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Techniques in Regional Anesthesia and Pain Management (2010) 14, 106-112

Cervical epidural injections for radicular pain

Antonio C. Tamayo, MD,a Jorge Guajardo-Rosas, MD,b Andrs Hernandez-Ortiz, MDa

From the aPain Medicine and Palliative Care Unit, Instituto Nacional de Ciencias Mdicas y Nutricin Salvador
Zubirn, Mexico City, Mexico; and the
b
Department of Pain Clinic and Palliative Care, Instituto Nacional de Cancerologa, Mexico City, Mexico.

KEYWORDS: The most widely accepted indication for applying steroid injections at the cervical level is to control
Cervical epidural; radicular pain generated by a herniated disk. A cervical radiculopathy is a neurological disease
Interlaminar; characterized by a dysfunction of the spinal cervical nerves or their roots. It has been upheld that the
Transforaminal consequence of alleviating pain by applying epidural steroids may be the result of inhibiting the
steroids; synthesis or releasing a significant amount of proinflammatory mediators as well as by causing an
Radicular pain analgesic effect where contact takes place. The epidural injection of steroids may be carried out by an
interlaminar or transforaminal approach. The cervical interlaminar epidural steroid injection (CIESI) is
the intervention method used to manage radicular pain. The cervical transforaminal epidural steroid
injection (CTESI) theoretically allows a greater concentration of medicine to reach the region that has
been affected. Recently, several reports have been published about catastrophic complications, such as
cerebral medular stroke and even death. It is believed that such catastrophic complications are caused
by occlusion of a segmental artery by the particles of the steroids that are injected. Therefore, many
authors currently question whether the CTESI practices should be followed. Additionally, in terms of
the vaso-occlusive effect caused by corticosteroids, it cannot be overlooked that the latter may produce
a considerable amount of adverse effects. Consequently, new alternatives for radicular pain are being
explored; however, these require more analysis.
2010 Elsevier Inc. All rights reserved.

Epidural steroid injections for pain management first This disease is commonly caused by the compression of the
emerged in 1952.1 This practice proliferated to such an nerve at the foramen due to the cervical espondilosis.3 The
extent that it is now one of the most popular intervention second most common cause is a herniated intervertebral disk.
methods for pain management. Disk herniation is the most common cause and occurs espe-
The most widely accepted application of a cervical ste- cially at the C5-6 and C6-7 levels, affecting the C6 and C7
roid injection is to control radicular pain caused by a hernia roots, respectively. The herniation of an intervertebral disk is
of the disk. Other indications include a narrow cervical typically related to the degenerative processes of aging but may
channel, chronic cervical pain as the side effect of a surgical occur after trauma. Other possible causes of radicular pain are
intervention, in addition to others that are less accepted.2 infections and tumors. Clinically, cervical radiculopathy causes
Cervical radiculopathy is a neurological disease character- cervical pain that irradiates toward the arm along with hypoestesia
ized by dysfunction of the spinal cervical nerves or their roots. and reduced strength that follow dermatomic patterns.3
Most patients with symptomatic cervical disk herniations
respond well to nonoperative treatment, including some
Address reprint requests and correspondence: Antonio C. Tamayo,
MD, Vasco de Quiroga 15 Colonia Seccin XVI, Tlalpan Mexico City, patients with nonprogressive radicular weakness. Reason-
14000 Mexico. ably good evidence shows that acute disk herniations de-
E-mail address: ancetaval@yahoo.com.mx. crease in size over time in the cervical region.

1084-208X/$ -see front matter 2010 Elsevier Inc. All rights reserved.
doi:10.1053/j.trap.2010.06.002
Tamayo et al Cervical Epidural Injections for Radicular Pain 107

It has been upheld that the effect of alleviating pain by


applying epidural steroids may be the result of inhibiting the
synthesis or releasing a significant amount of proinflamma-
tory mediators as well as by causing an analgesic effect
where contact takes place. Methods include blocking the
action of the phospholipase A2 (PLA2), inhibiting the ac-
tion of the neurological peptides, prolonging the suppres-
sion of the neurological impulse, and suppressing the sen-
sibilization of the neurons of the dorsal horns.4
The epidural injection of steroids may be carried out by
an interlaminar or transforaminal approach.

Cervical interlaminar epidural steroid


injection (CIESI)
CIESI is the most popular intervention method for radicular Figure 2 Interlaminar approach for epidural steroid injection.
pain. The idea behind this procedure is to reduce the in- Lateral view showing the distribution pattern of the contrast.
flammatory process at the nerve ending and the soft tissues
(Figures 1 and 2).5 The epidural space is approached with a
needle from the back, close to the halfway line between the as well as at the lumbar region, the spine is found to be more
adjacent vertebrae. perpendicular, which makes that approach easier.5
Epidural space is located in front of the laminates and
halfway in regard to pedicles.
Anatomical considerations The spinous process of the seventh cervical vertebra (C7)
is the most prominent. This causes the structure to be more
It is well known that vertebrae structure differs at the easily distinguished at the neck.5
various levels (cervical, dorsal, lumbar, and sacral). The While moving up in the cervical column, the epidural
classic vertebra has two laminas that merge halfway, space becomes narrower. Thus, CIESI is not recommended
thereby forming the spinous process. The angle of this above C6. On the posterior arch of C1, the small first
process changes at the different levels. In the cervical region cervical nerve passes out between the vertebral artery and
the arch on each side under cover of the posterior atlanto-
occipital membrane. The dorsal ramus of C1 supplies the
suboccipital muscles; the proprioceptive innervation of
these small muscles makes them important in cervicocapital
postural control. One of these small muscles is partly in-
serted into the posterior cervical dura to maintain its smooth
outline during cervical extension.
The roots of the second cervical nerve leave the spinal
canal close to the medial capsule of C1-C2. They join as the
spinal nerve passes transversely behind the joint, where the
large dorsal root ganglion dwarfs the small anterior root.
The large dorsal ramus forms the greater occipital nerve,
which hooks under the inferior oblique muscle of the head
to ascend through semispinalis capitis muscle into the pos-
terior scalp.
The cervical spinal nerves pass through the lower parts
of the intervertebral foramina, on the gutter-shaped trans-
verse processes just below the levels of the facet joints and
uncovertebral joints. To reach the intervertebral foramina,
the cervical nerves pass obliquely forward and laterally
from the spinal cord, so that in either extension or side-
bending they are likely to be stretched. In the intervertebral
Figure 1 Interlaminar approach for epidural steroid injection. foramina, they pass behind the vertebral arteries in grooves
Anteroposterior view demonstrating the needle in the interverte- on the anterior surfaces of the articular pillars. The dorsal
bral space. root ganglia of C5 through T1 are very large.
108 Techniques in Regional Anesthesia and Pain Management, Vol 14, No 3, July 2010

Table 1 Complications associated with CIESI


Complications may be classified as major and minor.
Minor complications include those that are resolved in less
Minor complications Major complications than 24 hours without significant effects.12 Table 1 summa-
Increased neck pain Epidural hematoma rizes the principle complications related to CIESI.
Headache Postdural headache
Facial flushing Intracraneal hypotension
Dural puncture Spinal cord injury
Cervical transforaminal epidural steroid
injection (CTESI)
The ligamentum flavum in the cervical region may not CTESI approaches involve directly injecting the nerve root
always merge at the midline. When this ligament is not where the lesion is located (Figure 3). This theoretically
found in the midline, then the epidural space may be allows greater concentration of the drug to be administered
reached without any change in the loss of resistance test; to the affected area.13
therefore, greater precaution must be taken.5 CTESI is indicated for radicular pain management
caused by a herniated disk or foraminal stenosis. Transfo-
Efficacy raminal injections may be done only with local anesthetics
for diagnostic purposes. Currently, debate continues about
Although there are several publications regarding the use whether or not to continue practicing this technique.
of epidural steroids, few include blind testing in which the
efficiency of the interlaminary injection is described.6-8 Stav Anatomical considerations
and colleagues examined the efficiency of methylpred-
nisolone injection plus lidocaine administered interlami- Nerve roots are wrapped inside dura mater, which ends
narly compared with the injection of the same drugs admin- in the proximinal margin of the dorsal root ganglion.13
istered in the posterior cervical muscles.6 The intensity of Roots merge and form the spinal nerve that exits through the
the pain, range of movement, and osteotendinous reflexes foramen.
were evaluated. Follow-up was undertaken 1 week and 1 The spinal nerve is located in the lower half of the
year after this procedure. According to the results, pain was foramen.14 The foramen is delimited in its higher and lower
reduced for 76% of the group that was administered the parts by the pedicle.13 The superior articular process of the
CIESI contrary to 35.5% that was not; after 1 year, the differ- facet joint delimits the posterior portion. The front part is
ence was 68% and 11.8%, respectively. Similarly, the range of delimited both by the vertebral body and the intervetabral
movement increased; however, the osteotendinous reflexes did disk. The spinal nerve is located posterior to the vertebral
not change. artery.
Moreover, Castagnera and colleagues observed that pa- The spinal cord is irrigated by descending branches of
tients could alleviate pain in short and even over the long the vertebral artery and by multiple radicular arteries de-
term (43 18.1 months).8 This alleviation did not change rived from the segmental artery.
significantly if morphine was added to the steroid that was The vertebral arteries emerge from the subclavia and
injected. ascend in the front part of the transverse process of C7.14
Rowlingson and colleagues retrospectively found that, in
25 subjects with cervical radiculopathy that were adminis-
trated CIESI, the pain was alleviated in 75% in terms of
40% of the patients and the pain completely ceased in 24%
of the patients. However, 3 patients did not improve.9 The
mean follow-up was 8.9 months.

Complications

Although it is considered that the interlaminar approach


is less risky than the transforminal, like in most cervical
procedures, it is not exempt from complications that could
be potentially fatal.10
The incidence of complications of the CIESI is relatively
low. According to one study carried out by 17 instructors of
the International Spine Intervention Society (ISIS), only 23
complications were observed out of the 4389 procedures
carried out (0.32%). However, Waldman reported 16.8% Figure 3 Anteroposterior view of a transforaminal approach for
incidence.11 epidural steroid injection. Courtesy of Dr. Elizabeth Ditonto.
Tamayo et al Cervical Epidural Injections for Radicular Pain 109

From there, these enter into the transverse of C6 or C5 until retrospective studies about the use of CTESI. According to
reaching C1 and from there to the magnum foramen.14 their research, efficiency is very low for patients suffering
From the subclavia and vertebral arteries arise the seg- from radicular pain due to secondary espondilosis related to
mented vessels (ascending cervical arteries and profound traumatic injury.21 Moreover, positive outcome has been
cervical), which cross the foramen and subdivide to form shown in patients in which CTESI for radicular pain not
the front and back radicular artery.15 The anterior and pos- related to nontraumatic cervical espondilosis, with excellent
terior spinal arteries arise from radicular artery. Addition- results in up to 60% of the patients.21
ally, the anterior spinal artery receives small arteries from
the radicular artery known as the radiculomedullar arter-
ies.15 The radicular arteries and radicularmeduar arteries Complications
can be located in the lower posterior portion of the foramen
near the target where the needle is placed for the transfo- In a survey carried out by ISIS instructors, it was re-
raminal injection.15 ported that the incidence of complications due to the trans-
foraminal injection was relatively low (0.32%); moreover,
Effectiveness Ma and collaborators reported that complications were
present early on after applying the CTESI in 1.66%. Despite
Scientific evidence that supports the effectiveness of the the fact that both studies report a relatively low incidence of
CTESI is still limited. There are several observational stud- complications, recently there have been reports about cata-
ies that report on the progress of patients with radicular strophic complications, such as a spinal and brain stem
cervical pain who received a CTESI. Because there are no infarction and even death.22-25 Therefore, many authors
control groups, the downside is that the effectiveness of the now question whether to continue applying CTESI.26
CTESI cannot be differentiated from the normal progress of It is believed that these catastrophic complications are
the ailment.14 To date, only one prospective, randomized, the result of an occlusion in the segmental artery by the
controlled trial exists. Anderberg and colleagues divided 40 steroid particles that are injected.15,27 Particulated steroid
patients with cervical radicular pain in 2 groups.16 Each may function as an embolus and occlude blood vessels that
group received transforaminal injections of the affected may condition brainstem and spinal infarction.
root. In the first group, mepivacaine and 40 mg of methyl- There are many variations in the level and location of the
prednisolone were injected, whereas the second group only origin of the radicular arteries and other vessels of lesser
received mepivacaine. No significant differences were importance that can nurture it. This was demonstrated in an
found in the clinical outcome of both groups. The absence article written by Hoeft and colleagues, who performed a
of positive results to support the effectiveness of CTESI in cadaveric dissection in which they observed that three
this study casts serious doubts over its use; however, these prominent branches of the radicular artery entered through
results could have been caused by the fact that the control
anterior portion of the foramen next to the left nerve root of
group received more than 1 transforaminal injection of local
C5, and through the right nerve root at C6 and C8.28 In C7,
anesthesic.17 Undoubtedly, it is necessary to carry out fur-
two prominent branches of the radicular artery enter by the
ther studies that are methodologically strong to be certain
posterior of the foramen in C7 bilaterally.28
that CTESI is effective in managing radicular pain.
The unpredictable irrigation of the cervical spine makes
In terms of observational studies, the information seems
it almost impossible to determine a safe manner to approach
different. Kolstad and colleagues for 4 months followed-up
to perform a CTESI without having the risk of intravascular
21 patients with cervical radiculopathy pain caused by es-
pondilosis or herniated disks in which CTESI was admin- injection. As a matter of fact, there have been many reports
istered. This study found a lower need for surgery (5 out of about unnoticed intravascular injections.29,30 Aspiration as a
the 21 patients decided not to have surgery) and significant method for verification to know whether we have reached a
clinical improvements at 6 weeks and at 4 months after vessel is the most ineffective method because, if the needle
CTESI. This clinical improvement was only seen in patients is located at a low-caliber vessel, when aspirating we may
with radicular pain irradiating to the arm but not for neck collapse it and not observe blood flowing into our syringe.
pain.18 Vallee and colleagues performed CTESI for patients Therefore, the practitioner could mistakenly believe that a
with cervical radicular pain. According to their studies, 56% vessel has not been reached. Injecting contrast media and
of the patients reduced the intensity of the radicular pain in later observing the image to confirm whether we are located
half 6 months after the CTESI was performed.19 Addition- in a blood vessel is also an inefficient method because the
ally, Cyteval and colleagues, during an observation prospec- time that has elapsed between the injection of the contrast
tive study consisting of 30 patients, found clinical improve- and the moment of obtaining an image at times is enough
ment in 60% of patients. From an initial mean VAS score of for the dye to be cleared from the vessel.31 To reduce the
6.3/10, the patients who improve had a reduced mean VAS risk of puncturing a blood vessel, it is highly recommended
score of 1.2/10 at 2 weeks and 0.7/10 at 6 months.20 Slip- to visualize the distribution of the contrast media in real
man and colleagues published several observational and time with digital subtraction.
110 Techniques in Regional Anesthesia and Pain Management, Vol 14, No 3, July 2010

Complications related to steroids Systemic effect of steroids


The size of the particles of the various steroids that are In addition to the vessel occlusion observed with steroids,
injected to the epidural space is also a factor to be consid- it should be remembered that they can produce considerable
ered. The greater the size of the steroid, the greater the adverse effects. The suppression of the suprarenal cortex
possibilities of conditioning the occlusion of a vessel. Ben- could produce grave complications. Prolonged therapy with
zon and collaborators compared the size of the particles of steroids can suppress the function of the hypothalamus
methylprednisolone (40 mg/dL), methylprednisolone (80 pituitaryadrenal axis (HPA) and recovery may be slow.4
mg/mL), triamcinolone (40 mg/mL), bethametazone sodium The incidence of the systemic effects of the steroids has
phosphate (3 mg/mL), bethametazone sodium phosphate/ been reported in 2.2% of the cases.4 Kay and collaborators
betamethasone acetate (6 mg/dL; Celestone Soluspan), be- observed that the weekly application of steroids through the
thametazone sodium phosphate/betamethasone acetate (6 epidural for 3 weeks might generate a very important sup-
mg/dL; betamethasone repository) alone and diluted with pression of the HPA axis. Recovery could take up to 3
lidocaine, with a saline solution and dexamethasone sodium months after applying the last steroid.35
phosphate not diluted. They observed that methylpred- Cushing syndrome has been reported after administering
nisolone 80 mg/mL had a greater concentration of particles 60 mg of methylprednisolone through the epidural as well
and a greater size than the rest of the steroids.32 It is as myopathy due to steroids after applying triamcinolone.36
important to point out that, even when diluted with saline These agents have been related to the psychiatric effects,
such as depression, mania, and psychosis.37 Rasmin and
solution, the number of larger particles in methylpred-
collaborators observed bouts of psychosis in a patient that
nisolone increased. Moreover, in dexametazone and be-
received an epidural injection at the cervical level.37
thametazone sodium phosphate 3 mg/mL, particles were not
In patients with diabetes, these agents must be used with
observed; from the remainder of the compounds the one
great precaution. Gonzalez and collaborators documented
with the smallest particles was bethametazone sodium phos-
glucose elevation to 106 mg/dL on average.38
phate/betamethasone acetate (Celestone Soluspan).32
All the complications related to the use of steroids have
The aforementioned study makes us suppose that dex-
forced researchers to test other substances for radicular pain
ametazone is less susceptible to conditioning vessel occlu- management. Table 3 lists substances that are being devel-
sion phenomena. It is important to note that soluble steroids oped for radicular pain management.39-45
are eliminated more quickly through the spinal channel,
thereby shortening their effects.32 The efficiency of the
Pulsed radiofrequency of the dorsal root ganglion
dexametazone for CTESI has been discretely less than tri-
amcinolone when compared33; however, it is important to The use of pulsed radiofrequency (PRF) is considered an
underline that one of the preserving agents for the conven- alternative for radicular pain management, specifically for
tional preparation of dexametazone is methylparaben, a patients for whom the use of corticosteroids may be detri-
substance that can cause lesions to the nerve structures with mental.
the correct concentration.34 Because information is sparse Evidence suggesting efficiency and safety of this proce-
regarding the safety of administering dexametazone by this dure is scarce. Van Kleef and collaborators conducted a
method (additionally efficiency studies are also scarce), it is prospective control study. They studied two groups of pa-
perhaps best not to employ this agent until more quality tients with cervical radicular pain. One group received dor-
control studies have been conducted. sal root ganglion (DRG) radiofrequency at 67C for 60
Other substances that may lesion the nerve structure are seconds. The number of patients with a positive outcome
benzyl alcohol and polyethylene glycol, both found in com- was higher in the RF-DRG lesion therapy group, compared
pounds such as methylprednisolone and traimcinolone di- with the sham group, and this difference was statistically
acetate.4 These factors must be taken into account when significant.46 The number needed to treat (NNT) for the RF
selecting the steroid to be used in these cases. Table 2 lists group was 1.4.47
the vehicles and preservatives found in the steroids that are Slappendel and colleagues did not observe any differ-
most commonly used. ence when comparing RF treatment at 40C with 67C. The

Table 2 Component vehicles and preservatives commonly found in different steroids.4,32

Triamcinolone Triamcinolone bethametazone sodium phosphate/


Methylprednisolone diacetate acetonide beta-methasone acetate Dexamethazone
Polyethylene glycol
Benzyl alcohol
Methylparaben
Tamayo et al Cervical Epidural Injections for Radicular Pain 111

Table 3 New alternatives for radicular pain

Substance Mechanism of action Authors Study Outcome


Etanercept Soluble TNF- Genevay et al. 40
Etanercept (IV) vs 75% pain reduction in the etanercept
receptors TNF- methyprednisolone (IV) group vs 17% methylprednisolone
Tobnick et al.41 Retrospective review of 55% reduction in the consumption of
patients that received analgesic
etanercept, 25 mg (SC)
Infliximab Monoclonal antibodies Karppinen et al.42 Infliximab infusion 3 mg/kg 75% of pain reduction in 60% of the
of TNF- (IV) vs placebo patients in the infliximab group vs 17%
of the placebo group
Korhonen et al.43 1-year follow-up of 80% of the patients treated with
Karppinen study infliximab persisted a 75% pain
reduction
Korhonen et al.44 Infiximab 5 mg/kg vs No significant differences were observed
placebo between both groups
IL-1Ra Blocks the biological Becker et al.45 Enriched serum with IL-1Ra There was a favorable tendency in the
effect of IL-1 (epidural) vs triamcinolone group that received IL-1Ra even though
5 mg y 10 mg (epidural) significance in reduction in VAS score
was only seen in week 22 of the follow-
up in favor of IL-1Ra vs 5 mg
triamcinolone
Abbreviations: IV, intravenous; SC, subcutaneous; IL-1Ra, interleukin-1 receptor antagonist.

40C group was considered the sham group. Both groups, further studies are warranted to establish safety and effi-
surprisingly, had a significant pain reduction with pain ciency.
scores at 1.5 and 3 several months after the procedure. After
this study, attention has been directed toward PRF.48
In PRF, high-frequency current is delivered in short
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