prevented unexpected movements of the headand tracheal compression.

The ability of fentanyl to increase muscletone is well known to anesthesiologists. Intra-venous fentanyl given during anesthesia causeschest rigidity and needs to be counteracted bymuscle relaxants.2,3 Preterm infants seem to beparticularly sensitive to fentanyl.4e7 Fortu-nately, muscle rigidity can be antagonized bybenzodiazepines,8,9 amantadine,10 and in cri-ses with naloxone.11 Although fentanyl mayact on mu opioid receptors in a similar wayto morphine, the beneficial effect of fentanylmay be nullified by increased chest rigidity.Until now, it was thought that chest muscle ri-gidity occurs only with high intravenous dosesof fentanyl. However, we think that this effect,which occurs in patients with motor neurondisease, may also be present in premature in-fants and muscle wasting in cachexia. Mor-phine is the only opioid drug with evidencedeffect in breathlessness, and perhaps fentanylshould be avoided for this purpose, especiallyin cachectic patients with weak muscles.

Zbigniew Zylicz, MDSt. Elizabeth HospiceIpswich, United KingdomMikolaj Kopernik UniversityBydgoszcz, Poland

Lia Lens van Rijn-van der Plaat, PhDSt. Peter and St. James HospiceLewis, United Kingdom

doi:10.1016/j.jpainsymman.2006.05.001

References1. Jennings AL, Davies AN, Higgins JP, Broadley K.

Opioids for the palliation of breathlessness in termi-nal illness. Cochrane Database Syst Rev 2001;CD002066.

2. Rosenberg M. Muscle rigidity with fentanyl:a case report. Anesth Prog 1977;24:50e52.

3. Askgaard B, Nilsson T, Ibler M, Jansen E,Hansen JB. Muscle tone under fentanyl-nitrous ox-ide anaesthesia measured with a transducer appara-tus in cholecystecomy incisions. Acta AnaesthesiolScand 1977;21:1e4.

4. Glick C, Evans OB, Parks BR. Muscle rigiditydue to fentanyl infusion in the pediatric patient.South Med J 1996;89:1119e1120.

5. Lindemann R. Respiratory muscle rigidity ina preterm infant after use of fentanyl during Caesar-ean section. Eur J Pediatr 1998;157:1012e1013.

6. Lemmen RJ, Semmekrot BA. Muscle rigiditycausing life-threatening hypercapnia following fen-tanyl administration in a premature infant. Eur JPediatr 1996;155:1067.

7. Lui PW, Lu PK, Hsieh JC, Lee TY. Post-operativemuscle rigidity in an infant. Eur J Anaesthesiol 1992;9:419e423.

8. Sanford TJ Jr, Weinger MB, Smith NT, et al. Pre-treatment with sedative-hypnotics, but not withnondepolarizing muscle relaxants, attenuatesalfentanil-induced muscle rigidity. J Clin Anesth 1994;6:473e480.

9. Mayumi T, Matsumiya N, Fujita S, Dohi S. Diaz-epam prevents fentanyl-induced muscle rigidity.J Anesth 1990;4:82e84.

10. Silbert BS, Vacanti CA. Amantidine in preven-tion of fentanyl-induced muscle rigidity. AnesthAnalg 1987;66:1338.

11. Muller P, Vogtmann C. Three cases with differ-ent presentation of fentanyl-induced muscle rigi-dityda rare problem in intensive care of neonates.Am J Perinatol 2000;17:23e26.

200 Vol. 32 No. 3 September 2006Letters

Successful Treatmentof Bronchorrhea with Octreotidein a Patient with Adenocarcinomaof the Lung

To the Editor:Bronchorrhea is defined as the production

of sputum of >100 mL/day.1 It is an uncom-mon symptom in lung cancer patients, and isusually associated with the bronchioloalveolarcarcinoma (BAC) subtype. It can cause exhaus-tion and make social integration difficult. Toour knowledge, an effective treatment regimenhas not been established. Case reports haveshown some treatments to be effective in indi-vidual patients. Inhaled indomethacin hasbeen reported to reduce sputum productionand improve quality of life in patients withBAC and bronchorrhea.2 Erythromycin andcorticosteroids may also reduce sputum pro-duction in these patients.3,4 In addition, sev-eral case reports have shown encouragingresults using the epidermal growth factor re-ceptor tyrosine kinase inhibitor, gefitinib.5,6

We report the successful treatment of bron-chorrhea with octreotide in a patient with ade-nocarcinoma of the lung. In September 2003,a 74-year-old woman presented to hospital witha 2-month history of breathlessness and

Vol. 32 No. 3 September 2006 201Letters

nonproductive cough. A chest radiographshowed consolidation of the left lower lobe.Sputum microscopy and culture showed nor-mal flora with a light growth of Candida albi-cans, and sputum cytology showed nomalignant cells. A computerized tomographicscan of the thorax and upper abdomenshowed nonspecific, widespread, bilateral,patchy ground glass opacification predomi-nantly in the lower lobes, with more confluentareas of consolidation at the left base (Fig. 1).Bronchoscopy showed frothy secretions well-ing up from basal bronchi bilaterally, moremarked throughout the left airway. Transbron-chial lung biopsies were taken from the leftlower lobe under fluoroscopic screening. His-tology showed a well-differentiated invasive ad-enocarcinoma of acinar subtype.

Her poor performance status precluded cy-totoxic chemotherapy, and management wassymptomatic. By Day 23, the cough had be-come productive, producing 200 mL of clearfrothy sputum per day. Oral morphine wasstarted to alleviate increasing dyspnea andmusculoskeletal chest pain. There was a tempo-rary reduction in the volume of sputum pro-duced, possibly as a result of the opioidtherapy; however, by Day 44, sputum produc-tion had increased to 500 mL a day. By Day55, sputum volume was in excess of 1 L perday and associated with a continuous anteriornasal drip. The patient was referred to the

palliative care unit, and octreotide was startedat 300 mg over 24 hours via a subcutaneoussyringe driver. The clinical effect was dramatic;by Day 57, the volume of sputum had de-creased to 150 mL a day and the dose of oc-treotide was increased to 500 mg over 24hours. By Day 58, sputum production had sub-sided completely. There were no side effectsfrom the treatment. The patient passed away16 days after starting octreotide, which wascontinued until death, and at no point didthe bronchorrhea return.

Octreotide is a synthetic analogue of the hy-pothalamic release-inhibiting hormone so-matostatin. The exact mechanism of actionof octreotide is not known, but its effects aresimilar to those of somatostatin and it is be-lieved to act at the same receptors. Octreotideinhibits the secretion of both pituitary and gas-trointestinal hormones, including serotonin,gastrin, vasoactive intestinal peptide, and se-cretin. This antisecretory effect of octreotideis used extensively in palliative medicine. It isuseful in thesymptomaticmanagementofbowelobstruction, ascites, diarrhea, and fistulae.7e9

It has been suggested that the mechanism ofbronchorrhea in patients with BAC is mainlythrough increased transepithelial chloride(Cl) secretion.2 This mechanism may play a sig-nificant role in bronchorrhea secondary toother lung diseases, including invasive adeno-carcinoma. The duodenal peptide secretin is

Fig. 1. Computerized tomographic scan of the thorax showing widespread, bilateral, patchy ground glassopacification.

Ketorolac in Neuropathic Pain

To the Editor:Neuropathic pain is the result of damage or

dysfunction to the nervous system along affer-ent sensory pathways. The lesion may be withinthe central nervous system or at the level of thedorsal root ganglion or peripheral nerve. Neu-ropathic pain often is described by the patientas shooting or burning pain, numbness, pares-thesias, or sensitivity to normal touch. Sensoryor motor loss is evident on examination withinthe area of pain, and often there is a paradoxi-cally altered sensation such as allodynia and hy-peralgesia. The prevalence of neuropathic painin cancer is 25%e50% according to a survey ofthose visiting pain clinics.1

Ketorolac is a nonsteroidal anti-inflamma-tory drug (NSAID) with greater systemic anal-gesic than anti-inflammatory potency. Unlikeother NSAIDs in the United States, ketorolaccan be administered parenterally.2 There arereports of responses to subcutaneous ketorolacin the management of cancer-related bone, vis-ceral, and neuropathic pain.1,3 Ketorolac is notcommonly used to treat neuropathic pain, asNSAIDs have limited evidence in the manage-ment of neuropathic pain.4

Despite advances in the understanding ofthe mechanisms that generate neuropathicpain, treatment remains a challenge and em-pirical. We describe a patient with recurrentmetastatic breast cancer and refractory neuro-pathic pain from a brachial plexopathy who

202 Vol. 32 No. 3 September 2006Letters

a potent stimulant of electrolyte and watermovement in pancreatic and biliary epitheliumvia activation of secretin receptors. Secretin re-ceptors are also present in human lung, and ac-tivation of these receptors by secretin potentlystimulates Cl efflux from bronchial epithelialcells.10 One possible mechanism by which oc-treotide may have reduced sputum productionis by lowering plasma levels of secretin, andhence reducing Cl efflux from bronchial epi-thelial cells.

The benefit of octreotide in reducing excesssputum production has not previously been re-ported. Octreotide may be a useful agent inthe management of bronchorrhea due to inva-sive adenocarcinoma of the lung, and maymerit investigation in other lung diseases, in-cluding BAC.

Emma Hudson, MRCPJason F. Lester, FRCRVelindre HospitalCardiff, Wales, UK

Richard L. Attanoos, FRCPathSeamus J. Linnane, MRCPLlandough HospitalCardiff, Wales, UK

Anthony Byrne, MRCPMarie Curie Holme Tower CenterPenarth, Wales, UK

doi:10.1016/j.jpainsymman.2006.05.003

References1. Keal EE. Biochemistry and rheology of sputum

in asthma. Postgrad Med J 1971;47:171e177.

2. Homma S, Kawabata M, Kishi K, et al. Successfultreatment of refractory bronchorrhea by inhaled in-domethacin in two patients with bronchioloalveolarcarcinoma. Chest 1999;115:1465e1468.

3. Suga T, Sugiyama Y, Fuji T, Kitamura S. Bronchio-loalveolar carcinoma with bronchorrhea treated witherythromycin. Eur Respir J 1994;7:2249e2251.

4. Nakajima T, Terashima T, Nishida J, Onoda M,Koide O. Treatment of bronchorrhea by corticoste-roids in a case of bronchioloalveolar carcinoma pro-ducing CA 19-9. Intern Med 2002;41:225e228.

5. Milton DT, Kris MG, Gomez JE, Feinstein MB.Prompt control of bronchorrhea in patients withbronchioloalveolar carcinoma treated with gefitinib(Iressa). Support Care Cancer 2003;13:70e72.

6. Takao M, Inoue K, Watanabe F, et al. Successfultreatment of persistent bronchorrhea by gefitinib in

a case with recurrent bronchioloalveolar carcinoma:a case report. World J Surg Onc 2003;10:1477e1478.

7. Mercadante S, Spoldi E, Caraceni A, Maddaloni S,Simonetti MT. Octreotide in relieving gastrointestinalsymptoms due to bowel obstruction. Palliat Med 1993;7:295e299.

8. Harvey M, Dunlop R. Octreotide and the secre-tory effects of advanced cancer. Palliat Med 1996;10:346e347.

9. Mercadante S. Treatment of diarrhoea due toenterocolic fistula with octreotide in a terminal can-cer patient. Palliat Med 1992;6:257e259.

10. Davis R, Page K, Dos Santos Cruz G, et al. Ex-pression and functions of the duodenal peptide se-cretin and its receptor in human lung. Am J RespirCell Mol Biol 2004;31:302e308.