15,2001 / VOLUME63,Nwww.aafp.org/afpAMILYHYSICIAN - PDF document

15,2001 / VOLUME63,Nwww.aafp.org/afpAMILYHYSICIAN laparotomy,herniorrhaphyand mastec-tomy. ain is thought to be inadequatelytreated in one halfofall surgicalprocedures.In addition to imme-diate unpleasantness,painful expe-riences can imprint themselvesindelibly on the nervous system (Figure 1), Pain, which is often inadequately treated, accompanies the more than 23 million surgi-cal procedures performed each year and may persist long after tissue heals. Preemptive See editorial on page 1924. can modulate activity in the dorsal horn,where these descending pathways may pro-vide a physiologic explanation for theincreased pain experienced by patients whohave high levels ofdepression and anxiety.Painful stimuli ultimately cause activity inboth the somatotopically appropriate portionofthe sensory cortex and the limbic system.The response to noxious stimuli can bemodulated by their repeated application.Forexample,peripheral nociceptors becomemore responsive with the repeated applicationofnoxious stimuli.Their sensitivity can befurther enhanced by many tissue factors andinflammatory mediators released in thecourse oftissue injury.The response ofneu-rons in the dorsal horn ofthe spinal cord ofexperimental animals has been found to bebiphasic.The initial response to a noxiousstimulus is briefand correlates with the sharp,well-localized initial pain.The second phase ofthe response is more prolonged and correlateswith the dull,diffuse pain experienced afterthe initial injury.Experimentally,this secondphase is associated with a growing region ofhypersensitivity around the point where thenoxious stimulus was initially applied.The process through which the neurons ofthe dorsal horn ofthe spinal cord become sen-sitized by prior noxious stimuli is oftenreferred to as ÒwindupÓor Òcentral sensitiza-tion.ÓMuch less is known about pain-inducedsensitization ofthe supraspinal componentsofthe CNS.Collectively,however,the abovemechanisms enhance sensitivity to noxiousstimuli and may increase the level ofpainexperienced following surgery.Preemptive AnalgesiaOne ofthe most critical observations con-cerning central sensitization is the role playedby the first phase ofthe pain response.Opiatesadministered before the first phase andreversed with the opiate antagonist naloxone(Narcan) before the expected onset ofthe sec-ond phase were capable ofpreventing this latestage ofthe pain response.Thus,preventingthe initial neural cascade could lead to long-term benefits by eliminating the hypersensi-tivity produced by noxious stimuli.Animal experiments demonstrated the ben-efits ofpreventing central sensitization byinfiltrating with local anesthetics,approach that was particularly effective withpain associated with deafferentation,as mightoccur with amputation.Collectively,resultslike these led to the concept ofpreemptiveanalgesiaÑinitiating an analgesic regimenbefore the onset ofthe noxious stimulus toprevent central sensitization and limit thesubsequent pain experience.Surgery may be the clinical setting wherepreemptive analgesia techniques will be themost effective because the onset ofthe intensenoxious stimulus is known (Figure 3)appreciate the design ofclinically effectivestrategies in this setting,it is essential to recog-nize that otherwise adequate levels ofgeneralanesthesia with a volatile drug such as isoflu-rane (Forane) do not prevent central sensiti-AMILYHYSICIANwww.aafp.org/afpOLUME63,N10 / M15,2001 uli are not experienced as pain. However, a traumatic injury can shift the 106420 Pain Sensitization Hyperalgesia response Stimulus intensityPain intensity. . . ILLUSTRATIONS BY DAVID KLEMM Thus,the potential for central sensi-tization exists even in unconscious patientswho appear to be clinically unresponsive tosurgical stimuli.EfficacyDespite solid demonstrations ofits effectsin some animal models,considerable contro-versy surrounds the use ofpreemptive analge-sia in clinical settings.This controversy existsbecause not all clinical trials ofpreemptiveanalgesia have resulted in clear demonstra-tions ofits efficacy.In evaluating clinical trialsofpreemptive analgesia,the timing oftheintervention is only one factor.It is also essen-tial to consider the ability ofthe interventionto prevent central sensitization and whetherother aspects ofthe perioperative pain experi-ence may be ofsufficient duration and inten-sity to mask any intraoperative benefits fromthe preemptive analgesia.Many clinical protocols have mirrored thelaboratory studies using animals that gavebirth to the concept ofpreemptive analgesia.However,these animal experiments employedpainful stimuli ofintensity,duration andsomatotropic extent that were generally far lessthan that experienced during even relativelyminor surgery in human patients.Therefore,it should not be surprising that interventionswith a limited capacity for preventing centralsensitization,when applied for only a smallportion ofthe perioperative period,fail todemonstrate a preemptive analgesia effect.Preemptive analgesia strategies have involvedinterventions at one or more sites along thepain pathway (Figure 2).These strategies haveincluded infiltration with local anesthetics,nerve block,epidural block,subarach-intravenous analgesicsinflammatory drugs.For example,infiltratingthe incision site with the long-acting local anes-thetic bupivacaine (Marcaine) after adminis-tering general anesthesia and before incisionwas found to be more effective for hernia repairpain than either spinal anesthesia or generalanesthesia alone,and these benefits appeared tolast many days.Although spinal anesthesia clearly providesa better intraoperative block ofthe surgicalstimulus,the more effective postoperativeanalgesia produced by infiltration with a long-acting local anesthetic may have been animportant factor in preventing central sensiti-zation.During routine laparoscopy with gen-eral anesthesia,infiltrating with local anes-thetic before incision was found to be moreeffective than infiltrating with saline beforePreoperative Pain Control15,2001 / VOLUME63,Nwww.aafp.org/afpAMILYHYSICIAN FIGURE 2. The pain pathway and interventions that can modulate activ-ity at each point. Redrawn with permission from Kehlet H, Dahl JB. The value of "multimodal" or "bal-anced analgesia" in postoperative pain treatment. Anesth Analg 1993;77:1049. Providing Postoperative Pain ReliefhornDorsal rootTrauma . . tract . . incision or infiltrating with local anesthetic atthe conclusion ofthe procedure.There wereno differences among patients who receivedeither saline or local anesthetic at the conclu-sion ofthe procedure.Blockade ofperipheralnerves with local anesthetics can have a benefi-cial effect on pain after hernia repair,outlastingthe duration ofthe nerve block even when therepair is performed with spinal anesthesia.Intravenous opiates or ketamine (Ketalar)administered before incision can lead todecreases in wound hyperalgesia days after thesurgery.Anti-inflammatory drugs may playan important role in perioperative pain man-agement by reducing the inflammatoryresponse in the periphery and thereby decreas-ing sensitization ofthe peripheral nociceptors.This should help attenuate central sensitiza-tion.However,clear demonstrations ofthislast hypothesis have yet to be made.EPIDURALTECHNIQUEOne ofthe most important techniques forperioperative pain control involves the use ofan epidural catheter.These catheters are usu-ally placed at a lumbar or thoracic interspacebefore the start ofmajor thoracic,abdominalor orthopedic procedures and can be main-tained for several days to provide postopera-tive analgesia.Typically,local anesthetics andopiates,alone or in combination,are adminis-tered through the epidural catheter as an infu-sion or a bolus to provide analgesia.Because a surgical level ofanesthesia can beachieved for procedures on the lower abdo-men and lower extremities with epidural anes-thesia alone,its intraoperative use might beexpected to provide one ofthe best means ofblocking noxious stimuli and preventing cen-tral sensitization.However,even when anepidural catheter has been placed for the pur-pose ofpostoperative pain control,manyphysicians hesitate to use it intraoperatively,and others employ epidural drug regimens oflimited efficacy.One reason for this is concernabout hypotension related to epidurallyadministered local anesthetic blockade oftheAMILYHYSICIANwww.aafp.org/afpOLUME63,N10 / M15,2001 ALLAN GOTTSCHALK, M.D., PH.D., is associate professor in the Department of Anes-thesiology & Critical Care Medicine at Johns Hopkins Hospital, Baltimore. He formerlywas assistant professor in the Department of Anesthesia at the University of Pennsyl-vania School of Medicine, Philadelphia, where he graduated from medical school. Healso obtained a doctorate in anatomy and completed a residency and a research fel-DAVID S. SMITH, M.D., PH.D., is associate professor and director of neurosurgical anes-icine. He received his medical degree and a doctorate in pharmacology from the Med-ical College of Wisconsin, Milwaukee, and completed a residency in anesthesia and afellowship in neuroanesthesia at the University of Pennsylvania School of Medicine.ogy & Critical Care Medicine, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD lus and decreases subsequent hypersensitivity, as shown in C. However,the most effective preemptive analgesic regimen is initiated beforeRedrawn with permission from Woolf CJ, Chong MS. Preemptive analgesiaÑ D. Presurgical and Hypersensitivity AAAA Hypersensitivity C. Presurgical analgesia afferent input Hypersensitivity Nociceptor input. of surgery sympathetic nervous system,despite datademonstrating that neuroaxial blockade withlocal anesthetics is beneficial in hemorrhagicAnother reason that indwellingepidural catheters are not used to full effect isuncertainty about the efficacy ofpreemptiveanalgesia and how to achieve it.One ofthe earliest studies ofthe efficacy ofpreemptive epidural analgesia involved lowerextremity amputation.Patients in the inter-vention group received several days ofepiduralanalgesia for their painful lower extremitybefore receiving epidural anesthesia duringsurgery.This was followed by several days ofpostoperative epidural analgesia.In the controlgroup,the amputation was performed withepidural anesthesia,and patients receivedintravenous and oral opiates for analgesia.One year after surgery,the interventiongroup demonstrated dramatic reductions inphantom limb pain,stump pain and phantomsensation when compared with the controlgroup.However,even the control group expe-rienced one-year postoperative phantom limbpain at one halfofthe historical rate of70 per-cent,presumably because performing theamputation with regional blockade limitedcentral sensitization.A number ofsubsequent studies reportedmixed results for lower extremity amputation,although a recent editorial that accompaniedone ofthe negative-outcome studies made astrong argument that the likelihood ofsuccessimproves with the ability to effectively preventcentral sensitization throughout the entireperioperative period.Preemptive epidural analgesia using opi-ates,local anesthetics or a combination ofthetwo is effective for both thoracic and abdomi-nal procedures.Short-term and long-termbenefits have been demonstrated for thoraco-tomy,although again,the extent ofbenefitvaries with the ability to prevent central sensi-tization.The benefits ofpreemptive epiduralanalgesia during abdominal surgeryclude decreased pain during hospitalization,reduced length ofhospital stay,more rapidreturn to preoperative levels ofactivity andless long-term residual pain.Some benefit has been observed when usingepidural opiates alone for mastectomy,racotomy,extremity surgeryand lowerabdominal surgery.In evaluating these andother studies,it is essential to assess the qualityofpostoperative pain relief.Aggressive postop-erative pain therapy with an epidural cathetermay be essential to preserve any benefitobtained intraoperatively in the interventiongroup,although it may bias the control groupin the direction ofthe intervention group.Thus,the process by which the nervous sys-tem becomes sensitized by noxious stimulioffers both an explanation for the pain thatpersists after a traumatic experience,and ameans for reducing the short-term and long-term painful effects ofsuch stimuli.The avail-able studies indicate that modest short-terminterventions are not likely to provide mean-ingful benefits in the face ofmassive tissueinjury.However,preincisional infiltrationwith a long-acting local anesthetic can be ben-eficial in appropriately chosen patients under-going minor surgery.Analgesic strategies for more extensive pro-cedures require interventions capable ofpre-venting central sensitization throughout theperioperative period and,therefore,require acommitment from the entire surgical team.Ultimately,multimodal approachesaddress multiple sites along the pain pathwaymay prove necessary to adequately preventcentral sensitization in many surgical proce-dures.Unfortunately,the resources to provideoutstanding pain relieffollowing surgery mayonly become available once the clinical andeconomic benefits ofpain reliefare clearlydemonstrated.Preoperative Pain Control15,2001 / VOLUME63,Nwww.aafp.org/afpAMILYHYSICIANis the use of an epidural catheter. 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