Secondary Logo

Share this article on:

The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015

Neal, Joseph M. MD*; Barrington, Michael J. MBBS, FANZCA, PhD; Brull, Richard MD; Hadzic, Admir MD§; Hebl, James R. MD; Horlocker, Terese T. MD; Huntoon, Marc A. MD**; Kopp, Sandra L. MD; Rathmell, James P. MD††; Watson, James C. MD

Regional Anesthesia and Pain Medicine: September/October 2015 - Volume 40 - Issue 5 - p 401–430
doi: 10.1097/AAP.0000000000000286
SPECIAL ARTICLES

Neurologic injury associated with regional anesthetic or pain medicine procedures is extremely rare. The Second American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine focuses on those complications associated with mechanical, ischemic, or neurotoxic injury of the neuraxis or peripheral nervous system. As with the first advisory, this iteration does not focus on hemorrhagic or infectious complications or local anesthetic systemic toxicity, all of which are the subjects of separate practice advisories. The current advisory offers recommendations to aid in the understanding and potential limitation of rare neurologic complications that may arise during the practice of regional anesthesia and/or interventional pain medicine.

What’s New The Second American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine updates information that was originally presented at the Society’s first open forum on this subject (2005) and published in 2008. Portions of the second advisory were presented in an open forum (2012) and are herein updated, with attention to those topics subject to evolving knowledge since the first and second advisory conferences. The second advisory briefly summarizes recommendations that have not changed substantially. New to this iteration of the advisory is information related to the risk of nerve injury inherent to common orthopedic surgical procedures. Recommendations are expanded regarding the preventive role of various monitoring technologies such as ultrasound guidance and injection pressure monitoring. New clinical recommendations focus on emerging concerns including spinal stenosis and vertebral canal pathologies, blood pressure management during neuraxial anesthesia, administering blocks in anesthetized or deeply sedated patients, patients with preexisting neurologic disease, and inflammatory neuropathies. An updated diagnostic and treatment algorithm is presented.

From the *Departments of Anesthesiology and Neurology, Virginia Mason Medical Center, Seattle, WA; †University of Melbourne, Melbourne, Victoria, Australia; ‡University of Toronto, Toronto, Ontario, Canada; §Ziekenhuis Oost-Limburg, Genk, Belgium; ∥Mayo Clinic College of Medicine, Rochester, MN; **Vanderbilt School of Medicine, Nashville, TN; and ††Harvard Medical School; Boston, MA.

Address correspondence to: Joseph M. Neal, MD, 1100 Ninth Ave (B2-AN) Seattle, WA 98101 (e-mail: Joseph.Neal@virginiamason.org).

Accepted for publication June 3, 2015.

Portions of this article were presented as part of the American Society of Regional Anesthesia and Pain Medicine’s Second Practice Advisory on Neurological Complications in Regional Anesthesia and Pain Medicine, San Diego, California, March 16, 2012.

The American Society of Regional Anesthesia and Pain Medicine provided standard travel reimbursement for members of the advisory who presented this work in open forum as part of the Society’s 37th Annual Regional Anesthesiology and Acute Pain Medicine meeting in San Diego, California, March 16, 2012. No panelist was paid for participation in the practice advisory process.

Dr Hadzic receives royalty payments from BBraun Medical for the BSmart injection pressure monitoring device. No other author has a conflict of interest related to the subject matter of this article.

In 2005, the American Society of Regional Anesthesia and Pain Medicine (ASRA) convened a group of experts to develop a practice advisory on neurologic complications associated with regional anesthesia and pain medicine. That initiative resulted in a series of articles published in 2008.1–6 Consistent with ASRA’s commitment to update its practice advisories as new knowledge emerges, the Society convened its second practice advisory in 2012 with the same goal, “to provide information for practitioners of regional anesthesia and pain medicine regarding the etiology, differential diagnosis, prevention, and treatment of neurologic complications.”4 As before, the current practice advisory focuses on neurologic injuries apart from those caused by hemorrhagic or infectious complications or local anesthetic systemic toxicity, which are the subjects of other ASRA-sponsored practice advisories.7–9 This executive summary condenses findings and recommendations from subtopics of the second practice advisory, which reflects both the proceedings of the conference and interval updates. Practitioners are encouraged to read the supporting articles that accompany this summary; they contain the details on which individual recommendations are based.10–16

“Consistent with a recent editorial call to focus practice advisory and consensus conference updates on new material,17 most supporting articles for individual topics considered by this advisory are built on 2 components. First, to provide perspective, those topics and associated recommendations for which no substantially new knowledge has emerged are reviewed briefly. To provide consistency across time or when appropriate, text and especially recommendations are presented essentially verbatim from those of our original work. The second component focuses on topics that have significantly new information to add to our previous understanding and/or that we felt deserved more extensive discussion than was provided in the first iteration of this advisory.”13 Completely new to the second practice advisory is an in-depth presentation of baseline nerve injury risk inherent to common elective orthopedic surgical procedures.11,12,14 With the growth of registries and their impact on determining accurate and contemporary incidences of complications, the panel added expertise in large epidemiologic studies. Similarly, emerging concerns relating to various ischemia-related neuraxial injuries led to the addition of expert neuroanesthesiologists.

Back to Top | Article Outline

METHODS

The Second ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine was convened on March 16, 2012, at the Society’s 37th Annual Regional Anesthesiology and Acute Pain Medicine meeting in San Diego, California. The ASRA Continuing Medical Education Committee and Board of Directors approved the first and second advisories. Lead members of the advisory panel presented their summaries in a daylong open forum at the annual meeting. Those advisory panelists are listed as authors of this executive summary; additional writers of the individual supporting documents are recognized in the acknowledgments and as individual authors on their articles. Primary panelists were chosen based on their demonstrated expertise in various issues related to neurologic injury and/or guideline creation. As with our first practice advisory, “panelists received no compensation for their contributions nor did any declare a conflict of interest pertinent to the topic” (Dr Hadzic’s disclosure appears in the attributions). Panelists were charged with performing an extensive review of the literature, summarizing and presenting their findings at the conference, and producing an article based on their scholarly work. During the San Diego conference, panelists and attendees discussed several issues related to neurologic injury in open forum format. All subsequent recommendations were reviewed and approved by members of the panel. Manuscripts were first peer reviewed internally by at least 3 members of the advisory panel and subsequently peer reviewed externally using this journal’s standard peer review process.4

Individual supporting articles10–16 describe the specific search methodology used to research that topic. In general, standard search engines and cross-referenced citations provided the literature basis for the updated material contained within this review.

As paraphrased from our 2008 review, “The strength of scientific evidence that is used to arrive at these recommendations is not easily measured by traditional stratification methodologies such as the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.”18 We have used this methodology to rate the level of evidence wherever possible (Appendix 1). However, because of the extreme rarity of the specific complications that are addressed in this article, traditional methodologies such as randomized controlled trials or meta-analyses rarely exist and are unlikely to exist in the future. Our recommendations are therefore based on methodologies that are necessarily less robust, such as anatomic or pathophysiologic studies of human cadavers or animals, nonrandomized trials, retrospective series, case reports, and/or expert opinion. The grading of recommendations offered by this practice advisory has been modified from an American College of Cardiology/American Heart Association construct19 that classifies the strength of guidelines for perioperative cardiac evaluation3,13 (Appendix 2).

“Readers of this manuscript are reminded that practice advisories are created when data on a subject are limited or nonexistent. Advisories rely on limited clinical and animal data and, as such, the synthesis and interpretation of data by 1 group of experts may differ from conclusions by another set of equally qualified experts. Thus, practice advisories represent a level of recommendation that is less than that offered by standards or clinical practice guidelines.20 The recommendations contained herein do not define standard of care. They are not intended to replace clinical judgment as applied to a specific patient scenario. Importantly, in this imperfect setting of controversial topics, limited data, and bias inherent to expert opinion, the Panel consistently tended towards conservative recommendations. These recommendations are intended to encourage optimal patient care but cannot ensure the avoidance of adverse outcomes. As with any practice advisory recommendation, these are subject to revision as knowledge of specific complications advances.”4,13

Back to Top | Article Outline

INCIDENCES OF NEUROLOGICAL INJURY

The incidence of peripheral nerve injury (PNI) has remained stable in recent decades, despite the introduction of ultrasound guidance.21 The reported frequency of long-term neurologic symptoms after peripheral nerve block using ultrasound guidance22–24 is virtually identical to that reported a decade earlier when peripheral nerve stimulation (PNS) was the primary nerve localization tool.25,26 In both cases, the reported rate of long-term injury is in the 2 to 4 per 10,000 block range. Conversely, accumulating evidence suggests a rising incidence of some catastrophic neuraxial complications associated with regional anesthetic and interventional pain medicine procedures. Whether these observations signal an absolute increase in complication rates is unclear. The reported increase in neuraxial complications may reflect more robust registries and improved reporting mechanisms that allow capture of large population data from single countries and institutions and/or databases from health insurers or national quality assurance records.22,27–35 It is also possible that incidences have increased as practitioners extend the limits of neuraxial blockade to sicker, older, and frailer patients who are at an increased risk from their comorbidities. Furthermore, perioperative nerve injury incidence data pertinent to either peripheral or neuraxial injury can vary widely between reports for a myriad of reasons, including 1) definition of the complication, 2) duration of follow-up, 3) associated risk factors specific to the cohort studied, 4) robustness of data recording (eg, retrospective vs prospective; registries vs quality assurance databases vs insurance company records vs self-report; single institution vs continent-wide); and 5) discriminating the cause of injury (eg, anesthetic vs surgical vs patient vs a combination; transient vs permanent).

Back to Top | Article Outline

Incidence of Neuraxial Injury

Neuraxial complications are extremely rare, but when they occur, they often result in life-altering injuries. For instance, there were 127 serious complications in more than 1.7 million neuraxial anesthetics performed during the 1990s in Sweden; 85 (67%) of which resulted in permanent injury.28 The relative occurrence of complications from this report is presented in Table 1. From a medicolegal perspective, closed claims analysis shows that spinal hematomas are the most common cause of neuraxial injuries that proceed to litigation, and these injuries are often permanent. Conversely, infectious complications have a higher likelihood of at least partial recovery.36

TABLE 1

TABLE 1

The incidence of neuraxial injury associated with regional anesthetic techniques varies widely—so much so that it is extremely difficult to cite a meaningful overall risk for injury. Indeed, incidence can even vary among cohorts within the same study. To illustrate this point, the previously noted Swedish study reported vastly different incidences of spinal hematoma—from a risk of 1:200,000 in young women having obstetric epidural blockade to a risk of 1:22,000 in elderly women undergoing hip fracture repair to 1:3600 for those undergoing knee arthroplasty.28 With regard to infectious complications, risks tend to rise in immunocompromised patients, with prolonged epidural catheterization, when the proceduralist unknowingly harbors virulent nasopharyngeal pathogens and does not wear a mask, and/or when practitioners breach aseptic technique.7,28,37–40

Table 2 lists studies reported since 1990 that document incidences of neuraxial injury (often combining hematoma, infection, direct spinal cord injury, etc). These studies point to several common themes. First, the risk of hematoma is higher with epidural than with subarachnoid techniques. Second, the risk of neuraxial injury increases when there are associated coagulation abnormalities (whether from disease or intended anticoagulation), increased age, or female sex. Furthermore, concurrent spinal stenosis or some preexisting neurologic diseases may worsen injury severity in the presence of neuraxial hemorrhage or infection. Third, risk is lower for obstetrical and higher for orthopedic surgeries. Fourth, risk varies when segregated by final outcome (temporary vs permanent vs death).

TABLE 2

TABLE 2

To illustrate how incidence data can vary depending on how they are collected and what specific population they reflect, consider the following approximations as presented in Table 2. Preexisting neurologic disease may affect overall injury incidence: patients with spinal canal pathology or some preexisting neurologic diseases (especially diabetes mellitus) may experience a transient or permanent new neurologic deficit, or worsening of an existing deficit, in 0.3% to 1.1% of neuraxial anesthetics.49,50,58 Conversely, in the general population, the incidence of neuraxial injury from any cause is much less, ranging from less than 0.001% to 0.07%. If one defines serious neuraxial complications based on the need for emergency decompressive surgery, injury incidence ranges from less than 0.01% to 0.05%. Indeed, when propensity scoring was used to remove important baseline differences between patients who underwent intermediate- to high-risk noncardiac surgery with either epidural or general anesthesia, there was actually no difference in the necessity for decompressive laminectomy at 30 days.67 Overall, 3 studies point to an approximate 1:8000 incidence of laminectomy after neuraxial blockade.27,52,67 Still another way to view incidence data is by using pessimistic versus optimistic estimates. The United Kingdom National Health Service has estimated the risk of paraplegia or death from neuraxial techniques from a pessimistic 1.8:100,000 (95% confidence interval [95% CI], 1.0–3.1) to an optimistic 0.7:100,000 (95% CI, 0–1.6). Similarly, the risk of permanent injury (but not death or paraplegia) ranged from a pessimistic 1:5800 adult epidural anesthetic blocks to an optimistic 1:12,200.27 Thus, incidence data from neuraxial injury vary widely in accordance with those circumstances that frame the reporting process.

Back to Top | Article Outline

Incidence of PNI

Similar to neuraxial injuries, the reported incidence of PNI associated with regional anesthesia and pain medicine techniques is quite variable. In addition to those factors mentioned for neuraxial injury, the type of peripheral nerve block and its use relative to other blocks may influence injury rate. Because proximal nerves contain a higher proportion of neural tissue as compared with connective tissue,68 it has been speculated that proximal nerve blocks are riskier than more distal approaches. However, there are no convincing data to confirm or refute this notion.22,26,35,69 Evidence strongly suggests that the choice to use a regional anesthetic technique (neuraxial, peripheral, or combined) for total joint arthroplasties does not inherently increase the risk for neurologic injury when compared with general anesthesia alone.70–72 A large retrospective study has also shown that peripheral nerve blocks are not an independent risk factor for perioperative nerve injury.73

Table 3 details the incidences of neurologic outcomes associated with peripheral nerve blockade reported since 1997. Consistent with previous reviews,35,100 early transient postoperative neurologic symptoms (PONSs) are very common in the first days to month after peripheral nerve blockade. However, the incidence is reduced sequentially with time—0% to 2.2% at 3 months, 0% to 0.8% at 6 months, and 0% to 0.2% at 1 year. Importantly, PNIs are not all block related. For perspective, the overall incidence of perioperative nerve injury in more than 380,000 operations conducted for 10 years at a single institution was 0.03%; perioperative nerve injury was associated with hypertension and smoking but not peripheral nerve block.73

TABLE 3

TABLE 3

In summary, the incidence of perioperative nerve injury is extremely difficult to pinpoint with any degree of accuracy. We have instead chosen to present several different approaches to incidence reporting. The incidence of injury after neuraxial blockade is extremely low, but the injuries are often permanent. Conversely, PONSs after peripheral nerve blockade are common but rarely result in long-term or permanent injury. Complicating this analysis are examples of how individual hospital systems can influence patient outcomes when practices are vigilant, evidence based, and use rapid diagnosis and early treatment.28,32,64 This implies that decreased injury rates and better patient outcomes are attainable when hospitals develop systems that signal risk factors for neuraxial complications (such as concurrent anticoagulation) or devise emergency diagnostic and therapeutic pathways for when a potentially reversible neuraxial injury is suspected.

Back to Top | Article Outline

NEUROLOGIC COMPLICATIONS OF ELECTIVE ORTHOPEDIC SURGERIES

New to this practice advisory is a series of articles11,12,14 that explore the rate of neurologic complications related to common elective orthopedic surgical procedures. Knowledge of these injuries and their mechanisms is beneficial for the perioperative physician to ascertain potential etiologies for perioperative neural deficits, which might include surgical, anesthetic, and patient-related factors (Table 4). In consultation with the operating surgeon and neurologist, the knowledgeable anesthesiologist might facilitate global awareness of possible injury mechanisms, which in turn may optimize postoperative diagnostic and therapeutic interventions. Despite this optimistic goal, determining causation in the setting of concurrent surgery and regional anesthesia is often challenging because of confounding factors such as double-crush injury and/or the technical limitations of diagnostic imaging and neurophysiologic testing. Furthermore, orthopedic surgery literature rarely designates nerve injury as a primary outcome, is often retrospective, and therefore lacks sufficient granularity to fully understand the mechanism of injury. These limitations likely result in underreporting. Thus, although the literature affords a glimpse into the “overall baseline nerve injury” associated with specific surgeries, precise determination of causation is often speculative.

TABLE 4

TABLE 4

Similar to anesthesia-related injuries, the vast majority of neural injuries associated with orthopedic procedures are transient, yet the rate of long-term injury is of consequence. Most injuries result from a short list of perioperative causes such as direct nerve trauma, positioning, stretch, retraction, or compression from hematoma or dressings. What follows is a brief summary of well-recognized injuries specific to surgery type. To more completely understand this topic, we urge study of the supporting articles and their excellent accompanying illustrations.11,12,14

Back to Top | Article Outline

Shoulder Surgery

The frequency and etiology of nerve injury associated with shoulder surgery vary by surgical approach. Arthroscopic shoulder surgeries are associated with nerve injury ranging from less than 0.1% to 10%,11 most of which are caused by surgical traction to improve exposure or by arthroscopic portal placement. Shoulder surgeries performed in the lateral decubitus position are associated with transient neuropraxia affecting the operated limb in up to 10% of patients, especially when documented by intraoperative somatosensory evoked potentials.101 Portal placement too close to typical nerve pathways is particularly risky for axillary or musculocutaneous nerve injury. These same nerves are at risk during open (nonarthroscopic) shoulder surgeries, but the cause is more likely surgical traction to the arm. Open rotator cuff surgery is associated with mostly transient injuries (<2%), but open shoulder stabilization procedures increase injury frequency up to 8.2%.102 Anatomic total shoulder replacement is most often associated with diffuse brachial plexus injuries, which may occur transiently in up to 17% of patients. Patients with stiff shoulders or prior shoulder surgery are at an increased risk.103 The 0.6% to 3.6% incidence of nerve injury associated with reverse total shoulder replacement11 is 11-fold higher than that reported for anatomic shoulder replacement and is primarily related to the permanent arm lengthening associated with that procedure.104

Back to Top | Article Outline

Elbow Surgery

Surgery of the elbow is particularly hazardous because of the minimal soft tissue protection available to the multiple nerves that traverse the joint. Ulnar neuropathy persists in up to 10% of elbow replacement patients.105 Up to 4.2% of elbow arthroscopies are associated with transient iatrogenic nerve injury106 in part because portals are placed blindly in a nerve-rich area.

Back to Top | Article Outline

Hip Surgery

The frequency of nerve injury after total hip arthroplasty (THA) varies widely but generally falls in the 1% range.12 The cause of these injuries is attributed to compression from retractors, traction from intraoperative hip dislocation and manipulation, or excessive leg lengthening. The common peroneal branch of the sciatic nerve is most frequently injured during THA (0.08%–3.7%)107; injuries to the femoral and superior gluteal nerves occur less often. Transient injury to the lateral femoral cutaneous nerve is frequent (15%–88%) after the anterior approach to THA.108,109 Two conditions uniquely increase the risk of nerve injury associated with primary THA—developmental dysplasia sometimes requires leg lengthening, which increases the risk 4-fold,110 whereas revision THA increases the risk 3-fold.111 The incidence of nerve injury associated with hip arthroscopy ranges from 0.4% to 13.3%12 and carries with it a unique set of traction-associated risks to the pudendal nerve (from longitudinal traction against the pudendal post) or to the sciatic and femoral nerves.12

Back to Top | Article Outline

Knee Surgery

The incidence of major nerve injury after total knee arthroplasty (TKA) ranges from 0.3% to 9.5%.12 The upper end of this incidence range represents injury to the common peroneal nerve, which is particularly at risk in those patients with severe valgus deformity (>12 degrees), flexion contractures (>10 degrees), prolonged tourniquet times (>120 minutes), or preexisting neuraxial neuropathy (spinal stenosis or lumbar radiculopathy). Disruption of the infrapatellar branch of the saphenous nerve and/or the cutaneous nerves of the thigh is quite common but tends to resolve within 2 years. Arthroscopic knee surgeries are associated with frequent (up to 25%) sensory loss to the anterior knee.112 Similarly, paresthesia from injury to the infrapatellar and sartorial branches of the saphenous nerve is common (up to 75%) after arthroscopic anterior cruciate ligament repair.113 Inside-out techniques for arthroscopic medial meniscus repair are associated with saphenous nerve injury from direct trauma or suture entrapment.

Back to Top | Article Outline

Foot and Ankle Surgery

Elective foot and ankle surgery using arthroscopy or involving joint replacement is a relatively new field. Literature related to nerve injury in these patients is sparse and mostly retrospective. Iatrogenic injury, especially to cutaneous nerves, seems to be relatively common, albeit mostly well tolerated by patients unless the sensory deficit involves the plantar aspect of the foot.14 Adequate surgical exposure for ankle arthroscopy places all nerves that cross the ankle joint at risk for traction neuropraxia. Cutaneous nerves of the foot are at risk from portal placement or direct surgical trauma during the anterior arthroscopic approach, ankle replacement, or open triple arthrodesis ankle fusion. Fortunately, persistent defects are rare (0.2% at 10 years).114 Total ankle arthroplasty carries an overall nerve injury rate of 1.3%115 and most commonly involves the peroneal nerve if the anterior approach is used. Cutaneous nerve sensory deficits after hallux valgus deformity (bunion repair) are poorly documented, and their reported incidence ranges widely.14

Back to Top | Article Outline

Recommendations

  • Awareness of the causation, location, and frequency of nerve injuries associated with elective orthopedic surgery might assist the anesthesiologist in diagnosis and treatment of perioperative nerve injury. Actual discrimination between surgical, anesthetic, and patient factors is often difficult (Class I).
  • Differential diagnosis should include prolonged use of a pneumatic tourniquet (>120 minutes), which has been associated with nerve injury. These injuries often present as diffuse sensorimotor deficits (Class I).
  • Consider delaying placement of regional blocks if assessment of postoperative nerve function is important for the surgeon (Class III).
Back to Top | Article Outline

ANATOMY AND PATHOPHYSIOLOGY OF NEURAXIAL INJURY

Since our 2008 practice advisory,3,4 we have expanded recommendations on 5 specific topics that relate to the anatomy and pathophysiology of spinal cord injury associated with regional anesthesia and pain medicine: spinal stenosis, blood pressure control during neuraxial anesthesia, neuraxial injury subsequent to transforaminal techniques, cauda equina syndrome (CES)/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain procedures in patients receiving general anesthesia or deep sedation.13,116 Recommendations that remain unchanged from 2008 are summarized in Table 5.

TABLE 5

TABLE 5

Back to Top | Article Outline

Spinal Stenosis

After gaining attention shortly before the creation of our 2008 advisory,28,51 evidence has continued to accumulate that suggests an increased risk of spinal cord injury after neuraxial techniques are performed in patients with spinal canal pathology, especially spinal stenosis.29,58 These studies suggest a slightly increased rate (compared with institutional norms) of new or worsening neurologic deficits in those patients with known spinal canal pathology who undergo spinal anesthesia.58 Conversely, studies also report the unexpected discovery of spinal stenosis when (especially elderly women) patients undergo neuroimaging during diagnostic workup for spinal hematoma and CES.28 It remains unclear if these observations represent cause and effect or simply associate spinal stenosis with the complication. Alternatively, the injuries could have been caused by surgical factors, natural progression of the underlying spinal pathology, or a combination thereof. From a pathophysiologic perspective, spinal stenosis may contribute to spinal injury by reducing the vertebral canal cross-sectional area, thereby inducing spinal cord ischemia via compressive mechanisms and/or by limiting the clearance or free distribution of local anesthetic within the neuraxis, thereby contributing to neurotoxicity.13 Although the preponderance of these injuries have been associated with epidural or combined spinal-epidural techniques,28 injuries have also been associated with spinal anesthesia.58,116

As supported by a few large population studies and a multitude of case reports and series,13 the advisory panel speculates that patients with spinal stenosis may be especially vulnerable to neuraxial injury in the concurrent settings of preexisting neuraxial disease, non-neutral positions during the perioperative period (eg, hyperlordosis or extreme lateral flexion), or other conditions that compete with the spinal cord for space within the vertebral canal, for example, epidural hematoma or abscess, spinal arachnoid cyst, or ankylosing spondylitis (Fig. 1). When the diagnosis of moderate-to-severe spinal stenosis is known, we recommend consideration of the risk versus benefit of a neuraxial technique. If such a technique is chosen, we suggest increased vigilance for signs of postoperative neurologic compromise. Finally, we acknowledge that significant spinal stenosis is common (19% prevalence in patients in their sixties118) and often unrecognized by both patients and their health care providers. The majority of patients with spinal stenosis tolerate neuraxial blockade without clinically apparent injury. Nevertheless, the panel advises that increased reporting of neuraxial injury in the setting of spinal stenosis should elevate the anesthesiologist’s awareness of this disease process. Our recommendations regarding spinal stenosis are presented in Table 6.

FIGURE 1

FIGURE 1

TABLE 6

TABLE 6

Back to Top | Article Outline

Blood Pressure Control During Neuraxial Anesthesia

The current advisory places increased emphasis on the importance of avoiding prolonged hypotension during neuraxial anesthetics (>20%–30% below baseline mean arterial pressure [MAP] especially for 20 minutes or longer).13 We base this recommendation on evolving knowledge that the lower limit of autoregulation (LLA) for cerebral and spinal cord blood flow (SCBF) is likely higher than previously believed and ongoing case reports and medicolegal experience wherein patients have suffered spinal cord ischemia or infarction in the setting of prolonged hypotension or hypoperfusion.

Perioperative spinal cord ischemia or infarction is an extremely rare event that is most often associated with specific surgeries (aortic, cardiac, spine). Other risk factors for spinal cord infarction include those classically recognized for vascular disease, that is, atherosclerosis, hypertension, and tobacco abuse. An insult to the spinal cord circulation that is sufficient to cause ischemia or infarction implies either mechanical injury to the spinal vasculature, an embolic event, or hypoperfusion, as may occur during prolonged periods of hypotension. Recent data and opinion suggest that the LLA for SCBF is likely closer to a MAP of 60 to 65 mm Hg rather than the classically understood MAP of 50 mm Hg.119–122 Moreover, direct and surrogate measures of the LLA for cerebral blood flow in humans suggest that the LLA varies widely among subjects and, contrary to common belief, is usually not related to or predicted by baseline blood pressure.121 There exists a “physiologic reserve” between the LLA and the blood pressure at which cellular injury or death actually occurs. Clinical experience suggests that the vast majority of patients whose blood pressure is low during a neuraxial technique do not suffer spinal cord ischemic injury most likely because 1) the blood pressure is not critically low for that individual (ie, the blood pressure is higher than that patient’s LLA or within their physiologic reserve) and/or 2) limited duration at the lower blood pressure. However, case reports also reveal that an extremely small subset of patients either have a higher set point for their personal LLA and/or cannot withstand prolonged periods of “low-normal” blood pressure. Moreover, the risk for ischemic injury is likely increased in these patients when hypotension is interposed with other factors that may compromise SCBF, such as vascular stenosis, embolic phenomena, non-neutral spinal column positioning (eg, hyperlordosis, extreme lateral flexion, or lithotomy), hypocapnia, raised intrathoracic pressure, and/or surgical retraction.

The extreme rarity of perioperative ischemic spinal cord injuries makes it impossible to assume cause and effect in those patients identified with concurrent periods of hypotension particularly when the degree of hypotension is not extreme and/or of extreme duration. Nevertheless, because the chance for recovery after spinal cord infarction is dismal and the ability to predict an individual patient’s LLA is clinically difficult if not impossible, the panel “recommends that anesthesiologists strive to maintain blood pressure within 20% to 30% of baseline and that persistent hypotension be treated.”13 If an ischemic injury is suspected, immediate neuroimaging is necessary to rule out a potentially treatable condition, such as spinal hematoma or abscess. If such a condition is excluded, the panel recommends normalizing or increasing the patient’s blood pressure to high-normal range and considering cerebrospinal fluid (CSF) drainage. The role of corticosteroids specifically for anesthesia or pain medicine–related injuries is unknown. The use of corticosteroids may be beneficial in instances of direct spinal cord trauma from interventional procedures. Conversely, the known linkages to worsened neurologic outcome from direct corticosteroid-induced neurotoxicity and indirect hyperglycemia lead us to recommend avoiding corticosteroids when spinal cord ischemia is suspected. In either case, maintain normoglycemia by using insulin in those patients with elevated glucose levels. These decisions are best made in consultation with neurological colleagues. Recommendations for the diagnosis and treatment of spinal cord ischemia or spinal cord infarction are presented in Table 7.

TABLE 7

TABLE 7

Back to Top | Article Outline

Transforaminal Pain Medicine Procedures

Our 2008 practice advisory4 made recommendations regarding the then emerging awareness of catastrophic neurologic injuries associated with transforaminal pain medicine procedures. In the interim, a collaboration took place between the US Food and Drug Administration Safe Use Initiative and a group with representation from specialties with expertise in interventional treatment of spinal disorders.123 This initiative puts forth a series of expert opinions meant to improve patient safety during the provision of transforaminal procedures. In addition, a number of case reports and small series continue to describe infarctions of the spinal cord, brainstem, cerebrum, or cerebellum after both cervical124,125 and lumbar126,127 transforaminal injections. More evidence for the role of particulate steroids in these injuries has come forth, including reports that the effectiveness of nonparticulate steroidal preparations, such as dexamethasone, may be similar to that of particulate preparations.128–130 Our previous recommendations regarding transforaminal injections have been modified based on these studies plus the US Food and Drug Administration Safe Use Initiative and are presented in Table 8.

TABLE 8

TABLE 8

Back to Top | Article Outline

CES, Local Anesthetic Neurotoxicity, and Arachnoiditis

Since the 2008 practice advisory,3,4 there has been relatively little new data on CES, local anesthetic neurotoxicity, and arachnoiditis—topics that we have loosely combined because of commonality to a presumed etiology that involves neural tissue toxicity. Recommendations specific to these entities are summarized in Table 9.

TABLE 9

TABLE 9

Back to Top | Article Outline

Cauda Equina Syndrome

Injury to the cauda equina manifests as bowel and bladder dysfunction with various degrees of bilateral lower extremity weakness and sensory impairment. There are multiple etiologies for CES, ranging from neural element compression from hematoma, abscess, or herniated intervertebral discs to poorly understood presentations associated with normal clinical settings. Known risk factors for anesthetic-related CES are supernormal doses of intrathecal local anesthetic and/or the maldistribution of local anesthetic spread within the intrathecal space. In recent years, reported cases of CES have been associated with previously undiagnosed spinal stenosis.25,26,28,51 In theory, a tight spinal canal may lead to pressure-induced spinal cord ischemia or limit normal local anesthetic distribution within the intrathecal sac, thereby exposing the cauda equina to high drug concentrations. Either of these conditions could promote local anesthetic neurotoxicity and could be exacerbated by additional compromise of the spinal canal, as may occur with non-neutral surgical positioning. In addition to these pathophysiologic explanations for CES, there seems to exist a subset of patients who suffer CES after receiving a standard neuraxial anesthetic. The advisory panel speculates that these patients might represent an extremely rare subset of patients who are predisposed to neurotoxicity from clinically appropriate doses of local anesthetic and/or who develop neural inflammation in response to the local anesthetic, adjuvant, needle trauma, surgical positioning, or factors unrelated to the anesthetic.13 Table 9 presents our recommendations regarding CES, which include risk-to-benefit consideration of neuraxial anesthesia in patients with known severe lumbar spinal stenosis, and to avoid exceeding the maximum recommended dose of intrathecal local anesthetic in the setting of a failed, partial, or maldistributed spinal anesthetic.

Back to Top | Article Outline

Local Anesthetic Neurotoxicity

Controversy remains as to whether transient neurologic symptoms (TNS) after spinal anesthesia are a forme fruste of local anesthetic neurotoxicity. Regardless, since the 2008 advisory, further clinical experience has come forth concerning TNS and intrathecal 2-chloroprocaine (2-CP).131,132 These studies suggest that the risk of TNS is very low when using 40 to 50 mg intrathecal 2-CP. Spinal 2-CP remains off-label in the United States; in 2013, a 1% 2-CP solution was approved for intrathecal use in Europe. Although the risk of TNS from 2-CP is low, there are insufficient data for the advisory panel to make recommendations with regard to 2-CP and CES. Indeed, 1 patient who received 2-CP in a recent study developed a transient case of incomplete CES that was confirmed by positive nerve conduction study and electromyography.132

Back to Top | Article Outline

Arachnoiditis

New to this iteration of the practice advisory is a discussion regarding arachnoiditis. This poorly understood diffuse inflammatory reaction of the meninges is classically associated with nonanesthetic conditions, such as infection, trauma, contrast media, or multiple back surgeries. Cases of arachnoiditis that stem directly from a neuraxial anesthetic, if they exist, are extremely rare and most likely related to an idiosyncratic reaction to an unknown provocation. Nevertheless, concern has recently been raised regarding the possibility of antiseptic solutions, particularly chlorhexidine/alcohol mixtures, causing arachnoiditis. The evidence for these concerns is circumstantial at best. Conversely, a retrospective cohort study of more than 12,000 patients reported no increased risk in neuraxial complications with the use of chlorhexidine as the skin disinfectant.60 Furthermore, an in vitro study found chlorhexidine at clinically used concentrations no more cytotoxic that povidone-iodine and calculated that, if allowed to dry, any residual chlorhexidine carried by the block needle tip from skin to subarachnoid space would be diluted 1:145,000.133 Based on the superiority of chlorhexidine as an antiseptic agent, the advisory panel stands with other national organizations in recommending it as the skin disinfectant of choice before neuraxial procedures.7,27,134 Table 9 summarizes our recommendations, which include allowing chlorhexidine/alcohol mixtures to fully dry (2–3 minutes) before starting the procedure and maintaining complete physical separation of chlorhexidine (or any disinfectant solution) or its applicator devices from aseptic equipment so as to avoid drip or splash contamination of needles, syringes, or drugs.13

Back to Top | Article Outline

Procedures on Anesthetized or Deeply Sedated Patients

One of the more controversial recommendations from our previous advisory concerns performing regional anesthetics or interventional pain medicine procedures on patients receiving general anesthesia or who are “deeply sedated to the point of being unable to recognize and/or report any sensation that the physician would interpret as atypical during block placement.”1,4 This topic is a good example of how groups of equally qualified experts can analyze the same limited data set and arrive at different advices, as is the case with North American and European interpretations of this topic. In the interim since our last advisory, a number of large registries from the United States and Europe30,56,135 have reaffirmed our previous recommendation that placing peripheral and neuraxial nerve blocks in anesthetized children seems not to increase injury above baseline risk estimates (which are derived mostly from studies of awake adults). Similarly, a report from the ASA Closed Claims study pointed to an apparent increased injury rate in those patients who underwent cervical interventional pain medicine procedures while anesthetized or deeply sedated.124 We believe that this report also reaffirms our previous advice not to routinely perform regional anesthetic or interventional pain medicine procedures in anesthetized or deeply sedated adult patients. Despite the controversy surrounding this topic, the panel views wakefulness as yet another monitor of patient well-being during procedural interventions and as such suggests that wakefulness could be considered a component of vigilant patient care, just as ultrasound guidance, PNS, and expert observation are.13 Recommendations for performing procedures on anesthetized or deeply sedated patients are presented in Table 10.

TABLE 10

TABLE 10

Back to Top | Article Outline

ANATOMY AND PATHOPHYSIOLOGY OF PNI

The pathophysiology and etiology of PNI associated with regional anesthetic techniques are exquisitely complex topics. Yet understanding these mechanisms is crucial if anesthesiologists are to develop risk avoidance strategies. Since the 2008 practice advisory,4 further studies have added to our understanding of how peripheral nerve microanatomy influences PNI. Similar knowledge gains have occurred regarding the relative roles of nerve localization and monitoring technologies. Although the next section of this article will summarize existing and new knowledge related to nerve injury pathophysiology, readers who desire a more complete understanding of this complicated topic are referred to the detailed supporting article contained within this series.10

Back to Top | Article Outline

Anatomic Considerations

Anesthesiologists are increasingly aware of the importance of peripheral nerve microanatomy as a key determinant of PNI risk. Nerve axons are bundled as fascicles and enveloped within the perineurium, which consists of layers of tightly fitting perineurial cells that prevent diffusion of potentially toxic substances into the fascicle and also partially protect against mechanical injury. Multiple fascicles are surrounded by a permeable epineurium, which contains the fascicles plus various amounts of interfascicular connective tissues that occupies an ever-increasing proportion of the nerve’s cross-sectional area as the nerve extends proximally to distally. This relative abundance of distal connective tissue explains why intraneural, but extrafascicular, needle tip placement is more likely to reside in a noncritical (ie, nonfascicular) portion of the nerve. Thus, neural microanatomy seems to correlate with ultrasound-enabled clinical observations that block needles were intraneural (subepineurium, but extraperineurium) more often than was previously assumed, but that this unanticipated occurrence was not associated with clinical evidence of PNI in most patients.136

Back to Top | Article Outline

Pathophysiology of PNI

The traditional mechanisms of PNI have been described in animal models as mechanical, injection, ischemic, and/or neurotoxic. Forceful needle-to-nerve contact and/or injection into the nerve are believed to set in motion a series of events that might lead to ischemia or neurotoxicity. Needle trauma to or rupture of the perineurium is believed to negate the fascicle’s protective environment, which then becomes a crucial contributory factor in determining the likelihood and severity of subsequent PNI. Direct application of (otherwise innocuous) local anesthetic to denuded axons can cause acute inflammatory reactions or neurotoxicity. Such insults are magnified in the setting of a disrupted perineurium137,138 and prolonged exposure to the local anesthetic (as might occur with vasoconstrictive adjuvants, which reduce drug clearance). If the needle does not completely disrupt the perineurium, injection can transiently elevate intraneural pressure and lead to ischemia. Bleeding around the nerve or microhematoma within the nerve can also lead to ischemia. Lastly, nonspecific inflammatory responses can affect single or multiple nerves and at sites proximate to or distant from the surgical site. Such inflammatory changes have been observed during surgical nerve bypass procedures for permanent phrenic nerve injuries associated with interscalene block.139

Back to Top | Article Outline

Etiology of PNI

The etiology of PNI continues to evoke explanations that include anesthetic, surgical, patient-related, or a combination of factors thereof. The evidence for the significance of these factors is summarized in Table 4.

Back to Top | Article Outline

Anesthetic Risk Factors

Recent large studies fail to link peripheral nerve block as an independent risk factor for perioperative nerve injury either in the general operative setting73 or in total joint arthroplasties.70–72 Nevertheless, PNI does occur as a consequence of anesthetic techniques. Controversy continues regarding the concept of intentional intraneural injection for the purpose of achieving more rapid onset of denser peripheral nerve blockade. Published reports of intentional intraneural injection have noted no nerve injuries, albeit in patient numbers too small to prove safety.140,141 Similarly, several small clinical studies have also reported no PNI despite unintentional intraneural injection.136,142 Nevertheless, the advisory panel interprets the majority of animal and human PNI studies as supporting the concept that anesthesiologists should not purposefully seek needle-to-nerve contact143 or intentional intraneural injection.

Back to Top | Article Outline

Surgical Risk Factors

Most surgical injuries are thought to occur from traction, stretch, transection, or compression injuries. These factors were reviewed in the previous section on surgically related neurologic complications.

Back to Top | Article Outline

Patient Risk Factors

Factors that place patients at an increased risk for anesthesia-related PNIs include metabolic, hereditary, toxic, and entrapment neuropathies and other preexisting neurologic injuries/conditions. Diabetic neuropathy is of particular concern because it seems to increase PNI at least 10-fold as compared with the general population.26 A large general surgical population study identified peripheral vascular disease, smoking, vasculitis, and hypertension as independent risk factors for perioperative nerve injury.73

Back to Top | Article Outline

The Role of Nerve Localization and Monitoring Techniques

Paresthesia

A single randomized clinical trial did not support the elicitation of paresthesia as a risk factor for PNI.80 The absence of a paresthesia does not reliably exclude the possibility of needle-to-nerve contact nor does it prevent PNI. Nevertheless, severe paresthesia that occurs with needle advancement or injection should prompt the cessation of either maneuver, and repositioning of the needle should be considered.

Back to Top | Article Outline

Peripheral Nerve Stimulation

Peripheral nerve stimulation is characterized by low sensitivity, but high specificity, for needle-to-nerve contact. When a motor response occurs at a low current output, such as 0.2 mA or lower, one cannot reliably discern if the needle tip is abutting the nerve or is subepineurial.10,144 Conversely, current output greater than 0.5 mA is generally associated with extraneural needle placement,141,145 although reports exist of intraneural needle tip placement at currents approaching 2.0 mA.

Back to Top | Article Outline

Injection Pressure Monitoring

Interest continues in the controversial practice of injection pressure monitoring. The clinical usefulness of this monitoring modality remains poorly defined. Avoidance of high resistance to injection seems to be a reasonable strategy during peripheral nerve blockade because studies consistently show that low opening pressures (<15 psi) are associated with injection into non-neural tissues. However, injection pressure monitoring seems to be most valuable as a negative predictor of PNI, that is, low injection pressure correlates with no PNI, but high injection pressure is not consistently linked to PNI. Unfortunately, anesthesiologists cannot reliably discern injection pressure based on syringe feel alone.146,147 With regard to direct pressure monitoring systems, studies suggest that the technique cannot reliably detect intraneural intrafascicular injection and that needle-to-nerve contact and intrafascicular injection can be indistinguishable from each other.148–150

Back to Top | Article Outline

Ultrasound Guidance

Ultrasound guidance has not been associated with a reduction of PONS or long-term PNI.21,22,33 The inability of ultrasound to reduce nerve injury may stem from technical and/or training limitations in discerning nerve from surrounding tissues (insufficient resolution to distinguish fascicles from connective tissue) or it may be related to anesthesiologists attempting to place the needle as close to the nerve as possible, thereby potentially increasing the risk for unintended subepineurial injection. Recent studies suggest that injecting local anesthetic adjacent to the brachial plexus, rather than within the fascial sheath, results in equivalent neural blockade.151

In summary, PNI is a diverse and complicated entity that may be associated with anesthetic, surgical, patient-related, or a combination of risk factors. In recent years, ultrasound studies have demonstrated that anesthesiologists place block needles within the nerve much more frequently than previously imagined and that most of these occurrences are not associated with PNI. The practice advisory panel interprets the weight of animal and human evidence to support the practice of avoiding needle placement that abuts or enters the nerve. Although there is no evidence that PNS, ultrasound, or pressure monitoring can prevent PNI, the panel believes it reasonable to consider using several of these modalities in combination when appropriate. Our advice is tempered by our limited knowledge of those factors that most influence PNI and recognition that those factors vary with the specific nerve involved, the peripheral block performed, and with unique patient and surgical factors. Recommendations regarding nerve localization techniques are presented in Table 11.

TABLE 11

TABLE 11

Back to Top | Article Outline

PATIENTS WITH PREEXISTING NEUROLOGIC DISEASE

The “double-crush” theory was first proposed by Upton and McComas152 in 1973. The theory maintains that patients with preexisting neurologic compromise anywhere along the neural pathway may be at increased susceptibility for subsequent nerve injury from a secondary low-grade insult such as might occur during the perioperative period from surgery or anesthetic causes. Moreover, the resultant nerve damage may exceed the additive effects of 2 low-grade injuries153 (Fig. 2). Preexisting neurologic conditions, many of them subclinical, might set the stage for subsequent double-crush scenarios, including such broad etiologies as mechanical, ischemic, toxic, metabolic, and autoimmune conditions. Preexisting neurological conditions have historically led to recommendations not to perform regional anesthetics.154 The intent of our practice advisory was to analyze and summarize current evidence so that clinicians and their patients can make better informed decisions when presented with the conundrum of whether or not to offer regional anesthetic or interventional pain medicine procedures to patients with preexisting neurologic disease.

FIGURE 2

FIGURE 2

Although new information on the issue of performing regional anesthetic techniques in patients with preexisting neurologic disease is limited, this evidence reinforces our previous recommendations regarding patients with diabetes mellitus and spinal stenosis. Furthermore, there is a substantial amount of new information on postsurgical inflammatory neuropathies (PSINs). More detailed discussion on the topic of performing blocks in patients with preexisting neurologic disease is contained in the supporting article by Kopp et al.16

Back to Top | Article Outline

Preexisting Peripheral Nervous System Disorders

Peripheral neuropathies are either hereditary or acquired. The most common inherited disorders are from the collective category of Charcot-Marie-Tooth (CMT) disease, which affects approximately 1 in 2500 humans. A few case reports and small case series describe the use of either peripheral or central regional anesthetic techniques in CMT patients without apparent worsening of their underlying condition. However, clinical evidence is too sparse to allow for definitive recommendations other than if a regional technique is chosen; extra precautions should be taken to minimize other surgical or anesthetic risk factors. Most patients with preexisting peripheral nervous system disease have acquired peripheral neuropathies such as diabetes mellitus or chemotherapy-induced neuropathies.

Back to Top | Article Outline

Diabetic Polyneuropathy

Diabetes mellitus is associated with several types of neuropathies, but distal symmetric sensorimotor polyneuropathy (diabetic polyneuropathy or DPN) is most common and is present in up to 50% of long-standing diabetic patients. Although animal studies155,156 consistently report that diabetic nerve fibers are more sensitive to the blocking effects of local anesthetics and may have increased susceptibility to local anesthetic neurotoxicity, it is unclear if these findings are clinically relevant in humans. A small number of clinical studies attest to higher peripheral nerve block success rates in diabetic patients,157 but such increased sensitivity to local anesthetics may not necessarily reflect increased susceptibility to neurotoxicity. However, a single-institution study reported that 0.4% (95% CI, 0.1%–1.3%) of patients with sensorimotor neuropathy or DPN who underwent spinal anesthesia subsequently developed new or progressive postoperative neurologic deficits, which is a higher incidence than that observed in the institution’s general surgical population.49 Although this finding does not absolutely link spinal anesthesia to increased risk in patients with DPN, it does suggest that the anesthetic may have been a contributing factor. Another area of concern in patients with DPN involves nerve localization technique; diabetic nerves are less sensitive to electrical stimulation, which theoretically increases the risk of intraneural needle placement when localizing nerves using a PNS.158 Although ultrasound guidance has not decreased the rate of PONS in the general population, it is possible that the advantages of ultrasound guidance—facilitating avoidance of intentional needle-nerve contact and reducing local anesthetic volume—may eventually prove beneficial in at-risk populations such as diabetic patients.21 In summary, patients with DPN may be more susceptible to double-crush injury, but current clinical evidence is suggestive rather than definitive. Nevertheless, we recommend that, in profoundly symptomatic patients, consideration be given to limiting local anesthetic concentration and/or dose, avoidance of adjuvant epinephrine,159 and ultrasound guidance to maintain needle tip distance from the nerve.

Back to Top | Article Outline

Chemotherapy-Induced Neuropathy

Approximately 30% to 40% of patients who receive neurotoxic chemotherapeutic agents (eg, cisplatin, vincristine, paclitaxel) develop peripheral neuropathy. The risk of nerve injury is increased further in those patients with preexisting neuropathic changes from diabetes mellitus or alcoholism. Many of these chemotherapy-induced neuropathies are subclinical. A note of concern pertinent to these patients was raised by an isolated case report of severe brachial plexopathy after peripheral nerve blockade in a patient with subclinical chemotherapy-induced neuropathy.160

Back to Top | Article Outline

Inflammatory Neuropathies

The inflammatory neuropathies include Guillain-Barré syndrome (GBS) and recently highlighted postsurgical inflammatory neuropathies (PSIN). Most case reports of GBS come from (usually successful) use of neuraxial blockade in obstetric patients. However, major concerns include the potential for autonomic instability and consequent exaggerated responses to neuraxial blockade and reactivation of previously dormant GBS symptoms, both of which have been reported.16 There are too few data to make recommendations on GBS and concurrent regional anesthetic techniques other than to suggest that decisions be made on an individualized basis that accounts for risk and benefit.

Back to Top | Article Outline

Postsurgical Inflammatory Neuropathies

There is growing awareness of inflammatory etiologies for perioperative nerve injuries, including Parsonage-Turner syndrome,161 lumbosacral radiculoplexus neuropathies,162 and PSIN.163,164 Distinguishing features of these neuropathies include their delayed appearance (within 30 days of surgery, although some may be apparent immediately), which is usually followed by a period of normal recovery. Clinical presentation also includes signs and symptoms outside of the expected location of anesthetic blockade or surgery and a period of intense pain out of proportion to what would be expected from the surgery, which then resolves, only to be followed by weakness. Postsurgical inflammatory neuropathy is thought to be an immune-mediated idiopathic response to a physiologic stress, such as infection, vaccination, or surgery.164 The associated neurologic deficits may be focal, multifocal, or diffuse. The greatest risk of PSIN is surgeons and anesthesiologists not considering its diagnosis and, in so doing, delaying potentially useful therapies. When patients present with this constellation of symptoms, urgent neurological consultation is warranted. Although the natural history without treatment is one of probable slow recovery, once diagnosed, many neurologists recommend suppressing the immune response with prolonged high-dose steroids or immunoglobulin to minimize the immune-mediated nerve injury, although such therapies have not been proven. In contradistinction from much perioperative nerve injury, most patients with PSIN improve with treatment if diagnosed early.

Back to Top | Article Outline

Preexisting Central Nervous System Disorders

As with preexisting peripheral nervous system disease, anesthesiologists historically were reluctant to offer regional anesthetic–based techniques to their patients with preexisting CNS diseases.154 Although modern data are limited, most studies of the general surgical population50 and obstetrics165,166 have not found that regional techniques place most patients with active disease at risk for new or worsening symptoms. Despite these reassuring findings, the decision to perform neuraxial anesthetic or interventional pain medicine procedures in patients with preexisting CNS disease still demands risk-to-benefit consideration.

Back to Top | Article Outline

Multiple Sclerosis

The focal demyelination that characterizes multiple sclerosis (MS) contributes to its classic “waxing and waning” pattern. When coupled with known perioperative stressors that can worsen the disease process, such as hyperpyrexia, infection, and/or emotional stress, it is often difficult to sort out the causes for perioperative progression or new onset of MS-related symptoms. Although classically considered a CNS disease, some portion of patients (from 5% to 47%)167,168 also have peripheral demyelination. The clinical significance of peripheral MS is unclear because there are very few case reports that link MS to injury after peripheral nerve blockade.169 Conversely, there are case series that support the general safety of neuraxial anesthesia in parturients with MS.165,170 Importantly, the obstetric model may not be ideal because MS patients have diminished frequency of relapse during pregnancy but an increased rate postpartum. To maximize safety in obstetric patients, it is recommended that the dose and concentration of local anesthetic be limited. Epidural anesthesia is considered safer than spinal anesthesia because it does not deposit local anesthetic directly adjacent to the CNS (ie, the spinal cord).

Back to Top | Article Outline

Postpolio Syndrome

Postpolio syndrome (PPS) is the most prevalent motor neuron disease in North America. The largest series (n = 79) of PPS patients to receive neuraxial anesthesia documented no worsening of symptoms.50 Nevertheless, the paucity of data on these patients suggests that the risk and benefit of a neuraxial technique be balanced against that of general anesthesia.

Back to Top | Article Outline

Amyotrophic Lateral Sclerosis

The greatest perioperative risks of amyotrophic lateral sclerosis (ALS) are respiratory and/or neurologic deterioration. A few case reports attest to the apparent safety of neuraxial or peripheral blockade in ALS patients,16 but these reports are insufficient for general recommendations. As with other CNS preexisting diseases, the risk and benefit of regional techniques should be balanced against those of general anesthesia.

Back to Top | Article Outline

Spinal Canal Pathology

Emerging concerns regarding patients with spinal stenosis were discussed in the section on neuraxial pathophysiology.13 With regard to previous spine surgery, a recent publication reported no evidence that these patients were at risk for developing new or progressive neurologic deficits when they underwent spinal anesthesia.58 Although previous spinal surgery should not be considered a contraindication to neuraxial anesthetic or interventional pain medicine techniques, consideration might be given to preprocedure imaging to better define relevant anatomy, deformity, and/or surgical implants.58

Back to Top | Article Outline

Neural Tube Defects

Congenital neural tube defects may present at birth as open spinal dysraphisms (eg, meningocele or meningomyelocele) or closed spinal dysraphisms, which range from isolated defects of posterior vertebral column closure (spina bifida occulta) or more serious malformations such as diastematomyelia (split cord malformations), tethered spinal cord syndrome, or dural ectasia (lumbosacral widening or caudad displacement of the dural sac). A few case reports have described successful spinal or epidural anesthesia in parturients who previously underwent surgical correction of open spinal dysraphisms. These cases were characterized by extensive cranial spread of a dense local anesthetic block, with limited caudad spread below the site of surgical correction. Thus, if the decision is made to provide neuraxial anesthesia in this subset of patients, it is recommended that the block needle is inserted cephalad to the original lesion.

The closed spinal dysraphisms are challenging because the proceduralist or patient may not always be aware of the defect. Failure of a single vertebral arch to fuse (isolated spinal bifida occulta) is common in the general population (10%–24%).171 It is recommended that needle insertion occur above the level of spinal abnormality, assuming its presence is known. A total of 11 cases of successful epidural anesthetics using normal doses of local anesthetic have been reported in isolated spina bifida patients.16 In contrast, patients with complex spina bifida should not receive neuraxial anesthesia. This recommendation is based on reports of neurologic complications in patients who underwent a variety of neuraxial techniques; in some of those cases, the defect was unrecognized before the procedure. Patients with complex spina bifida often have associated conditions, such as cutaneous manifestations over the level of abnormality, involvement of more than 1 lamina, or associated bowel, bladder, or neurologic symptoms. If the presence of a neural tube defect is known or suspected, the underlying neuroanatomy should be documented with radiographic imaging before considering a neuraxial technique. We recommend that complex closed spinal dysraphisms be considered a contraindication to neuraxial techniques. In patients with spina bifida occulta, neuraxial techniques may be considered after appropriate risk (technical difficulties, dural puncture, or atypical local anesthetic spread) is balanced against perceived benefit.

Recommendations for performing neuraxial or peripheral anesthesia/analgesia procedures in patients with preexisting neurologic disease are presented in Table 12.

TABLE 12

TABLE 12

Back to Top | Article Outline

DIAGNOSIS AND TREATMENT

Since our 2008 advisory,4,5 new information has evolved concerning postoperative inflammatory neuropathies. We have added new information on acute interventions that may possibly improve neurologic outcome, both acutely and in relation to long-term management of the neuropathic pain that occasionally results from these injuries. We have updated our previous algorithm that contains a structured approach to diagnosis and initial management (Fig. 3). Although this advisory focuses on nonhemorrhagic and noninfectious neurologic complications, these entities will be briefly noted throughout this section for both completeness and perspective. Readers are encouraged to refer to the ASRA practice advisories on these topics for details7,8 and should seek the most up-to-date versions of these works. Summary articles are available on the ASRA Web site (www.asra.com).

FIGURE 3

FIGURE 3

Back to Top | Article Outline

Timely Recognition of Perioperative Nerve Injury

Early recognition and appropriate stratification of suspected perioperative nerve injury into those that require emergent imaging and/or neurologic evaluation are of paramount importance to afford patients the best opportunity for full or partial recovery, especially in the case of neuraxial injuries. Nonetheless, our current advisory15 notes multiple barriers to appropriate recognition of perioperative nerve injury, including such factors as neurologic deficits being masked by sedation, concurrent analgesics, or continuous catheter use; the absence of ambulatory patient follow-up; or delayed recognition of sensorimotor deficits until after hospital discharge, which has been reported to occur in up to 90% of patients undergoing lower extremity arthroplasty.70,71 Delayed recognition is more likely to be associated with nonoperative causes of nerve injury, such as immobilization, dressing compression, infection, or inflammation. Such delays also confound the patient’s perception of onset. In the “blur” that accompanies typical perioperative events, patients can incorrectly report their symptoms as presenting immediately after surgery despite objective documentation of onset at 48 hours, as for example with perioperative ulnar nerve injury.172 The complexity of perioperative recognition, the absolute imperative in some cases to diagnose and treat emergently, and operators’ unique understanding of the expected consequences of their procedure, all speak to the advisability of direct, candid, and timely conversation between the anesthesiologist or pain physician and the neurologic consultant.15

Back to Top | Article Outline

Diagnosis and Treatment of Neuraxial Complications

Certain signs and symptoms after neuraxial blockade should raise suspicion for perioperative nerve injury. Weakness that is more intense than expected, recurrent after initial resolution, progressive, and/or in an area inconsistent with the block (eg, lower leg or foot weakness associated with a thoracic epidural) can be the first presenting symptoms of a significant neuraxial injury.36,173–175 Back pain is observed less frequently, whereas bowel or bladder symptoms are late. For those mass lesions amendable to emergent surgical decompression, full (40%–66%) or partial recovery is possible if decompression occurs within 8 to 12 hours of symptom onset, although a recent study challenges this assumption.61 The severity of neurologic deficit at the time of intervention also predicts outcome.176–178 Frequently noted in medicolegal claims36 is the failure of anesthesiologists to recognize and begin management of a neuraxial complication in a timely manner—all too often, neurologic deficits are wrongly attributed to the block itself. Inappropriate delays are all the more likely when unenlightened surgical or nursing personnel manage the patient in the absence of anesthesiologist expertise. When injury is suspected, magnetic resonance imaging (MRI) differentiates soft tissues, identifies coexisting spinal canal pathology, and locates an aberrantly placed catheter more effectively than does computerized tomography (CT). However, in the absence of immediately available MRI, an emergent CT scan can identify those space-occupying compressive processes most amenable to emergent surgical decompression (ie, spinal abscess or hematoma).

Table 13 presents the characteristics of neuraxial injury presentation that may aid differential diagnosis. Epidural hematoma is associated temporally with needle/catheter placement or catheter removal and in 75% of cases will have a fulminant presentation within 24 hours.177 Conversely, spinal epidural abscess or meningitis may have an insidious presentation—a delay of several days after the procedure, followed by indolent fever and back pain, followed by rapid progression to paralysis. Accurate diagnosis and therapy are important because spinal epidural abscess/meningitis have a 15% mortality; earlier diagnosis is also associated with less severe neurologic deficits.180 Anterior spinal artery syndrome may be heralded by back pain at the level of infarction and bilateral radicular discomfort in 75% of cases, with typically rapid progression to paraplegia or tetraplegia that spares the posterior columns (vibration and proprioception).181 Complete recovery is extremely rare. Direct spinal cord trauma from needles or catheters may present with unilateral or bilateral symptoms, depending on the anatomical lesion site. If the only symptom after suspected direct trauma is a persistent paresthesia that is nonprogressive and improving, observation alone may be warranted. However, more widespread sensory symptoms (ie, nondermatomal) or motor involvement should prompt MRI and possible neurologic consultation.

TABLE 13

TABLE 13

In summary, early recognition and appropriate intervention can improve outcome in those patients who have suffered a hemorrhagic, infectious, or inflammatory insult. Unfortunately, the same cannot be said for ischemic, local anesthetic neurotoxic, and/or direct mechanical injury causes. Recommendations for the diagnosis and treatment of neuraxial injuries are presented in Tables 14 and 15.

TABLE 14

TABLE 14

TABLE 15

TABLE 15

Back to Top | Article Outline

Diagnosis and Treatment of Peripheral Nerve Complications

Similar to neuraxial injuries, the diagnosis and treatment of PNIs should be approached urgently to rule out potentially correctable lesions, such as from extrinsic or intrinsic compression (casts, dressings, compartment syndrome, visible hematoma, or occult perineural microhematoma). If a hematoma is suspected, urgent imaging or ultrasonography should be considered. Acute surgical injury should also be ruled out by engaging the surgeon in candid discussion regarding the possibility of nerve transection, excessive traction, or wayward ligatures. Indeed, 1 review reported that more than 90% of surgically explored iatrogenic nerve injuries were linked to intraoperative causes.182 The goal of timely consultation is to alleviate potentially correctable causes or nonsurgical or anesthesia-related etiologies, such as stroke. Once the need for immediate treatment has been ruled out, the diagnosis of PNI can proceed as directed by initial presenting symptoms (Fig. 3). Pure sensory deficits that occur within the territory of the peripheral block74 or a classic compression point, for example, common peroneal nerve compression at the fibular head, can be observed and are expected to resolve within days to weeks. However, neurologic consultation should be considered when the deficit involves motor function, is progressive, is characterized by recrudescence of neural blockade, or is difficult to localize and/or reconcile with the expected distribution of the anesthetic block or surgery. Electrophysiologic studies for more severe or unclear cases are typically delayed for 2 to 3 weeks, when signs of Wallerian degeneration first appear. However, early electrophysiologic studies may we worthwhile to define preexisting pathology. Bilateral studies may be indicated if occult conditions are suspected to affect the nonoperative side. Such decisions are best made in consultation with a neurologist. When no or incomplete improvement has taken place by 3 to 5 months, consideration should be given for referral to a peripheral nerve surgeon. Recommendations for the diagnosis and treatment of PNIs can be found in Tables 14 and 15.

Back to Top | Article Outline

Postsurgical Inflammatory Neuropathies

Postsurgical inflammatory neuropathies were discussed previously in the preexisting neurologic disease section. When patients present with this symptom complex in the postsurgical period, urgent neurologic consultation is warranted.

Back to Top | Article Outline

Management of Chronic Pain After Perioperative Nerve Injury

A subset of patients who sustain perioperative nerve injury will develop chronic neuropathic pain. The pain medicine physician is often called on to provide long-term symptomatic management of these patients and to assume coordination of patient education, expectation, and physical therapy. New to this advisory are evidence-based recommendations for the care of these challenging patients, some of whom may have unanswered questions or unrealistic expectations consequent to suboptimal communication with various practitioners during the immediate postoperative episode.

Postsurgical neuropathic pain syndromes may result from surgical injury, such as intercostal neuritis after thoracotomy, or may be consequent to neural blocks administered during the perioperative period. There are several considerations for when it might be appropriate to refer patients with persistent postsurgical pain to a pain medicine specialist—severe pain out of proportion to that expected from a specific surgical procedure; pain that limits patient function; or pain that is progressive, multifocal, and/or difficult to localize. Other signs that should prompt early referral are those consistent with chronic regional pain syndrome, such as neurologic impairment in an area remote from the regional block, surgery, or compression or physical signs such as allodynia, edema, or hyperhidrosis. Readers are referred to the supporting article’s15 detailed recommendations regarding stepwise pharmacologic therapies for these patients, as well as reasonable indications for the use of diagnostic nerve blocks, such as stellate ganglion block. The evidence for neuromodulation therapy is less conclusive; the European Federation of Neurological Societies supports the use of spinal cord stimulation for chronic regional pain syndrome,183 although there are no supporting studies specific to postsurgical neuropathic pain.

In summary, the diagnosis and treatment of neuraxial injuries demands emergent stratification of those injuries that may be amenable to surgical decompression. Although the management of PNIs is less urgent (particularly when sensory predominant), practitioners are reminded that severe, progressive, or difficult-to-localize deficits demand urgent neurologic consultation to exclude potentially treatable causes such as from compressive etiologies. If a treatable cause is excluded, there is little that the physician can do to change the course of these injuries. However, pain physicians have a useful role to play in coordinating education, expectation management, and pain modulation in those patients who develop chronic neuropathic pain from their injury.

Back to Top | Article Outline

CONCLUSIONS

The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine provides a number of updates to the 2008 advisory. New information has been presented on the incidence of nerve injury inherent to common elective orthopedic surgeries. The advisory contains updated information regarding the pathophysiology of neuraxial and peripheral nerve injury. New or expanded information is presented, particularly with regard to spinal canal pathology, blood pressure control during neuraxial anesthetics, neurotoxicity-related neuraxial injuries, transforaminal pain medicine procedures, and the advisability of performing procedures in anesthetized or deeply sedated patients. The advisory also expands recommendations related to the diagnosis and treatment of these disorders.

Our final conclusion is very similar to that made in 2008: “Neurologic complications associated with regional anesthesia and pain medicine are rare—particularly those complications that do not involve hematoma or infection. Understanding the pathophysiology and risk factors associated with neuraxial and peripheral nerve injury may allow anesthesiologists to minimize the number of adverse neurologic outcomes. Unfortunately, even with flawless care of otherwise healthy patients by well-trained physicians, these complications are neither completely predictable nor preventable. This practice advisory offers a number of recommendations specific to common clinical scenarios encountered in everyday practice.”4

Back to Top | Article Outline

ACKNOWLEDGMENTS

The authors of this executive summary all served as members of the practice advisory panel. The authors thank the following colleagues who made substantial contributions to this project through participation in the open forum or authorship of the individual background articles from which this executive summary was drawn:

• CEU San Pablo University, Madrid, Spain: Miguel A. Reina, MD, PhD

• Mayo Clinic College of Medicine: Adam K. Jacob, MD; William L. Lanier, MD; Jeffrey J. Pasternak, MD

• University of Maryland Medical Center, Baltimore, Maryland: Paul E. Bigeleisen, MD, participated as a panelist at the open forum

• University of Toronto, Toronto, Ontario, Canada: Zahra Abbas, BSc; Vincent WS Chan, MD, FRCPC, FRCA; Phantila Cholvisudhi, MD; Michael Drexler, MD; Tim Dwyer, MBBS, FRACS, FRCSC; Patrick DG Henry, MD, FRCSC; Johnny Lau, MD, MSc, FRCSC; Peter Salat, MD; John S Theodoropoulos, MD, MSc, FRCSC; Andrea Veljkovic, BComm, MD, FRCSC; Daniel B Whelan, MD, MSc, FRCSC

Back to Top | Article Outline

REFERENCES

1. Bernards CM, Hadzic A, Suresh S, Neal JM. Regional anesthesia in anesthetized or heavily sedated patients. Reg Anesth Pain Med. 2008; 33: 449–460.
2. Hogan QH. Pathophysiology of peripheral nerve injury during regional anesthesia. Reg Anesth Pain Med. 2008; 33: 435–441.
3. Neal JM. Anatomy and pathophysiology of spinal cord injuries associated with regional anesthesia and pain medicine. Reg Anesth Pain Med. 2008; 33: 423–434.
4. Neal JM, Bernards CM, Hadzic A, et al. ASRA Practice Advisory on neurologic complications in regional anesthesia and pain medicine. Reg Anesth Pain Med. 2008; 33: 404–415.
5. Sorenson EJ. Neurological injuries associated with regional anesthesia. Reg Anesth Pain Med. 2008; 33: 442–448.
6. Lee L, Posner KL, Chaney FW, Caplan RA, Domino KB. Complications associated with eye blocks and peripheral nerve blocks: an ASA closed-claims analysis. Reg Anesth Pain Med. 2008; 33: 416–422.
7. Hebl J. The importance and implications of aseptic techniques during regional anesthesia. Reg Anesth Pain Med. 2006; 31: 311–323.
8. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010; 35: 64–101.
9. Neal JM, Bernards CM, Butterworth JF 4th, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010; 35: 152–161.
10. Brull R, Hadzic A, Reina MA, Barrington MJ. Pathophysiology and etiology of nerve injury following peripheral nerve blockade. Reg Anesth Pain Med. 2015; 40: 479–490.
11. Dwyer T, Henry PDG, Cholvisudhi P, et al. Neurological complications related to elective orthopedic surgery: part 1: common shoulder and elbow procedures. Reg Anesth Pain Med. 2015; 40: 431–442.
12. Dwyer T, Drexler M, Chan VWS, Whelan DB, Brull R. Neurological complications related to elective orthopedic surgery: part 2: common hip and knee procedures. Reg Anesth Pain Med. 2015; 40: 443–454.
13. Neal JM, Kopp SL, Lanier WL, Pasternak JJ, Rathmell JP. Anatomy and pathophysiology of spinal cord injury associated with regional anesthesia and pain medicine: 2015 update. Reg Anesth Pain Med. 2015; 40: 506–525.
14. Veljkovic A, Dwyer T, Lau J, et al. Neurological complications related to elective orthopedic surgery: part 3: common foot and ankle procedures. Reg Anesth Pain Med. 2015; 40: 455–466.
15. Watson JC, Huntoon MA. Neurologic evaluation and management of perioperative nerve injury. Reg Anesth Pain Med. 2015; 40: 491–501.
16. Kopp SL, Jacob AK, Hebl JR. Regional anesthesia in patients with preexisting neurologic disease. Reg Anesth Pain Med. 2015; 40: 467–478.
17. Kahn R, Gale EA. Gridlocked guidelines for diabetes. Lancet. 2010; 375: 2203–2204.
18. The Oxford 2011 Levels of Evidence. Available at: http://www.cebm.net/index.aspx?o=5653. Accessed March 2, 2015.
19. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol. 2002; 39: 542–553.
20. ASA Standards, Guidelines, Statements and Practice Parameters. Available at: http://www.asahq.org/resources/clinical-information. Accessed January 21, 2015.
21. Neal JM. Ultrasound-guided regional anesthesia and patient safety: an evidence-based analysis. Reg Anesth Pain Med. 2010; 35: S59–S67.
22. 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: 534–541.
23. Orebaugh SL, Williams BA, Vallejo M, Kentor ML. Adverse outcomes associated with stimulator-based peripheral nerve blocks with versus without ultrasound visualization. Reg Anesth Pain Med. 2009; 34: 251–255.
24. Orebaugh SL, Kentor ML, Williams BA. Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided peripheral nerve blocks by supervised trainees: update of a single-site database. Reg Anesth Pain Med. 2012; 37: 577–582.
25. Auroy Y, Narchi P, Messiah A, et al. Serious complications related to regional anesthesia. Results of a prospective survey in France. Anesthesiology. 1997; 87: 479–486.
26. Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France. The SOS regional anesthesia hotline service. Anesthesiology. 2002; 97: 1274–1280.
27. Cook TM, Counsell D, Wildsmith JA, Royal College of Anaesthetists Third National Audit Project. Major complications of central neuraxial block: report of the Third National Audit Project of the Royal College of Anaesthetists. Br J Anaesth. 2009; 102: 179–190.
28. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades in Sweden 1990–1999. Anesthesiology. 2004; 101: 950–959.
29. Pitkänen MT, Aromaa U, Cozanitis DA, Förster JG. Serious complications associated with spinal and epidural anaesthesia in Finland from 2000 to 2009. Acta Anaesthesiol Scand. 2013; 57: 553–564.
30. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg. 2012; 115: 1353–1364.
31. Volk T, Wolf A, Van Aken H, Bürkle H, Wiebalck A, Steinfeldt T. Incidence of spinal haematoma after epidural puncture: analysis from the German network for safety in regional anaesthesia. Eur J Anaesthesiol. 2012; 29: 170–176.
32. Wang LP, Hauerberg J, Schmidt JR. Incidence of spinal epidural abscess after epidural analgesia: a national 1-year survey. Anesthesiology. 1999; 91: 1928–1936.
33. Sites BD, Taenzer AH, Herrick MD, et al. Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Reg Anesth Pain Med. 2012; 37: 478–482.
34. Aromaa U, Lahdensuu M, Cozanitis DA. Severe complications associated with epidural and spinal anaesthesias in Finland 1987–1993. A study based on patient insurance claims [see comment]. Acta Anaesthesiol Scand. 1997; 41: 445–452.
35. Brull R, McCartney CJ, Chan VW, El-Beheiry H. Neurological complications after regional anesthesia: contemporary estimates of risk. Anesth Analg. 2007; 104: 965–974.
36. Lee LA, Posner KL, Domino KB, Caplan RA, Cheney FW. Injuries associated with regional anesthesia in the 1980s and 1990s. Anesthesiology. 2004; 101: 143–152.
37. Horlocker TT, Wedel DJ. Regional anesthesia and the immunocompromised patient. Reg Anesth Pain Med. 2006; 31: 334–345.
38. Rathmell JP, Lake T, Ramundo MB. Infectious risks of chronic pain treatments: injection therapy, surgical implants, and intradiscal techniques. Reg Anesth Pain Med. 2006; 31: 346–352.
39. Wedel DJ, Horlocker TT. Regional anesthesia in the febrile or infected patient. Reg Anesth Pain Med. 2006; 31: 324–333.
40. Wong MR, Del Rosso P, Heine L, et al. An outbreak of Klebsiella pneumoniae and Enterobacter aerogenes bacteremia after interventional pain management procedures, New York City, 2008. Reg Anesth Pain Med. 2010; 35: 496–499.
41. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric practice. Br J Anaesth. 1990; 64: 537–541.
42. Dahlgren N, Tornebrandt K. Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed over three years. Acta Anaesthesiol Scand. 1995; 39: 872–880.
43. Wulf H. Epidural anaesthesia and spinal haematoma. Can J Anaesth. 1996; 43: 1260–1271.
44. Giaufré E, Dalens B, Gombert A. Epidemiology and morbidity of regional anesthesia in children: a one-year prospective survey of the French-Language Society of Pediatric Anesthesiologists. Anesth Analg. 1996; 83: 904–912.
45. Horlocker TT, Abel MD, Messick JM Jr, Schroeder DR. Small risk of serious neurologic complications related to lumbar epidural catheter placement in anesthetized patients. Anesth Analg. 2003; 96: 1547–1552.
46. Ruppen W, Derry S, McQuay H, Moore RA. Incidence of epidural hematoma, infection, and neurologic injury in obstetric patients with epidural analgesia/anesthesia. Anesthesiology. 2006; 105: 394–399.
47. Ruppen W, Derry S, McQuay H, Moore RA. Incidence of epidural hematoma and neurologic injury in cardiovascular patients with epidural anesthesia/analgesia: systematic review and meta-analysis. BMC Anesthesiol. 2006; 6: 10.
48. DeVera HV, Furukawa KT, Matson MD, Scavone JA, James MA. Regional techniques as an adjunct to general anesthesia for pediatric extremity and spine surgery. J Pediatr Orthop. 2006; 26: 801–804.
49. Hebl JR, Kopp SL, Schroder DR, Horlocker TT. Neurologic complications after neuraxial anesthesia or analgesia in patients with preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy. Anesth Analg. 2006; 103: 1294–1299.
50. Hebl JR, Horlocker TT, Schroder DR. Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. Anesth Analg. 2006; 103: 223–228.
51. de Sèze MP, Sztark F, Janvier G, Joseph PA. Severe and long-lasting complications of the nerve root and spinal cord after central neuraxial blockade. Anesth Analg. 2007; 104: 975–979.
52. Cameron CM, Scott DA, McDonald WM, Davies MJ. A review of neuraxial epidural morbidity: experience of more than 8,000 cases at a single teaching hospital. Anesthesiology. 2007; 106: 997–1002.
53. Christie IW, McCabe S. Major complications of epidural analgesia after surgery: results of a six-year survey. Anaesthesia. 2007; 62: 335–341.
54. Pöpping DM, Zahn PK, Van Aken HK, Dasch B, Boche R, Pogatzki-Zahn EM. Effectiveness and safety of postoperative pain management: a survey of 18 925 consecutive patients between 1998 and 2006 (2nd revision): a database analysis of prospectively raised data. Br J Anaesth. 2008; 101: 832–840.
55. Li SL, Wang DX, Ma D. Epidural hematoma after neuraxial blockade: a retrospective report from China. Anesth Analg. 2010; 111: 1322–1324.
56. Ecoffey C, Lacroix F, Giaufre E, Orliaguet G, Courreges P, Association des Anesthésistes Réanimateurs Pédiatriques d’Expression Française (ADARPEF). Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective study of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth. 2010; 20: 1061–1069.
57. Wallace D, Bright E, London NJ. The incidence of epidural abscess following epidural analgesia in open abdominal aortic aneurysm repair. Ann R Coll Surg Engl. 2010; 92: 31–33.
58. Hebl JR, Horlocker TT, Kopp SL, Schroeder DR. Neuraxial blockade in patients with preexisiting spinal stenosis, lumbar disk disease, or prior spine surgery: efficacy and neurologic complications. Anesth Analg. 2010; 111: 1511–1519.
59. Liu SS, Buvanendran A, Viscusi ER, et al. Uncomplicated removal of epidural catheters in 4365 patients with international normalized ratio greater than 1.4 during initiation of warfarin therapy. Reg Anesth Pain Med. 2011; 36: 231–235.
60. Sviggum HP, Jacob AK, Arendt KW, Mauermann ML, Horlocker TT, Hebl JR. Neurologic complications after chlorohexidine antisepsis for spinal anesthesia. Reg Anesth Pain Med. 2012; 37: 139–144.
61. Bateman BT, Mhyre JM, Ehrenfeld J, et al. The risk and outcomes of epidural hematomas after perioperative and obstetric epidural catheterization: a report from the Multicenter Perioperative Outcomes Group Research Consortium. Anesth Analg. 2013; 116: 1380–1385.
62. Hemmerling TM, Cyr S, Terrasini N. Epidural catheterization in cardiac surgery: the 2012 risk assessment. Ann Card Anaesth. 2013; 16: 169–177.
63. Ehrenfeld JM, Agarwal AK, Henneman JP, Sandberg WS. Estimating the incidence of suspected epidural hematoma and the hidden imaging cost of epidural catheterization: a retrospective review of 43,200 cases. Reg Anesth Pain Med. 2013; 38: 409–414.
64. Pumberger M, Memtsoudis SG, Stundner O, et al. An analysis of the safety of epidural and spinal neuraxial anesthesia in more than 100,000 consecutive major lower extremity joint replacements. Reg Anesth Pain Med. 2013; 38: 515–519.
65. Kang XH, Bao FP, Xiong XX, et al. Major complications of epidural anesthesia: a prospective study of 5083 cases at a single hospital. Acta Anaesthesiol Scand. 2014; 58: 858–866.
66. Gulur P, Tsui B, Pathak R, Koury KM, Lee H. Retrospective analysis of the incidence of epidural haematoma in patients with epidural catheters and abnormal coagulation parameters. Br J Anaesth. 2015; 114: 808–811.
67. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A. Epidural anesthesia and survival after intermediate-to-high risk non-cardiac surgery: a population-based cohort study. Lancet. 2008; 372: 562–569.
68. Moayeri N, Bigeleisen PE, Groe GJ. Quantitative architecture of the brachial plexus and surrounding compartments, and their possible significance for plexus blocks. Anesthesiology. 2008; 108: 299–304.
69. 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. Study Group on Regional Anesthesia. Anesth Analg. 1999; 88: 847–852.
70. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR. Perioperative nerve injury after total hip arthroplasty: regional anesthesia risk during a 20-year cohort study. Anesthesiology. 2011; 115: 1172–1178.
71. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR. Perioperative nerve injury after total knee arthroplasty: regional anesthesia risk during a 20-year cohort study. Anesthesiology. 2011; 114: 311–317.
72. Sviggum HP, Jacob AK, Mantilla CB, et al. Perioperative nerve injury after total shoulder arthroplasty: assessment of risk after regional anesthesia. Reg Anesth Pain Med. 2012; 37: 490–494.
73. Welch MB, Brummett CM, Welch TD, et al. Perioperative peripheral nerve injuries. A retrospective study of 380,680 cases during a 10-year period at a single institution. Anesthesiology. 2009; 111: 490–497.
74. Borgeat A, Ekatodramis G, Kalberer F, Benz C. Acute and nonacute complications associated with interscalene block and shoulder surgery. A prospective study. Anesth Analg. 2001; 95: 875–880.
75. Hebl JR, Horlocker TT, Sorenson EJ, Schroeder DR. Regional anesthesia does not increase the risk of postoperative neuropathy in patients undergoing ulnar nerve transposition. Anesth Analg. 2001; 93: 1606–1611.
76. Weber SC, Jain R. Scalene regional anesthesia for shoulder surgery in a community setting: an assessment of risk. J Bone Joint Surg Am. 2002; 84-A: 775–779.
77. Bergman BD, Hebl JR, Ken J, Horlocker TT. Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg. 2003; 96: 247–252.
78. Capdevila X, Pirat P, Bringuier S, et al. French Study Group on Continuous Peripheral Nerve Blocks. Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: a multicenter prospective analysis of the quality of postoperative analgesia and complications in 1,416 patients. Anesthesiology. 2005; 103: 1035–1045.
79. Candido KD, Sukhani R, Doty R Jr, et al. Neurologic sequelae after interscalene brachial plexus block for shoulder/upper arm surgery: the association of patient, anesthetic, and surgical factors to the incidence and clinical course. Anesth Analg. 2005; 100: 1489–1495.
80. Liguori GA, Zayas VM, YaDeau JT, et al. Nerve localization techniques for interscalene brachial plexus blockade: a prospective, randomized comparison of mechanical paresthesia versus electrical stimulation. Anesth Analg. 2006; 103: 761–767.
81. Bishop JY, Sprague M, Gelber J, et al. Interscalene regional anesthesia for arthroscopic shoulder surgery: a safe and effective technique. J Shoulder Elbow Surg. 2006; 15: 567–570.
82. Ben-David B, Barak M, Katz Y, Stahl S. Retrospective study of the instance of neurological injury after axillary brachial plexus block. Pain Pract. 2006; 6: 119–123.
83. Faryniarz D, Morelli C, Coleman S, et al. Interscalene block anesthesia at an ambulatory surgery center performing predominantly regional anesthesia: a prospective study of one hundred thirty-three patients undergoing shoulder surgery. J Shoulder Elbow Surg. 2006; 15: 686–690.
84. Wiegel M, Gottschaldt U, Hennebach R, Hirschberg T, Reske A. Complications and adverse effects associated with continuous peripheral nerve blocks in orthopedic patients. Anesth Analg. 2007; 104: 1578–1582.
85. Lenters TR, Davies J, Matsen FA 3rd. The types and severity of complications associated with interscalene brachial plexus block anesthesia: local and national evidence. J Shoulder Elbow Surg. 2007; 16: 379–387.
86. Christ S, Rindfleisch F, Friederich P. Superficial cervical plexus neuropathy after single-injection interscalene brachial plexus block. Anesth Analg. 2009; 109: 2008–2011.
87. Fredrickson MJ, Kilfoyle DH. Neurological complication analysis of 1000 ultrasound guided peripheral nerve blocks for elective orthopaedic surgery: a prospective study. Anaesthesia. 2009; 64: 836–844.
88. Liu SS, Zayas VM, Gordon MA, et al. A prospective, randomized, controlled trial comparing ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery for posoperative neurological symptoms. Anesth Analg. 2009; 109: 265–271.
89. Davis JJ, Swenson JD, Greis PE, Burks RT, Tashjian RZ. Interscalene block for postoperative analgesia using only ultrasound guidance: the outcome in 200 patients. J Clin Anesth. 2009; 21: 272–277.
90. Perlas A, Lobo G, Lo N, Brull R, Chan VW, Karkhanis R. Ultrasound-guided supraclavicular block. Outcome of 510 consecutive cases. Reg Anesth Pain Med. 2009; 34: 171–176.
91. Sharma S, Iorio R, Specht LM, Davies-Lepie S, Healy WL. Complications of femoral nerve block for total knee arthroplasty. Clin Orthop Relat Res. 2010; 468: 135–140.
92. Liu SS, Gordon MA, Shaw PM, Wilfred S, Shetty T, Yadeau JT. A prospective clinical registry of ultrasound-guided regional anesthesia for ambulatory shoulder surgery. Anesth Analg. 2010; 111: 617–623.
93. Misamore G, Webb B, McMurray S, Sallay P. A prospective analysis of interscalene brachial plexus blocks performed under general anesthesia. J Shoulder Elbow Surg. 2011; 20: 308–314.
94. Singh A, Kelly C, O’Brien T, Wilson J, Warner JJ. Ultrasound-guided interscalene block anesthesia for shoulder arthroscopy: a prospective study of 1319 patients. J Bone Joint Surg Am. 2012; 94: 2040–2046.
95. Hara K, Sakura S, Yokokawa N, Tadenuma S. Incidence and effects of unintentional intraneural injection during ultrasound-guided subgluteal sciatic nerve block. Reg Anesth Pain Med. 2012; 37: 289–293.
96. Henningsen MH, Jaeger P, Hilsted KL, Dahl JB. Prevalence of saphenous nerve injury after adductor-canal-blockade in patients receiving total knee arthroplasty. Acta Anaesthesiol Scand. 2012; 57: 112–117.
97. Lecours M, Lévesque S, Dion N, et al. Complications of single-injection ultrasound-guided infraclavicular block: a cohort study. Can J Anaesth. 2013; 60: 244–252.
98. Rohrbaugh M, Kentor ML, Orebaugh SL, Williams B. Outcomes of shoulder surgery in the sitting position with interscalene nerve block: a single-center series. Reg Anesth Pain Med. 2013; 38: 28–33.
99. Nye ZB, Horn JL, Crittenden W, Abrahams MS, Aziz MF. Ambulatory continuous posterior lumbar plexus blocks following hip arthroscopy: a review of 213 cases. J Clin Anesth. 2013; 25: 268–274.
100. Neal JM, Gerancher JC, Hebl JR, et al. Upper extremity regional anesthesia. Essentials of our current understanding, 2008. Reg Anesth Pain Med. 2009; 34: 134–170.
101. Pitman MI, Nainzadeh N, Ergas E, Springer S. The use of somatosensory evoked potentials for detection of neuropraxia during shoulder arthroscopy. Arthroscopy. 1988; 4: 250–255.
102. Ho E, Cofield RH, Balm MR, Hattrup SJ, Rowland CM. Neurologic complications of surgery for anterior shoulder instability. J Shoulder Elbow Surg. 1999; 8: 266–270.
103. Nagda SH, Rogers KJ, Sestokas AK, et al. Neer Award 2005: peripheral nerve function during shoulder arthroplasty using intraoperative nerve monitoring. J Shoulder Elbow Surg. 2007; 16: S2–S8.
104. Lädermann A, Lübbeke A, Mélis B, et al. Prevalence of neurologic lesions after total shoulder arthroplasty. J Bone Joint Surg Am. 2011; 93: 1288–1293.
105. Gschwend N, Simmen BR, Matejovsky Z. Late complications in elbow arthroplasty. J Shoulder Elbow Surg. 1996; 5: 86–96.
106. O’Driscoll SW, Morrey BF. Arthroscopy of the elbow. Diagnostic and therapeutic benefits and hazards. J Bone Joint Surg Am. 1992; 74: 84–94.
107. Farrell CM, Springer BD, Haidukewych GJ, Morrey BF. Motor nerve palsy following primary total hip arthroplasty. J Bone Joint Surg Am. 2005; 87: 2619–2625.
108. Bhat R. Transient vascular insufficiency after axillary brachial plexus block in a child. Anesth Analg. 2004; 98: 1284–1285.
109. Goulding K, Beaulé PE, Kim PR, Fazekas A. Incidence of lateral femoral cutaneous nerve neuropraxia after anterior approach hip arthroplasty. Clin Orthop Relat Res. 2010; 468: 2397–2404.
110. Schmalzried TP, Amstutz HC, Dorey FJ. Nerve palsy associated with total hip replacement. Risk factors and prognosis. J Bone Joint Surg Am. 1991; 73: 1074–1080.
111. Schmalzried TP, Noordin S, Amstutz HC. Update on nerve palsy associated with total hip replacement. Clin Orthop Relat Res. 1997: 188–206.
112. Mochida H, Kikuchi S. Injury to infrapatellar branch of saphenous nerve in arthroscopic knee surgery. Clin Orthop Relat Res. 1995: 88–94.
113. Jameson S, Emmerson K. Altered sensation over the lower leg following hamstring graft anterior cruciate ligament reconstruction with transverse femoral fixation. Knee. 2007; 14: 314–320.
114. Ferkel RD, Heath DD, Guhl JF. Neurological complications of ankle arthroscopy. Arthroscopy. 1996; 12: 200–208.
115. Zaidi R, Cro S, Gurusamy K, et al. The outcome of total ankle replacement: a systematic review and meta-analysis. Bone Joint J. 2013; 95-B: 1500–1507.
116. Kopp SL, Peters SM, Rose PS, Hebl JR, Horlocker TT. Worsening of neurologic symptoms after spinal anesthesia in two patients with spinal stenosis. Reg Anesth Pain Med. 2015; 40: 502–505.
117. Neal JM, Rathmell JP. Complications in Regional Anesthesia and Pain Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.
    118. Kalichman L, Cole R, Kim DH. Spinal stenosis prevalence and associated symptoms: the Framingham Study. Spine J. 2009; 9: 545–550.
    119. Drummond JC. The lower limit of autoregulation: time to revise our thinking? Anesthesiology. 1997; 86: 1431–1433.
    120. Drummond JC, Lee RR, Owens EL. Spinal cord ischemia occuring in association with induced hypotension for colonic surgery. Anesth Analg. 2012; 114: 1297–1300.
    121. Joshi B, Ono M, Brown C, et al. Predicting the limits of cerebral autoregulation during cardiopulmonary bypass. Anesth Analg. 2012; 114: 503–510.
    122. Laflam A, Joshi B, Brady K, et al. Shoulder surgery in the beach chair positioin is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation beach chair study. Anesth Analg. 2015; 120: 176–185.
    123. Rathmell JP, Benzon HT, Dreyfuss P, et al. Safeguards to prevent neurologic complications after epidural steroid injections: consensus opinions from a multidisciplinary working group and national organizations. Anesthesiology. 2015; 122: 974–984.
    124. Rathmell JP, Michna E, Fitzgibbon DR, Stephens LS, Posner KL, Domino KB. Injury and liability associated with cervical procedures for chronic pain. Anesthesiology. 2011; 114: 918–926.
    125. Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: more dangerous than we think? Spine (Phila Pa 1976). 2007; 32: 1249–1256.
    126. Kennedy DJ, Dreyfuss P, Aprill C, Bogduk N. Paraplegia following image-guided transforaminal lumbar spine epidural steroid injection: two case reports. Pain Med. 2009; 10: 1389–1394.
    127. Lee JH, Lee JK, Seo BR, Moon SJ, Kim JH, Kim SH. Spinal cord injury produced by direct damage during cervical transforaminal epidural injection. Reg Anesth Pain Med. 2008; 33: 377–379.
    128. Benzon HT, Chew TL, McCarthy R, Benzon HA, Walega DR. Comparison of the particle sizes of the different steroids and the effect of dilution: a review of the relative neurotoxicities of the steroids. Anesthesiology. 2007; 106: 331–338.
    129. El-Yahchouchi C, Geske JR, Carter RE, et al. The noninferiority of the nonparticulate steroid dexamethasone and triamcinolone in lumbar transforaminal epidural steroid injections. Pain Med. 2013; 14: 1650–1657.
    130. Kennedy DJ, Plastaras C, Casey E, et al. Comparative effectiveness of lumbar transforaminal epidural steroid injections with particulate versus nonparticulate corticosteroids for lumbar radicular pain due to intervertebral disc herniation: a prospective, randomized, double-blind trial. Pain Med. 2014; 15: 548–555.
    131. Hejtmanek MR, Pollock JE. Chloroprocaine for spinal anesthesia: a retrospective analysis. Acta Anaesthesiol Scand. 2011; 55: 267–272.
    132. Vaghadia H, Neilson G, Lennox PH. Selective spinal anesthesia for outpatient transurethral prostatectomy (TURP): randomized controlled comparison of chloroprocaine with lidocaine. Acta Anaesthesiol Scand. 2012; 56: 217–223.
    133. Doan L, Piskoun B, Rosenberg AD, Blanck TJ, Phillips MS, Xu F. In vitro antiseptic effects on viability of neuronal and Schwann cells. Reg Anesth Pain Med. 2012; 37: 131–138.
    134. American Society of Anesthesiologists Task Force on Infectious Complications Associated with Neuraxial Techniques. Practice advisory for the prevention, diagnosis, and management of infectious complications associated with neuraxial techniques: a report by the American Society of Anesthesiologists Task Force on infectious complications associated with neuraxial . Anesthesiology. 2010; 112: 530–545.
    135. Taenzer AH, Walker BJ, Bosenberg AT, et al. Asleep versus awake: does it matter? Pediatric regional block complications by patient state: a report from the Pediatric Regional Anesthesia Network. Reg Anesth Pain Med. 2014; 39: 279–283.
    136. Liu SS, YaDeau JT, Shaw PM, Wilfred S, Shetty T, Gordon M. Incidence of unintentional intraneural injection and postoperative neurological complications with ultrasound-guided interscalene and supraclavicular nerve blocks. Anaesthesia. 2011; 66: 168–174.
    137. Whitlock EL, Brenner MJ, Fox IK, Moradzadeh A, Hunter DA, Mackinnon SE. Ropivacaine-induced peripheral nerve injection injury in the rodent model. Anesth Analg. 2010; 111: 214–220.
    138. Farber SJ, Saheb-Al-Zamani M, Zieske L, et al. Peripheral nerve injury after local anesthetic injection. Anesth Analg. 2013; 117: 731–739.
    139. Kaufman MR, Elkwood AI, Rose MI, et al. Surgical treatment of permanent diaphragm paralysis after interscalene nerve block for shoulder surgery. Anesthesiology. 2013; 119: 484–487.
    140. Bigeleisen PE. Nerve puncture and apparent intraneural injection during ultrasound-guided axillary block does not invariably result in neurologic injury. Anesthesiology. 2006; 105: 779–783.
    141. Bigeleisen PE, Moayeri N, Groen GJ. Extraneural versus intraneural stimulation thresholds during ultrasound-guided supraclavicular block. Anesthesiology. 2009; 110: 1235–1243.
    142. Sala-Blanch X, López AM, Carazo J, et al. Intraneural injection during nerve stimulator-guided sciatic nerve block at the popliteal fossa. Br J Anaesth. 2009; 102: 855–861.
    143. Steinfeldt T, Poeschl S, Nimphius W, et al. Forced needle advancement during needle-nerve contact in a porcine model: histologic outcome. Anesth Analg. 2011; 113: 417–420.
    144. Wiesmann T, Bornträger A, Vassiliou T, et al. Minimal current intensity to elicit an evoked motor response cannot discern between needle-nerve contact and intraneural needle insertion. Anesth Analg. 2014; 118: 681–686.
    145. Voelckel WG, Klima G, Krismer AC, et al. Signs of inflammation after sciatic nerve block in pigs. Anesth Analg. 2005; 101: 1844–1846.
    146. Claudio R, Hadzic A, Shih H, et al. Injection pressures by anesthesiologists during simulated peripheral nerve block. Reg Anesth Pain Med. 2004; 29: 201–205.
    147. Theron PS, Mackay Z, Gonzalez JG, Donaldson N, Blanco R. An animal model of “syringe feel” during peripheral nerve block. Reg Anesth Pain Med. 2009; 34: 330–332.
    148. Orebaugh SL, McFadden K, Skorupan H, Bigeleisen PE. Subepineurial injection in ultrasound-guided interscalene needle tip placement. Reg Anesth Pain Med. 2010; 35: 450–454.
    149. Robards C, Hadzic A, Somasundaram L, et al. Intraneural injection with low-current stimulation during popliteal sciatic nerve block. Anesth Analg. 2009; 109: 673–677.
    150. Gadsden JC, Choi JJ, Lin E, Robinson A. Opening pressure consistently detects needle-nerve contact during ultrasound-guided interscalene brachial plexus block. Anesthesiology. 2014; 120: 1246–1253.
    151. Spence BC, Beach ML, Gallagher JD, Sites BD. Ultrasound-guied interscalene blocks: understanding where to inject the local anesthetic. Anaesthesia. 2011; 66: 509–514.
    152. Upton AR, McComas AJ. The double crush in nerve entrapment syndromes. Lancet. 1973; 2: 359–362.
    153. Osterman AL. The double crush syndrome. Orthop Clin North Am. 1988; 19: 147–155.
    154. Dripps RD, Vandam LD. Exacerbation of pre-existing neurologic disease after spinal anesthesia. N Engl J Med. 1956; 255: 843–849.
    155. Kalichman MW, Calcutt NA. Local anesthetic–induced conduction block and nerve fiber injury in streptozotocin-diabetic rats. Anesthesiology. 1992; 77: 941–947.
    156. Willams BA. Toward a paradigm shift for the clinical care of diabetic patients requiring perineural analgesia: strategies for using the diabetic rat model. Reg Anesth Pain Med. 2010; 35: 329–332.
    157. Gebhard RE, Nielsen KC, Pietrobon R, Missair A, Williams BA. Diabetes mellitus, independent of body mass index, is associated with a “higher success” rate for supraclavicular brachial plexus blocks. Reg Anesth Pain Med. 2009; 34: 404–407.
    158. Sites BD, Gallagher J, Sparks M. Ultrasound-guided popliteal block demonstrates an atypical motor response to nerve stimulation in 2 patients with diabetes mellitus. Reg Anesth Pain Med. 2003; 28: 479–482.
    159. Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: neurotoxicity and neural blood flow. Reg Anesth Pain Med. 2003; 28: 124–134.
    160. Hebl JR, Horlocker TT, Pritchard DJ. Diffuse brachial plexopathy after interscalene blockade in a patient receiving cisplatin chemotherapy: the pharmacologic double crush syndrome. Anesth Analg. 2001; 92: 249–251.
    161. van Alfen N, van Engelen BG. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain. 2006; 129: 438–450.
    162. Dyck PJ, Windebank AJ. Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. Muscle Nerve. 2002; 25: 477–491.
    163. Ahn KS, Kopp SL, Watson JC, Scott KP, Trousdale RT, Hebl JR. Postsurgical inflammatory neuropathy. Reg Anesth Pain Med. 2011; 36: 403–405.
    164. Staff NP, Engelstad J, Klein CJ, et al. Post-surgical inflammatory neuropathy. Brain. 2010; 133: 2866–2880.
    165. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998; 339: 285–291.
    166. Crawford JS. Epidural analgesia for patients with chronic neurological disease. Anesth Analg. 1983; 62: 620–621.
    167. Misawa S, Kuwabara S, Mori M, Hayakawa S, Sawai S, Hattori T. Peripheral nerve demyelination in multiple sclerosis. Clin Neurophysiol. 2008; 119: 1829–1833.
    168. Pogorzelski R, Baniukiewica E, Drozdowski W. Subclinical lesions of peripheral nervous system in multiple sclerosis patients. Neurol Neurochir Pol. 2004; 38: 257–264.
    169. Koff MD, Cohen JA, McIntyre JJ, Carr CF, Sites BD. Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis. Anesthesiology. 2008; 108: 325–328.
    170. Kuczkowski KM. Labor analgesia for the parturient with neurological disease: what does an obstetrician need to know? Arch Gynecol Obstet. 2006; 274: 41–46.
    171. Kaplan KM, Spivak JM, Bendo JA. Embryology of the spine and associated congenital abnormalities. Spine J. 2005; 5: 564–576.
    172. Warner MA, Warner DO, Matsumoto JY, et al. Ulnar neuropathy in surgical patients. Anesthesiology. 1999; 90: 54–59.
    173. Cheney FW, Domino KB, Caplan RA, Posner KL. Nerve injury associated with anesthesia: a closed claims analysis. Anesthesiology. 1999; 90: 1062–1069.
    174. Engelsson S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Acta Anaesthesiol Scand. 1974; 18: 79–87.
    175. Lee P, Russell WJ. Preventing pain on injection of propofol: a comparison between lignocaine pretreatment and lignocaine added to propofol. Anaesth Intensive Care. 2004; 32: 482–484.
    176. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg. 1994; 79: 1165–1177.
    177. Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a literature survey with meta-analysis of 613 patients. Neurosurg Rev. 2003; 26: 1–49.
    178. Lawton MT, Porter RW, Heiserman JE, Jacobowitz R, Sonntag VK, Dickman CA. Surgical management of spinal epidural hematoma: relationship between surgical timing and neurological outcome. J Neurosurg. 1995; 83: 1–7.
    179. Wedel DJ, Horlocker TT. Risks of regional anesthesia—infection, sepsis. Reg Anesth. 1996; 21: 57–61.
    180. Reihsaus E, Waldbaur H, Seeling W. Spinal epidural abscess: a meta-analysis of 915 patients. Neurosurg Rev. 2000; 23: 175–204.
    181. Kumral E, Polat F, Güllüoglu H, Uzunköprü C, Tuncel R, Alpaydin S. Spinal ischaemic stroke: clinical and radiological findings and short-term outcome. Eur J Neurol. 2011; 18: 232–239.
    182. Kretschmer T, Heinen CW, Antoniadis G, Richter HP, König RW. Iatrogenic nerve injuries. Neurosurg Clin N Am. 2009; 20: 73–90.
    183. Cruccu G, Aziz TZ, Garcia-Larrea L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007; 14: 952–970.
    Back to Top | Article Outline

    APPENDIX 1. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence

    Table

    Table

    Back to Top | Article Outline

    APPENDIX 2. Strength of Recommendations

    Table

    Table

    Copyright © 2015 by American Society of Regional Anesthesia and Pain Medicine.