****

Compliance with the provisions in this 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 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 CDC reported
28% of men and 31.6% of women age  18 had lower back pain in the past three
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 pain1
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 three ways. Interlaminar (IESI) approaches the
epidural space from the posterior spine between the two vertebral laminae near
the midline. In the transforaminal approach (TFESI), the injectant is
delivered through the neuroforamen adjacent to the nerve root within the
intervertebral foramen. The caudal approach (CESI) 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\. Epidural steroid injection (ESI) will be considered medically reasonable
and necessary when the following three (3) requirements are met:

  *     * History, physical examination, and concordant radiological image-based diagnostic testing supporting one of the following5:

      * Lumbar, cervical or thoracic radiculopathy, radicular pain and/or neurogenic claudication due to disc herniation, osteophyte or osteophyte complexes, severe degenerative disc disease, producing foraminal or central spinal stenosis5; **OR**
      * Post-laminectomy syndrome6-8; **OR**
      * 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 four (4) weeks, and the inability to tolerate noninvasive conservative care or medical documentation of failure to respond to four (4) weeks of noninvasive conservative care **or** acute herpes zoster refractory to conservative management where a four (4) week wait is not required.9

2\. The ESIs must be performed under CT or fluoroscopy image guidance with
contrast,10 unless the patient has a documented allergy to low molecular
weight nonionic contrast. If the patient has such an allergy, ultrasound
guidance without contrast may be considered. If the patient is pregnant,
ultrasound guidance without contrast may also be considered.

3\. Transforaminal epidural steroid injections (TFESIs) involving a maximum of
two (2) levels in one spinal region are considered medically reasonable and
necessary. It is important to recognize that most conditions would not
ordinarily require ESI at two (2) levels in one spinal region.11

4\. Caudal epidural steroid injections (CESIs) and interlaminar epidural
steroid injections (ILESIs) involving a maximum of one 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 three 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 epidural steroid injections 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\. Patient's should be part of an active rehabilitation program, home
exercise program or functional restoration program.10,12

*Note: The scales used to measure of 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 (OSW), Quebec Back Pain Disability Scale (QUE), Roland Morris Pain Scale, Back Pain Functional Scale (BPFS), and the 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 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 low back pain (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 four (4) sessions per spinal region in a
rolling twelve (12) month period.7

7\. It is not considered medically reasonable and necessary for more than one
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 two (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 one (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, it is recommended
not to exceed 80 mg of triamcinolone, 12 mg of betamethasone, 15 mg of
dexamethasone per session.16

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 epidural steroid injections over 12 months may trigger a focused medical
review. Use beyond twelve 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 three 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 policy. 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
policy 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, 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 CMS payment policy manuals, any and all
existing CMS national coverage determinations, and all Medicare payment rules.

**Definitions**

_Acute Low Back Pain_ ** -** Low back pain, which is present for up to six
weeks.

_Caudal epidural steroid injection (CESI)_ ** - **The administration via
injection of contrast (absent allergy to contrast), followed by the
introduction of corticosteroids and possibly a local anesthetic 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. __

_Epidural steroid injection_ ** - **The administration via injection of
contrast (absent allergy to contrast), followed by the introduction of a
corticosteroid and possibly a local anesthetic 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

_Interlaminar epidural steroid injection (ILESI)_ ** - **An injection of
contrast (absent allergy to contrast), followed by the introduction of a
corticosteroid and possibly a local anesthetic 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 pseudoclaudication) The physical
manifestation of leg pain, leg weakness, or leg heaviness exacerbated by
walking and relieved with leaning forward or sitting down.

_Nonspecific low back pain_ ** - **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 low back pain 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 RFA
ablations) performed during one day.

_Transforaminal epidural steroid injection (TFESI)_ - An epidural injection
performed via a paramedian approach to enter the epidural space by placing the
needle in the intervertebral foramen (neuroforamen) to inject near the dorsal
root ganglion and exiting spinal nerve root (previously known as a selective
nerve root block).

_Selective Nerve Root Block (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 local anesthetic by inserting a
needle into the neuroforamen under fluoroscopic or computed tomography (CT)
guidance. SNRB's are erroneously referred to as a Transforaminal Epidural
Steroid Injection (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 low back pain 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 one 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 six to
twelve-week time period.

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

**Contractor Advisory Committee Meeting 2/11/2021**

****

A Multi-jurisdictional contract advisory committee 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.

Acute low back pain, defined as low back pain with less than four weeks
duration, has an excellent prognosis to recover within the first four to six
weeks. Initially, treatments include non-invasive therapies, including
pharmacologic and non-pharmacological measures. Patients with acute or
subacute nonspecific low back pain typically would not be considered
candidates for interventional therapies, as they could still improve with
noninvasive therapies, and there is little evidence on the efficacy of
invasive therapies in this circumstance.24 The American College of Physicians
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 non-steroidal anti-
inflammatory drugs (NSAIDs) as first line treatment, and muscle relaxants, as
second-line treatment.25 Systemic steroids may provide benefits with three
randomized control trials 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 low back pain. When back pain persists
over twelve weeks, it is considered chronic low back pain, 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 two 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 one specific category of medication.

Patients with low back pain 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 low back
pain.28 The American College of Radiology (ARC) offers evidence-based criteria
for imaging for low back pain.29 According to the ARC Criteria, patients who
have acute, subacute, or chronic low back pain or radiculopathy with
persistent or progressive symptoms during or following six 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 six weeks of medical management and physical therapy. Imaging
is classified as "may be appropriate", with magnetic resonance imaging (MRI)
of the lumbar spine without contrast classified as "usually appropriate" and
computed tomography (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 low back
pain, 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 two 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 intra-
arterial 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 interlaminar epidural steroid injection
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 IESI 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
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.15 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 Anesthesiologist 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 by 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 post-menopausal women who underwent a single ESI
(triamcinolone 80mg) 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 six 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 3000 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, 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 2000 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 two groups. One received injection with local
anesthetic (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 three
to six weeks. A diabetic patient's elevation in glucose levels may be seen
after ESI persisting for two to six 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 Subject matter experts 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 nonsteroidal anti-inflammatory drugs (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 fourteen 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.43 However, this report was limited to case studies, case series,
several observational studies, one large retrospective study, and one 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 three to five 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 ESI's is considered standard. A
2016 systematic review to determine the effectiveness and risks of non-image-
guided lumbar interlaminar epidural steroid injections 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 epidural steroid
injections included a recommendation that all cervical and lumbar interlaminar
ESIs 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 ESI's. 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 Oswestry Low
Back Pain Disability Questionnaire (ODQ) or Roland-Morris Disability
Questionnaire (RMDQ) to measure function, Visual Analogue Scale (VAS) or
Numerical Rating Score (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 sixteen patients >65 years old with
symptomatic lumbar stenosis with radiculopathy who selected IESI, 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 one 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
randomized controlled trial (RCT) looked at twenty-one patients previously
identified as operative candidates who delayed surgery; and underwent ESIs.
Seventeen of the twenty-one did not undergo operative intervention at the
five-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 multidisciplinary biopsychosocial rehabilitation
(MBR) for chronic low back pain included forty-one randomized controlled
trials (n=6858). It concluded there is moderate-quality evidence that patients
with chronic low back pain 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 local
anesthetic as part of a multimodal treatment regime to provide pain relief in
selected patients with radicular pain or radiculopathy.

**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 three weeks, the Oswestry score had
improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the
placebo group (95 percent confidence interval for the difference, -7.1 to
2.2), there was an improvement in leg pain in the steroid group at six weeks,
but no significant difference between the groups at three months. At 12
months, the cumulative probability of back surgery was 25.8 percent in the
methylprednisolone group and 24.8 percent 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 local anesthetics [LA] to LA or saline in adults
with lumbosacral radicular pain secondary to herniated intervertebral discs.
They reviewed data on numerical rating scale scores for pain, validated scores
for measuring physical disability and quality of life, and incidence of
surgery measured at one month to two 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% confidence interval, -1.42 to -0.51 points; P < 0.0001, I2 = 90%; GRADE weak recommendation; moderate-quality evidence) at three months after the interventions.
  * The TFESI with steroids did not decrease physical disability at one to three months after the intervention (GRADE strong recommendation; high-quality evidence)
  * The TFESI did not decrease the incidence of surgery at twelve months after the intervention (GRADE strong recommendation; moderate-quality evidence) compared with LA/saline.
  * The TFESI steroids provide modest analgesic benefit at three months in patients with lumbosacral radicular pain secondary to herniated intervertebral disks

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 thirty-nine
randomized controlled trials that compared the efficacy of ESIs for lumbar and
spinal stenosis performed with saline with steroids, local anesthetic alone,
or steroids with a local anesthetic. The review included nine placebo-
controlled trials evaluating ESIs, either with sodium chloride solution or
bupivacaine, compared to placebo injection, and twelve studies comparing local
anesthetic alone to local anesthetic with steroid. The meta-analysis of five
studies utilizing sodium chloride or bupivacaine with steroid showed a lack of
efficacy. Comparing lidocaine to lidocaine with steroids in seven studies
showed significant effectiveness from baseline to long-term follow-up, which
was considered three months. Meta-analysis showed similar effectiveness for
pain and function without non-inferiority of lidocaine compared to lidocaine
with steroid at three months and twelve months. The duration of follow-up
varied among the included trials with a minimum of three months, so the
twelve-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
seventy-one publications, including observational and RCTs addressing
fluoroscopically guided lumbar interlaminar epidural steroid injections 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.16 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 twelve 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 five years for follow-up. They found that despite a high
success rate at six months, most subjects experienced a recurrence of symptoms
at some time during the subsequent five 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 twenty-five clinical
trials with 2470 participants, comparing epidural corticosteroid injections to
placebo for lumbosacral radicular pain. Using GRADE methodology, eight 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% confidence interval [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 thirty-two observational cohort
studies, nine pragmatic trials, and two 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 one, three, six, and twelve months
respectively. The authors stated high-quality evidence for the effectiveness
of TFESI, based on outcomes of multiple randomized control trials and high-
quality observational studies. Most studies in this review showed treatment
benefits lasting three to six months, with some studies suggesting benefits at
one or even two years post-injection. However, they attribute the one to two-
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, randomized controlled trial
funded by the Agency for Healthcare Research and Quality 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 one or two injections and evaluation at six weeks from the
first injection. At six 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% confidence interval [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 eight 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 MIST Guidelines for lumbar spinal stenosis from
the minimally invasive spine treatment consensus group evaluated nine studies
(2 randomized controlled trials [RCTs]; 7 observational studies, four
prospective studies and three 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 two-year observational study on the use of TFESI for lumbar
spinal stenosis followed 68 consecutive patients at six weeks, one and two
years, to avoid decompressive surgery. Of these patients, thirty-two percent
opted for surgery, 24% had repeat injections, and 44% were satisfied with non-
surgical management at two 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.61 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
confidence intervals 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, randomized controlled trial
compared epidural injections of corticosteroid plus lidocaine versus lidocaine
for lumbar central spinal stenosis alone at sixteen clinical sites.
Participants had the option of blinded crossover after six weeks to receive
the alternate treatment. Disability was measured using the RMDQ. The authors
report at twelve months, both treatment groups maintained initial observed
improvements, with no significant differences between groups on the RMDQ
(adjusted mean difference, -0.4; 95% confidence interval [CI], -1.6 to 0.9;
P=.55), leg pain (adjusted mean difference, 0.1; 95% CI, -0.5 to 0.7; P=.75),
opioid use (corticosteroid plus lidocaine: 41.4% vs lidocaine alone: 36.3%;
P=.41), or spine surgery (corticosteroid plus lidocaine: 16.8% vs lidocaine
alone: 11.8%; P=.22). They did not observe a difference among participants who
crossed over at six 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 six weeks after
the initial injection, these outcomes were maintained at 12 months. They did
not receive additional benefits after three weeks based on the injectant type.
Additionally, if there was no improvement during the first six 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 four
observational studies; one 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 five
years after their initial procedure. Half of the patients were receiving
repetitive TFESIs every two to six 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 associated with spinal stenosis.68

A 2020 prospective comparative analysis of cost and quality of life (QOL)
compared lumbar ESIs to conservative management alone at three and six months.
One hundred forty-one patients were included, and the authors concluded at
three months, ESIs provided similar improvements in QOL outcomes relative to
medical management and at similar costs. At six months, neither ESIs nor
conservative management provided significant QOL 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 one month, 48% (35-61%) at three months, 43% (33-53%) at
six months, and 59% (45-73%) at one 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 overall 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 postherpetic neuralgia and 3/5 (range 1-5) for
acute herpes zoster associated pain.

**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 two prospective studies, with thirty-six 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 twenty-five patients to CESI and seventeen to
steroid/lidocaine injection into the posterior neck muscles with one to three
injections at two-week intervals and followed them for one 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 cervicobrachialgia 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 low back
pain. 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 IESIs 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 randomized controlled trials
comparing outcomes of epidural steroids versus placebo after lumbar discectomy
in lumbar disc herniation reported on 12 studies with 1006 patients (502 in
ESI group and 504 in placebo group) and found an unstandardized mean
difference 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 two
groups (0.92; 95% CI 0.47, 1.83), and reported no significant difference in
complications for ES application after lumbar discectomy in lumbar disc
herniation.71

A 2018 case-controlled series of sixty patients by Akbas et al. compared the
three different approaches (TFESI, CESI, IESI) for post lumbar surgery
syndrome and concluded that VAS, OSW, and patient satisfaction scores were
comparable across the three groups at all time intervals (P > 0.05), relative
to baseline, there were significant decreases in pain relief scores (VAS and
OSW) and functional assessment expressed by patients' satisfaction across all
time intervals and in all three groups (P < 0.01).70

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 overtime. 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
Interventional Pain Management Techniques - Quality Appraisal of Reliability
and Risk of Bias Assessment (IPM-QRB) methodology were included. There were
four 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 local
anesthetic with or without steroids, based on at least one high-quality
relevant randomized control trial 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 six months. Conservative treatment was pharmacotherapy
with gabapentin and/or nortriptyline, and PT, as indicated, and combination
therapy was ESI and pharmacotherapy with gabapentin and/or nortriptyline plus
PT. At one-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 one 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
para-midline interlaminar ESIs reported initial improvements at two 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 para-midline 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 numerical rating scale and functional status improvement using
the Neck Disability Index (NCI). 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 two years. They
report an average number of procedures of five to six 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 transforaminal epidural steroid injection for the
treatment of radicular pain included six randomized and eleven 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 local anesthetic with or without steroids for management of
chronic neck pain concluded that similar pain relief and function were
achieved between the two groups. This was limited by the lack of randomized
controlled trials, lack of heterogenicity in the included studies with only
one 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 six months of
CESI, 14.5% by one year, and 22.3% by five 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 two 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 subject matter expert 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 two studies,
one RCT and one 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 two
groups; one group received LA (n=55) and the other group LA with steroids
(n=55). They reported most patients had five to six procedures over two 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 one year. Seventeen
patients had a second injection for lumbar herniation (29.8%) and seven for
cervical herniation (15.6%) at a mean of 65.3 days (SD 46.5) and 47 days (SD
37.2), respectively. All but one 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) one 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, 1002 consecutive patients were
prospectively assessed on short-term response to ESIs for various indications.
They determined ten-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 two weeks
for a duration of up to one 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 three 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 WEST study was a multicenter, double-blinded randomized
placebo-controlled trial with 228 patients with sciatica. The patients were
randomized to either three lumbar ESIs with steroid or placebo (saline) at
intervals of three weeks. At three 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 nine 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 three or four 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 three months
of the index injection. 4,161 patients received single-level TFESIs for
radicular pain with or without radiculopathy. Between two weeks and one year
from index injection, 933 subjects (22.4%) had repeat injection within one
year. The data indicates that 18% of subjects had two injections, 3.6% had
three or more injections. They concluded there was cumulative benefit of
repeat injections within three 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 two 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 IESI 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 two-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 numerical rating scale =3 and received
scheduled repeat injections at two to three 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 one 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 four patients receiving more than three 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.

Subject matter experts were asked about their confidence that the evidence
demonstrates ESIs provided relief for a minimum of six 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 twelve-month time period with a range of three-four in twelve 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 one to three 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 two weeks to three 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".
  * Subject matter experts 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**

****

Epidural steroid injections usually contain local anesthetic (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 forty-three
studies which included saline, LA, and injections into muscle or ligament
(sham). In the indirect comparison, they concluded epidural non-steroidal
injections achieved positive outcomes (risk ratio, 2.17; 95% CI, 1.87-2.53)
and provided greater pain reduction scores (mean difference, -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 one
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 American Society of
Interventional Pain Physicians (ASIPP) criteria for assessing interventional
techniques looked at thirty-one trials seeking evidence on local anesthetics,
saline, steroids, and other solutions. They conclude equal efficacy for local
anesthetic with steroids and local anesthetic alone in multiple spinal
conditions. For disc herniation, they report superiority of local anesthetic
with steroids over local anesthetic alone.93 A 2021 systematic review of
randomized control trials 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 randomized controlled trial 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 six 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 six 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 twelve 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 six 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 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 randomized control trials where the research question was
not specific to determining the effectiveness of these non-steroid 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 non-steroid 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 epidural steroid injections. There
is not enough evidence to be confident that non steroid 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.95 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.96 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.97 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 steroids 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 40mg for methylprednisolone
acetate (MPA), 10-20mg for triamcinolone acetate, and 10mg (10mg/mL) for
dexamethasone phosphate. They recommend limiting the cervical interlaminar and
lumbar transforaminal volume to 4mL 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 to 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 epidural steroid injections in patients with low back
pain __ 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 magnetic resonance imaging [MRI]) demonstrates a correlative region of nerve involvement. Criteria for exemption of four 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 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 two levels), and for CESIs or ILESIs, only one 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 monitored anesthesia care 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 a 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_ 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 low back pain, non-radicular low back pain, or spinal stenosis, we recommend against offering spinal epidural steroid injections. (Strong against | Reviewed, New-added)
  * For the very short-term effect (less than or equal to two weeks) of reduction of radicular low back pain, we suggest offering epidural steroid injection. (Weak for | Reviewed, New-added)
  * For the treatment of low back pain, 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: American Society of Interventional Pain Physicians
(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
Interventional Pain Management Techniques-Quality Appraisal of Reliability and
Risk of Bias Assessment (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 one 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 caudal ESIs, lumbar ILESIs, and lumbar TFESIs and cervical ILESIs with a strong recommendation for long term effectiveness.
  * For thoracic disc herniation, based on one 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 one 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 one 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 one 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 American College of Radiology (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 one of the relevant and validated measurement tools, such as the ten-point numerical pain rating scale score or a visual analogue scale score (Roland-Morris Back Pain score, Oswestry Disability Index, 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.

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  * They list the following absolute contraindications:

  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

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  * They list the following relative contraindications:

  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 American College of Physicians (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 low back pain 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 nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation).
    * Recommendation 2: For patients with chronic low back pain, 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

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_American Society of Anesthesiologists (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

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_American Academy of Neurology (AAN)_

The American Academy of Neurology (AAN) published a technology assessment and
reported in March 2007 and reaffirmed in July 2010 on epidural steroid
injections to treat radicular lumbosacral pain.11,19 **** Their
recommendations and conclusions include:

  1. Epidural steroid injections may result in some improvement in radicular lumbosacral pain when determined between two and six 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, epidural steroid injections for radicular lumbosacral pain have shown no impact on average impairment of function, on the need for surgery, or long-term pain relief beyond three months. Their routine use for these indications is not recommended (Level B, Class I-III evidence).
  3. Data on the use of epidural steroid injections 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 American Association of Neurological Surgeons and the Congress of
Neurological Surgeons guidelines update for performance of fusion procedures
for degenerative disease of the lumbar spine reviewed injection therapies for
low back pain 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 three systematic reviews and an updated review of RCTs.
They conclude, "the medical literature continues to fail to support using
lumbar epidural 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 Epidural Steroid Injections: **** Grade C Lumbar epidural steroid injections (ESIs) are an option for the short-term relief of chronic low-back pain without radiculopathy in patients with degenerative disease of the lumbar spine (Level III evidence).
  * **** Caudal ESIs are an option for decreasing low-back pain of greater than six weeks' duration, without radiculopathy, in patients with degenerative disease of the lumbar spine (Level III)

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_Spine Intervention Society (SIS)_

The Spine Intervention Society (SIS) Patient Safety Committee published 2020
guidance on the frequency of epidural steroid injections8:

  * After an ESI, a period of up to 14 days may be needed to assess the clinical response. Systemic effects on the hypothalamic-pituitary-adrenal (HPA) axis may last three 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 two weeks and less than one 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)_ 103

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: Interlaminar ESIs (cervical, lumbar, sacral and thoracic) Transforaminal ESIs (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)_ _27_ _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.



Epidural steroid injections 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 subject matter expert panel,
where the experts expressed broadly differing interpretations of the
literature and opinions regarding the appropriate use of epidural steroid
injections. There is a body of literature of randomized controlled trials
comparing ESIs to various placebos, including local anesthetic, 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 randomized control trials. Meta-
analysis is to synthesize the effects of many different studies into one
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 local anesthetics, or
even saline, are equally effective to steroids and cannot be counted as a
placebo. To further complicate there are multiple randomized controlled trials
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 local anesthetic 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 radicular pain 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 six 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 six months did not find consistent evidence of
benefit for epidural steroid injections 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 multimodal
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
low back pain, complex regional pain syndrome, widespread diffuse pain,
spondylolisthesis, pain from neuropathy from other causes, or cervicogenic
headaches. The subject matter experts 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 three injections.
National data confirms that the use of more than four injections is used less
than five percent of the time in the Medicare population Simultaneously, the
literature is variable in terms of timing between injections with reported
ranges of two to twelve weeks. Observational data suggest a potential benefit
of a shorter interval between injections of two to three 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 -four injections in a year
for most patients. Additionally, the natural history of the diseases treated
with ESIs would rarely involve more than one region. In review of national
data less than 0.05% of ESI sessions involved more than one 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 two 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.

Epidural steroid injections 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 six 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 subject matter expert 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 one year must be combined with
multimodal therapy, which has been shown to optimize outcomes by treating pain
through a variety of modalities. For any patient continuing to need epidural
steroid injections 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. Subject matter experts 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 policy 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.