In 1996 Stephan Kapral M.D. had the great idea, after he had participated in an echocardiography workshop, that nerve structures could also be scanned and subsequently be blocked by using ultrasound techniques. From that time on the ultrasound guided technique to block nerves became one of the most successful interventions in the entire field of anesthesia. Today USRA provides a very safe technique for our patients without using general anesthesia for a variety of surgical procedures.

Regional anesthesia has various advantages over general anesthesia, such as targeted pain relief with less side effects, reduced perioperative morbidity, faster recovery and shorter hospital stays and enhanced postoperative analgesia. But, like any other medical procedure, regional anesthesia is not excluded from certain complications, which every anesthetist should be aware of. Complications in regional anesthesia include anesthetic systemic toxicity (LAST), infection, hematoma, cardiovascular disturbances and allergies. This package of complications is quite similar to all other interventional anesthetic procedures and is all well known. In this abstract the focus is targeted at another serious complication namely the nerve injury.

These nerve damages caused by different circumstances can have dramatic consequences for the patient and also for the anesthetist.

The majority of axons of the peripheral nerve system are covered by Schwann cells. These myelinated axons are bundled in fascicles surrounded by connective tissue layers called ‘perineurium’. Within the fascicles the connective tissue layers are called ‘endoneurium’.

Groups of fascicles of an entire nerve are covered by the epineurium. This sheath is the thickest and its collagen fibers are similar to the fibers of the dura.

The knowledge of this anatomical neural multi-layer sheath construction network is essential to understand the different types of nerve damage, which are assigned to two different classifications.

In daily practice the Seddon classification is more common. Nerve injury, as mentioned above, can lead to very severe complications. It is the most common complication in regional anesthesia. Starting with transient sensoric deficits, which are classified as Neuropraxia, with myelin damage and conduction reduction (s.a.) with a very good prognosis for complete recovery, up to a severe neurotmesis with a complete transection of the axon, myelin and endoneurium. Fortunately this usually does not happen in regional anesthesia. It is usually observed after massive trauma, sharp injuries or intraneural injection of noxious drugs. The incidence of nerve injury (NI) in RA in general is very varying due to the fact that there are a lot of heterogenous studies with ‘unsharp’ definitions. The incidence of long-lasting peripheral nerve injury (PNI) ranges from 2 to 4 per 10,000 patients [7,8]. In a study by Urban et al., mild paresthesias were not uncommon on postoperative day 1, occurring in 19% of axillary blocks and 9% of interscalene blocks. After 2 weeks, the incidence of neuropraxia fell to 5% in the axillary group and 3% in the interscalene group. After 4 weeks, only 0.4% of patients experienced symptoms . Overall, transient deficits lasting up to 2 weeks are not uncommon and can range from 8.2 to 15%. The study of Lupu et al. found out that using ultrasound guided technique nerve blocks with intraneural injections do not regularily result in permanent nerve damage. Interestingly there is no significant difference in postoperative neurologic symptoms comparing ultrasound technique versus stimulation technique

Such seemingly rare occurrences of PNB-related nerve injuries might be due to a lack of documentation (underreporting), improper follow-ups, or associated legal implications. Even the mildest, self-limiting, unintentional, and most frequent form of perioperative nerve injury (neuropraxia) can result in a medicolegal claim for extended hospitalization and additional treatment costs. It is also important to know that nerve injuries happen more often in the upper extremities than in lower extremities. The most injured nerve is the radial nerve in the upper limb, followed by the median and ulnar nerves, and the sciatic nerve in the lower limbs, followed by the peroneal and tibial nerves.

This sequence is based on the fact that much more blocks are provided on the upper extremity and that e.g. the sciatic nerve contains a lot of connective protective tissue layers comparing to nerves of the brachial plexus. The spinal nerves of the ventral rami of C5, C6, etcc consist of nearly pure nerve structures with very few connective tissue layers. So touching these nerves with the tip of the needle will be remembered by the patients for ever.

Nerve injuries can manifest as sensory or motor dysfunction, or both. Sensory dysfunction may present as numbness, tingling, or burning sensations, whereas motor dysfunction may present as weakness or paralysis of muscles supplied by the affected nerve.

Risk factors for nerve injury are patient and/or surgery related but also anesthesia related. Patient related risk factors are numerous like age, gender (women>men), smoking, preexisting disorders and of course anticoagulation. There are also a lot of surgery related risk factors like patient’s position, compression (cast, tourniquet), ischaemia, haematoma, perioperative inflammation, infection etc.. Especially the tourniquet issue causes an ongoing endless debate between surgeons and anesthetists. There are conflicting data about duration and pressure level when using a tourniquet. Usually there are fixed values used in daily practice for any kind of surgical procedures and patients. The main features of tourniquet compression result in vascular permeability, intraneural edema and especially in lower leg surgery nerve degeneration, due to higher pressures. According to long-ago recommendations, the tourniquet pressure should not be more than 150 mmHg above the systolic blood pressure, and the duration should not exceed 90minutes, or a maximum of 120 minutes with a 10-15 minute deflation phase.

Today we know how important it is to adapt the tourniquet pressure level to different operative settings. The widely used duration of 90 minutes has never been proven by studies, it has been more of a practical habit for decades. Now there are automatic pneumatic tourniquet devices available that are able to adapt the tourniquet pressure continuously with a predifined, adjustable value above the systolic blood pressure.

The anesthetic related risk factors are the ‘4 H’ (Hypotension, Hypothermia, Hypovolemia, Hypoxia) but also our needle skills, too deep sedation and last but not least the local anesthetics, which all of them especially combined can lead to nerve injuries.

Special attention should be given to patients with diabetes mellitus, especially those with preexisting diabetic neuropathies, which indeed is the most common complication of this metabolic disorder. These patients are highly endangered to suffer from nerve injuries after a ‘failed’ nerve block. The pathogenesis of this diabetic neuropathy is very complex. All the different biochemical cellular pathways lead to neural oxidative stress and subsequently to severe neural damage, which affects the myelin sheaths and also the axonal structures. The impaired vasculature and autoregulation are also very much involved to trigger diabetic neuropathy. The point is, that diabetic patients are at least twice as likely to require surgery than non-diabetics because of their comorbidities and the type of surgery performed. Other patients with preexisting diseases (metabolic, toxic, ischemic, etc...) who additionally suffer from nerve entrapment are on high risk for a double crush syndrome, especially when receiving nerve blocks.

To mitigate the risk of double crush syndrome in regional anesthesia, practitioners should be aware of the patient‘s prior neurological history. Patients with a history of peripheral neuropathy, whatever the reason is, should be evaluated for any signs of nerve compression, such as muscle weakness, sensory defects, or neuropathic pain, before and after the nerve block procedure. Generally, practitioners must be gentle during the procedure, minimizing the amount of pressure or manipulation applied to the patient‘s nerves. The best way to minimize neural damage is to train RA-skills as good as possible. It is very important to visualize the entire nerve including surrounding structures to avoid direct needle trauma to nerves or perforate close located vessels or other vulnerable structures. It is essential to provide structured professional training to improve fine motor skills because the learning curve in the beginning is quite flat. To visualize the needle in different angles and planes in a dynamic motion and at the same time focusing on the targeted nerve is very challenging in the beginning. Another challenging issue is learning anatomic structures from a 3- dimensional in a 2-dimensional model transmitted on a display. This cognitive challenge often leads to misinterpretations. All anesthesiology departments providing regional anesthesia should therefore implement structured programs for their interested colleagues starting with simple superficial located nerve blocks on the upper and lower extremity. For deep nerve blocks, where nerve visualization can be tricky, dual guidance technique, using ultrasound and nerve stimulator, is recommended. Using pressure monitoring devices to avoid intraneural injections is helpful, although this technique is not widely used because of the high extra costs. It is highly sensitive but lacks specificity. In other words, the absence of high injection pressure effectively rules out an intrafascicular injection. High opening injection pressure (>20 psi) determines the intrafascicular placement of the needle tip. Low opening pressure (

The needle selection is another very sensitive and much discussed topic among anesthetists. Using non-cutting blunt or short bevel tip (45°) needles are much less likely to penetrate epineurium and minimize nerve penetration. But they get easily bended, when piercing through rough skin. This can worsen visualization of the needle and can lead to unexpected nerve damage. Long-bevel tip needles (15°) are much sharper and therefore more likely to puncture epi- or even perineural structures. Self-explanatory the needle diameter is linked to the degree of nerve damage.

Summary: Complications in regional anesthesia are multifactorial and very complex. There are multiple surgical, anesthesiologic and patient related factors for nerve injury. The incidence of nerve damage in regional anesthesia varies significantly in a very low range. In most cases there are several combined factors that lead to a nerve damage. Histologically you will find damaged myelin layers and axonal degeneration. Fortunately this neuropraxia has the best outcome and perioperative neurological deficits will disappear completely in more than 95% of the cases. There are a lot of preprocedural precautions to provide good blocks and to avoid nerve injuries. Beginning with the medical explanation, consent of the patient, documentation of all the patients related factors, continuing in the holding area with monitoring, if necessary slight sedations, up to positioning of the patient and ergonomics of the anesthetist. Then choosing the optimal technique with the correct needle under sterile conditions with the minimal dosage of local anesthetics required will avoid side effects or even complications like LATS, hematoma, infections and last but not least nerve injuries. But the key point to mitigate nerve damages are in fact the skills of well trained anesthetists preferably with the support of high quality US machines with high resolution to detect needle and targeted nerves very precisely. In case of poor visibility the provider can use stimulation technique and even go for triple guidance technique using pressure monitoring devices aswell. Keeping all these facts and procedures in mind will provide perfect blocks without any harm to our patients.

References

1. 1.Macfarlane AJR, Prasad GA, Chan VWS, Brull R. Does regional anaesthesia improve outcome after total hip arthroplasty? A system- atic review. Br J Anaesth. 2009;103:335–45.

2. Hadzic A, Karaca PE, Hobeika P, Unis G, Dermksian J, Yufa M, et al. Peripheral nerve blocks result in superior recovery profile compared with general anesthesia in outpatient knee arthroscopy. Anesth Analg. 2005;100:976–81. This is a foundational manu- script that outlines the importance of nerve blocks compared to general anesthesia. compared with general anesthesia in outpatient knee arthroscopy.

3. Brull R, Hadzic A, Reina MA, Barrington MJ. Pathophysiology and etiology of nerve injury following peripheral nerve blockade. Reg Anesth Pain Med. 2015;40:479–90.

4. 4.Franco CD. Connective tissues associated with peripheral nerves. Reg Anesth Pain Med. 2012;37:363–5.

5. 5.Seddon HJ. A classification of nerve injuries. Br Med J 1942;2: 237–239.

6. 6.Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain 1951;74:491–516.

7. Urban MK, Urquhart B. Evaluation of brachial plexus anesthesia for upper extremity surgery. Reg Anesth United States. 1994;19:175–82.

8. Sondekoppam RV, Tsui BCH. Factors associated with risk of neu- rologic complications after peripheral nerve blocks. Anesth Analg. 2017;124:645–60.

9. Fredrickson MJ, Kilfoyle DH. Neurological complication analysis of 1000 ultrasound guided peripheral nerve blocks for elective or- thopaedic surgery: a prospective study. Anaesthesia. 2009;64:836– 44.

10. Lupu CM, Kiehl T-R, Chan VWS, El-Beheiry H, Madden M, Brull R. Nerve expansion seen on ultrasound predicts histologic but not functional nerve injury after intraneural injection in pigs. Reg Anesth Pain Med. 2010;35:132–9.

11. Deschner S, Borgeat A, Hadzic A. Chapter 69. Neurologic complications of peripheral nerve blocks: mechanisms & management. NYSORA Textbook of Regional Anesthesia and Acute Pain Management. Hadzic A (ed): McGraw-Hill Medical, New York; 2007. 1109-35.

12. Albers JW, Pop-Busui R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. Curr Neurol Neurosci Rep. 2014;14:473. 10.1007/s11910-014-0473-5 Knowing It Before Blocking It,’ the ABCD of the Peripheral Nerves: Part B (Nerve Injury Types, Mechanisms, and Pathogenesis) Kartik Sonawane 1, Hrudini Dixit 2, Navya Thota 1, Tuhin Mistry 1, Jagannathan Balavenkatasubramanian ‘Knowing It Before Blocking It,’ the ABCD of the Peripheral Nerves: Part C (Prevention of Nerve Injuries) Kartik Sonawane 1, Hrudini Dixit 2, Kaveri Mehta 3, Navya Thota 1, Palanichamy Gurumoorthi 1