Abstract
Easing physical distress is a major focus in the practice of palliative care in a child with malignancy throughout the disease course from diagnosis to cure and survivorship or death.
Physical suffering is a main contributor to global suffering of the ill child, his parents, other family members, and also other persons involved.
Physical suffering is multifactorial and stems from many causes, mainly the disease itself, side effects of anticancer treatment and its consequences, as well as various painful procedures.
Physical distress reflects the body organ(s) involved in the disease, and therefore symptoms and, mainly, pain may vary widely in form, intensity, location, and its ability to interfere with the child’s daily activity and life.
Common types of physical distress are fatigue, pain, respiratory problems such as shortness of breath, gastrointestinal discomfort due to functional and mechanical obstruction, mucositis, and damage to central and peripheral nervous systems with accompanying alterations in conscience, seizures, and motor dysfunctions.
Timely recognition of the various signs and symptoms of physical distress allows the physician and other members of medical team to convey appropriate treatment to the suffering child with cancer. Easing the physical distress should be of paramount concern for all those involved in the management of pediatric oncologic patient at all levels of care: primary pediatrician in the community clinic, pediatric oncologist in the hospital ward, or specialist in pediatric palliative care both in hospital and in hospice service.
Proper and timely delivered pediatric palliative care directed at the easing of physical distress of pediatric cancer patient also greatly facilitates easing of both psychological distress and preserving the dignity of the child and the rest of his/her family members.
In this chapter we will describe in a detailed manner the use of various techniques for easing the pain and other forms of physical suffering using various pharmacological and non-pharmacological techniques. The pharmacological techniques will include intravenous, enteral, or topical drugs along with implementation of minimally invasive procedures such as various nerve blockades and insertion of epidural and other catheters to deliver site-specific or regional treatment. Non-pharmacological techniques will include procedures to ease physical distress such as pleurocentesis and paracentesis as well as ventilatory support with high-flow nasal cannula and noninvasive positive pressure ventilation.
Management of symptoms related to the central nervous system as seizures, depressed levels of consciousness, and symptoms originating from dysfunction of pelvic organs (neurogenic bladder and rectum) is also discussed. Spinal cord compression, almost the only emergency condition encountered in children with cancer during the last phases of their lives, needs special attention, and therefore its diagnosis and management are also reflected in this chapter.
Although detailed discussion of palliative sedation as a mean of last resort in the management of unbearable suffering is beyond the scope of this chapter, its role in the easing of physical distress is shortly mentioned.
References
Wolfe J, Grier HE, Klar N, Levin SB, Ellenbogen JM, Salem-Schatz S, Emanuel EJ, Weeks JC (2000) Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342:326–333
Pritchard M, Burghen E, Srivastava DK, Okuma J, Anderson L, Powell B, Furman WL, Hinds PS (2008) Cancer-related symptoms most concerning to parents during the last week and last day of their child’s life. Pediatrics 121:e1301–e1309
Heath JA, Clarke NE, Donath SM, McCarthy M, Anderson VA, Wolfe J (2010) Symptoms and suffering at the end of life in children with cancer: an Australian perspective. Med J Aust 192:71–75
Theunissen JM, Hoogerbrugge PM, van Achterberg T, Prins JB, Vernooij-Dassen MJ, van den Ende CH (2007) Symptoms in the palliative phase of children with cancer. Pediatr Blood Cancer 49:160–165
Kreicbergs U, Valdimarsdóttir U, Onelöv E, Björk O, Steineck G, Henter JI (2005) Care-related distress: a nationwide study of parents who lost their child to cancer. J Clin Oncol 23:9162–9171
von Lützau P, Otto M, Hechler T, Metzing S, Wolfe J, Zernikow B (2012) Children dying from cancer: parents' perspectives on symptoms, quality of life, characteristics of death, and end-of-life decisions. J Palliat Care 28:274–281
Jalmsell L, Kreicbergs U, Onelöv E, Steineck G, Henter JI (2006) Symptoms affecting children with malignancies during the last month of life: a nationwide follow-up. Pediatrics 117:1314–1320
Mack JW, Hilden JM, Watterson J, Moore C, Turner B, Grier HE, Weeks JC, Wolfe J (2005) Parent and physician perspectives on quality of care at the end of life in children with cancer. J Clin Oncol 23:9155–9161
Wolfe J, Hammel JF, Edwards KE, Duncan J, Comeau M, Breyer J, Aldridge SA, Grier HE, Berde C, Dussel V, Weeks JC (2008) Easing of suffering in children with cancer at the end of life: is care changing? J Clin Oncol 26:1717–1723
Postovsky S, Ben Arush MW (2004) Care of a child dying of cancer: the role of the palliative care team in pediatric oncology. Pediatr Hematol Oncol 21:67–76
Schmidt P, Otto M, Hechler T, Metzing S, Wolfe J, Zernikow B (2013) Did increased availability of pediatric palliative care lead to improved palliative care outcomes in children with cancer? J Palliat Med 16:1034–1039
Cassel EJ (1982) The nature of suffering and the goals of medicine. N Engl J Med 306:639–645
Collins JJ, Byrnes ME, Dunkel IJ, Lapin J, Nadel T, Thaler HT, Polyak T, Rapkin B, Portenoy RK (2000) The measurement of symptoms in children with cancer. J Pain Symptom Manag 19:363–377
Wolfe J, Orellana L, Ullrich C, Cook EF, Kang TI, Rosenberg A, Geyer R, Feudtner C, Dussel V (2015) Symptoms and distress in children with advanced cancer: prospective patient-reported outcomes from the PediQUEST study. J Clin Oncol 33:1928–1935
Zhukovsky DS, Rozmus CL, Robert RS, Bruera E, Wells RJ, Chisholm GB, Allo JA, Cohen MZ (2015) Symptom profiles in children with advanced cancer: patient, family caregiver, and oncologist ratings. Cancer 121:4080–4087
Bower JE, Bak K, Berger A, Breitbart W, Escalante CP, Ganz PA, Schnipper HH, Lacchetti C, Ligibel JA, Lyman GH, Ogaily MS, Pirl WF, Jacobsen PB (2014) Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation. J Clin Oncol 32:1840–1850
Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR (2007) Mechanisms of cancer-related fatigue. Oncologist 12(Suppl 1):22–34
Ullrich CK, Mayer OH (2007) Assessment and management of fatigue and dyspnea in pediatric palliative care. Pediatr Clin N Am 54:735–756
Ullrich CK, Dussel V, Hilden JM, Sheaffer JW, Moore CL, Berde CB, Wolfe J (2010) Fatigue in children with cancer at the end of life. J Pain Symptom Manag 40:483–494
Hockenberry MJ, Hooke MC, Gregurich M, McCarthy K (2009) Carnitine plasma levels and fatigue in children/adolescents receiving cisplatin, ifosfamide, or doxorubicin. J Pediatr Hematol Oncol 31:664–669
Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, Ferraro B, Canestrari F, Baldelli AM, De Gaetano A, Giordani P, Testa E, Lai V (2002) Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer 86:1854–1857
Cruciani RA, Zhang JJ, Manola J, Cella D, Ansari B, Fisch MJ (2012) L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol 30:3864–3869
Hooke MC, McCarthy K, Taylor O, Hockenberry MJ (2015) Fatigue and carnitine levels over multiple cycles of chemotherapy in children and adolescents. Eur J Oncol Nurs 19:7–12
Brown RL (2011) Tyrosine kinase inhibitor-induced hypothyroidism: incidence, etiology, and management. Target Oncol 6:217–226
Torino F, Corsello SM, Longo R, Barnabei A, Gasparini G (2009) Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol 6:219–228
Olson K (2014) Sleep-related disturbances among adolescents with cancer: a systematic review. Sleep Med 15:496–501
Crabtree VM, Rach AM, Schellinger KB, Russell KM, Hammarback T, Mandrell BN (2015) Changes in sleep and fatigue in newly treated pediatric oncology patients. Support care cancer 23:393–401
Orsey AD, Wakefield DB, Cloutier MM (2013) Physical activity (PA) and sleep among children and adolescents with cancer. Pediatr Blood Cancer 60:1908–1913
Braam KI, van der Torre P, Takken T, Veening MA, van Dulmen-den Broeder E, Kaspers GJ (2013) Physical exercise training interventions for children and young adults during and after treatment for childhood cancer. Cochrane Database Syst Rev 4:CD008796
Reineke-Bracke H, Radbruch L, Elsner F (2006) Treatment of fatigue: modafinil, methylphenidate, and goals of care. J Palliat Med 9:1210–1214
Sharp V, Finlay F, Kevitiyagala D (2013) Question 1: is methylphenidate a useful treatment for cancer-related fatigue in children? Arch Dis Child 98:80–82
Hwang SS, Chang VT, Rue M, Kasimis B (2003) Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manag 26:604e614
World Health Organization (2012). WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. Geneva: WHO. http://whqlibdoc.who.int/publications/2012/9789241548120_Guidelines.pdf. Accessed 15 Feb 2016
Zernikow B, Smale H, Michel E, Hasan C, Jorch N, Andler W (2006) Paediatric cancer pain management using the WHO analgesic ladder––results of a prospective analysis from 2265 treatment days during a quality improvement study. Eur J Pain 10:587–595
Friedrichsdorf S, Finney D, Bergin M et al (2007) Breakthrough pain in children with cancer. J Pain Symptom Manag 34:209–216
International Association for the Study of Pain (IASP) (n.d.) Taxonomy. http://www.iasp-pain.org/. Accessed 8 Feb 2016
Anghelescu DL, Faughnan LG, Popenhagen MP, Oakes LL, Pei D, Burgoyne LL (2014) Neuropathic pain referrals to a multidisciplinary pediatric cancer pain service. Pain Manag Nurs 15:126–131
Voepel-Lewis T, Merkel S, Tait AR et al (2002) The reliability and validity of the face, legs, activity, cry, consolability observational tool as a measure of pain in children with cognitive impairment. Anesth Analg 95:1224–12298
Visual Analog Scale (VAS) (n.d.) http://www.partnersagainstpain.com/printout/A7012AS1.pdf. Accessed 12 Feb 2016
von Baeyer CL, Spagrud LJ, McCormick JC, Choo E (2009) Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children’s self-reports of pain intensity. Pain 143:223–227
Face Pain Scale - Revised (n.d.) URL http://www.iasp-pain.org/fpsr. Accessed 24 Jan 2016
Hicks CL, von Baeyer CL, Spafford PA et al (2001) The Faces Pain Scale—Revised: toward a common metric in pediatric pain measurement. Pain 93:173–183
The Oucher Photographic Scale (n.d.) www.oucher.org . Accessed 10 Feb 2016
Beyer JE, Denyes MJ, Villarreal AM (1992) The creation, validation, and continuing development of the Oucher: a measure of pain intensity in children. J Pediatr Nurs 7:335–346
Marec-Berard P, Gomez F, Combet S, Thibault P, Bergeron PLMC (2015) HEDEN Pain Scale: a shortened behavioral scale for assessment of prolonged cancer or postsurgical pain in children aged 2 to 6 years. Pediatr Hematol Oncol 32(5):291–303
de Martino M, Chiarugi A (2015) Recent advances in pediatric use of oral paracetamol in fever and pain management. Pain Ther 4:149–168
Ceelie I, de Wildt SN, van Dijk M, van den Berg MM, van den Bosch GE, Duivenvoorden HJ, de Leeuw TG, Mathôt R, Knibbe CA, Tibboel D (2013) Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA 309:149–154
Heard K, Bui A, Mlynarchek SL, Green JL, Bond JR, Clark RF, Kozer E, Koff RS, Dart RC (2014) Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases. Am J Ther 21:174–183
Koling S, Hempel G, Lanvers C, Boos J, Würthwein G (2007) Monitoring paracetamol metabolism after single and repeated administration in pediatric patients with neoplastic diseases. Int J Clin Pharmacol Ther 45:496–503
Wong I, St John-Green C, Walker SM (2013) Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth 23:475–495
Leese PT, Hubbard RC, Karim A, Isakson PC, Yu SS, Geis GS (2000) Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial. J Clin Pharmacol 40(2):124–132
Schnabel A, Reichl SU, Meyer-Frießem C, Zahn PK, Pogatzki-Zahn E (2015) Tramadol for postoperative pain treatment in children. Cochrane Database Syst Rev (3):CD009574
Zernikow B, Michel E, Craig F, Anderson BJ (2009) Pediatric palliative care: use of opioids for the management of pain. Paediatr Drugs 11:129–151
Siden H, Naiewajek V (2003) high dose opioids in pediatric palliative care. J Pain Symptom Manag 25:397–399
Rasmussen VF, Lundberg V, Jespersen TW, Hasle H (2015) Extreme doses of intravenous methadone for severe pain in two children with cancer. Pediatr Blood Cancer 62:1087–1090
Nielsen LM, Olesen AE, Branford R, Christrup LL, Sato H, Drewes AM (2015) Association between human pain-related genotypes and variability in opioid analgesia: an updated review. Pain Pract 15:580–594. See comment in PubMed Commons below
Morlion B, Clemens KE, Dunlop W (2015) Quality of life and healthcare resource in patients receiving opioids for chronic pain: a review of the place of oxycodone/naloxone. Clin Drug Investig 35:1–11
Kestenbaum MG, Vilches AO, Messersmith S, Connor SR, Fine PG, Murphy B, Davis M, Muir JC (2014) Alternative routes to oral opioid administration in palliative care: a review and clinical summary. Pain Med 15:1129–1153
Drake R, Longworth J, Collins JJ (2004) Opioid rotation in children with cancer. J Palliat Med 7:419–422
Kim HJ, Kim YS, Park SH (2015) Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care 14:41
Smith HS, Peppin JF (2014) Toward a systematic approach to opioid rotation. J Pain Res 7:589–608
Anghelescu DL, Faughnan LG, Oakes LL, Windsor KB, Pei D, Burgoyne LL (2012) Parent-controlled PCA for pain management in pediatric oncology: is it safe? J Pediatr Hematol Oncol 34:416–420
Howard RF, Lloyd-Thomas A, Thomas M, Williams DG, Saul R, Bruce E, Peters J (2010) Nurse-controlled analgesia (NCA) following major surgery in 10,000 patients in a children’s hospital. Paediatr Anaesth 20:126–134
Anghelescu DL, Snaman JM, Trujillo L, Sykes AD, Yuan Y, Baker JN (2015) Patient-controlled analgesia at the end of life at a pediatric oncology institution. Pediatr Blood Cancer 62:1237–1244
Zernikow B, Michel E, Anderson B (2007) Transdermal fentanyl in childhood and adolescence: a comprehensive literature review. J Pain 8:187–207
James PJ, Howard RF, Williams DG (2010) The addition of ketamine to a morphine nurse- or patient-controlled analgesia infusion (PCA/NCA) increases analgesic efficacy in children with mucositis pain. Paediatr Anaesth 20:805–811
Anghelescu DL (2011) Methadone use in children and young adults at a cancer center: a retrospective study. J Opioid Manag 7:353–361
Friedrichsdorf S, Nugent A (2013) Management of neuropathic pain in children with cancer. Curr Opin Support Palliat Care 7:131–138
Haywood A, Good P, Khan S, Leupp A, Jenkins-Marsh S, Rickett K, Hardy JR (2015) Corticosteroids for the management of cancer-related pain in adults. Cochrane Database Syst Rev 4:CD010756
Korzeniewska-Eksterowicz A, Przysło Ł, Fendler W, Stolarska M, Młynarski W (2014) Palliative sedation at home for terminally ill children with cancer. J Pain Symptom Manag 48:968–974
Anghelescu DL, Faughnan LG, Baker JN, Yang J, Kane JR (2010) Use of epidural and peripheral nerve blocks at the end of life in children and young adults with cancer: the collaboration between a pain service and a palliative care service. Paediatr Anaesth 20:1070–1077
Walker BJ, Long JB, De Oliveira GS et al (2015) Peripheral nerve catheters in children: an analysis of safety and practice patterns from the pediatric regional anesthesia network (PRAN). Br J Anaesth 115:457–462
Cooper MG, Keneally JP, Kinchington D (1994) Continuous brachial plexus neural blockade in a child with intractable cancer pain. J Pain Symptom Manag 9:277–281
Pacenta HL, Kaddoum RN, Pereiras LA, Chidiac EJ, Burgoyne LL (2010) Continuous tunneled femoral nerve block for palliative care of a patient with metastatic osteosarcoma. Anaesth Intensive Care 38:563–565
Fu J, Ngo A, Shin K, Bruera E (2013) Botulinum toxin injection and phenol nerve block for reduction of end-of-life pain. J Palliat Med 16:1637–1640
Chambers WA (2008) Nerve blocks in palliative care. Br J Anaesth 101:95–100
Sakamoto B, Kuber S, Gwirtz K, Elsahy A, Stennis M (2012) Neurolytic transversus abdominis plane block in the palliative treatment of intractable abdominal wall pain. J Clin Anesth 24:58–61
Hung JC, Azam N, Puttanniah V, Malhotra V, Gulati A (2014) Neurolytic transversus abdominal plane block with alcohol for long-term malignancy related pain control. Pain Physician 17:E755–E760
Gulati A, Shah R, Puttanniah V, Hung JC, Malhotra V (2015) A retrospective review and treatment paradigm of interventional therapies for patients suffering from intractable thoracic chest wall pain in the oncologic population. Pain Med 16:802–810
Sepsas E, Misthos P, Anagnostopulu M, Toparlaki O, Voyagis G, Kakaris S (2013) The role of intercostal cryoanalgesia in post-thoracotomy analgesia. Interact Cardiovasc Thorac Surg 16:814–818
Mercadante S, Nicosia F (1998) Celiac plexus block: a reappraisal. Reg Anesth Pain Med 23:37–48
Galloway K, Staats PS, Bowers DC (2000) Intrathecal analgesia for children with cancer via implanted infusion pumps. Med Pediatr Oncol 34:265–267
Aram L, Krane EJ, Kozloski LJ, Yaster M (2001) Tunneled epidural catheters for prolonged analgesia in pediatric patients. Anesth Analg 92:1432–1438
De Pinto M, Naidu RK (2015) Peripheral and neuraxial chemical neurolysis for the management of intractable lower extremity pain in a patient with terminal cancer. Pain Physician 18:E651–E656
Shimazaki M, Egawa H, Motojima F et al (2003) Intrathecal phenol block in a child with cancer pain–a case report. Masui 52:756–758
van der Geest IM, Darlington AS, Streng IC, Michiels EM, Pieters R, van den Heuvel-Eibrink MM (2014) Parents’ experiences of pediatric palliative care and the impact on long-term parental grief. J Pain Symptom Manag 47:1043–1053
Liben S, Langner R, Bluebond-Langner M (2014) Pediatric palliative care in 2014: much accomplished, much yet to be done. J Palliat Care 30:311–316
Pianosi P, Smith CP, Almudevar A, McGrath PJ (2006) Dalhousie dyspnea scales: pictorial scales to measure dyspnea during induced bronchoconstriction. Pediatr Pulmonol 41:1182–1187
Craig F, Henderson EM, Bluebond-Langner M (2015) Management of respiratory symptoms in paediatric palliative care. Curr Opin Support Palliat Care 9:217–226
Heyse-Moore LH, Ross V, Mullee MA (1991) How much of a problem is dyspnoea in advanced cancer? Palliat Med 5:20–26
Drake R, Frost J, Collins JJ (2003) The symptoms of dying children. J Pain Symptom Manag 26:594–603
Blume ED, Balkin EM, Aiyagari R, Ziniel S, Beke DM, Thiagarajan R, Taylor L, Kulik T, Pituch K, Wolfe J (2014) Parental perspectives on suffering and quality of life at end-of-life in children with advanced heart disease: an exploratory study. Pediatr Crit Care Med 15:336–342
Ban Banzett RB, Mulnier HE, Murphy K, Rosen SD, Wise RJ, Adams L (2000) Breathlessness in humans activates insular cortex. Neuroreport 11:2117–2120
Booth S, Kelly M, Cox N, Adams L, Guz A (1996) Does oxygen help dyspnoea in patients with cancer. Am J Respir Crit Care Med 153:1515–1518
Evans KC, Banzett RB, Adams L, McKay L, Frackowiak RS, Corfield DR (2002) BOLD fMRI densifies limbic, paralimbic, and cerebellar activation during air hunger. J Neurophysiol 88:1500–1511
Frost JJ, Wagner HN Jr, Dannals RF, Ravert HT, Links JM, Wilson AA et al (1985) Imaging opiate receptors in the human brain by positron tomography. J Comput Assist Tomogr 9:231–236
Gaytan SP, Pasaron R (1998) Connections of the rostral ventral respiratory neuronal cell group: an anterograde and retrograde tracing study in the rat. Brain Res Bull 47:625–642
Clemens KE, Klaschik E (2011) Dyspnoea associated with anxiety––symptomatic therapy with opioids in combination with lorazepam and its effect on ventilation in palliative care patients. Support Care Cancer 19:2027–2033
Thomas JR, von Gunten C (2002) Clinical management of dyspnoea. Lancet Oncol 3:223–228
Escalante CP, Martin CG, Eiting LS, Cantor SB, Harle TS, Price KJ et al (1996) Dyspnea in cancer patients. Etiology, resource utilization, and survival—implications in a managed care world. Cancer 78:1314–1319
Philip J, Gold M, Milner A, Di Iulio J, Miller B, Spuryt O (2006) A randomized, double blind, crossover-trial of the effect of oxygen on dyspnoea in patients with advanced cancer. J Pain Symptom Manag 32:541–550
Bruera E, de Stoutz N, Velasco-Leiva A, Schoeller T, Hanson J (1993) Effect of oxygen on dyspnoea in hypoxaemic terminal cancer patients. Lancet 342:13–14
Bruera E, Scholler T, MacEachern T (1992) Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: the use of the N of 1 randomised controlled trial. J Pain Symptom Manag 7:365–368
Clemens KE, Quednau I, Klaschik E (2009) Use of oxygen and opioids in the palliation of dyspnoea in hypoxic and non-hypoxic palliative care patients: a prospective study. Support Care Cancer 17:367–377
Abernethy AP, McDonald CF, Frith PA, Clark K, Herndon JE 2nd, Marcello J et al (2010) Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet 376:784–793
Spathis A, Wade R, Booth S (2006) Oxygen in the palliation of breathlessness. In: Booth S, Dudgeon D (eds) Dyspnoea in advanced disease. Oxford University Press, Oxford, pp 205–236
Banzett RB, Adams L, O'Donnell CR, Gilman SA, Lansing RW, Schwartzstein RM. Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response. Am J Respir Crit Care Med 2011; 184: 920–927
Al J, Davies AN, Higgins JP, Gibbs JS, Broadley KE (2002) A systematic review of the use of opioids in the management of dyspnoea. Thorax 57:939–944
Clemens KE, Klaschik E (2007) Symptomatic therapy of dyspnoea with strong opioids and its effect on ventilation in palliative care patients. J Pain Symptom Manag 33:473–481
Clemens KE, Klaschik E (2008) Effect of hydromorphone on ventilation in palliative care patients with dyspnea. Support Care Cancer 16:93–99
Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS (2001) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative For Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care 46:798–825
Barbour SJ, Vandebeek CA, Ansermino JM (2004) Increased tidal volume variability in children is a better marker of opioid-induced respiratory depression than decreased respiratory rate. J Clin Monit Comput 18:171–178
Thorns A, Sykes N (2000) Opioid use in last week of life and implications for end-of-life decision making. Lancet 3556:398–399
Clemens KE, Quednau I, Klaschik E (2008) Is there higher risk of respiratory depression in opioid-naïve palliative care patients during symptomatic therapy of dyspnoea with strong opioids? J Palliat Med 11:204–216
Currow DC, McDonald C, Oaten S, Kenny B, Allcroft P, Frith P et al (2011) Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study. J Pain Symptom Manag 42:388–399
Zebraski SE, Kochenash SM, Raffa RB (2000) Lung opioid receptors: pharmacology and possible target for nebulized morphine in dyspnea. Life Sci 66:2221–2231
Charles MA, Reymond L, Israel F (2008) Relief of incident dyspnea in palliative cancer patients: a pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. J Pain Symptom Manag 36:29–38
Ben-Aharon I, Gafter-Gvili A, Paul M, Leibovici L, Stemmer SM (2008) Interventions for alleviating cancer-related dyspnea: a systematic review. J Clin Oncol 26:2396–2404
Penson RT, Joel SP, Roberts M, Gloyne A, Beckwith S, Slevin ML (2002) The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide. Br J Clin Pharmacol 53:347–354
Mitchell-Heggs P, Murphy K, Minty K, Guz A, Patterson SC, Minty PS, Rosser RM (1980) Diazepam in the treatment of dyspnea in the pink puffer syndrome. QJM 193:9–20
Stark RD, Gambles SA, Lewis JA (1981) Methods to assess breathlessness in healthy subjects: a critical evaluation and application to analyse the acute effects of diazepam and promethazine on breathlessness induced by exercise or by exposure to raised levels of carbon dioxide. Clin Sci 61:429–439
Woodcock AA, Gross ER, Geddes DM (1981) Drug treatment of breathlessness; contrasting effects of diazepam and promethazine in pink puffers. BMJ 283:343–346
Man GC, Hsu K, Sproule BJ (1986) Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 90:832–836
Gililand HE, Prasad BK, Mirakhur RK, Fee J (1996) An investigation of the potential morphine-sparing effect of midazolam. Anesthesia 51:808–811
Navigante A, Cerchietti L, Cabalr M (2003) Morphine plus midazolam versus oxygen therapy in severe dyspnea management in the last week of life of patients with advanced cancer. Med Palliat 10:14–19
Dysart K, Miller TL, Wolfson MR, Shaffer TH (2009) Research in high flow therapy: mechanisms of action. Respir Med 103:1400–1405
Nava S, Ferrer M, Esquinas A, Scala R, Groff P, Cosentini R et al (2013) Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial. Lancet Oncol 14:219–227
Hui D, Morgado M, Chisholm G, Withers L, Nguyen Q, Finch C, Frisbee-Hume S, Bruera E (2013) High-flow oxygen and bilevel positive airway pressure for persistent dyspnea in patients with advanced cancer: a phase II randomized trial. J Pain Symptom Manag 46:463–473
Gay PC (2009) Complications of noninvasive ventilation in acute care. Respir Care 54:246–257
Hoffer FA, Hancock ML, Hinds PS, Oigbokie N, Rai SN, Rao B (2007) Pleurodesis for effusions in pediatric oncology patients at end of life. Pediatr Radiol 37:269–273
MacRedmond R, O’Connell F (1999) Treatment of persistent dry cough: if possible, treat the cause; if not, treat the cough. Monaldi Arch Chest Dis 3:269–274
Morice AH, Menon MS, Mulrennan SA et al (2007) Opiate therapy in chronic cough. Am J Respir Crit Care Med 175:312–315
Wee B, Browning J, Adams A et al (2012) Management of chronic cough in patients receiving palliative care: review of evidence and recommendations by a task group of the Association for Palliative Medicine of Great Britain and Ireland. Palliat Med 26:780–787
Yancy WS, McCrory DC, Coeytaux RR et al (2013) Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis. Chest J 144:1827–1838
Molassiotis A, Bailey C, Caress A et al (2010) Interventions for cough in cancer. Cochrane Database Syst Rev (9):CD007881
Smith SM, Schroeder K, Fahey T (2014) Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev (11):CD001831
Moroni M, Porta C, Gualtieri G et al (1996) Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients. Br J Cancer 74:309–311
Choudry NB, Fuller RW, Anderson N et al (1990) Separation of cough and reflex bronchoconstriction by inhaled local anaesthetics. Eur Respir J 3:579–583
Ryan NM (2015) A review on the efficacy and safety of gabapentin in the treatment of chronic cough. Expert Opin Pharmacother 16:135–145
Gibson PG, Vertigan AE (2015) Management of chronic refractory cough. BMJ 351:h5590
Gibson P, Wang G, McGarvey L et al (2016) Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest 149(1):27–44
Nannini LJ, Poole P, Milan SJ, Kesterton A (2013) Combined corticosteroid and longacting beta2-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Library (8):CD006826
Kellett F, Robert NM (2011) Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. Respir Med 105:1831–1850
Chatwin M, Ross E, Hart N et al (2003) Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J 21:502–508
Chatwin M, Simonds AK (2009) The addition of mechanical insufflation/exsufflation shortens airway-clearance sessions in neuromuscular patients with chest infection. Respir Care 54:1473–1479
Moran FC, Spittle A, Delany C et al (2013) Effect of home mechanical in-exsufflation on hospitalisation and life-style in neuromuscular disease: a pilot study. J Paediatr Child Health 49:233–237
Smith HS, Smith JM, Seidner P (2012) Opioid-induced nausea and vomiting. Ann Palliat Med 1:121–129
Baxter AL, Watcha MF, Baxter WV, Leong T, Wyatt MM (2011) Development and validation of a pictorial nausea rating scale for children. Pediatrics 127:e1542–e1549
Dupuis LL, Taddio A, Kerr EN, Kelly A, MacKeigan L (2006) Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents. Pharmacotherapy 26:1221–1231
Roila F, Aapro M, Stewart A (1998) Optimal selection of antiemetics in children receiving cancer chemotherapy. Support Care Cancer 6:215–220
Roila F, Feyer P, Maranzano E, Olver I, Clark-Snow R, Warr D, Molassiotis A (2005) Antiemetics in children receiving chemotherapy. Support Care Cancer 13:129–131
Patel P, Robinson PD, Orsey A, Freedman JL, Langevin AM, Woods D, Sung L, Dupuis LL. Chemotherapy-induced nausea and vomiting prophylaxis: practice within the children’s oncology group. Pediatr Blood Cancer. 63 (5), 887-892 2016
Jordan K, Roila F, Molassiotis A, Maranzano E, Clark-Snow RA, Feyer P, MASCC/ESMO (2011) Antiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009. Support Care Cancer 19(Suppl 1):S37–S42
Kris MG, Tonato M, Bria E, Ballatori E, Espersen B, Herrstedt J, Rittenberg C, Einhorn LH, Grunberg S, Saito M, Morrow G, Hesketh P (2011) Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 19(Suppl 1):S25–S32
Vrabel M (2007) Is ondansetron more effective than granisetron for chemotherapy-induced nausea and vomiting? A review of comparative trials. Clin J Oncol Nurs 11:809–813
Bodge M, Shillingburg A, Paul S, Biondo L (2014) Safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting in pediatric patients: a prospective, observational study. Pediatr Blood Cancer 61:1111–1113
Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM (2015) Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomized, double-blind, phase 3 trial. Lancet Oncol 16:385–394
Currow DC, Quinn S, Agar M, Fazekas B, Hardy J, McCaffrey N, Eckermann S, Abernethy AP, Clark K (2015) Double-blind, placebo-controlled, randomized trial of octreotide in malignant bowel obstruction. J Pain Symptom Manag 49:814–821
Watanabe H, Inoue Y, Uchida K, Okugawa Y, Hiro J, Ojima E, Kobayashi M, Miki C, Kusunoki M (2007) Octreotide improved the quality of life in a child with malignant bowel obstruction caused by peritoneal dissemination of colon cancer. J Pediatr Surg 42:259–260
Davies DE, Wren T, MacLachlan SM (2012) Octreotide infusion for malignant duodenal obstruction in a 12-year-old girl with metastatic peripheral nerve sheath tumor. J Pediatr Hematol Oncol 34:e292–e294
Mercadante S, Porzio G (2012) Octreotide for malignant bowel obstruction: twenty years after. Crit Rev Oncol Hematol 83:388–392
Garcia MK, McQuade J, Haddad R, Patel S, Lee R, Yang P, Palmer JL, Cohen L (2013) Systematic review of acupuncture in cancer care: a synthesis of the evidence. J Clin Oncol 31:952–960
Richardson J, Smith JE, McCall G, Richardson A, Pilkington K, Kirsch I (2007) Hypnosis for nausea and vomiting in cancer chemotherapy: a systematic review of the research evidence. Eur J Cancer Care (Engl) 16:402–412
Santucci G, Mack JW (2007) Common gastrointestinal symptoms in pediatric palliative care: nausea, vomiting, constipation, anorexia, cachexia. Pediatr Clin N Am 54:673–689
Phillips RS, Gibson F (2008) A systematic review of treatments for constipation in children and young adults undergoing cancer treatment. J Pediatr Hematol Oncol 30:829–830
Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (2006) Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 43:e1–13
Pashankar FD, Season JH, McNamara J, Pashankar DS (2011) Acute constipation in children receiving chemotherapy for cancer. J Pediatr Hematol Oncol 33:e300–e303
Rowinsky EK, Donehower RC (1991) The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol Ther 52:5–84
Fontana M, Bianchi C, Cataldo F, Conti Nibali S, Cucchiara S, Gobio Casali L, Iacono G, Sanfilippo M, Torre G (1989) Bowel frequency in healthy children. Acta Paediatr Scand 78:682–684
Fallon M, ONeill B (1997) ABC of palliative care. Constipation and diarrhoea. BMJ 315:1293–1296
Abrahm J (2000) A physician’s guide to pain and symptom management in cancer patients. Johns Hopkins University Press, Baltimore, MD
Bradfield SM, Sandler E, Geller T, Tamura RN, Krischer JP (2015) Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer. Pediatr Blood Cancer 62:1004–1010
Mokhtar GM, Shaaban SY, Elbarbary NS, Fayed WA (2010) A trial to assess the efficacy of glutamic acid in prevention of vincristine-induced neurotoxicity in pediatric malignancies: a pilot study. J Pediatr Hematol Oncol 32:594–600
Author S (2014) Treatments for constipation: a review of systematic reviews. Rapid response report: summary with critical appraisal. Canadian Agency for Drugs and Technologies in Health, Ottawa (ON)
Gordon M, Naidoo K, Akobeng AK, Thomas AG (2013) Cochrane review: osmotic and stimulant laxatives for the management of childhood constipation (review). Evid Based Child Health 8:57–109
Feudtner C, Freedman J, Kang T, Womer JW, Dai D, Faerber J (2014) Comparative effectiveness of senna to prevent problematic constipation in pediatric oncology patients receiving opioids: a multicenter study of clinically detailed administrative data. J Pain Symptom Manag 48:272–280
Leppert W (2015) Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction. Drug Des Devel Ther 9:2215–2231
Compendium of Pharmaceuticals and Specialities (2011) Methylnaltrexone product monograph. https://wwwe-therapeutics-ca.myaccess.library.utoronto.ca/cps
Rodrigues A, Wong C, Mattiussi A, Alexander S, Lau E, Dupuis LL (2013) Methylnaltrexone for opioid-induced constipation in pediatric oncology patients. Pediatr Blood Cancer 60:1667–1670
Flerlage JE, Baker JN (2015) Methylnaltrexone for opioid-induced constipation in children and adolescents and young adults with progressive incurable cancer at the end of life. J Palliat Med 18:631–633
Burness CB, Keating GM (2014) Oxycodone/naloxone prolonged-release: a review of its use in the management of chronic pain while counteracting opioid-induced constipation. Drugs 74:353–375
Leppert W (2014) Oxycodone/naloxone in the management of patients with pain and opioid-induced bowel dysfunction. Curr Drug Targets 15:124–135
Mercadante S, Casuccio A, Fulfaro F et al (2001) Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol 19:2898–2904
Wirz S, Wittmann M, Schenk M et al (2009) Gastrointestinal symptoms under opioid therapy: a prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine. Eur J Pain 13:737–743
Loeffen EA, Brinksma A, Tissing WJ (2015) Clinical implications of malnutrition in children with cancer. Support Care Cancer 23:2523–2524
Sala A, Pencharz P, Barr RD (2004) Children, cancer, and nutrition––a dynamic triangle in review. Cancer 100:677–687
Morley JE, Thomas DR, Wilson MM (2006) Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 83:735–743
Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K (2015) Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 7:17–29
KCH F (1992) The mechanisms and treatment of weight loss in cancer. Proc Nutr Soc 51:251–265
Tisdale MJ (2009) Mechanisms of cancer cachexia. Physiol Rev 89:381–410
Tisdale MJ (2008) Catabolic mediators of cancer cachexia. Curr Opin Support Palliat Care 2:256–261
Brinksma A, Huizinga G, Sulkers E, Kamps W, Roodbol P, Tissing W (2012) Malnutrition in childhood cancer patients: a review on its prevalence and possible causes. Crit Rev Oncol Hematol 83:249–275
Common Terminology Criteria for Adverse Events (CTCAE) (2009) Version 4.0 (v4.03: June 14, 2010). U.S. Department of Health and Human Services. National Institutes of Health. National Cancer Institute
Tisdale MJ (2006) Clinical anticachexia treatments. Nutr Clin Pract 21:168–174
Veldhuijzen van Zanten SE, van Meerwijk CL, Jansen MH, Twisk JW, Anderson AK, Coombes L, Breen M, Hargrave OJ, Hemsley J, Craig F, Cruz O, Kaspers GJ, van Vuurden DG, Hargrave DR, SIOPE DIPG Network (2016) Palliative and end-of-life care for children with diffuse intrinsic pontine glioma: results from a London cohort study and international survey. Neuro Oncol 18(4):582–588
Postovsky S, Eran A, Weyl Ben Arush M (2008) Unusual case of leptomeningeal dissemination of a diffuse pontine high-grade astrocytoma in a child. Pediatr Neurosurg 44:208–211
Sethi R, Allen J, Donahue B, Karajannis M, Gardner S, Wisoff J, Kunnakkat S, Mathew J, Zagzag D, Newman K, Narayana A (2011) Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma. J Neuro-Oncol 102:121–127
Vallero SG, Lijoi S, Bertin D, Pittana LS, Bellini S, Rossi F, Peretta P, Basso ME, Fagioli F (2014) End-of-life care in pediatric neuro-oncology. Pediatr Blood Cancer 61:2004–2011
Kuhlen M, Hoell J, Balzer S, Borkhardt A, Janssen G (2016) Symptoms and management of pediatric patients with incurable brain tumors in palliative home care. Eur J Paediatr Neurol 20(2):261–269
Postovsky S, Moaed B, Krivoy E, Ofir R, Ben Arush MW (2007) Practice of palliative sedation in children with brain tumors and sarcomas at the end of life. Pediatr Hematol Oncol 24:409–415
Postovsky S, Ash S, Ramu IN, Yaniv Y, Zaizov R, Futerman B, Elhasid R, Ben Barak A, Halil A, Ben Arush MW (2003) Central nervous system involvement in children with sarcoma. Oncology 65:118–124
Kebudi R, Ayan I, Görgün O, Ağaoğlu FY, Vural S, Darendeliler E (2005) Brain metastasis in pediatric extracranial solid tumors: survey and literature review. J Neuro-Oncol 71:43–48
Paulino AC, Nguyen TX, Barker JL Jr (2003) Brain metastasis in children with sarcoma, neuroblastoma, and Wilms’ tumor. Int J Radiat Oncol Biol Phys 57:177–183
Suki D, Khoury Abdulla R, Ding M, Khatua S, Sawaya R (2014) Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. J Neurosurg Pediatr 14:372–385
Morris EC, Harrison G, Bailey CC, Hann IM, Hill FG, Gibson BE, Richards S, Webb DK, Medical Research Council Childhood Leukaemia Working Party (2003) Prognostic factors and outcome for children after second central nervous system relapse of acute lymphoblastic leukaemia. Br J Haematol 120:787–789
Wusthoff CJ, Shellhaas RA, Licht DJ (2007) Management of common neurologic symptoms in pediatric palliative care: seizures, agitation, and spasticity. Pediatr Clin N Am 54:709–733
Boyette-Davis JA, Walters ET, Dougherty PM (2015) Mechanisms involved in the development of chemotherapy-induced neuropathy. Pain Manag 5:285–296
Hurwitz CA, Relling MV, Weitman SD, Ravindranath Y, Vietti TJ, Strother DR, Ragab AH, Pratt CB (1993) Phase I trial of paclitaxel in children with refractory solid tumors: a Pediatric Oncology Group Study. J Clin Oncol 11:2324–2329
Pollono D, Tomarchia S, Drut R, Ibañez O, Ferreyra M, Cédola J (2003) Spinal cord compression: a review of 70 pediatric patients. Pediatr Hematol Oncol 20:457–466
Duong LM, McCarthy BJ, McLendon RE, Dolecek TA, Kruchko C, Douglas LL, Ajani UA (2012) Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007. Cancer 118:4220–4227
Fraser S, Roberts L, Murphy E (2009) Cauda equina syndrome: a literature review of its definition and clinical presentation. Arch Phys Med Rehabil 90:1964–1968
Prewett S, Venkitaraman R (2010) Metastatic spinal cord compression: review of the evidence for a radiotherapy dose fractionation schedule. Clin Oncol (R Coll Radiol) 22:222–230
Wu JS, Wong R, Johnston M, Bezjak A, Whelan T, Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group (2003) Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594–605
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Postovsky, S., Lehavi, A., Attias, O., Hershman, E. (2018). Easing of Physical Distress in Pediatric Cancer. In: Wolfe, J., Jones, B., Kreicbergs, U., Jankovic, M. (eds) Palliative Care in Pediatric Oncology. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-61391-8_7
Download citation
DOI: https://doi.org/10.1007/978-3-319-61391-8_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-61390-1
Online ISBN: 978-3-319-61391-8
eBook Packages: MedicineMedicine (R0)