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Neurologic complications of neuraxial and peripheral blockade

From the Department of Anesthesiology, Mayo Medical School, Mayo Clinic, Rochester, Minnesota, USA.

Address correspondence to: Dr. Terese Horlocker, Department of Anesthesiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905 USA. Phone: 507-284-9694; Fax: 507-284-0120; E-mail: horlocker.terese{at}mayo.edu

PERIOPERATIVE nerve injuries may be divided into two categories: those which are unrelated to the regional anesthetic technique (but coincide temporally) and those that are a direct result of the regional anesthetic. Risk factors contributing to neurologic deficit after regional anesthesia include neural ischemia, traumatic injury to the nerves during needle or catheter placement, infection, and choice of local anesthetic solution.^1–3 However, postoperative neurologic injury due to pressure from improper patient positioning or from tightly applied casts or surgical dressings, as well as surgical trauma are often attributed to the regional anesthetic. Patient factors such as body habitus or a preexisting neurologic dysfunction may also contribute. Prevention of complications, along with early diagnosis and treatment are important in the management of regional anesthetic risks.

Incidence and etiology of neurologic complications

A prospective survey in France recently evaluated the incidence and characteristics of serious complications related to regional anesthesia.¹ A total of 103,730 regional anesthetics, including 40,640 spinal and 30,413 epidural anesthetics, 21,278 peripheral nerve blocks, and 11,229 iv regional anesthetics, were performed over a five-month period. The incidence of cardiac arrest and neurologic complications was significantly higher after spinal anesthesia than other types of regional procedures (Table I). Neurologic complications related to the regional anesthetic technique occurred in 34 patients; recovery was complete within three months in 19 of 34 patients. In 12 of 19 cases of radiculopathy after spinal anesthesia, and in all cases of radiculopathy after epidural or peripheral block, needle placement was associated with either paresthesia during needle insertion, or pain with injection. In all cases, the radiculopathy had the same topography as the associated paresthesia. The authors concluded that needle trauma and local anesthetic neurotoxicity were the etiologies of most neurologic complications.

Nerve injury from needle and catheter placement

Direct needle- or catheter-induced trauma rarely results in permanent or disabling neurologic injury. A recent retrospective study of 4,767 spinal anesthetics noted the presence of a paresthesia during needle placement in 298 (6.3%) of patients. Importantly, four of the six patients with a persistent paresthesia postoperatively complained of a paresthesia during needle placement, identifying elicitation of a paresthesia as a risk factor for a persistent paresthesia.⁵ Currently, it is unknown whether clinicians should abandon the procedure if a paresthesia is elicited (rather than replacing the needle), in an effort to decrease the risk of nerve injury during neuraxial block.

Conversely, many anesthesiologists intentionally elicit a paresthesia during the performance of peripheral regional techniques. Although the elicitation of a paresthesia may represent direct needle trauma and increase the risk of persistent paresthesia associated with regional anesthesia, there are no clinical studies that definitively either prove or refute the theory.^6–8 Selander et al.⁶ reported a higher incidence of postoperative nerve injury in patients where a paresthesia was sought during axillary block (2.8%) compared to those undergoing a perivascular technique (0.8%). However, the difference was not significant. Importantly, 40% of patients in the perivascular group reported unintentional paresthesias during the procedure, demonstrating the difficulty with standardization of technique and analysis of neural injury. Postoperative neurologic deficits ranged from slight hypersensitivity to severe paresis, and persisted from two weeks to greater than one year. In a prospective study utilizing a variety of regional anesthetic approaches including paresthesia, transarterial and nerve stimulator techniques, Urban and Urquhart⁷ noted that mild paresthesias were common the day after surgery, occurring after 9% of interscalene blocks and after 19% of axillary blocks. At two weeks the incidence had decreased significantly, with near complete resolution noted at four weeks. Stan et al.⁸ reported a 0.2% incidence of neurologic complications after axillary blocks performed with the transarterial approach. However, vascular complications such as transient arterial spasm, unintentional vascular injection and hematoma formation occurred in 1.4% of patients. Theoretically, localization of neural structures with a nerve stimulator would allow a high success rate without increasing the risk of neurologic complications, but this has not been formally evaluated. Indeed, serious neurologic injury has been reported following uneventful brachial plexus block using a nerve stimulator technique.⁹ Currently, no compelling evidence exists to endorse a single technique as superior with respect to success rate or incidence of complications. Needle gauge, type (short vs long bevel), and bevel configuration may also influence the degree of nerve injury, although the findings are conflicting and there are no confirmatory human studies.^10,11

The passage and presence of an indwelling catheter into the subarachnoid or epidural spaces or a peripheral nerve sheath presents an additional source of direct trauma. Laboratory studies have demonstrated demyelination and inflammation adjacent to the catheter tract in both the spinal root and cord of rats following placement of indwelling subarachnoid catheters. The use of a catheter may indirectly contribute to neurologic injury. Poor mixing resulting from very slow injection rates through spinal microcatheters may increase the risk of developing high concentrations of hyperbaric local anesthetics in dependent areas of the spinal canal. This is the presumed mechanism of cauda equina syndrome following continuous spinal anesthesia.¹²

The risk of neurologic complications resulting from brachial plexus or peripheral nerve catheters remains undefined. While difficulty during catheter insertion may lead to vessel puncture, tissue trauma and bleeding, significant complications are uncommon and permanent sequelae are rare. The largest series of continuous brachial plexus block included 597 patients.¹³ The authors reported toxic reactions in 17 (2.9%) cases, nerve injury in three (0.5%) cases and one case of axillary hematoma in a heparinized patient which compromised circulation to the upper extremity.

Local anesthetic toxicity

Although most local anesthetics administered in clinical concentrations and doses do not cause nerve damage, prolonged exposure, high dose and/or high concentrations of local anesthetic solutions may result in permanent neurologic deficits. There is both laboratory and clinical evidence that local anesthetic solutions are potentially neurotoxic and that the neurotoxicity varies among local anesthetic solutions.^3,14,15 For example, cauda equina syndrome has been reported after single dose and continuous spinal anesthesia, intrathecal injection during intended epidural anesthesia, and repeated intrathecal injection after failed spinal block with lidocaine.^1,2,16 Presumably, injection (or reinjection) results in high concentrations of local anesthetic within a restricted area of the intrathecal space and causes neurotoxic injury. Attention to patient positioning, total local anesthetic dose and careful neurologic examination (evaluating for preferential sacral block) will assist in the decision to inject additional local anesthetic in the face of a patchy or failed block.

Differences in neurotoxicity are dependent on pKa, lipid solubility, protein binding and potency. In histopathologic, electrophysiologic, and neuronal cell models, lidocaine and tetracaine appear to have a greater potential for neurotoxicity than bupivacaine at clinically relevant concentrations.¹⁵ Additives such as epinephrine and bicarbonate may also affect neurotoxicity. Addition of 5 µg•ml^–1 of epinephrine increases the toxicity of both lidocaine and bupivacaine. The presence of a preexisting neurologic condition may predispose the nerve to the neurotoxic effects of local anesthetics.¹⁴

Transient neurologic symptoms
Transient neurologic symptoms (TNS) were first formally described in 1993. Multiple laboratory and clinical studies have been performed in an attempt to define the etiology, clinical significance, and risk factors associated with TNS. The incidence has ranged between 0% and 37%, and is dependent on anesthetic, surgical and, possibly, undefined patient factors. A large multicentre epidemiologic study involving 1863 patients was recently performed to identify potential risk factors for TNS.¹⁷ The incidence of TNS with lidocaine (11.9%) was significantly higher than that with tetracaine (1.6%) or bupivacaine (1.3%). The pain was described as severe in 30% of patients and resolved within a week in over 90% of cases. Outpatient status, obesity and lithotomy position also increase the risk of TNS for patients who receive lidocaine. This suggests that the risk of TNS is high among outpatients in the lithotomy position (24.3%) and low for inpatients having surgery in positions other than lithotomy (3.1%). However, these variables were not risk factors with tetracaine or bupivacaine. The authors also reported that neither gender, age, history of back pain or neurologic disorder, lidocaine dose/concentration, spinal needle/type/size, aperture direction, nor addition of epinephrine increased the risk of TNS.

The clinical significance of TNS is unknown. While many anesthesiologists believe that the reversible radicular pain is on one side of a continuum leading to irreversible cauda equina syndrome, there are currently no data to support this concept. It is important to distinguish between factors associated with serious neurologic complications, such as cauda equina syndrome, and transient symptoms when making recommendations for the clinical management of patients. For example, increasing the concentration/dose of lidocaine and adding epinephrine increases the risk of irreversible neurotoxicity, but has little effect on the risk of TNS. Therefore, the clinician must determine the appropriate intrathecal solution, including adjuvants, given the surgical duration and intraoperative position for each individual patient.

Neural ischemia

The blood supply to the spinal cord is precarious due to the relatively large distances between the radicular vessels. Systemic hypotension or localized vascular insufficiency with or without a spinal anesthetic may produce spinal cord ischemia resulting in flaccid paralysis of the lower extremities, or anterior spinal artery syndrome. Characteristics of anterior spinal artery syndrome, spinal abscess, and spinal hematoma are reported in Table II. The addition of epinephrine or phenylephrine theoretically may produce local cord ischemia. However, most animal studies fail to show a significant decrease in spinal cord blood flow¹⁵ and large studies have failed to identify the use of vasoconstrictors as a risk factor for temporary or permanent deficits. Most presumed cases of vasoconstrictor-induced neurologic deficits have been reported as single case reports, often with several other risk factors present.^1,18

Hemorrhagic complications (spinal hematoma)

Although hemorrhagic complications can occur after virtually all regional anesthetic techniques, bleeding into the spinal canal is perhaps the most serious hemorrhagic complication associated with regional anesthesia because the spinal canal is a concealed and nonexpandable space. The reader is referred to The Consensus Statements on Neuraxial Anesthesia and Anticoagulation published by the American Society of Regional Anesthesia for a more detailed discussion on regional anesthetic management of the anticoagulated patient.^20–24

The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown; however, the incidence cited in the literature is estimated to be less than one in 150,000 epidural and less than one in 220,000 spinal anesthetics. Vandermeulen et al.²⁵ reported 61 cases of spinal hematoma associated with epidural or spinal anesthesia. In 42 of the 61 patients (68%), there was evidence of hemostatic abnormality; while in 25% of patients, the needle or catheter insertions were difficult or bloody. Thus, in 53 of the 61 cases (87%), either a clotting abnormality or needle placement difficulty was present. A spinal anesthetic was implicated in 15 patients. The remaining 46 patients received an epidural anesthetic, including 32 patients with an indwelling catheter. In 15 of these 32 patients, the spinal hematoma occurred immediately after the removal of the epidural catheter. Neurologic compromise presented as progression of sensory of motor block or bowel/bladder dysfunction, not severe radicular back pain. Importantly, although only 48% of patient had partial or good neurologic recovery, spinal cord ischemia tended to be reversible in patients who underwent laminectomy within eight hours of onset of neurologic dysfunction Regional technique also influenced risk.

The decision to perform neuraxial anesthesia and the timing of catheter removal in a patient receiving anticoagulants perioperatively should be made on an individual basis, weighing the small, though definite risk of spinal hematoma with the benefits of regional anesthesia for a specific patient. It is generally accepted that except in extraordinary circumstances, neuraxial blockade should be avoided in patients who have known coagulopathies, have significant thrombocytopenia, or have received thrombolytic therapy within the previous 24 hr.²⁴ The patient's coagulation status should be optimized at the time of spinal or epidural needle/catheter placement, and the level of anticoagulation must be carefully monitored during the period of epidural catheterization (Table III). Prolonged therapeutic anticoagulation appears to increase risk of spinal hematoma formation, especially if combined with other anticoagulants or thrombolytics.^4,20,21 Indwelling catheters should be not removed in the presence of therapeutic anticoagulation, as this appears to significantly increase the risk of spinal hematoma. Patients should be closely monitored in the perioperative period for early signs of cord compression such as severe back pain, progression of numbness or weakness, and bowel and bladder dysfunction. A delay in diagnosis may lead to irreversible cord ischemia.

Infectious complications

Infection can complicate any regional technique, but are of greatest concern when infection occurs within the spinal canal. The infectious source can be exogenous due to contaminated equipment or medication, or endogenous secondary to a bacterial source in the patient seeding to the remote site of needle or catheter insertion. In addition, indwelling catheters may be colonized from a superficial site and subsequently serve as a wick for spread of infection from the skin to the epidural space (or other neural sheath). An alternative mechanism may be contamination with viridans streptococci from the operator's buccal mucosa.

Although individual cases have been reported in the literature, serious central neural infections such as arachnoiditis, meningitis, and abscess following spinal or epidural anesthesia are rare. In a combined series of more than 65,000 spinal anesthetics, there were only three cases of meningitis. A similar review of approximately 50,000 epidural anesthetics failed to disclose a single epidural or intrathecal infection.²⁶ Despite the apparent low risk of central nervous system infection following regional anesthesia, anesthesiologists have long considered sepsis to be a relative contraindication to the administration of spinal or epidural anesthesia. This impression is based largely on anecdotal reports and conflicting laboratory and clinical investigations.

Meningitis after dural puncture
In a recent (and clinically relevant) study, Carp and Bailey²⁷ investigated the association between meningitis and dural puncture in bacteremic rats. Twelve of 40 rats subjected to cisternal puncture with a 26-gauge needle during E. coli bacteremia subsequently developed meningitis. In addition, bacteremic animals not undergoing dural puncture, as well as animals undergoing dural puncture in the absence of bacteremia did not develop meningitis. Meningitis occurred only in animals with a blood culture result of >50 colony forming units•ml^–1 at the time of dural puncture. Treatment of a group of bacteremic rats with a single dose of gentamycin immediately prior to cisternal puncture apparently eliminated the risk of meningitis, as none of these animals developed infection. This study demonstrates that dural puncture in the presence of bacteremia is associated with the development of meningitis in rats, and that antibiotic treatment before dural puncture reduces this risk.

Epidural abscess after epidural anesthesia
Several studies have specifically examined the risk of epidural abscess in patients receiving epidural anesthesia and/or analgesia. The safety of epidural analgesia in 75 patients admitted to the intensive care unit was prospectively evaluated by Darchy et al.²⁸ There were no epidural abscesses. However, five of nine patients with positive cultures of the catheter insertion site also had positive catheter tip cultures; Staphylococcus epidermidis was the most commonly cultured microorganism. Local infection of the catheter site was treated with catheter removal, but antibiotic therapy was not specifically prescribed. The authors noted that the presence of both erythema and local discharge is a strong predictor of local and epidural catheter infection.

Chronic epidural catheterization in cancer patients is also a potential risk for epidural infection. Du Pen et al.²⁹ studied 350 patients in whom permanent (tunnelled) epidural catheters were placed. The authors examined three areas of the catheter track for evidence of infection: exit site, superficial catheter track, and epidural space. The rate of epidural and deep track catheter-related infections was one in every 1702 days of catheter use. Bacteria cultured were most frequently skin flora. All 19 patients with deep infections were treated with catheter removal and antibiotics; none required surgical decompression or debridement. Catheters were replaced in 15 of the 19 patients who requested them after treatment with no recurrent infections.

Epidural anesthesia and analgesia in a patient with a known systemic or localized infection (such as removal of infected artificial joint components) remains controversial. It is difficult to determine the actual risk of epidural abscess in patients with chronic localized infections who undergo epidural catheter placement due to the small number of patients studied and the rarity of this complication. Therefore, the clinician must maintain vigilance in neurologic monitoring to assure early recognition and treatment (Table II). As with spinal hematoma, neurologic recovery is dependent on the duration of the deficit and the severity of neurologic impairment before treatment.

Patients with preexisting neurologic disorders

Patients with preexisting neurologic disease present a unique challenge to the anesthesiologist. The presence of preexisting deficits, signifying chronic neural compromise, theoretically places these patients at increased risk for further neurologic injury. The presumed mechanism is a "double crush" of the nerve at two locations resulting in a nerve injury of clinical significance. The double crush concept suggests that nerve damage caused by traumatic needle placement/local anesthetic toxicity during the performance of a regional anesthetic may worsen neurologic outcome in the presence of an additional patient factor or surgical injury. Progressive neurologic diseases may also coincidentally worsen perioperatively, independent of the anesthetic method. If a regional anesthetic is indicated or requested, the patient's preoperative neurologic examination should be formally documented and the patient must be made aware of the possible progression of the underlying disease process.

Regional anesthetic management is based on the theory that patients with preoperative neurologic deficits may undergo further nerve damage more readily from needle or catheter placement, local anesthetic systemic toxicity, and vasopressor-induced neural ischemia. Dilute or less potent local anesthetic solutions should be used when feasible to decrease the risk of local anesthetic toxicity. The potential risk of vasoconstrictor-induced nerve ischemia must be weighed against the advantages of improved quality and duration of block. Because epinephrine and phenylephrine also prolong the block and therefore neural exposure to local anesthetics, the appropriate concentration and dose of local anesthetic solutions must be thoughtfully considered.

Diagnosis and evaluation of neurologic complications

It is imperative that all preoperative neurologic deficits are documented to allow early diagnosis of new or worsening neurologic dysfunction postoperatively. Postoperative sensory or motor deficits must also be distinguished from residual (prolonged) local anesthetic effect. Imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI) are useful in identifying infectious and inflammatory processes as well as expanding hematomas.

Although most neurologic complications resolve completely within several days or weeks, significant neural injuries necessitate neurologic consultation to document the degree of involvement and coordinate further work-up. Neurophysiologic testing, such as nerve conduction studies, evoked potentials, and electomyography (EMG) are often useful in establishing a diagnosis and prognosis. A reduced amplitude in evoked responses indicates axonal loss, while increased latency occurs in the presence of demyelination. Fibrillation potentials are present during active axonal degeneration. They appear two to three weeks after injury and are maximal at one to three months (Table IV). Because of the decreased number of axons present in patients with neurologic conditions, there is a reduction in neuron recruitment during voluntary effort. The degree of reduction parallels the severity of the disorder. Despite many applications, nerve conduction studies have several limitations. Typically only the large sensory and motor nerve fibers are evaluated; dysfunction of small unmyelinated fibers would not be detected. In addition, abnormalities will not be noted on EMG immediately after injury, but rather require several weeks to evolve. Although it is often recommended to wait until evidence of denervation has appeared before performing neurophysiologic testing, a baseline study (including evaluation of the contralateral extremity) would be helpful in ruling out underlying pathology or a preexisting condition.

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