Compliance with the provisions in this Local Coverage Determination (LCD) may
be monitored and addressed through post payment data analysis and subsequent
medical review audits.

**History/Background and/or General Information**

Low back pain (LBP) is highly prevalent, with reports of 50-84% of adults
experiencing back pain at some point, with a high prevalence in adults 65 and
older and the highest cause of disability globally. Low back and neck pain can
influence the quality of life and function, and is associated with depression
and anxiety.1,2 In a 2018 National Health Interview Survey, the Centers for
Disease Control (CDC) reported 28% of men and 31.6% of women age  18 had
lower back pain in the past 3 months.3 There is debate and a lack of consensus
on which modalities are best to treat chronic low back pain (CLBP).4

The epidural space lies outside the dural membrane inside the spinal canal. It
runs the length of the spine and, in addition to the exiting nerve roots,
contains fatty tissue and blood vessels. The spinal nerve roots can be
affected by a number of processes as they travel through the epidural space,
including but not limited to compression from herniation of the nucleus
pulposus of the intervertebral discs, degenerative changes involving
combinations of the spinal ligaments, discs, zygapophyseal (facet) joints,
intraspinal synovial cysts, osteophytes, and mechanical derangements of the
spine such as spondylolisthesis. As a result of mechanical irritation,
inflammation, injury to a spinal nerve root or other processes, the spinal
nerve roots can become a significant and disabling source of radicular pain.1
Epidural steroid injections (ESIs) have been used as a non-surgical modality
to treat low back and neck pain. These procedures typically involve the
injection of a solution containing corticosteroids and/or anesthetic into the
epidural space, although saline may be included at times.

The ESI can be performed in 3 ways. Interlaminar epidural steroid injection
(ILESI) approaches the epidural space from the posterior spine between the 2
vertebral laminae near the midline. In the transforaminal epidural steroid
injection (TFESI) approach, the injectant is delivered through the
neuroforamen dorsal to the nerve root within the intervertebral foramen. The
caudal epidural steroid injection (CESI) approach enters through the sacral
hiatus at the sacral canal to access the epidural space.1,4

The treatment of individuals with spinal disorders, including pain, can be
complex, and it is recommended that all individuals being considered for
interventional spinal procedures undergo a thorough evaluation and be treated
following development of a comprehensive care plan.

**Covered Indications**

  1. ESI will be considered medically reasonable and necessary when the following 3 requirements are met: 
    * History, physical examination, and concordant radiological image-based diagnostic testing and supporting 1 of the following5: 
      * Lumbar, cervical or thoracic radiculopathy, radicular pain and/or neurogenic claudication due to central disc herniation, osteophyte or osteophyte complexes, severe degenerative disc disease, producing foraminal or central spinal stenosis5; **OR**
      * Post-laminectomy syndrome6-8
      * Acute herpes zoster associated pain6

**AND**

  *     * Radiculopathy, radicular pain and/or neurogenic claudication is severe enough to greatly impact quality of life or function. An objective pain scale or functional assessment must be performed at baseline (prior to interventions). The same scale* must be repeated at each follow-up for assessment of response.

**AND**

  *     * Pain duration of at least 4 weeks, and the inability to tolerate noninvasive conservative care or medical documentation of failure to respond to 4 weeks of noninvasive conservative care **or** acute herpes zoster refractory to conservative management where a 4-week wait is not required.9

  2. The ESIs must be performed under computed tomography (CT) or fluoroscopy image guidance with contrast,10 unless the patient has a documented contrast allergy or pregnancy where ultrasound guidance without contrast may be considered.
  3. TFESIs involving a maximum of 2 levels in 1 spinal region are considered medically reasonable and necessary. It is important to recognize that most conditions would not ordinarily require ESI at 2 levels in 1 spinal region.11
  4. CESIs and ILESIs involving a maximum of 1 level are considered medically reasonable and necessary.11
  5. It is medically reasonable and necessary to perform TFESIs bilaterally only when clinically indicated.
  6. Repeat ESI when the first injection directly and significantly provided improvement of the condition being treated may be considered medically reasonable and necessary when the medical record documents at least 50% of sustained improvement in pain relief and/or improvement in function measured from baseline using SAME scale* for at least 3 months.7,8 If a patient fails to respond well to the initial ESI, a repeat ESI after 14 days can be performed, using a different approach, level and/or medication if appropriate, with the rationale and medical necessity for the second ESI documented in the medical record.
  7. An initial injection of contrast is required to confirm epidural placement, unless the patient has a contraindication to contrast. The subsequent ESIs should include corticosteroids and may be combined with anesthetics or saline.1
  8. The ESIs should be performed in conjunction with conservative treatments.9
  9. Patients should be part of an active rehabilitation program, home exercise program or functional restoration program.10,12

*Note: The scales used to measure pain and/or disability must be documented in the medical record. Acceptable scales include but are not limited to: verbal rating scales, Numerical Rating Scale (NRS) and Visual Analog Scale (VAS) for pain assessment, and Pain Disability Assessment Scale (PDAS), Oswestry Disability Index (ODI), Oswestry Low Back Pain Disability Questionnaire (ODQ), Quebec Back Pain Disability Scale (QBPDS), Roland Morris Pain Scale, Back Pain Functional Scale (BPFS), and the Patient-Reported Outcomes Measurement Information System (PROMIS) profile domains to assess function.

**Limitations**

  1. Injections performed without image guidance or by ultrasound are not considered reasonable and necessary except in cases of documented contraindication to contrast media (e.g., allergy, pregnancy).13-15
  2. ESIs performed with biologicals or other substances not Food and Drug Administration (FDA) designated for this use is considered investigational and not medically reasonable and necessary.
  3. It is not considered medically reasonable and necessary to perform multiple blocks (ESI, sympathetic blocks, facet blocks, trigger point injections, etc.) during the same session as ESIs, with the exception of a facet synovial cyst and ESI performed in the same session.
  4. Use of moderate or deep sedation, general anesthesia, and monitored anesthesia care (MAC) is usually unnecessary or rarely indicated for these procedures and, therefore, not considered medically reasonable and necessary.16 Even in patients with a needle phobia and anxiety, typically oral anxiolytics suffice. In exceptional and unique cases, documentation must clearly establish the need for such sedation in the specific patient.
  5. ESIs to treat non-specific LBP, axial spine pain, complex regional pain syndrome, widespread diffuse pain, pain from neuropathy from other causes, cervicogenic headaches are considered investigational and therefore are not considered medically reasonable and necessary.6,17,18
  6. ESIs are limited to a maximum of 4 sessions per spinal region in a rolling 12-month period.7
  7. It is not considered medically reasonable and necessary for more than 1 spinal region to be injected in the same session.11
  8. It is not considered medically reasonable and necessary to perform TFESIs at more than 2 nerve root levels during the same session.11
  9. It is not considered medically reasonable and necessary to perform CESIs or ILESIs at more than 1 level during the same session.11
  10. It is not medically reasonable and necessary to perform CESIs or ILESIs bilaterally.14
  11. It is not medically reasonable and necessary to prescribe a predetermined series of ESIs.8
  12. Steroid dosing should be the lowest effective amount.
  13. It generally would not be considered medically reasonable and necessary for treatment with ESI to extend beyond 12 months.19,20 Frequent continuation of ESIs over 12 months may trigger a focused medical review. Use beyond 12 months requires the following: 
    1. Pain is severe enough to cause a significant degree of functional disability or vocational disability.
    2. ESI provides at least 50% sustained improvement of pain and/or 50% objective improvement in function (using same scale as baseline).
    3. Rationale for the continuation of ESIs including but not limited to patient is high-risk surgical candidates, the patient does not desire surgery, recurrence of pain in the same location relieved with ESIs for at least 3 months.
    4. The primary care provider must be notified regarding continuation of procedures and prolonged repeat steroid use.
  14. ESIs should not be performed when contraindicated including but not limited to: suspected or active localized spinal infection, significant systemic infection, compressive lesions of the spinal cord, conus medullaris or cauda equina, suspicion or major risk factors for cancer.11

**Provider Qualifications**

Medicare Program Integrity Manual states services will be considered medically
reasonable and necessary only if performed by appropriately trained providers.

Procedures listed and included in this LCD do not constitute anesthesia
services. Evaluation, methods and techniques specified are not considered
routine for surgical or perioperative anesthesia.

Patient safety and quality of care mandate that healthcare professionals who
perform epidural injections/procedures for chronic pain (not surgical
anesthesia) are appropriately trained and/or credentialed by a formal
residency/fellowship program and/or are certified by either an accredited and
nationally recognized organization or by a post-graduate training course
accredited by an established national accrediting body or accredited
professional training program whose core curriculum includes the performance
and management of the procedures addressed in this LCD. Credentialing or
privileges are required for procedures performed in inpatient and outpatient
settings.21,22

All aspects of care must be within the provider's medical licensure and scope
of practice. Reimbursement for procedures utilizing imaging techniques may be
made to providers who meet training requirements for the procedures in this
LCD only if their respective state allows such in their practice act and
formally licenses or certifies the practitioner to use and interpret these
imaging modalities (ionizing radiation and associated contrast material,
magnetic resonance imaging (MRI), ultrasound). At a minimum, training must
cover and develop an understanding of anatomy and drug pharmacodynamics and
kinetics as well as proficiency in diagnosis and management of disease, the
technical performance of the procedure, and utilization of the required
associated imaging modalities.

**Notice:** Services performed for any given diagnosis must meet all of the
indications and limitations stated in this LCD, the general requirements for
medical necessity as stated in Centers for Medicare and Medicaid Services
(CMS) payment policy manuals, any and all existing CMS national coverage
determinations (NCDs), and all Medicare payment rules.

**Definitions**

_Acute LBP_ **** - **** LBP, which is present for up to 6 weeks.

__

_CESI_ ** ** - The administration via injection of contrast (absent allergy to
contrast), followed by the introduction of corticosteroids and possibly a
local anesthetic (LA) into the epidural space of the spine by inserting a
needle through the sacral hiatus under fluoroscopic guidance into the epidural
space at the sacral canal.

__

_Cervicobrachialgia_ \- Pain in the neck radiating to the arm, caused by
compression of nerve roots of the cervical spine.

__

_Conservative Therapy_ **** - **** Consists of an appropriate combination of
medication (for example, non-steroidal anti-inflammatory [NSAIDs], analgesics,
etc.) in addition to physical therapy, spinal manipulation therapy, cognitive
behavioral therapy (CBT), home exercise program, or other interventions based
on the individual's specific presentation, physical findings, and imaging
results.

__

_Disability_ - Activity limitations and/or participation restrictions in an
individual with a health condition, disorder or disease.23

_Discogenic Pain_ - Pain originating from damaged vertebral disc,
particularly, but not always, due to degenerative disc disease.

__

_ESI_ ** ** - **** The administration via injection of contrast (absent
allergy to contrast), followed by the introduction of a corticosteroid and
possibly a LA into the epidural space of the spine.

__

_GRADE_ - A system developed by the GRADE Working Group to address the
shortcomings of present grading systems in healthcare. The GRADE system uses a
common, sensible, and transparent approach to grading the quality of evidence.
The results of applying the GRADE system to clinical trial data are displayed
in a table known as a GRADE profile.

__

_Impairment_ - A significant deviation, loss, or loss of use of any body
structure or body function in an individual with a health condition, disorder
or disease.23

__

_ILESI_ ** ** - **** An injection of contrast (absent allergy to contrast),
followed by the introduction of a corticosteroid and possibly a LA into the
epidural space of the spine either through a paramedian or midline
interlaminar approach under fluoroscopic guidance.

__

_Level_ - The spinal roots that enter and exit the spinal column between each
of the vertebral segments cervical (C1-C8), thoracic (T1-T2), lumbar levels
(L1-L5), and sacral (S1-S5).

__

_Multidisciplinary Biopsychosocial Rehabilitation (MBR)_ - Targets physical as
well as psychological and social aspects of LBP, and involves a team of
healthcare providers with different professional backgrounds and training.10

__

_Non-Radicular Back Pain_ - The radiating non-neuropathic pain which is not
causally related to a spinal nerve root irritation and does not produce
reproducible neuropathic symptoms in an objective dermatomal pattern.

__

_Neural Foramina_ - (also called intervertebral foramen) The openings between
each pair of vertebra where a number of structures pass through.

_Neurogenic Claudication_ - (also known as pseduoclaudication) The physical
manifestation of leg pain, leg weakness, or leg heaviness exacerbated by
walking and relieved with leaning forward or sitting down.

__

_Nonspecific LBP_ ** ** - **** Back pain that cannot be attributed to a
specific disease or spinal pathology **.**

__

_Osteophyte_ - An exostosis or benign osteoma of the facet joints or vertebral
endplates.

__

_Osteophyte Complex_ - The protrusion of disc material, buckling of the
ligamentum flavum, joint hypertrophy, and osteophytes.

__

_Peripheral Neuropathic Pain_ - Pain is causally related to a lesion or
disease of the peripheral somatosensory nerves.

__

_Post-Laminectomy Syndrome_ - A group of symptoms following a lumbar
laminectomy which include diffuse LBP with associated dull and aching pain
involving the legs.

__

_Radicular Back Pain_ - Radicular pain is nerve root pain radiating from the
affected spinal segment in a distribution concordant with the known
distribution of the nerve root.

__

_Radiculopathy_ - Radiating neuropathic pain causally related to the spinal
nerve root irritation, which extends distally, producing neuropathic pain in a
myotomal or dermatomal pattern.

__

_Radiculitis_ **** - **** Inflammation of the nerve roots which produces
radicular pain without objective neurological findings on physical
examination.

__

_Session_ - A time period, which includes all procedures (i.e., medial branch
blocks (MBB), intraarticular injections (IA), facet cyst ruptures, and
radiofrequency ablations (RFAs)) performed during 1 day.

__

_TFESI_ - An epidural injection performed via a paramedian approach to enter
the epidural space by placing the needle in the posterior-superior quadrant of
the intervertebral foramen (neuroforamen) to inject near the dorsal root
ganglion and exiting spinal nerve root (previously known as a selective nerve
root block (SNRB)).

__

_SNRB_ - A diagnostic injection of contrast (absent allergy to contrast) of a
single nerve root to assist with surgical planning, followed by the
introduction of a LA by inserting a needle into the neuroforamen under
fluoroscopic or CT guidance. SNRB's are erroneously referred to as a TFESI,
although technically, SNRB's involve the introduction of anesthetic only used
for diagnostic purposes.

__

_Spinal Stenosis_ - The narrowing of the central spinal canal or foraminal
openings, usually due to spinal degeneration that occurs with aging. It may
also be the result of spinal disc herniation, osteoarthritis, or a tumor.
Lumbar spinal stenosis results in LBP and pain or abnormal sensations in the
legs, thighs, feet, or buttocks, or loss of bladder and bowel control.
Neurogenic claudication is often a clinical condition that results from spinal
stenosis.

__

_Spondylolisthesis-_ A disorder of the spinal cord in which 1 vertebra slips
onto the vertebra below it resulting in pain in lower back or legs.

__

_Subacute Pain_ - The temporal definition of pain occurring during the 6 to
12-week time period.

_Chronic Pain_ **** - **** The temporal definition of pain occurring 12 weeks
after the onset of the pain.

**Contractor Advisory Committee (CAC) Meeting 2/11/2021**

****

A Multi-jurisdictional CAC meeting of subject matter experts (SMEs) was
convened on 02/11/2021 regarding epidural injections and procedures. The
transcript, voting results, and audio are available on each MACs website. The
panel consisted of experts in pain management including anesthesiology and
physical medicine and rehabilitation, as well as neuroradiology, internal
medicine and a certified nurse anesthetist with representation throughout the
country and including academic and clinical experts. The panel will be
referred to as SMEs, and their input incorporated through the review to
correlate the evidence with expert input.

**Summary of Evidence**

Acute LBP, defined as LBP with less than 4 weeks duration, has an excellent
prognosis to recover within the first 4 to 6 weeks. Initially, treatments
include non-invasive therapies, including pharmacologic and non-
pharmacological measures. Patients with acute or subacute nonspecific LBP
typically would not be considered candidates for interventional therapies, as
they could still improve with non-invasive therapies, and there is little
evidence on the efficacy of invasive therapies in this circumstance.24 The
American College of Physicians (ACP) offers a strong recommendation for non-
pharmacological measures as the first line treatment. Recommended non-
pharmacological measures include conservative measures such as superficial
heat, exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-
based stress reduction having moderate-quality evidence. For pharmacologic
therapy, they recommend NSAIDs as first line treatment, and muscle relaxants
as second-line treatment.25 Systemic steroids may provide benefits with 3
randomized control trials (RCTs) showing benefit, especially in the short
term. The benefit of anticonvulsants and antidepressants is overall low
quality, but there is potential benefit in some patients.26 A systematic
review comparing ESIs to conservative treatment for patients with lumbosacral
radicular pain reported that ESIs were more effective for alleviating
lumbosacral radicular pain but not function in both short- and intermediate-
term compared to conservative treatment; however, this effect was not
maintained at long-term follow-up.27 It is standard practice to utilize
conservative treatment measures for the management of acute LBP. When back
pain persists over 12 weeks, it is considered CLBP, and spontaneous recovery
is less likely. The SMEs voted 3/5 (range 2-5) that there is evidence to
support periods of conservative management prior to treatment with epidural
injections. The panel discussed time for conservative care is related stronger
to the natural history of the disease than the evidence, as it has not been
well studied. The panel voted low confidence (2/5; range 1-5) in terms of
evidence to support documentation of failure of at least 2 classes of
medication prior to ESI. The use of medication is more controversial due to
the risk associated with non-steroidal anti-inflammatory, specifically
gastrointestinal complications, and the risk of opioid addiction with opioid
use. Other medications remain available, but there is not strong evidence to
support 1 specific category of medication.

Patients with LBP should be evaluated for the underlying condition, and
targeted treatments implemented. History and physical examination, including a
neurological exam to evaluate for radicular pain, should be performed. Imaging
should be targeted to identify specific differential diagnoses and is not
typically indicated in the early evaluation of LBP.28 The American College of
Radiology (ACR) offers evidence-based criteria for imaging for LBP.29
According to the ACR criteria, patients who have acute, subacute, or chronic
LBP or radiculopathy with persistent or progressive symptoms during or
following 6 weeks of conservative management are considered candidates for
surgery or intervention. Imaging may be considered for patients who have had
no improvement in their back pain after 6 weeks of medical management and
physical therapy. Imaging is classified as "may be appropriate", with MRI of
the lumbar spine without contrast classified as "usually appropriate" and CT
if MRI is unavailable as needed for diagnostics. The American College of
Occupational and Environmental Medicine guidelines state that while diagnostic
tests are not indicated for the majority of LBP, the literature supports CT or
MRI.30 The ESIs are utilized as an option for a specific diagnosis, and
therefore a thorough evaluation to achieve diagnosis is a necessary step prior
to consideration of ESIs. In most cases, by the time ESIs are considered,
imaging has been completed as part of the evaluation. Any prior imaging should
be reviewed for anatomy prior to interventional procedures. The SMEs voted low
confidence (2/5; range 1-4) that radicular pain should be concordant with a
radiologist's interpretation of an advanced diagnostic study demonstrating
compression of the involved nerve root. The concern was that the imaging study
is a static image in a dynamic process and the compression may be missed in
the supine position even if present. The SMEs felt there was benefit in
obtaining imaging to aid in diagnosis, such as to reveal anatomical features
that may guide treatment options or alter approach, selection of needle size
and appropriate segmental level. There was also concern that imaging would not
reveal non-anatomical sources like chemical radiculitis.

****

**Safety**

Epidural administration of corticosteroids has not been approved by the FDA
and is classified as "off-label" use. While complications with ESIs are rare,
they can be devastating. In 2014, the FDA issued a drug safety communication
about the epidural injection of glucocorticoids, noting the potential for rare
but serious adverse effects, and the effectiveness has not been established.31
The warning followed 2 separate outbreaks of fungal meningitis 2002 and
2012-2013 linked to ESIs and multitudes of case reports on related
complications. After the FDA warning, there was a flurry of papers to document
safety and provide protocols and/or guidelines to improve safety. The reported
risk of ESIs includes loss of vision, stroke, dural puncture, infection,
spinal cord injury, paralysis, and death. In addition to IA injections of
particulate steroids, arachnoiditis, nerve damage, osteomyelitis, hemorrhage,
and epidural abscess have been reported.1,32 In a 2015 review on trends in
safety and complications, the author explains the reasons for these risks
stating "significant neurological complications associated with transforaminal
injections include stroke and spinal cord injury, which arise due to the need
to place the needle within the intervertebral foramina. This space contains
radicular arteries that perfuse the spinal cord and course adjacent to the
targeted spinal nerve root, creating a challenge when variations in anatomical
structure are present."1 A 2018 survey of 249 interventional pain management
physicians (13.8% response rate) demonstrated a high level of variability and
lack of standardized practices. They reported that in ILESI practice patterns,
there is a lack of standardization in needle sizes, use of imaging, and choice
of injectant.33 The lack of evidence-based standardized practice makes it
difficult to interpret the literature since these variables exist across
existing studies.

A 2015 review on key safety when administering ESIs states the FDA identified
131 neurological adverse events, including 41 cases of arachnoiditis and 700
cases of fungal meningitis following injection of contaminated steroids. They
further explain that most complications were related to TFESIs, specifically
cervical TFESIs. They conclude that proper technique can avoid injury, and
lumbar TFESIs can be performed safely; however, they warn that cervical TFESIs
"must not be performed until appropriate evidence develops and safe
preparations of steroids are available."32 A 2015 multidisciplinary workgroup
stated concern regarding the injection of ESIs under sedation and without
appropriate precautionary steps, such as injection of radiographic contrast
medium under fluoroscopy, resulting in spinal cord injury. They also expressed
concern for using particulate steroids, such as methylprednisolone,
triamcinolone, or betamethasone which have been linked to cerebrovascular
occlusion associated with cervical TFESIs.14 This review called for more
standardized safety protocols and research in best practices.

A 2016 multi-institutional study on adverse event rates associated with TFESI
and ILESI reported no major adverse events in 16,638 consecutive procedures in
all spine segments (14,956 TFESI; 1,682 ILESI). The most common adverse event
was a vasovagal reaction in 1.2% of procedures (p=0.004). Dural punctures
occurred in 0.06% of procedures, more commonly after ILESI (0.2% vs 0.04%,
p=0.006). Central steroid response (sleeplessness, flushing, non-positional
headache) was seen in 2.6% of TFESI and ILESI patients. Patients that reported
increased pain included 2.1% of TFESI and 1.8% of ILESI patients. No long-term
sequelae were seen from any immediate or delayed minor adverse event at the
time of the procedure or follow-up.34 A 2012 prospective study on 10,261
fluoroscopic guided epidural procedures included 2,376 cervical interlaminar
epidural injections, 301 thoracic interlaminar epidural injections, 1,450
lumbar interlaminar epidural injections, 1,395 caudal epidural injections,
1,310 lumbar transforaminal epidural injections, and 839 caudal epidural L
adhesiolysis procedures. The authors reported an adverse rate of overall
intravascular penetration of 4.3%, local bleeding of 63%, 0.5% rate of dural
punctures with 0.05% post-lumbar puncture headache, 0.85% transient nerve
irritation of 0.08% as well as transient spinal cord irritation and other
minor complications, but no major complications.35

The WIP Benelux Work Group developed evidence-based safety guidelines based on
existing literature. In reviewing major complications, they reported that the
majority involved direct nerve trauma or spinal cord injury. To reduce the
risk of nerve damage, they recommended avoidance of deep sedation so the
patient can alert the provider to any paresthesia during needle placement to
minimize this risk.16 The SMEs agreed that evidence supports that ESI should
not be performed with moderate sedation or general anesthesia with a score of
3/5 (range 1-5). The American Society of Anesthesiologists (ASA) provides
definitions on the continuum of the depth of sedation. Minimal sedation
anxiolysis is defined as a drug-induced state during which patients respond
normally to verbal commands. Although cognitive function and physical
coordination may be impaired, airway reflexes, and ventilatory and
cardiovascular functions are unaffected.36 Progressing depth of sedation
beyond minimal is moderate or "conscious," deep and general. Monitored
Anesthesia Care or "MAC" is not a depth of sedation, but a specific anesthetic
service allowing a deeper level of analgesia than can be provided moderate
sedation.

The impact of glucocorticoids injected into the epidural space is not fully
defined. Evidence supports that even a single injection risk includes bone
demineralization and increased risk of fractures in postmenopausal women,
suppression of the hypothalamic-pituitary adrenal axis, immune dysregulation,
and hyperglycemia in patients with diabetes mellitus.1,16 A small prospective
study in which 28 postmenopausal women who underwent a single ESI
(triamcinolone 80 mg) had bone mineral density (BMD) measurements completed
and showed a significant decline in the hip BMD of 0.018 g/cm2 (0.028  0.007,
P=0.002) at 6 months compared with baseline as compared to age-matched control
population and concluded there is a potential deleterious effect of ESI with
steroids on BMD.37 A large retrospective cohort study matched 3,000 patients
who had ESIs to 3,000 similar non-injected patients. Based on their analysis,
they conclude each successive injection increased the fracture risk by a
factor of 1.21 (95% confidence interval [CI], 1.08 to 1.30) after adjustment
for covariates (p=0.003), concluding a 21% increased risk of fracture risk per
ESI injection.1,38

In contrast, a 2,000 prospective study on the effect of corticosteroids and
dose relationship on weight gain and BMD receiving steroids through the
neuraxial block included ESI and facet joint injections. Data were collected
on 123 patients divided into 2 groups. One received injection with LA plus
steroids, and the other LA alone. A BMD study was conducted at baseline and
repeated at 3, 6, and 12 months and concluded no significant change in BMD at
12 months from baseline.39 However, the ESI doses in this study were lower
than routinely used, so results must be interpreted cautiously. The lack of
standardized injectant and dosing make it difficult to determine if there is a
safe threshold in this population. A 2019 retrospective paper reported on 172
postmenopausal women with osteoporosis and with half receiving ESIs. The mean
number of ESIs was 6.2, and the mean cumulative administered dose of
glucocorticoids (dexamethasone) was 31 mg. The incidence of fractures in the
medication only (for back pain) and ESI groups were 22% and 24%, respectively,
in the thoracolumbar spine, and 2% and 5%, respectively, in the hip joint.
There was no significant difference in the incidence of osteoporotic fractures
between the groups suggesting a maximum cumulative dexamethasone dose of 31 mg
could be safely used in postmenopausal women with osteoporosis.40 This was
limited by retrospective design and a small sample size. The WIP Benelux
Guidelines cite each ESI increases the fracture risk by 31% and recommends
keeping the corticosteroid exposure to a minimum, especially for high-risk
individuals such as the elderly and women with prior history of osteoporosis
or osteopenia.16

There are reported cases of suppression of the hypothalamic-pituitary-adrenal
(HPA) axis after ESI causing Cushing syndrome. While the incidence of Cushing
syndrome is low, HPA access suppression is frequent and can continue for 3 to
6 weeks. A diabetic patient's elevation in glucose levels may be seen after
ESI persisting for 2 to 6 days after the initial injection with a risk of
hyperglycemia. There is also concern about the impact of corticosteroids on
the immune system, and dose-dependent suppression of the immune system has
been reported after ESI.16 In a retrospective study, it was found that
corticosteroids reduced the effectiveness of the vaccine and patients were at
increased risk for developing influenza after a major joint injection with
corticosteroids (relative risk, 1.52; 95% CI, 1.20-1.93).41 This led to
recommendations to avoid elective procedures and reduce steroid dosing for
necessary procedures in elderly and high-risk patients during the COVID-19
pandemic.42 SMEs agreed with high confidence (4/5; range 2-5) that there is
evidence to support a maximal steroid dose for corticosteroid limits for the
injection. The precise maximum is not established with variations in the
literature, but there is consistent evidence to use the lowest effective
dose.16

Bleeding risks are a significant concern for patients undergoing ESIs. An
epidural hematoma can create an expanding volume that compresses the spinal
cord and/or nerve roots and can result in potentially catastrophic
neurological complications. This risk is a possibility for hematologically
normal patients but significantly higher if on anti-coagulation. The practice
of holding anticoagulation to perform ESIs is controversial. While holding
anticoagulation may potentially reduce the risk of bleeding, there is an
increased risk of thromboembolic events during the time patients are off anti-
coagulants. A 2012 survey of 325 interventional pain physicians reported the
number of bleeding complications after ESI was similar regardless of whether
anticoagulation was held. Still, the reported number of thromboembolic events
was 17-times greater when anticoagulants were held compared with when not
held.43 In the American Society for Interventional Pain Physicians (ASIPP)
updated Comprehensive Evidence-Based Guidelines Part II: Guidance and
Recommendations, the authors report44:

  * Good evidence for risk of a thromboembolic phenomenon in patients with antithrombotic therapy if discontinued, spontaneous epidural hematomas with or without traumatic injury in patients with or without anticoagulant therapy to discontinue or normalize the international normalized ratio (INR) with warfarin therapy, and the lack of necessity of discontinuation of NSAIDs, including low dose aspirin prior to performing interventional techniques.
  * Fair evidence with excessive bleeding, including epidural hematoma formation with interventional techniques when antithrombotic therapy is continued, the risk of a higher thromboembolic phenomenon than epidural hematomas with discontinuation of antiplatelet therapy before interventional techniques and to continue phosphodiesterase inhibitors (dipyridamole, cilostazol, and Aggrenox).
  * Limited evidence to discontinue antiplatelet therapy with platelet aggregation inhibitors to avoid bleeding and epidural hematomas and/or continue antiplatelet therapy (clopidogrel, ticlopidine, prasugrel) during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic fatalities.
  * Limited evidence about dabigatran (Pradaxa) and rivaroxaban (Xarelto) to discontinue to avoid bleeding and epidural hematomas and are continued during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic events.

The American Society of Regional Anesthesia (ASRA) published a 2018 systematic
review of 14 articles for evidence regarding risks associated with either
continuing or ceasing anticoagulant and antiplatelet medication in patients
having image-guided interventional spine procedures using GRADE methodology.
Interlaminar procedures carried a greater risk of hemorrhagic complications
regardless of whether the anticoagulants were ceased or continued, while other
procedures did not carry that risk and could be performed while continuing
anticoagulation. Three articles reported adverse effects of ceasing
anticoagulants, with serious consequences, including death.45 However, this
report was limited to case studies, case series, several observational
studies, 1 large retrospective study, and 1 large prospective study with broad
heterogenicity, multiple different neuraxial procedures included, and
nonuniformed protocols making it difficult to draw clear conclusions.

A summary of current literature supports that withholding anticoagulation
medication to reduce the risk of major bleeding such as hematoma from ESIs may
increase the risk of thromboembolic events. A 2015 review concludes, "the
decision should be considered in the context of a clear understanding of the
patient's anatomy, established guidelines and the perspectives of the patient
and prescriber of the anticoagulation medication(s)."1

The SME panel agreed on the absolute contraindications included in the LCD
with voting of 3 to 5 for each of the listed contraindications. However, the
panel had low confidence score 2/5 (range 1-4) that the evidence supports the
continuation of anticoagulation for epidural injections. The wide range
demonstrates the continued controversy which is not resolved among variations
in societal guidance.

**Image Guidance Procedures**

****

The use of imaging during the performance of ESIs is considered standard. A
2016 systematic review to determine the effectiveness and risks of non-image-
guided lumbar ILESIs reviewed 92 primary publications using GRADE methodology
and concluded that these procedures should be performed with image guidance
and procedures without imaging should be restricted to the rare settings where
fluoroscopy is not available.13 A 2015 multi-disciplinary workgroup to improve
the safety of ESIs included a recommendation that all cervical and lumbar
ILESIs should be performed with image guidance plus a test dose of contrast
medium. They further state that cervical and lumbar TFESIs should be performed
by injecting contrast medium under real-time fluoroscopy or digital
subtraction imaging.14 Multiple other societies also endorse imaging
requirements for ESIs. The North American Spine Society (NASS) Choosing Wisely
recommendations include "elective spinal injections, such as epidural steroid
injections, should be performed under imaging guidance using fluoroscopy or CT
with contrast enhancement (unless contraindicated) to ensure correct placement
of the needle and to maximize diagnostic accuracy and therapeutic efficacy."46
The NASS published guidelines suggest that while there is some evidence to
support ultrasound-guided lumbar TFESI, this data is limited and, due to the
risk of serious complications with ESIs, it is not considered standard
care.47,48

**Evaluation of Success**

****

Once an ESI is performed, the patient must be assessed to determine if the
injection was successful. This requires a clear definition of success. Success
should include a reduction in pain symptoms and/or as improvement in function.
Most research protocols studying the efficacy of ESIs used the ODQ or Roland-
Morris Disability Questionnaire (RMDQ) to measure function, VAS or NRS to
measure pain, and a variety of questionnaires to measure the quality of life,
depression and other outcomes. Most studies used a threshold of 50%
improvement from baseline to consider the ESI successful. While questionnaires
may be burdensome in clinical practice, a standard measure for improvement is
important to determine if the treatment is effective. Further research for
simple assessment tools is needed.

A 2020 prospective observational study for 16 patients >65 years old with
symptomatic lumbar stenosis with radiculopathy who selected ILESI or medical
management were followed with the Short Physical Performance Battery (SPPB)
and numeric pain score. The SPPB score includes a 4-meter walk test, chair
stand time, and balance score. There was statistically significant improvement
reported in SPPB score at 1 month for the injection group, but not in the
medication group. Most studies on ESIs use metrics that include improvement in
pain scores and/or questionnaires. There are few studies that measure
functional outcomes. The RMDQ is a validated measure of disability and
patient-reported function but does not include objective or observable
measures. This study, while too small in number for conclusive results, offers
a functional parameter to measure improvement after ESI, stating the SPPB is a
quick and feasible screening tool. They state, "the SPPB is an easy-to-use
tool to measure changes in physical function in older adults and could easily
be integrated into the outpatient pain clinic setting. Even a 1-point change
in an SPPB score and its subsets is clinically meaningful and correlates with
decreased mortality and disability."49

Success may also be defined as avoidance of surgery. A small double-blinded
RCT, looked at 21 patients previously identified as operative candidates who
delayed surgery and underwent ESIs. Seventeen of the 21 did not undergo
operative intervention at the 5-year mark. The authors concluded that
injections can avoid operative intervention.50 Limitations are the very small
sample size and risk of selection bias. Throughout the evidence review below
there are studies which do not show a reduction in need for surgery, while
others demonstrate a trend in reduction of surgical management, with no
moderate- or high-quality literature to confirm this observation.

The SMEs were asked about their confidence that the clinical literature
supports that ESIs provided at least 50% pain relief and voted 3/5 (range
1-5). The panel expressed high confidence in using a measure of function for
ESIs success with a score of 4/5; range 2-5. The panel discussed that a
clinical success must be a combination of both improvement in pain and/or
function and that standardized scales used in the setting of research may not
be practical for clinical practice. The panel does acknowledge the need for
some standardized measurement of successful outcomes of the procedures.

**Multi-Modality Approach**

A 2014 Cochrane review on MBR for CLBP included 41 RCTs (n=6858). It concluded
there is moderate-quality evidence that patients with CLBP receiving MBR are
likely to experience less pain and disability than those receiving usual care
or physical treatment. They also correlated a positive influence on work
status.10

The ASA Task Force of Pain Management recommends ESIs with or without LA as
part of a multimodal treatment regime to provide pain relief in selected
patients with radicular pain or radiculopathy.12

**Lumbosacral Radicular Pain**

__

The effectiveness of ESIs has been a source of controversy. Multiple studies
and systematic reviews reported favorable results, but several reports offered
conflicting evidence. A 1997 RCT published in the New England Journal of
Medicine with 158 patients with disc herniation and pain were randomized to
ESI with glucocorticoid or placebo. At 3 weeks, the Oswestry score had
improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the
placebo group (95% CI for the difference, -7.1 to 2.2), there was an
improvement in leg pain in the steroid group at 6 weeks, but no significant
difference between the groups at 3 months. At 12 months, the cumulative
probability of back surgery was 25.8% in the methylprednisolone group and
24.8% in the placebo group (P=0.90). They concluded there was short-term
improvement from ESIs for herniated disc but without significant functional
benefits or reduction in the need for surgery.51 In 2015, the Agency for
Healthcare Research and Quality (AHRQ) released a technology report consisting
of a systematic review of RCT of patients with lumbosacral radiculopathy,
spinal stenosis, non-radicular back pain, or chronic post-surgical back pain.
Quality of evidence was assessed for risk of bias using Cochrane Back Review
Group criteria. Meta-analysis was performed and stratified by time. Seventy-
nine RCTs of ESIs were included. Thirty placebo-controlled trials evaluated
epidural corticosteroid injections for radiculopathy. For radiculopathy,
epidural corticosteroids were associated with a greater immediate-term
reduction in pain (weighted mean difference on a scale of 0 to 100, -7.55 [95%
CI, - 11.4 to -3.74]; strength of evidence [SOE], moderate), function
(standardized mean difference after exclusion of an outlier trial, -0.33 [CI,
-0.56 to -0.09]; SOE, low), and short-term surgery risk (relative risk, 0.62
[CI, 0.41 to 0.92]; SOE, low). For ESIs compared to placebo, they concluded
that the magnitude of effects on pain and function was small. They did not
meet predefined thresholds for minimum clinically important differences,
lacked longer-term benefit, and did not demonstrate effectiveness (SOE:
insufficient to low). The authors concluded that corticosteroid injections for
radiculopathy were associated with immediate but short-term benefits and did
not reduce the long-term risk of surgery. Limitations of this paper included
methodological shortcomings of the RCTs evaluated.52

A 2016 systematic review and meta-analysis included RCTs comparing TFESI with
steroids (with or without LA to LA or saline in adults with lumbosacral
radicular pain secondary to herniated intervertebral discs. They reviewed data
on NRS scores for pain, validated scores for measuring physical disability and
quality of life, and incidence of surgery measured at 1 month to 2 years after
the interventions were meta-analyzed. Evidence was rated with GRADE. Eight
studies were included, including 771 patients (336 in steroid group and 405 in
the comparator group). They concluded that TFESI has no impact on physical
disability or incidence of surgery. They reported the following:

  * Patients who received TFESI steroids reported a significant, but clinically modest, reduction in mean pain scores (0-10 scale) compared with LA/saline (-0.97 points; 95% CI, -1.42 to -0.51 points; P<0.0001, I2 = 90%; GRADE weak recommendation; moderate-quality evidence) at 3 months after the interventions.
  * The TFESI with steroids did not decrease physical disability at 1 to 3 months after the intervention (GRADE strong recommendation; high-quality evidence)
  * The TFESI did not decrease the incidence of surgery at 12 months after the intervention (GRADE strong recommendation; moderate-quality evidence) compared with LA/saline.
  * The TFESI steroids provide modest analgesic benefit at 3 months in patients with lumbosacral radicular pain secondary to herniated intervertebral discs.

Limitations were the high degree of heterogeneity among the publications
included in this meta-analysis.53

In the same year, a systematic review of 52 RCTs with placebo-control or
active-control design looked at the efficacy of ESIs in the management of
chronic spinal pain. The quality of each article was assessed by Cochrane
review criteria, as well as the Interventional Pain Management Techniques-
Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). The
authors concluded there was Level II evidence for managing lumbar disc
herniation or radiculitis for long-term improvement either with caudal,
interlaminar, or transforaminal epidural injections with no significant
difference in approaches. They challenged the methodology of the contrasting
report and stated the limitations are the paucity of high-quality randomized
trials literature which continues to confound the evidence.54

A 2016 comparative systematic review and meta-analysis included 31 RCTs that
compared the efficacy of ESIs for lumbar and spinal stenosis performed with
saline with steroids, LA alone, or steroids with a LA. The review included 9
placebo-controlled trials evaluating ESIs, either with sodium chloride
solution or bupivacaine, compared to placebo injection, and 12 studies
comparing LA alone to LA with steroid. The meta-analysis of 5 studies
utilizing sodium chloride or bupivacaine with steroid showed a lack of
efficacy. Comparing lidocaine to lidocaine with steroids in 7 studies showed
significant effectiveness from baseline to long-term follow-up, which was
considered 3 months. Meta-analysis showed similar effectiveness for pain and
function without non-inferiority of lidocaine compared to lidocaine with
steroid at 3 months and 12 months. The duration of follow-up varied among the
included trials with a minimum of 3 months, so the 12-month outcome data were
from the limited number of trials extended for that duration. They concluded
ESIs for radiculopathy or spinal stenosis with sodium chloride solution or
bupivacaine were shown to be ineffective. Lidocaine alone or lidocaine in
conjunction with steroids was significantly effective.55

A 2017 systematic review and a meta-analysis using GRADE methodology evaluated
71 publications, including observational and RCTs addressing fluoroscopically
guided lumbar ILESIs to determine the effectiveness and risk of a variety of
etiologies, including lumbar radiculopathy. They evaluated the body of
literature for specific underlying etiologies. They reported most evidence
regarding lumbar ILESI was observational and low-quality. They concluded
radicular pain due to lumbar disc herniation provides a statistically
significant short-term improvement in pain.17 A 2019 Korean review using GRADE
concluded a high level of evidence [LoE] for ESI for radicular pain with the
strength of recommendation [SoR] as strong. They favored TFESI over ILESI
(LoE: moderate, SoR: weak) and CESI (LoE: moderate, SoR: strong).26

Few studies address long-term outcomes, with most going to 12 months as the
longest duration. A 2018 prospective cohort study contacted patients who had
received single-level lumbar TFESIs for herniated nucleus pulposus to evaluate
long-term outcomes. Of the original 78 patients enrolled, they could contact
39 (50%) at 5 years for follow-up. They found that despite a high success rate
at 6 months, most subjects experienced a recurrence of symptoms at some time
during the subsequent 5 years. This concludes that lumbar disc herniation is a
disease that can be effectively treated in the short-term by TFESI or surgery,
but long-term recurrence rates are high regardless of treatment received.56

In 2020, a Cochrane database systematic review reported 25 clinical trials
with 2,470 participants, comparing epidural corticosteroid injections to
placebo for lumbosacral radicular pain. Using GRADE methodology, 8 trials were
considered high-quality.57 They report the overall body of literature ranged
from very low to moderate. The study concludes there is limited evidence for
the use of ESIs in people with lumbosacral radicular pain as the treatment
effects are small, mainly evident at short-term follow-up, and may not be
considered clinically important by patients and clinicians (i.e., mean
difference lower than 10%). No minor or major adverse events were reported at
short-term follow-up. The report limitations included insufficient information
on how or when adverse events were assessed for immediate and long-term
follow-up.

Key findings reported include:

  * The ESIs were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference [MD] -4.93, 95% CI -8.77 to -1.09 on a 0 to 100 scale; 8 trials, n=949; moderate-quality evidence [downgraded for risk of bias]).
  * For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD -4.18, 95% CI -6.04 to -2.17, on a 0 to 100 scale; 12 trials, n=1367; moderate-quality evidence [downgraded for risk of bias]).
  * The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e., MD lower than 10%).
  * There is uncertain evidence if ESI makes no difference compared to placebo injection in the frequency of minor adverse events (risk ratio [RR] 1.14, 95% CI 0.91 to 1.42; 8 trials, n=877; very low-quality evidence [downgraded for risk of bias, inconsistency, and imprecision]).

A 2020 systematic review by Smith et al. evaluated the effectiveness of lumbar
transforaminal injection of steroid for the treatment of radicular pain. This
review used GRADE methodology and reviewed 32 observational cohort studies, 9
pragmatic trials, and 2 explanatory trials published between 1997-2017. Using
a reduction of pain of =50%, the authors reported the success rate across the
included studies. They reported a success rate for disc herniations of 63%,
74%, 64% and 64%, at 1, 3, 6, and 12 months respectively. The authors stated
high-quality evidence for the effectiveness of TFESI, based on outcomes of
multiple RCTs and high-quality observational studies. Most studies in this
review showed treatment benefits lasting 3 to 6 months, with some studies
suggesting benefits at 1 or even 2 years post-injection. However, they
attribute the 1 to 2-year benefit likely related to the natural history of
lumbar radicular pain rather than a direct effect of the corticosteroids. One
of the challenges with this body of literature is that the follow-up interval
is highly variable among the studies, and co-interventions are prominent, so
it is difficult to determine the true durability of the intervention. The
literature reviewed showed a trend towards a reduction in surgery in patients
who reported success with ESIs.58

While the overall clinical experience of the SMEs leaned towards a reduction
in surgery with the use of ESIs they agreed this was not consistently
reproduced in the literature with a score of 2/5 (range 2-5). Overall, the
panel felt that there was some evidence to support that ESIs reduced the need
for opiates with a score of 3/5 (range 1-4), however studies to specifically
address this are lacking.

**Lumbar Spinal Stenosis**

**__**

The evidence surrounding the use of ESIs for lumbosacral spinal stenosis is
conflicting. A 2014 double-blind, multisite, RCT funded by the AHRQ reported
on 400 patients with lumbar central spinal stenosis with moderate to severe
pain (>4/10 at baseline) and a disability score of 7 or higher on the RMDQ to
receive ESI with glucocorticoids plus lidocaine or lidocaine alone. The
patients received 1 or 2 injections and evaluation at 6 weeks from the first
injection. At 6 weeks, there was no significant difference between the groups'
RMDQ scores (adjusted difference in the average treatment effect between the
glucocorticoid-lidocaine group and the lidocaine-alone group, -1.0 points; 95%
CI, -2.1 to 0.1; P=0.07) or leg pain scores (adjusted difference in the
average treatment effect, -0.2 points; 95% CI, -0.8 to 0.4; P=0.48). They
concluded ESI with LA and glucocorticoids offered minimal or no short-term
benefit compared to ESI with LA alone.59 This was met by support for surgical
management or trial of conservative measures for lumbar spinal stenosis and
criticism from members of the interventional pain management community.60 A
2015 systematic review and meta-analysis, including 8 trials on ESIs for
spinal stenosis, concludes there were no clear effects of ESIs for spinal
stenosis with the strength of evidence rated low to moderate.52 The 2019
Minimally Invasive Spine Treatment (MIST) Guidelines for lumbar spinal
stenosis from the minimally invasive spine treatment consensus group evaluated
9 studies (2 RCTs; 7 observational studies, 4 prospective studies and 3
retrospective studies) of minimally invasive spine treatments and reported
there is Level I evidence for percutaneous image-guided lumbar decompression
as superior to lumbar ESIs. The consensus group developed treatment algorithms
to guide management.61

On the contrary, there are several papers that support the use of ESI for
spinal stenosis. A 2-year observational study on the use of TFESI for lumbar
spinal stenosis followed 68 consecutive patients at 6 weeks, 1 and 2 years, to
avoid decompressive surgery. Of these patients, 32% opted for surgery, 24% had
repeat injections, and 44% were satisfied with non-surgical management at 2
years. The authors conclude TFESI is a reasonable treatment for lumbar spinal
stenosis, provides long-term relief in a high proportion of patients, and can
reduce the need for surgical management.62 There are prospective studies
supporting this use.63 A 2015, double-blinded RCT compared the effectiveness
of lumbar ILESI with LA only to lumbar ILESI with corticosteroids and LA with
central spinal stenosis. Assessments to measure success were defined as = 50%
pain relief at 3,6,12, 18, and 24 months. They reported 72% (95% CI: 61-83%)
of patients receiving lidocaine and corticosteroids and 73% (95% CI: 62-85%)
receiving lidocaine alone had significant pain relief at 24 months; concluding
ESI with LA with or without steroids were equally effective and beneficial.64
However, overlapping CIs suggest the treatments are equivalent at those
timeframes, so it does not provide evidence for long-term improvement. In the
2015 systematic review of 52 RCTs with placebo-control or active-control
design looking at the efficacy of epidural injections in managing chronic
spinal pain, they concluded Level II evidence for caudal and lumbar
interlaminar epidural injections with Level III evidence for lumbar
transforaminal epidural injections for lumbar spinal stenosis. The evidence is
Level II for cervical spinal stenosis management with an interlaminar
approach.54

Even further conflicting papers support a short-term, but not long-term,
benefit. A 2017 multicenter, double-blind, RCT compared epidural injections of
corticosteroid plus lidocaine versus lidocaine for lumbar central spinal
stenosis alone at 16 clinical sites. Participants had the option of blinded
crossover after 6 weeks to receive the alternate treatment. Disability was
measured using the RMDQ. The authors report at 12 months, both treatment
groups maintained initial observed improvements, with no significant
differences between groups on the RMDQ (adjusted MD, -0.4; 95% CI, -1.6 to
0.9; P=0.55), leg pain (adjusted MD, 0.1; 95% CI, -0.5 to 0.7; P=0.75), opioid
use (corticosteroid plus lidocaine: 41.4% vs lidocaine alone: 36.3%; P=0.41),
or spine surgery (corticosteroid plus lidocaine: 16.8% vs lidocaine alone:
11.8%; P=0.22). They did not observe a difference among participants who
crossed over at 6 weeks. They conclude for lumbar spinal stenosis symptoms,
epidural injections of corticosteroid plus lidocaine offered no benefits from
6 weeks to 12 months beyond that of injections of lidocaine alone in terms of
self-reported pain and function or reduction in the use of opioids and spine
surgery. However, in patients with improved pain and function 6 weeks after
the initial injection, these outcomes were maintained at 12 months. They did
not receive additional benefits after 3 weeks based on the injectant type.
Additionally, if there was no improvement during the first 6 weeks, repeated
injections of either type provided no added long-term benefit.65 A 2017
systematic review and a meta-analysis using GRADE methodology reported on 4
observational studies; 1 RCT concluded the evidence suggests a lack of
effectiveness of lumbar ILESI in treating primary axial pain related to spinal
stenosis, but does suggest significant short-term improvements in radicular
pain with stenosis.17

A 2019 meta-analysis reviewed non-surgical medical treatment in the management
of pain due to lumbar disc prolapse. Fifty-eight studies in global effects and
74 studies in pain intensity analysis were included, with 65.5% rated as high
risk for bias. They found CESI and TFESI had higher short-term scores at
follow-up while biologicals and manipulation had a higher score at long-term
follow-up for pain intensity; however, no treatment was found to be superior
when comparing multiple outcomes and periods. The TFESI was reported to be an
effective short-term treatment. They reported a lack of high-quality studies
as a limitation.66,67

There is little evidence showing a benefit for long-term outcomes. A 2020
retrospective cohort of 54/90 patients who underwent TFESI for controlling
lumbar spinal stenosis induced radicular pain were interviewed at least 5
years after their initial procedure. Half of the patients were receiving
repetitive TFESIs every 2 to 6 months or were taking oral pain medication; 25%
had undergone surgical intervention. The authors report poor long-term pain
relief with surgery as well and conclude ESIs offer a safe option for
controlling radicular pain associate with spinal stenosis.68

A 2020 prospective comparative analysis of cost and quality of life compared
lumbar ESIs to conservative management alone at 3 and 6 months. One hundred
forty-one patients were included, and the authors concluded at 3 months, ESIs
provided similar improvements in quality of life outcomes relative to medical
management and at similar costs. At 6 months, neither ESIs nor conservative
management provided significant quality of life outcomes.69

In the 2020 systematic review by Smith et al. for lumbar spinal stenosis,
using a =50% pain relief criteria, the studies (range) reported success rates
of 49% (43-55%) at 1 month, 48% (35-61%) at 3 months, 43% (33-53%) at 6
months, and 59% (45-73%) at 1 year. The author offers low-quality evidence
according to GRADE methodology and notes the lack of corroboration from
appropriately controlled studies.58

The MIST Guidelines on lumbar spinal stenosis consensus group concludes there
is ample evidence to support the use of ESIs in the management of symptomatic
lumbar spinal stenosis. Depending on the duration and extent of relief, these
options can be repeated or continued to more surgical treatment solutions
(grade B, level II-2, consensus strong).61

Overall, the SMEs felt there was evidence to support a benefit of ESIs for
spinal stenosis voting 4/5 for lumbar central spinal stenosis (range 2-5),
foraminal stenosis (range 1-5) and subarticular stenosis (range 1-5).

**Herpes Zoster**

**__**

Herpes zoster may lead to severe zoster-associated pain (ZAP) and post
neuralgia pain (PNP) to the degree of interfering with activities of daily
living. Several studies have explored the role of ESIs in the management of
ZAP. A 2017 retrospective review of 137 patients with ZAP who underwent TFESI
for management of ZAP was included. They compared those who had the TFESI
within the first 30 days to those who had the procedure between 30-90 days.
They concluded that early application of TFESIs in the acute phase was a
useful option to control ZAP-related pain. Those who received the injection
earlier had a significantly shorter time to pain relief with a lower incidence
of postherpetic neuralgia (PHN).6 This was limited by the retrospective nature
of the study, lack of control group, or comparison to other treatment options
such as antivirals, topical analgesic, or pharmacological treatment. There are
several trials evaluating continuous epidural infusion for the management of
ZAP, but no studies that compare infusion to injections.

The SMEs had low confidence voting 2/5 (range 1-3) that there is evidence to
support the use of ESIs for PHN and 3/5 (range 1-5) for acute herpes ZAP.

**Cervicogenic Headaches and Cervicobrachialgia**

__

The CESI is considered by many interventional pain management specialists to
be a reasonable option for patients who have failed conservative treatments
for cervicogenic headache. A 2014 review on CESI for cervicogenic headache
found no RCTs, and 2 prospective studies, with 36 patients in the studies
combined, that support a role of CESI for this indication; however, there is a
paucity of literature to support this indication.18

Cervicobrachial is used to describe pain in the neck radiating to the arm due
to nerve root compression typically caused by disc herniation or spinal
stenosis. A non-controlled randomized trial in 1993 on CESI for
cervicobrachialgia randomized 25 patients to CESI and 17 to steroid/lidocaine
injection into the posterior neck muscles with 1 to 3 injections at 2-week
intervals and followed them for 1 year. One week after the last injection,
they found that pain relief was rated as very good and good in 76% of the
patients in the CESI group, compared to 35.5% of the patients in the posterior
neck muscle injection group.70

The SMEs voted 3/5 (range 1-5) that there is evidence to support the use of
ESIs for cervicogenic headaches and 4/5 (range 1-5) for cervicobrachialgia.
The SMEs indicated that cervicobrachalgia is caused by disc herniation and
spinal stenosis, where ESIs are beneficial.

**Non-Specific Back Pain**

There is a lack of literature on the use of ESIs for non-specific LBP. Most of
the literature for non-specific pain support exercise therapy and multi-
modality conservative treatments. A 2017 systematic review reported on 71
publications addressing lumbar ILESIs regardless of etiology. They found low-
quality evidence using GRADE methodology and concluded lack of effectiveness
of lumbar ILESIs for treatment of primary axial pain regardless of etiology.
They report that most studies on radicular pain due to lumbar disc herniation
and stenosis reports statistically significant short-term improvement.17

The SMEs voted not confident 1/5 (range 1-2) that there is evidence to support
the use of ESIs for non-specific back pain, widespread diffuse back pain, and
non-organic back pain.

**Post-Surgical Back Pain**

A 2018 systematic review and meta-analysis of RCTs comparing outcomes of
epidural steroids versus placebo after lumbar discectomy in lumbar disc
herniation reported on 12 studies with 1,006 patients (502 in ESI group and
504 in placebo group) and found an unstandardized MD of VAS of back pain at 1
week and 1 month, leg pain at 1 week and 1 month, morphine consumption and
hospital stay was - 0.53 (95% CI - 1.42, 0.36) score, - 0.89 (95% CI - 1.36, -
0.42) score, - 0.63 (95% CI - 0.75, - 0.50) score, - 0.47 (95% CI - 0.78, -
0.15) score, - 8.47 (95% CI - 16.16, - 0.78) mg and - 0.89 (95% CI - 1.49, -
0.30) days lower when compared to placebo after lumbar discectomy in patients
with lumbar disc herniation. Ten studies compared complications and found no
significant difference between the 2 groups (0.92; 95% CI 0.47, 1.83), and
reported no significant difference in complications for epidural steroid
application after lumbar discectomy in lumbar disc herniation.71

A 2018 case-controlled series of 60 patients by Akbas et al. compared the 3
different approaches (TFESI, CESI, ILESI) for post lumbar surgery syndrome and
concluded that VAS, ODQ, and patient satisfaction scores were comparable
across the 3 groups at all time intervals (P>0.05), relative to baseline,
there were significant decreases in pain relief scores (VAS and ODQ) and
functional assessment expressed by patients' satisfaction across all time
intervals and in all 3 groups (P<0.01).72

A 2020 systematic review by Smith et al. states a paucity of literature for
TFESI for failed back surgery syndrome.58

The SMEs voted 3/5 (range 1-5) that there is evidence to support the use of
ESIs for post-laminectomy pain syndrome.

**Cervical Radicular Pain**

Intervertebral disc-related pain can be caused by disc degeneration or
herniation in the cervical spine region. Cervical disc herniation is a common
source of cervical radicular pain. The natural history of this condition is
spontaneous resolution over time. The NASS Guidelines from 2011 reported 43%
of patients' symptoms resolve in the first few months of experiencing mild or
intermittent symptoms, and 27% continue to have chronic pain.73 Safety issues
associated with cervical epidural injections include the risk of spinal cord
injury, vascular injury, spinal infarct, and ischemia. Cervical TFESI has been
associated with a higher risk of neurovascular complication and possible
infarction off the spinal cord, brain stem, cerebrum, or the cerebellum. The
interlaminar technique is associated with increased risk of direct trauma to
the spinal cord.16

A 2015 systematic review reports on the long-term efficacy of cervical ILESI
and TFESI to treat neck pain. Seven manuscripts between 1966-2014 using IPM-
QRB methodology were included. There were 4 papers rated high quality, all
authored by the same author who was also the lead author on this systematic
review. They reported Level II evidence for the efficacy of cervical
interlaminar epidural injections with LA with or without steroids, based on at
least 1 high-quality relevant RCT in each category for disc herniation,
discogenic pain without facet joint pain, central spinal stenosis, and post-
surgery syndrome.74 In the 2015 systematic review, also published by this
group, on the efficacy of epidural injections for chronic spinal pain, they
rate the evidence Level II for long-term management of cervical disc
herniation with ILESI, Level II for cervical spinal stenosis management with
an interlaminar approach, Level II for post cervical surgery syndrome treated
with cervical ILESI, and Level II to III in managing thoracic disc herniation
with an interlaminar approach.54 These systematic reviews rated a higher level
of evidence than an earlier review on the same subject with overlapping
authors but using a different methodology for the assessment of the
literature, and the literature was older,75 but similar to the 2021 consensus
reports from ASIPP Guidelines for methodology.76

A 2014 multi-centered RCT of 169 patients with cervical radicular pain
compared ESIs, conservative treatment, or combination treatment for cervical
radicular pain over 6 months. Conservative treatment was pharmacotherapy with
gabapentin and/or nortriptyline, and physical therapy (PT), as indicated, and
combination therapy was ESI and pharmacotherapy with gabapentin and/or
nortriptyline plus PT. At 1-month, arm pain scores were 3.5 (95% CI, 2.8 to
4.2) in the combination group, 4.2 (CI, 2.8 to 4.2) in ESI patients, and 4.3
(CI, 2.8 to 4.2) in individuals treated conservatively (P=0.26). Combination
group patients experienced a mean reduction of -3.1 (95% CI, -3.8 to -2.3) in
average arm pain at 1 month versus -1.8 (CI, -2.5 to -1.2) in the conservative
group and -2.0 (CI, -2.7 to -1.3) in ESI patients (P=0.035). For neck pain, a
mean reduction of -2.2 (95% CI, -3.0 to -1.5) was noted in combination
patients versus -1.2 (CI, -1.9 to -0.5) in conservative group patients and
-1.1 (CI, -1.8 to -0.4) in those who received ESI (P=0.064). Three-month post-
treatment, 56.9% of patients treated with combination therapy experienced a
positive outcome versus 26.8% in the conservative group and 36.7% in ESI
patients (P=0.006). The authors reported a lack of significant difference
between the groups, with the combination therapy providing better improvement.
These results support an interdisciplinary approach to neck pain may improve
outcomes; confirmatory studies are needed.77

A 2014 prospective observational study of 143 patients who received cervical
paramidline ILESIs reported initial improvements at 2 weeks in 115 of 143
patients (80.8%). Patients with paresthesia only and no pain showed
significantly fewer improvements after ESIs (11/19, 57.9%) than patients with
pain (104/124, 83.9%) (p=0.013). The authors conclude that fluoroscopic
paramidline ILESIs can effectively manage cervical radiculopathy, irrespective
of the cause or zone of nerve root compression, and patients with paresthesia
only experienced fewer improvements.78

A 2018 randomized trial compared cervical interlaminar epidural injections in
post-surgery syndrome with LA with steroids to LA alone using a = 50%
improvement on NRS and functional status improvement using the Neck Disability
Index (NDI). The authors report similar improvements in both groups, with 69%
of patients receiving LA and 71% of subjects receiving LA and steroids showing
significant improvement at the end of 2 years. They report an average number
of procedures of 5 to 6 with an approximate 12 weeks of significant
improvement per procedure. Limitations of the study were multiple co-
interventions, and variability in the frequency and number of interventions,
and lack of true control group.79

A 2020 systematic review and meta-analysis on the effectiveness of
fluoroscopic guided cervical TFESI for the treatment of radicular pain
included 6 randomized and 11 nonrandomized comparative studies with pain
improvement at least 50% from baseline. Using GRADE methodology, they reported
approximately 50% of patients experienced = 50% pain reduction at short- and
intermediate-term follow-up. However, they acknowledged the literature was
very low quality according to GRADE criteria and the lack of existing studies
with adequate control groups.80

A 2020 systematic review and meta-analysis on the effectiveness of epidural
injections with LA with or without steroids for management of chronic neck
pain concluded that similar pain relief and function were achieved between the
2 groups. This was limited by the lack of RCTs, lack of heterogenicity in the
included studies with only 1 group publishing on this topic, and lack of
control groups within the RCTs.81

A 2020 retrospective report on the proportion of patients requiring surgery
after CESIs reported 11.2% of patients underwent surgery within 6 months of
CESI, 14.5% by 1 year, and 22.3% by 5 years. Patients with stenosis and
herniation were more likely to undergo surgery than those with radiculopathy.
They report repeat injections reduced risk for subsequent surgery with a mean
of 1.7 to 5.5 injections in follow-up over 2 years. The study is limited by
its retrospective nature, varying numbers of repeat injections and duration of
time between injections, and lack of specific indications for injections or
subsequent surgery or surgical candidacy. It is difficult to conclude that the
steroid injections reduce the risk for subsequent surgery as the natural
disease course points towards improvement alone.82

Multiple papers review the safety concerns surrounding cervical ESIs. The risk
of spinal cord injury increases as the epidural space narrows moving
cranially, so many authors and recommendations conclude that cervical
injections should be restricted to C6-C7 or C7-T1. Additional safety measures
include a review of pre-procedural imaging and avoiding particulate steroids
in cervical injections.1,14 A report addressing key safety issues states,
"overall cervical and thoracic transforaminal epidurals constitute 2.4% of all
epidural injections and less than 5% of all transforaminal epidural
injections; however, they contribute to over 99% of the complications related
to intra-arterial injection of particulate steroids" and recommends against
the use of cervical TFESI injections.32

The SME panel was asked their confidence for evidence to support cervical ESIs
and they voted 4/5 (range 1-5).

****

**Thoracic Epidural Injections**

A 2012 systematic review of thoracic ILESI used the United States Preventive
Task Force (USPTF) rating of evidence methodology and reviewed 2 studies, 1
RCT and 1 observational study. The review concluded the evidence for thoracic
epidural injection treating chronic thoracic pain is considered fair and
limited for post-thoracotomy pain.83 The USPTF grading has been revised since
2012, but at that time fair was considered sufficient evidence to determine
the effect on health outcome, but the strength of evidence was limited, and
limited/poor was insufficient evidence to assess.

A 2014 RCT without a placebo group with 110 patients was randomized to 2
groups; 1 group received LA (n=55) and the other group LA with steroids
(n=55). They reported most patients had 5 to 6 procedures over 2 years and
reported improvement in 71% in LA alone and 80% in LA plus steroids.
Limitations included lack of placebo group and variability in timing and
number of procedures.84

The SME panel voted 4/5 (range 2-5) that the evidence supports the benefits of
ESIs outweighs risk for thoracic radicular pain. The panel discussed that
thoracic radicular pain is far less common and has not been well studied.

****

**Frequency, Laterality and Multiple Level Injections**

Existing evidence and societal guidance support conservative management for
acute back pain. There is little data regarding the frequency of ESIs for
patients who are candidates for intervention. A 2018 prospective cohort study
of 102 patients who had ESI for radicular symptoms related to disc herniation
(n=57) or cervical disc herniation (n=45) and had a second injection
administered for persistent pain were followed for 1 year. Seventeen patients
had a second injection for lumbar herniation (29.8%) and 7 for cervical
herniation (15.6%) at a mean of 65.3 days (standard deviation [SD] 46.5) and
47 days (SD 37.2), respectively. All but 1 patient who had surgery responded
satisfactorily with a mean VAS for leg pain of 8.8 mm (SD 10.3) and a mean VAS
for arm pain of 6.3 mm (SD 9) 1 year after the second injection, respectively.
They concluded repeat injections were acceptable treatment in symptomatic
patients without satisfactory relief after the first injection.85 Limitations
of this study conducted in Europe were different standards for ESI and repeat
injection, risk of recall bias, and varying times to the second injection. In
a study by the same authors, 1,002 consecutive patients were prospectively
assessed on short-term response to ESIs for various indications. They
determined 10-day outcomes of the second injection were as good as the outcome
of the primary injection for a lumbar herniation: (72.2% better, 24.7% the
same, and 3.1% worse following 295 primary injections compared with 70.1%
better, 24.8% the same, and 5.1% worse after 117 second injections; p=0.593).
For cervical herniation, the improvement was reported in 63.1%, the same in
28.6%, and worse in 8.3% after 84 primary injections compared with 52.2%
better, 34.8% the same, and 13% worse after 23 second injections; p = 0.602).
This study was also a European population and did not use validated outcome
scores.86 Other studies have also reported improvements with second
injections, but high variability in timing and number of injections and
inclusion of other spinal procedures challenge interpretation. A 2016
prospective observational study included 184 patients who underwent TFESI for
axial neck or radicular arm pain due to herniated disc or spinal stenosis. A
group of partial responders (n=108) was scheduled to undergo repeat injection
at two-three weeks. The other group (n=76) of partial responders received
repeat injections for aggravation of pain. They concluded the scheduled repeat
injection group showed a significantly longer time to reinjection and improved
clinical benefits.67 This was limited by a lack of a control group, lack of
standardization in the total number of injections, and unclear randomization.

A 2014 retrospective observational study evaluated 933 patients with a total
of 2,087 TFESI. Injections were repeated at intervals of at least 2 weeks for
a duration of up to 1 year from index injection. Of the total patients in the
database (933/4,161) 22.4% received repeat injections during the study period,
and the cohort showed a significant decrease in improvement with subsequent
injections (p=0.0311). This study is limited by retrospective design and high
variability in the duration between injections and steroid preparations. They
found most patients did not require repeat injections for treatment of lumbar
radicular pain but did find those with an incomplete initial response who
received early repeat injections within 3 months can achieve a cumulative
benefit.87

On the contrary, several authors reported no difference in long-term outcomes
in patients receiving a second injection nor a reduction in the need for
surgery.88,89 The 2005 Wessex Epidural Steroids Trial (WEST) study was a
multicenter, double-blinded randomized placebo-controlled trial with 228
patients with sciatica. The patients were randomized to either 3 lumbar ESIs
with steroid or placebo (saline) at intervals of 3 weeks. At 3 weeks, they
discovered that the ESI group had a transient benefit over the placebo group
(75% improvement in ODQ, 12.5 vs. 3.7%; number needed to treat, 11.4). No
benefit was demonstrated from 6 to 52 weeks. They concluded that ESIs did not
improve physical function, hasten return to work or reduce the need for
surgery and did not find a benefit of repeated ESIs over single injection.
They advocate a multidisciplinary approach for management.90 Limitations were
the use of 75% cut off for improvement while most studies use 50%, and
assessment of disability but not pain assessment.

A 2013 systematic analysis identified 9 studies with = 50% pain relief after
TFESIs for radicular pain after a single injection and reported 94% required a
single injection and 4% required a second injection to achieve this level of
pain relief. The use of 3 or 4 injections was rare.7

A 2014 retrospective observational study investigated if repeat lumbar TFESIs
resulted in pain relief which has waned since index injection, and if a
cumulative benefit could be achieved by repeat injections within 3 months of
the index injection. Four thousand one hundred sixty-one patients received
single-level TFESIs for radicular pain with or without radiculopathy. Between
2 weeks and 1 year from index injection, 933 subjects (22.4%) had repeat
injection within 1 year. The data indicates that 18% of subjects had 2
injections, 3.6% had 3 or more injections. They concluded there was cumulative
benefit of repeat injections within 3 months of the index injection.87
Limitations of the study included the retrospective design, a high number of
patients lost to follow-up and no standardization in terms of timing of the
repeat injection(s).

Using quality assurance databases from radiology and 2 medicine and
rehabilitation (PM&R) practices, 16,638 consecutive procedures in all spine
segments (14,956 TFESI; 1,682 ILESI) were evaluated for major and minor
adverse safety outcomes. The most frequent complication was a vasovagal
reaction in 1.2% and dural puncture in 0.06%. They reported no major adverse
reactions, no long-term sequelae from any intermediate or delayed minor
adverse events. They concluded both TFESI and ILESI are safely performed with
low immediate and delayed adverse event rates when informed by evidence-based
procedural guidelines. Of note, multiple patients in this population had
bilateral procedures or 2-level injections without additional safety
concerns.34

A 2016 study was conducted for 184 patients who underwent TFESI for axial neck
and radicular arm pain with single ESI. Group A (n=108) was comprised of
partial responders defined as a NRS = 3 and received scheduled repeat
injections at 2 to 3 weeks after the first injection. Group B (n=76) was
comprised of partial responders who did not receive a repeat injection but
received intermittent injections for aggravation of pain. Total number of
injections within 1 year and NRS score <3 were recorded, and they concluded
Group A showed a significantly longer time to re-injection and a longer time
between injections. The average number of injections was 2.48 in Group A, with
4 patients receiving more than 3 injections and 2.98 in Group B with 16
patients receiving >3 injections.91 This study is limited by retrospective
design and selection bias as patients who did not follow-up for a year or
choose surgery were excluded.

SMEs were asked about their confidence that the evidence demonstrates ESIs
provided relief for a minimum of 6 weeks after injection with score of 4/5
(range 1-5).

  * The panel was split regarding repeating ESIs if the initial treatment did not result in substantial pain relief with the majority feeling that repeating in a different level would be appropriate (3/5; range 1-5), but not at the same level that did not achieve improvement with ESI.
  * When asked if there is literature on a safe or harmful number of ESIs per year 7/11 SMEs voted no. There was not a consensus among the panel in terms of the number of ESIs that would be considered safe or harmful in a 12-month time period with a range of 3-4 in 12 months suggested.
  * In response to the question concerning the literature providing input on the safety of multiple levels of ESIs performed in the same session, 6 out of 11 voted no. When asked the number of levels they felt would be safe the range was 1 to 3 per session.
  * Half (5/10) did not feel the literature provides input on a safe duration of time between the administration of separate ESIs in the same spinal region and the recommended duration ranged from 2 weeks to 3 months. One SME stated, "the need for individual assessment and response to prior injections as well as goals of treatment management versus resolution are factors that can influence this decision".
  * SMEs were asked about their level of confidence in the evidence to support repeat epidural injections for long-term management of chronic back pain >6 months and there was not a consensus. Comments included lack of supporting evidence for ESIs for chronic pain management. This must be balanced against patients who do have good results with injections and wish to avoid surgery when clinical benefit is evident.

****

**Injectants**

****

ESIs usually contain LA and glucocorticoids. The optimal combination and
dosing have not been determined. The role of epidural nonsteroidal injections
remains controversial. A 2013 systematic review and meta-analysis looked at
the control arm of 43 studies which included saline, LA, and injections into
muscle or ligament (sham). In the indirect comparison, they concluded E
epidural non-steroidal injections achieved positive outcomes (RR, 2.17; 95%
CI, 1.87-2.53) and provided greater pain reduction scores (MD, -0.15, 95% CI,
-0.55 to 0.25). Indirect comparison does not qualify as the same level of
evidence as a randomized comparison, and the study was limited by only 1
included study being ranked as high quality using GRADE methodology and
inadequate numbers to detect in effect by size, but suggest that the
nonsteroidal injections were not entirely placebo.92 A 2015 systematic review
of RCTs using Cochrane review criteria and the ASIPP criteria for assessing
interventional techniques looked at 31 trials seeking evidence on LAs, saline,
steroids, and other solutions. They conclude equal efficacy for LA with
steroids and LA alone in multiple spinal conditions. For disc herniation, they
report superiority of LA with steroids over LA alone.93 A 2021 systematic
review of RCTs by Manchikanti et al. compared sodium chloride solution alone,
steroids alone, or sodium chloride solution with steroids in managing spine
pain secondary to disc herniation or spinal stenosis. The authors reported
utilizing a single-arm analysis that both epidural saline and epidural
steroids with saline were effective in reducing 20% of pain, however, only
reducing disability score by 10 to 20%.94 Several 2020 systematic reviews and
meta-analysis looking at the difference in efficacy between lidocaine alone
versus lidocaine and steroids in the management of lumbar disc herniation or
spinal stenosis concluded there were similar effects associated with lidocaine
alone or in combination with steroids.95,96

This study contradicts multiple other studies that showed steroids were
superior to saline or other placebos. The Friedly et al. multicenter, double-
blinded RCT compared epidural injections of corticosteroids plus lidocaine
versus lidocaine alone in 400 patients with confirmed spinal stenosis. In this
study, patients had the option of blinded crossover after 6 weeks to receive
the alternate treatment. However, fewer participants randomized to
corticosteroids plus lidocaine (30%, n=60) versus lidocaine alone (45%, n=90)
crossed over in 6 weeks (p=0.03) and 93% indicating a lack of effectiveness as
a reason to cross-over. Using an intention to treat (ITT) analyses, a small,
but consistent difference favoring steroids plus LA over LA alone was
observed. At 12 months there was no significant difference between the group.
This study did not show repeat injections of either type offering additional
benefit if injections in the first 6 weeks did not improve pain.65 A
systematic review by Bicket et al. evaluating control injections in RCTs
reports that ESIs may provide a benefit compared to non-ESIs while
acknowledging this was based on few, low-quality studies directly comparing
controlled treatment and short-term outcomes. However, this review with 3,651
patients from 43 studies represents the largest analysis comparing ESI with a
steroid to a nonsteroidal alternative including, LA alone, etanercept, saline,
intramuscular or ligamentous injections, and dry needling. The authors
concluded the benefit from ESIs was limited but suggested it may not
constitute a placebo effect.92

While systematic reviews and meta-analysis have suggested a role in non-
steroidal injections, these studies are limited because they rely on
previously conducted RCTs where the research question was not specific to
determining the effectiveness of these nonsteroid injections. The data set
utilized is subject to significant heterogenicity (I2 >50-99%), variability of
the patient population, and small sample sizes. Studies dedicated to the
investigation of the nonsteroid injections are necessary as well as studies
with longer-term follow-up periods to understand if there is a role for
nonsteroidal injections in lieu of ESIs. There is not enough evidence to be
confident that nonsteroid injections are equally effective to steroid
injections based on the current body of literature.

A 2016 study reported improvement in pain with particulate compared to non-
particulate steroids.97 Spinal cord ischemia and posterior circulation
infarction have been reported after cervical ESIs. Concern arose that this
risk was greater for particulate compared to non-particulate steroids
prompting further investigations and recommendations. In 2011 the FDA required
a label change for triamcinolone stating it should not be used for ESI.98 A
2017 systematic review and meta-analysis comparing particulate steroids to
non-particulate counterparts conclude that particulate steroids are not better
in relieving pain compared to their non-particulate counterparts but may offer
an improved safety profile. They conclude with the recommendation to consider
switching to non-particulate steroids.99 Another 2017 systematic review by
Mehta et al. agreed concluding, no benefit to particulate steroids and
recommending non-particulate steroids with performing cervical TFESI, with
Grade of Recommendation: B. For lumbar TFESI they state particulate vs. non-
particulate as equivocal with Grade of Recommendation: B for pain reduction
and C for function with an overall recommendation for non-particulate steroids
for lumbar TFESI.100

Steroid dosing, dilution, and additives are not standardized and are another
area of controversy. There is evidence that different dilutions such as sodium
chloride and local anesthetic can alter the steroid's particle size and
distribution. There is concern about the toxicity of additives (such as benzyl
alcohol and polyethylene glycol). Based on the potential risk associated with
systemic corticosteroid absorption the WIP Benelux Workgroup recommends using
the lowest effective dosing, which amounts to 40 mg for methylprednisolone
acetate (MPA), 10-20 mg for triamcinolone acetate, and 10 mg (10 mg/mL) for
dexamethasone phosphate. They recommend limiting the cervical interlaminar and
lumbar transforaminal volume to 4 mL and inject slowly.16

Etanercept is a soluble p75 tumor necrosis factor fusion protein administered
subcutaneously for inflammatory arthritis and other rheumatological
conditions. While it has been explored in several studies with preliminary
positive results, it is not FDA approved for injection into the epidural
space, and therefore is not considered medically reasonable and necessary.
Additional agents such as platelet-rich plasma, amniotic fluid, gabapentin,
and others have been investigated, but there is not sufficient evidence to
support use and are considered investigational.

**Multiple Procedures**

****

Since injectants may have a bilateral effect or spread to adjacent levels,
diagnostic interlaminar or caudal ESIs are seldom used. Diagnostic TFESIs are
sometimes used to determine the level of radicular nerve root pain to
differentiate radicular from non-radicular pain, to evaluate a discrepancy
between image studies and clinical findings, to identify the source of pain in
the prevalence of multi-level nerve root compression, and to help identify the
level of pathology at a previous operative site. Selective spinal nerve blocks
may also be used to identify the source of pain. The cumulative steroid dose
and long-term safety has not been studied in the setting of multiple
injections administered in the same session.

The SMEs were split in terms of multiple procedures during a single session,
with half of the experts (6/11) voting that evidence supported the
administration of ESIs at the same time as other interventional procedures.
However, there was no additional supporting literature provided, and others
brought up the concern of lack of diagnostic specificity when multiple
procedures are performed in the same session.

**Society Guidance**

****

_North American Spine Society (NASS)_

The 2020 NASS Evidence-Based Clinical Guidelines for Multidisciplinary Spine
Care: Diagnosis & Treatment of Low Back Pain concludes that there is
insufficient evidence to make a recommendation for or against the use of
caudal or interlaminar ESIs in patients with LBP with Grade of Recommendation:
I (good evidence for or against recommending intervention).15

The 2020 NASS Epidural Steroid Injections & Selective Spinal Blocks offers
evidence-based coverage recommendations when possible and in the absence of
strict evidence-based criteria recommendations are based on multidisciplinary
experience and expertise of the authors. Evidence in this coverage policy are
not graded11:

  * ESIs can be performed to provide relief of radicular or referred pain when 2/4 are present: pain is severe enough to cause a degree of functional and/or vocational impairment or disability; pain duration of at least 4 weeks, and/or inability to tolerate or failure to respond to 4 weeks of noninvasive care, objective findings of radiculopathy or sclerotomal referred pain pattern are present and documented on examination, and advanced imaging (CT or MRI) demonstrates a correlative region of nerve involvement. Criteria for exemption of 4-week delay is moderate to severe pain with functional loss at work and/or home, pain unresponsive to outpatient medical management, inability to tolerate non-surgical non-injection care to a coexisting medical condition or severe pain or prior successful injection therapy for same condition achieving greater than 50% relief.
  * ESIs are contraindicated for axial or nonspecific pain without radiating pain, most cancer or strong clinical suspicion of cancer, infection and compression lesions of the spinal cord, conus medullaris or cauda equina. Relative contraindications to the performance of ESIs may include coexisting medical conditions such as uncontrolled bleeding disorders, poorly controlled diabetes (if corticosteroids are going to be used), immune system impairment, history of severe allergic reaction to components, etc. In these situations, the risk/benefits of the procedure should be considered in the medical decision-making process.
  * Procedural based recommendations include the use of image guidance, ILESIs should not be performed above C7, injection of contrast media under real time fluoroscopy or digital subtraction imaging, use of a non-particulate steroid with the exception of thoracic and cervical spine, extension tubing for provider safety, and appropriate provider training.
  * Suggested frequency of ESIs were based on author's expert opinion included no more than 4 ESIs and/or suprascapular nerve blocks (SSNBs) should be performed in a 6-month period of time, no more than 6 ESIs and/or SSNBs should be performed in a 12-month period of time regardless of the number of levels, no more than 2 TFESIs should be performed at a single setting (e.g., single level bilaterally or 2 levels), and for CESIs or ILESIs, only 1 level per session may be performed and NOT in conjunction with a TFESI injection.
  * Local anesthesia is sufficient for most cases. Occasional minimally to moderate conscious sedation is appropriate and if MAC is utilized the need for such stations should be clearly documented in the medical record.
  * They report that studies found that most patients who respond to ESIs do so with 3 or less injections for a specific episode of back and radicular pain. They provide non-evidence-based criteria for instances when they consider it medically appropriate to perform more than 3 injections. These circumstances include performance of SSNBs for surgical planning after failed ESIs, the presence of new injuries after resolution of prior conditions or after interval surgery since prior ESIs, prior injections were done without fluoroscopy or were inaccurately placed, exacerbation of symptoms that responded well to prior ESIs, and patients who responded well to prior ESIs that are not surgical candidates due to comorbid medical conditions.

_US Department of Veterans Affairs (VA)/US Department of Defense (DoD)_ 19 __

The 2017 VA/DoD Clinical Practice Guideline for Diagnosis and Treatment of Low
Back Pain **** utilized GRADE methodology. The original guidelines were
developed in 2007. In 2017 the literature was reviewed and recommendations
were added (New-added).

  * For the long-term reduction of radicular LBP, non-radicular LBP, or spinal stenosis, we recommend against offering spinal ESIs. (Strong against | Reviewed, New-added)
  * For the very short-term effect (less than or equal to 2 weeks) of reduction of radicular LBP, we suggest offering ESI. (Weak for | Reviewed, New-added)
  * For the treatment of LBP, we suggest against offering intra-articular facet joint steroid injections. (Weak against | Reviewed, New-added)

_American Society of Interventional Pain Physicians (ASIPP)_

The ASIPP released updated 2021 Epidural Interventions in the Management of
Chronic Spinal Pain: ASIPP Comprehensive Evidence-Based Guidelines.76 This
extensive evidence synthesis utilized a modified approach to the grading of
evidence101 and a recommendations grade table published in the British Medical
Journal in 2001. This grading system utilizes the type of study and the number
of studies. In contrast, the GRADE system, defined in definitions above and
commonly used in guideline development, focuses on the quality of the studies
with up or downgrading based on methodology. The quality of each article was
assessed by IPM-QRB. ** ** Recommendations were made based on the National
Guideline Clearing Extent Adherence to Trustworthy Standards instrument. While
many of the recommendations were moderate to strong and based on Level I-II
evidence paucity of literature with many of these areas is based on 1 study.

Evidence:

  * Disc Herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for CESIs, lumbar ILESIs, and lumbar TFESIs and cervical ILESIs with a strong recommendation for long-term effectiveness.
  * For thoracic disc herniation, based on 1 relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.
  * For spinal stenosis, the evidence is based on 1 high-quality RCT in each category. The evidence is level II-III for fluoroscopically guided caudal epidural injections with moderate-to-strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate-to-strong recommendation for long-term effectiveness.
  * The evidence for lumber TFESIs is Level III-IV with moderate recommendation with fluoroscopically guided lumbar TFESIs for long-term improvement.
  * For axial discogenic pain, the evidence without facet joint pain or sacroiliac joint pain in the lumbar, and cervical spine with fluoroscopically guided caudal, lumbar and cervical ILESIs, based on 1 relevant high-quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids.
  * The evidence for lumbar and cervical post-surgical syndrome based on 1 relevant high-quality RCT with fluoroscopic guidance for caudal and cervical ILESIs, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement.

_The ACR, the American Society of Neuroradiology (ASNR), the American Society
of Spine Radiology (ASSR), the Society of Interventional Radiology (SIR), and
the Society of NeuroInterventional Surgery (SNIS)_

ACR-ASNR-ASSR-SIR-SNIS Practice Parameter for the Performance of Image-Guided
Epidural Steroid Injection (2019) is a Collaborative guideline.

  * When an ESI is performed, success is defined as the achievement of significant pain relief, reduced disability, and/or improved quality of life. These should be measured by at least 1 of the relevant and validated measurement tools, such as the 10-point numerical pain rating scale score or a VAS score (Roland-Morris Back Pain score, ODI, The Short Form (36) Health Survey, or similar outcome tool to measure pain, disability, and/or quality of life). It is generally accepted that a minimum of 20% change in pain scores is clinically meaningful, based upon previous trials and FDA requirements.

****

  * They list the following absolute contraindications:

  1.     1. Coagulopathy not correctible
    2. Concurrent systemic infection
    3. Infectious spondylitis
    4. Acute spinal cord compression
    5. Myelopathy or cauda equina syndrome
    6. Inability to obtain informed consent
    7. Infection at the skin puncture site

****

  * They list the following relative contraindications:

  1.     1. Uncorrected anticoagulation therapy - ILESIs and TFESIs are considered intermediate-risk procedures with a moderate risk of bleeding.
    2. Hypersensitivity to administered agents - Allergy to contrast may be treated with premedication with antihistamine agents or an alternative approach (such as using CT guidance with air as the contrast medium may be considered).
    3. Pregnancy - Although such interventions may be performed without image guidance in pregnant patients, there is a 30% rate of incorrect placement [106]. Other options include MRI-guided injections and ultrasound-guided injections as image-guided procedures have a significantly greater margin of safety and should be utilized when feasible.
    4. Hepatitis - When performing neuraxial blockade in hepatitis C patients, thrombocytopenia must be excluded in order to avoid hematoma formation and its associated neurologic complications.
    5. Uncontrolled diabetes mellitus- Insulin-dependent diabetics are at risk of elevated blood sugars after steroid injections.
    6. Congestive heart failure - The steroid may lead to fluid retention.
    7. Immunosuppressed state- Preprocedural antibiotics may be considered.
    8. Patient improving on medical and physical therapy.
    9. Severe spinal canal stenosis
    10. No response to previous well-performed ESI
    11. Complication to steroid therapy (Cushing's etc.)

_Agency for Healthcare Research and Quality (AHRQ)_

The AHRQ 2015 Technology Assessment for Pain Management Injection Therapies
for Low Back Pain2

  * The 2015 AHRQ technology assessment played a pivotal role in epidural injection for pain. While this report has not been updated since 2015 due to loss of funding for this project, this report remains significant as it was funded by AHRQ, so there was low-risk of outcome reporting bias, and leads to questions regarding the effectiveness and utility of ESIs for pain. The report includes a systematic review of RCTs of patients with lumbosacral radiculopathy, spinal stenosis, non-radicular back pain, or chronic post-surgical back pain. Quality of evidence was assessed for risk of bias using the Cochrane Back Review Group criteria. Meta-analysis was performed and stratified by time. A total of 79 RCTs of epidurals were included. The results were: "For ESIs versus placebo interventions for radiculopathy, the only statistically significant effects were on mean improvement in pain at immediate-term follow-up (weighted mean difference [WMD] -7.55 on a 0 to 100 scale, 95% CI -11.4 to -3.74) (strength of evidence [SOE]: moderate), the mean improvement in function at immediate-term follow-up when an outlier trial was excluded (standardized mean difference [SMD] -0.33, 95% CI -0.56 to -0.09) (SOE: low), and risk of surgery at short-term follow-up (relative risk [RR] 0.62, 95% CI 0.41 to 0.92) (SOE: low). The magnitude of effects on pain and function was small, did not meet predefined thresholds for minimum clinically important differences, and there were no differences in outcomes at longer-term follow-up. Evidence on effects of different injection techniques, patient characteristics, or comparator interventions estimates was limited and did not show clear effects. Trials of epidural corticosteroid injections for radiculopathy versus non-placebo interventions did not clearly demonstrate effectiveness (SOE: insufficient to low). Evidence was limited for epidural corticosteroid injections versus placebo interventions for spinal stenosis (SOE: low to moderate) or nonradicular back pain (SOE: low), but showed no differences in pain, function, or likelihood of surgery. Serious harm from injections were rare in randomized trials and observational studies, but harm reporting was suboptimal (SOE: low)." The authors concluded that corticosteroid injections for radiculopathy were associated with immediate but short-term benefits and did not reduce the long-term risk of surgery. They also conclude that ESI is not effective for spinal stenosis or non-radicular back pain.

_The American College of Physicians (ACP)_ ****

  * The ACP created the Clinical Practice Guidelines for Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain (2017) using the ACP grading system methodology and based on published systematic reviews and a systematic review of RCTs through April 2015 to develop the following recommendations25:
    * Recommendation 1: Given that most patients with acute or subacute LBP improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select NSAIDs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation).
    * Recommendation 2: For patients with CLBP, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation).

This report was updated in 2017 with some changes in recommendations for
initial pharmacological management, but other conclusions were relatively
unchanged.102

****

****

_American Society of Anesthesiology (ASA)_

  * The American Society of Anesthesiologist Task Force developed Practice Guidelines for Chronic Pain Management, which were last updated in 2010. At that time, they stated, "ESI, with or without local anesthetics, may be part of a multimodal treatment regimen to provide pain relief in selected patients with radicular pain or radiculopathy. Shared decision-making regarding epidural steroid injections should include a specific discussion of potential complications, particularly regarding the transforaminal approach. Transforaminal epidural injections should be performed with appropriate image guidance to confirm correct needle position and spread of contrast before injecting a therapeutic substance; image guidance may be considered for interlaminar epidural injections."12

****

_American Academy of Neurology (AAN)_

The AAN published a technology assessment and reported in March 2007 and
reaffirmed in July 2010 on ESIs to treat radicular lumbosacral pain.12,20
Their recommendations and conclusions include:

  1. ESIs may result in some improvement in radicular lumbosacral pain when determined between 2 and 6 weeks following the injection, compared to control treatment (Level C, Class I-III evidence). The average magnitude of the effect is small, and the generalizability of the observation is limited by the small number of studies, limited to highly selected patient populations, the few techniques and doses studied, and variable comparison treatments.
  2. In general, ESIs for radicular lumbosacral pain have shown no impact on average impairment of function, on the need for surgery, or long-term pain relief beyond 3 months. Their routine use for these indications is not recommended (Level B, Class I-III evidence).
  3. Data on the use of ESIs to treat cervical radicular pain are inadequate to make any recommendation (Level U).

_American Association of Neurological Surgeons (AANS) and the Congress of
Neurological Surgeons (CNS)_

The AANS and the CNS guidelines update for performance of fusion procedures
for degenerative disease of the lumbar spine reviewed injection therapies for
LBP in Part 13 of their guideline update and reported no new evidence that
changes recommendations from their original publication in a 2014 update.103
The guidelines were based on a review of literature through 2011 and focuses
on 3 systematic reviews and an updated review of RCTs. They conclude, "the
medical literature continues to fail to support using lumbar epidural L
injections for long-term relief of chronic back pain without radiculopathy.
There is limited support for the use of lumbar epidural injections for short-
term relief in selected patients with chronic back pain."

  * Lumbar ESIs: Grade C Lumbar ESIs are an option for the short-term relief of CLBP without radiculopathy in patients with degenerative disease of the lumbar spine (Level III evidence).
  * CESIs are an option for decreasing LBP of greater than 6 weeks' duration, without radiculopathy, in patients with degenerative disease of the lumbar spine (Level III)

**__**

_Spine Intervention Society (SIS)_

The SIS Patient Safety Committee published 2020 guidance on the frequency of
ESIs8:

  * After an ESI, a period of up to 14 days may be needed to assess the clinical response. Systemic effects on the HPA axis may last 3 weeks or longer. These factors must be considered when determining if or when another ESI is indicated.
  * There is no evidence to support the routine performance of a "series" of repeat injections without regard to the clinical response to an initial injection.
  * Two separate studies suggest that repeat injections may improve outcomes in patients with a partial response to a first (index) ESI. Repeat ESI at greater than 2 weeks and less than 1 year from the index injection has also been shown to result in a statistically and clinically significant decrease in pain, and patients with acute to subacute symptoms recover all prior benefit with a statistically significant cumulative benefit.

_The American Society of Regional Anesthesia and Pain Medicine, the European
Society of Regional Anesthesia and Pain Therapy, the American Academy of Pain
Medicine, the International Neuromodulation Society, the North American
Neuromodulation Society, and the World Institute of Pain provided updated
guidelines for Interventional Spine and Pain Procedures in Patients on
Antiplatelet and Anticoagulant Medications (Second Edition)_ 104 __

This updated guideline addresses "Pain Procedures Classification According to
the Potential Risk of Serious Bleeding" and indicates:

  * Intermediate risk defined as patients with a high risk of bleeding (e.g., old age, history of bleeding tendency, concurrent uses of other anticoagulants/antiplatelets, liver cirrhosis or advanced liver disease, and advanced renal disease) undergoing low- or intermediate-risk procedures should be treated as intermediate or high risk, respectively includes: ILESIs (cervical, lumbar, sacral and thoracic) TFESIs (cervical, lumbar, sacral and thoracic).
  * Recommends review of radiological imaging prior to performance of the procedure to assess for central and foraminal stenosis, disk herniations that compromise canal diameter, ligamentum flavum hypertrophy, epidural fibrosis, and previous surgical scarring, which can alter the level of procedural difficulty.
  * Provides summary and guidance for multiple drugs including aspirin, NSAIDs, coumadin, heparin, low molecular weight heparin, fibrinolytic agents, etc.

_The National Institute for Health and Care Excellence (NICE)_ 28  _provided
guidelines for "low back pain and sciatica." Assessment and management
recommendations include:_

  * Support use of epidural injections for acute and severe sciatica
  * Recommends imaging if it may change future management, including consideration for epidural or spinal surgery.

ESIs are a common pain management procedure for use in acute and chronic back
pain. There are many areas of controversy regarding ESIs. This controversy was
reflected among the SME panel, where the experts expressed broadly differing
interpretations of the literature and opinions regarding the appropriate use
of ESIs. There is a body of literature of RCTs comparing ESIs to various
placebos, including LA, saline, and sham procedures. However, few new trials
have been conducted in recent years to further address the questions and
issues surrounding ESIs. Instead, there is a multitude of systematic reviews
and meta-analyses of the previously conducted RCTs. These reviews have
produced divergent conclusions despite using a similar body of literature.
Meta-analysis is limited as there is a great deal of heterogenicity among the
RCTs. Meta-analysis is to synthesize the effects of many different studies
into 1 single effect, which can be a powerful tool to expand the number of
subjects and help to determine the real or true effect. However, when
heterogenicity is high, it may not be appropriate to pool the data as we
cannot be certain there is a real or true effect behind the data. Single arm
analysis is not sufficient to resolve this limitation.

There is a lack of a well-defined control in the studies conducted on the
effectiveness of ESI. The SMEs did not agree on the definition of placebo with
an extensive discussion surrounding the concept that LAs, or even saline, are
equally effective to steroids and cannot be counted as a placebo. To further
complicate there are multiple RCTs that showed inferiority of LA alone
compared to LA with ESIs. The lack of standardization among the studies,
including the route of administration, the type of steroid used, what it is
combined with (such as LA or saline), the amount of steroid, type of needle
used, the use of imaging, the indication for the procedure, the frequency of
injections, and the comorbidities among the patient population create
additional challenges in interpreting the literature. There are a large number
of variables that have not been adequately accounted for in the existing data.
There is a paucity of evidence addressing long-term effectiveness or quality
of life outcomes. New studies specifically addressing these issues are
limited, and most new reports are systematic reviews and not specifically
designed to answer these questions. For these reasons, we must critically
assess the existing body of literature and focus on nationally accepted
standards for the grading of evidence to ensure consistency and transparency
in the analysis of evidence. We also looked towards societal guidance and
expert input to aid in decision-making regarding this policy.

The natural disease course of lumbar radiculopathy from disc herniation is
acute pain that typically resolves spontaneously. While pain may be
debilitating during this time, outcomes are overall favorable. Conservative
management may improve pain and function and is considered the standard of
care in the acute phase. When pain persists past the acute phase, overall
outcomes are still favorable for improvement. The existing evidence was
consistent for a short-term benefit of ESIs to reduce pain and improve
function for patients experiencing this type of pain and potentially reducing
the need for surgery for a condition that may improve spontaneously with time.
The continued use of ESIs past 6 months is not well supported by the existing
evidence. Most trials did not go past 12 months, and those trials that did
investigate the past 6 months did not find consistent evidence of benefit for
ESIs in chronic management. While the evidence does not support the continued
use of ESIs, societal guidance and expert input identifies a subset of
patients who are not good candidates for surgery, or even unsuccessful with
surgery, where ESIs may provide improvement in their function and quality of
life.

In spinal stenosis, the natural disease may result in improvement over time.
Still, in settings of long-term and chronic pain, spontaneous improvement is
less likely due to the physical impingement of the nerve involved in the
stenosis. There is low-quality evidence to support the role of ESIs in the
short-term management of spinal stenosis and a trend towards improvement that
may allow time for spontaneous improvement. There is no high-quality evidence
showing a benefit for long-term outcomes. Societal guidance varies with
recommendations both in support and against use for spinal stenosis. Despite
conflicting evidence, we agree with SMEs that patients in the setting of
shared decision making and risk and benefit discussion can elect a trial of
ESIs as recovery can occur in greater than half of the patients without
surgery.

Evidence to support the use of ESIs in post-surgical back syndrome is limited.
However, alternative treatment options in this patient group are also limited.
For patients experiencing chronic back pain, especially those with previous
back surgery, multimodal therapy is an important aspect of comprehensive
treatment. Despite weak evidence, we support shared decision-making and risk
and benefit discussion of ESIs as part of the treatment plan. In multi-modal
therapy, ESIs may play a role to optimize pain and function in this population
but should not be a sole treatment option.

There was insufficient evidence to support the use of ESIs for non-specific
LBP, complex regional pain syndrome, widespread diffuse pain, pain from
neuropathy from other causes, or cervicogenic headaches. The SMEs were divided
with some supporting use for these indications; however, with the lack of
supporting literature and controversy amongst the experts, we maintain that
the use of ESIs in these conditions is not medically reasonable and necessary.

Studies support that a single injection can relieve pain in appropriately
selected patients. This is consistent with the natural history of the disease
course, which will result in spontaneous improvement over time. Repeat
injections were necessary for a minority of patients, about 20%, in the
existing literature with less than 5% receiving more than 3 injections.
National data confirms that the use of more than 4 injections is used less
than 5% of the time in the Medicare population. Simultaneously, the literature
is variable in terms of timing between injections with reported ranges of 2 to
12 weeks. Observational data suggest a potential benefit of a shorter interval
between injections of 2 to 3 weeks after initial injection, concluding that
overall pain and number of injections are reduced with this approach. This
however must be balanced against the cumulative steroid exposure and not
allowing enough time for treatment to be fully effective. A series of
injections is not supported by the literature and there is agreement for the
same among the SMEs.

While there are outliers and differing opinions as demonstrated amongst the
SMEs the existing evidence aligns with a maximum of 4 injections in a year for
most patients. Additionally, the natural history of the diseases treated with
ESIs would rarely involve more than 1 region. In review of national data less
than 0.05% of ESI sessions involved more than 1 region in the same session.

Regarding levels, no studies compared single injections to multi-level
injections to understand if the second level truly improved pain and function.
Existing data did not show increased safety risk of a second-level, and almost
no studies reported more than 2 levels in the same session. Because the drug
is not localized with more tendency to spread, second levels would not be
indicated for the caudal or interlaminar routes.

ESIs have played a role in pain management for a long time. While there is
controversy on their role in back and neck pain management, it is established
that patients have benefited at least in the short term to improve pain and
function. Existing evidence does not support that ESIs result in long term
improvement but rather provide pain relief to allow time for the natural
disease course to result in improvement. This may reduce the need for opiates
and surgery in patients suffering from extreme pain and dysfunction who would
not be able to wait for the improvement through conservative modalities. While
the risk of adverse outcomes associated with ESIs is rare, they can be
serious; therefore, appropriate use is critical. Little evidence exists to
support the use of epidural steroids over the long-term as the existing data
largely demonstrates a benefit in the short-term (less than 6 months)
management of back and neck pain. Also, continued use of steroids over the
long term may exacerbate underlying medical conditions, with an increased risk
for osteoporosis and fracture. Each intervention also carries the risk of
complications, and radiation exposure potentially causes more harm than good.
Based on our SME input, there is an understanding that there are unique
circumstances where a patient is not a good surgical candidate or strongly
opposes surgery. This may provide an option for pain and function relief and
improved quality of life.

For this reason, the use of ESIs beyond 1 year must be combined with multi-
modal therapy, which has been shown to optimize outcomes by treating pain
through a variety of modalities. For any patient continuing to need ESIs
beyond a year, evaluation of alternative treatment options and the risk and
benefit of continued use are an important aspect of care. The involvement of
the patient's entire medical team, including primary care physicians who
manage other underlying diseases and understand the procedure's impact on
other health outcomes, should play a role in the risk and benefit discussion.

There is a lack of standardization in the use of ESIs, including the approach
to the injection, type of injection, amount of injectant, duration of time and
criteria for repeat injection would be considered, indications for injections,
and measurements of outcomes. SMEs and societal guidance are conflicting. The
literature does not provide clear answers to these questions, and the high
variability in the individual studies makes consolidation of these reports in
the form of meta-analysis difficult to interpret because the studies are so
different that it is comparing "apples to oranges." Additional research is
necessary to reconcile the controversial areas and fully understand the role
of ESIs in pain management. The coverage determined within this LCD is based
on the available literature and maintains access to this service, despite the
limitations and unknowns, to ensure access to non-surgical options for
beneficiaries.