Friedrich, Jason M.; Harrast, Mark A.
The use of lumbar epidural steroid injections (LESI) has increased dramatically since their inception in the 1950s. While our understanding of the pathophysiology and natural history of herniated nucleus pulposis (HNP), lumbar spinal stenosis (LSS), and other spinal disorders has improved, some controversy remains regarding the efficacy of LESI fueled by the lack of well designed, placebo-controlled studies. Instead, published data report a wide range of success rates in heterogeneous patient populations, using a variety of procedural techniques, control populations, and outcome measures. Notwithstanding the limitations of the available literature, a thoughtful and rational approach to the use of LESI can help improve clinical outcomes and decrease risks.
RATIONALE FOR THE USE OF LESI
Radicular pain occurs as a result of both mechanical nerve compression and a chemoinflammatory response. Mechanical compression, such as that from herniated disc material or foraminal osteophytes, can cause local structural changes to nerve roots leading to demyelination, axonal transport block, vascular changes, intraneural edema, and stimulation of an inflammatory reaction (5). However, mechanical compression by itself may not produce pain in every patient, even when compressive pathology is evident on advanced imaging.
Alternatively, one can have classic radicular pain without neural impingement on magnetic resonance imaging (MRI). This is attributable to the chemoinflammatory response that is best understood as a result of HNP. An annular tear exposes the highly antigenic nucleus pulposis, triggering an inflammatory cascade that contributes to localized neural edema, altered nerve function, and sensitization (5). Sensitizing chemicals and inflammatory mediators have been identified at the site of disc injury, including glutamate, phosholipase A2, substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide (24,33). Further, neuropeptide receptors have been found in potential pain generators, including the dorsal root ganglion (DRG), annulus, and ligaments (24,33). While the exact role of each substance is not known, placement of autologous nucleus pulposis around the DRG does cause sustained nerve discharges consistent with nociception (33). This chemoinflammatory reaction may sensitize nerve endings such that even minor irritation may produce radicular pain in sensitized nerve roots.
Given the chemoinflammatory contribution to pain, corticosteroids provide a rational treatment approach. Corticosteroids decrease inflammation through inhibition of prostaglandins in the arachadonic acid cascade, which may improve microcirculation through decreasing capillary permeability, nerve root edema, and ischemia (23). Steroids also directly inhibit the excitation of pain-generating c-fiber neurons (33). Still, all the mechanisms by which corticosteroids act are not understood completely.
Theoretically, LESI place a higher concentration of corticosteroid at the site of pathology compared with more systemic oral therapy, which likely would have more systemic side effects. Moreover, some animal models report possible synergistic effects of local anesthetics with steroids for improving inflammation after HNP and improving intraneural blood flow in a compressed nerve root (25).
LESI is used for a variety of reasons. Diagnostically, it can be useful in cases of chemical radiculitis, which may not be evident on electrodiagnostic testing or advanced imaging, or multilevel pathology. A selective nerve root block, similar to a transforaminal LESI, is often used for diagnostic purposes. LESI also may assist in predicting postoperative prognosis after decompression surgery (16,32). However, the most common indications for LESI are therapeutic: radicular pain related to HNP, followed by neurogenic claudication or radiculopathy from LSS and, to a much lesser extent, discogenic pain. Specific evidence for each indication will be discussed later in this article. The following sections aim to provide some background on the most common indications. In reviewing these indications, the reader should understand that LESI is best used as one part of a comprehensive treatment program, which typically includes activity modification and rehabilitation while the patient is hopefully following the general natural history of lumbar radiculopathy (spontaneous improvement over time).
Radicular Pain From HNP
The natural history of radicular pain from HNP is favorable with similar outcomes in surgically and nonsurgically treated patients at 10-yr follow-up (39). The lifetime incidence of lumbar radicular pain from HNP is 13%-40%, with an annual incidence of 1%-5%, peaking in the fourth to fifth decades and declining thereafter (19). Most HNP occur at L4-5 or L5-S1. Approximately 80% of HNP improve with conservative care (9), with 75% feeling better within 4-6 wk, 60% recovered within 3 months, and 70% within 6 months (29). Resolution of HNP on imaging may trail clinical improvement, with 50%-80% of HNP showing greater than 50% reduction in size within 1-2 yr (39). It is interesting to note that large extrusions have the greatest likelihood of complete resolution (39).
The available literature does support the use of fluoroscopically guided LESI for the treatment of radicular pain associated with HNP for more early pain relief, decreased need for surgical intervention, and to facilitate participation in an active therapy program (5). There is no correlation between improvement after LESI and severity of symptoms or severity of pathology on advanced imaging.
Neurogenic Claudication From LSS
LSS may include narrowing of the central canal, lateral recess, and/or neural foramen. The hallmark is neurogenic claudication, where leg pain is worsened with lumbar extension and relieved with lumbar flexion. LSS also may present as a radiculopathy. While the natural history of degenerative LSS is not understood entirely, rapid neurological deterioration is rare. Limited studies of nonoperative treatment for LSS report that 15%-45% improve, 15%-30% worsen, and up to 70% remain stable symptomatically over time (23). In a study with 8- to 10-yr follow-up comparing surgical with nonoperative therapy, early outcomes at 1 and 4 yr favored surgical management, but most long-term outcomes were similar (23).
There is probably a role for LESI for symptomatic relief during flares of LSS as part of a comprehensive rehab program. Except in severe cases, delaying surgery to consider nonoperative management is rational and does not negatively impact postoperative outcomes (23). Spinal dimensions do not seem to predict efficacy of LESI (12). LSS literature more strongly supports LESI for polyradicular pain than for axial low back pain (LBP).
Discogenic pain (or intrinsic disc pain) is thought to result from degenerative disc, annular tear, or HNP (which more typically causes extrinsic disc pain from nerve root irritation) causing axial or referred symptoms without radiculopathy. Compared with radicular pain, less literature exists to support the use of LESI for discogenic pain. Theoretically, discogenic pain could result from the same local chemoinflammatory response following exposure of the antigenic nucleus pulposis and sensitization of the annular or ligament nerve endings. Therefore, a trial LESI would be reasonable in select refractory cases of discogenic pain, recognizing that conclusive evidence for this patient population is lacking (43).
LESI generally is safe, and few absolute contraindications exist: uncompensated coagulopathy, infection, history of severe allergic reaction to any of the injected materials, local malignancy, acute spinal cord compression, and inability to obtain informed consent. LESI also should be avoided in patients with uncontrolled diabetes or uncompensated congestive heart failure. Fluoroscopy for LESI is contraindicated in pregnancy. Extra caution should be taken in immunocompromised patients, possibly including laboratory testing and periprocedure antibiotics.
Coagulopathies include bleeding disorders or the presence of anticoagulant and some antiplatelet medications. Clearance from the prescribing provider should be obtained before discontinuing anticoagulant medications. In certain cases of cardiac stenting and valve replacements, cardiologists will not allow temporary suspension of anticlotting agents for elective procedures. Warfarin therapy should be stopped 4-5 d before injection, and the international normalized ratio (INR) should be normalized preinjection (22). Antiplatelet agents, including clopidogrel and ticlopidine should be stopped 7 and 14 d, respectively, before injection. Low-molecular weight heparin should be held for at least 12 h in prophylactic dosing and 24 h in therapeutic dosing. Continuation of aspirin or nonsteroidal antinflammatory agents has not been found to be a contraindication to LESI. The risks of discontinuing anticoagulant medications need to be considered in light of case reports of stroke in patients whose medications were suspended for LESI (31).
Though not absolute contraindications, factors that negatively affect outcomes should be considered in the risk-benefit analysis prior to LESI. For instance, worse outcomes have been found in smokers, chronic pain syndrome, axial-only pain or diffuse pain, opioid dependence, and disability claims (1).
There is no consensus as to the timing, frequency, and optimal steroid for LESI. A recent review found no basis for a series of three, but could not make a definitive determination about the most appropriate frequency of injections because of lack of research (35). With fluoroscopic guidance, a single, well placed injection may be adequate; if this fails, then an alternate approach may be considered. Most studies and clinical experience demonstrate an average of one to three injections for significant improvement (8,32,37,46). For transforaminal LESI, to achieve greater than 70% improvement, most subjects averaged two injections (46). DePalma's 2005 review recommends a trial of four injections before considering surgical intervention for radicular pain (15). International Spine Intervention Society (ISIS) guidelines recommend no more than four injections in a 6-month period (6), although some argue to limit injections to three in 1 yr to decrease the risk of systemic steroid side effects.
A reasonable approach would be to inject no more frequently than every 2 wk, as steroids from any single injection may take a full week to take effect. If significant partial improvement is present, consider repeating the injection. If no improvement, consider an alternate diagnosis. If a true radicular pattern is present, consider repeating the injection with a different approach and/or different steroid, but plan not to exceed three injections in 1 yr in most cases. If excellent improvement occurs, then maximize rehabilitation and observe clinically.
There is not enough literature to support greater efficacy of any one type of corticosteroid over another in LESI. Anecdotally and theoretically, particulate steroids, such as triamcinolone, may remain longer at the site of pathology, which could improve efficacy. However, as will be discussed, intravascular injection of particulate steroids is a known cause of spinal cord infarct, whereas no such reports exist with nonparticulate steroids, such as dexamethasone (22). Dexamethasone particles are 10 times smaller than red blood cells (RBC), methylprednisolone particles are mostly smaller than RBC but can be densely packed, and both triamcinolone and betamethasone particles are of variable sizes (some larger than RBC) and aggregating, thus potentially more likely to cause a symptomatic embolism (17).
TECHNIQUES AND ASSOCIATED INDICATIONS
Three approaches exist for entrance to the lumbar epidural space, including caudal, interlaminar (ILESI), and transforaminal (TFESI). As will be explained in detail later, TFESI has the best literature support, but a role likely exists for all three approaches, depending on the individual's symptoms, anatomy, and pathology. For all three approaches, the use of fluoroscopy is essential to maximize accuracy and safety, as the miss rate for blind ILESI and caudal ESI is 30%-40% even in experienced hands (23), and aspiration alone is insensitive for detecting potentially catastrophic intravascular needle placement (22).
In a caudal ESI, the needle is directed to the sacral hiatus, and a relatively larger volume is injected to distribute the steroid cephalad (Fig. 1). Still, the injectant is unlikely to reach above the L4-5 level, thus treating more cephalad pathology with a caudal ESI generally is not recommended. The injectant typically travels in both the anterior and posterior epidural space (2). This approach is used for L4-5 and L5-S1 pathology, when symptoms are more diffuse (not monoradicular, when a TFESI would be desirable) or if there is concern of epidural scarring in a postoperative patient (when an ILESI would risk dural puncture). Thus, caudal ESI could be considered in the patient with nonlocalizing, bilateral symptoms of neurogenic claudication with MRI-confirmed L5-S1 stenosis.
ILESI is most commonly performed at the L4-5 level, but may be used at any level in the lumbar spine. Typically, the needle enters the posterior epidural space via a paramedian approach, utilizing a "loss of resistance" technique (Fig. 2). The injectant may travel one to two levels caudad or cephalad, and it flows to the anterior epidural space 36%-76% of the time, bilaterally in 16%-86% (depending on how far medial or lateral the needle is placed) (7,13,47,48). Thus ILESI could be considered in the patient with diffuse, nonlocalizing bilateral symptoms of neurogenic claudication with central canal stenosis on MRI (including higher lumbar levels not reached with a caudal approach), or with unilateral monoradicular symptoms in the patient with severe multilevel neuroforaminal stenosis limiting access for a TFESI. This approach should be avoided at levels of previous posterior spinal surgery or severe central stenosis that obliterates the posterior epidural space, increasing the risk of intrathecal penetration.
The transforaminal approach accesses the epidural space via an oblique angle to the lateral neural foramen (Fig. 3). It can be performed at any level, is thought to be the most selective of the three approaches, allows the best access to the ventral epidural space near the disc, and may be the most effective for a monoradiculopathy because of HNP. This approach also carries the greatest risk of intravascular injection into or injury to the radicular artery; therefore, careful use of fluoroscopy and digital subtraction angiography (DSA) is recommended. Thus a patient with right L5 radicular symptoms and MRI evidence of an L4-5 paracentral HNP may benefit from a right L5-S1 TFESI, placing the injectant near the exiting L5 nerve root. The best level for TFESI is still debated, as some would prefer a right L4-5 TFESI in this case, with a goal of placing the injectant potentially closer to the HNP and site of compression near the preganglionic L5 nerve root, before it exits through L5-S1 neuroforamen (26).
Complications from LESI are rare and can occur as a result of the procedure itself or from the solutions injected. Procedural complications include infection, hematoma, intravascular injection, dural puncture, air embolism, vasovagal syncope, and allergic reaction.
Severe infection is exceedingly rare, with a reported incidence of 0.01%-0.1% for all spinal injections (22). Most often the result of needle introduction of skin flora with inadequate sterile technique, reported infections include meningitis, epidural abscess, vertebral osteomyelitis, and discitis (22).
Epidural hematomas are rare in patients with normal clotting factors, with an overall incidence reported to be 1 in 150,000 epidurals (22), with an unknown proportion developing neurologic injury. A recent case report described spinal cord compression from epidural hematoma after ILESI in a patient with unrecognized idiopathic thrombocytopenic purpura (50).
Intravascular uptake occurs at a rate of 8% for all lumbar injections, 2% for ILESI, 11% for all TFESI, and 21% for TFESI at the S1 level (22). There are no reported severe effects of intravascular injection of contrast or local anesthetic at concentrations used for LESI. Theoretical effects of intravascular anesthetic may include dizziness, tinnitus, nausea, muscle twitching, metallic taste, cardiac arrhythmia, seizures, or coma. There have been multiple reports of paraplegia, presumably from injection of particulate steroids into the artery of Adamkiewicz. This artery provides the main supply to the anterior spinal artery in the lumbar region and typically enters the spinal canal on the left side between T9 and L2. However, in 15% of people, entry is lower than L2, and it is on the right side 37% of the time (22). There have been no reported complications of injection of nonparticulate steroids (23). Negative aspiration is inadequate at detecting intravascular penetration 50% of the time (20). Risk of intravascular injection is further reduced by not only using contrast with intermittent live fluoroscopy, but also with DSA, which allows improved visualization of vascular structures (41).
Nerve damage also is a theoretical risk with nerve puncture and associated intraneural hematoma formation. Any solution injected into a nerve could potentially be neurotoxic, but this is unlikely to occur in an awake patient who is well aware if the needle tip even grazes the nerve.
Dural puncture is rare but with relatively greater risk in ILESI. Important indicators include cerebrospinal fluid flashback and contrast patterns representative of subdural and subarachnoid spread. Dural puncture alone is not dangerous, but may lead to a spinal headache, which is generally self-limiting. Intrathecal injection of local anesthetics results in variable levels of spinal block, and intrathecal injection of any substance, particularly corticosteroid, carries the potential risk of arachnoiditis (22).
Vasovagal syncope is a risk with any type of injection, typically occurs in 1%-2% of LESI, and has a significantly higher incidence (8%) in cervical injections (45). Symptoms are self-limited with removal of the needle and supportive care.
Complications related to the solutions injected are rare. Hypersensitivity or anaphylactic reactions most often occur with contrast but occasionally to anesthetic or its preservative. Premedication with steroid and antihistamine or using gadolinium are options in cases of iodinated contrast allergy.
Corticosteroids have inherent side effects with oral systemic therapy and can occur to a lesser extent with LESI. Important considerations include elevation of blood sugars in diabetics with an average increase of 106 mg·dL−1 on the evening of the injection and significant increased levels for 3 d (21). Some fluid retention can occur, and thus caution is taken in patients with congestive heart failure. Case reports also exist of LESI causing Cushingoid syndrome and temporary adrenal suppression, but evidence has not yet linked LESI directly to bone loss or osteonecrosis (22).
Evaluation of the efficacy of LESI is challenging. Many limitations hinder the comparison of studies: variable treatment protocols and patient selection, lack of appropriate controls or uniform outcome measures, and lack of fluoroscopy in many studies. Given the heterogeneity of primary research, review articles and guidelines understandably arrive at mixed conclusions. The only consensus across review articles is that LESI likely offers some short-term relief for radicular pain, with variable levels of evidence for longer-term relief, disability, axial pain, and avoidance of surgery (4,14,15,38). The many recent studies and reviews have focused on TFESI. Roberts used strict inclusion criteria and offers a detailed review of nine randomized-controlled, fluoroscopically guided, lumbar TFESI with clinically based outcome measures, and concludes that TFESI is more effective than placebo for short- and long-term pain relief from radicular pain, and it could be used as a surgery sparing intervention (38).
The following sections aim to provide an evidence-based and clinically relevant review of the utility of LESI for avoidance of surgery, to predict surgical outcome, and to improve pain and disability related to HNP, LSS, and LBP, and to affect return to work and opiate use.
To Avoid Surgery
Only one study has compared surgical rates in patients who were deemed surgical candidates for radicular pain from HNP or LSS (37). At 1-yr follow-up, they found significantly decreased surgical rates in patients treated with up to four TFESI compared with those given a transforaminal injection of local anesthetic only (29% vs 67%). A follow-up study at 5 yr determined that up to 81% who avoided surgery at 1 yr still avoided it at 5 yr, regardless of initial treatment group (36), indicating that LESI may be a temporizing measure to get patients through acute flares and allow the body to heal itself.
Butterman compared fluoroscopically guided ILESI to discectomy (11). He found that patients who fail 6 wk of conservative care for back and leg pain from HNP have similar improvement in self-reported back pain and disability after 3 months and leg pain after 6 months. Discectomy tended to provide earlier symptom improvement. Limitations included lack of blinding, cross-over group, variable steroid doses, atypical injection frequency (three injections, 1 wk apart), and no quantification of leg and back pain.
To Predict Surgical Outcome
Retrospective evidence exists that fluoroscopically guided TFESI or ILESI that produce greater than 80% immediate improvement in leg symptoms (local anesthetic effect) and greater than 50% relief for at least 1 wk predicts greater than 50% relief with surgical decompression (with a positive predictive value of 85%-91% and a negative predictive value of 77%, regardless of duration of symptoms) (16). These conclusions also are supported by a prospective series showing that only 5% of patients with no response to LESI will go on to have significant pain relief with decompression surgery (32).
To Decrease Self-Reported Pain and Disability Related to Radicular Pain
Most randomized controlled studies of LESI fall into this category, but each study approach has methodological limitations. The abundant uncontrolled studies will not be reviewed. The best available studies tend to be those of TFESI.
In a placebo-controlled study, Vad compared TFESI to saline trigger point injection (TPI) and found that in patients with leg pain greater than back pain from HNP for at least 6 wk, significantly more patients treated with TFESI declared at least 50% pain relief and at least 5-point improvement on the Roland-Morris Disability Index than those treated with TPI (84% vs 48%) (46). The study was not blinded, and raw data and baseline characteristics were not provided.
Karpinnen compared TFESI with transforaminal saline injections and found that in patients with clinical evidence of radicular leg pain, those treated with either steroids or saline showed significant improvement over time, with greater improvement in the steroid group at 2 wk (27). Limitations included technical quality of injection (lower than expected local anesthetic effect) and only one injection allowed. This study does bring to light the possible therapeutic effect of saline as a washout of chemoinflammatory mediators in the epidural space.
Ng compared TFESI with transforaminal injection of bupivicaine-only in patients with chronic radicular pain from HNP or LSS (34). They found decreased pain and disability at 6 and 12 wk in both groups, with shorter duration of symptoms being the only predictor of better outcome. It is interesting to note that the steroid group had a longer duration of symptoms at baseline, which may confound the results.
Several studies compare TFESI with other approaches, but interpretation of each is limited by methodological concerns. Ackerman used strict selection criteria for 90 patients with S1 radiculopathy and randomized patients to TFESI, ILESI, or caudal ESI (2). Oswestry disability scores were similarly improved for all groups, while pain improvement was reported to be better for TFESI, attributed to more anterior spread of medication. However, pain scores were not reported, making clinically relevant differences difficult to discern. In a small sample of 31 patients, Thomas found that fluoroscopically guided TFESI improved pain greater than blind ILESI, which is of no surprise given the high miss rate with blind injections (44). Kolsi found that both fluoroscopically guided TFESI and ILESI provide similar improvement at 2 wk, but follow-up beyond 2 wk was not reported (30). Finally, Candido compared ILESI and TFESI in patients with LBP and unilateral radicular symptoms and found no significant differences in visual analog scale scores, but significant cross-over limits interpretation of this outcome (13).
There are still no high-quality, prospective, controlled studies specifically evaluating the efficacy of fluoroscopically guided ILESI or caudal ESI. The available controlled studies with and without fluoroscopy still do tend to support some relative short-pain relief from ILESI or caudal ESI, with variable long-term benefit beyond 4 wk (3,10,28,40,49).
To Decrease Self-Reported Pain and Disability Related to LSS
Because of limited research, no strict conclusions can be made about the use of LESI for LSS, nor which injection technique is best. Previous nonfluoroscopically guided studies showed at least some short-term benefit (23). More recent fluoroscopically guided studies also demonstrate short-term benefit with variable long-term results (23). The best study is by Botwin, a prospective cohort study that evaluated 34 patients with unilateral radicular symptoms secondary to degenerative LSS who were given a mean of 1.9 TFESI (8). All patients had central, lateral recess, and neural foraminal stenosis. At 2 months and 1 yr, patients showed significantly improved pain, disability, standing/walking tolerance, and satisfaction compared with preinjection baseline. Clearly, limitations exist, including lack of a control group. More recently, Koc compared fluoroscopically guided ILESI through "the most stenotic level" to inpatient physical therapy (PT) and control group in 29 patients with LSS on MRI (28). All groups were significantly improved at 6 months. Those who received PT or ILESI improved faster, with ILESI offering the earliest improvement. Poorly described symptom distribution and small sample size limit the usefulness of this study.
To Decrease Axial LBP
Even less research exists for the use of LESI to treat axial LBP. A retrospective study evaluated 84 patients with axial LBP refractory to conservative treatment at 3 months and MRI evidence of disc pathology at L4-5 or L5-S1, without stenosis, who received a fluoroscopically guided caudal ESI. At an average follow-up of 28 months after the injection, only 23% met strict criteria for successful outcome (42). More recently, Sayegh compared up to two blind caudal ESI to caudal injection of lidocaine, in patients with LBP for more than 1 month, with or without sciatica, and MRI evidence of HNP or disc degeneration (40). They found significant improvement in Oswestry Disability Index in both groups over time up to 1 yr, with earlier improvement in disability and straight-leg raise tolerance in the steroid group.
To Improve Return to Work or Opioid Use
No studies have evaluated directly return to work or opioid use after LESI as a primary outcome in a prospective controlled setting. Conclusions regarding secondary outcome return to work rates are mixed. Friedly looked retrospectively at a large veteran population with diagnoses of HNP, radiculopathy, spinal stenosis, degenerative disc disease, and other LBP syndromes and found no significant decrease in opioid use in patients who received a LESI (18). Many patients received injections for axial-only pain, further exemplifying the need for careful diagnosis and patient selection to achieve the best outcomes following LESI.
LESI is best used for radicular symptoms with the goal of pain management in the acute to subacute setting to help patients be more comfortable as they progress through the generally favorable natural history of spontaneous improvement. The transforaminal route, which has been studied most recently, appears to be the most efficacious approach for mono-radicular symptoms secondary to a disc protrusion. Further placebo-controlled studies are necessary to define more conclusively the role of LESI for the various causes of radicular pain and to define the best technique for each indication.
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