Vol. 13 No. 5 May 1997 Letters 251

Recently, we carried out a double-blind, double-dummy, crossover study to compare the efficacy, tolerability, and time of onset of analgesia after the administration of 10 mg of morphine via both oral and rectal routes (as a m i c r o e n e m a ) in 34 op io id -na ive c a n c e r patients with pa in /S ign i f i can t pain relief was achieved faster after rectal administration (10 minutes) and lasted longer (180 minutes) than after oral administration, after which pain relief was delayed for 60 minutes and lasted 120 minutes. No significant difference in tolerability was observed between the two routes. These results led us to consider that rectal morph ine is particularly indicated in treating breakthrough pain.

In another study, 3 the plasma concentra- tions of free morphine and its 6-glucuronated metaboli te were measured after short- term oral, sublabial , rectal , and s u b c u t a n e o u s administrat ion of morph ine hydrochlor ide. The bioavailability of free m o r p h i n e and m o r p h i n e - 6 - g l u c u r o n i d e , a n d the ra t ios between the two were not statistically different whatever administration route was used.

As far as methadone is concerned, we evalu- ated the analgesia, tolerability, and absorption profile of 10 mg of methadone hydrochloride administered rectally (as a microenema) in six opioid-naive cancer patients with pain. 4 Pain relief was statistically significant as early as 30 minutes and lasted over 8 hours after metha- done administration. None of the patients reported significant side effects. The pharma- cokinetics of rectal methadone showed a rapid and extensive distribution phase, followed by a slow elimination phase and a wide interindi- vidual variability. These data were confirmed by Bruera et al. 5

Our clinical experience with both rectal morph ine and methadone administration is extremely positive. The advantages of the h o m e m a d e mic roenema administrat ion are (a) it is easily prepared both in the hospital and at home, (b) it has a low cost, (c) it causes no discomfort for the patient, (d) it provides the means to adjust the dosage as required, (e) it yields rapid absorption with respect to suppositories, and (f) it offers the possibility of using an alternative route of administration in countries where commercial preparations of rectal opioid analgesics are unavailable.

Carla Ripamonti, MD and

Franco De Conno, MD Pain Therapy & Palliative Care Division National Cancer Institute Milan, Italy

PII S0885-3924(97)00048-1

References 1. Warren DE. Practical use of rectal medications

in palliative care. J Pain Symptom Manage 1996;11: 378-387.

2. De Conno F, Ripamonti C, Saita L, MacEachern T, Hanson J, Bruera E. Role of rectal route in treat- ing cancer pain: a randomized crossover clinical trial of oral vs rectal morphine administration in opioid-naive cancer patients with pain. J Clin Oncol 1995;13:1004-1008.

3. Breda M, Bianchi M, Ripamonti C, Zecca E, Ventafridda V, Panerai AE. Plasma morphine and morphine-6-glucuronide patterns in cancer patients after oral, subcutaneous, sublabial and rectal short- .term administration. IntJ Clin Pharm Res 1991;11: 93-97.

4. Ripamonti C, Zecca E, Brunelli C, et al. Rectal methadone in cancer patients with pain: a prelimi- nary clinical and pharmacokinetic study. Ann Oncol 1995;6:841-843.

5. Bruera E, Watanabe S, Fainsinger RL, Spachyn- ski K, Suarez-Almazor M, Inturrisi C. Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain. Pain 1995;62:141-146.

6. De Boer AG, Moolenaar E De Leede LGJ, et al. Rectal drug administration: clinical pharmacoki- netic considerations. Clin Pharmacokinet 1982;7: 285-311.

Adverse Effects of Epidural Spinal Cord Stimulation on Bladder Function in a Patient with Chronic Spinal Cord Injury Pain

To the Editor: Epidural spinal cord stimulation (ESCS)

consists of electrical depolarization of the pos- terior spinal cord over the dura mater via imp lan t ed e lec t rodes within the ep idura l space. 1 In spinal cord injury (SCI), it has been used mainly for con t ro l o f ch ron ic pain a n d / o r spasticity. Recently, we observed an unusual response in a 41-year-old male with a T12-LI incomplete SCI, who presented with a

252 Letters Vot 13 No. 5 May 1997

4-year h is tory o f severe cauda equ ina syn- drome, refractory to conservative pain man- agement . Following a successful t e m p o r a r y trial of ESCS (frequency, 100 Hz; pulse ampli- tude, 3.5 V), he underwent surgical p lacement o f a p e r m a n e n t e p i d u r a l s t i m u l a t o r (Medtronic Itrel) and electrode (Medtronic Resume) via a laminotomy at T10. Over the next 4 months, pulse ampli tude was progres- sively increased to 6.5 V in order to maintain adequa te cont ro l o f pain. Dur ing epidura l stimulation at these amplitudes, however, the pat ient was unable to pass a catheter into his b l a d d e r d u r i n g a t t e m p t s a t se l f - catheterization, secondary to urethral sphinc- teric spasm. These episodes of spasm, which would persist for approximately 3 hours fol- lowing st imulator deactivation, disrupted his b ladder -management p rogram by causing uri- na ry re ten t ion and r ecu r r en t u r inary tract infections (requiring hospitalization and intra- venous antibiotics).

A two-part urodynamic study was p e r f o r m e d to characterize b ladder function in response to ESCS: a baseline study without ESCS and a repea t study following st imulator activation. Basel ine eva lua t ion revea led the onse t o f hyperreflexic bladder contraction at an intra- vesical volume of 41 mL and peak intravesical pressure of 56 cm H 2 0 , increasing to 193 mL and 66 cm HzO , respectively, dur ing epidural s t imulat ion. In addi t ion, dyssynergic func- tional obstruct ion of the membranous ure thra was much more p rominen t with the st imulator activated, which accounted for the difficulty in passing the catheter per urethra. The pat ient elected to have the stimulator removed and 6 months later underwent a dorsal root entry zone (DREZ) procedure that p roduced com- plete pain relief.

The u rodynamic findings in this pa t i en t have previously been described in SCI patients and have impor tan t implications for the pain pract i t ioner using ESCS. Katz et al. 2 examined voiding dysfunction in 23 patients before and after ESCS, with two patients demonst ra t ing prolongat ion of dyssynergic episodes during ESCS, and Meglio et al. "~ demons t r a t ed an increase in b ladder capacity f rom 147 to 217 mL in three patients. These studies indicate that the urodynamic response to ESCS in SCI patients is unpredictable. 2'~ Therefore , tempo- rary trials o f ESCS in SCI pat ients should

incorpora te an examina t ion of u rodynamic function using different parameters of electri- cal stimulation to de te rmine whether a clear threshold exists above which adverse effects on the ur inary tract may be detected.

Paul G. Loubser, MD The Institute for Rehabilitation and Research Baylor College of Medicine Houston, Texas

PII S0885-3924(97)00047-X

References 1. North RB, Ewend MG, Lawton MT, Piantodosi

S. Spinal cord stimulation for chronic intractable pain. Pain 1991;44:119-130.

2. Katz PG, Greenstein A, Severs SL, Zampieri TA, Sahni KS. Effect of implanted epidural stimulator on lower urinary tract function in spinal cord injured patients. Eur Urol 1991;20:103-106.

3. Meglio M, Cioni B, D'Amico E, Ronzoni G, Rossi GF. Epidural spinal cord stimulation for the treatment of the neurogenic bladder. Acta Neuro- chir 1980;54:191-199.

Re: Metoclopramide for Chronic Nausea

To the Editor: I was pleased to see another retrospective sur-

vey by Bruera and colleagues in the March 1996 issue (J Pain Symptom Manage 1996;11:147- 153). I would, however, like to raise two points. Although the algorithm for the t reatment of chronic nausea is portrayed as a four-step ladder, the text indicates that no pat ient p roceeded from step 3 to step 4. This means that step 4 (antiemetics other than metoclopramide and dexamethasone) is better described as an alter- native step 1/step 2. Thus, if clinical evaluation suggests that an alternative antiemetic regimen may be appropr i a t e , the pa t i en t would be changed to this sooner rather than later. This emphasizes that de termining the most likely clinical cause is an essential first step in the treat- ment of nausea and vomiting, that is, diagnosis before treatment. I believe Bruera et al. at least partly obscure this basic tenet by overemphasiz- ing the utility of metoclopramide and dexam- ethasone.

My second point relates to the difficulty of scoring nausea relief and vomit ing relief retro-