Intraspinal opioid therapy for chronic nonmalignant pain: Current practice and clinical guidelines

*eciuI

Section on opioids fm Nonmdignanc

Pain, Part 3‘

Intriispinal Oploid Therapy for Chronic Nonmalignant Pain: Current Practice and Clinical Guidelines

Chronic pain. hesides causing untold sulfering for mil!ions of patients worldwide, lean at rhe vcrv economic nod social fdhric of our culture. It’is esdmawd &u approximarcl~ 3o:L 01 the general populadon of 01‘: L!r.ited Stara su.Tcn fro.m chronic pain;’ this accouno tar 7O.OOO.C00 people. According 10 Lemrow er at., !nck pain is Ltle wrond leading rcacon for hospital admissions in the United Stares.’ In a 1992 stmiy on the dollar impact on 12 divene.

necame of the m,ll,tdil,,el,cir.n;II na,~re o! cbrwlic pain. treaunen, op,ions for thczc patim are “““W‘o:H Trca,mcn, strdtcgie for chronic nonma1.g nan, pain ,+outd obey the principle It,&, Ircc invasive and less cosll:~ in,cr\rc,irms lw par: treahnen, should he toed hcforc .,sint: nwrr costly and more iovarivc in,crwnuon\ Uriliring Lhis princ;plc:. in,-rvcnlions lor syndrome:specific, chronic pain stare% are liswd hx onlet of inva;ivcnes\ and co<,. This liz,ing of in:crventionc hy incrcaing order of complexi,) and cost is crllcd a rdin treatment con,it:rrwu or pain ,rea,mcn, atgorilhm. Lor ir,\rri\e and less expensive ,rra,men,s arc :II,:3 bcfox more invasive and more rxpcwivc imel vew lions and dirralded hasrd on lbtlnre of rcsponsc for more complex 2mI ~~os,l!; interbentions until an ,n,crvenliorl 8s f.iurrd ,h;rr i\ cflicacious. Spinal analgesia. au illvasivc and cosdy ,cchnologicdt mwiAi,y for p;:‘n ,re;,,men,. including spinal opioids, don have A n,ional ptare in ,hi* ,rea,n;en~~ ro;r,irwum for the trc.atmem ef somr chronic nc.-lmalignali, pain paiems. Opioid ,hcrapy for non-canrer-related pain. stilt [cd+ xmainz a cx,roversidl iswc with many lay pmons, gover”n,e”, legutators. and even healthcarc professionals believing rha, the use of opioids are coniraindicatcd rind counterproductive in ,hcrc pa,icn,s. There people erroneously believe rha, rhc use of opioidr for r.onmaliguzan, pain HI!I inr?liabl) lead IO ,olera~e. druy: abuse, and addiction. These fean. now pcru-asive. were hxwd on da,a ohtlinrd bg questioning a populatior: of addicts a( to how ,hey became addicvd to opioids. That dru suggerted a causal rclatiowhip be,~ecn zddirtion and ,be ia,rogenic prescription of opioid medira,ions for pain control hy physicians.‘,” Unforrunawly, ,bese s,udies were inrricsically biawd by Lhe far, tba, ,hc sample popularion s,,,died were all addicu. Theses s,udies were no, conrrolled 1~) seeking inpu, from non-addicted parier:;s given opioid medications ,o control ,h:-;r pain. In the las, IO pan. howver, mnny re,roS~CCI~VC and prospecrive s,udi.:s, ,e?,ing samples of patienu with nonmalignant pain treated wilh opioid mediadons, sugge\r a ton incidence of ,olerdnce formation. few if an) pharmacological advcne consequences, and 1 low incidence of ia,rogenic addiction with the

Fig. I. A pain trcaunenf ront~nuum. and ali SnGhle vcatmcnt modalit es that are appropriac 101.the paticn~‘r specific pain s)mdromr. Chronic pain is almost newer uoidimensional. but almost always muiiidimcnsional involving neurophyriologir;xi mechanisms as well as emotional and twhavioral mechanisms. Because of the multidimensionaiir; of chronic pain, the developmen! of a mullidisciplinary ;~isessment and trealmenl plan is maadarrry Lo asure a wccessfol outcome. Choicn for the treatment of chronic nonmalignant pail,. utilizing molridiw-iplinary interventions, inctuoc cognili\e,‘hchavioraI pychologiral tbenpirs. fiznrtional rehahilitalion therapies, orthopedic and nr.lrological surgcrv, pharmacolherdpin, anestheti< biocking wchniqucs. neoroaugmcntarive proredures. and finally neur )drstrortivr prorrdurcr. An example of a treatment continu~*!n Ibtmg inwrvcntions by increasing complexity and invasiveness is found in Figor? I. Psychologic mrchanisms arc operant in manypatienlrwirh chronic pain. A: the ;‘c:‘v Ieat, some :hronic pain patienLs mav meleli lack coping skills neceuary ior intcnoal. self pain modulation. while wmc paticnn m:?) derive onconscious cecond.u 1’ gain* from hav ing pcnislenl pains. SorIle palien nlay ba\c personality or neurotic barrier3 to sl~cccssful pain rlranagrmrnt including .iddicti!c pcnooalit& bpteria, hypochondriasis. or dcpresGon. AL the other psychologi: cxm~~~ penis-

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Medical management of chronic pain patients should include rhe skills of a widr variety of hralth-cdre profcsConals and mav include thr skills of ancrthcsiologtsts, nrurologisu, swqerns, physiatrists. nurses. ph+cal rhrrapita. occupational therapis& psyrhologislr. psychiarrists. addictionolot+s. and cocational rehabilitation specialia. The treaunent of chronic pain patients should have, a one of its primal y goals. the restoration of prvcholol(ic. rrrlotir,:irl. amI physical function. The goals of psychologic ueatment is to rcstol~ emotional well-being through r;w development of enhancing WCcessful coping stralcgies and improring social interaction. The goal of p!lyrical resrontion is to restore, through excrcisc, ph!rical :berdpy, and occupdtional therapy, the pwen~. to a.. near-to-normal phriral function as thcv had prior to their injury or pain proces,. Pharmacologic medical managemmr of chc patient with chronic pai. utilize5 medications that have bee;) shown to be eftiracious foletdrL1 n,k
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longer acting opioids include methadone; levorphanol; long-acting. c~ui~rollc~’ -J-M morphine prqurationr: and the transdermal dclivrrv of fenl;lnyl. Z!nlike MAIDS, which have ciiling effect, opioids do not. Dosages 01 opioids can consistently be clrwed to rnw~ the increasing requirement of the paint’s pain. More drug, if ride cffwls do not occur. might, in fact. he hrttrr than less drug. Side effect, of opioid medications include inanicitrn. I )s2 of appcrirc. nausea and vomiting, sedatiorl, corlsrlp3rion. ur;naly rewnrion, depreGon of the h}po,halamir/l)iruItary axis, hallurinadons. dry mauh. weaGog, aad rrcprarory drpression. Sot all patients develop sioe rffcca to opioids. and not all patients share the wne intolermccc IO opioids. Sonic patient.\ may tolerate ooe or more of the oi’ioidr. but not all: some patienu may WL mlcrate ally; and 5ome pairnts rmy Iolerav all. II a patient fails to loleratc onr opioid, anorhcr shwld he tried until one produws analgesia without undue sidr eficr&. This seqwntial drug wial should he performed before abandoning opioi? therapy. Nonopioid, nonarnntgesic tab&d medica!mns, o!her than th< iVSAlDs. that have some dcgrec of analgesic elfiraq for chronic pain syodromrs are called. as a class, adjurlctive mediiations. These adjunctive medications include !he herrroc~vctic anddcpressanlc, the nouherc Iwzclic. serotoninenhancing antidcprcssanu \ ~CFL4.s). the anriconwlsant medications. y-3’ ‘:nohutync acid (MBA) ~:lalogws. Na ‘~bawc~ blocking agents. memhnnr SCMiring agcn~r, Ca”
agent tAxz~ time and patienrs should he LOUOseled to have paience. As one can see from this iredm~eni LOIItinuum. interventional pain managrmen,. and certainly implanlable .echnologic~ for pan control. such aq implantable infuGon:*l analgesia, should be therapies of 1~ resort hefore neuroablaive and ncurodest: uctivc procrdurec. Implantable trchno!ogies for pain control are more recent advances for the treatment of rhwnir pain and are reiativcsy expensive compalrd to nonsurgical mferve?tions for pain conlroi. Inlrdspinal opioid lhcrapy for nonmalignant pain should be used when more coxervative. noninvasive rhrlapies fail 10 provide analgesia. As WC w+ll WC. intraspinal opioid therapy, when used apprw prialely. in an appropriate manner, in :he appropriate patient, will add immeawnhl~ 10 the aforementioned @ols-of-thc-trade for the pain care warn.

Ztlfusionai and Drug

spinal Analgesia Administration Systems

The discovery of opioid receptors and endo enous compounds in the spin&! g cord’ -I4 provided a rationalc for ear:) aaempta to deliver opioid drugs inhxspinally, first in experimental animab”~“ and then in patiencs with chronic pain.“.‘” Tbb experience with “sekcliw qht analpiTa-“’ appcmd 1” oficr specitic beneli& to some patienti and H-AS followed by trial:. of ~ontinuom subararhnoid opioid inhrsions using im lamed pump with factory prerat flow laws. L&l‘- During the pat decde, pubtished repom and abwaco in dr U.S. literature have repeatedly documented the safety and efficacy of implanted nonprogrammable and programmable pumps for Ihe lo;lgterm subarachnoid delivery of o ioid drugs in dvmzma~e-nnf cancer pain’-” and nonl’hn doc~w~~,,ed efficacy. howw, may be subiect to sperilic opioid-responsive or opmidresistant pain sylldromvs.“‘-” ‘~ocic?ptiix $r. defined ac pain mediaccd b+ oociceplors, wideI! distribu’ed in the aoma UC the bfxl;, Is often chafi?wistically dew&cd by patien~r in such terms as “dull. aching, sharp. or throbbing pain.” Socicepton respond to mcrhacicat. (hermal, and chemical noxious sGrnuli awl “uanc duce” Ibis nw.wu~ inLi:nation inlc eleclrical

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Surgical Tectniqw In our practice. all patients wirh nonmzatignant who Law failed ~.onwr\ativc. ICD invaivr proccdurn, who hav: rrreivcd a positive wiat for innxrpinal oploid therapy. zw’ implxned with Mcdwonir Sy~~chromcd 8615-S pump\ wilh side ports. Ycdtronic, 8703-M’. rilaslic calhetrn are alway, placed inrruhrcatlv. anr! the calhe~er tip is placed as close to rhe spinal cord level mediating and prucessmg rhc paticm’s pain. Thhcre pumps, unlike the Infw said, model 400 pumps arc programmable and therefore mow versalile in tailoring the therapy to the rarying needr of the paCent. The use of a side port in 111r pump alla3 the pracUoner ease of problem solving any future loss of analgesia Uar might he hardware or cahcter r&&d. The Medtronic Synchromed totally programmable pump s\aems (model 8611 and 6615), figure 6, and the Infusaid model 400 factory pre-set flow Exe pump. Figlrre 7, rep resent wo di&rent implantable sy~wms that have been approved by Ihe Food and Drug Administration for clioical USE.

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11 ir our practice to perform this qnmtion under f!uorosco?ir guidanre. Placing a calhwx aqwhcre in;a Ihe thcral sac suffice\ if om- is io rely wtety on hydrophilic opioid agew:. such as morphine, ;md,‘or hgdromorpho!w. C’onrmuous infusion of these hydrophilic opioids is fotlorxd hy general mixiq of these agals throq$our the c-rwbmt spinal flvid. Chcr rime. these agents, if plxcd anyuherc inw the cclrbral +nal fluid. wilt “butMe-up” LO high spiral segments and ruplastrinal ccolc13. If it bccomcs ncwssar) lo IISC lipophitic opioids. such as mcperidinc, fenranyt. sufcnwnit, or methadone at some flmwe Lime, it is important 10 place the catheter tip as close PS possible 10 the spinal scgmcnr mediating the patient’s pain. These tipophilic ;~gen~q dilfusc directly into the lipid aubswncc of the spinal cord around Ihe tip of the intnspinal cathrwr and usoually do not buhhte-up in the rerehral spinal fluid 10 higher spinal wgmrnls 01 supraspmat centers. tkwusc ot this kl. it i\ imperative 10 uw ftuoxoscopic guidance to place rbe spinnt cathctcr lip ;L\ close as possihlc 10 !he spinal regrmw mediating the parirnt’s pain. Afwr anrihiotir prophylaxis and inducdon anesthesia. the patient is poritionrd iv the left lawratdccuhitus position :f the operative wrgeon is right handed, or in the right tdre~a!decubiws poGlion if the ao~geon ia lefi handed. This paCent pori!ioning farititares surgeon‘s comfh for ptacemrnt of [!w tooh? needle from rhe caudal-to-rowat plane. The: innwpcrative ftuoroscopic unit (C-arm) is then placed rro,s-table from the position or the surgeon. The paricm is now prcppcd and draped in the usual surgtcat mamer. &%iuse this opcrdCon nccessiutes a mid low-back incision for

placement of’ the inrraspinal catheter a3 well as a h’ abdominal incision lor placement of the toMy implanted subcutanrorts drug adminis [ration system. both area mum be draped “out” for surgical access. In our operating room, rhic is accomp!ished using a split drape system. Split drapes are placed ahovc and below the prepped back, Ilank, and lower quadrant of the ahdomen. with the flanges of the spli: drape system outlining the bark and abdomen. As prwiously stared, the first procedure of the operation is inrlalhecal placemrnt of the spinal catheter da a I&gauge tuohy . $durdl needle. It is the standard procrdure of some surgeorn to place the intrathecal needle through the skin with fluoroscapic guidance, prior to making an incision. Onre the catheter is advanced into rhc thecal sac to the spinal “targrc.” a5 determined hy the dermatome of origin of the patient’s pain, an incision is made around the needle and carried down to the supraapinouj fascial plane. It is our practice, however. to make an in&ion from the skin ;o Ihr suprdspinous Pacia prior to placing the tuohy needle. which is then advanced through this incision. Our usual location for this skin incision is between L’L-3 and 1.4. At this point and Ficqcently during tie operation, meticulous hcmoqtaqir is provided by electror-autcry, and the wound is copiously irrigated with an antibiotic solution. The appropriate length of the iccision depends upon the amount of subcuwn:ous fat tissue. Because the in&on ha the dllal Iunction of ailoHio both anchoring and II-nneling of the catheter, a smail I- to 1.5inch incision ur*~ally suffices in patients who are extremely thin. A large; iucirion may be req,tircd fol patients who are obese. Prior to placing the nec.dlr, a small subcutaneous “shelf’ is created at the base of the wound dt the level of 1:~ supr~spinollr fascia using a combinwioo of sharp and blunt dissection. This shelf. underlying the suhcolanews tiswrs a, th: lewl of the suprapinola fascia or peril.tmhar l%xia. permiti excess intraspinal rarhe,cr. exiting the la+ ch. ,o have a gentle curve and swwp for cow nection to the “pump” catheter. F;rilure to create thts genrle curve in the cathctrr br,fore tunneling might cauw kinks in the iathrtcr later on hy scarring around the ca!bcter. Iikewise. it is also important that the needle entel

the supracpinous fascia at the rostra! and not rbe Laudal end of the incision. This maneuvr; also inuucs thar the inlzxpinal catheter, exiting tbc supraspinous fascia. has rufficirnt room raudally for a gentle and not-toabrupr sweep for connection to tbr pump cathetrr. To facilitate easy and I-eladvely ohstructio:~ ltcc catheter plaremem. we recommrild a shallorr, angled paramedian placemertit oi the tuohy needle. This mane~~ver allwn eas) rostrdl .xdwncemcnt of [he intraspirlal catheter in the intndwcal space. If III- ncrdle (men the intrathccdl space with .a very PCIIW or strep angle (SW-30’). a !J often seer? when using a midline needle rrpproach. nt is the natural inclination for the carhrte~, wbcn ddvnnccd. to ahut against Lhc an:erior thecal sac, making it wowwhat difficult to adnncc the catheter ro5rrally. One czn xe ,;nt dlc shallower and lets acute the placement of the needle. rhr eaicr it would be to adnncc the cathrter rortrally. L!>ing a shallow. less than 45’ angle, our nrtdlc tip usually enten rhe suprxspinous fatcia from a paramedian approach at 1.2-3 or I-34 Hith the needle tip finally rnrexing the thecal sac at ahout L1 o: 1.2. This paramedian approach also precludes tenting or sanduiching of rhe pow~ior dural sac against the antcrior dural sac by the adxmcing tuohy needle sometimes seen osing the midline approach. W’hcn sandwiching of the posterior to anterior dura: membranes occurs, cerebrospinal fluid flow is obwuaed, making it difficult to asce:tain chrlhrr or nor the ncedlc is indeed within [he intnthccal space. It i3 verv important to ensue that adequate hemosusis is accomplished hcfore closing thcsv in&ions. The use of direct pressure on bleeding points or the judiciou UK of the eler~rocaurery is mandatory in ensuring that proper hcmo%asis is accomplbhed. Closure of wounds on active hlceding ma)- lead to exccssise postopcraive infections. Once the cathew tip is placed at the spinal segmer., prowssing *he patient’s pain, it is thr practice of Fonle nlrgeom to place .I purjestring !?Xl silk xrture into the supnspinou5 fascia around rhe Itrohy ntedle before rem&r,! the needle to prevent cerebrospmal !iuid ((SF) from entering the subcu~~e~:~~s shelf from around the nevlie. A collccrion c.f CSF from this hack flow along the cxheter into the subcutaneous space is cal1v.i a CSF hygroma.

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The silaic cowring over ,hc nipple ou~lc~ of ,Jle pump murt be rernovcd to allo,, f,rc Ilow of the purged drug, and ,bc. p,,mp is replaced into a bath of WI m ,c; ho, wwr ,o enwre proper hca,ing of ,hc pump. Some of the Medtrorlic 8615 pumps and the Inf’waid model 400 pwnpc are prorided ldth suture loops 10 secure them to the abdominal fascia under [he pump porke:. Other SYRIChroMed Medtronic pumps are provided \;i,h a Dacron pouch which should hr carefully placed over the pump. The Dacron pouch suvcs the same ancfioring func,io,, as the su,urc Io+ps. ficr ,imr. tibroblarls inradr this

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receptor aftinicy, cross rhr dwa awl enter thr lipid subswncr of rhr spinal cord slowly, hut remain bound for prolonged period\ 01 lime. Il~nre, the onset of analgesic action for hwlrophilic opioids is slow. hut andlgcC~ is genrrallv prolonged for approxim;.tely 12-24 hr. Berause of iIs low lipid wluhility. or high hydrophilicity, more drug remains in rhc. (ZSF and thrrcfore is available 10 asrend 10 sllprd’pinal ccntvs through bulk flow of CSF. Because rf thic hydrophilic properr> of drops such ar morphine. placrmen~ of a cdlhcwr for intralhccal infusion of the *h”g an)whcrc in the !hecat sac ensures dnatgeCr an!vhere in the hady. Risks of CSF side elfera such a5 sedatiorl. nausea and vomi.ing. and rrrpiralory dcplession are greater in this hgdrophili< group of opioid5 rhdn in those 16th higher hpid roluhility and higher rccepmr afiini[y such ac fenmnyl or rufcnr;lnil. As expccred from its physical-chemical proper;ies. lipophilic drnpr. wch as sufrnranit, have a rapId ~nsc~ of a. don nnd a prGngrd duntiou of action. Once receptors arc 5x11. rdred with sufc ntani!, drug becomes awit.lbtc for rediclribwion through spinal w~scl uptake and CSF buik Ilow. Oversedation then can becomr a prohlcm. Becauw lipophilic agents enLer lie substance of rhc- lipidionraining spinal cord rapidly and arc quickly rliminared from thr CSF, catheter tip placement is eswntial for optimal analgesia. If one Sara !o use lipophilir agenu, and one should atway? pl;rn for such an evenuxdiry. the intrapindl cad1. cter tip should atways he placed a\ closr as pouibtr 10 the spinal cord segmenr processing and modxlating rhe pn:-m’s pain. The appropriare dose ofopioid for epiduml or inwathecal we ix highly individualized and depends on the patiem’s age, the patient’s pa” y.;rome. and the s)stemic dose of :hr Cn:g nerded for anatgesia before rhr decision LO move 10 inrrapinal dctivery. h a general rule, paliena with ncuropathic pain may require higher doses then normally seen with nociceptivc pain, and eldclly padealr usoally

tequil-c lers dose than patients who are )oungcr. The, closing 8x1 all pxientb, however, should bc illdivldualized. Figure 9 rrprescn~r the inuaspi.lal anversion that WC use in our cliuic for nwrphinc. For xariow reanon~. we oilen find ir ncccssary Lo use opioid agcnm other than morphine, ewn though these agents arc PJI lahcled for intraspinal we. Some patients do nor rotcratc morphine, hur tolcr.~tc rrhrr hydrophilic agents such as tl\rtr~,mort~h(lrl~~. ?n~metirnes. WC may HZ”, IO use more lipophitic agents. such as sufentanil, IO dccrexw supnrpinat effects such ar severe na~wx. Figxc IO representi a suggested cquianalgesic dosing chart for converting morphine 10 other opioid agenw. After impl?nution. we tin1 choose 10 deliver the 24hr inwatherat opiold dose .I\ :I continuous infwon. II is &en later found thal some pdticw do hr(wr with b&s or mixed continuous and bolus dosing. Some cancer p.ltients and more frequcnrl) parienls with mxmwlignant pain syndromes WC h as “failedhxh” syndromr Gnd their pain inrrcased at c:rlain Cmcs of the day. Therefore. ;:lese patirnrs. may benefit from a timed bolu\ dose :iddidon a( that appropriaw time of the day.

Inira.spk~l Admixtuvs for the Treatment of Chronic Pain If parienrs do not respand to sequential intmspinat opioid trials with different opioids, a srrateb~ wing Ihe pharmacologic property of synergy of wo distinclly differing clxs of aitive drugs ha.5 been shown cc be effcctiv~ in allimai:E,55m5” Several recent c!inical reporb show pwidve xralgcsic resr?vs:~ using admixtures of opioids with either local anc>thetics 01 alpha-adrenergic agents for 0~: rrcamen~ of’ cancer and non-cancer-related pain.“-“” Admixrures of morphine hydrochloride, hupiwcaine hydrochloride. and clonidinr hydra (hloride have bran shown IO h stable in rcscrvcnr b.tgs for up 10 90 dajs.“’

In our clinic, when padeors no longer leceivc analgesia with increasing doses of inwaspinal opioidy 1” an arhiwary ceiling ~120 mg of morphine intrdlhecal cquivalrnls, WC add the local anesthetic. bupivacaine 1” the opioid as an admixurr. Our slatic?; do9 of hupivacainc is 3 mg/day using Ihe h;ghcst available concrnwaGon of bupiucaine tc ensure relatively long rrlill periods This drse of hupivacaine is incrrawd by 20% per wxk until analgcsin or side r!Tects occur. Acrording 1” van Dongen et al., “eurologic side eifeclb I” inwalhecal bupivacaine do not occur before 25 mgi24 hr arc infused.”

Maqemenf

of Com$ications

During and after implanudon of a pump for intrapinal opioid therapy, the physician mw be prepared for problems that ariw. ?-?e complicationc ran bc hroadlv ratepw riled into surgical. mechanical, and pharmacological. B&ding Ulecding occw~ naturally with all surgical incisions and dissection. The avoidance of control of surgical hlccding requires that surgconr screen palienls appropriawly for coagu lopalhin. especially 111cancer patienu undcrgoing chemotherapy. who may have low plalelct count or in those padents (akmg cxccssiw amounts of NSAIDs. Paticnls who are anticoagulated are 1101 candidates for lhcsr procedures ~rntil the coagulopahy returns 1” normal. In spite of good surgical c~alualivc 213 technical skills. surgical bleeding is “lien unavoidable. A good rule to follow is nc\cr 1” close a wound when lucre exisw actiw unconrrollcd hlceding. Rlood collcc~ons provide a good medi:lm for the glowah of bacteria, leading I<>postopcradve iofcrtions. Bwaurr the technique for implarnation of drug+Ielivery systems most “fern use tuohy needles 1” “blindly” plxe inuathrcal drug catherc= into the lhecal WC, bleeding can occur nitbin the epiduial space ~ilhoul the surgeon being aware of ir Thb bieedirlK. if signiIicmr, could Icad 1” epidural hemxoma. spinal coni c”mpwzl3n. lad the e-adaequioa s)lldromr of paresis leading 1” paaiysis with bowel sod bladder d+unction. The surgeon should expect this cowplicdtion if the paiienr complains of pusis

lntrathecd inf:ctionr are rare The diagrw sis should he rxpeclcd IT the paGent prrsrnM with fever, stiff nech. and posldve stwch signs including Kcmig’s and Brudrinsky tigus. Dingnosis is conlirmed by CSF lindinp con\i%enr witi bacterial inferlion. IJowever, crutiorl in contirnung rhc diagnosis, hclbre action (surgical removal 01 hardware), is mandawry. II is the author’s cxpcriencc rtla1 3 large percentage of palienls witi newly implanwd intrxbccat ralbewlr will develop a fever spike up IO RJ high as 38.5’C wrhin the lint 7? hr of implaw cation. These noninfectious fever spikes ma) be associltcd with a slight stiff neck due 10 CSF teak from Ihe dwa rrowld Ihe newly implznwd catheter ant’ posstble porrhpinal headache. The CBC is olien normal. CSS clratm from rbe pump Gde port. if ana1yn.d. olicn only reveals a leukocyrosis and elcvnwd protein dth .a nrgaivr gram stain or cutnur for bacteria. This teukocytosis is common and presumably due to spinal tissue reaction to tbc implanted lntrathecat catheter. The fete1 ;Ilwa)~~ abdrec within 48-72 hr. 1~ IS imporwnt. here. I,) nemembrr lhar this picturr may be Gmitar to meningitis and does nix require rcmont of Ihe bardwdrc. tk guided by the CSF analpis. Epidurat infccrions. if left unwcarrd, Irad 10 epidunl abscess. Like epidura! hcmatom~c, epidural abwesse7 are cxpand~ng cpidulal nlds5.~5 that may compress 1hr Ibecal sac 311d damage scnsidve intrathecal neural lissurs. Like rhc epidural hemaroma. rhr abscess too can lead IO the cauda cquind syndrome of paresis. leading w paralysis with bowel and bladder dysfunction. The d;agnosis, as \rared above, is expected on clinicA signs and symptoms and conlirmcd by MRI or CT, with contrast. of lhr spinr. Trcarmenc consists of removal of aIt foreign material and appropriate antibiotic therapy.

lmplanlation of the spinal aad~cwr ic usually performed with blind needle ~::cbn+~s to place rdtheren for drug delivery into me spinal canal. Placement of these needle. Ihcugh performed under fluoroscopy, could lead IO damage 10 nerve rooLc or Ihe spinal cord ia:lf. Damage to nerve roots could rcsutt in pa&i and/or radicnlitis tilh resultmt neuropabic pd n in Ihr distribution of the damaged nerve root. r)amage

to the spinal cord could also lead to painful ti rstlmi~ 01 myelo@xc pain h.low rhr level of the damage spinal cord. Because mixing and spread in CSF of the infused drug depends on its lipid and wter wluhilily, it is advantageous 10 i~iace the drugdelivery inlrdtheral calheler tip as close iL3 possible w the pain-mediating spinal segment. This ensures Olat more lipophilic agents, such as s,dicntrrlil, could be med if more bydrophilir agents, such :I morphine or bydromo~hone, led IO inwactable rupmspinal side eliecu. I’lxing die cndwter tip close to the mediaing spinal sepncm require\ advancement of the: catheter ~owally from the lumbar segments. Adv~ncrnwnt of Ihe cabcuts inrta&xally for drug dclivwy of opioidq could also lrad to suhxrxhnoid romplicalions. such as damage to rbr nerve roode~\. Ihe anus medxlaris, or rhr spiuat cord itself. Damage 10 the!.e tissues could lrad 10 radiculitis. myeli&. pa8 a:ysis, parcsk. loss of bowel and bladder control. antl.101. myeloparhic pain. I.ong-term catheter placemem close to the subsr;mcc of the spinal cord could Icatl LO nolb
lb,. I, .%I. 6/w

fYY6

roperitom,al ~~is~us,such as the kidney, or CVYI the lcng from chest wdl: mnncling. Care mw guide the surgeon when tunneling these devices across the s~~bcutancous tissues of the abdomen. flank. or chest wall. Perforation of small or large bowl could lead to pcritonitib. and should be expected if the patient romplains of severe poslopcrativc abdominal pain asswiatcd with sign\ of peritonitis. Thex signs include ileus. splinting of the abdominal mu~cler, rigidity of the abdomina! wall with rebound rendernns. and n;wsea and vomiting. Peritonitis i\ a;rsociated with a postope~ltive fever. clcnwd sedimentation rate, and leukocyrori\. Abdominal radiographs will show signs of bowel ob,[rucdon including “airwater” levels and dilawd loops of bowel. Pcrfontion of the lung itself will rewlr in hemop w&s and obvious pneumothorax. Perforated &us is a surgica; emergency and should be handled as such. P~rforaion of a ~dthcvr into howl requires removal of the rathcler, hccausc thcrc is gross conwmination.

The placement of an intrathccal drug debvery cathewr through a ruohy nccdlc involm placing the lwedlc through the hack incision, the intaupino~s ligament. [he I@ menturn flavum. and !he cpidural space hcfore pullcmring tbc dw~. A r.+\hewr 1ha1 is squaller in si/e thar. the needle is the:, placed thioqh the needle into the d1ec.4 sac .rnd :~dvaal~ecl to :hr desired spinal lcvcl When [be nerdlc is removed, it leaves a hole in the durdl sac surrounding the catheter [ha1 is larger than rhc ra[he[er iuell: A CSF leak into the cpidural space is. thcle.brc. inevitable. Penis~cm CSF lrak can lead 10 po$rspinal headache in many patirnls. The treaunent of posupinal hax!nchc 1s aulo~ogolls epidural blood patchi1.g. This s!muld bc peiformed. paying carcftd ,~.~entio~~ LO sterile technique. under Iluoroxopic guidanw to avoid injur: to Ihe rpinal catheter. In our c.!inic, the raw of postspinal Ladache approaches 205:. Of course. :hrsc hraddches usuallv disappear over [ime. and wmporiring may hc all ri1.1[ ;s ncresaary. It i, this author’s cxperirncc, I~~we~er, that [hew headaches are considered v:w c by the qdtient thm the primary pain syndrr,r.~c that is being trrnwd. These complicatir ns should be rrcatcd aggre&ely.

147

Aflcr surgery. bw:wse the body abhors a r~cuum, newly created pump pock,% might de&&p a fluid collection or wroma th it ma) last Iii; up w l-2 months po~rimplanwion. These fluid collections are self-limiting and usually arc: of no clinical significance. I’xtienl w~~suram c i? usually the onl) [realmem nerrswr. If f!ud collection is excessive and bathww.rx u, the patient. an abdominal binder WighI be hrlpful ic dccrra~ing dir six of the reroma and promore healing. II infections is suspccwd an aspiraion for gram %ain. and culture wcl senndvi~ should be perfl>mwd. Reswrd, gram slains musL show hach!rid 10 diffctentiate from simple seroma .4ll Jerome contain large amoon of white blood Ceils. If thele IS a proven barterid contamination of ;he wound. the patient should be placed on inirxenou:; antihioucs. Antibiotic irrigation of rhc pocket iwell is recormuended. CO~SC~Mtive m:magemcnl at &is ninl would he 10 rrn,o\e ,he pun: 1 :,nd all cadlrlers, tnnvevcr, some infections have hcen managed wi!b apF.roplirle antibiotic Lhcrapy. If one ~lecls XI “treat and wtch.” punctnrc: oili;:: pump rrdll or side ports is conh-aindira& toi &i of contaminating the pump iwelf. If there are any sigus of spread of ;nfecdon along the catheter at this time or if the infccdon don not revolve. [hen the pump and catheter musk he removed.

348

Mechanical catheter complications include breaking, kinking, discnnnection oi the nriOIS nrressary conncrrion~. obstruction at the: catheter tip, and dislodgemem ,fthr ra~hrwr. These complirations lead to loss of anaig&a due to failure of the pumped analgesic gelling 10 the target organ, the spinal cord. I.ors ol analgesia, how*ever, can also he rausrd b) increasing diseaw (as in spreading of cancer). tolerance hxmation. an increase in the inwnsiy of the pain necnsitating higher medica lion dose:, or a rhan:c in the pain ~yndromc leading to opioid nonresponsiveness. Clinically, the patiw!. o\cr a period of ume, rxlw ricnccs 10s~ of good anzlgesic ronrrol. in spite of incrcuing the doses of the analgesic used. Contirmadon 01. mechanical carhcter prob lcms are easily confirmed rrsi:$ imaging techniques. A simple radiograph including the spine and pwnp will confirm if the catheter has dislodged, ha broken complewly. is discormected from rhc pump. 01 if the spinal catheter ha\ become disconnerrrd from the larger pumt~ catheter. 2’nfortun.1rely, simple radiographs will not confirm if there is obstruction at the catheter tip obstructing pump flow, a minor break with leakage of analgesic 10 nontarget ticsues. or if Lherr is a kink in the system If the pump bar a side port. TimpIe injection of nonionic radiographic dye mdcr fluoroscopic visualization will allow correct diagmxis of major and minor cathoer breakage. kinking, disconnection of the various necessary conncaions, ohctruction at the carhcter Up, and di4odgrmcr.t of the rathctrr. The phrician must understand, howmu, that this maneuver could lead to dire conscquencc. Injection of this dye through the side port of a pump could lead to an ovcrdosc of mcdication. especially if there exists a high concent~dlion of the medication in the drsdjpare of the catheter system. If the dead-space of the catheter is not apirated before injecting contrast material. the patient will recciw an extremely high dose of med;cation as a sing!c hohIS. If the pu~~p does nor have a side port, the task of diag:&ng this problem becomes more diffirulr. In this instance. ii is recommended to UK’ radio-labeled technetium as a tracer

hhlmr,

- 1% I1 x0. 6/unt 19%

mawrial. The reconra?alded procedure is IO vrnpty rhc pun;t,. fill the pump wirh tcchneGum, then program the pump to deliver a holuc injection? of the technetium. After a cermin period of “me, the cxheter rip is scanned for presence of :hc radio nuclide to insure Ihal *.hrre il normal technerium flow into the CSF and that the carhetcr is indeed in the inrmthcral ,pace. The wauner~ of mcchaniral cahewti complicarions wquites the removal and rcimpldnlotion of carhewn that are obstructed ar the tip ol 01,. catbcwr, reirnptantation of dislodged caherers or ihe reconnection of disconner1cd cattlercr~. Surgical correction of kinked caherrrs might require simply the freeing up o1’wme minor scarring around the catheter cawing lbe hink, or may rcquirc removal a!:d rct>tacelncnt of the catherer ~wcnurc ol’.xwrc scar formation. making disseuion and freeing rhe cxheter impossible.

t’rogrammnb!v pump complications in&de overfilling of Ihe pump, battery failure. pump failure. hyl,nd I:~ihwr. and torTion or flipping of a frrcl~ movr.able pump i&l’, Ratrrry Glurc or pump failure for an) reason ;s hcralded, like rahewr problems, bf a loss of analgesia. The normal battery life of a programmahh~ pur.lp depends 011 the prognmmx! llow raw and may Ins1 bawcen 3 md 5 ycan Pump, can he damaged hy overp~eswri~dlion from overfilling or by incompacible drug\ placed into Ihe pump. Overpressuri7ation may MN only Icz~d to pump damage and failure. hm way lad 10 overdoGog of Ihe patient. It is strongly suggested that only Yedtronir relill ki~r be used (or tilling of thaw programmable pumps. Thcsc kiti contain a manornrler system that will tell the physiriarl or m.ne if the system is ovcr~,rqrsurircd. Drug and pump inrompaubdly can lrad to break down of the internal cathctrr system and corrosion of the internal workings of rhc pump. Hybrid faitun:, failux of the electronic telemetric receiving module. prevents the pomp lrom rcc&ing programned instructions. Thew pumps will rontinuc LO function, hut. in fact. become cowant flow raw pumps. delivering drug at the lw programmed rate. Battery failure. or pump failure require explant of the old pump and rc-implant of a

“ew ow. Hyhrid f&ilurc. however, may no1 require pump rh-ac * IX;, decision depends on the 1mpor1anr~ “r prti(;rammability 10 1he physician and/or ..he padent. Free movemert of the pump wi!hi” its po~iet can, in addition IO heins uncomforlable 10 Ihc pa1ien1, also cause aorquiog of the pump ann stress 1rjG>-. 5” 1be rarhc1er ys1em or actual tlipk,ing of the pump itself. Bcrause of this phc lomenon. cathewn have ariually bcen pulled directly out of Ihc inlrathecal space. once again an event henldcd by 1019 of analgesia. When a pump flips owr on iuetf, hecause of free movemen within the pocke1. it becomes impossible 10 refill 1hc pump. This problem usunlly presents itself :II the time of refill. Failure of tetcmclry tiith programmablc pumps suggests this possibili1y. Confirmation of a flipped pump is made by radiograph or image.i”tensitied fluorowopy. Surgical revision of the pump pockr1 arid aruzhorirlg of the pump is Ihe sugges1cd rrmedy of rhir situation. RqWng and hgramming Errm Retitling erron can lead to disaster and include reprogramming errors, doGng errors, or errors of the refilling procedure icsclf. Pumps cant-din drug reservoirs tha1 need 10 he lilled every so often depending on 1hc C~IICCIItration of the drug used and rhe dew Ihal is delivered daily. Each relit1 of the drug is ha.ardors and risky to the patient. Several of rhe punps in 1he United States includirlg Ihe Infusaid. model 400 pump and the Medtronic, Synchromcd pumps, models 8615 and 861.M. contain side poru. The Synchromed, 86155 pump has a screened side port that only allows entry of a 25.gauge wedlc 10 prwcu: injccling rhe side port when refilling rhc pump 1hrough the crnlrdt fill port wi1h the recommended ‘LP-gauge huher needle. Ally injrctiorl ofdrug into Lhe cathcler side por1 could lead IO an overdosage of Ihe drug, morbidi1y. and CW:II de&. The morhidi1y associa1cd with massive overdoses of in1rathccnl opioids is well desctibed in 1he Ii,cr.aw:e. and inctudcs muscle rigidity, severe myoclonus. seizure activily, hypertension. rardiuvascular rollapse. and severe respiraory deprc~on.~‘~‘” Arlimal s1udies have show” some severe muro1oxicily 11: ovrrdows of i!llrapi”a! opioids.“‘~”

\Vhclr allempdng 10 .wce\s ,L*, -wxvoir fill por1 of pumps orhcr [ha” rho Swrhromed R615-S programmahlr pump, one mu<1 he absolu1ely certain Lha1 the needle ic xirhm the ren1rat fill por1 and not the side port. To ensure rcrrect filling procedures. i1 is impcralive rha1 0x1~ trained irldividuals perlarm refilling of these pur.xps. Some of Lhr manufaclurer\ of P”mps p-ondc rclill kiu lha1 contail. approprialc rcmpla1cr of their pumps 10 ensure proper tilling rechnique. If rhc paden is obese. if th., padem ha .a pump with a side port, or if palpation 01 the pump and iu ccn1rdl till por1 is diITicul1. iI is strongly rwommended that refitlillg be performed under fluoruscopic locaiiation of 1he till pow If rhc person retilllng rhr pump is aware of 1he po\sihle complications of refilling the pumps, ac~( with care a”d caution. and fotlova 1he above guidelines, complications can he avoided. Some physiciam, howewr. would nor uke rhc risk of usirlg pumps with tide par% Thcsc ph+cians feel 1ha1 the pre%~rcc of the side porr is wo risky for rhc bcnelits of e+ problem solving of cathcwr problems. These physicians, therefore, only implwl pumps wi1hou1 si le porw. Like reilling the pump, reprogramming a programm;lble pump could also lead 10 dire or even disasuous conrequcnce. These pumps .are 1elenwtric~lly inswucwd 10 perform according 10 Lhr ph+ianr’ Gshc? within the constrain1s of 1hc software cor.tincd in the programm.:r. Programming a drug concenuxlion tiat i; higher or lourr than the actual drug corlcawation within tie pump could teird 10 underdosing. tedding lo ixrewing pam or were abstinence Tndrome. or owrdosing, lea&g 10 morbidily or even de&. Likewise, programming higncr or lower doses lha” intended hy .t..e rcfiller could also lcad 10 morhidit? or death. Sewer sof1wxe dxa1 is atitable stir LI c :.:~,luv~~;c PI~~,F;~~,...~,~:,:c pumps arid >rogrammen a&s the programmer if be or :he ha made the right choice5 and is, therefore. safer fw 1he palienr. Nevertheless, the prograrr.ncr should check and recheck his or her work before discharging the pa&t. Should an owrdosc occur from either a refiiting error or reprogmmi:lg error and the physician is x+xre of the er?x. it is rerommended Iha1 CSF be immcdiale;y removed

and replaced with s;lline. Verx.us ICCCS%should bc obtained and lhr paticut should he mo\cd immediately VI the hospital, prcfcrAhty :br intens...e care unit. for ohrcrcldou. Should there be s;gns of rmpiratorv depression. naloxorw should be given immrdiarrly by holus injrruon and followed hy cominuou~ infusion. Because m~loxone my increase the bypawnsion produced by the effect ofmxcsivr dorcs of opioids on the centrdt ~~ervous s)~~ern.~’ it k preferable IO ohscrve Ibe pxxict:; for \iKm of dewloping respintory deprrkon bcforr iniristing rhc start of .tw uloxo~:e. O!hrr sign5 of r:otral ncrwu% ryrm toxicity, includinp scimre activity and myoclonw. G~ould bc treated ympwmatic;llly in tlw intensive c3rc unit.

G3nclusion A mtionat appr?.:rh to the mana~rment ot chronic nonmalIg~~~n~ pait> wing a tr~dtm~nt rontirruum has bceo prewntcd. Special empharls of this wuclc has been on rhr raiona; use of intraspinal opioid therapies for patients Gith chronic, nor~malign.mt pain s!ndromcs. Mana:;~mer~ guideline, and raiooale for these pidriinrs have hren prewnrcd. It is ctear that inrrapioal opioid themp): because it is an rxpcnsivc and inxxive therapy, shotlId bc a therapy of la51 resort bcforr mow imasivc, neurodeslruclive procedures. Spinall\ .ldminiwrcd opwid\ should only he uwt in tile rontcxt of a rrratmrnr rontimlum and oniy after :;~ndromr-sprcilic. ronxr\ari\c therapies, including sequential drug trials with swemically adminiswred opioids tuw failed. Alt patient for iniraspinal opioid thenapv should meet appropriate \elecCon criteria including absence of untreated drug hahi[u:rlions, ~~).chologic inrcrview and clearance, a trial for efficacv. and absence of any wrgical coutraindicarions. The risk and complications of implautablc technologies and remedies of dlesc romp1ic.l. lions have been prescnred hew. !f good patient education and cwnmuniration k pai{: rareful attention. if propcr patient selection and rejection is practiced, if good wrgical and stczile technique is followal n-.:tigiously. anil if there exists knowledge of tis!a 3 .I compiirationr xd their remedies, these technoloKie~ ritl add successfultv IO the pain prxtiuoner’s ‘bols of tie trade.”

lfl. Rch.ar M. Olshuan, ft. !&ROKI F. PI al. Lpirluml morphine in ,rca,n.en, of pain. I.zuxcr 197~‘.l::i27. 19. Cousins MJ, Matbrr LF. Glyn CJ, I’_ al S&-cwc spinal analgoia. Lanrrr 1979;l:I 141-l 142. 20. Onofrio RM.Kbh 1‘1.. Arnold t%. tin,inuour tow dose intratheral morphinr adml,+,ra,ion in ,he ,rra,mcn, of Lhronic pain ot malignarl, oriyi:). Map Clin Proc 198l,55:4ffl. 21. Cmmbs “W, Slundrrr RL. C+lor A,. c, .,I. Fpdural narcotic infuvon. implan,auon lrcbniquc and effiracy. i’nerrhcsiology lY81;55 469. 22. Harhaugh RE. C:oombs LW. Sdundcrs RI.. Implan,~ .I condnuour cpidoral morpbinr ~nfunon spem J Sr”rowrg 1YY2$6:no3-806. 23. fir,.!~bs DN’, WY,.... c,. ‘.rs RI., Gnylor MS Rcticfof co,,,i~~. o’ s cnronic pain by irmaspinal narro,ir\ mfuvor: I i an implanted rcwnoir JAMA l!tX3;?50: 2136-z; .J 24. ILran,rr ES, Cemhow J, Glawbq A. c, al. (.B,,rinuous ir.furion ot rpinrlly administcrrd ,urco,ics for ,hr r( lick of pair, dur ,u mahgn~, diu)rt!cvs Cancrr IYH5;5616Y&iC2. 25. Shctwr A<;. Hadley MN. Wdhirwm F. Admmis ,ra,ion of in,r~pin.d molybi,w for ,hc treatmcn, of cancer pain. Neurosurgery lYtUi:l8:74&747. 26 Rnn RI), Pace JA. Chronic. imrdthrcal morpbirw for inu;rublc pain. J K;eun~ur~ 1987:67:1~%186 27. Dennis CC. D&WV

RI.. Manaucmcn, of inlnc-

2F. Rrurnor (A. t or~K-‘crm in,ra,bec.d xllni~li~rrawm of rv,rphmr: a compa,iwr, of bolur mjcction via reservoir with con,in,mur lnfurion b\ ,mplan,rd pomp. Ycurosurtq~ l!tU7.21~484-4Yl. 29. Onofrio BY. y&h 1‘L. Long-term pain rclwt produced bv intnthccal infub,o,, m 53 pa,icnr\ J Sruro5urg IYW *7”.“0@wl. -30. Znmmcrma,t CC.. Hurchiel MI. The WC of in,ra,nrcat opiares for malignan, and nonmalignant pat”: manaRr,,,cn, 01 ,hir,)-ninr twirnrs. Prcn- A,,, Pain Sot lYYl:Y7. 31. Vargr CA Chronic- adminislmrion 01 inlnpiml local anrc,hr,ics in the w~~unc,,, of ,n.diqnan, pain. Proc An, Pam .Sw I:iiG:i 1. 32. Foltr, M. Ili,
IIL!C primp reservoirs chrw:ic p:,in \\ndronw\. YY4,Y%tf+.3I I.

61. Tanc1i.n IX. Cousin\ MJ Failurr ot epidur~ opiold to control cancer oam in a oartent o~cwouclv

62. Berde CB. Selhna Sk. Conrad IS. e, at. Sut, arachnoid budvxxmr annlnc\ia for seven month:

63. Nitexu I’. lrnnart A. Linder I., CI al. Epidurdl verxs intrarhccal nlorphinc-hupinrainr: assessment ofconwcutive ~rcamrr~b in ad~;rnced c.unx pin. J Pain Stmprom Manage 1990;5,id-26. 64. DuPen SI., Williams AR Management of padenl~ rccching comhincd epidural morphine and bupirarainc for [be veannen~ olcancer pain. J Pam Symptom Ydnage 1992:27:125-127. 65. Krames ES. Laming RU. Intratbcrrl infu&mA

for ltle mrrrdgemeni of I t’.w, Svmrxom Manace ”

74. Bo\ke GA. Partoperar;vr myocl~ :!os 2nd rtgiditv after anesthesia with opioids. Ane%h Analg 1994;7P.7t33-iR6. 75. (;roudinc SB. Crewllli-L)akms C. Lumh PI). Surccs\~~ul treatment of a massive irltr.lrhecal morpninr cvcrdow. Anesthrrinlo~ 19Y5.R2:292-295. 76. Coombs IN. Colburn IW, Delco J>\, flooper PJ. ‘Tuiwhcll BB. Compdratiw spinal neuropatholoq of hydromorphonc and morphine after 9 and 30&y clxdunl ndminirlrauoo in Thcrp. Anerlh Analg 1994;78~674-681. 77. Kaual S. Nuubr.en I., Haj PP. et al. Behxriomi and hirlopathological cflecl~ following inwathecal ~dmin~wafon of butorphanol. sulentanil. and n&uphmr in sheep. AnrJrheriolqn 1991;75:1025-1034. 78. Saltier K, Kaufm:m HII, Rloomfmld SM, Clint S, Bnnkr D. Trcanvn~ 01 highdow intrxhecal morphinr overdo*. J Neurosurg 1994381:14.%146.