1 Shackelton Department of Anaesthesia, Southampton General Hospital, Tremona Road, Shirley, Southampton SO14 6YD, UK. 2 Department of Anaesthesia, Poole Hospital NHS Trust, Poole, UK. 3 Department of Anaesthesia, North Hampshire Hospital, UK
*Corresponding author. E-mail: isobelrice@yahoo.co.uk
Accepted for publication: March 13, 2003
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Abstract |
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Br J Anaesth 2004; 92: 10920
Keywords: anaesthetic techniques, epidural; complications; spinal cord, arachnoiditis
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Introduction |
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Although the incidence of irreversible neurological complications after epidural anaesthesia is very low,28 the Woolley and Roe case27 in 1954 serves to illustrate the catastrophic effect neural damage caused by central nerve block can have. After this report, public confidence in spinal anaesthesia disappeared for two decades. Increasingly, pregnant women are asking about the risks of arachnoiditis after an epidural. This information is not readily available. We therefore conducted a review of the current literature for any evidence of obstetric epidurals causing CAA.
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Nature of arachnoiditis |
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Anatomy |
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Intercellular pores have been demonstrated in animal and human arachnoid.101 In rabbits, these are large enough to allow the passage of erythrocytes.103 Arachnoid mater covering the ventral and dorsal roots of spinal nerves has proliferations of cells, which form villi.101 These have been classified depending upon their degree of protrusion through the dura. Types IV and V breech the dura, with Type V also protruding into the epidural space (see the two parts of Fig. 1).
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Pathology |
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It would appear that although in the past CAA has been described mainly in the thoracic or cervical region, since the 1950s there has been a trend towards a higher incidence in the lumbar spine. In 1978, Shaw reported that 71% of cases involved the lumbosacral spine alone.102 This may reflect a change in aetiological factors.
The arachnoiditis adhesions generally occur on the dorsal segments;68 the reason for this is not fully understood. With the exception of rare cystic forms, the adhesions are arranged peripherally and have been described as looking like the bark of a tree, when viewed by myelography.68
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Clinical features |
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Back pain with or without leg symptoms (e.g. pain, paraesthesia, or weakness) is typical, but a wide range of neurological abnormalities have been associated with CAA.52 Physical signs are not specific, although there is generally some abnormality to be found. As yet, a typical clinical syndrome has not been identified. Reported case series show a variety of symptoms and signs (Table 1).
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Earlier case series described CAA as a progressive disease.39 Most of these patients had cervical or thoracic CAA.102 With fewer cases being secondary to infection, most CAA now occurs in the lumbar region.102 Although the course of CAA is typically irregular, more recent case series report the disease as progressive in 1.833% of patients and static in 5059%.46 69 102
Laboratory studies are not helpful in the diagnosis of CAA. Some have reported an increase in CSF proteins with CAA,81 but this is not thought to be a reliable indicator of the disease.8 19 46 60 102 Clinical neurophysiological testing (e.g. electromyelography) is also not useful in the diagnosis of CAA.19 46 69
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Radiological features |
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Proposed definition of CAA |
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Back pain, increasing with activity.
Leg pain, which may be bilateral.
Some neurological abnormality on examination, most commonly hyporeflexia.
MRI changes consistent with CAA (myelography changes were accepted for earlier studies).
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Suspected aetiologies |
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Contrast media
Since the 1970s, contrast myelography has been a common cause of arachnoiditis. Ethyliophendylate (Myodil in UK, Pantopaque in USA) is an ionized fatty acid compound that is extremely radio-opaque. The incidence of adhesive arachnoiditis after its use is dose-dependant and has been quoted as 1%.102 It has a prolonged excretion time, sometimes up to 1 yr. It has therefore been suggested that the contrast media should be removed from the CSF immediately after imaging.61 However, there is no evidence that this reduces the incidence of arachnoiditis. A study in dogs has shown an increased inflammatory reaction with ethyliodophendylate plus blood and it is now advised to abandon the procedure if a bloody tap occurs.57 The use of oil-based iodine agents has largely been abandoned,56 but water-based agents are also capable of producing arachnoiditis, thought to be related to their tonicity.105 Metrizamide is thought to be the safest; its clearance from the CSF has a half-life of 4 h, and there have been no reported cases of arachnoiditis after its use in humans (although arachnoiditis can be induced in monkeys using very high concentrations).61
Epidural steroids
Injection of corticosteroid preparations into the epidural space in an attempt to relieve back pain is a common procedure. Corticosteroids used include: hydrocortisone acetate, methylprednisolone acetate (MPA), methylprednisolone succinate, and triamcinolone. MPA (e.g. Depomedrone) is the most commonly used. There have been reports of CAA after intrathecal injection of MPA,12 13 75 91 leading to calls to abandon its use.10 13 Some doubt the validity of these claims.112
MPA is suspended in polyethylene glycol (a non-ionic detergent), and myristyl gamma chloride (a long chain fatty acid) to reduce its aqueous solubility. It is thought that polyethylene glycol is the trigger for CAA.10 12 75 Other steroid agents do not contain polyethylene glycol but do contain bacteriostatic agents, for example benzyl alcohol or phenol, which are considered more noxious.13
Some authors feel that MPA should not be used in the epidural space, because of the potential for transfer to the intrathecal space, possibly leading to CAA.75 However, animal experiments have not shown significant inflammatory changes in the meninges after epidural MPA or triamcinolone.4 25 31 Dilution of steroid with saline or local anaesthetic before injection into the epidural space lowers the concentration of polyethylene glycol.10 This may be why there are no reports of CAA after uncomplicated injection of epidural corticosteroids. Indeed, Abram and OConnor found no cases of CAA after administration of epidural corticosteroids in their large review.3
Blood
It has been suggested that blood in the CSF can lead to an inflammatory reaction. Cases of CAA have been reported after SAH, the so called aseptic haemogenic meningitis occurring several days post-SAH.48 107 Nelson reported a case in which post-mortem studies showed an increase in inflammation of the pia-arachnoid leading to fibrosis after SAH.76 It has been suggested that the breakdown products of haemoglobin form free radicals, which can cause damage to nerves.58 82 Indeed, placement of the breakdown products of blood into the CSF of dogs causes more meningeal inflammation than does fresh blood.58 Other researchers have found that the deliberate placement of autologous blood in the epidural space produced no more tissue reaction than a normal lumbar puncture and so does not result in chemical meningitis.33 Obviously, this is relevant to those patients requiring an epidural blood patch for treatment of postdural puncture headache. Furthermore, bleeding into the epidural space can occur on insertion of an epidural needle or catheter, a bloody tap. Incidences for this have been quoted up to 18%.72 Evidence that minor bleeding is not uncommon with the insertion of epidural catheters has been found at epiduroscopy.15
A case has been reported in which an epidural blood patch was alleged to have caused CAA.5 Several attempts were made to locate the epidural space in a 34-yr-old woman in labour. After an epidural catheter had been inserted, the injection of 10 ml of bupivacaine 0.25% resulted in sensory analgesia to T2, suggestive of subdural placement of the catheter. After delivery, 19 ml of autologous blood were injected down the catheter as prophylaxis against postdural puncture headache. Five days later, the patient complained of backache, a burning sensation in both feet, and photophobia. An MRI scan showed a subdural haematoma, atypical clumping of the nerve roots, and also an extradural collection of blood. The patient was treated with anti-inflammatory drugs and phenytoin, but did not improve significantly. Although the patient had good clinical and MRI evidence of arachnoiditis, it was probably a result of the subdural, rather than epidural, blood patch. The use of the catheter to place the blood patch must be questioned, as it was already doubtful that the tip of the catheter was in the epidural space.
Abouliesh2 followed up 118 epidural blood patches over a 2-yr period. He found 19 cases of residual backache, three cases of limited back movement, and two cases with occasional radicular pain down both legs, but no cases of CAA. However, the study contains little detail of how the patients were followed up. Although it would appear that some were examined, there is no mention of further investigations including myelography or MRI.
Trauma
It is well known that CAA occurs after spinal surgery, particularly if it is either extradural,17 81or repeated. It has been implicated for many years as a factor in Failed Back Surgery Syndrome.
It has been suggested that the epidural catheter may cause an inflammatory reaction in the epidural space, particularly if left in the epidural space long-term.62 65 In rats, a fibrous sheath has been shown to form around an epidural catheter after it had been left in situ for several days.36 Moderate inflammatory changes can be seen at post-mortem in some patients who have had continuous epidural catheters in situ, with thickening along the indentations of the dura where there had been contact with the catheter.114 It should be noted that epidural catheters are not commonly left in situ for long periods of time in obstetric practice.
It was recognized in the 1960s that traumatic lumbar puncture led to an increase in CSF proteins, which did not occur in uncomplicated cases.9 71 This was postulated to be evidence of meningeal irritation; an inflamed meningeal barrier would allow more protein to cross into the CSF. Transient paraesthesiae occur during 2444% of epidural catheter placements indicating possible trauma.87 There is no evidence, however, to suggest that this meningeal irritation progresses to CAA. It has been suggested that the incidence of prolonged neurological abnormalities may be increased if paraesthesiae are elicited during insertion of an epidural needle or catheter.114
Reynolds documented seven cases, six obstetric and one surgical, in which neurological damage followed spinal or combined spinal epidural (CSE) anaesthesia.83 All patients experienced pain during the insertion of the spinal needle, which was believed by the operator to be at the L2/L3 interspace. MRI showed irrefutable evidence of spinal cord damage. However, there was no CAA demonstrable on MRI.
Haisa47 reported a case in Tokyo of CAA after obstetric epidural anaesthesia. At the time of epidural insertion, the patient felt a sudden sharp pain radiating down the left leg, and continued to complain of pain in her left leg and buttock. After a presumed diagnosis of disc herniation, the symptoms were treated by repeated epidurals each containing local anaesthetic and steroid. She also underwent myelography before an MRI, which was diagnostic of CAA. Unfortunately, this case report did not reveal details as to which drug was placed in the epidural and subarachnoid spaces during the many injections the patient received. It is therefore difficult to determine the exact aetiology of the CAA, but it should be noted that there were contributing factors including the traumatic epidural insertion, use of repeated epidural steroids, and myelography.
Detergents and contaminants
The Woolley and Roe case of 1954 famously advanced contamination with detergents as a cause of neurological abnormalities after spinal anaesthesia.27 Indeed, at laminectomy, Cecil Roe had thickening and cyst formation of his arachnoid mater, suggestive of CAA. Several cases have been described of neurological abnormalities,113 aseptic meningitis,43 96 and CAA,79 after subarachnoid blocks. The authors all postulated that these were because of contamination with detergents used to clean instruments. However, none put forward good evidence to support their claims.
Aseptic meningitis has been reported after CSE for analgesia during labour, thought to be a result of contamination by the chlorhexidine spirit used to clean the patients back.49 Experimentally, intrathecal detergents can cause a pronounced cellular proliferation of the arachnoid in monkeys, dependant upon the detergent used and its concentration.32 111 However, concentrations used were far in excess of those that could contaminate spinal anaesthetic equipment under normal clinical conditions.
The needle-through-needle technique is probably the commonest method of establishing CSE.26 Some are concerned that friction between the needles produces metallic fragments that are then introduced into the subarachnoid space, causing an inflammatory reaction.37 This has been postulated as a cause of aseptic meningitis.38 However, it is debatable whether metallic fragments are indeed produced.23 50 51 Medical grade stainless steel needles do not cause inflammation in nickel-sensitive patients.40
Vasoconstrictors
Boiardi and colleagues reported four cases of CAA occurring after non-obstetric epidural anaesthesia, using epidural bupivacaine with epinephrine.16 The authors suggested that a subarachnoid hyperaemic reaction had occurred secondary to drug placement in the epidural space. No detergents were used, but it is not clear whether preservatives were present in the solutions used. Chliapparini and colleagues reported 16 cases of serious neurological deficit after lumbar epidural anaesthesia over a 7-yr period, including nine cases of CAA developing 1 month to 8 yr later.24 Only one case involved an obstetric epidural. All used bupivacaine, with six also using epidural epinephrine (concentration unstated). CAA was diagnosed using MRI in seven cases and myelography in the remaining two. The obstetric case had epidural bupivacaine with epinephrine for analgesia during labour. Ten months later, she developed spastic paraparesis and decreased sensation. There was a delay of 10 yr before MRI findings diagnosed CAA. The authors allude to the fact that preservatives in the epidural solution may have been the causative factor, although which preservatives were used was not stated.
Preservatives
Sghirlanzoni and colleagues99 reported six patients from Italy, diagnosed with CAA using myelography, up to 3 yr after receiving non-obstetric epidural anaesthesia between 1983 and 1988. All their cases had received epidural local anaesthetics from multiple dose vials containing the preservatives, methyl and propyl paraben. Sklar and colleagues106 reported seven cases of CAA diagnosed using MRI, which were referred to their Miami hospital after epidural analgesia in labour, 2 months to 12 yr previously. All these women originated from South America and it is thought that they may all have received lidocaine 2% with the preservatives metabisulfite and methylparaben. Both these preservatives were banned in the USA at the time of this study, as they were known to have toxic effects. Indeed, Gissens study in rabbits demonstrated the neurotoxicity of sulfite-containing preservatives, although there was no comment on the reaction of the meninges.42
Local anaesthetics
Gemma and colleagues41 reported a case of CAA diagnosed by MRI after a non-obstetric epidural of bupivacaine 0.5% without epinephrine. An epidural catheter was not used. Little information was given on this case. No information was reported concerning the use of detergents or preservatives. The patient suffered from lumbar pain with paraesthesiae in his big toes, more prominent on the left side.
Arachnoid reactions to local anaesthetics are thought to be a function of their histotoxic properties.44 Topically applied local anaesthetics cause altered perineural permeability and oedema of nerve fibres.74 Myers74 suggested that ester local anaesthetics (e.g. chloroprocaine and tetracaine) are more neurotoxic, producing significant oedema of perineural tissues at clinically relevant concentrations. Topical application of increasing concentrations of bupivacaine to rabbit sciatic nerves in vitro showed increased adherence of nerves to each other, suggestive of a dose-dependant inflammation of perineural tissues.98 Although hyperglycaemia worsens neurological recovery after an ischaemic event, the addition of glucose 7.5% does not appear to increase neurotoxicity.92 There is no proof that allergic sensitivity of the meninges to local anaesthetic occurs.44 Cases of CAA who were tested for allergy to local anaesthetics have proved negative.63 64
CAA and cauda equina syndrome have been widely reported after spinal anaesthesia using a continuous micro-catheter technique.63 66 86 93 Drasner reported a case of cauda equina syndrome after continuous epidural analgesia in a 52-yr-old man.34 However, there was doubt as to whether the tip of the epidural catheter was extradural throughout the case. It has been shown by the use of glass spine models that injection of lidocaine 5% with glucose 7.5% has a non-uniform distribution in the CSF, because of the slow flow rate as it leaves the tip of the microcatheter.66 85 It is thought that this maldistribution unmasks the neurotoxic potential of local anaesthetics, by facilitating areas of high concentration within the CSF.86 This is potentiated by the use of hyperbaric solutions.86 Animal studies have shown that neurotoxicity can occur at clinically used concentrations of lidocaine and bupivacaine with a continuous infusion down a spinal microcatheter.35 67
Opioids
Opioids are widely used in the epidural and intrathecal space for pain relief in the perioperative, obstetric, and chronic pain settings. Fentanyl, alfentanil, diamorphine, and morphine are those most commonly used in the UK. Unfortunately there are no data from controlled trials investigating the long-term side effects of neuraxial opioids. Histopathological studies after long-term administration of intrathecal morphine in monkeys,1 and epidural administration of morphine and bupivacaine in humans,104 109 showed no evidence of arachnoiditis. A review of the literature by a panel of experts in chronic pain relief noted that the intrathecal administration of morphine and fentanyl at clinically effective concentrations appeared to be safe.9
Epidural solutions commonly used in UK
In 1992, Holdcroft53 found that 69% of respondents at the annual meeting of the Obstetric Anaesthetists Association used epinephrine in epidurals, either as a test dose or to establish block. Twenty per cent of those using epinephrine whilst establishing analgesia, and 76% of those using epinephrine as part of their test dose, chose a premixed solution of bupivacaine with epinephrine (which contains the preservatives sodium metabisulfite and hydrochloric acid). In total, 17 (19.5%) respondents used a premixed solution of local anaesthetic containing preservatives.
Burnsteins 19967 survey of epidural analgesia in the UK revealed that the most commonly used epidural test dose was 3 ml bupivacaine 0.25%, with only 9.5% regularly using lidocaine 2% as a test dose.21 Only five (3%) regularly added epinephrine to the test dose in this survey, in contrast to Holdcrofts findings. No comment was made as to whether premixed solutions containing epinephrine were used. Ten millilitre bupivacaine 0.25% was most often used to initiate analgesia. A trend towards the increasing use of low concentrations of bupivacaine was shown with 89.1% using bupivacaine 0.125% plain or less for maintenance of analgesia. Opioids were added to the epidural solutions in 88.1% of units, with fentanyl being the most common, but alfentanil and diamorphine were also used. A CSE for labour analgesia was regularly used in 24% of units, the Queen Charlottes regime being the most common (1 ml bupivacaine 0.25% plain with 1525 µg fentanyl intrathecally, and bupivacaine 0.1% with fentanyl 2 µg ml1 as an infusion or bolus doses).
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Evidence for back pain after epidural analgesic |
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Evidence for neurological deficit after epidural analgesic |
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A review of adverse drug reactions in Sweden over 30 yr included 21 reports of neurological abnormalities secondary to epidural analgesia.80 Since 1965, it has been compulsory to report all suspected new or adverse drug reactions to the Swedish Adverse Drug Reactions Advisory Committee. All reports from this large database concerning peripheral nerve injury associated with epidural or subarachnoid administration were reviewed. No cases of CAA were reported from this large database. There was only one case of an obstetric epidural leading to neurological deficit. This patient had a plain bupivacaine epidural for labour analgesia. She developed low back pain radiating to both legs with perineal dysaesthesia and incontinence, 27 months after delivery. Complicating factors included blood in the epidural catheter on first insertion and a forceps delivery. The incidence of peripheral neurological deficit is increased by use of the lithotomy position,110 and instrumental delivery.45 77 Indeed, Murray found that 85% of postpartum obstetric paralyses were associated with instrumental deliveries.73
The Patient Injury Act in Finland provides a no fault scheme for all patients. Claims are therefore made against the Patient Insurance Association (PIA) rather than the party implicated. A review spanning 5 yr uncovered 38 reports of neurological damage after central nerve block among the 23 500 claims for compensation filed with the PIA.7 It was estimated that 55 000 spinals and 170 000 epidurals were performed during this time. This large study revealed no documented cases of CAA. Two obstetric cases were reported in this review. After epidural analgesia for labour, one patient suffered an L5 lesion whilst the other had an unspecified permanent neurological deficit. There are no details as to the clinical findings or investigations, making it difficult to determine the cause or type of neurological deficit.
Scott and Hibbard published the results of an extensive retrospective questionnaire sent to all obstetric units in the UK, requesting data of any serious adverse events during and after extradural block in the previous 5 yr.95 Information was received from 203 units covering 516 000 deliveries, thus representing 78% of all births reported to the Royal College of Obstetricians and Gynaecologists during that time. Scott and Hibbard estimated that 506 000 epidurals for labour were performed during the 5 yr. There were 38 cases of neuropathy, all of which were a result of the damage of a single nerve or nerve root. They were of limited duration (up to 3 months), except for one case of permanent peripheral nerve damage. No cases of CAA were reported.
A multidisciplinary prospective audit in North-West Thames had 35 notifications of neurological deficits.54 During the 1-yr study period, notification of any postpartum neurological deficit was requested from obstetricians, anaesthetists, neurologists, rheumatologists, urologists, orthopaedic surgeons, GPs, and health visitors. Of 48 066 deliveries, 13 007 patients had an epidural and 629 had a spinal. An independent neurologist reviewed the notes of the 35 women with neurological deficits. Seven women had no neurological problems (joint problems), eight had no clinically identifiable lesion, one had multiple sclerosis, and 19 had neurological problems associated with pregnancy and delivery (an incidence of one in 2530). Seven of these patients had deficits persisting at 1 yr. No anaesthetic technique could be identified as a contributory factor. However, none of the women were examined or given an MRI scan, and no diagnosis was given to the neurological deficits.
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Conclusions |
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It is now generally accepted that contrast media can lead to CAA, ethyliodophentylate in particular.57 61 102 105 A link has been suggested between the use of epidural steroids and CAA.75 It would seem that meningeal irritation can be caused by blood or its breakdown products in the CSF.48 58 76 106 The epidural catheter itself may lead to inflammation of the meninges.114 There is no evidence to suggest that this meningeal inflammation causes long-term problems, including CAA. It is possible that bupivacaine with epinephrine may cause CAA, although the evidence is not conclusive.16 24 There is fairly good evidence to link the use of preservatives with CAA.99 106 From Burnsteins survey, it would seem that local anaesthetics containing preservatives or epinephrine are not used regularly in anaesthetic practice in the UK.21
Prospective studies show that epidurals do not cause chronic backache.56 70 81 Studies of backache or neurological complications after central nerve block do not show a link between epidural anaesthesia and CAA. However, all are lacking in detail, and do not cover a sufficient time period to be sure that they would detect CAA. Reviews of insurance claims,7 adverse drug reactions,80 and reports of adverse events after epidurals,95 rely on a connection being made between the symptoms of CAA and the epidural. We cannot be certain that this connection would have been made, as CAA presents in a wide variety of ways and often many years after the aetiological event.
There are a few cases in the literature of CAA after epidural anaesthesia (Table 2). However, only one case has been reported after an uncomplicated (non-obstetric) epidural using bupivacaine without preservatives, detergents, or vasoconstrictors.41 This report contains insufficient detail to be used as scientific evidence of a link between epidural bupivacaine and CAA.
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