.

1 Therapeutic indications

Marcain Heavy 0.5% solution for injection is indicated in adults and children of all ages for
intrathecal (subarachnoid) spinal anaesthesia for surgery (urological and lower limb surgery
lasting 23 hours, abdominal surgery lasting 4560 minutes).

Bupivacaine is a long-acting anaesthetic agent of the amide type. Marcain Heavy has a rapid
onset of action and long duration. The duration of analgesia in the T10T12 segments is 23 hours.

Marcain Heavy produces a moderate muscular relaxation of the lower extremities lasting 22.5
hours. The motor blockade of the abdominal muscles makes the solution suitable for
performance of abdominal surgery lasting 4560 minutes. The duration of the motor blockade
does not exceed the duration of analgesia. The cardiovascular effects of Marcain Heavy are
similar or less than those seen with other spinal agents. Bupivacaine 5 mg/ml with glucose 80
mg/ml is exceptionally well tolerated by all tissues with which it comes in contact.

4.2 Posology and method of administration

Posology

Adults and children above 12 years of age

The doses recommended below should be regarded as a guide for use in the average adult.

The figures reflect the expected average dose range needed. Standard textbooks should be
consulted for factors affecting specific block techniques and for individual patient requirements.

The clinician's experience and knowledge of the patient's physical status are of importance in
calculating the required dose. The lowest dose required for adequate anaesthesia should be used.
Individual variations in onset and duration occur, and the extent of the spread of anaesthesia may
be difficult to predict, but will be affected by the volume of the drug used, especially with the
isobaric (plain) solution.

Dosage recommendations

Intrathecal anaesthesia for surgery:

2-4 ml (10-20 mg bupivacaine hydrochloride).

The dose should be reduced in the elderly and in patients in the late stages of pregnancy, see
Section 4.4.

Neonates, infants and children up to 40 kg

Marcain Heavy may be used in children.

One of the differences between small children and adults is a relatively high CSF volume in
infants and neonates, requiring a relatively larger dose/kg to produce the same level of block as
compared to adults.

Paediatric regional anaesthesia procedures should be performed by qualified clinicians who are
familiar with this population and the techniques.

The doses in the table should be regarded as guidelines for use in paediatric patients. Individual
variations occur. Standard textbooks should be consulted for factors affecting specific block
technique and for individual patient requirements. The lowest dose required for adequate
anaesthesia should be used.

Dosage recommendations in neonates, infants and children

Body weight (kg) Dose (mg/kg)

<5 0.40-0.50 mg/kg

5 to 15 0.30-0.40 mg/kg

15 to 40 0.25-0.30 mg/kg

The spread of anaesthesia obtained with Marcain Heavy depends on several factors including the
volume of solution and the position of the patient during and following the injection.

When injected at the L3L4 intervertebral space, with the patient in the sitting position, 3 ml of
Marcain Heavy spreads to the T7T10 spinal segments. With the patient receiving the injection in
the horizontal position and then turned supine, the blockade spreads to T4T7 spinal segments. It
should be understood that the level of spinal anaesthesia achieved with any local anaesthetic can
be unpredictable in a given patient.

The recommended site of injection is below L3.

The effects of injections of Marcain Heavy exceeding 4 ml have not yet been studied and such
volumes can therefore not be recommended.

Method of administration

Route of administration: For intrathecal injection.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to local anaesthetics of the amide type.

Intrathecal anaesthesia, regardless of the local anaesthetic used, has its own contraindications,
which include:

Active disease of the central nervous system such as meningitis, poliomyelitis, intracranial
haemorrhage, sub-acute combined degeneration of the cord due to pernicious anaemia and
cerebral and spinal tumours.

Spinal stenosis and active disease (e.g. spondylitis, tuberculosis, tumour) or recent trauma (e.g.
fracture) in the vertebral column.

Septicaemia.

Pyogenic infection of the skin at or adjacent to the site of lumbar puncture.

Cardiogenic or hypovolaemic shock.

Coagulation disorders or ongoing anticoagulation treatment.

4.4 Special warnings and precautions for use

Intrathecal anaesthesia should only be undertaken by clinicians with the necessary knowledge
and experience.

Regional anaesthetic procedures should always be performed in a properly equipped and staffed
area. Resuscitative equipment and drugs should be immediately available and the anaesthetist
should remain in constant attendance.

Intravenous access, e.g. an i.v. infusion, should be in place before starting the intrathecal
anaesthesia. The clinician responsible should take the necessary precautions to avoid
intravascular injection and be appropriately trained and familiar with the diagnosis and treatment
of side effects, systemic toxicity and other complications. If signs of acute systemic toxicity or
total spinal block appear, injection of the local anaesthetic should be stopped immediately, see
sections 4.8 & 4.9.

Like all local anaesthetic drugs, bupivacaine may cause acute toxicity effects on the central
nervous and cardiovascular systems, if utilised for local anaesthetic procedures resulting in high
blood concentrations of the drug. This is especially the case after unintentional intravascular
administration or injection into highly vascular areas.

Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have
been reported in connection with high systemic concentrations of bupivacaine. Should cardiac
arrest occur, a successful outcome may require prolonged resuscitative efforts. High systemic
concentrations are not expected with doses normally used for intrathecal anaesthesia.

There is an increased risk of high or total spinal blockade, resulting in cardiovascular and
respiratory depression, in the elderly and in patients in the late stages of pregnancy. The dose
should therefore be reduced in these patients.

Intrathecal anaesthesia with any local anaesthetic can cause hypotension and bradycardia which
should be anticipated and appropriate precautions taken. These may include preloading the
circulation with crystalloid or colloid solution. If hypotension develops it should be treated with
a vasopressor such as ephedrine 1015 mg intravenously. Severe hypotension may result from
hypovolaemia due to haemorrhage or dehydration, or aorto-caval occlusion in patients with
massive ascites, large abdominal tumours or late pregnancy. Marked hypotension should be
avoided in patients with cardiac decompensation.

Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during
intrathecal anaesthesia.

Intrathecal anaesthesia can cause intercostal paralysis and patients with pleural effusions may
suffer respiratory embarrassment. Septicaemia can increase the risk of intraspinal abscess
formation in the postoperative period.

Neurological injury is a rare consequence of intrathecal anaesthesia and may result in

paraesthesia, anaesthesia, motor weakness and paralysis. Occasionally these are permanent.

Before treatment is instituted, consideration should be taken if the benefits outweigh the possible
risks for the patient.

Patients in poor general condition due to ageing or other compromising factors such as partial or
complete heart conduction block, advanced liver or renal dysfunction require special attention,
although regional anaesthesia may be the optimal choice for surgery in these patients.

Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be kept under close
surveillance and ECG monitoring considered, since cardiac effects may be additive. (See section
4.5)

4.5 Interaction with other medicinal products and other forms of interaction

Bupivacaine should be used with caution in patients receiving other local anaesthetics or agents
structurally related to amide-type local anaesthetics, e.g. certain anti-arrhythmics, such as
lidocaine and mexiletine, since the systemic toxic effects are additive.

Specific interaction studies with bupivacaine and anti-arrhythmic drugs class III (e.g.
amiodarone) have not been performed, but caution is advised (see also section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no evidence of untoward effects in human pregnancy. In large doses, there is evidence of
decreased pup survival in rats and an embryological effect in rabbits if Marcain is administered
in pregnancy. Marcain should not therefore be given in early pregnancy unless the benefits are
considered to outweigh the risks.

It should be noted that the dose should be reduced in patients in the late stages of pregnancy, see
section 4.4.

Breast-feeding

Bupivacaine enters the mother's milk, but in such small quantities that there is generally no risk
of affecting the child at therapeutic dose levels.

4.7 Effects on ability to drive and use machines

Marcain Heavy has minor influence on the ability to drive and use machines. Besides the direct
anaesthetic effect, local anaesthetics may have a very mild effect on mental function and co-
ordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and
alertness.

4.8 Undesirable effects

4.8.1 General

Tabulated list of adverse reactions

The adverse reaction profile for Marcain Heavy is similar to those for other long acting local
anaesthetics used for intrathecal anaesthesia.

Frequencies are defined as very common (1/10), common (1/100 to <1/10), uncommon
(1/1,000 to <1/100), rare (1/10,000 to<1/1,000), very rare (<1/10,000) or not known (cannot
be estimated from the available data).

Table of Adverse Drug Reactions

System Organ Class Frequency Classification Adverse Drug Reaction

Immune system disorders Rare Allergic reactions, anaphylactic shock

Nervous system disorders Common Postdural puncture headache

 Uncommon Paraesthesia, paresis, dysaesthesia

Rare Total unintentional spinal block,

paraplegia, paralysis, neuropathy,
arachnoiditis

Cardiac disorders Very Common Hypotension, bradycardia

Rare Cardiac arrest

Respiratory, thoracic and Rare Respiratory depression

mediastinal disorders

Gastrointestinal disorders Very Common Nausea

Common Vomiting

Musculoskeletal and Uncommon Muscle weakness, back pain

connective tissue disorders

Renal and urinary disorders Common Urinary retention, urinary incontinence

Adverse reactions caused by the drug per se are difficult to distinguish from the physiological
effects of the nerve block (e.g. decrease in blood pressure, bradycardia, temporary urinary
retention), events caused directly (e.g. spinal haematoma) or indirectly (e.g. meningitis, epidural
abcess) by needle puncture or events associated to cerebrospinal leakage (e.g. postdural puncture
headache).

4.8.2 Acute systemic toxicity

Marcain Heavy, used as recommended, is not likely to cause blood levels high enough to cause
systemic toxicity. However, if other local anaesthetics are concomitantly administered, toxic
effects are additive and may cause systemic toxic reactions.
Systemic toxicity is rarely associated with spinal anaesthesia but might occur after accidental
intravascular injection. Systemic adverse reactions are characterised by numbness of the tongue,
light-headedness, dizziness and tremors, followed by convulsions and cardiovascular disorders.

4.8.3 Treatment of acute systemic toxicity

No treatment is required for milder symptoms of systemic toxicity but if convulsions occur then
it is important to ensure adequate oxygenation and to arrest the convulsions if they last more than
1530 seconds. Oxygen should be given by face mask and the respiration assisted or controlled if
necessary. Convulsions can be arrested by injection of thiopental 100150 mg intravenously or
with diazepam 510 mg intravenously. Alternatively, succinylcholine 50100 mg intravenously
may be given but only if the clinician has the ability to perform endotracheal intubation and to
manage a totally paralysed patient.

High or total spinal blockade causing respiratory paralysis should be treated by ensuring and
maintaining a patent airway and giving oxygen by assisted or controlled ventilation.

Hypotension should be treated by the use of vasopressors, e.g. ephedrine 1015 mg

intravenously and repeated until the desired level of arterial pressure is reached. Intravenous
fluids, both electrolytes and colloids, given rapidly can also reverse hypotension.

Paediatric population

Adverse drug reactions in children are similar to those in adults, however, in children, early signs
of local anaesthetic toxicity may be difficult to detect in cases where the block is given during
sedation or general anaesthesia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Marcain Heavy, used as recommended, is not likely to cause blood levels high enough to cause
systemic toxicity. However, if other local anaesthetics are concomitantly administered, toxic
effects are additive and may cause systemic toxic reactions. (See section 4.8.2 and 4.8.3).

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC code): N01B B01

Bupivacaine is a long acting local anaesthetic agent of the amide type.

Moderate muscular relaxation of lower extremities.

Motor blockade of the abdominal muscles.

Marcain Heavy is hyperbaric and its initial spread in the intrathecal space is affected by gravity.

5.2 Pharmacokinetic properties

Rapid onset of action and long duration i.e. T10T12 segments duration 23 hours.

Muscular relaxation of lower extremities lasts 22.5 hours.

Blockade of the abdominal muscles lasts 4560 minutes. The duration of motor blockade does
not exceed duration of analgesia.

In children the pharmacokinetics are similar to that in adults.

5.3 Preclinical safety data

Bupivacaine hydrochloride is a well-established active ingredient.

Adults
Your doctor/nurse will
tell you how many injections y
ou will require for the condition
you are being treated for, and when you will get them.
Joints
- the normal dose for the injections into joint will depend on the size of the
joint. Large joints (e.g. knee, ankle and shoulder) may require 20 - 80 mg (0.5
2 ml),
medium sized joints (e.g. elbow or wrist)
10 - 40 mg (0.25 1 ml) and small joints
(e.g. finger or toe joints) may require a 4 - 10 mg (0.1 -0.25 ml) dose.
Joint injections may be given weekly over
a period of several weeks, depending on
how quickly you respond to treatment.
Bursitis, epicondylitis (tennis elbow) and tendonitis
the usual dose is between 4-30
mg (0.1 - 0.75 ml). In most cases repeat in
jections will not needed for bursitis and
epicondylitis. Repeat injections may be necessary to treat long standing
tendonitis

Steroids inhibit the inflammatory response caused by chemical and mechanical

sources of pain. Steroids also work by reducing the activity of the immune system to
react to inflammation associated with nerve or tissue damage. A typical immune
response is the body generating white blood cells and chemicals to protect it
against infection and foreign substances such as bacteria and viruses. Inhibiting the
immune response with an epidural steroid injection can reduce the pain associated
with inflammation.

Several common conditions that cause severe acute or chronic low back pain and/or leg pain
(sciatica) from nerve irritation can be treated by steroid injections. These conditions include:

A lumbar disc herniation, where the nucleus of the disc pushes through the outer ring
(the annulus) and into the spinal canal where it pressures the spinal cord and nerves.

Read Lumbar Herniated Disc: What You Should Know

Degenerative disc disease, where the collapse of the disc space may impinge on nerves
in the lower back.

See Lumbar Degenerative Disc Disease (DDD)

Lumbar spinal stenosis, a narrowing of the spinal canal that literally chokes off nerves
and the spinal cord, causing significant pain.

See Lumbar Spinal Stenosis: A Definitive Guide

Compression fractures in a vertebra.

Read When Back Pain is a Spine Compression Fracture

Cysts which are in the facet joint or the nerve root and can expand to squeeze spine
structures.

See Synovial Cyst in the Lumbar Spine

Annular tear, a painful condition where a tear is present in the outer layer of the disc.

Who Should Avoid Epidural Steroid Injections

Several conditions could preclude a patient from having an injection:

Local or systemic infection

Pregnancy (if fluoroscopy, a type of X-ray, is used)

Bleeding problems - patient taking blood thinners (Coumadin, etc), or patients with a
bleeding problem (hemophilia, etc)

Epidural steroid injections should also not be performed on patients whose pain could be related
to a spinal tumor. If suspected, an MRI scan should be done prior to the injection to rule out a
tumor.

Efficacy of epidural steroid injections (ESIs)

Although numerous articles have supported the benefit of ESIs for LBP, especially if the pain is
caused by radiculopathy, other studies have disputed the efficacy of these procedures.
Unfortunately, most of the earlier studies (those that failed to show a benefit from the injection)
had significant limitations. Aside from using a less-than-desirable research methodology, most of
these studies did not use fluoroscopy and radiographic contrast to document accurate placement
of the injected substance into the epidural space. Many also failed to demonstrate that injection
was performed at a presumed level of pathology, which has been shown to be critical to the
success of ESIs.

Studies have reported that without fluoroscopy and radiographic contrast confirmation, incorrect
injection placement (ie, placement outside the epidural space) occurs in 30% of cases, on
average, even when ESI is performed by experienced injectionists. These methodologic problems
most likely were the major factors that led to the mixed assessment of ESIs.

Factors affecting the efficacy of ESIs

As with other medical procedures, the efficacy of the ESIs is related to many factors. Aside from
the clinician's experience and training, other factors that play an important role include patient
selection, symptom duration, underlying pathophysiology, ESI approach, the use of fluoroscopy
and contrast enhancement, and the vocational status, as well as the socioeconomic and
psychological circumstances, associated with the individual patient.

In general, patients who have had symptoms for less than 3 months have response rates of 90%.
When patients have had radiculopathy symptoms for less than 6 months, response decreases to
approximately 70%. Response decreases to 50% in patients who have had symptoms for over 1
year. Patients with symptoms of shorter duration have more sustained relief than those with
chronic pain. Patients with chronic back pain generally have better response if they develop an
acute radiculopathy. Patients with factors favoring the use of ESIs also include those who have
not had previous back surgery, who are not on workers compensation, who are aged younger
than 60 years, and who are nonsmokers.

In a cross-sectional study design at a university spine center, 76 patients with sciatica were
followed for a mean of 122 days after receiving transforaminal ESIs. Of these patients, 47%
experienced improvement, 28% were unchanged, and 16% worsened. The least favorable
outcomes were associated with patients receiving Social Security Disability Insurance (SSDI) or
workers compensation payments and with those whose work required heavy lifting.

Patient response to ESIs is also related to underlying pathophysiology. In general, acute radicular
pain from lumbar disk herniation responds more favorably than does radicular pain from lumbar
spinal stenosis. Patients with radicular pain after lumbar spine surgery frequently receive less
benefit from ESIs unless the radicular pain is from a recurrent herniated nucleus pulposus. Still,
ESIs are often helpful for radicular pain from stenosis.

Lumbar transforaminal epidural injections

The following research demonstrated the efficacy of lumbar transforaminal epidural injections
(see Approaches for Epidural Injections) in patients with persistent sciatica from lumbar disk
herniation or spinal stenosis:

In 2002, Vad and colleagues reported a prospective randomized study comparing

transforaminal lumbar epidural injection with lumbar paraspinal trigger-point injection. [2]
They randomized 48 patients with sciatica from herniated disk pulposus (confirmed by
lumbar spine MRI) into 2 groups. One group received transforaminal lumbar epidural
injection, and the other received a lumbar paraspinal intramuscular injection with saline.
The average follow-up period was 16 months. The authors used patient satisfaction, the
Rolland-Morris scale, and pain reduction extent as indices for efficacy. The success rate
in the transforaminal injection group was 84%, compared with 48% in the saline group.

Botwin and colleagues demonstrated the efficacy of the transforaminal epidural injection
in their retrospective cohort study in patients with sciatica (caused by lumbar spinal
stenosis). [3] Thirty-four patients who did not respond to nonsteroidal anti-inflammatory
agents and oral analgesics received 1.9 injections (average). At 1 year, 75% of the
patients had greater than 50% pain reduction, 64% improved their walking duration, and
57% increased their standing tolerance. An additional benefit of ESIs in many patients is
that the injections can potentially obviate the need for hospitalization and surgery in
many patients.

Riew and colleagues reported results from a prospective, randomized, double-blinded,

controlled clinical trial on 55 patients with severe sciatica from spinal stenosis or lumbar
disk herniations. [4] These patients had not responded to 6 weeks of conservative treatment
and were considered to be surgical candidates. The patients were divided into 2 groups; 1
group received lumbar epidural injection with bupivacaine and steroid, while the other
group received only bupivacaine. Up to 4 lumbar epidural injections were delivered if
needed. The follow-up period was 2-3 years. The study demonstrated that only 23% of
 patients in the group that received lumbar ESIs needed surgery, while 67% of patients in
the bupivacaine injection group underwent surgery. The difference was statistically
significant.

A follow-up study at 5 years found that 17 (81%) of 21 patients surveyed still had still not
opted for surgery. [5] This report demonstrated a benefit from lumbar ESIs in patients who
had been diagnosed with lumbar spinal stenosis or herniated nucleus pulposus, with the
injections helping to reduce the need for surgery.

A recent systemic review of 14 randomized and 10 nonrandomized studies on the efficacy

of lumbar transforaminal epidural steroid injections for lumbar radicular pain was
performed by Manchikanti L et al. [6] The results demonstrated that the efficacy is good
for radiculitis secondary to disk herniation with local anesthetics and steroids and fair
with local anesthetic only, efficacy is fair for radiculitis secondary to spinal stenosis with
local anesthetic and steroids, and efficacy is limited for axial pain and postsurgery
syndrome using local anesthetic with or without steroids.

Lumbar caudal epidural injections

Results from studies on caudal epidural injections are as follows:

Barre and colleagues reported that in 35% of patients with symptomatic lumbar spinal
stenosis who received caudal ESIs, a visual numeric score improvement of 50% or
greater was seen. [7] Long-term treatment success was seen in 35% of patients after a
mean follow-up of 32 months.

Anwar and coauthors demonstrated that caudal injections could benefit patients with
limited straight leg raise and symptoms of radicular pain or spinal stenosis; in this study,
65% of patients were noted to have some improvement at 3 months.

A systematic appraisal of the literature on caudal epidural steroid injections included 11

randomized trials and 5 nonrandomized studies. This study concluded that for lumbar
disk herniation, the efficacy is good for short- and long-term relief of chronic pain
secondary to disk herniation or radiculitis with local anesthetic and steroids and is fair
with local anesthetic only. In managing chronic axial or diskogenic pain, spinal stenosis,
and postsurgery syndrome, the indicated evidence is fair. [8]

Lumbar interlaminar epidural injections

A systematic review included 15 fluoroscopically guided randomized trials and 11

nonrandomized studies. The efficacy is good for radiculitis secondary to disk herniation with
local anesthetics and steroids and fair with local anesthetic only, whereas it is fair for radiculitis
secondary to spinal stenosis with local anesthetic and steroids and fair for axial pain without disk
herniation with local anesthetic with or without steroids. [9]
A prospective study demonstrated that as compared with conventional lumbar interlaminar
epidural injections, the lateral parasagittal interlaminar epidural approach has higher rate of
contrast spread into the anterior epidural space. [10]

A recent prospective randomized study compared the efficacy of lumbar ESI using a parasagittal
interlaminar (PIL) approach and midline interlaminar (MIL) approach. Thirty-seven patients
were randomized to receive injection of 80 mg methylprednisolone either by the PIL (n = 19) or
MIL (n = 18). A maximum of 3 injections were performed with 15-day intervals between
injections, if necessary. Follow up was 6 months post injection. Patients were evaluated for
effective pain relief (50% from baseline) by visual analog scale and improvement in disability
by the modified Oswestry Disability Questionnaire at intervals of 15 days and 1, 2, 3, and 6
months. The results demonstrated that PIL approach has better ventral epidural spread in contrast
(89.7% in the PIL vs 31.7% in the MIL group). At the end of 6 months, the PIL group had a
significantly higher percentage of pain relief in the visual analogue scale (PIL 13 [68.4%] of 19)
vs MIL 3 [16.7%] of 18)and improvement of disability using Oswestry disabilityquestionnaire
score, as well as fewer total injections (29 in PIL vs 41 in MIL, P = .043). [11]

It is important to know that at least 3 cases of lumbar paraplegia have been reported, and each
developed after interlaminar lumbar epidural steroid injections. [12] The suspected mechanism is
similar to a paraplegia caused by a lumbar transforaminal ESI in which the epidural needle
penetrates the radicular medullary artery, and the particulate corticosteroid being injected into
this artery inside the spinal canal results in an embolism of spinal cord and subsequent
paraplegia.

In fact, the anatomical studies have demonstrated that after the radicular medullary arteries enter
the neuroforamen in the anterior aspect of exiting nerve root and dorsal root ganglion, they often
travel a distance superiorly and laterally in the lateral epidural space to join the anterior spinal
artery supplying the anterior two thirds of the spinal cord. Additionally, in about 63% of cases of
cadaver studies, there is a posterior branch of the radicular medullary artery going to the dorsal
aspect of the cauda equina. It is conceivable that the epidural needle in the interlaminar lumbar
epidural steroid injection will very likely encounter the radicular medullar artery in the lateral
aspect of the epidural space or midline posterior epidural space.

As the paraplegia after interlaminar lumbar ESIs is often underreported, the exact frequency of
this event cannot be determinted. It is clear that in light of the anatomical positions of these
radicular medullary arteries inside the spinal canal as described above, neither midline nor
parasagittal interlaminar lumbar ESIs are completely risk free with respect to vascular injury and
paraplegia. The alternative approach using the Kambin triangle may be the better choice (see
below for description).

Comparison of interlaminar vs transforaminal lumbar epidural injections

More evidence favors the use of transforaminal ESIs in the lumbar spine compared with the
cervical spine. Although the interlaminar approach (see Approaches for Epidural Injections) may
allow the injectate to flow to the site of pathology by migrating around the thecal sac and into the
ventral epidural space, the transforaminal route is presumably more reliable for delivering the
steroid to the affected area in cases of disk herniation in which the disk comes into contact with
the nerve root.

Rhee and colleagues found a difference in patients undergoing interlaminar and transforaminal
ESI. [13] Those patients who underwent transforaminal injections had a 46% reduction in their
pain score, and 10% went on to need surgery. In contrast, patients who had interlaminar
injections had a 19% reduction in pain, and 25% required surgery.

Recently, a randomized, prospective, blinded, and controlled trial on the 38 patients with lumbar
subacute radicular pain was conducted. The study demonstrated that while both groups
improved, the transforaminal ESIs provided better pain relief in up to 16 days post injections
compared with the interlaminar group. [14]

However, a separate randomized and prospective research study enrolled 32 patients in each
group with chronic lumbar radiculopathy and 6 months follow up; the study again revealed the
improvement in pain and disability in both groups. However, no significant differences were
noted in pain reduction and the Oswestry disability scale between the transforaminal and
interlaminar groups at the end of 6 months. [15]

The above discrepancy of efficacy may be due to the lower response to epidural steroid
injections in general because of the chronicity of the radiculopathy; alternatively, it may reflect
the differences of timing in follow up between the 2 studies. It is generally agreed that ESIs offer
short-term (several months) pain relief.

ESIs may avoid unnecessary surgery

The Spine Patient Outcomes Research Trial (SPORT) is a prospective, multicenter study of
operative versus nonoperative treatment of lumbar intervertebral disk herniation. The results
demonstrated a significant difference in the preference for surgery between groups (19% in the
ESI group compared with 56% in the non-ESI group, P < .001). No difference was noted in
primary or secondary outcome measures at 4 years between the groups. A higher percentage of
patients changed from surgical to nonsurgical treatment in the ESI group (41% vs 12% in non-
ESI, P < .001). [16]

No deleterious effects on diskectomy

Buttermann and colleagues conducted a study involving individuals with a lumbar disk
herniation of greater than 25% of the cross-sectional area of the spinal canal; the patients were
administered ESIs one level above the herniation. [17] The patients received up to 3 injections,
with 42-56% of these individuals reporting the treatment to be effective. There was a cross-over
of patients who first underwent ESIs and then diskectomy. For those who underwent an initial
trial of ESIs, the delay in surgical decompression was not found to be detrimental to neurologic
recovery at time of follow-up.

Cervical ESIs
No randomized, controlled trials have been performed to date on the efficacy of ESIs for the
cervical spine and treatment of upper limb radicular pain. A prospective study by Rowlingson
and Kirschenbaum described significant reduction in upper limb pain after cervical ESIs, and
other studies (retrospective and prospective) identified radicular pain relief via interlaminar and
transforaminal approaches. [18]

Given the similar mechanisms of radicular pain postulated for the lumbar and cervical regions,
compelling evidence regarding the efficacy of lumbar ESIs might be applicable to treatment of
upper lumbar interlaminar ESIs. A systematic review included fluoroscopically guided 15
randomized trials and 11 nonrandomized studies. The evidence is good for radiculitis secondary
to disk herniation with local anesthetics and steroids and fair with local anesthetic only, whereas
it is fair for radiculitis secondary to spinal stenosis with local anesthetic and steroids and fair for
axial pain without disk herniation with local anesthetic with or without steroids. [9]

In terms of potential efficacy, transforaminal cervical ESIs are preferred over the interlaminar
approach by several authors, because the transforaminal cervical injections allow for the delivery
of higher concentrations of medications to isolated nerve roots and neuroforamina where stenosis
may be present. [19]

A systematic review of cervical interlaminar epidural injections concluded that such injections
are effective for relief of cervical radicular pain in the upper limbs; the report strongly
recommended the procedure. However, there were no randomized trials identified in this review.

Rationale for fluoroscopy and contrast

Reports suggest that injection without fluoroscopic guidance (ie, blind injection) results in 30-
40% of needle misplacements, such as needle tip placement outside the epidural space (including
intravascular injection) and placement not at the presumed level of pathologic process.
Therefore, it is recommended that ESIs be performed under fluoroscopic guidance and with
radiographic contrast documenting appropriate placement in order to improve the safety,
accuracy, and potential efficacy of ESIs.

Fluoroscopy in conjunction with contrast is used to improve efficacy and minimize potential
complications. Furman and coauthors discovered that for lumbar spine ESIs, using flash or
positive blood aspirate to predict intravascular injections was 97.9% specific but only 44.7%
sensitive. [20] This suggests that negative aspiration of blood does not ensure a lack of vascular
uptake. Similarly, in the cervical spine, vascular uptake injections occurred at a rate of nearly
20% with the use of fluoroscopy (confirmed by contrast injection), via a transforaminal
approach. Again, a visible flash of blood in the needle hub or positive aspiration of blood
demonstrated similar specificity and sensitivity to the lumbar injection study.

In a prospective study involving 191 patients who underwent single-level lumbar transforaminal
epidural injection, simultaneous epidural and vascular injection was found to be 8.9%. Therefore,
live fluoroscopy is recommended during contrast injection for confirmation of lumbosacral
transforaminal epidural injections
HYALURONIC ACID INJECTION (VISCOSUPPLEMENTATION)

Agents HA is produced either from harvested rooster combs or via bacterial

fermentation in vitro[61]. The injectable hyaluronan products that are approved by
FDA are sodium hyaluronate, Hylan G-F 20, and high-molecularweight hyaluronan.
Injection schedules vary from 1 to 5 injections and patients are generally advised to
repeat the injection schedule by 6 mo if they are satisfied with the previous
injection course. Although the basic science evidence studies seem to suggest that
the use of both low molecular weight hyaluronic acid and high molecular weight
hyaluronic acid (HMWHA) have disease modifying effects, comparative clinical
studies and meta-analyses tends to favor the efficacy of HMWHA for knee OA[62-
66]. Nevertheless, the current literature is inconclusive because of heterogeneity of
studies[63-65,67].