6 Vol. 30 No. 1 July 2005Letters

References1. Bruera E, MacMillan K, Kuehn N, Hanson J,MacDonald RN. A controlled trial of megestrolacetate on appetite, caloric intake, nutritional status,and other symptoms in patients with advancedcancer. Cancer 1990;66:1279–1282.

2. Loprinzi CL, Ellison NM, Schaid DJ, et al. Con-trolled trials of megestrol acetate for the treatmentof cancer anorexia and cachexia. J Natl Cancer Inst1990;82:1127–1132.

3. Tchekmedyian NS, Hickman M, Siau J, et al. Meg-estrol acetate in cancer anorexia and weight loss.Cancer 1992;69:1268–1274.

4. Rowland KM, Loprinzi CH, Shaw EG, et al. Ran-domized double blind placebo-controlled trial ofcisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer:a North Central Cancer Treatment Group Study.J Clin Oncol 1996;14:135–141.

5. Pascual Lopez A, Roque M, Urrutia G, et al. Sys-tematic review of megestrol acetate in the treatmentof anorexia-cachexia syndrome. J Pain SymptomManage 2004;27:360–369.

6. Jatai A, Kumar S, Sloan JA, Nguyen PL. On appe-tite and its loss. J Clin Oncol 2000;15:2930–2932.

7. Beller E, Tatersall M, Lumley T, et al. Improvedquality of life with megestrol acetate in patients withendocrine-insensitive advanced cancer: a randomi-sed placebo-controlled trial. Ann Oncol 1997;8:277–283.

8. Bruera E, Ernst S, Hagen N, et al. Effectiveness ofmegestrol acetate in patients with advanced cancer: arandomized, double-blind, crossover study. CancerPrev Control 1998;2:74–78.

9. Desport JC, Gory-Delabaerre G, Blanc-VincentMP, et al. Standards, options and recommendationsfor the use of appetite stimulants in oncology (2000).Br J Cancer 2003;89(Suppl 1):S98–S100.

Lidocaine Intoxication at Very SmallDoses in Terminally IllCancer Patients

To the Editor:Parenteral lidocaine is often used in the treat-

ment of neuropathic pain.1–3 Although lido-caine intoxication can be fatal or produce sideeffects that impair the patient’s quality of life,4

there have been no reports of lidocaine intoxi-cation in palliative care settings. We present twocases of toxicity associated with excessive concen-trations during low-dose lidocaine treatment.

Case 1An 82-year old woman with mucinous adeno-

carcinoma of unspecified primary site wasadmitted to our palliative care unit for paincontrol. On admission, she had severe backpain and neuropathic pain of both lower ex-tremities due to lumbar vertebrae collapse andspinal cord compression. Radiological exami-nations revealed no liver metastases or cirrhosis.Laboratory examination showed normal liverfunction (total bilirubin 0.5 mg/dl, GOT 17 IU,GPT 12 IU, alkaline phosphatase 290 IU). Theserum creatinine level was normal (0.73 mg/dl),and blood urea nitrogen (BUN) level and pot-assium were slightly elevated (BUN 39 mg/dl,potassium 6.0 mEq/l).

Her pain had been partially controlled byradiation, a nonsteroidal anti-inflammatorydrug (NSAID), and transdermal fentanyl at adose of 50 µg/hr. On Day 14, we added intrave-nous lidocaine in a daily dose of 300 mg forfurther pain palliation. Two days later, pain waswell controlled, but one week later, she devel-oped severe somnolence. Laboratory examina-tion showed normal renal function, sodium andcalcium levels, and liver function (total biliru-bin 0.5 mg/dl, GOT 97 IU, GPT 13 IU, alkalinephosphatase 298 IU, creatinine 0.62 mg/dl,sodium 128 mEq/L, calcium 7.8 mg/dl). Serumconcentration of lidocaine was 8.4 µg/ml. Weattributed the main etiology of the patient’ssomnolence to overdose of lidocaine, whichwas immediately withdrawn. The next day, hersomnolence had improved, and we restartedthe lidocaine infusion at a dose of 100 mg/day. She demonstrated no clinical symptomsof lidocaine intoxication and achieved effectivepain control until she died on Day 28.

Case 2A 70-year old woman with ovarian cancer was

admitted to our palliative care unit for paincontrol. She had abdominal and back pain dueto an intra-pelvic tumor and peritoneal dissemi-nation. Radiological examinations revealed noliver metastases or cirrhosis. Laboratory exami-nation showed normal liver and renal function(total bilirubin 0.2 mg/dl, GOT 12 IU, GPT 5IU, alkaline phosphatase 194 IU, creatinine0.42 mg/dl, BUN 14 mg/dl).

Her pain had been well controlled with aneurolytic inferior mesenteric plexus block,NSAIDs, and transdermal fentanyl at a dose of

Vol. 30 No. 1 July 2005 7Letters

Mini-Dose Titrationof the Transdermal FentanylPatch—A Novel Approachby Adjusting the Area of Absorption

To the Editor:The transdermal fentanyl system (Duragesic,

Janssen Pharmaceutica, Beerse, Belgium) providescontinuous transdermal delivery of fentanyl citrate(TDF) for 72 hours. The standard formulationof Duragesic is available in four sizes (10, 20,30, and 40 cm2), which delivers fentanyl at ratesof approximately 25, 50, 75, and 100 µg/hr. Withan identical composition per unit area in all foursizes, the amount of fentanyl released from eachsystem is directly proportional to the surfacearea, with a release rate of 25 µg/hr per 10 cm2.

Although the TDF patch has been shown toprovide satisfactory pain relief in a wide rangeof clinical settings, there are a number of disad-vantages associated with this unique formula-tion. Among them, the lack of a lower dose(e.g., 12.5 µg/hr) has caused much incon-venience to clinicians.1 It is not uncommon thatpatients who exhibit intense nausea and vom-iting with the lowest dose of TDF currently avail-able (i.e., 25 µg/hr), have to be excluded fromTDF administration because of the lack of asmaller patch. The package insert issued by thepharmaceutical company also does not allowthe patch to be cut into smaller pieces in fearof damage to its integrity.

The initial dose of TDF is usually chosenbased on daily consumption of opioids. Therecommended daily dose of oral morphineequivalent to a 25 µg/hr patch has varied,2,3

and is now 45–134 mg.3 The marked variationin morphine dosage strongly suggests the lackof a fixed conversion ratio between daily mor-phine and TDF patch. As a result, it would beimpossible to convert a variable dose, e.g., lessthan 45 mg/24 hr of oral morphine, into equia-nalgesic TDF patch. This inability to providemini-dose titration as flexible as other opioidpreparations is a critical disadvantage for theclinical use of TDF. Although the use of TDFin pediatric patients has been reported,4,5

severe side effects have also occurred.6 Also,no study has described the method of downwarddose titration in children.

75 µg/hr, and continuous intravenous infusionof morphine at a dose of 80 mg/day. On day100, she developed neuropathic pain in the leftlower extremity due to progressive intra-pelvictumor. We added intravenous lidocaine in adaily dose of 200 mg for pain palliation, and twodays later, pain was moderately improved. Theserum concentration of lidocaine was 4.3 µg/ml.One week later, she developed increasing som-nolence. Laboratory examinations showednormal liver and renal function, and sodiumand calcium levels (total bilirubin 0.2 mg/dl,GOT 12 IU, GPT 5 IU, alkaline phosphatase 203IU, creatinine 0.46 mg/dl, sodium 139 mEq/l,calcium 7.0 mg/dl). Serum concentration oflidocaine was then 8.4 µg/ml. Thus, we attrib-uted the main etiology of the patient’s somno-lence to lidocaine overdose, and lidocaine wasimmediately withdrawn. Two days later, somno-lence disappeared without an increase in pain.

CommentIn both cases, lidocaine was administered as

a smaller dosage than usually is recommended,and liver function was normal. Nonetheless,serum concentrations of lidocaine increased tomore than 8.0 µg/ml. These cases suggest thatclinicians should note that lidocaine intoxica-tion may occur in terminally ill cancer patients,even if the dose is very low. Measuring theserum concentration of lidocaine could thusbe helpful for avoiding lidocaine intoxicationand maximizing patient comfort.

Yo Tei, MDTatsuya Morita, MDHideki Shishido, MDSatoshi Inoue, MDSerei Hospice, Seirei Mikatahara HospitalShizuoka, Japan

doi:10.1016/j.jpainsymman.2005.05.005

References1. Attal N, Gaude V, Bresseiur L, et al. Intravenouslidocaine in central pain. Neurology 2000;54:564–574.

2. Mao J, Chen LL. Systemic lidocaine for neuro-pathic pain relief. Pain 2000;87:7–17.3. Chong MS, Bajwa ZH. Diagnosis and treatmentof neuropathic pain. J Pain Symptom Manage 2003;25:S4–S11.

4. McCaughey W. Adverse effects of local anesthe-tics. Drug Safety 1992;7:178–189.