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  Table of Contents  
Year : 2022  |  Volume : 59  |  Issue : 2  |  Page : 265-268

Refractory cancer pain in young child at end-of-life: Can we alleviate the suffering?

Department of Onco-Anaesthesia and Palliative Medicine, Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Date of Submission10-Jun-2020
Date of Decision10-Jun-2020
Date of Acceptance02-Aug-2020
Date of Web Publication29-Jun-2022

Correspondence Address:
Seema Mishra
Department of Onco-Anaesthesia and Palliative Medicine, Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_635_20

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 » Abstract 

Pain is a common and highly distressing symptom in children with advanced malignancies and it is often multifactorial at the end-of-life. The prognosis of cancer pain is reported to be worse in those with mixed pain type, high pain severity, daily opioid use, and poor emotional well-being. We describe a case of 13-year-old boy, known case of metastatic Ewing sarcoma right iliac bone, who presented to our palliative care ward with intractable pain and was finally discharged home for terminal care with high doses of morphine, ketamine, and midazolam infusion through elastomeric pump attached to a peripherally inserted central catheter (PICC line). The suffering of imminently dying children should be reduced, and judicious dose escalation of opioids along with adjuvants is appropriate and often necessary.

Keywords: Elastomeric pumps, ketamine, neuropathic, opioids, pediatric

How to cite this article:
Agarwal S, Singh VP, Sangwan A, Mishra S. Refractory cancer pain in young child at end-of-life: Can we alleviate the suffering?. Indian J Cancer 2022;59:265-8

How to cite this URL:
Agarwal S, Singh VP, Sangwan A, Mishra S. Refractory cancer pain in young child at end-of-life: Can we alleviate the suffering?. Indian J Cancer [serial online] 2022 [cited 2022 Nov 30];59:265-8. Available from:

 » Introduction Top

Pain is one of the common and distressing symptoms experienced by cancer patients. Patients with advanced cancer experience physical, psychological, spiritual, and emotional distress, all of which contribute to “suffering”.[1] Refractory cancer pain is defined as pain that is nonresponsive to standard doses of opioid with or without coanalgesic therapy, and incidence reported is 10–20%.[2] The various risk factors are young age, neuropathic pain, psychological stress, prior opioid use, previous addiction, and impaired neurological status.[3] Neuropathic pain towards end-of-life has mixed nociceptive and neuropathic mechanisms.[4] The management of neuropathic pain in pediatric oncology poses a great challenge. Dose regimen escalation along with various other pharmacological therapies is often required.

We hereby report a case of 13-year-old boy, known case of metastatic Ewing sarcoma right iliac bone, who presented to our palliative care ward with intractable pain and was finally managed with high doses of morphine, ketamine, and midazolam infusion through elastomeric pump.

 » Case Top

A 13-year-old boy, known case of metastatic Ewing sarcoma of right iliac bone, presented to our palliative care ward with complaint of pain in bilateral foot for past 3 months. The pain was pricking, burning type, and continuous in nature. Patient was asymptomatic one and half years back, when he had pain in right lower limb, evaluated outside and magnetic resonance imaging showed a tumor in right iliac bone involving acetabulum and sacroiliac joint. Biopsy was suggestive of Ewing sarcoma. However, his parents did not take any treatment for 6 months and opted for alternative therapy. When the child started having proptosis of bilateral eyes, then they went to a cancer hospital. He received multiple lines of chemotherapy and palliative radiotherapy there, but the disease progressed. The patient received multiple analgesics in last 3 months before coming to our center, which included low dose oral opioids (morphine 5 mg thrice a day), gabapentin, paracetamol, and naproxen. Epidural catheter was placed thrice during pain management at various private hospitals due to peri-catheter leak. The pain relief was adequate for 1 month, but it became intolerable with disease progression. The patient was given epidural bupivacaine 0.0625% at 5 ml/hour and morphine 1.5 mg twice a day along with intravenous infusion of morphine at 1 mg/hour and midazolam at 0.5 mg/hour, but pain relief was inadequate by these different interventions, so they self-referred to our center for further management of pain.

In our ward, we started morphine and midazolam infusion and later ketamine infusion was also added. The dose was increased to 5 mg/hour of morphine, 1 mg/hour midazolam, and 5 mg/hour of ketamine. The child just wanted to sleep initially as he had not slept since a few days due to pain. Although he could sleep for a few hours, but the pain relief was inadequate. Methadone could not be opted as the child had prolonged QT interval in baseline electrocardiogram (ECG). Contrast enhanced computed tomography scan was done which showed a huge mass originating from right iliac bone and a large paravertebral mass from T12 to L5, multiple skeletal and brain metastasis. It was decided to give palliative radiotherapy, five fractions to the paravertebral mass to decrease the pain. The parents were explained about epidural analgesia/neurolysis, but they refused any further invasive intervention. The analgesic titration was done with morphine at high doses again along with ketamine and midazolam infusion. Various adjuvants like paracetamol, pregabalin, dexamethasone, and flupirtine were added. The pain was settled on rest. The parents were counseled about the advanced nature of disease. They were explained about hospice care and homecare. However, they did not prefer to take the child to hospice due to some familial constraints. They also had a younger daughter to take care, and the father had to continue his job to overcome the financial crisis in the family. The patient himself wanted to spend his last days of life with his sister as he understood about the prognosis of his disease very well. Thus, they decided to take the child home for terminal care, and he was discharged with morphine infusion at 20 mg/hour, ketamine at 2 mg/hour, and midazolam at 0.5 mg/hour through elastomeric pump. A peripherally inserted central catheter (PICC) {Groshong catheter, Bard access systems} was already in situ in the right arm as patient had received chemotherapy previously. The PICC line was patent, and there were no signs of any inflammation and pain at the local site. Thus, we attached the elastomeric pump (NeofuserVario, VL 17) with a capacity of 275 mL to the PICC line. The child got admitted multiple times in 1 month duration in our ward for inadequate pain relief. Every time we titrated and increased the doses. The child was finally discharged with morphine infusion at 35 mg/hour, ketamine at 3 mg/hour, and midazolam at 2 mg/hour, and rescue doses of morphine were explained. They were reassured that the purpose of attaching the pump is not to hasten the death but it is to manage the pain and provide comfort care to the child. We gave our telephone number for telecommunication, and they were assured that they could call us at any time. This relieved the stress and anxiety of the parents to a great extent. They used to come to the hospital on every fourth day for refill of the pump. Besides physical pain, the child also had psychosocial component of pain, although he understood his disease well. Upon further assessment of other dimensions of pain, it was found that he was distressed due to issues in his family. His parents were planning to get separated and had frequent fights. This led to development of anxiety in the child. In addition, the child felt lonely and depressed due to loss of school days and unable to meet his friends.

The parents were explained about these psychosocial factors that affected the child and his pain. They were counseled about futility of further treatment and that their family should remain as a closely knit unit with a sick child at home. We also explored the spiritual component of pain, but he did not seem to be in spiritual distress. The child finally had adequate pain relief in physical, psychological, and social components of pain. The physical pain was managed with high dose of analgesics, and psychological component was managed by antianxiety medications and repeated counseling. His relatives and friends were encouraged to come and meet him often, so he did not feel lonely and social component of pain was also managed to an extent. After few days, the child expired peacefully at his home.

 » Discussion Top

Children with advanced malignancies have pain as one of the common and highly distressing symptoms in terminal stage. Malignant solid tumors cause pain due to direct infiltration of the nerves or the nerve roots.[5],[6] Pain can be either pure neuropathic or mixed nociceptive type as perceived by 40% of adult and teenage cancer patients.[7] Pain should be assessed promptly and underlying pathology should be corrected along with analgesic medications.

Patients with mixed pain type, high pain intensity, emotional distress, and opioid dependence have poor prognosis of cancer pain.[3] Our patient also had poor prognosis for cancer pain as he had mixed pain and was in emotional distress because of his family issues and incompatibility between parents.

Neuropathic pain is well described in adult patients with malignancy; however, limited literature is available in children with malignancies.[8],[9] Neuropathic pain can be caused by somatosensory system injuries that can be due to tumor leading to neuropathic pain, postsurgical neuropathic pain, chemotherapy-induced neuropathy, and the complex circumstances of neuropathic pain towards the end-of-life.[10]

Total pain is a concept of managing pain in a holistic way and aims to improve the quality of life of patients with life-threatening illnesses. Pain in children with advanced malignancy is usually managed by combined pharmacological and nonpharmacologic modalities. This multimodal approach helps in reducing psychosocial and existential distress in patients and families and help in medical pain management. Psychosocial interventions can help in reducing the severity of pain experienced by the patient.[11] Adolescents usually require extra care in psychosocial aspect of pain.

Opioid medications are the mainstay of management of cancer pain in children in advanced stages; however, the doses are highly variable. This is due to change in pharmacokinetics of drugs depending upon age and different mechanisms of pain.[12] The literature on the role of opioids for management of cancer pain in children is very limited. The maximum dose for opioids is not described; however, dose needs to be titrated till pain is controlled adequately or serious side effects are observed. The common misconceptions on the opioid use for pain relief like it might hasten death, chances of addiction, and side effects from medication may act as barriers to achieve satisfactory pain relief. The suffering of imminently dying children due to refractory pain should be reduced by escalating the doses of opioid rapidly and opioid rotation should be considered.[11] In our patient also, rapid titration was done with high doses of morphine along with nonopioid adjuvants to relieve the suffering of the child in the terminal stage. The dose requirement of opioids also increased as the disease progressed.

Along with opioids, adjuvants such as ketamine and methadone can be useful for management of mixed pain in terminal stages. These adjuvants act by antagonism of N-methyl-D-aspartate receptors. These receptors have a role in central sensitization, the development of hyperalgesia, and allodynia in chronic pain, and these phenomena are reversed when ketamine binds to these receptors.[13] Recent studies show that descending inhibitory pathway can be activated when ketamine is used.[14] There are a few studies showing improved pain control with ketamine in children with cancer pain but no randomized controlled trials are found. When ketamine is combined with benzodiazepines, hallucinations and feelings of depersonalization/derealization are not reported.[15] In our patient, we used low-dose ketamine infusion with midazolam infusion to relieve the intractable pain.

Elastomeric pumps are small, and portable, have low-rate of complications, high-efficacy, and can last longer than 24 hours,[16] whereas syringe drivers need battery to operate, appropriate staff training, and last for 24 hours. There are chances of pain and inflammation at local site if subcutaneous route is used. Daily visits from community nurses and professionals may be required for checking the syringe drivers.[17],[18] Therefore, we used elastomeric pumps in this case for pain management as we do not have community-based nurses in our set up who are adequately trained in using syringe drivers. We have very few hospice services in our resource limited setting and homecare services are provided by nongovernmental organizations in certain areas only. In our set up, usually we do not send patients on home infusions. It was our first experience of using elastomeric pump in palliative setting and sending the child home on infusion. A large number of oncology patients have long-term intravenous access in the form of PICC lines and portacaths for chemotherapy, which can later be used to give intravenous infusions for symptom management at end-of-life. These Groshong type of PICC lines can be used for prolonged duration and are ideal for homecare management due to quality of pure silicon, presence of valve, and specially made closed tip.[19] We utilized it in a better way under these circumstances.

Psychosocial interventions are essential part of holistic management of patient even in the terminal stage. The end-of-life care discussions including planning for terminal care and preferred place of death should be done with patients and their families. These discussions lead to patients and family members preferring home as place of death and thus parents feel a sense of preparedness and are comfortable in caring during the terminal stage.[20] This was done in our case as we repeatedly counseled the parents regarding advanced nature of disease and about futility of treatment. Thus, they were prepared to take the child home for his terminal care once the pain was managed.

 » Conclusion Top

Pain management should be aggressive in children with advanced cancer in the terminal stage to decrease the suffering and distress of the patient and family. Patients with advanced cancer often require escalation of opioid doses to achieve adequate pain relief, but individual factors affect the opioid dose required to achieve sufficient pain relief. We used intravenous route in our patient for symptom management at end-of-life as long-term access in form of peripherally inserted central catheter (PICC line) was available. Intravenous route is usually better in hospitalized patients or in acute pain and subcutaneous route for homecare, especially in resource limited settings—depending on feasibility.


The authors gratefully acknowledge the work of their colleagues and supporting hospital staff for holistic management of the patient and would also acknowledge the cooperation of parents of the patient for understanding the prognosis of the disease and thus helping in dignified end-of-life care.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

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Afsharimani B, Kindl K, Good P, Hardy J. Pharmacological options for the management of refractory cancer pain—what is the evidence? Support Care Cancer 2015;23:1473-81.  Back to cited text no. 2
Fainsinger RL, Nekolaichuk CL. A “TNM” classification system for cancer pain: The Edmonton classification system for cancer pain (ECS-CP). Support Care Cancer 2008;16:547-55.  Back to cited text no. 3
Snaman JM, Baker JN, Ehrentraut JH, Anghelescu DL. Pediatric oncology: Managing pain at the end-of-life. Paediatr Drugs 2016;18:161-80.  Back to cited text no. 4
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Ingelmo PM, Fumagalli R. Neuropathic pain in children. Minerva Anestesiol 2004;70:393-98.  Back to cited text no. 6
Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kassa S. Prevalence and aetiology of neuropathic pain in cancer patients: A systematic review. Pain 2012;153:359-65.  Back to cited text no. 7
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Jacob E. Neuropathic pain in children with cancer. J Pediatr Oncol Nurs 2004;21:350-57.  Back to cited text no. 9
Anghelescu DL, Tesney JM. Neuropathic pain in pediatric oncology: A clinical decision algorithm. Paediatr Drugs 2019;21:59-70.  Back to cited text no. 10
Turk DC, Swanson KS, Tunks ER. Psychological approaches in the treatment of chronic pain patients—when pills, scalpels, and needles are not enough. Can J Psychiatry 2008;53:213-23.  Back to cited text no. 11
Zernikow B, Michel E, Craig F, Anderson BJ. Pediatric palliative care: Use of opioids for the management of pain. Paediatr Drugs 2009;11:129-51.  Back to cited text no. 12
Quibell R, Prommer EE, Mihalyo M, Tywcross R, Wilcock A. Ketamine. J Pain Symptom Manage 2011;41:640-49.  Back to cited text no. 13
Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: A current view of their possible interactions. Pain 1995;62:259-74.  Back to cited text no. 14
Bredlau AL, Thakur R, Korones DN, Robert H. Ketamine for pain in adults and children with cancer: A systematic review and synthesis of the literature. Pain Med 2013;14:1505-17.  Back to cited text no. 15
Sosa DS, Lopes ADV, Ferreira JP. Advantages of using elastomeric infusion pumps. Medicina Palliativa 2010;17:135-39.  Back to cited text no. 16
Cruickshank S, Adamson E, Logan J, Brackenridge K. Using syringe drivers in palliative care within a rural, community setting: Capturing the whole experience. Int J Palliat Nurs 2010;16:126-32.  Back to cited text no. 17
Costello J, Nyatanga B, Mula C, Hull J. The benefits and drawbacks of syringe drivers in palliative care. Int J Palliat Nurs 2008;14:139-44.  Back to cited text no. 18
Spaziani S, Micheli T, Vincenzi B, Campisi C. Groshong PICC and homecare: An opportunity. Clinical experience after the first 200 implants. J Vasc Access 2000;1:108-11.  Back to cited text no. 19
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