Incidence (per 10,000 blocks)
Cauda equina syndrome
Cauda equina syndrome
Incidence of temporary neuropathy after peripheral nerve block 
Estimated rate of occurrence (%)
Popliteal nerve block
Because of their severity, these problems require close scrutiny to determine etiology, establish principles of management to minimize disability and prevent future occurrences. The focus of this chapter is to identify how peripheral nerves may be damaged during upper and lower extremity regional anesthesia procedures. This includes direct trauma from the block needle, but also complications due to incorrect placement of the block needle (pneumothorax, intravascular injection, block of unwanted neural elements).
The investigation of an individual patient should recognize that other factors are often frequent causes of postoperative nerve injury. In the last decade, knowledge of contributing factors of postoperative nerve injury has advanced significantly. The etiology, incidence, diagnosis, management, and prevention of neurological complications of peripheral block will be discussed. However, prevention has to be the guiding principle because of the very limited capacity of the nervous system for either repair or recovery.
Peripheral Nerve Injury
Injury to peripheral nerves is not quite as catastrophic as to the neuraxis, but can still result in considerable patient morbidity. Peripheral nerves can be injured by direct trauma, chemical neurotoxicity , ischemia, compression, infection, and by stretching. Many of these may affect the surgical patient without involving regional techniques, but the greatest concerns here are direct needle trauma and intraneural injection .
Three layers of tissue closely invest peripheral nerves: the epineurium, perineurium, and endoneurium. Although needle placement or injection within any of these layers is undesirable, recent evidence suggests that it is injection within the perineurium that is most likely to cause significant injury . The epineurium is an external enveloping layer surrounding the fascicles and connective tissue within the nerve. The perineurium is a multilayered epithelial sheath that surrounds individual or groups of fascicles. Needle placement within the fascicle can cause injury directly or through pressure-related ischemia after injection .
Short bevel needles are purportedly less likely to injure nerves than long bevel needles ; however, there is little epidemiological evidence to support this assertion. What is more certain is that the injury is less severe if the needle is inserted with the bevel “parallel” to the line of the axons, rather than at right angles when fascicles will be transected rather than split longitudinally . Neurotmesis, complete disruption of axon and myelin sheath, is far more likely to cause permanent injury than neuropraxis due to compression or stretch because the myelin sheath is preserved.
The use of ultrasound guidance should, theoretically, reduce the risk of direct needle trauma to the nerve. However, because of the relatively low incidence of complications from peripheral nerve blocks, studies have not been able to establish a benefit of ultrasound guidance compared to nerve stimulation alone in terms of nerve injury [8, 9].
The peripheral nerves are reasonably well protected from chemical injury, but solutions containing preservatives and their accidental contamination are best avoided. There is no evidence to suggest that local anesthetics, in clinically used concentrations, have any more adverse effect on peripheral nerves than they do on the neuraxis. However, occasional laboratory studies, such as the observation that local anesthetics have toxic effects on cell cultures , do raise questions. Such “toxicity” is related to both concentration and duration of exposure, but the implications of these findings to man are unclear given the large numbers of patients who receive the drugs annually. However, it would seem prudent to use the lowest concentration of drug possible to achieve the desired effect, especially when an infusion technique is used .
Local anesthetic adjuvants (other than epinephrine) are used to prolong the duration of single injection techniques. Multiple agents have been studied including clonidine, dexmedetomidine, midazolam, neostigmine, and dexamethasone. Electron micrography of isolated rat nerves demonstrates histologic evidence of damage associated with some additives when used alone or in combination . Further, most have limited prolonging effects at the expense of unwanted side effects such as excessive sedation, hypotension, and bradycardia with clonidine . Dexamethasone alone (667 μg/mL) combined with ropivacaine (0.25 %) appears to have minimal issues with neurotoxicity in rats , and minimal side effects with the greatest effect on prolonging block duration in human trials . Combining multiple perineural adjuvants enhances toxicity in rat neuronal cell cultures . Other important factors to consider include the preparation of the adjuvant. Specifically, multidose preparations often contain preservatives that can be neurotoxic. While sodium bisulfite appears to be fairly neutral, benzyl alcohol is a potent neurotoxin. Furthermore, use of perineural adjuvants is “off-label” and practitioners should carefully weigh the risks and benefits of their use. Finally, specifically regarding dexamethasone and dexmedetomidine, there is emerging evidence suggesting that intravenous administration of these drugs may also prolong analgesic duration, without the safety concerns of perineural injections [15, 16].
Most local anesthetic drugs have a vasoconstrictor effect at low concentrations, but there are no data to suggest that this contributes to injury, even when a solution containing clinical concentrations of epinephrine is used. Many upper and lower limb blocks will be performed in patients whose surgery will be performed under tourniquet and they can have a much more profound effect especially if poorly applied, so that there is mechanical distortion or excessive pressure. Compression due to hematoma or abscess is possible, these lesions having the same risk factors as after central blocks, but they tend to spread more readily through the peripheral tissues, so high pressures are not generated.
It has been argued, in the context of nerve entrapment syndromes , that patients with a pre-existing neurological problem are more likely to suffer injury if a second, more distant insult occurs: the “double crush” phenomenon. However, the relevance of this to the risk of a patient with peripheral nerve disease (e.g., diabetic neuropathy) suffering injury from a peripheral block is unclear. Peripheral nerve injury requires disruption of the perineurium and, in practice, this is very difficult to accomplish; recent experience with ultrasound indicates that nerves are difficult to impale, tending to move away from approaching needles. Even if a nerve is pierced, it is difficult to maintain the needle within the nerve, most of the solution leaking out of the epineurium after a small volume has been injected .
Temporary sensory or motor impairment may occur in nearly 3% of patients after a peripheral nerve block, but most symptoms resolve within days or weeks of surgery . Permanent injury is more rare; Auroy and colleagues reported this in an average of only 2.4 instances per 10,000 blocks . There is quite marked variation in the incidence of both temporary and permanent syndromes, with popliteal block having the greatest incidence of permanent injury (31.5 per 10,000 patients). Risk factors can be related to patient, surgical, and anesthetic factors. Patient factors include pre-existing neurological disorder, diabetes mellitus, extremes of obesity, male gender, and extremes of age. Surgical factors include direct surgical trauma, compressive dressings, tourniquet pressure and/or time, compression by hematoma or abscess, and poor patient positioning .
Diagnosis and Management
Symptoms suggestive of postoperative neuropathy (persisting sensory or motor symptoms beyond 48 h after last dose of local anesthetic) should prompt a full history to identify any predisposing risk factor or causative element in the anesthetic or surgical technique, plus a detailed neurological examination to define the problem precisely. As noted above, most injuries have an excellent prognosis, but the symptoms of even a minor deficit can be distressing, so considerable patient reassurance may be required. More severe deficits, or those which fail to resolve within 2–3 weeks, should be referred to a neurologist or neurosurgeon for further investigation and management. However, it is important that the anesthetist is fully involved in this process because surgical colleagues (and patients) can, quite correctly, become irritated if the anesthetist fails to follow up such problems. Conversely, the anesthetist (or department) taking this seriously will build a relationship between colleagues that will, in turn, facilitate the practice of regional anesthesia and future referral if necessary.
Having made that point it is important that the evaluation of any postoperative neurological deficit includes a search for factors unrelated to anesthesia technique. The incidence of nerve injury arising during surgery is several orders of magnitude greater than during regional anesthesia, so this must be considered before assigning responsibility to any one technique or practitioner. For example, the risk of nerve injury during total hip arthroplasty is as high as 1–2 % , and similar estimates are quoted for other orthopedic procedures. Surgery may predispose to nerve injury through direct trauma or stretching, tourniquet pressure, compressive dressings, hematoma or abscess formation, and improper patient positioning during surgery. However, some of these are considered to be the joint responsibility of surgeon and anesthetist .
As with central blocks, thorough preoperative assessment and careful attention to the detail of block technique are essential in the prevention of neurological injury after peripheral blocks. It also seems advisable to use the lowest concentration of local anesthetic possible, particularly when infusions are used for postoperative analgesia.
More specifically, evidence suggests that a major factor predisposing to peripheral nerve injury is intraneural (or more accurately intrafascicular) needle placement or injection. Traditional teaching states that both of these produce severe pain and should therefore be easily detectable, so that needle position can be corrected if it occurs. However, recent studies suggest that neither intraneural needle placement nor injection is always painful, with ultrasound suggesting that they have been performed in an unrecognized manner for many years. Robards and colleagues  found that when typical final currents (0.2–0.4 mA) were achieved for popliteal nerve block the needle tip was intraneural in 100 % of cases. Similarly, Macaire and colleagues , using nerve stimulation for median nerve block at the wrist, identified that the needle tip was intraneural on several occasions, with this placement explaining the faster block onset seen in their nerve stimulation group .
Such observations may have led to the suggestion that intentional intraneural injection might optimize success without invariably leading to injury . However, a paucity of evidence remains, even with from animal models, to support deliberate intraneural injection . Further, it is difficult to avoid the conclusion that the high incidence of neuropathy after popliteal block  is directly related to the ease with which intraneural needle placement occurs during this technique . Until there is much evidence to the contrary, intraneural needle placement and solution injection are practices to be avoided. Recent evidence suggests that several factors, apart from a gentle technique and inserting the needle with the bevel parallel to the nerve, may reduce the likelihood of severe injury, all of them aimed at preventing accidental intraneural injection (Table 11.3).
Factors which may indicate intraneural needle placement, and actions to reduce the risk of subsequent peripheral nerve injury
Pain on needle placement or injection
Withdraw needle, stop injection, and redirect needle
High injection pressure
Withdraw needle until pressure to inject decreases 
Current threshold <0.4 mA
Withdraw needle until threshold >0.4 mA 
Sonographic visualization of nerve expansion
Stop injecting. Redirect needle 
High electrical impedance
Withdraw needle until impedance decreases 
Many of the warning symptoms of direct nerve contact outlined above require a conscious, or only mildly sedated, patient to report them, and this would suggest that blocks should not be performed after administration of heavy sedation or anesthesia. However, this is a matter of some controversy .
Local Anesthetic Toxicity
A rare complication but nonetheless possible across all peripheral nerve blocks is the potential for local anesthetic systemic toxicity (LAST ) . Barrington et al. found an incidence of LAST of 0.98 per 1000 blocks . This was similar to the incidence reported by Auroy of 0.8 per 1000 blocks . The use of ultrasound guidance further reduces this risk. Orebaugh et al. reported no incidences of LAST in 2146 ultrasound-guided blocks, compared to 5 incidences of LAST in 3290 nerve stimulator (non-ultrasound guided) nerve blocks (1.5 per 1000 blocks) . Similarly, Sites et al. reported an incidence of 0.08 per 1000 of LAST in ultrasound-guided peripheral nerve blocks  and, when Barrington et al. analyzed complications based on nerve localization technique, they found the incidence of LAST when ultrasound guidance was used was only 0.8 per 1000 blocks compared to 1.2 per 1000 blocks with nerve stimulator localization .
There are multiple causative factors including rapid uptake from highly vascularized tissues, to excessive dosing, to inadvertent intravascular injection. If block needles traverse veins, unknown to the practitioner due to compression, larger conduits for local anesthetic absorption or direct intravascular injection may result. Practitioners should take care to intermittently release pressure on the probe and scan for venous structures, inject in incremental doses, and observe local anesthetic expansion. Many practitioners commonly add epinephrine to local anesthetic solutions to provide an earlier signal (from increasing heart rate) of intravascular injection .
Upper Extremity Block Procedures
Block Site Specific Complications
Interscalene brachial plexus block (ISB) targets the nerve roots of the brachial plexus and is appropriate for shoulder/proximal arm procedures. Most complications are of a self-limited/benign nature lasting the duration of the local anesthetic. These include: (1) Hoarseness due to ipsilateral recurrent laryngeal nerve block and (2) Horner’s syndrome due to ipsilateral stellate ganglion block.
Anesthesiologists should be aware of the possibility of injury to the spinal accessory nerve, long thoracic, or dorsal scapular when performing ISB by the posterior approach as these nerves course through the middle scalene muscle. Case reports of permanent injury due to inadvertent transection en-route to the brachial plexus have been described .
Potentially more severe is block of the ipsilateral phrenic nerve that can compromise pulmonary function by approximately 25 %. ISB should therefore be avoided in patients who would not tolerate such a decrease. Volumes greater than 10 ml result in 100 % ipsilateral phrenic nerve block , while volumes as low as 5 ml, still producing reliable analgesia, reduce the incidence of phrenic nerve block by about 50 % [30, 31].
There are other rare case reports of more devastating complications including epidural or intrathecal spread of local anesthetic causing significant harm. These were due to injection of excessive local anesthetic volume and migration of an in situ continuous catheter, respectively.
Equally rare is CNS toxicity from injection into the vertebral artery and pneumothorax. However due to their rarity ultrasound guidance may not decrease the incidence of these complications .
Supraclavicular brachial plexus block (SCB) targets the brachial plexus at the level of the trunks. It had fallen out of favor due to risks of pneumothorax with landmark/nerve stimulation guided techniques, but has experienced a recent resurgence since the advent of ultrasound. While the theoretical risks of phrenic nerve block (~50 %), Horner’s syndrome, and intravascular injection persist, large case series demonstrate an incidence of <1 % . Despite ultrasound guidance, pneumothorax still remains a potential complication causing significant morbidity [33, 34].
Infraclavicular brachial plexus block (ICB) targets the brachial plexus at the level of the cords. There is minimal risk of phrenic nerve palsy and pneumothorax. The risk of intravascular injection is present as the inferior cord is often in close proximity to the axillary vein. However, previous case series have demonstrated a very low complication rate (<1 %) .
Complications associated with axillary brachial plexus block (AXB) , except for LAST , are fairly minor and self-limited. The potential for cephalad spread to block unwanted neural elements is exceedingly low. More common are hematoma due to the close proximity of nerves to the axillary artery and vein.
Lower Extremity Block Procedures
Block Site Specific Complications
Lumbar Plexus/Psoas Compartment
The lumbar plexus consists of T12–L4 spinal nerves. Soon after exiting their respective intervertebral foraminas, these spinal nerves form the lumbar plexus within the psoas muscle, anterior to the transverse processes. Due to its location, lumbar plexus block is often referred to as psoas compartment block. Terminal branches arising from the lumbar plexus (ilioinguinal, iliohypogastric, genitofemoral, lateral femoral cutaneous, femoral, obturator) have major contributions to the sensory and motor functions in the groin, hip, and thigh. Because injection of local anesthetic at this single location can block multiple branches supplying the lower limb, lumbar plexus block is the preferred peripheral nerve block for some practitioners as their first choice for lower limb analgesia. However, due to the deep location of the lumbar plexus and its close proximity to other important structures, there is more potential for adverse events compared to other peripheral nerve blocks (Table 11.4).
Reported complications from lumbar plexus block in the literature
Trauma to kidney
Epidural/spinal spread of local anesthetic
In the large survey from France by Auroy et al., lumbar plexus blocks were the only peripheral nerve block technique linked to cardiac and respiratory arrests out of more than 50,000 procedures . The only death reported in the peripheral nerve block group was after a lumbar plexus block. Overall the authors estimated the incidence of serious complications after lumbar plexus block at 80/10,000 . In all these reported cases of serious complications, high dermatomal level and bilateral mydriasis were observed, suggesting intrathecal spread of local anesthetic. Other cases of intrathecal local anesthetic injection during lumbar plexus block have subsequently been reported . Epidural spread of local anesthetic from lumbar plexus block can also cause significant complications. In a prospective, multicenter case series, Capdevila et al.  reported three cases of severe hypotension out of 20 lumbar plexus blocks. The authors attributed the hemodynamic instability to unintended epidural anesthesia .
Misplacement of needle during lumbar plexus block can cause other complications such as renal injury/hematoma and intraperitoneal injections . Similar to other peripheral nerve blocks, the lumbar plexus block is not immune to post-block neurologic symptoms and seizures resulting from intravascular injections. There are also case reports in the literature of psoas abscesses after lumbar plexus blocks .
Bleeding after lumbar plexus block is a bigger concern than other peripheral nerve blocks due to the deep needle penetration required and the vascularity in the area. Retroperitoneal hematoma has been reported for a patient receiving lumbar plexus block less than 24 h after low molecular weight heparin . The American Society of Regional Anesthesia and Pain Medicine has subsequently published guidelines for regional anesthesia and anticoagulation . The guidelines distinguished lumbar plexus block from more superficial peripheral nerve blocks in that bleeding for this “deep” block carries more significant morbidity. As such it was suggested that the same precaution for anticoagulation and neuraxial blocks should apply to lumbar plexus blocks as well. However, evidence suggests that avoiding anticoagulation at the time of needle insertion is not enough to eliminate retroperitoneal bleeding after lumbar plexus block .
Femoral nerve block targets the femoral nerve at the level of the femoral crease as it exits below the inguinal ligament, lateral to the femoral artery. The proximity of the nerve to major vessels increases the risk of vascular puncture and local anesthetic toxicity. However occurrence is exceptionally rare, in particular with the use of ultrasound guidance [9, 27].
There have, however, been some case reports of bleeding and major hematoma formation with the use of femoral nerve catheters in patients on prophylactic low molecular weight heparin therapy . The location of femoral nerve blockade also renders continuous catheters prone to bacterial colonization (28.7–57 %); however, the incidence of bacterial complications remains small (0.01–0.07 %) [39, 45].