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Current Anaesthesia & Critical Care (2004) 15, 239–246

KEYWORDAnalgesia,Anesthesiaepidural;Epidural spComplicatiNarcotics;AnticoagulBupivacaintoxicity;Analgesia,obstetrical

0953-7112/$ - sdoi:10.1016/j.c

�Tel.: +44-16E-mail addr

www.elsevier.com/locate/cacc

FOCUS ON: REGIONAL ANAESTHETICS

Epidural anaesthesia and analgesia in major surgery

Tim Meek�

James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, England, UK

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42-854600; fax: +44-16ess: tim.meek@stees.n

Summary This review article aims to broadly look at a few of the moreinteresting, controversial, important or recurrent themes in epidural anaesthesiaand analgesia: asepsis, factors influencing success, methods to aid location of theepidural space, loss of resistance—saline versus air, length of catheter to thread,nerve damage, treatment of bupivacaine toxicity, some recent findings relating toepidural opioids, epidurals and anticoagulation, and obstetrics.& 2004 Elsevier Ltd. All rights reserved.

Introduction

The use of epidurals is now routine both intra- andpostoperatively. Nonetheless, a straightforwardMedline search for English language publicationsunder the MeSH headings ‘analgesia, epidural’ or‘anesthesia, epidural’ published in the last 5 yearsreturns over 2200 hits. Consequently, this reviewwill concentrate on some of the more interesting,controversial, important or recurring themes,which will be of interest to the everyday anaes-thetist. Specifically not covered are local anaes-thetic agents or outcome, both of which arecovered elsewhere in this journal.

Elsevier Ltd. All rights reserv

42-282818.hs.uk (T. Meek).

Asepsis

There are currently no universally agreed guide-lines regarding the extent of aseptic precautions tobe taken. Most epidural abscesses are caused byskin organisms, most usually Staphylococci, soappropriate skin preparation is important. Chlor-hexidine in alcohol is known to be better thanpovidone iodine for skin preparation in placementof vascular catheters. In one comparative study ofthe use of the two solutions for skin preparationprior to epidural catheter placement, chlorhex-idine was more effective at preventing colonizationof epidural catheters: catheter tips were less likelyto yield organisms, colonization occurred lessfrequently and culture of surrounding sites was lesslikely to yield organisms at catheter removal.1 Inanother comparative study, skin specimens weretaken and studied both by culture and Gram

ed.

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T. Meek240

staining. The use of chlorhexidine resulted in alower likelihood of organism growth (5.7% vs.32.4%), despite the fact that organisms were seenin the hair follicles in similar proportions.2 Chlor-hexidine was effective earlier and more potentlyagainst all organisms grown. In a study solely ofpovidone iodine skin preparation, microbial cul-tures were positive for skin swabs (3.5%), epiduralneedles (34.6%) and catheters (45.8%).3 There wereno spinal abscesses in any of these studies, but thesuperior performance of chlorhexidine has ledmany practitioners to favour its use. There arethree important caveats: it must be allowed to dryto be effective; pooling must be avoided toeliminate the risk of inadvertent ignition bydiathermy; and care must be taken not to con-taminate neuraxial needles and catheters with thealcohol-containing solution. In addition to choosingthe correct skin preparation, the minimal time andexpense involved in wearing cap, mask, gown andgloves for every regional anaesthetic seems aworthwhile investment. It is difficult to see anyrisk to the patient from adopting this approach, butthe potential benefits are clear. In one case report,four cases of iatrogenic meningitis following spinalanaesthesia were associated with a single anaes-thetist who did not wear a mask.4

Factors influencing success

The aim is to locate the epidural space at the firstattempt. Multiple attempts are associated withcomplications and may be traumatic to tissue and/or unpleasant for the patient. A prospective studyof epidural and spinal anaesthesia in 1481 patients,of which epidurals accounted for 637, examinedpredictors of successful block.5 All aspects of theblock were at the operator’s discretion. Assess-ments were made of: patient characteristics(biotype, body habitus, quality of anatomicallandmarks), technical factors (degree of spineflexion, needle type, approach, level, patientposition (lateral vs. sitting)), operator experienceand complications. The block was considered asuccess if surgery could proceed without supple-mentation with opioid or general anaesthesia. Thestudy found that operators with greater than 5years experience had significantly higher success,whereas those with less than 6 months experiencehad significantly higher failure. Of the otherfactors, ability to attain good spine flexion andgood quality of anatomical landmarks were the onlyones to significantly increase success rate. Theimplications of these findings are two-fold: we need

to ensure the best possible positioning of patients,which is facilitated greatly by having an experi-enced and trained assistant, but also need toensure junior trainees are appropriately super-vised. Prior assessment of patients scheduled forepidurals may allow forward planning, includingavailability of senior supervision.

Methods to aid location of the epiduralspace

Accessing the epidural space at an appropriatelevel is important in determining the level of theresulting block. It has been demonstrated thatanaesthetists are poor at accurately determiningvertebral level by palpation. In a study where MRIwas used to confirm or refute anaesthetists’assessments, they were one space higher than theythought in 51% of cases, two higher in 15.5%, threehigher in 1%, and in one case (0.5%), four spaceshigher.6 The level of the tenth rib has been shownto be a useful landmark in ascertaining lumbarvertebral level.7 Typically, on lumbar flexion, itcorresponds with a median level of the L1�2

interspace. Its distribution is at least as reliableas that of Tuffier’s line, but it may be more easilypalpable in larger subjects. Ultrasound has beenproposed as a useful technology to aid correctplacement of epidural catheters. It has been shownto identify the correct anatomical level signifi-cantly more often than by palpation alone (71% vs.30%) and was never wrong by more than onespace.8 It has been used to identify the ligamentumflavum and epidural space and thus gauge needletrajectory more accurately.9 It has been demon-strated to result in fewer puncture attempts,increased first time success rate and decreasednumber of levels punctured,10 and has been shownto be associated with a reduction in postoperativepain and increased patient satisfaction.11

Loss of resistance—saline vs. air

There is no consensus on this question. However,there are many case reports describing a number ofcomplications relating to the use of air.12 Pneumo-cephalus has been reported many times, even aftervolumes as little as 3mL. It is often asymptomaticbut can be accompanied by a severe headache,nausea and vomiting, seizures or hemiparesis.Nerve root compression has been described, withcomputerised tomography confirming air bubblesimpinging on the symptomatic root. Delayed

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Epidural anaesthesia and analgesia in major surgery 241

recovery of neurological deficits has also beenreported. Subcutaneous air has been reported,associated commonly with multiple attempts.Venous air embolism causing cardiovascular col-lapse has been reported in children, and Dopplerstudies have demonstrated intracardiac air embo-lism. Inadequate analgesia following use of loss ofresistance to air has been postulated to be due toair surrounding a root or roots, preventing localanaesthetic penetration, and there is radiographicevidence to support this. With no adverse compli-cations reported relating to loss of resistance tosaline, it is difficult to strongly support the use ofair. Indeed, use of saline may be positivelyprotective: injection of 10mL of normal saline viathe epidural needle prior to passage of the catheterhas been shown to decrease the rate of venouscannulation.13 A commonly quoted defence of theuse of air, namely that it makes it easier to detectdural puncture is debatable, and if operators likethe feel of compressibility that comes with usingair, it is possible to use a syringe of air, but with theneedle ‘loaded’ with saline and the syringe filledwith saline and air.

The hanging drop method has recently beenreappraised.14 Compared with loss of resistance toair, it resulted in the Tuohy needle protruding agreater distance into the epidural space, possiblyfurther increasing the risk of puncturing the dura.One stated benefit of the hanging drop method isthat the operator grasps the wings of the Tuohyneedle with two hands, potentially conferringgreater stability and control. A system has beendesigned and successfully trialled which has thedual benefit of allowing this two handed grasp,whilst retaining loss of resistance to saline techni-que. The physical feel of loss of resistance to salinewas transduced into an auditory signal.15 In thetrial, a second operator applied pressure to the lossof resistance syringe. To make the device clinicallyuseful, pressure could be generated mechanically,and trials of just such a modification are planned.

Length of catheter to thread

The optimal distance that a multiorifice cathetershould be threaded into the epidural space hasbeen studied in labour analgesia,16 where 5 cminsertion was associated with the highest incidenceof satisfactory analgesia. Insertion of 7 cm wasassociated with the highest rate of insertioncomplications. The proximal orifice of the catheteris usually just less than 3 cm from the tip, and soinsertion depths close to this runs the risk of

excessive inadvertent catheter withdrawal. Thisstudy has not been repeated in a non-obstetricpopulation, but the results would seem to begenerally applicable.

Nerve damage

Nerve injury can occur at the time of epiduralinsertion, usually via mechanical trauma, whichwill elicit symptoms in the awake patient. This isthe most powerful argument for performing epi-durals awake. Nerve injury can also becomeapparent later, with the most worrying causesbeing unrecognized trauma, epidural haematoma,epidural abscess, or meningitis. Less commonly,local anaesthetic toxicity, intracranial haematomaand anterior spinal artery syndrome have beenreported. All studies agree that severe or disablingcomplications of epidurals are rare. Because of thisrarity it is a difficult phenomenon to study unlesslarge numbers of patients are included. However,the incidence of persistent peripheral neuropathyfollowing epidural is consistently less than 0.1%.For instance, in a combined review of 50,000patients17 there was one case of cauda equinasyndrome, one case of paraplegia and three casesof meningitis. Cheney and Auroy and their collea-gues have published two recent studies18,19 thatprovide useful information, concentrating predo-minantly on nerve damage following regionaltechniques.

Cheney et al.18 reviewed cases in the AmericanSociety of Anesthesiologists’ Closed Claims Project,which takes information from the files of 35 USprofessional liability companies. Of the 4183 claimson the database, 670 were relating to nervedamage, the second most common cause, withonly death being more common. Nerve damage wasmore commonly associated with a regional anaes-thetic technique than general anaesthetic damagein both spinal cord injuries (58%) and lumbosacralroot injuries (92%). Of the 4183 claims, 2651 werenew since the group’s last report in 1990. Of those,445 were for nerve injury and were analysed indepth. The commonest causes of spinal cord injurywere epidural haematoma, chemical injury, ante-rior spinal artery syndrome and meningitis. Wherethere was a spinal cord injury, 50 (68%) were in acase where a regional anaesthetic was adminis-tered. These included 35 lumbar epidurals, fourthoracic epidurals and nine spinals. Major associa-tions were blocks for chronic pain, and blocksperformed in-patients receiving systemic antic-oagulation. In the latter (13 cases), all suffered

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Table 1 Complication rates, per 10,000 epidurals(95% confidence limits), data taken from Auroyet al.19

Cardiac arrest 1.0 (0.2–2.9)Death 0Seizures 1.3 (0.4–3.4)Neurological injury 2.0 (0.4–3.6)Radiculopathy 1.6 (0.5–3.8)Cauda equina syndrome 0Paraplegia 0.3 (0–1.8)

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epidural haematoma resulting in paraplegia (11epidurals, 2 spinals). All were vascular surgerypatients, undergoing surgery or diagnostic proce-dures, and all had intraoperative heparin. A majorrecommendation was that care be taken wheninterpreting persistent postoperative lower extre-mity weakness in such patients. Where there was alumbosacral nerve root injury, 62 (93%) wereassociated with spinal or epidural (37/62 and 25/62, respectively). Importantly, major associatedfactors were paraesthesia on needle or catheterpassage or on drug injection, or multiple attempts(although these factors were disproportionatelyless common with epidurals than with spinals).The introduction of low molecular weight heparinsaw a new flurry of case reports of epiduralhaematoma after regional anaesthesia, more com-monly with epidurals than with spinals. All theclaims in the database at the time of analysispredated the introduction of these drugs, so futureanalyses will be interesting from this viewpoint.

Auroy et al.19 analysed a prospective multicentreseries of more than 100,000 regional anaesthetics,including over 40,000 epidurals. Six complicationswere specifically sought, and the findings arepresented in Table 1. The risk of complicationswith epidurals was less than with spinals for allexcept seizures and paraplegia. Increased seizurerisk may be explained by the greater volume oflocal anaesthetic used in epidural blocks. In thesingle case of epidural-associated paraplegia, thepatient had suffered intraoperative hypovolaemichypotension, so cord ischaemia may have been themechanism for this outcome. In summary, thisseries confirms that serious consequences of epi-dural anaesthesia are rare.

Treatment for bupivacaine toxicity

Severe systemic bupivacaine toxicity can result inhaemodynamic collapse, intractable dysrhythmias

and death. Traditionally, bretylium has beenadvocated as the only specific agent of treatment.There is now evidence that Intralipid 20% is anextremely effective treatment. In animal studies,it has been shown to increase the toxic dose20 andto reverse cardiovascular collapse deliberatelyinduced with bupivacaine.21 The postulated me-chanisms are that the lipid simply acts as a ‘sump’for bupivacaine in the plasma, or has some morecomplex effect on mitochondrial enzyme systems.In the event of bupivacaine-induced cardiac arrestthat is unresponsive to standard therapy, in addi-tion to standard cardio-pulmonary resuscitation,the following dose regime has been recom-mended:22

�

Intralipid 20%, 1mL/kg over 1min, � repeat every 3–5min, up to 3mL/kg total dose, � then (or sooner if stability is restored), convert

to an infusion at a rate of 0.25mL/kg/min,continuing until haemodynamic stability is re-stored,

�

a maximum total dose of 8mL/kg should beobserved.

Because of the rarity of such serious toxicity,there are as yet no case reports of this regime beingused in humans.

Epidural opioids—some recent findings

Diamorphine, and more frequently fentanyl, arethe usual opioids used via the epidural route in UKpractice. Dorsal horn m-receptors offer the possibi-lity of providing analgesia without the motorweakness produced by local anaesthetic agents.Additionally, opioids can be reversed with nalox-one, whereas nerve conduction block cannot bereversed. Usually, epidural opioids are used inconjunction with local anaesthetics, allowing alesser concentration of each to be used; each has adose-sparing effect on the other. A combination isgenerally accepted as the most effective option.The conventional view is that lipophilic drugs suchas fentanyl and diamorphine are rapidly taken upinto the circulation or absorbed by epidural fat andwhite matter and exert their effect systemically.Morphine, being hydrophilic and ionized, lingerslonger in the cerebro-spinal fluid. Its low lipidsolubility means that it is preferentially taken up bythe grey matter of the spinal cord, where theopioid receptors are, rather than by the whitematter. This mechanism is supported by the resultsof a recent study, which used a microdialysiscatheter technique in pigs to measure directly for

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Epidural anaesthesia and analgesia in major surgery 243

the first time the pharmacokinetics of epidurallyadministered opioids.23 However, the true pictureis not so simple, as recent papers have shown thatfentanyl can have a selective spinal action. Ginosarand colleagues24 have found evidence that whenlipophilic opioids are given alone, i.e. with no localanaesthetic, by infusion they do indeed actsupraspinally, but that when given by bolus, theyhave a predominantly spinal action. This suggeststhat the common practice of adding fentanyl toepidural local anaesthetic is not simply a conve-nient way of given a systemically acting opioid.However, in clinical practice, epidural opioids areusually given in conjunction with a local anaes-thetic. When a continuous infusion of 0.125%bupivacaine was given in labour, co-administeredfentanyl was three times more potent if it wasgiven by the epidural than by the intravenousroute.25 This suggests synergy; the addition of localanaesthetic confers spinal activity to the fentanyl.Similar results have been produced for sufentanil,another lipophilic opioid, in-patients undergoingmajor abdominal surgery.26 This apparent synergyhas even been demonstrated with bupivacainesolutions as dilute as 0.01%.27 Diamorphine isrelatively lipid soluble, but it is converted to lipidinsoluble morphine in the tissues. This allows it tocombine the benefits of epidural fentanyl (rapidonset) with epidural morphine (prolonged actionwith a small dose). Perhaps because of its pecu-liarity to the UK, studies of diamorphine are almostexclusively limited to its use in spinal anaesthesiaor in labour epidurals, and there is far more datarelating to fentanyl. However, epidural diamor-phine has been shown to produce equivalentanalgesia to epidural fentanyl (both in combinationwith low dose bupivacaine), with a similar side-effect profile,28 and it has been shown in acomparative trial to require smaller dosages whencompared to the subcutaneous route.29 In the realclinical world, the issue is further clouded by thenumber of possible local anaesthetic/opioid per-mutations, the number of bolus/infusion/combina-tion administration regimes and the wide variety ofclinical applications. We are far from identifyingany one ideal regime. For a comprehensive reviewof all the commonplace and experimental spinallyacting anaesthetic/analgesic agents, readers aredirected to Bowen and colleagues’ recent article.30

Epidurals and anticoagulation

The most worrying risk relating to placement of anepidural in an anti-coagulated patient is of epiduralhaematoma leading to permanent neurological

damage. In the literature, the risks relating toepidurals and spinals are often studied together.There have been a number of large case reviews;which when taken together, amount to hundreds ofthousands of patients, demonstrating no or verylow numbers of epidural haematomas or neurolo-gical sequelae.31 Whilst not all patients werespecifically anti-coagulated, this demonstrates thatepidural insertion is clearly a safe technique. Evenin case studies where anti-coagulants were given(orally or systemically), large numbers of patientshave received epidural anaesthesia with no hae-matoma reported. However, none of this shouldencourage complacency. It is worth noting thatwhen case reports of epidural haematomas areanalysed, the majority of patients have some typeof coagulopathy present, sometimes iatrogenic,sometimes pathological. Technical difficulty or abloody tap is a frequent feature of these cases.

Clopidogrel is a newer drug, which inhibitsplatelet function by antagonizing platelet adeno-sine diphosphate receptors,32 and whose effectpersists for 7 days after discontinuing treatment.Most practitioners therefore stop clopidogrel for7–14 days pre-operatively.

The European Society of Regional Anaesthesia(ESRA) has produced a draft set of clinical practiceguidelines relating to neuraxial techniques in-patients receiving thromboprophylaxis.33 A sum-mary is presented in Table 2. A final version is duelater this year and will include clopidogrel andother newer agents (personal communication, Dr.Barrie Fischer). It remains important that anywritten protocols are agreed locally. This isespecially important in those clinical specialityareas where abnormal clotting (whether iatrogenicor pathological) frequently coincides with regionalanaesthesia techniques (e.g. vascular surgery,obstetrics).

Obstetrics

There is a high rate of epidural use in obstetrics.Parturients have high expectations of anaesthetistsduring this time. They also expect a rapid return tonormal function following childbirth.

Postdural puncture headache

The condition and its treatment have recently beencomprehensively reviewed.34 Accidental duralpuncture may or may not be noticed at the timeof passing the epidural needle. Puncture of thedura with a 16 gauge epidural needle will result in

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Table 2 Summary of European Society for Regional Anaesthesia’s draft guidelines for thromboprophylaxis inpatients receiving regional anaesthesia.

In all cases, monitor patients’ neurological status carefully. Treat suspected spinal bleeding as an emergency (ifdecompression takes place48 h after onset of paraplegia, prognosis is poor). Generally, single shot spinals aresafer than epidurals. If epidurals are used, low dose local anaesthetic regime with opioid is generallyrecommended (easier to monitor motor power)

Oral anti-coagulants Stop medication prior to procedureInternational normalized ratio (INR) or prothrombintime should be checked and seen to be normalbefore regional anaesthesiaCaution with interactions with other drugsDoubt exists regarding safe timing of catheterremoval (INR o1.5 recommended)

Anti-platelet agents Very low risk if no other risk factorsIf possible, discontinue 3 days prior to surgery (lesspermissible for some non-steroidal anti-inflammatory drugs)Spinal preferable to epidural if therapy continued

Fibrinolytics/thrombolytics Very high risk—great caution advisedConsider risk vs. benefit carefully in individual cases

Low-dose unfractionated heparin prophylaxis Delay administration until 1 h post needle placementor catheter removalWait 4 h after dose to remove any catheterCare when other drugs used

Low molecular weight heparinLow dose (e.g. enoxaparin 40mg) Delay administration for 6–8 h post needle or

catheter placement or catheter removalWait 10–12 h after dose before administering blockor removing catheterEvening dose on day prior to and day of surgery isacceptable

High dose (e.g. enoxaparin 1mg/kg) Wait 24 h before needle placementAvoid use of catheter techniques if high dose regimeto continue postoperatively

Therapeutic anticoagulation with unfractionatedheparin

Intraoperatively, up to 5000 iu heparin i.v. is notcontraindicated (if no other risk factors and withappropriate postoperative monitoring)Wait41 h after needle or catheter placementPartial thromboplastin time (PTT) should be checkedand kept p1.5 upper limit of normalWait 4 h after stopping infusion and ensure normalPTT before removing any catheter

T. Meek244

headache in approximately 70% of cases. Manytreatments have been suggested as helpful: bedrest, hydration, abdominal binders, desmopressin,adrenocorticotropic hormone, caffeine, sumitrip-tan, and epidural infusions of saline or dextrans.None have been shown to be efficacious incomparative trials. Epidural blood patching is theonly treatment that has been shown to be effectivefor headaches that do not respond to conservativemanagement.

Neurological complications of obstetricregional analgesia

It is very common to be asked to review post-natalpatients with a neurological deficit apparentlyassociated with epidural (or spinal) use. All suchreferrals should be taken seriously and assessedwithout delay. The ‘normal’ spectrum of epidural-related complications is seen, and these problemsshould be assessed and treated in the normal

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Epidural anaesthesia and analgesia in major surgery 245

fashion. Perhaps the most common is transientweakness or numbness in a single root distribution.Most problems will recover spontaneously over daysto weeks. It is also important to remember thatthere are a number of obstetric nerve palsies, i.e.those which occur as a result of the process ofchildbirth.35 Generally, these are peripheral nervelesions affecting the nerves supplying the lowerlimb, commonly the lateral cutaneous nerve of thethigh, obturator nerve, femoral nerve, and com-mon peroneal nerve. With these, patients cangenerally be reassured that they are unrelated tothe epidural. Recovery is generally to the sametimescale as non-obstetric nerve palsies.

Backache

We can now reassure parturients that epidurals forlabour do not appear to cause or worsen backache.In a randomized controlled trial, 369 women inlabour were allocated to receive either epidural ornon-epidural analgesia. There was no differencebetween the groups in backache at 3 or 12months.36 Further follow-up of 306 of the womenat 2 years demonstrated no difference in self-reported incidence of back pain or mobility, nor inphysical measures of mobility.37

Future

The epidural is a well-tested anaesthetic andanalgesic technique, but as this article demon-strates, there remain many areas for fruitfulresearch which will help us further improve itssafety, simplicity and efficacy in a wide variety ofclinical situations.

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