Vol. 30 No. 2 August 2005 Journal of Pain and Symptom Management 183

Original Article

Temporary Sympathectomy in the Treatmentof Chronic Refractory AnginaRoger Moore, BSc, CHBMB, David Groves, PhD, Clare Hammond, BSc, CHBMB,Austin Leach, BSc, CHBMB, and Mike R. Chester, MDThe Cardiothoracic Center (R.M.), and the National Refractory Angina Center (D.G., C.H.,A.L., M.R.C.), The Cardiothoracic Center, Liverpool, United Kingdom

AbstractThe aim of this study was to investigate the safety and efficacy of the two most commonlypracticed temporary sympathectomy techniques in the treatment of chronic refractoryangina. Fifty-nine consecutive refractory angina patients commencing outpatient temporarysympathectomy from November 1, 2000 to November 1, 2002, were prospectively auditedfor duration of pain relief and procedural complications over a two-year period. A total of227 stellate ganglion blockades (SGB) and 100 paravertebral blockades (PVB) wereperformed on 59 chronic refractory angina (CRA) patients naı̈ve to sympathectomy. Themean period of pain relief obtained following SGB was 3.48 weeks (SD 3.38) and themean relief following PVB was 2.80 weeks (SD 2.00). Mild, fully reversible complicationsoccurred in 3% of SGB and 3% of PVB procedures, with one patient requiring overnighthospitalization. This study demonstrates that temporary sympathectomy may provide a safeand effective outpatient procedure in refractory angina patients when applied as part ofholistic care. J Pain Symptom Manage 2005;30:183–191. � 2005 U.S. Cancer PainRelief Committee. Published by Elsevier Inc. All rights reserved.

Key WordsStellate ganglion, refractory angina, angina

IntroductionDespite continuing advances in coronary re-

vascularization, increasing numbers of patientsare presenting to cardiologists with angina andcoronary anatomy disease or co-morbid condi-tions that make them unsuitable for furtherrevascularization. These patients are often se-verely disabled by their symptoms of angina andare frequently admitted with acute exacerba-tions. In response to this burgeoning group of

Address reprint requests to: Roger Moore, BSc, CHBMB,The Cardiothoracic Center Liverpool NHS Trust,Thomas Drive, Liverpool L14 3PE, United Kingdom.Accepted for publication: February 9, 2005.

� 2005 U.S. Cancer Pain Relief CommitteePublished by Elsevier Inc. All rights reserved.

0885-3924/05/$–see front matterdoi:10.1016/j.jpainsymman.2005.02.016

patients who are “refractory” to revasculariza-tion, there has been a re-emergence of interestin alternative treatments that were commonlyused to treat angina before the advent of revas-cularization.1,2 In 1998, the UK National Refrac-tory Angina guideline group examined theevidence base for all of the therapies in use forchronic refractory angina in the UK and set outa patient-centered care pathway that is designedto optimize the quality of life of patients andtheir carers. The guideline (www.angina.org)ranks possible treatment options according topatient-defined criteria of acceptable risk andreversibility. The guideline, fully imple-mented at the National Refractory AnginaCenter (NRAC) in 1999, recommends out-patient temporary cardiac sympathectomy for

184 Vol. 30 No. 2 August 2005Moore et al.

patients who fail to respond to earlier stages inthe care pathway: optimal medication, rehabili-tation, and transcutaneous nerve stimulation.

To understand the theoretical basis fortemporary sympathectomy in the treatment ofchronic refractory angina, it is necessary tounderstand the role of the sympathetic nerves.In common with other viscera, the heart lackssensory nerves and it is accepted that the sympa-thetic autonomic nervous system is responsiblefor the transmission of angina from ischemicmyocardium to the central nervous system.3,4

The precise trigger for sympathetic afferentactivation is not known. However, myocardialischemia is associated with the release ofseveral excitatory chemical substances, suchas adenosine5–7 and bradykinin,8,9 which areknown to activate sympathetic nerve endings.

The sympathetic afferent fibers coalesce toform the cardiac sympathetic plexus and thecardiac nerves then link these structures toadjacent swellings within the cervical region ofthe paravertebral sympathetic ganglion chain,predominantly on the left side. These structuresare termed the middle and stellate cervicalsympathetic ganglia. The sympathetic pathwaysthen connect with the intermediolateral graycolumn of the upper thoracic spinal cordthrough the white and grey rami communican-tes.10 The majority of the cell bodies from thecardiac sympathetic afferents are found inthe dorsal root ganglia between the T2 and T6spinal segments.11 ‘Angina’ signals have beenshown to ascend to pain processing centerswithin the brain via contralateral spinothalamictracts, but exactly how the incoming afferentsympathetic nerve signals gain access to thesespecialist pain pathways is unknown.

The concept of treating the symptoms of car-diac chest pain by interruption of sympatheticpathways was first proposed by Frank in 1899.He suggested that blockade of the middle cervi-cal and stellate ganglion could lead to a diminu-tion in perceived angina. Jonnesco performedthe first surgical cervical sympathectomy forangina in 1916.12 During the next three decadesvarious surgical sympathectomy procedureswere employed, including the removal of cervi-cal ganglia and paravertebral chain or dorsalrhizotomy of the cervicothoracic trunk.13–15

Overall, these studies demonstrated completeor partial symptom relief for 80–90% of pa-tients,16 but these early destructive techniqueswere associated with irreversible complications.

The observation that local anesthetic infiltra-tion around the stellate ganglion may result inpain relief outlasting the duration of action ofthe local anesthetic drug in angina suffererswas first reported in 1933.17 Over the sub-sequent years, left stellate ganglion blockade(SGB) became a popular form of treatment forangina, but no serious investigation was under-taken until 1966, when Wiener18 performed asmall placebo-controlled trial in angina sufferers.This trial demonstrated that SGB was more ef-fective than placebo in reducing symptoms onexercise. Previously, we reported that tempo-rary sympathectomy can be highly effective inselected patients.19 More recently, we reporteda patient whose symptoms were successfullycontrolled with repeat SGB after the failure ofmultiple procedures.20 The role of placebo isat present undergoing evaluation in a double-blind, randomized, controlled trial sponsoredby the British Heart Foundation.

Regional anesthesia using stellate and para-vertebral blockade (PVB) has been used widelyby pain specialists for treating chronic painsyndromes for many years.21 Both stellateganglion and paravertebral blockade are inwidespread use in non-cardiac chronic painconditions, and have been shown to be safe daycase procedures in large observationalseries.22,23 The aim of this study was to examinein a large case series of CRA patients the utilityof temporary sympathectomy as a method ofalleviating angina. In addition, the study aimedto provide information on the complicationrate of the procedure in this setting and thecost implications of providing the therapy.

MethodsSince November 2000, data have been col-

lected prospectively on all patients undergoingtemporary sympathectomy at the NRAC,Liverpool, UK. Audit staff and clinicians rou-tinely collect demographic details and medicalhistory, and record procedural complications.All patients had undergone a trial of transcuta-neous electrical nerve stimulation (TENS). Aspart of routine TENS management. patientswere trained to monitor changes in symptomsand to contact NRAC to arrange immediatefollow-up in the months before stellate ganglionblock. Stellate ganglion block was offered on the

Vol. 30 No. 2 August 2005 185Temporary Sympathectomy and Refractory Angina

basis of the failure of optimized medication,rehabilitation, and TENS to achieve satisfactoryangina control. Patients were extensively edu-cated about the theory and practice of sympa-thectomy on at least two occasions one weekapart as part of our routine consent process. Inaddition, approval for use of audit material wasprospectively obtained from the LiverpoolResearch Ethics Committee and written per-mission was obtained from all participants.Following their temporary sympathectomy pro-cedure, patients were asked to closely monitortheir angina symptoms, and on any recurrenceof their chest pain, to immediately contactthe clinic coordinator to arrange a further ap-pointment for a repeat procedure. Timed voice-mail recorded off-hours calls.

SubjectsThe diagnosis of chronic refractory angina is

a clinical one.1,2 All patients had been referredto the refractory angina clinic following angio-gram review by a consultant cardiologist and aconsultant cardiac surgeon, and it had beenagreed that revascularization was unfeasible orthe risks unjustified. The UK guideline defini-tion suggests an important role for pain special-ists to exclude non-cardiac causes for chest painsymptoms. All NRAC patients are seen in a com-bined cardiology/pain clinic and a diagnosis ofchronic refractory angina can only be madeif both consultants concur. Patients with Syn-drome X and non-cardiac angina-soundingpain were not included in the study. Complica-tions were defined prior to the study and catego-rized as hypotension, convulsion/brainstemdysfunction, persistent sympathetic blockade,pneumothorax, hematoma, or wound infection.

Once the diagnosis is made all patients un-dergo an extensive educational and rehabilita-tion program, during which medication isoptimized. Patients who remain unsatisfiedwith their level of symptom control are of-fered TENS before being offered temporarysympathectomy.

There are three techniques to achieve tempo-rary cardiac sympathectomy: stellate ganglionblock, paravertebral block, and high thoracicepidural. SGB is offered first in view of its theo-retical and practical advantages over PVB. Pa-tients who failed to experience clinical benefitwith SGB are offered paravertebral blockade.Epidural sympathectomy is not suitable for

repeated therapy in stable chronic refractoryangina and is reserved for selected patients withunstable symptoms.

Pain Relief Outcome MeasureIn the management of chronic refractory

angina, the objective of alleviating angina painis to improve patient-defined quality of life byabolishing symptoms or by modifying the un-pleasant nature of angina. Pain is a purely sub-jective emotional experience and changes inthe nature of that experience are notoriouslydifficult to measure. Therefore, for the purposeof the present study, we recorded presence orabsence of pain post-treatment.

Statistical AnalysisBinary logistic regression analysis was used to

determine whether baseline characteristicscould predict a positive response to treatment.The multivariate model was constructed usinga forward stepwise approach used to adjust forthe effect of covariates. Covariates entered intothe model were age, sex, number of anginamedications, left ventricular function, priorcoronary artery bypass, prior percutaneouscoronary intervention, previous myocardial in-farction, presence of hyperlipidemia, presenceof diabetes, and presence of hypertension.

Left Stellate Ganglion Blockade TechniqueThis technique has been described pre-

viously.20 All patients are taught relaxationtechniques prior to admission to the day unit.The procedures are performed in an outpa-tient daycase setting with pulse, blood pres-sure, and oxygen monitored throughout, andwith full resuscitation facilities available. Afterobtaining written consent, the patient is re-clined to 20–30� with a pillow placed behindthe head, with the face facing forward and themouth partly open in order to relax sternoclei-domastoid muscles. After preparing the skin, a21G needle is attached via manometer tubingto a syringe containing 20 mL of 0.5% bupiva-caine. The use of tubing allows easier controlof the needle tip and prevents needle migrationduring depression of syringe plunger. The cri-coid cartilage is palpated with the middle fingerof the non-dominant hand, which is thenmoved laterally to the left until the bony promi-nence of the transverse process of C6 is felt,simultaneously retracting the carotid artery.

186 Vol. 30 No. 2 August 2005Moore et al.

The needle is then passed over the middlefinger and through the skin until it rests gentlyupon bone, with care taken to ensure that thecarotid artery pulsation remains lateral withrespect to the needle track. After gently aspirat-ing to check that the needle tip is not in avascular space, 15 mL of 0.5% bupivacaine isinjected slowly, aspirating after every 4 mL, withcare taken to avoid movement of the needletip. Aspiration is repeated if the patient swal-lows. The needle is then removed and pressureapplied. If blood is aspirated the needle shouldbe withdrawn, pressure applied and the needlere-sited. Sympathectomy is confirmed by thepresence of Horner’s sign.

Paravertebral TechniqueThe patient sits upright, resting their arms

on a pillow. The back is prepared with cleaningmaterial and the upper thoracic spinous pro-cesses located by palpation. Local anestheticis then instilled 3–4 cm left lateral to the spinousprocess of T3 or T4 to a depth of the transverseprocess. The 16-gauge Tuohy needle is theninserted perpendicular to the skin planes untilthe tip is in contact with bone. It is then re-angledsuperiorlyand advanced until it slips overthe upper border of the transverse process. Alow friction syringe is then connected to theneedle. As the needle passes through the costo-transverse ligament and enters the paraverte-bral space, resistance to saline injection isreduced indicating correct position. Followingaspiration, 15 mL of 0.5% bupivacaine isinjected.

ResultsFrom November 1, 2000, to November 1,

2002, 327 temporary sympathectomy proce-dures (227 SGB, 100 PVB) were undertaken on59 CRA patients naive to sympathectomy. Thebaseline characteristics of the study group aregiven in Table 1.

Stellate Ganglion BlockadeDuring the study period, 227 separate SGB

procedures were undertaken on 46 patients.The mean period of complete pain relief follow-ing SGB was 3.48 weeks (SD 3.38); however,the range was considerable (0–40 weeks). Ourexperience has suggested that temporary sym-pathectomy is not an appropriate strategy in

Table 1Baseline Characteristics of the Study Group

(n � 59)

Characteristics n (%)

Mean age in years (SD) 62.0 (9.4)Sex

Male 49 (83)Female 10 (17)

DiagnosisPrevious MI 42 (71)Previous CABG 43 (73)Previous PTCA 26 (44)Left ventricular dysfunction 29 (49)

Risk factorsEx or current smoker 49 (83)Hypertension 19 (32)Elevated cholesterol 52 (88)Diabetic 9 (15)

Medications for anginaBeta blocker 35 (59)Calcium antagonist 50 (85)Nitrates 45 (76)Potassium channel opener 39 (66)

patients who fail to obtain at least two weekspain relief following their first SGB/PVB. Wetherefore use the two-week pain relief as a cutpoint for responders and non-responders. The31 patients who had responded with at least 2weeks pain relief following SGB received 180procedures, with mean pain relief duration of3.80 weeks (SD 3.36). The overall response ratewas 67%. The distribution of relief from anginafor this group is given in Figure 1. Twenty-five(54%) patients felt sufficient benefit to con-tinue treatment for at least four treatmentcycles and 23 (50%) patients were still receivingtreatment by the end of the audit period.

ComplicationsAdverse reactions occurred in 6 (3%) proce-

dures. One patient experienced an episode ofhypotension as a consequence of a vasovagalreaction. Acute short-lasting symptoms of ver-tigo were provoked by inadvertent vascularinjection on one instance. On two occasions,patients displayed signs of prolonged stellatesympathectomy. One patient reported an epi-sode of frozen shoulder after blockade andthere was a significant hematoma reported onone occasion. Overnight hospitalization was notrequired and no complication led to any pa-tient suffering a permanent disability.

To assess overall complication rates, we in-cluded patients (n � 37) who had alreadyundergone their first successful block before

Vol. 30 No. 2 August 2005 187Temporary Sympathectomy and Refractory Angina

0<1 21 43 65

Block duration (weeks)

Num

ber o

f SG

Bpr

oced

ures

87 9 10 >10

10

20

30

40

Fig. 1. The spread of pain relief duration in weeks following stellate ganglion blockade for those patients whohad demonstrated at least two weeks’ pain relief with the procedure.

the beginning of the trial period and were un-dergoing repeat SGB as part of long term treat-ment. Overall, 569 separate SGB procedureswere undertaken on 83 patients in the studyperiod. Adverse reactions occurred in 14 (2%)procedures. Overnight hospitalization was re-quired for two patients, although no complica-tion led to any patient suffering a permanentdisability.

Paravertebral BlockadeDuring the study period 100 separate PVBs

were undertaken on 21 patients. The meanperiod of complete pain relief following PVBwas 2.80 weeks (SD 2.00), (range 0 to eightweeks). The 11 patients who had respondedwith at least two weeks pain relief received 77procedures, with mean pain relief duration of3.19 weeks (SD 1.85). The response rate was52%. The distribution of relief from angina forthis group is given in Figure 2. Eight (38%)patients felt sufficient benefit to continue treat-ment for at least four treatment cycles and five(24%)patients were still receiving treatment bythe end of the follow-up period.

ComplicationsAdverse reactions occurred in 3 (3%) pro-

cedures. Patients experienced 2 episodes of

hypotension as a consequence of profound sym-pathectomy; administration of intravenousfluids and vasopressors was necessary. Hypoten-sion and temporary paresis were provoked byinadvertent epidural injection on one occasion.Overnight hospitalization was required for twopatients, although no complication led to anypatient suffering to a permanent disability.

Overall, including patients who had com-menced PVB before the start of the audit, 193separate PVB procedures were undertaken on34 patients in the study period. Adverse reac-tions occurred in 6 (2%) procedures. Over-night hospitalization was required for threepatients, although no complication led to anypatient suffering a permanent disability.

Cost ImplicationsDuring the two-year study period, including

patients who were receiving temporary sympa-thectomy prior to the start of the study andwere therefore not included in the audit, over762 procedures were performed on 99 patients.On average, it is easily possible to perform 6procedures in a single outpatient session. Thus,it is possible to calculate that once a steady-state has been reached 1.5 sessions a week areneeded to maintain 99 patients in a sympathec-tomy program. The main annual personnel

188 Vol. 30 No. 2 August 2005Moore et al.

0<1 21 43 6 to 105

Block duration (weeks)

Num

ber o

f PVB

proc

edur

es

10

20

30

Fig. 2. The spread of pain relief duration in weeks following paravetebral blockade for those patients who haddemonstrated at least two weeks’ pain relief with the procedure.

costs for 1.5 sessions are the operator (£7.5K),the nurse (£2K) and disposables (@ £20 perunit). The total annual costs are around£11,500. The cost per patient is around £100–200 per year.

Prediction of Response to TemporarySympathectomy

The only baseline parameter that predictedsuccessful response to therapy was the numberof different classes of anti-angina medicationsprescribed at the onset of treatment. Patientstaking increasing numbers of different classes ofanti-angina medications had significantly betterresponse rates (P � 0.019, CI 1.5–10.7).

DiscussionThis single largest consecutive series demon-

strates that repeated temporary sympathectomycan be used as part of a comprehensive programto ameliorate disabling angina in patients withinoperable or high risk coronary artery disease.It was anticipated that patients suffering fromcardiac disease who would inevitably be pre-scribed multiple hypotensive medications could

be at greater risk of hypotensive complicationswith sympathectomy. However, the complica-tion rate in our study was lower than that ob-served in a large series of patients withnoncardiac disease22 and none of the adverseexperiences over the study period resulted inany persistent disability. This is particularly im-portant, as the mean period of symptom relieffor either temporary sympathectomy techniqueis between three and four weeks, requiringpatients to undergo regular repeat proceduresto gain continuing relief.

The majority of new patients in this studyderived some benefit from temporary sympa-thetic blockade. Of those patients who demon-strated a response to SGB, 74% continued withtreatment throughout the study period. Thisobservation of continuing long-term relief withthe technique is in keeping with our overallexperience. Although the initial response toPVB was similar to SGB, a lower proportion ofpatients achieved sustained relief. The observa-tion that fewer patients elected to continue withPVB maybe explained by the fact that only pa-tients who had failed to find SGB an effectivetherapy were offered the procedure. In addi-tion, PVB is more invasive and presents

Vol. 30 No. 2 August 2005 189Temporary Sympathectomy and Refractory Angina

greater technical difficulty to obtain repeatedsuccessful sympathetic blockade. Nevertheless,PVB is an acceptable treatment option for asmall but significant number of patients withrefractory angina who do not respond to SGB.Fluoroscopy-guided needle placement, which isincreasingly becoming a standard method fortemporary sympathectomy, offers enhanced ac-curacy for anesthetic delivery and may provideimproved clinical efficacy in this group. Individ-uals within the temporary sympathectomy pro-gram have been successfully sustained withtreatment for up to seven years in one case,each individual having judged that the reliefobtained from the procedure outweighs the in-convenience of repeated treatments.

Sympathetic blockade for the relief of anginahas been achieved using other techniques, in-cluding video-assisted thorascopic sympathec-tomy (VATS),24 high thoracic epidural,25

radiofrequency ablation of SGB,26 and spinalcord stimulation.27 These therapies are rela-tively more invasive, with higher rates of irre-versible complication in comparison totemporary sympathectomy. We have, therefore,reserved these treatment options for patientswho have declined or not obtained clinical ben-efit from temporary sympathectomy, in linewith the UK refractory angina guidelines.

Possible Mechanisms of Actionof Local Sympathectomy

Blockade of the transmission of cardiac sym-pathetic afferent nerve traffic, using local anes-thesia at relay sites in the stellate ganglion andupper paravertebral chain, might be pre-dicted to afford temporary relief of angina.Many patients, however, experience symptomrelief far beyond the period of action of thelocal anesthetic. This has been explained bythe neuro-adaptive theory, which proposes thatcontinual bombardment of neurons within thegrey matter of the thoracic spine from visceralsympathetic afferents can activate cellularmechanisms leading to hyperalgesic states.28

Central sensitization has been shown in stud-ies in other visceral organs. Ness et al. demon-strated that repeated stimulation of the greymatter neurons by repeated balloon dilationof the colon in human subjects increases painsensitivity and expands the area of referredpain,29 findings which have been verified in

animal models.30 It has, therefore, been pro-posed that temporarily impeding stimulationof sympathetic afferents using local anestheticcould reverse these cellular mechanisms,thereby reducing the threshold for activationof the cardiac neural network and consequentlyproviding a prolonged alleviation of angina forrefractory angina patients.20

Clinical Role of Temporary SympathectomyIt is important to realize that, although we

have shown that temporary sympathectomyreduces symptoms in the majority of patientswith chronic refractory angina, it is only offeredas part of a comprehensive treatment approach.In our experience, failure to follow the currentACC-AHA-ACP-ASIM guidelines on educationin the management of stable angina (www.ac-c.org) will reduce the effectiveness of sympa-thectomy and other specific therapies used inthe treatment of CRA. We have routinely pro-vided the patient and their carers with continu-ing education, counseling, and help withrelaxation and cognitive behavior therapy aspart of an integrated care algorithm. This path-way is commenced prior to sympathectomy andcontinued throughout the patient’s involve-ment in the treatment program. It provides anopportunity to reassure, change lifestyle pat-terns (such as minimal physical activity), andgain agreement with patients about realistictreatment goals. We believe that this holisticapproach enables the patients to gain maxi-mum benefit from specific pain treatment in-cluding SGB and PVB.

Future ResearchThese observational data provide evidence

for the efficacy of temporary sympathectomyin the treatment of refractory angina and hasprompted a randomized, double-blind study ofthe technique. Further studies are required toinvestigate whether temporary sympathectomycan beneficially influence markers of myocar-dial ischemia and provide information com-paring the clinical usefulness of temporarysympathectomy with other therapies for refrac-tory angina, such as neuromodulation and en-hanced external counterpulsation.

Limitations of StudyPain is a subjective experience. Changes in

continuous angina variables such as frequency,

190 Vol. 30 No. 2 August 2005Moore et al.

intensity, or duration might have yielded inter-esting information but were not recorded for anumber of reasons. It is known that pain experi-ence in general and angina in particular varieswith attention, and the additional attentionneeded to make detailed recording of symp-toms might have had the effect of alteringangina symptoms before and after treatment.Furthermore, the typical chronic refractoryangina patient experiences frequent episodesof pain of varying severity and regression to themean could explain any observed changes infrequency or intensity following intervention.Our experience of SGB since 1996 has shown usthat, for the majority of patients, there is an“all or nothing” effect. Patients were trainedto record the presence or absence of anginasymptoms. By using the least subjective categori-cal measure of presence or absence of angina,we have minimized both reporting error and thepossibility that our results might be explainedby regression to the mean.

This non-blinded observational clinical studywas designed to examine the role of tempo-rary sympathectomy in CRA and it was not possi-ble to exclude the possibility of a placebo effect.The role of placebo in SGB is the subject of aseparate BHF funded study currently underway.

In this study group, sympathectomy is offeredas a part of a holistic care program that involvesextensive education and continuing rehabilita-tion. Whether isolated SGB or PVB would pro-duce the same results is unclear and, therefore,cannot be recommended.

ConclusionThe growing number of patients presenting

with inoperable disabling angina is already asignificant problem and novel treatment ap-proaches are needed. Our prospective study ofconsecutive patients undergoing the simpleoutpatient procedure of temporary sympathec-tomy shows that it may be an effective, well-tolerated, and low risk treatment option forsuch patients as part of holistic care.

AcknowledgmentsThe authors thank Pauline Barlow, ECG

technician.

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