 ml of local anesthetic solution according to the block we are placing (if seizures do not occur before we finish the injection). On the contrary, with the multiple injection technique we can not inject intravascularly more than 5 7 ml of local anesthetic solution.

Thus, the multiple injection technique provides shorter onset time, better success rate and potentially less risk for toxic reactions during peripheral nerve block than the single injection technique. Nonetheless, most anesthesiologists are concerned with using the multiple injection technique, because of the theoretically increased risk for direct nerve injury by moving the stimulating needle toward a partially anesthetized nerve. However, this concern is only theoretical, and no clinical evidence supports it. First of all, our problem is usually represented by the long latency of peripheral nerve blocks: placing a block with the multiple injection takes never longer than 5 min, while the block onset time (especially if we use reduced volumes of local anesthetic solution) requires 15 20 minutes. Second, we always use a "radar" to place the block, that is represented by the nerve stimulator: if we go again toward a nerve we already injected we will elicit again the twitch if this occurs within 5 min after the first injection. Furthermore, a prospective observational study on nearly 4,000 nerve blocks performed with the multiple injection technique (6) clearly demonstrated that the risk for permanent nerve injury with the multiple injection technique is similar to that reported in a prospective evaluation of severe complication on nearly 100000 regional anesthetics (20), and lower than that recently reported in a study evaluating acute and nonacute complications associated with interscalene block performed with a single injection technique (21). There is no doubt that minor neurological complications most likely remain undiagnosed if a proper follow-up is not planned and performed, and properly designed, randomized studies should be advocated to clarify this crucial and controversial question. Nonetheless, no clinical evidence supports the hypothesized risk for increased nerve injury during block placement when a multiple injection rather than a single injection technique is used.

Withdrawing and redirecting the stimulating needle to elicit multiple muscular twitches during the same nerve block might cause more discomfort to the patient (6); however, a slight sedation-analgesia before block placement with very small doses of benzodiazepine and opioid drugs minimizes the discomfort experienced by patients undergoing multiple injection for nerve block placement, whilst producing minimal sedation and optimizing acceptance of the anesthetic procedure (22).

In conclusion, simply looking for multiple nerve branches when placing a peripheral nerve block with a nerve stimulator provides successful nerve block in less time and with less volume of local anesthetic solution than that required with the single injection technique, without increasing the risk for nerve injury.

References:

1. Riegler FX. Brachial plexus block with the nerve stimulator: motor response characteristics at three sites. Reg Anesth 1992;17:295-9.
2. Fanelli G. Peripheral nerve block by electric neurostimulation. Minerva Anestesiol 1992;58:1025-6.
3. Davies MJ, McGlade DP. One hundred sciatic nerve blocks: a comparison of localization techniques. Anaesth Intensive Care 1993;21:76-8.
4. Jones TS. Comparison of axillary block techniques: is there a difference in success rate? ANAA Journal 1997;65:257-9.
5. Baranowski AP, Pither CE. A comparison of three methods of axillary brachial plexus anaesthesia. Anaesthesia 1990;45:362-5.
6. Fanelli G, Casati A, Garancini P, Torri G. Nerve stimulator and multiple injection technique for upper and lower limb blockade: failure rate, patient acceptance and neurologic complications. Anesth Analg 1999; 88:847-52.
7. Lavoie J, Martin R, Tetrault JP, Cote DJ. Axillary plexus block using a peripheral nerve stimulator: single or multiple injections. Can J Anaesth 1992;39:583-6.
8. Koscielniak-Nielsen ZJ, Hesselbjerg L, Fejberg V. Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary block by 45 ml of mepivacaine 1% with adrenaline. Acta Anaesthesiol Scand 1998;42:570-5.
9. Koscielniak-Nielsen ZJ, Rotboll Nielsen P, Sorensen T, Stenor M. Low dose axillary block by targeted injections of the terminal nerves. Can J Anaesth 1999;46:658-64..
10. Fanelli G, Casati A, Beccaria P, et al. Interscalene brachial plexus anaesthesia with small volumes of ropivacaine 0.75%: effects of injection technique on the onset time of nerve blockade. Eur J Anaesthesiol 2001;18;54-8.
11. Gaerter E, Kern O, Mahoudeau G, Freys G, Golfetto T, Calon B. Block of the brachial plexus branches by the humeral route. A prospective study in 503 ambulatory patients. Proposal of a nerve-blocking sequence. Acta Anaesthesiol Scand 1999;43:609-13.
12. Bailey SL, Parkinson SK, Little WL, et al. Sciatic nerve block: a comparison of single versus double injection technique. Reg Anesth 1994;19:9-13.
13. Paqueron X, Bouaziz H, Macalou D, Labaille T, Merle M, Laxenaire MC, Benhamou D. The lateral approach to the sciatic nerve at the popliteal fossa: one or two injections? Anesth Analg 1999:89:1221-5.
14. Casati A, Fanelli G, Beccaria P, Cappelleri G, Berti M, Aldegheri G, Torri G. Effects of the single or multiple injection technique on the onset time of peripheral nerve blocks with 0.75% ropivacaine. Anesth Analg 2000;91:181-4.
15. Sparks CJ, Quinn M. Selective block of nerves in the axillary approach to the brachial plexus. Reg Anesth 1992;17:300-2.
16. Bouaziz H, Narchi P, Mercier FJ, Khoury A, Poirer T, Benhamou D. The use of a selective axillary nerve block for outpatient hand surgery. Anesth Analg 1998;86:746-8.
17. Casati A, Fanelli G, Beccaria P, Magistris L, Albertin A, Torri G. Effects of single or multiple injections on the volume of 0.5% ropivacaine required for femoral nerve blockade. Anesth Analg 2001;93:183-6.
18. Ellis JS Jr, Ramamurthy S. Seizure following stellate ganglion block after negative aspiration and test dose [letter]. Anesthesiology. 1986:64:533-4.
19. Klein SM, Benveniste H. Anxiety, vocalization, and agitation following peripheral nerve block with ropivacaine. Reg Anesth Pain Med 1999;24:175-8.
20. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia. Anesthesiology 1997;87:479-86.
21. Borgeat A, Ekatodramis G, Kalberer F, Benz C. Acute and nonacute complications associated with interscalene block and shoulder surgery. Anesthesiology 2001;95:875-80.
22. Kinirons BP, Bouaziz H, Paqueron X, et al. Sedation with sufentanil and midazolam decreases pain in patients undergoing upper limb surgery under multiple nerve block. Anesth Analg 2000;90:1118-21.

	Figure 1: Anatomy of the sciatic nerve. Very often the sciatic nerve is constituted by its two terminal branches (the common peroneal and tibial nerves), which are already divided when getting out from the foramen ischiaticus often running close one to each other but each with its separate perineural fascia until they definitely divide at the level of the popliteal fossa.
	Figure 2: Anatomy of the femoral nerve. Just below the inguinal ligament the femoral nerve divides into 6 - 7 branches which run at an increasing distance one from each other.

Table 1: Specific muscular twitches which we can look for when using a multiple injection technique.

The multiple stimulation and injection technique for the performance of peripheral nerve blocks has been advocated in recent years, mainly by European investigations. Suggested indications include interscalene, axillary, humeral, femoral and lateral sciatic nerve blocks. When compared with single injection techniques, investigators have claimed a higher success rate (axillary, lateral sciatic), shorter onset time and quicker readiness for surgery (interscalene, axillary, femoral), and a reduction of the minimal local anesthetic dose needed to achieve satisfactory results (femoral), as main advantages of the multiple stimulation and injection approach. On first sight, these arguments appear to be convincing. However, a closer examination of benefits, possible risks and disadvantages associated with the multiple stimulation technique may lead to a different conclusion.

The multiple stimulation and injection technique was first described for the axillary block. Based on the concept of septa dividing the brachial plexus sheath into several compartments (1) and preventing local anesthetic spread, the authors thought it necessary to perform several injections in order to block all four brachial plexus nerves. Although, anatomic studies have shown that these septa are incomplete (2) and do not prevent local anesthetic spread in between compartments, investigations have recommended different numbers and combinations of necessary brachial nerve stimulations. Koscielniak Nielsen et al. (3) and Inberg et al. (4) have reported significantly higher success rates of axillary plexus blocks with a multiple injection technique (three and two nerves, respectively) compared with a single injection technique. However, the percentage of complete blocks in the single injection groups was only 43% and 52%, respectively, surprisingly low and in contrast to previous investigations (5) and our own data (6). Accordingly, the difference in success rates between a single and double injection technique for the lateral approach to the sciatic nerve described by Paqueron et al. (7)^ are in contrast to the success rate observed by a single injection technique published by Hadzic and Vloka (8). Since the data are not conclusive, it remains uncertain how much stimulation is really needed to produce satisfactory axillary and lateral sciatic nerve blocks. It appears, that location and proper technique may be of more importance for successfully performed blocks than the number of injections.

Fanelli and Casati et al. reported an 8 min reduction for the interscalene block (9)^ and a 20 min reduction of onset time for the femoral nerve block (10), when three different injections were used for each approach. Koscielniak-Nielsen (3) demonstrated a 13 min reduction in time until readiness for surgery with the stimulation of three different brachial plexus nerves compared with single nerve stimulation. However, since a local anesthetic with a rather long onset time (ropivacaine) was solely used in two of these three studies, it is questionable if the rather small differences would have also been observed when using a local anesthetic with a short onset time (e.g.,mepivacaine). In addition, onset time might be of importance when a nerve block is performed in the OR, with the surgeon waiting. In our institution, peripheral nerve blocks are performed prior to surgery in a designated block room. This not only allows performance of the nerve block without being rushed, but also verification of good block quality and completion of incomplete blocks if necessary, before the patient is brought to the OR and exposed to the surgeon.

Casati et al. (11) reported a reduction in the local anesthetic volume needed to produce the same degree of sensory and motor blockade from 29 mL to 21 mL for the femoral nerve block, using 0.5% ropivacaine and a multiple (three) stimulation technique. It is questionable whether this reduction represents a clinically significant achievement. Local anesthetic toxicity is estimated to have an incidence of 4:10,000 to 11:10,000 (12). Newer local anesthetic agents such as ropivacaine and levobupivacaine have been demonstrated to be associated with an extremely low level of toxicity (13), especially when maximum recommended dosages are not exceeded and are therefore most likely associated with an even lower incidence of adverse events.

The underlying mechanism of peripheral nerve injury caused by regional anesthesia techniques remains controversial (14). Multiple factors are thought to be responsible for this complication. However, direct contact between the needle used for the peripheral nerve block and the nerve itself may contribute to the development of peripheral nerve injury. In this setting, the risk of inflicting a nerve injury would be directly proportional to the number of stimulation attempts, making it advantageous to use as few stimulation attempts as possible. In addition, some multiple stimulation techniques may require the induction of the needle through an area in which local anesthetic was injected previously. The patient may be unable to report discomfort, pain or paresthesia as a result of needle to nerve contact because the nerve may already have been partially or completely blocked. Although this has not been investigated in a controlled randomized fashion, this particular aspect of the multiple stimulation technique could present an increased risk for peripheral nerve injury, especially if sedation is provided during nerve block performance. On the other hand, if no sedation is provided, patients would experience discomfort during multiple injection techniques, resulting in a low desire to choose the same anesthetic technique for future surgery (15).

During their regional anesthesia rotation, our residents get exposed to both, single and multiple stimulation techniques. Multiple stimulation approaches are considered to have a steeper learning curve (16) and therefore require a higher level of training and experience. It comes as no surprise that most residents perform their first successful blocks with a single injection rather than with a multiple stimulation technique. As a result, most of our residents prefer single stimulation techniques to multiple stimulations at the end of their training and are more likely to use these techniques, once they start their own practice.

In conclusion, the data published in the literature do not convince me to endorse the multiple stimulation and injection technique. The potentially higher risk of peripheral nerve injury, the low acceptance by unsedated patients and the higher level of training required that are associated with multiple stimulations appear to outweigh the rather clinically irrelevant benefits. I believe, that the number of attempted nerve stimulations should be kept as low as possible and therefore multiple stimulations should mainly be chosen in settings in which single stimulation techniques are not available (e.g., humeral canal approaches).

References:

1. Thompson GE, Rorie DK. Functional anatomy of the brachial plexus sheaths. Anesthesiology 1983; 59: 117-22
2. Partridge BL, Katz J, Benirschke K. Functional anatomy of the brachial plexus sheath: implications for anesthesia. Anesthesiology 1987; 66: 743-7
3. Koscielniak-Nielsen ZJ, Stens Pedersen HL, Lippert FK. Readiness for surgery after axillary block: single or multiple injection techniques. Eur J Anaesthesiol 1997; 14: 164-71
4. Inberg P, Annila I, Annila P. Double injection method using peripheral nerve stimulator is superior to single injection in axillary plexus block. Reg Anesth Pain Med 1999; 24: 509-13
5. Schroeder LE, Horlocker TT, Schroeder DR. The efficacy of axillary block for surgical procedures about the elbow. Anesth Analg 1996; 83: 747-51
6. Gebhard RE, Greger J, Al-Samsam T, Matuszczak M, Rieger A. Single injection high axillary block Comparison with the multiple stimulation technique. Anesthesiology 2001; 95: A968
7. Paqueron X, Bouaziz H, Macalou D, Labaille T, Merle M, Laxenaire MC, Benhamou D. The lateral approach to the sciatic nerve at the popliteal fossa: one or two injections? Anesth Analg 1999; 89: 1221-5
8. Hadzic A, Vloka JD. A comparison of the posterior versus lateral approaches to the block of the sciatic nerve in the popliteal fossa. Anesthesiology 1998; 88: 40-6
9. Fanelli G, Casati A, Beccaria P, Cappelleri G, Albertin A, Torri G.
Interscalene brachial plexus anaesthesia with small volumes of ropivacaine 0.75%: effects of the injection technique on the onset time of nerve blockade. Eur J Anaesthesiol 2001; 18: 54-8
10. Casati A, Fanelli G, Beccaria P, Cappelleri G, Berti M, Aldegheri G, Torri G. The effects of the single or multiple injection technique on the onset time of femoral nerve blocks with 0.75% ropivacaine. Anesth Analg 2000; 91: 181-4.
11. Casati A, Fanelli G, Beccaria P, Magistris L, Albertin A, Torri G. The effects of single or multiple injections on volume of 0.5% ropivacaine required for femoral nerve blockade. Anesth Analg 2001; 93: 183-6
12. Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional anesthesia: results of a prospective study in France. Anesthesiology 1997; 87: 479-86
13. Mather LE, Chang DH. Cardiotoxicity with modern local anaesthetics: is there a safer choice? Drugs 2001; 61: 333-42
14. Horlocker TT. Peripheral nerve injury following regional anesthesia: Diagnosis, prognosis and prevention. ASA 2001, Annual meeting refresher course lectures
15. Fanelli G, Casati A, Garancini P, Torri G. Nerve stimulator and multiple injection techniques for upper and lower limb blockade: Failure rate, patient acceptance, and neuologic complications. Anesth Analg 1999; 88: 847-52
16. Koscielniak-Nielsen ZJ, Hesselbjerg L, Fejlberg V. Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary block by 45mL of mepivacaine 1% with adrenaline. Acta Anaesthesiol Scand 1998; 42: 570-75