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Epiral Injections update

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DR JOIIN TANNER 'MBBS Bsc, Dip.M-S Med, Dip.Sports Med.


---- -----'•   ---------------

27 Green Lane,
'    Northwood, Middlesex, HA62PX

6 Harley Street, London, WINlAA.

Oving Clinic,
Church  Lane Oving,



Born   Cape Town, South Africa. 23 March 1953
Nationility  British



MD BS (London  1978) MD (London  1992)
GMC'Certificate of Specialist Statusl996

1967-1970    Mill Hill Public School

1971-1978    Royal Free Hospital Medical SchoOl, University of London


Dr Iames Cynax, Honoray Consultant in'Orthopedic Medicine  St Thontas' Hospital London and visiting ProfCssor in reee6710:51 02/02/2012Orthopaedic Medicine,  Universlly of
Rochcster  Medical Centre New York.    .r-

1982-1995    • The conservative  ntanagemeot of $Jllaal dlsordcfS aud lbe path0111orpbological changes  which pany their utural resolution•,.:...


A Controlled Study of Caudal Epidural lujectlons  of Triamcinolone Plus Procaine Cot  lbe Management of IJitractable Sciatica.  Spine 16:
572-575, 1991    .    .

The Natural History of Sciatica, A Prospective Study with Independent Radiological Review. Spine 17: 1205-1212,   1992

Lower  Back Pain and Scilica: How best to manage  them. Brit. I Hosp Med Vol 15, No 5: 216-22!. 1994

Back Cue: What to do and When to Refer. Brit I Tber py aud Rellab. Vol 2, No 3: ll27 113'Z, 199

Epidural Inj ctions in lbe Management  of Lower  Back  Lumbar Spine  Disorders
Vol 2  Ed: Pro£ Richard  Porter, World Scientific. 174-194. 1996

The Outcome of Cer;ical Radiculopathy Treated  with P riradlculu/Epidural  Corticosteroid Injections:• a Pwspecth•e Study with
Independent  Clinical Review. F.uro Spine 1. 5:319-325,  1996

The Pathomorphological  Changes That Accompany  the Resolution of Cen•ical  Radiculopathy: A Pros cti,•e St\ld• with Repeat
Magnetic  Resonance  Imaging. Spine Vol 22, No 2:183-186, 1997

Conscn•atl\•e   Treatment  of Cervical Disc Disease. Bai.lliere's Clinical orthopaedics:  Cer'\'lcal Disc Deg neration  Ed: Professor  Sean
Hughes Pub Bailliere Tludall (in press)



... •.

1980-to date    Orthopaedic  Medical Practice

1992-to date        Examiner: The Diploma in Musculoskeletal Medicine, Society or Apothecaries

1993-to date    Advisory Editorial Board, Spine

199-1 aad 1995    Hoaorary  Coaswtaat OrtbopaedJj: Sargeoa
Tbe  Royal atioaal Orthopaedic Hospital Tt11st. Loadoa



DOB:  5th May 1952.     ADDRESS: Tarigmere Cottage, Tangmere RoadTangmere,
Chichester, West Sussex, P020 6HW.  Tel:  01243 773167.  PLACE OF BIRTH: Redhill, Surrey.  NATIONALITY: British  STATUS: Married (3 children). EDUCATION: Eastbourne College- Top Scholarship,  London Hospital Medical College.  QUALIFICA'IIONS: B.Sc. Psychology 1973 (ULU), MBBS (London)  1977.
,Diploma in Musculoskeletal Medicine l.Q93, Diploma in Sports Medicine 1993, GMC
Registration Number: 2376257.  CURRENT EMPLOYMENT: Private  practitioner­ Orthopaedic/Osteopathic and Sports Medicine at:  Oving Clinic, Church Lane, Oving, Chichester, West Sussex, P020 6DG.  Tel: 01243 773167, Fax: 01243 530567.  Staff Grade Rheumatology and Rehabilitation, Salisbury District Hospital, Member of Pain Management Team.  Examiner: London Society of Apothecaries, Diploma in Musculoskeletal Medicine.  Lecturer: British Institute ofMusculoskeletal Medicine, Modular Courses at Southampton General Hospital for post graduates. London Hospital Diploma Course in Sports Medicine.  Chichester and Worthing GP refresher and trainee courses.  Orthopaedic Physician:• Hampshire Consta.bulacy and Fire Service on a , consultancy basis. South West Trains, Connex South Central, TRANSCO.  Chairman: Physical Medicine Research Foundation - UK.  Responsible for organising and lecturing at National and International courses run by the PMRF.  Honorary Treasurer:  British Institute of Musculoskeletal Medicine.  Advisor: To BUPA Clinical Team on Back P'ain Initiative.  PREVIOUS  EMPLOYMENT: Aug. 1977- Jan. 1978- House physicain to Drs.D.D.Gibbs and Lair, Silver and Mantell, London Hospital. Feb. 1978 - Aug. 1978 - House surgeon to Messers J.L.Grogono and D.W.Cairn, Amersham General Hospital.
Sep. 1978 - March 1979 - Locum GP in various practices in the London area.  March
1979- June 1980-  Locum SHO (Obstetrics), Royal Bucks Hospital, Aylesbury.  June
1980 - July 1981 - Locum casualty officer, Stoke Mandeville Hospital. Aug 1980 - Aug
1981 - GP trainee with Drs.Dooley, Dooley, Holmes, Smith and Thirlwall, 300
Meadowcroft,  Aylesbury. Sep 1981 - 1984 .. Part-time assistant to Dr. A. French, Wing, Bucks in General Practice.  Sep 1981 - 1988 - Private Practitioner- Orthopaedic Medicine and Sports Medicine. Director of Milton Keynes Sports Injury Clinic. Sep 1985 • 1988 - Medical Advisor to Champneys on Health and Fitness and Orthopaedic edicine.   May
1988- Sep 1991 -Orthopaedic Physician, Hamilton, Bermuda, with Dr.H.B.O'Neill,  MD, LCOM.   Associate Medical Staff, King Edward VII  Memorial Hospital, Special procedural privileges in Department of Surgery.   RESEARCH EXPERIENCE AND PUBLICATIONS:    1972/73 - Experimental Psychology projects, 1973 .. Research project in Community Psychiatry service atSt.Ciements Hospital, London, Dr.D.Jones•. •
1977 - Leukaemia Project, Royal Marsden Hpspital, Dr.Humphrey Kay.  Author of
'Beating  Back Pain', Dorling Kindersley, 1987.  Several articles published in Journal of
Orthopaedic Medicine. Editorial, British Journal of Therapy and Rehabilitation, 1996.



Despite widespread  and continued use of epidural steroids for low back pain (LBP) and sciatica for over 40 years recent adverse publicity based on a few case reports of severe neurological sequelae has led to publication of several review articles and re evaluation of the

The most notable and extensive evaluation was conducted by the National Health and Medical Research Council of Australia in 1994 from which the authors of this report will be quoting frequently.(!).

The current. problem arises from the recent statement specific recommendation was withdrawn from the Data sheet.  Bristol-Myers Squibb made their decision on the lack of evidence for the efficacy of the treatment ,and 5 DAP reports in which triamcinolone acetonide (Kenalog) was implicated in the development of severe adverse reactions, in one case leading to death, within hours or days of epidural steroid administration.

Following a  meeting between representatives of  the  British Institute  of  Musculoskeletal Medicine and Bristol Myers Squibb in May 1997 it was decided that an Expert Report for a Type II Variation for Kenalog should be presented to the MCA.  In the UK as in most other parts of the developed world the use of epidural steroids for LBP and sciatica is practised by a variety of clinicians including rheumatologists, orthopaedic surgeons, pain specialists  and musculoskeletal/orthopaedic physicians. The treatment is now available in  every  District hospital in the UK where such specialists are employed. Furthermore a minority of general practitioners trained in orthopaedic medicine techniques use caudal epidural steroid injections on an outpatient basis. In some centres specially trained physiotherapists are  giving this treatment under supervision of rheumatologists.

Depomedrone (methyl prednisolone), manufactured by Upjohn is the steroid most widely used but  a  sizeable minority have traditionally  used  triamcinolone acetonide  or  hexacetonide (Adcortyl, Kenalog, Lederspan). Most of the available literature including controlled studies refers to the use of methylprednisolone and the few case reports of serious adverse reactions tend to involve Depomedrone/Depomedrol.

In this report we are including all published material referring to epidural steroid injections
(E.S.I.) rather than singling out triamcinolone acetonide since the issue revolves around the use    I
of corticosteroids as a generic group in this method of treatment  There are of course important
distinctions between steroid formulations. in terms  of excipients used, which  may  have a bearing on safety issues, but in terms of therapeutic action in ESI no useful distinctions have yet been made.

Epidural steroids have been used in medical practice since 1952, although the control of spinal pain via caudal epidural local anaesthetic was first intr<;>duced by Sicard in 1901.

ESI  have been administered by different routes in different regions of the spine.  Most of the literature describes the use of ESI for complaints arising in the lumbosacral spine in which ESI have been given either via the sacral (caudal) or lumbar route. There have been some reports of the use of ESI  in the cervical region but this is far less common.  In recent. years clinicians
have taken to using ESI via the transforaminal route in the lumbar or cervical region but only uncontrolled studies on this have been published.
The literature describing ESI use is international, appearing in Italian, French, Belgian, Finnish,
German, Polish, Japanese, Scandinavian, European, English, Australia, New Zealand, Canadian and American literature reflecting the global interest accorded this procedure.

In the last two decades several reviews have been undertaken.  These reviews found that with widespread use of ESI the majority of published medical opinion supported their use. Both Corrigan and Bogduk's reviews recognised that intrathecal injections of steroids could result in nerve damage, but referred to the then available literature attesting to the chemical safety of corticosteroid preparations used in the epidural space. Kepes and Duncalf (3) note.that in over 100 reports of ESI over 25 years in which success rates claimed vary from 20% .. 80% no standardised treatment has resulted.  Techniques, drugs, criteria for treatment and success differ considerably from one observer to another .  Major complications were extremely rare but the rational for the use of ESI had not yet been scientifically proven.

Benzon's   reviews in 1985 concluded that ESI result in greater improvement and  faster recovery for patients with nerve root irritation.  The addition of steroid to an epidural local
anaesthetic or saline gave better results when compared to local anaesthetic or saline alone. Patients with sciatic root irritation of shortr duration fare better. He advised adequate dilution of the steroid in at least 5-10 ml. volume to ensure sufficient spread of the solution to the affected   area   and   to   dilute excipients such as   polyethylene glycol   (used   with methylprednisolone). He concluded that the relative safety of ESI was well docwnented but further study should be undertaken to validate the therapy identify the optimun number of injections, the ideal volume, to compare lumbar and caudal approaches in patients both with and without laminectomies, and the difference between saline and local anaesthetic as diluent.

Bogduk's more recent review in 1995 points out that methylprednisolone has a reversible local anaesthetic effect and that the mode of action of  ESI has not  been put to  the  test  in  a prospective study  on  which inflammation of  the  nerve roots has  been  identified  befor treatment.  He also states that enthusiasm for ESI based on open, uncontro led se rrhie3slJ    ot been matched y the results of controlled trials. 'He advocates strongly that    . •    er ran 6'mised ; controlled studies be undertaken.    ••

All review articles concluded that intrathecal steroids are not indicated in the treatment of spinal pain of benign origin due to the known complications arising from repeated or frequent injection (6,7).

All the causes of pain due to pathology of the s ie have not been clearly established.

Early approaches to pain relief included anaesthetising painful nerve roots, large  volume injections which were presumed to have a mechanical or counter irritative effect, and of course, surgery to remove a• protruding disc, osteophyte or more rarely tumour.

Many observations speak against a purely mechanical theory: the lack of correlation between radiological findings and clinical symptoms, the presence of disc protrusions and even large hemiations on MR imaging in the absence of pain, and more recently evidence of an inflammatory component.

=r .•
•'    '


Lindahl.and Rexed biopsied posterior nerve roots during laminectomy. They were found to be inflamed and oedematous, showing proliferative responses (8),                  •
Olsson (9) caused cervical disc protrusion in dog experiments. He found that the size of the disc
.d the amount of compression were less. important than the accompanying inflammation in
symptomatology. The inflammation changes dynamic factors such as nerve root blood supply, local venous drainage and nerve root mobility.                                        •

The next logical step was to employ corticosteroids in the vicinity of nerve roots to counteract inflammation. Animal studies seemed to confirm the beneficial effects of steroids.  Feldman and Behar introduced talcum intracisternally in cats and caused adhesive arachnoiditis and CSF pleocytosis. Intrathecal hydrocortisone  pre:vented adhesions• from developing (10).     The theory
that this was a direct local eff ct rather thatl.•a systemic one is supported by Lehrer et al.  Brain
tissue  steroid  concentration was  studied..  after  intracisternal administration of  tritiated
methylprednisolone 21-acetate.  The white matter attained 5-10 times higher concentrations that those attained by systemic administration of the se dose(11).

Ito was able to show increased capillary permeability re.sulting from inflammation occurred in patients with sciatica. The radiation clearance of Iodine 131 sodium and PSP was accelerated in these patients (12).                                                                                                                                                                                      •

Green et al studied a patient with nerve root swelling caused by a hemiated disc. lrttramuscular dexamethasone caused a reduction in •swelling•••of the. nerve root (shown by myelography)

More recent basic research has demonstrated that nuclear material is toxic to t::terve roots oth in

without a change in size of disc herniation (13).

-I      '

(Olmarker 1995).  High concentrations of phospholipe  A2    (PLA2) are found in herniated

terms of producing inflammation and neurophysiological change (14,15),    •   Nucleus pulposus
material in the epidural space induces l ucotaxis and an increase in vascular penneability

discs (16)   and PLA2 is known . to propagate the inflammatory cascade. with liberation of arachnidonic acid and other mediators such as leukotrienes and prostaglandins (17).

Mononuclear cells are found at• the margin of extruded .discs,  These express inflammatory mediators which might induce neovascularisation and persistent inflammation (18).

Corticosteroids are thought to reduce inflammation by inhibiting PLA2 activity.  The changes
•I    in nerve root morphology and function induced by autologous nuclear material can be reduced


by intravenous corticosteroids (19) and prednisolone has been shown to afford some protection against nerve degeneration in experimentat' radiculitis (20).

On the basis of the aforementioned •experimental evidenclargely gained from mammalian experiments it seems probable that locally placed steroids may be beneficial.

1    . .

Other effects of corticosteroids . include: stabilisation of nerve root membranes by suppressing

ectopic  discharges, blocking c


. transmissionreduction of  capillary  penneability,



inhibition of cytokine release from immune cells, reduced migration ..and  accwnulation of
lymphocytes, blocking passage .  of  immune complexes across the  base  ent   membrane, inhibition of prostaglandin synthesis, suppression of  superoxide radicals, stabilisation of
lyosomal enzymes at supraphysiologic concentration and inununosuppression of primarily T
rather than B cells.    •    ••    .



The anti-inflammatory action of  corticosteroids is• reasonably well  understood  and summarised in the preceding section.

As stated previously there are no formal studies which demonstrate beyond doubt the existence of pre-existing inflammatory radiculopathy subsequently treated by BSI which show its' specific mode of therapeutic action in a clinical setting other than by the resolution of symptoms such as pain and im.•.mobility.
In discogenic sciatica diagnosis is principalLy made on clinical signs supported by appropriate
imaging  with . the  emphasis  being  on  a  mechanical  cause  of  nerve  root  irritation  or compression.

Marshall developed an immunofluorescent antibody test to human nuclear glycoproteins and was able to demonstrate a rise in titre in the weeks following an acute mechanical strain of the
lumbar spine in nine cases (21).  Unfortunately no formal imaging was obtained to support the


diagnosis of a disc lesion although most had sciatic root irritation.  He argued cogently that     '(

sciatica could be  caused  by perineural spread of  the  contents of  the  nucleus  pulposus     '(
occurring through an annular rupture without direct mechanical compression.  This theory is supported by observers at operation and by discography, (22-24)  who noted complete; disc rupture without herniation and the absence of nerve• root compression in many of their cases. Unfortunately there seems to  be no  further development of a  test  for  clinical  or experimental. use in the last twenty years.  The animal studies by Olmarkt?r (15,19), however; strongly suggest that the degenerating d. isc enzyme ma. trix plays an inflammatory role.
There  are  no  studies  on  dose-response  relationship,  optimal  dose   or  conditions   of!
. admiriistration..,

There  are  no  studies •   on  the  pharmacokinetics  of  triamcinolone acetonide   or   other corticosteroids when given epidurally although there is     body of literature on this subject .. when injectable steroids are given intra-articularly or intramuscularly (for which they are licensed). ( See B.M.S.)    .         •
There  is  a  large  body  of  knowledge  on  the  systemic  action  and  unwanted  effects  of corticosteroids summarised in the data sheets for Kenalog and Adcortyl. (Appendix 1)

Hypothalamo -Pituitary- Adrenal Axis Suppression

The effect of ESI on the hypothalamo - p tui.tary - adfenal (HPA) axis has been studied (25,26,27). These studies demonstrated that both••methylprednisolone in a dose of 80 mg and triamcinolone acetate (80 mg) caused suppressiO'n of plasma cortisol levels and muting of adrenocorticotrophic hormone response to stimulation for up to 3-4 weeks post injection.  The lowest levels were found between the 7th and 14th day after injection. :Since the synacthen test was able to elicit at least a doubling•ofplasma cortisol, it could be arg1:1ed that clinically the,. degree of suppression does not pose any major risk to the patient mounting sufficient response •.: to an acute stress such as surgery. However, it is probable that several ESis, if given at short intervals, may do.

..• •••--  -••••••-'•"•-• •••-••-•--• I


Central Nervous Tissue Uptake
Plasma methyl prednisolone levels were undetectable throughout Jacobs and Pullen's study(21i)                         .[
indicating that systemic absorption of the steroid is not responsible for the observed HPA axis s'tippression.   This agrees with Lehrer's work who demonstrated  that when tritiated methyl prednisolone  was injected  intrathecally  in cats direct uptake by the brain was very fast
•whereas absorption into the blood stream was slow because of the high solubility of the
steroid (lt).   It is probable that following ESI high concentrations are quickly achieved in the subarachnoid space and r pid absorption by the central nervous tissue follows resulting in HPA suppression. These patients are unlikely to be at risk from other systemic  effects of glucocorticoid excess.

See figs. 1,2 from Jacobs and Pullen's article..


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1    r



'1  •
ltt   •
4-  •

0    ,     ,...,    tu

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l._    J

Q ) l.CC"
F:.   -
("\    '    0
rt -S     
Fig. 1.:
Mean (SEM) 09.00 hours plasma ACTH and   cortisol •   levels  in    six   patients follO\ving a single extradural injection of
80mg methyl- prednisolone  acetate at time 0.      None of the patients had received exogenous  cortico- steroids for at least 2 months prior to the study. The horizontal dashed line represents the lower limit of detection  for the ACTH assay.

Fig. 2.:
Mean    .(SEM)    09.00    hours    plasma
cortisol in  six patients before (I ),  30 minutes after (l\)  and 60 minutes after (ij) intra,•enous    injection    of    250g _ synthetic  ACTH betore 1, 7, 14 and 21 days after a single extradural  injection
of  80mg methyl prednisolone  acetate.    -:
None  of  the  patients had    received exogenous corticosteroids for at least 2
1)1onths prior to the study.

I    .

r  1



The effects of ESI on nerves and meninges.
••"' Delaney (2,8)  studied the effect of triamcinolone diacetate in a vehicle (polyethylene glycol
3%, _polysorbate 80, benzyl alcohol• 0.9%) and of the vehicle itself in 48 cats after lutnbar epidural injections. Six animals were not injected, 12 had 2% lidocaine,  15 vehicle only with
2% lidocaine, and 15 had 2% lidocaine with 0.7mg/kg triamcinolone diacetate with vehicle. When the animals wet:y sacrificed at 30-120 days, specimens of the spinal root, root exit zone and the meninges at the level of inje tion and level above and below were obtained.  Because all the histologic changes were found to be mild it was concluded that local anaesthetic 'steroid
.  combinations do not cause significant damage to neural tiss es.  1

Careful scrutiny of this study shows that-2 out of 5 cats sacrificed after 30 days in Group 3 (lidocaine plus 'vehicle')  showed meningeal thickening!   When these paraffin embedded tissues were sectioned thinner than 1 to 3 urn and studied under light microscopy there was evidence of .   arachnoidal proliferation and dural thickening?   The  occasional  presence  of rounded and enlarged arachnoid cells  in these areas .was  considered  to  be  a. signific

•deviation from normal since they are usually flattene.d.    .

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In those animals sacrificed and examined after 120 days there was no meningeal thickening or
infiltration in any of the 4 groups.  They•.•erroneously concluded that any changes seen at 30 days had largely resolved at 120 days- yet these were different cats.  Furthermore,' only 32 cats were examined in total of which 10 were from Group 3. An alternative conclusion might have been that 2 out of 10 cats showed a toxic reaction which may or may not have resolved -
.     an incidence of 20%.     !     .

The above study used triamcinolone diacetate in vehicle, 2% lidocaine only, lidocainewith vehicle and triamcinolone in vehicle plus lidocaine.

Another stl,ldy by Cicala (29) tested methyl prednisolone with 1% lidocaine, Ringer's solution, and. normal saline and talc (as a positive control) on rabbits injected epidurally.

However, the histologic studies were performed on paraffin embedded tissues sectioned in 4 thickness studied with light microscopy.  All these sections would appear to be thicker than those used in Delaney's study;   The study by Cicala is a pilot study and the authors themselves state that _the  ''lack  of changes in this series certainly does not  preclude  the 9 possibility of inflammatory reaction in other speCies or of individual sensitivity to this agent.
'Further  studis   using  other  species,  multiple  injections,  and  various  combinations   of medications are needed to ftu,lther evaluate possible toxicity of corticosteroid preparations in the epidural space." These studies, as far as we are aware, have not been done.
<l:. •- .

_ _j

Intraneural injection of steroids.
Mackinnon has shown that a variety of injectable steroids may damage peripheral nentes.• 224 injections were made in 112 male wistar rats into their sciatic nerves either intrafascicularly or extrafascicularly.  ive  agents were tested:
Dexamethasone    (Decadron)
Hydrocortisone sodium succinate    (Solucortef) Triamcinolone Acetonide    (Kenalog)
•Methylprednisolone Acetate    (Depomedrol) Triamcinolone Hexacetonide   (Lederspan)

. ----•------- - -- -•--- --   --------••---- -- - -  .j


Saline (as a control)

The nerves were examined at 9-12 days and 8 weeks.
Those nerves injected with dexamethasone showed minimal damage while those injected with     I
triamcinolone hexacetonide and hydrocortisone showed severe widespread axonal and myelin degeneration 1affecting both large and small fibre populations.   Triamcinolone acetonide (Kenalog) and methylprednisolone presented an intermediate picture (30) •
,.•,_        .
Sections of neryes at 8 weeks showed evidence of advanced regeneration regardless of agent
used. This latter occurence is a phenomenon not borne out by clinical experience of patients • with such  damage who  rarely  recover  more  than  partially .if  at  all.     Injections  given extrafascicularly caused no such injury pattern.

This study shows a direct neurotoxic effect of certain steroid agents and/or their associated vehiCle when injected intraneurally.  BSI are unlikely to cause such damage since the caudal route is safely distant from any large nerve roots and the  idline approach .is usually chosen for the lumbar route to avoid paramedian blood vessels and exiting nerves and to enter at a point  where the  epidural space  is  most  capacious:    However,   blind'  lumbar  ESI  are recognised to stray from true on occasion and nerve root damage has very occasionally been reported.     •

Steroids and the intervertebral disc (SIDT).
Although ESI are unlikely to directly enter the disc space there is a recent study  (31)  on methylprednisolone acetate intradiscal injections in rabbits of indirect relevance.

Intradiscal steroids have been usd  sporadically and by a small number of clinicians since Feffer (165) in 1956 claimed significant benefit in the treatinent of disc herniation.  There have been  reports  of  patients  developing  'calcification of  the  disc  and  epidural  space; after administration of SIDT with triamcinolone (Dequesnoy (166),  Menkes) (167)..•

Aoki (31) studied Depomedrol and Solmedrol at a dose of 4 mg in the L3-4 and L4-5 discs of rabbits. Saline was injected into the L5-6 disc.

Another group of rabbits was injected with polyethylene glycol mixture (P2G) 30 mg/ml into
L3-4 and P2G 60 mg/ml, 0.1 mls into the L4-5 disc.

Twenty four weeks later histological evaluation showed nucleus pulposus and inner annulus  ' degeneration  with  the  presence  of  matrix  vesicles  (an   indication  of   primary  tissue calcification) in the Depomedrol (acetate) group.   No such changes were observed in the Solumedrol (sodium succinate) group or saline controls.  All rabbit discs injected !with P2G   11 showed degenerative changes and primary tissue calcification, with loss of intranucleus cell&.

Injectable steroid formulations and their excipients.  (See Table 1)
All injectable steroids are preserved with various bacteriostatics, stabilisers, buffers and other preservatives.    Although they  are  often  referred to  as "inert"  or  "inactive"  ingredients,
Golightly (32) in a thorough medical toxicology review revealed that this is clearly not so. It is
more appropriate to refer to them as pharmacological excipients.    '•



The literature was reviewed  by the National  Health and  Medical  Research Council of
Australia (I) in its commissioned report on BSI concerning the following ch mical entities.

F••"o' rmulations
polysorbates (tweens)
citrates    •
ethylenediamine tetra-acetic acid (EDTA) sodium sulphite    •    ,., polyethylene glycol
benzyl alcohol hydroxybenzoates (parabens)
myristyl gamma picolinium chloride •
benzalkonium chloride phenolic compounds

.   The findings were as follows:

Only to be used if it can be assured that the nature and concentration• of the agents(s) employed are suitable for contact with the cerebrospinal fluid (33),   :No iltrormation :was fotmd on the use of phosphate buffers for intrathecal or epidural injections,   /

Polysorbates (tweens)

No reports of adverse effects, and no increase in body temperature when given intrathecally

Induce convulsive activity in mice w en given by spinal injection, possibly by chelating divalent cations in the CSF (35).

Induce convulsive activity in mice when given by spinal injection, possibly by chelating divalent cations in the CSF (35).    •• •.::.    ''     '    • •

Sodium sulpltite


--    '     ..    I
Subarachnoid administration produced .irreversible paralysis in rabbits 36,37.

i 1
I    ..

I  l     9

I    Table 1

The-composition of injectable steroid preparations available in the United Kingdom

'           I
I    I






40mg/ml •

,.t.,riamcinolone hexacetonide benzyl alcohol  }    0.9%.
polysorbate 80           0.2 % . sorbitol solution        70    % water for injeCtion    to 100    %

triamcinolone acetonide
benzyl alcohol    q
sodium carboxymethylcellulose Tween 80 (polysorbate80) sodium chloride
water for injection

triamcinolone acetonide benzyl alcohol    '.i
sodium carboxymethylcellulose Tween 80 (polysorbate80) sodium chloride
water for injection

Methyl prednisolone
Polyethylene glycol    !

Myristyl-gamma-picolinium chloride






Hydrocortisone acetate
Polyethylene glycol <    r
Polysorbate 80     I
Sodium carboxymethylcellulose    1:
Dexamethasone phosphate
Creatinine - stabiliser Methyl para OH benz.oate Propyl para OH benzoate
:Sodium citrate    ;
Sodium hydroxide
Sodium metabisulphite



•   Polyethylene. glycol
Allegations of  neurotoxicity attributable •to  polyethylene glycol  (6)    have  been  based  on misquotations of  studies  of  propylene  glycol  .    While• related,  propylent;' glycol  and
'j)olyethylenglycol are not 1he same chemical, but ii.l principle they may have similar toxic effects.  Nevertheless,. studies cited to impugn polytpylene glycol .investigated the effects of
80 per cent and 100 per cent concentrations of propylene glycol (38.39) whereas commercial
preparations of corticosteroids  (or spinal use contain polyethylene glyco,l in concentrations not  greater  than  3  per  c nt   (40).        ;Hd • the  cited  studies  investigated  more  realistic concentrations of the  glycol  there  may . have  been  grounds  for  concern.    .The  extreme concentrations. studied preclude leg timate extrapolation to the use of epidural steroids.   In contrast, the one study of 3 per cent polyethylene glycol that  as been .conducted found no
impaiqnent of neural function af er 30 minutes application to rabbit vagus nerves (40).
.     .    .•   .

Wood  (41),   however, 'exposed   rat   sciatic ' nerves •to   weekly   injections   of   either methylprednisolone acetate, the  vehicle alone, chloroprocaine 1%,  repeated  'dry'   needle punctures, or no injection.   •                                                                                          •   .

Nerves treated with either the steroid or its vehicle showed similar incidence and severity of • patchy  d generation,  including  de111yelination,   axonal  disorganisation  and   endoneuria! collagen formation. Lesion severity increased with frequency of injection. Curiously none of the animals howed signs o. f• d. eficit in of m.otor or sensory function.     •
The clinical signifiGance •of the e. findings are uncertain but suggest caution with rep ated, closely timed injections with such a•preparation near mixed motor or sensory nerves.     .

Benzyl alcolzol
On intrathecal administration bacteriostatic water containing benzyl alcohol  is  associated with:

• flaccid paraplegia artd demyelination with 5 mL of bacteriostatic water (42)
• flaccid paraplegia from 40mL of normal saline containing 1.5 per cent• benzyl alcohol (43)
• nerve degeneration and paraplegia from 20mL of methotrexate injection• containing   0.9 per cent benzyl alcohol (44)
• flacciparalysis ( 45)
• leg paralysis (46)                                                                                                                                             '  '


• neurological damage (paraplegia) (44)





• neuronal block (paraparesis) (47)

• neurotoxicity, paraparesis (45)

• leg paralysis (46) •


r  1
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Myristyl gamma picolinium chloride

No reports. of adverse effects found on its use in intrathecal formulations.

Benzalkonium chloride
No.reports were found of the effects of benzalkonium on peripheral nerves or nerve roots but, in concentrations greater than those found in commercial preparations of steroids used for spinal
injection, benzalkonium has been used experimentally as a neurotoxin in the alimentary tract (48-
50)    .    .•

Phenolic compounds
Chemical meningitis has occurred and phen:ols may also induce seizures (51)

Other Possible Causes of Meningeal Irritation

As early as 1954, D.C.Moore advised that local anaesthetics administered epidurally should be free of preservativesi. This recommendation is largely adhered to by clinicians but few have been as diligent in regards to the vehicle accompanying the•steroid (53)

A report in the literature was found  concerning the use of hydrocortisone  sodium  succinate (Solu-Cortef) intrathecally (52)  which shows the dangers of using the water-soluble preparation due to it causing a rapid ionisation effect in the CSF, which in turn leads toshort term chemical meningitis.

All injectable steroids contain excipients but in much smaller •amounts than those shown to be harmful experimentally and in the above case reports.  It is well established that talc and other foreign body materials can lead to arachnoidal proliferation.  Hurst investigated the effects of a wide  range  of  chemical  types  including  ionic  and  non-ionic  detergents  and   quaternary ammonium compounds introduced in small amounts into the CSF of rhesus monkeys.  He found that "although the pathological process begins immediately after introduction of the irritant and proceeds steadily to its termination the early stages may be almost or wholly asymptomatic and the clinical picture is then one of severe and progressive signs and symptoms arising  after a latent period"(54)

From  the  available  evidence  the  NHMRC  concluded  that  there  was  no  evidence  of  any deleterious effect of steroid preparations provided they were injected accurately into the epidural space, but also that none of the commercially available formulations of steroids was free of at     i least some  potential risk  of  deleterious  effects  if  they  were  to  be  injected  deliberately  or
inadvertently into the intrathecal space.     I

How do d ugs cross the dura?
Many physicians are not aware that there are other routes by which epidurally injected  agents may reach the subarachnoid space than by in,advertent puncture.

Shantha and Evans (55) studied the micro and macroscopic relationships of the neural membranes to provide a new basis for re-evaluating the spread and locus of action of epidural anaesthesia.


The spinal and root dura are continuous withe  peripheral nerve 1:\S   neural and perineural connective issue.   The perineurium is a continuation of the pia arachnoid' which invests the entire central nervous system. When India ink particles are injected into the subarachnoid space itf the horse's lumbar spine they accumulate in the root JUSt proximal to the orsal root ganglion. This is called the ink cuff space and it is here that the arachnoid covering shows some remarkable histological features: .     proliferated arachnoid cells form  villi which breach the dura mater to varying degrees, some even invading the endothelium  of epi ura. venules. This has been demonstrated in several mammals including primates and humans. !Prior
•to this it was thought tliat the •dura was impermeable:• although Usubiaga showed in careful
quantitative studies in 1967, that there was 0  transfer of procaine from epidural to subarachnoid space by some 'diffusion pr cess'.   Bromage (170) showed only very little radio actively labelled lidocaine remained  in  the  dura  itself,  indicating  some  other  mechanism  than  trans dural diffusion.

The endothelium of arachnoid villi has lipoid pores large enough to allow passage of eythrocytes
67 ll through in addition to CSF.

In :the India ink injections of the subarachnoid space some particles are found over the DRG and
•even distant parts of  peripheral nerves.    This centrifugal spread  is  due  to  the  anatomical continuity of central and peripheral membranes. Centripeta1 spread may also occur as shown by Moore with intra neural injection of Methylene blue colourd  Efocaine - (it reaches the spinal cord within 2-5 minutes;        ' •    .
'    r­
Further evidence for there being a transport mechanism rather than a simple• diffusion proce s

comes from the recent study by Byrod and Olmarker (56).    They found Evans blue labelled albumen present in the  intraneural capillaries of pig spinal nerve roots one minute after epidur f application.\ Ink angiography de onstrated small venules that connected the epidural vein plexus and the intraneural capillaries. Thihelped  to explain previous findings that  pidurally  applied autologous nucleus pulposus causes focal nerve degeneration in the pig• spinal nerve roots - located in the central fascicles (15).    The labelled atbumen was also scattered  in  numerous capillaries in the DRG.

They conclude the potential barrier properties of the dura/arachnoid seem less than effective for preventing substances in the epidural space from reaching the endoneural space of nerve roots. These demonstrated transport routes may also be related to the mechanisms behind epidural anaesthesia and spinal nerve root infiltration;

Quite clearly• a certain amount of whatever we inject epidurally  may reach the subarachnoid space and spinal vasculature system.  Therefore, the composition, concentration and osmol 1ity,• of the mixture is very important.


c'ppidural is associated with certain known and potential hazards which need'-to be considered before and during execution of the procedure.  Each of the techniques carries unique risks and risks in common.   Furthermore, different risks can be  attributed to different aspects of the procedure; some relate to.the chemistry of the steroid used,•others to the local anaesthetic used, and others to the act of introducing a needle into the epidural space.





JIIM- illin!IMIUI--<Glii<OitU'•'It'-'do'n     ..     ...                   !


Reported complications of epidural steroid use
The NHMRC (Australia) performed an .extensive analysis!of the cqmplications of ESI1from the 1
'published literature. •  The following account draws from this excellent analysis, and further new information is added.


(a)    audal epidural steroids
No mention is made of complications in five published studies of caudal epidural steroids (57-61).   Others explicitly specify incurring no complications (62-63).      One  study reports exacerbation of back and leg pain for 24 hours but does not state its iticidence. (64)

The complications which .are reported by authors who specified their incidence are summarised in Table 2.   Headache arid dural puncture are the two leading complications, neither of which is ascribable to the' use of steroids.  Dural puncture is a technical risk of simply introducing a needle into the epidural space. • The mechanism of headache after epidural steroids is not known.   It may relate to undetected dural puncture and. leak of cerebrospinal fluid, or it may in some way be related to the injection of large volumes of fluid into the epidural space and temporarily raising intrathecal pressure.


The complications of caudal epidural steroids based on the literature that provides sufficient numerical data to calculate incidence



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ofpts     Nature

.    Number of cases    Incidence

Goebert et al. (66)    113    Procaine sensitivity    1     0.9
Spinal anaesthesia (a)    1    0.9
Cardiac failure (b)     1    0.9

Beliveau  (65)    48
Mount (67)    542

Headache    10    21
Increcwed pain    2     0.4
Spinl anaesthesia    1    . '0.2    '•.

(a)  implies dural puncture
(b)  attributable to fluid tetention caused by the steroids

Because studies differ in the number of patients treated, the observed incidence of various complications vades considerably from study to study,  A representative incidence can be    i' obtained by determining a weighted mean Incidence which is calculated by dividing the
number of reported cases of the complication by the total number of patients treated in all of the studies that observed .that complication.  The results of such calculations are shown in Table 3.




It is evident that the reported complications of caudal epidural s eroids are q ite rare except in the case of headache.  The calculated incidence of 21 per cent could be an overestimate because only one small study reported this complication.  On the other hand, its incidence could be this high or greater if other authors did not consider headache to be a serious enough complaint to warrant being called a complication and therefore being reported.

Table 3
The weighted mean incidence of complications of caudal epidural steroids.


Number of Cases     Total Treated

Weighted Mean Incidence (ll) (%)

Headache Dural puncture Spinal anaesthesia

10     48
4     703
2     655


(a) calculated by dividing the number of cases reported by the total number of patients treated in all the studies noting that complication.

A retrospective survey_ of 47 practitioner' clinical experience of 75,000 caudal ESI based on physicians' recalr"ofmajor complications was conducted by J.Tanner 1995 (68)   The majority used  preservative free  local  anaesthetic  of  varying  volume  (20-50cc)  and  90%  used triamcinolone acetonide (Kenalog, Adcortyl). The results are outlined below.     (Table 4)


' ....




Number. of



Dural punctures Anaphylaxis Hypersensitivity Prolonged hypertension Skin infection
Epidural abscess


Neurologic complication


Severe aggtavation of pain less than 24 hours

(Prolonged aggravation of pain)
more than 72 hours

.    9







0.01 o.02





(Only one with very poor outcome)

Acute -lower limb paralysis probably due to LA effects. Chronic- multi-level neurological symptoms occurring 7 days later.

One leading to surgery.

Other complications

No fatalities



•. •'.•,

Worsening chest infections. Diabetes mellitus precipated. Suspected peptic ulcer aggravation. Cushing id changes.

Bizarre symptoms    . '


iQp the basis of this summary it appears that caudal ESI are relatively safe.


il  .





No mention is made of complica ions in nine studies of lumbar epidural steroids, (69-77) and a further study by Hickey (78)  explicitly  stated incurring no complications  in 250 patients.   Without specifying incidence, several •authors• have reported  headache, (79,80) exacerbation of pain, (80-82) • hypotension,(80) fluid retention (66)  and  dural puncture (83). From those studies that speCify actual incidence,. the complications of lumbar epidural steroids are shown in Table 5.   •

The weighted mean incidence of complications from lumbar epidural is shown in Table 6
It would seem evident that the incidence of complications from lumbar epidural steroids is appreciably greater than that for caudal epidural steroids;  most notably, the incidence of dural puncture is far greater.

In addition  to this  data drawn• froin clinical  studies  of lumbar• epidural  steroids,  the literature contains several case reports of complications.  While such case reports provide no insight into the possible inCidence of such complications, they serve to highlight the possibility of certain complications not otherwise• recorded in the literature.   These are summarised in Table 7.


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Table 5
The complications of lumbar epidural st roids based on the literature that provides sufficient numerical data to calculate incidence.


Author     Number of        Complications:     Incidence Patients•     Nature         Number of        (%) Treated                 Cases

(  '    Warr et al. (79)    500    pural puncture    7     1.4
Exacerbated pain    2    0.4
l !    Harley (85)    50    Headache    1    2
.   Exacerbated pain    1    2
Ito  12)    296    Headache    17     6
Exacerbated pain
5    2
Sayle-Creer (86)    325    Dural  puncture    11    3

Ridley et al. (87)    21    Dural  puncture    2     9
. Dilke et al. (82)    35    Dural puncture    6     17
Jurmand (88)    3544    Dural puncture    183    5
Headache    33    1
Gilly (89)    50    Dural  puncture    2    4
Exacerbated pain    2     4
Berman et al. (89)    367    Hypotension    10
I    Difficulty voiding    5
Severe paraesthesiae    4
Angina    1
Sinus arrhythmia    1
Spinal anaesthesia    1
Headache    1

Table 6
The weighted mean incidence of complications of lumbar epidural steroids

.  Incidence (a)

(a)    calculated  by dividing the number of cases reported by the total number of patients treated in all the studies noting that complication.

I: I
I, i

i   1
I    18


I    ••"

Table 7
A list of complications attributed to lumbar epidural steroid injections in case reports

Source     Complication


'   I

Shealy (90)
Dougherty and Fraser  (91) Abram and Cherwenka (92) Knight and Burnell (25) Stambough et al. (93)

... ,.

Epidural abscess Meningitis Headache. Hypercorticism Hypercorticism

I      '   '

,  I

Gutknecht (94)
Chan and Leung (95) Simon et al. (96) Williamson (97)
Sekel (98)
.  Goucke  ai1d Graziotti (99)

Intrathecal injection with chemical meningitis
Epidural abscess Allergy to steroid Subdural injection Tethered dural sac Extradural abscess

The complications of lumbar epidural steroids can thence be grouped into:

\     •    side effects attributable to the pharmacology of the steroid injected;
,    I     the effects of adjuvant agents injected;

,   _I


enigmatic complications;
dural puncture/intrathecal injection.

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Steroid side-effects

The literature on epidural steroids. mentions very few complications that can be attributed to the chemistry or pharmacology of the steroid injected.  Adrenal suppression occurs but is rarely manifest clinically.  It is known from several studies that the epidural injection of steroids has an effect of suppressing the secretion of glucocorticoids by the adrenal ghi.nd for about 2-3 weeks (84,26).                                                 ..                                                                                                                                    •
No deleterious effects of this suppression have been docwnented, but some authors warn that this should be taken into consideration in patients due to undergo surgery durin'g 'that time period (26).      One case of  steroid allergy has  been reported.   Fluid retention  leading to congestive cardiac failure has been noted in the literature but appears to be very uncommqn. One investigator has reported minor digestive disturbances and occasional   patients with minor changes in serum glucose.(88).   Overt endocrinological effects, however, have rarely been encountered with the use of  epidural steroids.  There have been  case reports of .overt steroid side-: effects in the form of Cushingoid hypercorticism (93, 94)   but this has  usually occurred when extraordinary and inordinate doses have been used (betwen 200 mg and 400 mg of methylprednisolone over one to three days), although one such patient received only two injections of 80 11;1g me hylprednisolone one week apart.


Side-effects of other agents

Local anaesthetics anaesthetise small   diameter afferent• fibres and   sympathetic efferent
Consequently, when used as an adjunct to minimise the pain of epidural injections of steroids, local anaesthetics can cause side-effects such as spinal anaesthesia and hypotension.

Enigmatic complications

Enigmatic complications of  epidural steroids are  those  without a  known  or  apparent physiological basis. These are headache and temporary exacerbation of sciatic pain.

Analysis of the literature indicates that exacerbation of sciatic pain is related to the injection of large volumes of fluid into the epidural space, and it has been suggested that this symptom can be avoided by injecting slowly.(82)

Headache is a complaint known to be associated with epidural anaesthesia for childbirth and is therefore not a complaint unique to epidural  steroids.(lOO)  Its mechanism remains obscure. In the context of epidural steroids it may• well be due to unrecognised dural punctllres. In this regard, Jurmand (88)  incurred headache in 33 patients in the course of 3544  injections - an incidence of 1 per cent, but these occurred only in the 183 patients who sustained a dural pUncture- an incidence of 18 per cent. Headaches could occur following unrecognised dural puncture as a result of cerebral spinal fluid leakage or as a result of inadvertent injection of air into the subarachnoid space.(92,10l).

.  Infection

Infection is a risk of any procedure that involves penetration of the body with a needle, but it is minimised by adherence to strict aseptic technique. Its incidence following lumbar epidural steroids is extremely rare, having been noted only in four case reports (Table 7).

Dural  puncture

The most consistently reported and the most common complication of epidural steroids is dural puncture, particularly in the case of  lumbar epidural steroids.  It should  be noted , however, that although the caudal approach is  designed to  avoid this  complication, it nonetheless can occur even with that approach (Tables 3,4).                                     •   •            •

White et al (102)    who used radiographic controls in their study pf300  caudal and lumbar•
epidural injections warn of incorrect needle placement. In their study needles were incorrectiy located in 25 per cent of caudal injections and in 30.4 per cent of lumbar injections•. In the
case of caudal injections these incorrect placements included failure to enter the sacral canal and intravascular placement, but dural puncture was never encountered. In the case of lumbar injections penetration of the dural sac occurred 'several times' but the exact incidence was not specified. To some operators well-skilled in epidural techniques these figures appear unduly high,(JoJ, 104) but they do serve to illustrate that incorrect needle placement can occur.

[1    20

f1     In a related study Mehta et al (lOS) studied the accuracy of needle pla ement in the course of 85
Ll    lumbar, six thoracic and nine cervical epidural local anaesthetic blocks in 100  patients..  He
encountered inaccurate placements in 17 per cent,\rendered evident by obtaining  radiographs
; I    ••"' following a test injection of 0.2mL of contrast medium.  None of the inaccurate placements,
'   .    however, involved puncture of the dural• sac.  Nine fell short of entering the vertebral canal
and did not even reach the epidural space. One only partially entered the epidural space.  On seven occasions the injection was made partially into •the  epidural and  partially  into the subdural space. This study, like that of White et al.. indicates that incorrect needle placements can occur during the execution of epidural injections, but more specifically it demonstrates that under-penetrat on rather than over penetration is more likely.

Inaccurate needle placement also occurs with the caudal approach when used for epidural steroids (106-7) or  for epidurography.(tos)  In  the course of •epidurography :.incorrect needle 11 placement was seen to occur in some 14 per cent ofcases1but the failures involve missing the sacral hiatus or intravascular injection rather than over-penetration.
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I    To avoid performing injections when needles have peen incorrectly placed, some authors have advocated that epidural steroid injections  are best performed under fluoroscopic control (106). White et al. recognised that radiographic control . would not be appealing to all who used epidural steroids, but reported that it had become routine in their own institution.

Abrams and O'Connor (109) in a more recent review note that most of the warnings regarding the potential hazards of ESI are based on complicat.ions following repeated subara_chnoid steroid injections. (6,110 llOa,9l,lll). The relevance of this to the use ofESI is limited.  The risk of dural puncture in lumbar ESI is 5% (see •above) and in caudal ESI 0.6% or lower.   This represents a complication only in that it is an unintended component of the procedure and of course dural puncture is a routine procedure in neurological practice, (lumbar  puncture), radiology  (myelography), anaesthetics• (spinal  anaesthesia).     Some  authors  (6)  have extrapolated this risk to imply that the operator through not recognising he has entered the subarachnoid space proceeds to inject the steroids and local anaesthetic mixture.  The greater proportion of dural punctures. are.recognised at the time, so when epidural injection is desired, the procedure is aborted.

Relationship Between Arachnoiditis and Subarachnoid and Epidural Steroids
Abrams and O'Counor (109)

One of the commonly voiced argumeqin  favour of the neurotoxicity of intraspinal• steroids is the notion that arachnoiditis does not    exist in the absence of some form of i trogenic intervention .  Roche (8) for instance, in reference to a group of  patients with radiographic evidence of arachnoiditis, states "These patients have had subarachnoid steroid injections a:s either the only procedure or the most likely procedure that could have induced such changes. Adhesive arachnoidits has not been found at this hospital in the absence of some type of
•intervention.    However,   casual  literature  search  for   the   spontaneous  occurrence •    of
arachnoiditis (i.e., without antecedent spinal injections of any   sort) yield more than a few references.

I       •..
I              .--,


In 1972 Ransford and Harries (121)   published a report of five patients.exhibiting arachnoiditis at the time of laminectomy in w, " predisposing cause of the arachnoiditis other than the  disk  lesions  could  be  implicated".     These  patients  had  not   undergone   previous
'•myelography or steroid injections.  In addition to citation of these cases, the authors presented an extensive review of the previous literature on the occurrence of arachnoiditis and its association  with  spinal  injections,  infection,  injury,  surgery,  degenerative  lesions  of  the vertebrae and disc and tumours.  Two other referenpes to cases that occurred in conjunction with  lumbar  disc  lesio s   are  cited  (122-3)       along   with  three  reports   of   arachnoiditis accompanying degenerative cervical spine disease (124-6) .    There is a fairly extensive list of references to cases of arachnoiditis  occurring after  spinal  surgery (127-31)  .   One  of  these references (127)  refers to a case of calcific.. arachnoiditis (arachnoiditis ossificans).   Many of these  cases  were  reported  before  the  introduction  of  subarachnoid  or  epidural  steroid injections.  Two citations (132-3)    referred to cases of arachnoiditis that occurred without any apparent inciting cause. Two cases of arachnoiditis ossificans hi the absence of subarachnoid injections were reported by  Wise(B4).

Several more recent reports document the existence of arachnoiditis in the absence of spinal injections Epstein et al.   (135)     reported  five cases of  sev:ere  obliterative  arachnoiditis  in partients with spinal stenosis.  In all of these cases, araclmoiditis was confirmed at the time of surgery.  Only one patient had undergone any type of intraspinal injection, a myelogram that had been done 23 years previously.  Brodsky (136), Vloeberghs et al. (37), and Quiles et al. (138), have reported cases of arachnoiditis in patients without previous surgery or spinal injections.
• Duke and Hashimoto (139)  reported cases of severe arachnoiditis that occurred spontaneously in six members of the same family.

Much  of  the  evidence •   for  implicating   subarachnoid  steroids   in  the  pathogenesis   of arachnoiditis comes from cases of multiple sclerosis treated with subarachnoid MPA.   While there is little data regarding the incidence of spontaneously occurring arachnoiditis in multiple sclerosis, there are reports of such occurrences.(I40-I).

The fact that arachnoiditis can occur in the absence of subarachnoid injections does not rule out the possibility  that such injections  can  cause arachnoiditis.    Indeed, there  is  a  well" accepted relationship between the use of subarachnoid contrast agents such as Pantopaque and Lipiodol  and  the  subsequent  development  of  arachnoiditis  (6,54,142,143).         However,   the relationship between the use of depot/steroids and arachnoiditis is not as clear.   On the one hand, there are case reports that   raise suspicion of such a causal relationship (110,112,144). Conversely,  there  have  been no  experimental  data  in  animals  to  confirm  a  relationship between subarachnoid steroid injections and arachnoiditis.   In 8 series of such injections involving 358 patients, there was no clinical evidence of arachnoiditis (145,146,72,148,149-51).

It is  the• perceived  risk  of  subarachnoid  injection  which  has  been  the  source  of  much controversy and alarm in relation to the possible development of arachnoiditis following the procedure of epidural injection.

Foremost, it is conspicuous that of the patients reported as suffering arachnoiditis following intrathecal steroids about whom sufficient details have been published, all had undergone multiple injections  of  steroids or  other  intrathecal  procedures.    Of the  first  two  patients reported with arachnoiditis, (112) one had received 23 intrathecal injections of steroids, and the



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other had received five injections and had undergone myelography with •an oil based contrast medium (a known cause of arachnoiditis).  Of four cases subsequently reported (113) only one
•-"was detailed. This patient had undergone 16 injections of intrathecal steroids and an oil based    I
myelogram. The patient reported by Bemat (110) had undergone 12 injections of intrathecal               •I
steroids. 1:he patient reported by Coh(m (111) had undergone four myelograms, four lumbar operations and 14 intrathecal injections of steroids.                                                     •

These reports clearly describe excesses and stand in contrast to the reports of the use of intrathecal  steroids for multiple sclerosis without complications.(l14-7).  Furthermore,   and paradoxically, in contrast to intrathecal steroids allegedly causing lumbar arachnoiditis, they have actually been reported as beneficial in the treatment of this same cond;ition.(I18-20).

The lack  of  evidence of  a  relationship between epidural steroid •administration and arachnoiditis is quite remarkable. In our review of the literature, we found no case reports
documenting such a relationship and our review. of •64 series of steroid epidurals, which    (
included nearly 7,000 patients, failed to reveal a single report of arachnoiditis. (NHMRC 1994)    -\-


There appears to be little risk of serious complications associated with the use of epidural steroid injections. Animal studies tend to confirm the safety of neuraxial administration of depot steroids. Allegations that the 3% polyethylene glycol vehicle of MPA and other depot steroids is capable of producing neurologic damage appear to be unfounded. The doses of corticosteroids commonly used are capable of producing. adrenal suppression for up to several weeks, and there are occasional reports of cushingoid side effects from the doses of steroids that are usually given.  Epidural steroid injections should be used with caution in diabetic patients, who may be at added risk for epidural infections and whose glucose control may be •
•compromised.    Because of the immuno.suppression  associated with the steroid, aseptic technique should be meticulous.

Essentially all the literature documenting the safety of epidural steroids comes from reports on the use of a small number of injections, usually one to three and with modest doses, usually
40 to 80 mg MPA or 40 mg triamcinolone diacetate. Extrapolation of these data to situations in which these procedures are done repeatedly or in which  much higher doses are used is
risky. There are no data to support the safY of this treatment under such circumstances;

There is  some evidence that complicati hs  can  occur following subarachnoid steroid injections. Aseptic meningitis and bacterial meningitis appear to be uncommon but real risks. • Arachnoiditis  and conus medullaris syndrome have been reported, but these cases are generally seen after• multiple injections over a prolonged time interval. The possibility that a serious complication will occur after a single accidental subarachnoid steroid injection is probably very low, provided that strict aseptic technique is used and no contraindications, such as history of untreated tuberculosis or fungal disease or recent septic processes, are present.



••For the purposes of tlus report only ESI studies given by the caudal or lumbar route will be reviewed.

The attraction of the caudal route is that it is easily performed and decreases the risk of inadvertent dural puncture and therefore the possibility of intrathecal injection.

The majority. of investigators "have sed     methylprednisolone or triamcinolone  as  the corticosteroid and have mixed either with substantial volumes of local anaesthetic or normal saline.

.     The local anaesthetic, which is preservative free, provides a convenient vehicle to increase the volume of the mixture with the added advantage of temporary relief of pain and the onset of numbness or other changes in the appropriate dermatome which serves to indicate  correct needle placement.

All uncontrolled studies on caudal ESI have been favourable with respect to benefit. (61,62,66,IS2)

Although encouraging, such reports do not and should not vindicate the use of caudal epidural steroids, for aside from other shortcomings;they  offer no control observations.  Other studies, however, have provided such data.

Koes et al (ISJ)   reviewed the controlled studies on both caudal and lumbar ESI set out in tables below  (Table 8).

On reviewing the four studies on caudal ESI there are methodological difficulties.   Yates'  (S9) report comparing the effects of four different compositions of injection purported to show that the addition of steroid to any base mixture resulted in greater improvements, but insufficient raw data were published to allow this claim to be evaluated critically.

Furthermore his report did not address pain relief but focused on improvement in• straight leg raising (SLR) which seemed to correlate with pain relief.

Matthews (154) found no difference between steroid treated group and placebo at one month, but a significant difference at three months in favour of the steroid group.   UnfortUJ;lately insufficient raw data were published for critical evaluation.                                                  •

Beliveau's  (65)  study does not appear to be formally randomised but allocated alternately  to steroid plus 0.5% procaine and 0.5% procaine alone.  Although there was no difference in the short term (3 months) he found that patients with a long history of severe sciatica (mean 16 months) the inclusion of steroids appeared to show a significant improvement.

"•     __

. .•-.,_.,-    ;•;."" .     .  c. ; ; ,O!I-11'''• • '    •;•     •.    •.    •
-..    -.:    _...._

Table 8

Authors        Epidural sh:roid injection/route    Injections    Reference tn:atmc:nt(s)    Methods    Results     }
(no. of patic:nts)    (n)    (n patients)    score   
Snoek et al.        (i)    80 mg (2 ml) methyl  prednisolone,  lumbar        (ii)  2 ml saline (11 = 24)    72    %patients improved  after  2 days  with  regard  to  LBP:   (i)  33"u. (ii)
(81)        route  (n = 27)                25%; radiating  pain: (i) 26o/o, (ii) 13%;  sciatic nerve stretdi tokran.:e:

Math..:ws ..:t al.     (i)   80 mg (2 ml) methyl prednisolone+ 20 m!
(15-1)    bupivacaine (0.125%). caudal route  (n = 23)

1-3     (ii)  2 mllignocaine,    67 subcutaneously (n = 34)

(i)  36%,  (ii)  25%;  subjective improvement: (i)  67"o. (ii)  -1:2"•-        "o
patients who underwent surgical treatment within 14 ± 6 months atkr treatment:  (i) 58%, (ii) 52%.    No statistically  signiticant dlfterences.
%patients recovered  after 1 month: (i) 67%, (ii) 56%.    Not stgnificant. After  3 months:     (i)  significantly  more  pain-free   than  (ii).       No significant differc:nce.

(73)     procaine (I%), lumbar route  (11 = 42)

Bush and Hillier

,•   ,..

-i l ...   i

(I%)(11 "'31)

significant.     Long-term  follow-up (about 20 months} showed  no significant differences.                                                 •

52 weeks:  (i) 44, 73, 80; (ii) 63, 65, 74.                                       _
Short-term: (i)  significantly better results (pain, SLR}.-  Long-term: pain not significantly different.     (i) straight leg  raise significanlly bettt:r. (no  data presented}.  .          •                                                                                        •

Serrao et al.        (i)    10 m!_saline+ 80 mg prednisolone (epiduml)    I (pair)    (ii)  10 ml saline (epidural)+ 2    52    No. of patients reporting  initial improvement  and after2 months:  (i) 3.
(155)        = 3 ml aextrose  (5%, i.t.), lumbar route        mg midazolam +dextrose        5;  (ii)  10, 7.    No significant differences for .Pain and activity  scores.

(n= 14)
Klenc:rml!n et al.     (i)   20 m!saline+ 80 mg methyl prednisolone.
(/56}     lumbar mute  (11 • • 1 'J)

:•      ' I

l; 1    •.•

Dilke c!l al.     ( i)   10 ml saline + 80 mg methyl prednisolone.
(lil)    lumbar route  (n ". 51 )



(3 ml, 5o/o, i.t.)  (n = 14)
(ii}  20 ml saline (n = 16)     50
(iii) 20 ml bupivacaine (0.25%)
(n= 16)
(iv) dry needling.interspinous ligament (11 = 12)
(ii)   I ml saline (n = 48)     50

(ii) significantly less self-administered medications.     •
No. ofpatients improved  or cured according to clinician:.   (i)  15. (ii)
11,  (iii} 11,  (iv) 10.   No signiticant differences.

No. ofpatic:nts not returned  to work at 3 months:  (i) 3 of36,• (ii)  14tlf
35.     Di1Ten.'11cc is significant.  N<, difft.."f'cnccs in no. days of  hcd  re't and days in hospitaL     No. of patients  r<.-porting none and• itut !><:\ere pain after 3 months:  (i) 16, 24; (ii) 8, 20.

Rocco et al.

Ridky  cl al.

(i)  50 mg' litnricaine + 75 mg triamcinolone
(157)    ,    (l0.9ml).lumbarroute (n=8)
(ii)  50 mg li h aine + 75 mg triamcinolone + 8
mg morphine (10.9 m1) (n = 7}
(i)    I0 m!saline+ 80 mg. methyl prcJnisolonc.



(iii) 50 mg lignocaine+ 8 mg morphinc(10.9 ml)(n=7)

(ii)  saline (2 ml). interspinous



Mean   improvement  Qn  VAS  after   1  month:     (i)  0.9. ,:(ii)  - 0.6 (deterio tion) (iii) 0.4.   No. <lfpatients reporting  long-tc:m1. rdi.:f: • (il
I,(ii) o. (iii) 0.   No significant differences.   •

%  patients  reporting  improvement after  2  weeks:   (i) 90%(ii) 19 o.

(87)        lumbar route  (n = 19}        ligament(11=  16)        Short-term (i) significantly better in relieving pain.
lldiveau        (i}    40 ml procaine{0.5%) + 80 mg (2 ml)    1-2    (ii)  42 m!procaine (0.5%)    45    No.  of  patic:nts  improved   or  completely   relieved  during   3  months



methypr nisolone, caudal route  (n = 24)
(i)   60 mg trifl.m inolone (3 ml) + 47 ml saline(-}     1-4

(n = 24)
(iii) 50 m!saline  H

follow-up  period:  (i) 18, (ii) 16.   No significant difference.
17     (i) and (ii)  better  than (iii)  and (iv) regarding  improvement in straight

(59)     (ii)  60 mg lriamcinolonc (3 ml) + 47 tit!
lignocaine (0.5%) (-J

(iv) 50 m1lignocaine (0.5%) (-)

let raising.  No data on patient level presentc:d.

-.-Rcsuils ot the most important Ol!lcomc m l.o;urcs-accol:-o"""li-igto the-<mtl1(ir -;,ltflc study_    --... --•-•--
p <0.05 were taken as significant.


Bush's study (63} appeared to show a significant improvement within the steroid treated group at four weeks on all outcome measures, which did not occur in the placebo group.  At one year only improvement in SLR reached statistical significance in the steroid group.  However
•this study has been criticised on •statistical grounds because the analysis used only showed change within the active group not a difference between the groups,  Re-analysis using X2 tests indicated that the study lacked sufficient power to demonstrate such a difference because . the numbers were too small.
.    ..
When the same re-analysis is applied to the data. of Breivik et al (60) the difference in outcome
between treated and untreated groups is not significant.  Only if the cross-over patients are included does the difference in outcome achieve statistical significance but this step can be seriously questioned.

In an obscure and rarely quoted article because of its language Czarski (158)  demonstrated statistically significant and clinically significant differences in outcome comparing the use of caudal epidural injections of novocaine and hydrocortisone and novocaine alone in the treatment of patients with prolapsed lumbar intervertebral disc (Table   .9).  Unfortunately, however, the duration of follow-up was not specified• in this study and it is not clear how enduring either the benefit or the difference was.                •

Table  9
Treatment of prolapsed intervertebral disc with caudal epidural injections of 1OmL
novocaine 1 per cent (nov) and 25 mg hydrocortisone (HC) or 10 mL novocaine alone

Treatment     Number     Relief

------------------------------------------------------------ -------------
Complete    Significant    Marginal     None or worse


.   Nov

123    22    64    14
60    0    8     35

17  .

---------------------------------------------------------------------------------- ------------------ ------------
Source: Based on Czarski (158)

The balance of the published evidence supports the therapeutic use of caudal epidural steroids but  does  not  vindicate it.    There are  no  contrary  or  hostile .   publications,  but  several enthusiastic, supportive publications. Open trials claim good results in the treatment of sciatic pain, and the results of controlled trials approach  but do not achieve convincing, statistical significance.               •

'•\     '
The remaining studies involve  the lumbar route whose perceived advantage  is  that  the
injection can be targeted more closely to the assumed site of pathology and a lower volume is
•required. The disadvantage is the greater risk of dural puncture.

The literature on lumbar epidural steroids is largely supportive of their use, although more negative studies have been published than in the case of caudal epidural steroids.  One aspect of uniformity has been that virtually all trials, both open and controlled, have evaluated the use of lumbar epidural steroids in patients with symptoms of sciatica or nerve root pain.  Only Jurmand (88) included an additional large group of patients with simply low back pain . White


et al (102) studied patients with a variety of carefully defined diagnoses but did not specify how . many patients with each diagnosis were treated,
. Uncontrolled trials that do not specify the period of follow-up record good results in between
18. er cent and 90per cent of patients.(12,69,75,85,88,89,158)
Most of the studies on lumbar ESI have used methyprednisQlone.

Table  10
Preparations reported for lumbar epidural injections of steroids

Author    Saline    Local anaesthetica    Steroidb    Total
(mL)    ------------------------
.Drug     o;o    mL    ---- ---------------
Drug     mg    volume
Zappala (159)    HC    100    3
Yamazaka (164)    HC    25
Barry & Kendall (83)    20    MP    80    22
Harley (85)    MP    80    2
Burn & Langdon (80)    lig    0.75 40    MP    80    43
+HC    25
Swerdlow & Sayle,
Creer(86)    3    MP    80    5
Ito (12)    PN    20    ?
Winnie et al. (ISO)    MP    80    2
Warr et al (79)    lig    40    MP    80    43
+HC    25
Jurmand (88)    ns     4
Dike et al (82)    10    MP    80     12
Hartman et al (75)    MP    80    2
D'Hoogue et al (69)    10     MP    80     12
Snoek et al (81)    MP    '    80    2
•Brown (72)    lig    1    3     MP
Bullard &    cpc    1    1    DX    8    6
. Houghton (160)    +MP    200
Heyse-Moore (70)    lig    1    20    MP    80    22
White et al (102)    bup    0.25    5    MP    60    7
Green et al (74)    6     MP    808
Jackson et al. (76)    10     MP    120    3
Berman et al (89)    bup,.._    0.5    10    MP    100    13'
Cuckler et al (73)    pro    1    5    MP    80    7
Hickey (78)    7     MP    120    10
Anderson & Mosdal (71)    lig    1    18    MP    80    20
Rid ey et al. (87)    10     MP    80    12.
Rosen (77)    MP    80    2
a   proc: procaine; lig: lignocaine; cpc: chlorprocaine; bup: bupivacaine;
b   HC: hydrocortisone; MP: methylprednisolone; PN: prednisolone; DX: dexamethasone;
ns: not specified.


On reviewing the controlled trials from Koes' review (153) (see Table 8)  Snoek's trial received the highest methodological score.  This trial is however flawed because patients were assessed only twenty four hours after injection which is an inappropriately short period in which to
••"  evaluate the anti-inflammatory effect of a long acting steroid preparation. Furthermore only 2
mls of the active treatment were administered which may not have reached the target disc level.

Cuckler's trial (73) which also showed no treatment effect can be criticised on similar grounds. Responses were evalu ted at twenty {our hours , and all injection) were made at the L3/4 level rather t!lan the lower two levels where 90% of disc lesions occur.  Furthermore patients who had undergone previous laminectomy were included in which epidural scarring could have limited the spread ofthe injected mixture.

Serrao's study (155) compared steroid and saline epidurally plus 3 mls dextrose intrathecally with 10 mls saline epidurally and 3 mg midazolam with dextrose intrathecally.   This trial seemed to show a benefit of midazolam intrathecally for chronic mechanical low back pain. No conclusion can be drawn about ESI in this sample of patients who did not represent the common indication for ESI - sciatic root irritation.

Rocco's study (157) also included post-laminectomy patients and was comparing  lignocaine and triamcinolone with 8 mg morphine and lignocaine.  Once again no conclusions can be drawn about the efficacy of ESI for sciatica.

Two controlled trials have given favourable results for lumbar epidural steroids.  Dilke et al. (82) studied 100 patients with unilateral sciatica.   Active treatment consisted of a lumbar epidural injection of 80 mg methylprednisolone in 10 ml normal saline; control treatment was an injection of 1ml of normal saline into an interspinous ligament. Significantly more patients receiving the active treatment had their pain  'clearly  relieved'.    A greater  proportion  of actively treated patients had no pain at three months, took no analgesics and resumed work at three months (Table  11).  Fewer actively treated patients underwent subsequent surgery or other, non"'surgical treatment but these latter differences were not statistically significant.

The Dilke study (82) has been replicated by Ridley et al (87).   These investigators studied 35 patients with sciatic pain with numbness or paraesthesiae in the same distribution as the pain or an appropriate neurological deficit. Active treatment consisted of an epidural injection of
10 mL of normal saline to which 80 mg of methylprednisolone had been added.  The control
treatment was an injection of 2 mL of normal saline into an interspinous ligament. A second injection of the same agent was repeated at one week if there had been little or no improvement.    If placebo had been used initially and lack of improvement  persisted for another week, patients were given active treatment.


il    .....
I    !

r    j


Table 11
Outcome measures following lumbar epidural injection of 40 ml 0.75 per cent lignocaine with 80 mg methylprednisolone (treated) or 1 ml of normal saline (control) injected into an interspinous ligament.


lJ    Pain during admission
[j    Control
X2 = 10.48,p<O.Ol

Clearly relieved .


Clearly not .relieved



Pain at three months Treated Control
X2=13.89,p < 0.01



Not severe




Work at three months


Not Resumed

X2 (with Yates' correction)=  8.1, p=0.004
u    Fisher's exact test: p = 0.002
---------------------------------------------- --------------------- ---------------------------------------------
Source:  Results ofDilke et al. (82) (abridged)

Ninety per cent of the patients treated act.ively showed at least some improvement compared with 19  per cent of patients in the control group.  Patients receiving  active treatment  showed significant improvements in pain at both one and two weeks following treatment.   This improvement was maintained  up to 12 weeks but deteriorated  by 24 weeks  to pre-treatment levels.  Only 11 of the 17 patients who responded favourably maintained their pain-relief.

Both  these  studies  demonstrate   a  statistically  significant  benefit  of  the  lumbar   epidural injections to patients with sciatica but the benefit is of limited duration.   Significant' effects were evident only at one week and at three months after which the benefit decreased.

The only relevant controlled  study from Koes' review on lumbar ESI with a negative  result was Klenerman's  (156).   This seems to indicate a similar proportion of patients  (approximately
75%) with sciatica of less than six months duration improve whether treated by saline, depomedrone,  bupivacaine  or needling  of the interspinous  ligament.   This  study  contained limited numbers in each group and therefore may not have been powerful enough to detect a statistically significant difference (Table 12).

L  i

,            I


Table 12
Responses to lumber epidural injections.

•             I


•Response     Treatment

I;  I






l_ J

Not failed

5     4    5
11'    15     11

2     16     25%
10     47     75%

Source:  Klenerman et al. (156)

Of the studies on lumbar ESI included in Koes' systematic review which faithfully addresses the question only one is negative (156)  whereas two are positive in showing the benefit of lumbar ESI albeit in the short term. (82,87).

I 1
I    i
'  I

I    1

r  l
L  i

.   j

' _.J

Of the caudal ESI studies, 4 tudies suggest a positive efficacious effect, (59,60,63,154)Nersus one study showing no benefit (65),     These latter studies however have been criticised on methodological and statistical grounds.

Subsequent to these reviews Carette et al (161) published a significant paper in 1997: in a randomized double blind trial they administered up to three epidural injections of methylprednisolone acetate (80 mg in 8 ml of isotonic saline) or isotonic saline (1ml) to 158 patients  with  sciatica due  to  a  herniated  nucleus pulposus.    All  patients  had  Oswestry disability scores higher than 20 (on a scale of 1 to 100, with scores of 20 or less indicating minimal disability and higher scores greater disability).  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% confidence interval for the difference, 7.1 to 2.2)  Differences in improvements between the groups were not significant, except for improvements in the finger to floor distance (p =
0.006)   and   reversal  of   sensory   deficits   (p   =  0.003),   which   were   greater   in.  the
methylprednisolone group.    After six weeks, the only significant difference was the improvement in leg pain which was greater in the methylprednisolone group   (p = .0.03). After three months, there were no significant differences betwen the groups.    The Oswestry score had improved by a mean of 17.3 in the methylprednisolone group and •15.4 in the
.   placebo group (95% confidence interval for the difference, 9.3 to 5.4).  At twelve months the
cumulative probability of  back surgery was 25.8% in the methylprednisolone  group  and
24.8% in the placebo group (p = 0.90).  They concluded that although epidural injections of methylprednisolone may afford short term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus, this treatment offered no significant functional benefit, nor did it reduce the need for surgery.


30    i


In 1995 Watts and •silagy (162) performed a meta analysis (162).    The efficacy of epidural cofticosteroids in  the  management of  sciatica  was investigated by meta  analysis  of  all randomized controlled trials. Eleven suitable trials of good qualitY were identified involving a total of907 patients. The use of epidural (caudal or lumbar) steroid in the short term (up to 60 days) increased the odds ratio (OR) of pain relief (over 75% improvement) to 2.61 (95% Cl
1.90 - 3.77) when compared with placebo.  Despite some variations in trial characteristics
there was little evidence 'Of  significant heterogeneity (p = 0.07).   When the  trials  were analysed for near or total relief of pain in'"the short term the OR is 279 (95% Cl 1.92 - 4.06),

for heterogeneity (p

0.07). For long term relief of pain (up to twelve months) the OR is 1.87

(95% Cl 1.31 - 2.68).  Efficacy is independent of the route of injection; for caudal epidural
steroid the OR is 3.80 (95% Cl 1.36- 10.6) and for the lumbar epidural steroid 2.43 (95% Cl                     i
1.177 - 3.74).   Adverse events included dtiral tap (2.5%), transient headache (2.3%)  and                      '
transient increase in pain (1.9%).   There were no reported long term adverse events.    In conclusion, they present quantitative evidence  from  meta analysis of  pooled  data  from randomized trials that epidural administration of corticosteroids is effective in the management of lumbosacral radicular pain.    .

Rapps in 1994 performed a meta analysis of six studies from sixteen identified controlled studies.  Criteria for analysis were English language, human adults with I.:BP and/or sciatica, randomized  controlled  trials  which  were  double  blinded  or  had a  blinded  observer, abstractable data and outcomes assessed at least one week post injection (163).

The test for heterogeneity was not significant at p< 0.05 indicating that data could be pooled.

r        Out of the six studies that met inclusion criteria acute radiculopathy was the diagnosis of five of them.

The difference between the proportion improved in the steroid group minus the control group
(saline or local anaesthetic) produced an effect size (ES) of 0.137, 95% Cl (0.032, 0.242) see
I  '         graph.  Data were insufficient to comment on functional changes including: medication use, return to work, resumption of normal activities, complications, or future utilization.



- •--•-•------•-------------  -------•---- ------------ •--------------- --- --------....    ;     ..     .,     .,        ......- .,.........,..._•.,.._..... ..........:....-l,.,...ll,.,.,...".



Effect Size of Epidural Injection  on Pain Relief
(Treatment- Control)

,. ---------- ---- "--------•---------------------- ------------------- ----- -----•---- -- ---- -------------

Olinded RCTs

Blinded RCTs

-0.5    ()


-0. s

()     o.s    .I

.       .._

Cl•(0.032, 0.242)

J     Conclusions

These results suggest  that  ESI has a small but statistically  significant benetit in relief from  low  back  pain  secondary  to acute  radiculopathy.    The  results suggest  that  on average •14% of individuals who would not have otherwise improved would so so with ESI.  Future studies following an adequate study design with sutl1cient patient numbers are needed to address functional outcomes and cost effectiveness.



I  '
I   I


. J


On the basis of three positive (versus pne negative) controlled studies on lumbar BSI, four controlled studies on caudal BSI, and two favourable meta analyses in the presence of a wealth of evidence of relative safety in clinical usage over mariy years the use of epidural steroid injections are vindicated with certain reservations.

Corticosteroids havbeen  introdpced  into the epid  ral  space . for  almost  half a century. Over this period sev.eral preparations, including Kenalog, have been used extensively on an international basis•.

Despite this vast experience, reported  complications of this technique are excessively  rare.   Furthermore, there is no evidence to suggest that  the correct administration of epidural corticosteroids results in any significant short  or long term complications.

Epidural  corticosteroids have been proposed for the. management of a number of spinal syndromes.  However, although the literature  is conflicting, there  is only evidence to support their efficacy in the management of sciatica. •

Based on the previous material that we have reviewed, we would recommend that the statement, suggesting that  Kenalog is not to be used in the epidural  space, should be removed from the data  sheet.  We believe that more research is needed to .fully establish the efficacy of epidural  corticosteroids in the  management  of certain spinal syndromes.                                                                     •


Data Sheets:

1. Kenalog TM I tra-Articular/Intra-Muscular 1998

2. Adcortyl TM Intra-Articular/ Intradermal1998

32    •I




.    ' ....

.    1.
I      i



I:    5.

• ''f
lftj    9.




National Health and MRC report on Epidural Use of Steroids 1994
Corrigan B., Carr G.,  Tugwell  S. (1982) Intraspinal corticosteroid injections. Med.J. Australia. Mar.222-25.     •
Kepes,  Edith R., Duncalf D - Treatment of Backache with Spinal Injections of Local
Anaesthetics, Spinal and Systemic Steroids.  A Review- Pain 22 (1985) 33-47.
Benzon, Honorio T.-  Epidural Steroid Injections for Low Back Pain and  Lumbosacral     I
Radiculopathy- Pain 24 (1986) 277 295.
Bogduk, Nikolai- Spine Update, Epidural Steroids- SpineVol20, No.7, 845-848. Nelson,  D.A.  -  Dangers  from  methylprednisolone  acetate  therapy  by  intraspinal injection.   Arch.Neurol. 45, 1988, 804-806.
Roche, J.- Steroid induced arachnoiditis.   Med.J.Australia. March 1994.
Lindahl 0. & Rexel B. -Histologic changes in spinal nerve roots of operated cases of
sciatica.   Acta. Orthop. Scand. 20 (1950) 215-225.     .
Olsen, S.E.- The dynamic factors in spinal compression.  A study in dogs with special reference to cervical disc protrusion.   J. Neurosurgery 15 (1958) 308-32.1.
Feldman S. & Behar A.J.  Effect of intrathecal hydrocortisone on advanced adhesive
arachnoiditis and CSF pleocytosis:experimental study.     Neurology (Minneap.) 11 (1961) 251-256.

11.         Lehrer G.M., Maker H.S. and Weissbarth S.  Brain uptake of Methylprednisolone from the CSF and systemic sites.   Arch. Neurol. (Chic.) 28 (1973).
12.     Ito R.  The treatment of LBP and sciatica with ESI and its pathophysiological  basis, Nippon Saikingeka Zasshi 43 (1971) 769-777.
13.     Green P.W. , Burke A.J..,Weiss C.A..  The role of BSI in the treatment of discogenic
LBP  Clin., Orthop., 153 (1980) 121-125.
14.     McCann, Autologous NP inflammatory effect in epidural space. Spine 1987.
15.         Olmarker K., Rydevik B. - Autologous nucleus pulposus  induces  neurophysiologic and histologic changes in potcine cauda equina nerve roots.   Spine 1993; 18. 1425-32.
16.     SaalJ.S.- The role of inflammation in lumbar pain.   Spine Vol20, 1995, 1821-27.
17.     Takahashi. At site of HNP, cytokines produced which increases PGE2.  Spine 1996
18.     Doita - Mononuclear•cells at the margin of extruded discs.   Spine 1996.     .
19.     Olmarker K., Byrod G., Comefjord M, Nordborg  Cl, Rydevik B.   Effects of methyl prednisolone on nucleus pulposus induced nerve root injury.   Spine 1994, 19: 1803:-8.
20.     Wehling -Prednisolone protects against nerve degeneration in experimental radiculitis.
Spine 1996.
21.     Marshall  L.L.  Trethewie  E.R.,  Curtash  C.C:     Chemical  radiculitis  -  a  clinical, physiological and immunological study.   Clin.Orthop. & Ref. Research April1977.
22.     Perey 0. Contrast exam of the LV. disks of the lumbar spine.   Act. Orthop.Scand. 20:
327 1951.
23.     Walk L. Clinical significance of discography.   Acta. Radiol. 46:36 1956.
24.     Norlander S., Saler E. Discography in LBP and sciatica.  Acta. Orthop. Scand. 28:90
25.     Knight, C.L. et al - systemic side effects of extradural steroids -  Anaesthesia, 1980, Vol. 35, 593-594.



. 27.
. "'









Jacobs, S.   et al - Adrenal suppression  following  extradural  steroids  -   Anaesthesia,
1993 Vol38, 953-956.
Kay, J., Findling J.W.,  Raff     H.,     Epidural  triamchiolone  suppresses  the  pituitary­
adrenal axis in human subjects.   Anaesth. Analg.  1994, 79: 501-5.
Delaney,     Thomas  J. et  al  - Epidural     Steroid  Effects  on  Nerves  and  Meninges  - Anaesthesia and Analgesia, Vol59, No 8, Aug. 1980.
Cicala, Roger S. et al - Methylprednisolone Acetate  Does Not  Cause  Inflammatory
Changes in the Epidural Space -   Anaesthesiology 72: 556-558, 1990.
Mackinnon S.E., Hudson A.R. -Peripheral nerve injection injury with steroid agents. Plast. Reconstr. Surg., 69: (1982) 482-489.
Aoki  M., Kato F.,  Mimatsu  K.,  Histologic  changes  in  the  intevertebral   disc  after
injections rabbits.   Spine 22; 127 1997.
Golightly, Larry K. et al - Pharmaceutical Excipents,  Adverse Effects Associated with
Inactive Ingredients in Drug Products- Medical Toxicology 3: 128-165 (1988). British Pharmacopoeia,  Volume 11 Her Majesty's Stationery Office, 1988, p758.
Dib  B.  Effects  of  intrathecal   capsaicin  on  autonomic  and  behavioural   heat  loss responses in the rat.  Pharmacal  Biomchem Behav 1987; 28:65-70.
Hornfeldt  C.S., Larson A.A.,.    Seizures  induced  by fluoracetic  acid and  fluorocitric acid may involve chelation of divalent cations in the spinal cord.     Eur. J. Pharmacal
1990; 179:307-313.
Wang B.C., Hillman D.E., Spielholtz N.I., TurndorfH. Subarachnoid  neurotoxicity  of acetone sodium bisulfite antioxidant in tetracaine hydrochloride  in rabbits.     Anaesth.
Analg. 1983; 62: 289-290.

37.  •   Wang B.C., Hillman D.E., Spielholtz N.I., Turndorf H.  Chronic neurological  deficits and Nesaclaine - CE - an effect of the anaesthetic, 2-chlorprocaine,  or the antioxidant,
sodium bisulfite?   Anaesth. Analg. 1984; 63:445-447.



Margolis G., Hall H.E., Nowill W.K.  An investigation of efocaine, a long-acting  local anaesthetic agent. I animal studies.   Arch Surg.1953; 67:715-730.
Chino N., Awad E.A., Kottke  F.J.   Pathology  of propylene  glycol  administered  by perineural and intramuscular injection in rats.     Arch. Phys.Med. Re4ab. 1974; 55;33-

40.     Benzon et al - Effect of polyethylene glycol on mammalian nerve impulses. -  Anaesth and Analg. 66: 553-9, 1987.
41.     Wood, K.M., Arguelles J. and Norenberg  M.D., - Degenerative  lesions  in rat sciatic nerves  after  local  injections  of  methylprednisolone  in  aqueous   solution.        Reg. Anaesth. 5 (1980) 13-15.
42.   . Feasby, T.E. et al -Neurotoxicity of Bacteriostatic  Water- The New England Journal ofMedicine, April21, 1983 Vol. 308, No.16.                                                        •
43.     Craig,   Douglas   B.   et   al   -  Flacci4   Paraparesis   Following   Obstetrical   Epidural Anaesthesia:  Possible Role of Benzyl Alcohol -  Anaesthesia and Analgesia,  Current Researches, Vol56,  No2 March-April1977.
44,     Saiki  J.H.  Thompson  S,  Smith  F.,  Atkinson  R.    Paraplegia  following  intrathecal chemotherapy.  Cancer 1972; 29:370-374.
45.     Hahn A.F., Feasby T.E., Gilbert J.J., Paraparesis following intrathecal  chemotherapy.
Neurology 1983; 33:1032-1038.     •
46.     Bagshawe K.D., Magrath I.T., Golding  P.R. Intrathecal methotrexate.    Lancet  1969;


47.     Nathan P.W., Sears T,A., Action of methyl hydroxybenzoa.te on nervous conduction.
Nature 1961; 192: 668-669.

.•"' .



















Goto S, Grosfeld J.L. The effect of neurotoxin  (bezalkonium chloride)  on the lower oesophagus.   J. Surg. Res. 1989; 47: 117-119.
Holle G.E. Changes in the structure and regeneration mode of the rat small intestinal
mucosa  following  benzalkonium  chloride  treatment.    Gastroenterology  1991;  101:
Zucoloto S, Diaz J..f\., Oliveira J.S.M., Muccilo G, Sales Netvo V.N., Kajiwara  J.K., Effect of chemical ablation of myS'nt ric neurones on intestinal cell proliferation,   Cell
Tissue Kinet 1988; 21:213-219.
Bernat J.L., Sadowsky C.H., Vincent F.M., Nordgren R.E., Margolis G., Sclerosing pachymeningitis: a complication of intrathecal administration of Depo-Medroile for multiple sclerosis.   J.Neurol. Neursurg. Psychiat. 1976; 39: 1124  112 .
Stratton I. Dangers of intrathecal  hydrocortisone  sodium  succinate. • Med.  J. Aust
1976;  2.650.
Moore  D.C., Rain  R.H.  -  Importance  of  the  perineural  spaces  in  nerve  blocking. JAMA 156: 1954, 1050-1053.
Hurst,  E.  Weston  - •Adhesive  Arachnoiditis   and  .Vascular  Blockage   Caused   by
Detergents and Other Chemical Irritants:   An Experimental Study -     J. Pathol.  38., Bacteriol. Vol. 70, 167-178 (1955).
Shantha, T.R., Evans, J.E., - Relationship of epidural anaesthesia to neural membranes
and Arachnoid Villi-    Anaesth. V.37 No 5 Nov. 1972.                                                                               I Byrod G., Olmarker K. - Rapid transport  route between the epidural  space  and the                         I intraneural capillaries ofthe nerve roots.   Spine 20; 1995. 138-143.
Lindholm R, Salenius P. Caudal, epidural administration of anaesthetics and corticoids in the treatment of low back pain.   Acta. Orthop. Scand. 1964; f14-116.
Gordon J. Caudal extradural injection for the treatment of low back pain.   Anaesthesia
1980;. 35:515-516.
Yates D.W. A comparison of the types of epidural injection commonly  used in the treatment of low back pain and sciatica.  Rheum.Rehab 1978; 17:181-186.
Breivik H, Hesla P.E., Molnar 1., Lind B. Treatment  of chronic low  back pain  and
sciatica.     Comparison     of     caudal     epidural     injections      of     bupivacaine     and methylprednisolone  with  bupivacaine  followed  by  saline.     In:  Bonica  J.J.,  Albe­ Fessard D, eds.   Advances in pain  esearch  and therapy, Vol 1. New York;  Raven Press 1976, pp 927-932.                                     ,  . Sharma R.K. Indications, technique and results of caudal epidural injection for lumbar disc retropulsion.   Postgrad MedJ. 1977; 53:1-6.                 .   , Mount  H.T.R.  Hydrocortisone  in'••the  treatment  of  intervertebral  disc  protrusion. C .Med.Assoc.J 1971, 105:1279-1280,..
Bush K, Hillier S.A.  A controlled study of caudal epidural injections of trimacinolone                       ,  I
plus procaine for the managemnet of intractable sciatica.   Spine 1991; 16:572-575..
Gardner W.J., Goebert H.W., Sehgal A.D. Intraspinal corticosteroids in the treatment                          '   I
of sciatica.   Trans Am Neurol Assoc. 1961; 86:214-215.
Beliveau   P.   A   comparison   between   epidural   anaesthesia   with   and   without •
corticosteroids in the treatment of sciatica.   Rheum.Phys.Med. 1971; 11.40-43.
Goebert H.W., Jallo S.J., Gardner W.J.,  Wasmuth C.E.  Painful radiculopathy trefl.ted with epidural injections of procaine and hydrocortisone acetate: results in 113 patients. Anesth Analg 1961; 140: 130-134.


67.     Mount H.T.R. Epidural injection  of  hydrocortisone for  the  management  of  acute lumbar disc protrusion.   In Morley T.P. ed. Current controversies in neurosurgery.
••"'    Philadelphia: Saunders 1976, pp67-72.
68    Tanner J.A. - Retrospective survey of complications from caudal epidural steroids.
J.Ortho.Med. 18(3) 1996.
69.     D'Hoogue   R.,  Compere  A.,   Gribmont  B.,  Vincent  A.   Peridural   injection   of corticosteroids    in   the   treatment   of   the   low   back   pain/sciatica    syndrome. Acta.Orthop.Belg.1976; 42:157-165,  •
70.     Heyse-Moore G.H.. A rational  approach to  the use of epidural medication  in  the
treatment of sciatic pain.  Acta.Orthop.Scand. 1978; 49:366-370.
• 71.    Andersen K.H., Mosdal C., Epidural application of corticosteroids in low-back pain and sciatica.  Acta. Neurochir 1987; 87:52-53.
72.     Brown F.W.  Management of diskogenic pain using epidural and intrathecal steroids.
Clin. Orthop., 1977; 129:72-78.
73.     Cuckler J.M., Bernini P.A., Wiesel S.W., Booth R.E., Rothman R.H., Pickens G.T.
The use of epidural steroids in the treatment of radicular pain.     J. Bone Joint Surg.
1985; 67A:53-66.
74.     Green P.W.B., Burke A.J.,   Weiss C.A., Langan P; The role of epidural cortisone injection in the treatment of diskogenic low back pain.   Clin. Orthop. 1980; 153:121-
75.     Hartman J.T.,   Winnie A.P., Ramaurthy S., Meyers H.L.   Intradural and extradural corticosteroids for sciatic pain.   Orthop. Rev. 1974; 3:21-24.
76.     Jackson D.W., Rettig A.,  Wiltse  L.L.  Epidural  cortisone injections  in  the  young athletic adult.  Am. J. Sports Med. 1980; 8:239-243.
77.     Rosen C.D., Kahanovitz N., Bernstein R., Viola K. A retrospective analysis of the efficacy of epidural steroid injections.   Clin. Orthop. 1988; 228:270-272.
78.     Hickey R.F. Outpatient epidural steroid injections for low back pain and lumbosacral radiculopathy.    NZ Med.J. 1987; 100:594-596.
79.     Warr A.C., Wilkinson J.A., Burn J.M.B., Langdon L. Chronic lumbosciatic syndrome
treated by epidural injection and manipulation.  Practitioner 1977; 209:53-59.
80.     Burn J.M.B., Langdon L.  Lumbar  epidural injection for the  treatment  of  chronic sciatica.  Rheum. Phys.Med. 1970;10:368-374.
81.    Snoek W,    Weber H. Jorgensen  B. Double blind evaluation of  extradural  methyl
prednisolone for herniated lumbar disc.  Acta. Orthop. Scand. 1977; 48:635-641.
•  82.    Dilke  T.F.W.,  Burry  H.C.,   Grahame  R.  Extradural  corticosteroid  injection   in management oflumbar nerve root compression.  Brit .Med.J. 1973; 2.635-637.
83.     Barry P.J.C., Kendall P.H. Corticosteroid infiltration of the extradural space.•

"  ....

Phys. Med. 1962; 6:267-273.
84.    Burn J.M.B., Langdon L. Duration of aCtion of epidural methyl prednisolone.  A study
.  in patients with the lumbosciatic syndrome.  Am.J.Phys.Med. 1974;53:29-34.    i
85.    Barley C. Extradural corticosteroid infiltration. Ann.Phys.Med. 1967; 9:22-28.     i
86.    Swerdlow M, Sayle-Creer W.  A study of extradural medication in the relief of the
lumbosciatic syndrome. Anaesthesia 1970; 25:341-345.
87.     Ridley M.G., Kingsley G.H., Gibson T.,    Grahaem R.  Outpatient lumbar epidural•
corticosteroid injection  in  the  management of  sciatica.    Brit.J.Rheumatol.  1988;•
88.    Jurmand S.H., Corticotherapie peridurale des lombalgies et des sciatiques d'origine discale.    Concours Medicale 1972; 94:5061-5070.


89.    Gilly R. Essai de traitement de 50 cas de sciatiques et de radiculalgies lombaires par le
Celestene chronodose  en  infiltrations  pararadiculaire.    Marseille  Medicale  1970;
••"90.    Shealy C.N.  Dangers of spinal injections without proper diagnosis.     JAMA 1966;
197:No13 1104-1106.
91.    Dougherty J.H., Fraser  R.A.R.    Complications following  intraspinal  injections  of steroids  J. Neurosurg 1978; 48: 1023-1025.
92.    Abram S.E., Cherwenka R.W.    Transient headache immediately following  epidural
steroid injection. •Anaesthesiology 1979; 50:461-462. •
93.        Stambough J.L., Booth R.E., Rothman R.H.  Transient hypercorticism after epidural steroid injection.  J Bone Joint Surg. 1984; 66A 1115-1116.
94.    Gutknecht D.R.  Chemical meningitis following epidural injections of corticosteroids.
Am.J.Med. 1987; 82:570.
95.    Chan S.T., Leung S.  Spinal epidural abscess following steroid injeCtions for sciatica;
case report;  Spine 1989; 14:106-108.
96.        Simon  D.L., Kunz R.D.,  German J.D.,  Zivkovich V.     Allergic  or  pseudoallergic reaction. following epidural steroid deposition and• skin testing.   Regional  Anaesth.
1989; 253-255.    .
97. •    Williamson  J.A.     Inadvertent  spinal  subdural  injection  during  attempted  spinal epidural steroid therapy.    Anaesth.Intens.Care 1990; 18:406-408.
98.    Sekel R. Epidural depo-medrol revisited. Med. J. Aust. 1984; 141:688.
99.    Goucke C.R., Graziotti P.  Extradural abscess following local anaesthetic and steroid injection for chronic low back pain. Brit.J.Anaesth. 1990; 65:427-429.
'100.    MacArthur C,  Lewis  M,  Knox  E.G.    Investigation of  long  term  problems  after obstetric epidural anaesthesia. Brit.Med.J. 1992; 304: 1279-1282.
101.    Katz J.A, Lukin R, Bridenbaugh P.O., Gunzenhauser L.   Subdural intracranial air: an
unusual cause ofheadache after epidural steroid injection.    Anaesthesiology 1991; 74:
102.    White A.H., Derby R, Wynne G.   Epidural injections for diagnosis and treatment of low-back pain.  Spine 1980; 5:78-8().
103.    Bogduk N., Cherry D.  Epidural corticosteroid agents for sciatica.     Med.J.Aust. 1985;
143: 402-406.
104.    Abram S.E.     Perceived dangers from intraspinal steroid injections (Letter).     Arch.
Neural. 1989; 46:719-720.
105    Mehta M., Salmon N.  Extradural block.  Confirmation of the injection site by  X-ray monitoring.  Anaesthesia 1985; 40: 1009-1012.
106.    El-Khoury G.Ehara  S., Weinstein• J.W., Montgomery W.J. Kathol M.H..         Epidural steroid injection: a procedure ideally performed with fluoroscopic control.     Radiology
1988: 168:554-557.
107.    Renfres, Donald L., et al- Correct Placement of Epidural Steroid Injections-    A.J.N.R
12:1003-1007, Sep./Oct. 1991.
108.    Stewart H.D., Quinnel R.C., Daim N.  Epidurography in the management of sciatica.
Brit. J. Rheumatol1987; 26: 424-429.
109.    Abrams  S.E.,  O'Connor   T.C.    9omplications   associated  with  epidural  steroid injections.    Reg. Anaesth. 21(2): 149-162, 1996.
110.    BernatJ.L.  Intraspinal steroid therapy. Neurology 1981:31:168-171.


.       , I


i  L  j

, I
I    I

11Oa.  Carta F, Canu C, Datti R, Guiducci G, Pisani R, Silvestro C.   Calcification and ossification    of the  spinal  arachnoid after  intrathecal injection  of  Depo-Medrol. Zentralbl. Neurochir. 1987 48: 256-261.
'•'"111.    Cohen F.1..  Conus medullaris syndrome following multiple intrathecal corticosteroid
injections.    Arch.Neurol. 1979: 36:228-230.
112..   Nelson D.A., Vates T.S., Thomas R.B. C9mplications from intrathecal steroid therapy in patients with multiple sclerosis.  Acta. Neurol. Scand. 1973: 49: 176-188.
113.    Nelson D. Arachnoiditis from intrathecally given corticosteroids in the treatment of
multiple sclerosis (Letter).    Arch.Neurol. 1976; 33:373.
114.    Baker A.G.   Intrathecal methylprednisolone for multiple sclerosis:   evaluation  by a standard neurological rating.  Ann. Allergy 1967; 25:665-672.
115.        Goldstein N.P., McKenzie B.F., McGuldn W.F.   Changes in _cerebrospinal fluid of patients with multiple sclerosis after treatment with intrathecal methylprednisolone acetate: a preliminary report.   Proc.Mayo.Clin, 1962; 37:657-668.
116.    Rivera V.M. Intraspinal steroid therapy. Neurology 1981; 31:1060-1061.
117.    Rivera V. Safety of intrathecal steroids in multiple sclerosis (Letter).     Arch.Neurol.
1989; 46:718.
118.    Wilkinson H.A.    Intrathecal depo-medrol:   A lit rature  review.    Clin.J.Pain  1992;
119.        Sehgal A.D.,  Garner W.J., Dohn  D.F.    Patopaque  'arachnoiditis':   treatment  with subaraclmoid injections of corticosteroids.  Clev.Clin.Q. 1962;  29:177-188.
120.    Tkaczuk H. Intrathecal prednisolone therapy in postoperative arachnoiditis following
operation of herniated disk.    Acta.Ortho.Scand. 1976; 47:388-390.
121.     Ransford A.O., Harries B.J.  Localized arachnoiditis complicating lumbar disc lesions.
J Bone Joint Surg. 1972: 54B: 656-665.
122.    French J.D. Clinical manifestations oflumbar spinal arachnoiditis.   Surgery 1946: 20:
123.    Blau J.W., Logue V.  Intermittent claudication in the cauda equina.     Lancet 1961: 1:
124.    Davis L.E.    The principles of neurological surgery, 4th ed.    London.     H.Kimpton
Medical Publisher, 1_953: 394-398.    .
125.    Ramamurthy B. Spinal arachnoiditis. Indian J.Med.Sci. 1961: 15: 776-781.
126.    Jacobsen H.H., Lester J.  Diagnosis of spinal aranchoiditis by air myelography.     Acta
Neurol Scand 1969:45:376-380.
127.    Slager U.T. Araclmoiditis ossificans.  Arch.Pathol. 1960: 70: 322-329.
128.    Feder B.H., Smith  J.L.  Roentgen therapy in chronic spinal arachnoiditis.     Radiology
1962:78: 192-197.
129.    Teng P., Papatheodorou C.  Myelographic findings in adhesive spinal arachnoiditis.

Br.J.Radiol. 1967:40: 201-210.    ..    •
130.    Davidoff L.M., Gass H. Grossman J.  Postoperative spinal adhesive arachnoiditis anq
recurre1it spinal cord tumour.    J. Neurosurg. 1947: 4: 451-457.
131.    Smolik E.A., Nash F.P. Lumbar spinal arachnoiditis: A complication of intervertebral
:      -
I     I    disc operation.  Ann.Surg. 1951: 133:490-4'?6.
lJ    132.    Grinker R.R..., Chronic arachno-peritonitis with the syndrome of Froin    J. Nerv.Mental
Dis. 1926: 64: 616-622.
133.    Kulowski J., Scott W.  Localized •adhesive spinal arachnoiditis.    J Bone Surg. 1934:
16:699-704.     .
134.    Wise B.L.  Spinal arachnoiditis ossificans.  Arch.Neurol. 1965: 13:391-394.


135.    Epstein  J.A., Epstein B.S., Lavine L.S.,  Rosenthal A.D., Decker R.E.,  Carras  R.
•obliterative arachnoiditis complicating lumbar spinal stenosis.    J.Neurosurg 1978: 48
13'6.    Brodsky A.E.  Cauda equina arachnoiditis.  A correlative clinical and roentgenologic study. Spine 1978: 3: 51-60.
137.    Vloeberghs  M.,  Herregodts  P;  Stadnik  T.,   Goossens  A.,  D'Haens   J.      Spinal araclmoiditis mimicking a spinal •cord tumour.   A  case report and  review  of  the literature.    Surg. Neurol. 1992:37: 211-215.
138.        Quiles M., Marchisello P.J., Tsairis P.  Lumbar adhesive arachnoiditis.  Etiologic and pathologic aspects.  Spine 1978: 3: 45-50.
139.    Duke R.J., Hashimoto S.A.     Familial spinal arachnoiditis.   Arch.Neui'ol. 1974: 30:
140.    Selinsky  H. Disseminated spinal arachnoiditis.    Arch:Neurol. Neurosurg. Psychiatry
1936. 35: 1262-1279.
141.    Barre J.A. Arachnoidite et sclerose en plaques.  Paris Med. 1929: 2: 297.
142.    Sehgal A.D., Gardner W.J., Dohn D.F.  Pantopaque "arachnoiditis".     Cleve. Clin. Q.
1962: 29: 177-188.
143.    Dolan R.A. Spinal adhesive arachnoiditis.  Surg. Neurol1993: 39: 479-484.
144.    Bernat J.L., Sadowsky C.H., Vincent F.M., Nordgren R.E., Margolis G.   Sclerosing spinal pachymeningitis.   J. Neurol. Neurosurg. Psychiatry 1976: 39: 1124-1128.
145.    Gardner W.J., Goebert H.W., Sehgal A.D.•  Intraspinal corticosteroids in the treatment of  sciatica.  Trans.Am. Neurol. Assoc. 1961: 86: 214-215.
146..  Hartman J.T., Winnie A.P., Ramamurthy S.,  Mani M.R.,  Meyers H.L.  IntradlU'al and extradural corticosteroids for sciatic pain.   Ortho Rev 1974: 3: 21-24.
147.        Erdemir  H., Mann K., Gelman S.    Intradural  and  extradurald  corticosteroids  for posthtminectomy syndrome.  Ala.J.Med.Sci. 1982: 19: 136-138.
148.    Ryan M.D., Taylor T.K.F.  Management of lumbar nerve root pain by intrathecal and epidural injection of depot methylprednisolone acetate.   Med. J. Aust. 1981: 2: 532-
149.    Abram S.E.   Subarachnoid corticosteroid injection following inadequate response to epidural steroids for sciatica.  Anaesth. Analg. 1978: 57: 313-315.
150.    Winnie A.P., Hartman J.T., Meyers H.L., Ramamurthy S., Barangan V.  Pain clinic II: Intradural and extradlll'al corticosteroids for sciatica.   Anaesth. Analg. 1972: 51: 990-
151.    Tkaczuk H.  Intrathecal prednisolone therapy in postoperative arachnoiditis following operation of herniated disc.  Acta. Orthop. Scand. 1976: 47: 388-390.
152.    Bush K., Cowan N., Katz D.E., Gishen P.  Natural History of sciatica associated with
disc pathology.  A prospective study with  clinical and independent radiologic follow up.   Spine 17: 1205-12: 1992.    ,
153:    Koes B.W., Scholten R.J.P.M., Mens J.M.A., Bouter L.M.  Efficacy of epidural steroid injections for LBP and sciatica:   A systematic review of  RCT's.      Pain '63:279-
154:        Matthews J.A., Mills S.B., Jenkins V.M., Grimes S.M., Morkel M.J.,  Matthews W., Scott. C.M., Sittampalam Y.  Back pain and sciatica: controlled trials of manipulation, traction, sclerosant and epidural injections.   Brit.J.Rheumatol.-1987;26:416-423.
155.    Serrao J.M., Marks R.L., Morley •s.J., Goodchild C.S.  Intrathecal medazolan for the
treatment of chronic mechanical LBP:  A controlled comparison with epidural steroid in a pilot study.    Pain 48: 5 -12: 1992.


I /
l --


It  .  -----

1' l,.








.... 157.











Klenerman L., Greenwood R.; Davenport H.T., White D.C.,    skett S.     Lwnbar epidural injections in the treatment of sciatica.    Brit. J. Rheumatol1984; 23: 35-38. Rocco A.G.,  Frank E., Kaul A.F., Lipson S.J., Gallo J.P.  Epidural steroids, epidural morphine and epidural steroids combined with morphine in the  treatment of post laminectomy syndrome.  Pain 36:297-307: 1989.
.Czarski Z. Leczenic rwy kulszowej wstrzykiwaniem hydrokortyzonu I nowokainy do rozworu krzyzowego.  Przeglad Lekarski. 1965; 21: 511-513.
Zappala G. Iniezione peridurale segmentaria di Hydrocortone nella sindrome doloro a da emia discale• Policlinico-  Sez Prat 1955; 62: 1229-1231.    .
Bullard J.R.,Houghton F.M.  Epidural treatment of acute hemaited nucleus pulposus. Anaesth. Analg. Curr. Res. 1977; 56: 862-863.
Carette S., LeClaire R., et al.   Epidural corticosteroids for sciatica due to herniated nucleus pulposus.    N.E.J.M. June 1634-40, 1997.
Watts R.W., Silagy C.A.  Meta-analysis on the efficacy of epidural corticosteroids in the treatment of sciatica.  Anaesth. Intens. Care: 23: 564-9, 1995.
Rapp S.E., Haselkom J.K., Elam K., Deyo R.A., Ciol M.A. Epidural steroid injection in the treatment ofL.B.P.  A meta-analysis.  Anaesth. 81 (JA) A 923-1994.
Yamazaka N. Interspinal injection of hydrocortisone or prednisolone in the treatment of intervertebral disc herniation.    J.JPN Orthop Assoc. 1959: 33, 689.
Feffer H.L. Therapeutic intradiscal_ hydrocortisone. A long term study.     Clin.Orthop.
Dequesnoy B., Debiais F., Heuline E. et al.   Unsatisfactory results of intradiscai injection    of triamcinolone hexacetonide in  the  treatment of  sciatica  cau ed  by intravertebral disk herniation.   Presse Med 1992;21:1801-4.


r      1
:     I

l _j

r   ,


167.    Menkes C.J., Vallee C., Giraudet-Le-Qunitres J.S.     Calcification of epidural space
after hexacetonide.    Presse Med 1989; 18:1707.
168.    Bush    K,    Hillier    S.        Outcome    of.   cervical   radicuopathy    treated    with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review.   Bur Spine J. 1996 5:319-325.
169.    Lutz  EG,  Dunn  RN,  Wisneski  RJ.    Transforaminal lumbar  epidural  steroids.
Int.Spinal Inj.Society - 3rd Scientific Meeting proceedings. Sept. 1995.
170.    Bromage PR.  Physiology and pharmacology of epidural analgesia.     Anaesthiology
1967 28: 592-622


r. 1I        



_ ••