chemotherapy. N Engl J Med , 305 (3), 170 . Brater, D. C. (1999). Eff ects of nonsteroidal anti-infl ammatory drugs on renal function: focus on cyclooxygenase-2 \200\223selective inhibition. Am J Med , 107 (6), 65 \200\22370 . Coombs, D. W., Saunders, R. L., Fratkin, J. D., Jensen, L. E., and Murphy, C. A. (1986). Co ntinuous intrathecal hydromorphone and clonidine for intractable cancer pain. J Neurosurg , 64 (6), 890 \200\223894 . Breitbart, W. (1998). Psychotropic adjuvant analgesics for pain in cancer and AIDS. Psychooncology , 7 (4), 333 \200\223345 . D \200\231Angio, G. J. (1983). Early and delayed complications of therapy. Cancer , Broomhead, A., Kerr, R., Tester, W., O \200\231Meara, P., Maccarrone, C., Bowles, R., et al . (1997). Comparison of a once-a-day sustained-release morphine formulation with standard oral morphine treatment for cancer pain. J Pain Symptom Manage , 14 (2), 63 \200\22373 . 51 (12 Suppl), 2515 \200\2232518 . Davis, A. M. and Inturrisi, C. E. (1999). D-methadone blocks morphine tolerance and N-methy l-D-aspartate-induced hyperalgesia. J Pharmacol Exp Th er , 289 (2), 1048 \200\2231053 . Brose, W. G. and Cousins, M. J. (1991). Subcutaneous lidocaine for treatment Davis, M. P. and Walsh, D. (2001). Methadone for relief of cancer pain: a review of pharmac okinetics, pharmacodynamics, drug interactions and protocols of administration. Support Car e Cancer , 9 (2), 73 \200\22383 . of neuropathic cancer pain. Pain , 45 (2), 145 \200\223148 . Bruera, E., Ripamonti, C., Brenneis, C., Macmillan, K., and Hanson, J. (1992). A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic canc er pain. J Pain Symptom Manage , 7 (3), 138 \200\223140 . Delarue, A., Bergeron, C., Mechinaud-Lacroix, F., Coze, C., Raphael, M., Patte, C., et al. (2008). Pediatric non-Hodgkin \200\231s lymphoma: primary surgical management of patients p resenting with abdominal symptoms. Recommendations of the Lymphoma Committee of the French Society to Combat Pediatric Cancers (SFCE). J Chir , 145 (5), 454 \200\223458 . Buchanan, D. D., and J MacIvor, F. (2010). A role for intravenous lidocaine in severe cance r-related neuropathic pain at the end-of-life. Support Care Cancer, 18 (7), 899 \200\223901 . Devers, A. and Galer, B. S. (2000). Topical lidocaine patch relieves a variety of neuropath ic pain conditions: an open-label study. Clin J Pain , 16 (3), 205 \200\223208 . Burt, N., Dorman, B. H., Reeves, S. T., Rust, P. F., Pinosky, M. L., Abboud, M. R., et al . (1998). Postdural puncture headache in pediatric oncology patients. Can J Anaesth , 45 (8) , 741 \200\223745 . Dunbar, P. J., Buckley, P., Gavrin, J. R., Sanders, J. E., and Chapman, C. R. (1995). Use o f patient-controlled analgesia for pain control for children receiving bone marrow transpla nt. J Pain Symptom Manage , 10, 604 \200\223611. Campbell, F. A. (2001). Are cannabinoids an eff ective and safe treatment option in the man agement of pain? A qualitative systematic review. Br Med J , 323 (7303), 1 \200\2236 . Caraceni, A., Zecca, E., Bonezzi, C., Arcuri, E., Yaya Tur, R., Maltoni, M., et al . (2004) . Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol , 22 (14), 2909 \200\2232917 . Dunbar, P. J., Chapman, C. R., Buckley, F. P., and Gavrin, J. R. (1996). Clinical analgesic equivalence for morphine and hydromorphone with prolonged PCA. Pain , 68 (2 \200\2233), 26 5 \200\223270 . SECTION 4 pain in specific populations and diseases 168 Grond, S., Radbruch, L., Meuser, T., Loick, G., Sabatowski, R., and Lehmann, K.A. (1999). H igh-dose tramadol in comparison to low-dose morphine for cancer pain relief. J Pain Symptom Manage , 18 (3), 174 \200\223179 . Dworkin, R. H., O \200\231Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jens en, T. S., et al . (2007). Pharmacologic management of neuropathic pain: evidence-based rec ommendations. Pain , 132 (3), 237 \200\223251 . Gupta, H., Davidoff , A. M., Pui, C. H., Shochat, S. J., and Sandlund, J. T. (2007). Clinic al implications and surgical management of intussusception in pediatric patients with Burki tt lymphoma. J Pediatric Surg , 42 (6), 998 \200\223 1001 ; discussion 1001. Eisenach, J. C., DuPen, S., Dubois, M., Miguel, R., and Allin, D. (1995). Epidural clonidin e analgesia for intractable cancer pain. Th e Epidural Clonidine Study Group. Pain , 61 (3) , 391 \200\223399 . Ellemann, K., Sjogren, P., Banning, A. M., Jensen, T. S., Smith, T., and Geertsen, P. (1989 ). Trial of intravenous lidocaine on painful neuropathy in cancer patients. Clin J Pain , 5 (4), 291 \200\223294 . Guti rrez-Guti rrez, G., Sereno, M., Miralles, A., Casado-S enz, E., and Guti r rez-Rivas, E. (2010). Chemotherapy-induced peripheral neuropathy: clinical features, diagno sis, prevention and treatment strategies. Clin Transl Oncol , 12 (2), 81 \200\22391 . Ellison, N., Loprinzi, C. L., Kugler, J., Hatfi eld, A. K., Miser, A., Sloan, J. A., et al . (1997). Phase III placebo-controlled trial of capsaicin cream in the management of surgic al neuropathic pain in cancer patients. J Clin Oncol , 15 (8), 2974 \200\2232980 . Halpin, T. J., Holtzhauer, F. J., Campbell, R. J., Hall, L. J., Correa-Villasenor, A., Lane se, R., et al . (1982). Reye \200\231s syndrome and medication use. JAMA , 248 (6), 687 \200\223691 . El-Tahtawy, A., Kokki, H., and Reidenberg, B. E. (2006). Population pharmacokinetics of oxy codone in children 6 months to 7 years old. J Clin Pharmacol , 46 (4), 433 \200\223442 . Hanif, I., Mahmoud, H., and Pui, C. H. (2006). Avascular femoral head necrosis in pediatric cancer patients. Med Pediatr Oncol , 21 (9), 655 \200\223660 . Hardy, J. R., Rees, E. A., Gwilliam, B., Ling, J., Broadley, K., and A \200\231Hern, R. (20 01). A phase II study to establish the effi cacy and toxicity of sodium valproate in patien ts with cancer-related neuropathic pain. J Pain Symptom Manage , 21 (3), 204 \200\223209 . England, R. J., Pillay, K., Davidson, A., Numanoglu, A., and Millar, A. J. (2012). Intussus ception as a presenting feature of Burkitt lymphoma: implications for management and outcom e. Pediatr Surg Int , 28 (3), 267 \200\223270 . Ernst, D. S., MacDonald, R. N., Paterson, A. H. G., Jensen, J., Brasher, P., and Bruera, E. (1992). A double-blind, crossover trial of intravenous clodronate in metastatic bone pain. J Pain Symptom Manage , 7 (1), 4 \200\22311 . Field, T., Cullen, C., Diego, M., Hernandez- Reif, M., Sprinz, P., Beebe, K., et al . (2001). Leukemia immune changes following massage therapy. J Bodywork Movement Th er , 5 (4), 271 \200\223274 . Harke, H., Gretenkort, P., Ladleif, H. U., Rahman, S., and Harke, O. (2001). Th e response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and susta ined-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Anesth Analg , 92 (2), 488 \200\223495 . Hiruki, T., Fernandes, B., Ramsay, J., and Rother, I. (1992). Acute typhlitis in an immunoc ompromised host. Report of an unusual case and review of the literature. Dig Dis Sci , 37 ( 8), 1292 \200\2231296 . Finkel, J. C., Finley, A., Greco, C., Weisman, S. J., and Zeltzer, L. (2005). Transdermal f entanyl in the management of children with chronic severe pain: results from an internation al study. Cancer , 104 (12), 2847 \200\2232857 . Finkel, J. C., Pestieau, S. R., and Quezad o, Z. M. (2007). Ketamine as an adjuvant for treatment of cancer pain in children and adole scents. J Pain , 8 (6), 515 \200\223521 . Howlader, N., Noone, A. M., Krapcho, M., Neyman, N., Aminou, R., Altekruse, S. F., et al . (2012). SEER cancer statistics review, 1975 \200\2232009 (vintage 2009 populations), based on November 2011 SEER data submission . Bethesda, MD: National Cancer Institute . Fitzgibbon, D. R., and Ready, L .B. (1997). Intravenous high-dose methadone administered by patient controlled analgesia and continuous infusion for the treatment of cancer pain refr actory to high-dose morphine. Pain , 73 (2), 259 \200\223261 . Huang, T. T. and Ness, K. K. (2011). Exercise interventions in children with cancer: a review. Int J Pediatr , 2011, 461512 . Hughes, D., Ladas, E., Rooney, D., and Kelly, K. (2008). Massage therapy as a supportive ca re intervention for children with cancer. Oncol Nursing Forum, 431 \200\223442 . Friedman, T., Slayton, W. B., Allen, L. S., Pollock, B. H., Dumont-Driscoll, M., Mehta, P., et al . (1997). Use of alternative therapies for children with cancer. Pediatrics , 100 (6 ), e1 . Hunt, A., Joel, S., Dick, G., and Goldman, A. (1999). Population pharmacokinetics of oral m orphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr , 135 (1), 47 \200\22355 . Frisk, P., St lberg, E., Str mberg, B., and Jakobson, \205 . (2001). Painful periphe ral neuropathy aft er treatment with hig h- dose ifosfamide. Med Pediatr Oncol , 37 (4), 37 9 \200\223382 . Hurwitz, E. S., Barrett, M. J., Bregman, D., Gunn, W. J., Schonberger, L. B., Fairweather, W. R., et al . (1985). Public Health Service study on Reye \200\231s syndrome and medicatio ns. Report of the pilot phase. N Engl J Med , 313 (14), 849 \200\223857 . Fulfaro, F., Casuccio, A., Ticozzi, C., and Ripamonti, C. (1998). Th e role of bisphosphona tes in the treatment of painful metastatic bone disease: a review of phase III trials. Pain , 78 (3), 157 \200\223169 . Galeotti, N., Vivoli, E., Bilia, A. R., Vincieri, F. F., and Ghelardini, C. (2010). St. Joh n \200\231s Wort reduces neuropathic pain through a hypericin-mediated inhibition of the pr otein kinase Cgamma and epsilon activity. Biochem Pharmacol , 79 (9), 1327 \200\2231336 . Huskey, A. (2006). Cannabinoids in cancer pain management. J Pain Palliat Care Pharmacother , 20 (3), 43 \200\22346 . Jadad, A. R., and Browman, G. P. (1995). Th e WHO analgesic ladder for cancer pain manageme nt: stepping up the quality of its evaluation. JAMA , 274 (23), 1870 \200\2231873 . Garrido, M. J., Habre, W., Rombout, F., and Troconiz, I. F. (2006). Population pharmacokine tic/pharmacodynamic modeling of the analgesic eff ects of tramadol in pediatrics. Pharmaceu t Res , 23 (9), 2014 \200\2232023 . Jay, S. M., Ozolins, M., Elliott, C. H., and Caldwell, S. (1983). Assessment of children \200\231s distress during painful medical procedures. Health Psychol , 2 (2), 133 \200\2231 47 . Geiser, C. F., Bishop, Y., Jaff e, N., Furman, L., Traggis, D., and Frei, E., 3rd. (1975). Adverse eff ects of intrathecal methotrexate in children with acute leukemia in remission. Blood , 45 (2), 189 \200\223195 . Kannan, T. R., Saxena, A., Bhatnagar, S., and Barry, A. (2002). Oral ketamine as an adjuvan t to oral morphine for neuropathic pain in cancer patients. J Pain Symptom Manage , 23 (1), 60 \200\22365 . George, R. M. and Ahmedzai, S. H. (2000). Th e management of neuropathic pain in cancer: cl inical guidelines for the use of adjuvant analgesics. Indian J Cancer , 37 (1), 4 \200\2239 . Katz, E. R., Kellerman, J., and Siegel, S. E. (1980). Behavioral distress in children with cancer undergoing medical procedures: developmental considerations. J Consult Clin Psychol , 48 (3), 356 \200\223365 . Goldschneider, K. R., Racadio, J. M., and Weidner, N. J. (2007 ). Celiac plexus blockade in children using a three-dimensional fl uoroscopic reconstruction technique: case reports. R eg Anesth Pain Med , 32 (6), 510 \200\223515 . Khojainova, N., Santiago-Palma, J., Kornick, C., Breitbart, W., and Gonzales, G. R. (2002). Olanzapine in the management of cancer pain. J Pain Symptom Manage , 23 (4), 346 \200\2233 50 . Goodarzi, M. (1999). Comparison of epidural morphine, hydromorphone and fentanyl for postop erative pain control in children undergoing orthopedic surgery. Paediatr Anaesth , 9 (5), 4 19 \200\223422 . Kokki, H., Rasanen, I., Lasalmi, M., Lehtola, S., Ranta, V.P., Vanamo, K., et al . (2006). Comparison of oxycodone pharmacokinetics aft er buccal and sublingual administration in chi ldren. Clinical Pharmacokinet , 45 (7), 745 \200\223754 . Grande, L. A., O \200\231Donnell, B. R., Fitzgibbon, D. R., and Terman, G. W. (2008). Ultra -low dose ketamine and memantine treatment for pain in an opioid- tolerant oncology patient . Anesth Analg , 107 (4), 1380 \200\2231383 . CHAPTER 17 pediatric cancer pain 169 gastrointestinal symptoms due to malignant inoperable bowel obstruction. Support Care Cance r , 8 (3), 188 \200\223191 . Kokki, H., Rasanen, I., Reinikainen, M., Suhonen, P., Vanamo, K., and Ojanpera, I. (2004). Pharmacokinetics of oxycodone aft er intravenous, buccal, intramuscular and gastric adminis tration in children. Clin Pharmacokinet , 43 (9), 613 \200\223622 . Mercadante, S., Casuccio, A., and Genovese, G. (1998). Ineff ectiveness of dextromethorphan in cancer pain. J Pain Symptom Manage , 16 (5), 317 \200\223322 . Kornick, C. A., Kilborn, M. J., Santiago-Palma, J., Schulman, G., Th aler, H. T., Keefe, D. L., et al . (2003). QTc interval prolongation associated with intravenous methadone. Pain , 105 (3), 499 \200\223506 . Meyer, C. T., Wilsey, M. J., Hale, G. A., Monforte, H. L., and Danielson, P. D. (2012). Pri mary Burkitt \200\231s lymphoma of the colon \200\224an uncommon cause of acute constipatio n and abdominal pain. Fetal Pediatr Pathol , 31 (4), 254 \200\223259 . Krane, E. J. and Heller, L. B. (1995). Th e prevalence of phantom sensation and pain in ped iatric amputees. J Pain Symptom Manage , 10 (1), 21 \200\22329 . Krantz, M. J., Lewkowiez, L., Hays, H., Woodroff e, M. A., Robertson, A. D., and Mehler, P. S. (2002). Torsade de poi ntes associated with very-high- dose methadone. Ann Internal Med , 137 (6), 501 \200\223504 . Miaskowski, C., Cleary, J., Burney, R., Coyne, P., Finley, R., Foster, R., et al . (2004). Guideline for the management of cancer pain in adults and children, APS Clinical Practice G uidelines Series, No. 3 . Glenview, IL : American Pain Society. Krantz, M. J., Rowan, S. B., Schmittner, J., and Bucher Bartelson, B. (2007). Physician awa reness of the cardiac eff ects of methadone: results of a national survey. J Addict Dis , 2 6 (4), 79 \200\22385 . Miser, A. W., Dothage, J. A., Wesley, R. A., and Miser, J. S. (1987a). Th e prevalence of p ain in a pediatric and young adult cancer population. Pain , 29(1), 73 \200\22383. Lauretti, G. R., Lima, I. C., Reis, M. P., Prado, W. A., and Pereira, N. L. (1999). Oral ke tamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for ca ncer pain management. Anesthesiology , 90 (6), 1528 \200\2231533 . Miser, A. W., McCalla, J., Dothage, J. A., Wesley, M., and Miser, J. S. (1987b). Pain as a presenting symptom in children and young adults with newly diagnosed malignancy. Pain , 29( 1), 85 \200\22390. Murray, A. and Hagen, N.A. (2005). Hydromorphone. J Pain Symptom Le Deley, M. C., Rosolen, A., Williams, D. M., Horibe, K., Wrobel, G., Attarbaschi, A., et al . (2010). Vinblastine in children and adolescents with high-risk anaplastic large-cell l ymphoma: results of the randomized ALCL99-vinblastine trial. J Clin Oncol , 28 (25), 3987 \200\2233993 . Manage , 29 (5), 57 \200\22366 . Otto, M., Bach, F. W., Jensen, T. S., and Sindrup, S. H. (2007). Health-related quality of life and its predictive role for analgesic eff ect in patients with painful polyneuropathy. Eur J Pain , 11 (5), 572 \200\223578 . Lesko, S. M. and Mitchell, A. A. (1999). Th e safety of acetaminophen and ibuprofen among c hildren younger than two years old. Pediatrics , 104 (4), e39. Patt, R. B., Proper, G., and Reddy, S. (1994). Th e neuroleptics as adjuvant analgesics. J Pain Symptom Manage , 9 (7), 446 \200\223453 . Lindeman, G., Keff ord, R., Stuart-Harris, R., Legha, S. S., and Mollman, J. E. Pitetti, R., Singh, S., Hornyak, D., Garcia, S.E., and Herr, S. (2001). Complementary and a lternative medicine use in children. Pediatr Emerg Care , 17 (3), 165 \200\223169 . (1990). Cisplatin neurotoxicity. N Engl J Med , 323 (1), 64 \200\22365 . Liossi, C. and Hatira, P. 2003). Clinical hypnosis in the alleviation of procedure-related pain in pediatric oncology patients. Int J Clin Exp Hypnosis , 51 (1), 4 \200\22328 . Portenoy, R. K. (1994 ). Tolerance to opioid analgesics: clinical aspects. Cancer Surv , 21 , 49 \200\22365 . Ljungman, G., Gordh, T., Sorensen, S., and Kreuger, A. (1999). Pain in pediatric oncology: interviews with children, adolescents and their parents. Acta Paediatr , 88(6), 623 \200 \223630. Portenoy, R. K. (1993). Adjuvant analgesics in pain management. In D. Doyle, G. W. C. Hanks , and N. MacDonald (eds) Oxford textbook of palliative medicine , pp. 187 \200\223203. Oxfo rd: Oxford University Press . Ljungman, G., Gordh, T., Sorensen, S., and Kreuger, A. (2000). Pain variations during cance r treatment in children: a descriptive survey. Pediatr Hematol Oncol , 17 (3), 211 \200\223 221 . Post-White, J., Fitzgerald, M., Savik, K., Hooke, M.C., Hannahan, A. B., and Sencer, S. F. (2009). Massage therapy for children with cancer. J Pediatr Oncol Nurs , 26 (1), 16 \200 \22328 . Lussier, D., Huskey, A. G., and Portenoy, R. K. (2004). Adjuvant analgesics in Poyhia, R., Vainio, A., and Kalso, E. (1993). A review of oxycodone \200\231s clinical phar macokinetics and pharmacodynamics. J Pain Symptom Manage , 8 (2), 63 \200\22367 . cancer pain management. Oncologist , 9 (5), 571 \200\223591 . Lynch, M. E. (2005). A review of the use of methadone for the treatment of chronic noncancer pain. Pain Res Manag , 10 (3), 133 \200\223144 . Prommer, E. (2004). Th e other NMDA antagonists, amantadine, memantine, dextromethorphan: r ole in cancer therapeutics. J Clin Oncol (Meeting Abstracts) , 8223 . Magni, G. (1991). Th e use of antidepressants in the treatment of chronic pain. A review of the current evidence. Drugs , 42 (5), 730 \200\223748 . Magni, G., Arsie, D., and DeLeo, D. (1987 a). Antidepressants in the treatment Pud, D., Eisenberg, E., Spitzer, A., Adler, R., Fried, G., and Yarnitsky, D. (1998). Th e N MDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain , 75 (2 \200\2233), 349 \200\22335 4 . of cancer pain. A survey in Italy. Pain , 29 (3), 347 \200\223353 . Magni, G., Conlon, P., and Arsie, D. (1987 b). Tricyclic antidepressants in the treatment o f cancer pain: a review. Pharmacopsychiatry , 20 (4), 160 \200\223164 . Marchese, V. G., Ch iarello, L. A., and Lange, B. J. (2003). Eff ects of physical therapy intervention for chil dren with acute lymphoblastic leukemia. Pediatr Blood Cancer , 42 (2), 127 \200\223133 . Ramachandran, V. S. and Rogers-Ramachandran, D. (1996). Synaesthesia in phantom limbs induc ed with mirrors. Proc Biol Sci , 263 (1369), 377 \200\223386 . Reddy, A. T., and Witek, K. (2003). Neurologic complications of chemotherapy for children w ith cancer. Curr Neurol Neurosci Rep , 3 (2), 137 \200\223142 . Mattano, L. A. Jr, Sather, H. N., Trigg, M. E., and Nachman, J. B. (2000). Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Chi ldren \200\231s Cancer Group. J Clin Oncol , 18 (18), 3262 \200\2233272 . Reinders-Messelink, H. A., Van Weerden, T. W., Fock, J. M., Gidding, C. E., Vingerhoets, H. M., Schoemaker, M. M., et al . (2000). Mild axonal neuropathy of children during treatment for acute lymphoblastic leukemia. Eur J Paediatr Neurol , 4 (5), 225 \200\223233 . McCleane, G. J. (1999). Intravenous infusion of phenytoin relieves neuropathic pain: a rand omized, double-blinded, placebo-controlled, crossover study. Anesth Analg , 89 (4), 985 \200\223988 . Rheingans, J. I. (2007). A systematic review of nonpharmacologic adjunctive therapies for s ymptom management in children with cancer. J Pediatr Oncol Nurs , 24 (2), 81 \200\22394 . McGrath, P. A. (1996). Development of the World Health Organization guidelines on cancer pa in relief and palliative care in children. J Pain Symptom Manage , 12 (2), 87 \200\22392 . Richter, P. A. and Burk, M. P. (1992). Th e potentiation of narcotic analgesics McGrath, P. J., Beyer, J., Cleeland, C., Eland, J., McGrath, P. A., and Portenoy, R. (1990) . Report of the Subcommittee on Assessment and Methodologic Issues in the Management of Pai n in Childhood Cancer. Pediatrics , 86 (5 Pt 2), 814 \200\223817 . with phenothiazines. J Foot Surg , 31 (4), 378 \200\223380 . Ripamonti, C., De Conno, F., Groff , L., Belzile, M., Pereira, J., Hanson, J., et al . (199 8). Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: co mparison of two clinical experiences. Ann Oncol , 9 (1), 79 \200\22383 . Mercadante, S., Ripamonti, C., Casuccio, A., Zecca, E., and Groff , L. (2000). Comparison o f octreotide and hyoscine butylbromide in controlling SECTION 4 pain in specific populations and diseases 170 Tremont-Lukats, I. W., Megeff, C., and Backonja, M. M. (2000). Anticonvulsants for neuropat hic pain syndromes: mechanisms of action and place in therapy. Drugs , 60 (5), 1029 \200 \2231052 . Roberts, S. B., Wozencraft , C. P., Coyne, P. J., and Smith, T. J. (2011). Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. J Palliat Med , 14 (3), 371 \200\2233 73 . Ugur, F., Gulcu, N., and Boyaci, A. (2006). Intrathecal infusion therapy with dexmedetomidi ne - supplemented morphine in cancer pain. Acta Anaesthesiol Scand , 51 (3), 388 \200\22338 8 . Rosen, L. S., Gordon, D., Kaminski, M., Howell, A., Belch, A., Mackey, J., et al . (2001). Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, compar ative trial. Cancer J, 7 (5), 377 \200\223387 . Van Daele, D. J., Finnegan, E. M., Rodnitzky, R. L., Zhen, W., McCulloch, T. M., and Hoff m an, H. T. (2002). Head and neck muscle spasm aft er radiotherapy: management with botulinum toxin A injection. Arch Otolaryngol \200\224Head Neck Surg , 128 (8), 956 \200\223959 . Rowbotham, M. C., Davies, P. S., Verkempinck, C., and Galer, B. S. (1996). Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain , 65 (1), 39 \200\22344 . Voute, P. A., Hoefnagel, C. A., and de Kraker, J. (1988). 131I-meta- iodobenzylguanidine in diagnosis and treatment of neuroblastoma. Bull Cancer , 75 (1), 107 \200\223111 . Rozans, M., Dreisbach, A., Lertora, J .J. L., and Kahn, M. J. (2002). Palliative uses of me thylphenidate in patients with cancer: a review. J Clin Oncol , 20 (1), 335 \200\223339 . Watanabe, S. and Bruera, E. (1994). Corticosteroids as adjuvant analgesics. J Pain Symptom Manage , 9 (7), 442 \200\223445 . Safa-Tisseront, V., Th ormann, F., Malassine, P., Henry, M., Riou, B., Coriat, P., et al . (2001). Eff ectiveness of epidural blood patch in the management of post-dural puncture hea dache. Anesthesiology , 95 (2), 334 \200\223339 . Webster, L., Andrews, M., and Stoddard, G. (2003). Modafi nil treatment of opioid-induced sedation. Pain Med , 4 (2), 135 \200\223140 . Sandier, S. G., Tobin, W., and Henderson, E. S. (1969). Vincristine-induced neuropathy A cl inical study of fi ft y leukemic patients. Neurology , 19 (4), 367 \200\223374 . Wee, L., Lam, F., and Cranston, A. (2008). Th e incidence of post dural puncture headache in children. Anesthesia , 51 (12), 1164 \200\2231166 . Wei, S. Y., Esmail, A. N., Bunin, N., and Dormans, J. P. (2000). Avascular necrosis in chil dren with acute lymphoblastic leukemia. J Pediatr Orthopaed , 20 (3), 331 \200\223335 . Sandler, D. P., Smith, J. C., Weinberg, C. R., Buckalew, V. M. Jr., Dennis, V. W., Blythe, W. B., et al . (1989). Analgesic use and chronic renal disease. N Engl J Med , 320 (19), 12 38 \200\2231243 . Weinbroum, A. A., Bender, B., Bickels, J., Nirkin, A., Marouani, N., Chazam, S., et al . (2 003). Preoperative and postoperative dextromethorphan provides sustained reduction in posto perative pain and patient-controlled epidural analgesia requirement: a randomized, placebo- controlled, double-blind study in lower-body bone malignancy-operated patients. Cancer , 97 (9), 2334 \200\2232340 . Scher, C., Amar, D., Ginsburg, I., Reinsel, R., McDowall, R., and Barst, S. (1992). Post du ral puncture headache in children with cancer. Anesthesiology , 77 (3A), A1183 . Shaiova, L., Berger, A., Blinderman, C. D., Bruera, E., Davis, M. P., Derby, S., et al . (2 008). Consensus guideline on parenteral methadone use in pain and palliative care. Palliat Supp Care , 6 (02), 165 \200\223176 . Weisman, S. J. and Wishnie, E. (1996). Postoperative hydromorphone epidural analgesia in ch ildren. Poster presentation at 8th World Congress on Pain, Vancouver, Canada. Silberstein, E. B. (1993). Th e treatment of painful osseous metastases with phosphorus-32- labeled phosphates. Semin Oncol , 20(3 Suppl 2), 10 \200\22321. Silberstein, E. B. (1994). Th e treatment of painful osteoblastic metastases: what can we expect from nuclear oncology ? J Nucl Med , 35 (12), 1994 \200\2231995 . Silberstein, E. B., Elgazzar, A. H., and Kapili vsky, A. (1992). Phosphorus-32 radiopharmaceuticals for the treatment of painful osseous me tastases. Semin Nucl Med , 22 (1), 17 \200\22327 . Westlin, J. E., Letocha, H., Jakobson, A., Strang, P., Martinsson, U., and Nilsson, S. (199 5). Rapid, reproducible pain relief with [131I]iodine- meta-iodobenzylguanidine in a boy wi th disseminated neuroblastoma. Pain , 60 (1), 111 \200\223114 . Windebank, A. J., and Grisold, W. (2008). Chemotherapy-induced neuropathy. J Periph Nerv Syst , 13 (1), 27 \200\22346 . Silberstein, E. B. and Williams, C. (1985). Strontium-89 therapy for the pain of osseous metastases. J Nucl Med , 26 (4), 345 \200\223348 . World Health Organization. (1990). Cancer pain relief and palliative care. Report of a WHO expert committee . Geneva: World Health Organization. Simpson, D. M., Brown, S., and Tobias, J. (2008). Controlled trial of high- concentration c apsaicin patch for treatment of painful HIV neuropathy. Neurology , 70 (24), 2305 \200\2232 313 . Yee, J. D. and Berde, C. B. (1994). Dextroamphetamine or methylphenidate as adjuvants to op ioid analgesia for adolescents with cancer. J Pain Symptom Manage , 9 (2), 122 \200\223125 . Sindrup, S. H., Madsen, C., Bach, F. W., Gram, L. F., and Jensen, T. S. (2001). St. John \200\231s wort has no eff ect on pain in polyneuropathy. Pain , 91 (3), 361 \200\223365 . Yuan, C. S. and Foss, J. F. (2000). Oral methylnaltrexone for opioid-induced constipation. JAMA , 284 (11), 1383 \200\2231384 . Srivastava, S. C., Atkins, H. L., Krishnamurthy, G. T., Zanzi, I., Silberstein, E. B., Mein ken, G., et al . (1998). Treatment of metastatic bone pain with tin-117m Stannic diethylene triaminepentaacetic acid: a phase I/II clinical study. Clin Cancer Res , 4 (1), 61 \200\223 68 . Yuan, C. S., Foss, J. F., O \200\231Connor, M., Osinski, J., Karrison, T., Moss, J., et al . (2000). Methylnaltrexone for reversal of constipation due to chronic methadone use. JAMA , 283 (3), 367 \200\223372 . Stuart, J. J. and Pisko, E. J. (1981). Choline magnesium trisalicylate does not Zeltzer, L. K., Altman, A., Cohen, D., LeBaron, S., Maunuksela, E. L., and Schechter, N. L. (1990). Report of the Subcommittee on the Management of Pain Associated with Procedures in Children with Cancer. Pediatrics , 86 (Suppl.5), 826 \200\223831 . impair platelet aggregation. Pharmatherapeutica , 2 (8), 547 \200\223551 . Sutton, L. N., Molloy, P. T., Sernyak, H., Goldwein, J., Phillips, P. L., Rorke, L. B., et al . (1995). Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery. J Neurosurg , 83 (4), 583 \200\223589 . Zeltzer, L. K., Dolgin, M. J., LeBaron, S., and LeBaron, C. (1991). A randomized, controlle d study of behavioral intervention for chemotherapy distress in children with cancer. Pedia trics , 88 (1), 34 \200\22342 . Tanelian, D. L. and Brose, W. G. (1991). Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine. Anesthesi ology , 74(5), 949 \200\223951. Zeltzer, L. K., Jay, S. M., and Fisher, D. M. (1989). Th e management of pain associated wi th pediatric procedures. Pediatr Clin North Am , 36 (4), 941 \200\223964 . Tanelian, D. and Cousins, M. J. (1989). Celiac plexus block following high- dose opiates fo r chronic noncancer pain in a four-year-old child. J Pain Symptom Manage , 4 (2), 82 \200 \22385 . Zeppetella, G. (2000). An assessment of the safety, effi cacy, and acceptability of intrana sal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study. J Pain Symptom Manage , 20 (4), 253 \200\223258 . Th omas, J., Karver, S., Cooney, G. A., Chamberlain, B. H., Watt, C. K., Slatkin, N. E., et al . (2008). Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med , 358 (22), 2332 \200\2232343 . CHAPTER 18 Pain management in major pediatric trauma and burns Greta M. Palmer and Franz E. Babl Summary Pain management in major pediatric trauma and burns is chal- lenging. It involves m any phases including pre-hospital and emer- gency department care, ward management frequent ly including intensive care, and multiple operative and procedural interven- tions (as inpa tients and later outpatients). Distress, anxiety, post- traumatic stress disorder (from the primary event and the ensuing in-hospital and post-discharge course), itch, neuropathic pa in (in addition to pain of nociceptive origin), and sleep disorders fre- quently aff ect ma jor trauma and burns victims and can persist long term. An evidence-based discussion follow s of the pharma- cological and non-pharmacological interventions employed dur- ing these va rious phases to address pain and the associated issues in these patients. Case example: trauma A 14-year-old girl is inebriated and out with her teenage friends at midnight. Th ey are \200\230train-surfi ng \200\231 \200\224 standing on top of a mov- ing suburban train. Her two friends get off at a station but she decides to remain on and they see her balancing o n top of the carriage, as the train moves away at speed. Shortly aft er leaving the station she is thrown from the roof of the train. Her friends see this and call emergency services with paramedics (ambulance offi cers) attending the scene within 10 min. She is crying in pain, confused, and smells of alcohol. She is tachypnoeic, tachycardic, and hypotensive. Sh e has left chest wall tenderness and marked bruising over her upper abdomen; her right thig h is swollen, deformed, and tender. Case example: burns Introduction Pediatric patients with major trauma and burns represent sig- nifi cant pain m anagement problems and present frequently to pre- hospital systems and emergency department s (EDs). Trauma and burn injury of moderate severity require ward and, when severe, intensi ve care unit (ICU) admission. Hospital stays may be pro- longed. Surgery is commonly requir ed, involving many surgical services. Pain, sedation, and anxiety management challenges occ ur throughout the patient \200\231s in-hospital stay and may persist during rehabilitation and post discharge. A 2-year-old boy is reported to have pulled a large saucepan of hot water from a stove top. Th e scalding water has led to burns of his face and anterior chest. His mother puts him u nder running water in the shower for 2 min and calls emergency services. Th e paramedics fi nd a screaming toddler with extensive blistering, swelling, and redness extending from his face to below his rib cage. He has no hoarseness or stridor. Th e rest of his body is not aff ected. Pre-hospital care Care by paramedics occurs in a very diff erent environment from hospital: resources are limited, backup is unavailable or only available remotely; initial assessmen t and care is oft en initiated in hostile environments, exposed to the elements with limite d vis- ibility; patients can be trapped requiring prolonged extrication; information can be limited and confusing; during transportation assess- ment and procedures may be complicate d by patient movement, crowding, and noise. Basic measures to assist with pain manage- ment include immobilization and splinting of fractured limbs, the dressing of wounds, and cover ing of burns. Burns should be cooled under running tap water for 20 min, even if initial co oling is delayed (Allison and Porter, 2004; ANZBA, 2012) as supported Aims Th is chapter details pain management of children with major trauma covering their ove rall trauma care and the patient journey from pre-hospital, through in-patient care to disc harge highlighting: \227\206 Acute pain management pre-hospital, in the ED and perioperatively. \227\206 Procedural sedation provided in the ward setting. \227\206 Weaning and step-down analgesic regimens. Th is chapter addresses considerations specifi c to burn injuries. Evidence for practices, when available, will be included. Where possible, variations in international practice are presented. SECTION 4 pain in specific populations and diseases 172 by porcine data (Rajan et al., 2009). While decreasing ongoing heat-related tissue damage a nd providing pain relief, cooling of burn wounds in children can cause hypothermia. With la rger burns and younger children, the wound should be cooled and the patient warmed (Allison and Porter, 2004). Temporary burns dressings should be applied in the pre-hospital setting to reduce pain caused by contact and draft and maintain wound sterility while allowing ins pection of the underlying burn. Th ey should not be applied circumferentially as the burnt and periburn tissue can swell with oedema and blistering, causing further pain and vas- cul ar compromise. Such temporary burns dressings include cel- lophane type kitchen wrap and cl ean/sterile sheets (Allison and Porter, 2004; ANZBA, 2012) solution (50 mcg/ml; Borland et al., 2011; Crellin et al., 2010). Th e standard concentrati on solution has advantages of wide availability, lower cost, and potentially less error bec ause it avoids stocking two concentrations of fentanyl. Limited data are available on pre-hospital use of other opioids such as diamorphine, nalbup hine, and tramadol (Hyland-McGuire and Guly, 1998; Mackenzie, 2000; Roberts et al., 2003; V ergnion et al., 2001; Ward et al., 1997; Woollard et al., 2004). Successful pre- hospital u se of femoral nerve blocks has also been reported (Barker et al., 2008; Lopez et al., 2003; Park et al., 2010). Data in children for these agents and techniques are scant. Methoxyfl urane is an inhaled volatile fl uorinated hydrocarbon anesthetic agent available in a portable, compact delivery system. In Australia and some other countries, it is admini stered as an analgesic by paramedics from a plastic tube inhaler. Th e dose lasts approxima tely 30 min. Th e total weekly dose must not exceed 15 ml because of the risk of cumulative dose-related irreversible nephro- toxicity (Medical Developments International, n.d.). Th ere is limited high-level data on pre-hospital pain care for traumatic injuries in child ren. In adults and children with obvi- ous traumatic injury, pre-hospital analgesic adminis tration occurs in a low percentage of patients (Rogovik and Goldman, 2007; Swor et al., 200 5). Th e level of pain care provided in pre- hospital systems is largely determined by the type of staff , their level of training and competency, and the protocols guiding pre- hosp ital analgesic use. Protocols permit the early administration of analgesics by paramedical staff without requiring permission from a remote medical control physician. Earlier increas ed use of morphine (Pointer and Harlan, 2005; Porter, 2004) occurred when pre-hospital prot ocols were modified to improve analgesic care. Case series indicate that it is an effi cacious analgesic in children and adults (Bendall e t al., 2011; Grindlay and Babl, 2009). In addi- tion to nephrotoxity, it has been implicate d rarely in hepatotoxicity (Joshi and Conn, 1974). Th e previous manufacturer, Abbot, with- drew it from the US market in 2001, and the US Food and Drug Administration (FDA) has sinc e removed it from the drug register because of the safety concerns (FDA, 2005). Th e mechanism of methoxyfl urane \200\231s nephrotoxicity is unknown. Methoxyfl urane is c ontraindicated in renal impairment, diabetes, concurrent use of enzyme-inducing drugs or te tracycline, a his- tory of liver damage secondary to anesthesia, malignant hyper- thermia o r hypersensitivity to fl uorinated anesthetics (Medical Developments International, n.d.). Morphine and fentanyl are extensively used in the pre-hospital setting including in air-tra nsported pediatric trauma patients (DeVellis et al., 1998; Krauss et al., 2011). Th ere may be advantages of fentanyl over morphine (see Sethna et al., Chapter 46, this vol- ume). In a systematic review of pre-hospital adult analgesia with intravenous (IV) morphine and IV fentanyl (Park et al., 2010), no patients required ventilatory support and only one patient in each group required naloxone. More recently intranasal fentanyl (INF) has been used in pre-hospital systems and in EDs. INF has similar analgesic effi cacy and time to onset comp ared to IV morphine. A recent review (Hansen et al., 2012) summarizes pediatric INF use as investigated in a number of randomized controlled trials (RCTs). Comparison of INF with est ablished analgesic agents showed simi- lar decreases in pain scores. No major adverse event s occurred with pediatric analgesic INF use and Glasgow coma scale (GCS) and vital signs we re unaff ected (Hansen et al., 2012). Minor adverse events include nausea, vomiting, prurit is, drowsiness, and a bad taste in the mouth. INF as a sole agent has a low incidence of em e- sis. Th e hazards to staff of IV or intramuscular (IM) administra- tion in a moving vehi cle combined with diffi culties of establishing IV access in children makes INF attractive (Bendall et al., 2011; Johnston et al., 2011). INF is administered by either a mucosal atom izer device (MAD ; attached to a syringe for metered dosing) or a drop-by-drop technique. Usual dosing is 1.5 mcg/kg, divided between each nostril. Th is administration route bypass es gastroin- testinal and hepatic elimination (Hansen et al., 2012; Panagiotou and Mystakid ou, 2010). A maximum volume limit of 0.15 ml was suggested to avoid pharyngeal run off (Dal e et al., 2002; Hansen et al., 2012). In past studies high concentrations of usually 100 mc g/ ml to 300 mcg/ml have been used (Borland et al., 2007; Hansen et al., 2012). However, tw o recent pediatric studies have dem- onstrated similar analgesic effi cacy of INF using the standard IV Nitrous oxide (N 2 O) use on ambulances was described fi rst in 1970 (Baskett, 1970). Recen t reports indicate its continuing avail- ability on ambulances in many pre-hospital systems (Bledsoe et al., 2005; Roberts et al., 2003; Siriwardena et al., 2010). It is usually admi nistered in fi xed concentration (50% N 2 O and 50% oxygen) with a demand valve that limits its utility to children over 4 years of age, who can generate adequate negative pressure t o open the valve. It is also problematic in cold environments (Borland et al., 2002). Traum a patients who have potential air trapping (e.g. suspected pneumothorax) may not receive N 2 O.