786 Vol. 26 No. 3 September 2003Letters

This case illustrates several key issues in pallia-tive medicine. First, we are often dealing withelderly patients who may have other concomi-tant disease. Second, a thorough past medicalhistory, pain history and physical examinationare essential in assessment. Third, we must beflexible in our treatment approach, respectingautonomy to maximize patient concordancewith medication.

Paul Perkins, MA (Hons) (Cantab), MB, BCh, MRCP(UK), Dip Pall Med

Sue Morgan, MB, BCh, BMedSci (Hons), Dip TherSusan P. Closs, FRCP, FRCPathTy Olwen Palliative Care ServiceMorriston HospitalSwansea NHS TrustSwansea, United Kingdom

doi:10.1016/S0885-3924(03)00280-X

References1. Lavee J, Schneiderman J, Yorav S, et al. Complica-

tions of saphenous vein harvesting following coro-nary artery bypass surgery. J Cardiovasc Surg 1989;30:989–991.

2. Pagni S, Ulfe EA, Montgomery WD, et al. Clinicalexperience with the video-assisted saphenectomyprocedure for coronary bypass operations. AnnThorac Surg 1998;66:1626–1631.

3. Nair NR, Griffiths G, Lawson RAM. Postoperativeneuralgia in the leg after saphenous vein coronaryartery bypass graft: a prospective study. Thorax 1988;43:41–43.

4. Mountney J, Wilkinson GAL. Saphenous neural-gia after coronary artery bypass grafting. Eur J Cardio-thorac Surg 1999;16:440–443.

5. Senegor M. Iatrogenic saphenous neuralgia: suc-cessful therapy with neuroma resection. Neurosur-gery 1991;28:295–298.

6. Bernstein JE, Korman NJ, Bickers DR, et al. Topi-cal capsaicin treatment of chronic post-herpetic neu-ralgia. J Am Acad Dermatol 1989;21:265–270.

7. Drake HF, Harris AJ, Gamester RE, et al. Ran-domised double-blind study of topical capsaicin fortreatment of postherpetic neuralgia. Pain 1990;5(S):S58.

8. Zhang WY, Wan Po AL. The effectiveness of topi-cally applied capsaicin: a meta-analysis. Eur J ClinPharmacol 1994;46:517–522.

9. McCarthy GM, McCarty DJ. Effect of topical cap-saicin in the therapy of painful osteoarthritis of thehands. J Rheumatol 1992;19:604–607.

10. Baranowski R, Lynn B, Pini A. The effects oflocally applied capsaicin on conduction in cutaneous

nerves in four mammalian species. Br J Pharmac1986;89:267–276.

Possible Exacerbation of AdrenalSuppression from IntrathecalMorphine in a Patient ReceivingPulsed Dexamethasone for MultipleMyeloma

To the Editor:The development of central hypogonadism

from intrathecally and orally administered opi-oids has been described recently.1–3 Althoughthe evidence suggests a high prevalence for cen-tral inhibition of gonadal function, evidencefor other forms of hormonal derangement fromchronic opioid use, viz., hypoadrenalism or hy-pothyroidism, is less clear. A recent study ofpatients receiving intrathecal opioids reporteda prevalence of adrenal suppression that was sig-nificantly higher than the general population.4

Adrenal suppression is a well-known effectof chronic steroid exposure and cessation ofsteroids is usually done by a gradual taper.5 Forpatients exposed to steroids on a short-termbasis, cessation may be done without the taper.One of the chemotherapeutic regimens for thetreatment of multiple myeloma involves theuse of thalidomide and pulsed dexametha-sone.6 Since the dexamethasone is given fora short period, no taper is generally instituted.The following case illustrates possibly in-creased adrenal suppression from intrathecalmorphine in a patient already receiving pulseddexamethasone for multiple myeloma.

Case ReportThe patient was a 61-year-old woman who

was diagnosed with multiple myeloma twomonths prior to her initial consultation withthe pain management service. For her multiplemyeloma, she had been started on thalido-mide 150 mg/day and dexamethasone 32 mgper oz. daily for 4 days followed by a breakfor 4 days. This cycle was repeated three timesfollowed by a 7-day break. A review of her medi-cal record showed she tolerated the chemother-apy very well except for complaints of mildfatigue during the treatment.

Vol. 26 No. 3 September 2003 787Letters

She had ongoing complaints of mid-backpain and imaging studies had confirmed thepresence of several compression fractures. Heropioid regimen at presentation to the painclinic was oxycodone in both sustained-releaseand immediate-release preparations, with atotal dose of 90 mg daily. Due to the severe“incident” nature of her pain, the decision wasmade to proceed with intrathecal therapy withthe eventual goal of implementing a combina-tion of bupivacaine and morphine. A Med-tronic SynchroMed� intrathecal pump wasplaced without incident and initial intrathecalinfusion of morphine sulfate was started at 0.6mg daily. On Postoperative Day 2, she beganher next course of thalidomide with 4 days ofdexamethasone at 32 mg per day. The dexa-methasone was stopped on Postoperative Day6. During her follow-up visit to the pain clinicon Postoperative Day 8, her pain was not ade-quately controlled and the infusion was in-creased to 1.0 mg daily.

Two days after the staff increased her in-trathecal dose, the patient arrived in the clinicand stated she felt very poorly. She describedfeeling very weak and fatigued to such a degreeshe could not tolerate the condition she wasin. Her Edmonton Symptom Assessment Scale7

(ESAS) scores are in Table 1. We hypothesizedthat she might be feeling the effects of havingstopped her dexamethasone four days earlier.

Table 1ESAS Numerical Scores Before and During

Intrathecal Therapy and After Completion ofMethylprednisolone Taper

IntrathecalIntrathecal Dose

Dose Maintained;Increased; 5 days After

Before Dexameth- Methylpred-Intrathecal asone Pulse nisolone Taper

Symptom Therapy Completed Completed

Pain (Worst) 10 6 6Pain (Usual) 8 4 3Pain (Now) 9 4 3Fatigue 3 10 3Feeling of 2 10 0

well-beingDifficulty 0 9 0

thinkingclearly

Depression 0 1 0Anxiety 0 0 0Insomnia 3 10 0

0 represents the best score and 10 the worst.

We started her on a tapered dose of methylpred-nisolone (Medrol� Dose-Pak). Her initial dosewas 24 mg with a 4-mg decrease every day forsix days. Five days after completing the steroidtaper, the patient reported dramatic improve-ment in her fatigue and feeling of well-being(see Table 1).

CommentOur case raises the interesting possibility that

this patient may have developed an exacerba-tion of adrenal insufficiency with concurrentadministration of intrathecal opioids with oraldexamethasone. This patient had previouslytolerated multiple courses of pulsed dexameth-asonewithonly a slight increase in fatigue.Whenintrathecal therapy was initiated, she reportedgood pain relief but became profoundly symp-tomatic when her dexamethasone was stopped.Her symptoms resolved completely when amethylprednisolone taper was initiated (Fig. 1).

The mechanism by which opioids affect adre-nal function is not well understood. Althougha recent study demonstrated a significantlyhigher frequency of adrenal suppression in pa-tients exposed to intrathecal opioids, ACTHlevels were unchanged.4 Only serum cortisollevels were significantly lower in the opioidgroup. A similar finding has been shown pre-viously in the methadone maintenance group.8,9

Methylprednisolone has been shown to de-crease fatigue in cancer patients10 and it is possi-ble that this patient’s fatigue was alleviateddirectly by the steroid and not mediatedthrough an adrenal mechanism. However, fivedays after completion of the taper, the patientcontinued to report improved fatigue scores(Table 1). This suggests her improvement mayhave been related to improved adrenal functionrather than a direct steroid effect.

We did not formally evaluate this patient’shypothalamic-pituitary-adrenal axis because ofthe short duration of her symptoms. The possi-ble development of hypoadrenalism may needto be considered in any patient in whom in-trathecal opioid therapy is considered, espe-cially if the patient needs concurrent steroidtherapy. Further research is warranted to betterevaluate this possibility.

Arun Rajagopal, MDSavita Kala, MDSection of Cancer Pain ManagementDepartment of Anesthesiology

788 Vol. 26 No. 3 September 2003Letters

Fig. 1. ESAS Symptom Profile for pain, fatigue and well-being. dex. � dexamethasone; methpred. � methylpred-nisolone; IT � intrathecal; ESAS � Edmonton Symptom Assessment System.

Post-Surgical Herpes Zoster of thePlantar Aspect of the Foot

To the Editor:Herpes zoster (shingles) has been known to

present in a dermatomal distribution correlated

University of Texas M. D. Anderson Cancer CenterHouston, Texas, USA

Eduardo Bruera, MDDepartment of Palliative Care and

Rehabilitation MedicineUniversity of Texas M. D. Anderson Cancer CenterHouston, Texas, USA

doi:10.1016/S0885-3924(03)00281-1

References1. Roberts LJ, Finch PM, Goucke CR, et al. Out-

come of intrathecal opioids in chronic non-cancerpain. Eur J Pain 2001;5:353–361.

2. Paice JA, Penn RD, Ryan WG. Altered sexualfunction and decreased testosterone in patients re-ceiving intraspinal opioids. J Pain Symptom Manage1994;9:126–131.

3. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL,et al. Hypogonadism and sexual dysfunction in malecancer survivors receiving chronic opioid therapy. JPain Symptom Manage, in press.

4. Abs R, Verhelst J, Mayaert J, et al. Endocrineconsequences of long-term intrathecal administra-tion of opioids. J Clin Endocrinol Metab 2000;85:2215–2222.

5. Williams GH, Dluhy RG. Diseases of the adrenalcortex. In: Fauci AS, Braunwald E, Isselbacher KJ,

et al., eds. Harrison’s Principles of Internal Medicine.14th ed. New York: McGraw-Hill, 1998:2056.

6. Ribas C, Colleoni GW. Advances in the treatmentof multiple myeloma: the role of thalidomide. LeukLymphoma 2003;44:291–298.

7. Chang VT, Hwang SS, Feuerman M. Validationof the Edmonton Symptom Assessment Scale. Cancer2000;88:2164–2171.

8. Dackis CA, Gurpegui M, Pottash ALC, et al.Methadone induced hypoadrenalism. Lancet 1982;2:1167.

9. Fachinetti F, Volpe A, Farci G, et al. Hypothala-mus-pituitary-adrenal axis of heroin addicts. DrugAlcohol Depend 1985;15:361–366.

10. Bruera E, Roca E, Cedaro L, et al. Action of oralmethylprednisolone in terminal cancer patients: aprospective randomized double-blind study. CancerTreat Rep 1985;69:751–754.