Ann Goldman

Symptoms in Children/Young People With Progressive Malignant Disease: United Kingdom Children's Cancer Study Group/Paediatric Oncology Nurses Forum Survey

AIM. The purpose of this study was to survey symptoms in children/young people with progressive cancer and identify which are the most important and which are the most difficult to treat effectively. PATIENTS AND METHODS. This was a questionnaire survey of 22 United Kingdom Childrens Cancer Study Group centers. Data were collected by clinical nurse specialists in pediatric oncology regarding children/young people between 0 and 20 years of age, using 2 questionnaires. The first collected demographic details and the second data about the occurrence and perceived impact of symptoms. RESULTS. There were 185 children/young people from 20 centers registered in the study, aged 4 months to 19 years (mean: 8.7 years), who received palliative care for a median of 34 days (range: 0–354 days). Data were analyzed for 164 children/young people who died during the study. Between referral to palliative care and death, there were significant increases in the number of symptoms reported and children/young people experiencing pain (70.6% vs 91.5%). Symptoms included some that often go unrecognized in children/young people, for example, anorexia, weight loss, and weakness. The nature of the underlying malignancy significantly influenced the prevalence of some symptoms. There were significant differences between the symptoms associated with central nervous system tumors and other groups. Pain other than headache occurred more commonly in children with solid tumors (98.4%) than in others (87%). Neurologic symptoms, including headache, were universal among those with central nervous system tumors. CONCLUSION. This study documents the frequency of symptoms and contrasts the experiences of children/young people with different groups of malignant disease. With access to skilled symptom control, pain can be effectively treated in most children/young people. Some other symptoms often remain intractable. The study highlights the need for further research to establish the effectiveness of therapeutic interventions for symptom control and their impact on the quality of life for children/young people dying from cancer.

Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain

OBJECTIVES (1) To determine the pharmacokinetics of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) in children with cancer receiving morphine as immediate-release morphine liquid or sustained-release tablets. (2) To determine differences with age within the group and from adults. (3) To explore relationships between plasma concentration and pain measurements. STUDY DESIGN Blood samples were collected and plasma analyzed by high-performance liquid chromatography with electrochemical and fluorescence detection. Population pharmacokinetic parameters were derived with the program P-PHARM. RESULTS Forty children with a median age of 11.4 years (range 1.7 to 18.7 years) received a median dose of 1.4 mg/kg/d (range 0.4 to 24.6 mg/kg/d). A median of 4 blood samples per child was collected. Plasma clearance of morphine was 23.1 mL/min per kg body weight. The volume of distribution was 5.2 L/kg. Molar ratios of M3G/morphine, M6G/morphine, and M3G/M6G were 21.1, 4.7, and 4.2, respectively. Children <11 years had significantly higher clearance and larger volume of distribution for morphine and its glucuronides than older children and adults. Regression analysis indicated average plasma morphine concentration equal to dose (mg/kg/d) x 8.6 (95% confidence interval 7.4 to 9.9). Significant pain was present in 30% of the children. Higher pain scores were recorded in children with average morphine concentrations <12 ng/mL (P <.01 MW). CONCLUSION Age differences in morphine pharmacokinetics exist within children and compared with adults. The study supports a starting dose of 1.5 to 2. 0 mg/kg/d to provide plasma morphine concentrations >12 ng/mL in children with cancer pain unrelieved by mild to moderate strength analgesia.

ABC of palliative care. Special problems of children.

The death of a child has long been acknowledged as one of the greatest tragedies that can happen to a family, and care for seriously ill children and their families is central to paediatrics. It is only recently, however, that the needs for palliative care of children with life limiting illnesses and their families have been considered as a speciality within paediatrics: the most suitable approaches to care are still being developed, and the provision of services nationally is uneven and sometimes inadequate. #### Numbers of children with life limiting illness ##### Annual mortality from life limiting illnesses ##### Prevalence of life limiting illnesses In a health district of 250 000 people, with a child population of about 50 000, in one year Fortunately, deaths in childhood that can be anticipated, and for which palliative care can be planned, are rare. A recent joint report by ACT (Association for Children with Life Threatening or Terminal Conditions and their Families) and the Royal College of Paediatrics and Child Health offers the most up to date information about epidemiology (see box of further reading). Paediatric palliative care may be needed for a wide range of diseases, which differ from adult diseases and many of which are rare and familial. The diagnosis influences the type of care that a child and family will need, and four broad groups have been identified. View this table: Groups of life limiting diseases in children RETURN TO TEXT Palliative care may be needed from infancy and for many years for some children, while others may not need it until they are older and only for a short time. Also the …

Not knowing—the problem of pain in children with severe neurological impairment

This study uses a grounded theory approach to explore the diagnostic and clinical decision-making processes used by parents and healthcare professionals in relation to pain in children with severe to profound neurological impairment. Three forms of knowledge are required for optimal pain assessment and management (1) knowing the child, (2) familiarity with children with the same or similar conditions and (3) knowing the science. Pain relief can be compromised by systems of care that fragment rather than integrate care. A model which integrates knowledge of child, population and science is proposed together with an intersubjective attitude to assessing pain.

Immunolocalization of neuroblastoma using radiolabeled monoclonal antibody UJ13A.

The monoclonal antibody UJ13A, raised after immunization of mice with human fetal brain, recognized an antigen expressed on human neuroblastoma cell lines and fresh tumors. Antibody was purified and radiolabeled with iodine isotopes using chloramine-T. In preclinical studies, 125I-labeled UJ13A was injected intravenously into nude mice bearing xenografts of human neuroblastoma. Radiolabeled UJ13A uptake by the tumors was four to 23 times greater than that by blood. In control animals, injected with a similar quantity of a monoclonal antibody known not to bind to neuroblastoma cells in vitro (FD44), there was no selective tumor uptake. Nine patients with histologically confirmed neuroblastoma each received 100 to 300 micrograms UJ13A radiolabeled with 1 to 2.8 mCi 123I or 131I. Sixteen positive sites were visible on gamma scans 1 to 7 days after injection: 15 were primary or secondary tumor sites, and one was a false positive; there were two false negatives. In two of the 15 positive sites, tumor had not been demonstrated by other imaging techniques; these were later confirmed as areas of malignant infiltration. No toxicity was encountered.

Home management of the dying NICU patient

Intensive aggressive medical therapy does not always result in cure. For some neonates it is a futile exercise that may prolong a short life of suffering. In this article, we will discuss the babies for whom aggressive therapy may not be appropriate, and how home centered palliative care can be effectively managed. We will outline the holistic multidisciplinary approach to care, with the parents as primary carers, empowered to make informed choices in the medical care of their dying baby. Symptom management will be discussed, based on the experience of an established palliative care team. We will also look at the practical and emotional preparation for death and bereavement support for the family. We hope that more families will be given the opportunity to spend time at home with their dying baby and that, through appropriate care and support, the memory of this time will be treasured.

The role of oral controlled-release morphine for pain relief in children with cancer

Effective pain control is a key part of the care of children with cancer. We report our experience with controlled-release morphine tablets (MST Continus, NAPP) given as analgesia to 60 children who were terminally ill from a range of malignant diseases. MST was given over periods ranging from 1-165 days (median 14 days). We found that the appropriate initial dose was 1 mg/kg/dose for children whose pain was not controlled by mild analgesics or weak opioids. Maximum doses up to 41.6 mg/kg/dose were needed to maintain analgesia. Provision of a short-acting opioid is essential for breakthrough pain. The main side-effects were temporary drowsiness and constipation. Careful education of parents and health-care professionals in the correct use of MST is important. MST proved an effective and acceptable strong analgesic for children, particularly convenient for the terminally ill at home.

Pain Assessment in Children

Although indirect, behavioural measures are the only approaches that can be used in babies, the very young, and those with severe neurological problems. Depending upon age, developmental level and sociocultural considerations, some children will be able to use scales and descriptions that are identical to adults’, such as numerical and visual analogue scales. A variety of scales featuring face scales, colour and poker chip tools and ladders have been adapted for younger children [2] . The range of tools available utilise a combination of aspects of cry, facial expression, posture, body movements and verbal expression. The limitations are that these measures may not discriminate clearly between pain and distress for other reasons. Different tools have been developed for different situations; most have been tested for reliability and validity. The behavioural changes that occur with acute pain seem to differ from those in chronic pain. All these tools are proxy measures using the parents’ or professional’s assessment, not the child’s personal experience. Body charts, drawing and play give children the opportunity to explain more about their pain in ways that might be easier for them than verbal description. Nevertheless, self-report remains the most reliable method. A detailed pain history can provide information about pain and indications as to whether it is visceral, boney or neuropathic in origin. Precipitating and relieving factors may add to the clues about origin. Since past experience of pain may be significant, it may influence pain management. For chronic pain, diaries can help provide a longterm profile. Introduction

Living well and dying well - facing the challenges at a children's hospital

We outline a process, undertaken at a large tertiary childrens hospital, intended to provide practical guidance and support for those involved in the management of children with life-limiting conditions. Initial discussions with representatives of clinical and support services identified communication problems and ethical dilemmas as key issues. These were further explored in multidisciplinary hospital meetings, culminating in a conference (Living Well, Dying Well) where individual perspectives - clinical, multi-faith, parental and legal - and cases were presented. Communication problems were found to involve unrealistic expectations, failures of anticipation and difficulties in discussing sensitive issues, while ethical dilemmas arose from balancing burdens and benefits, clinical uncertainty, respecting autonomy and achieving equity and justice in delivery of care. An integrated service has been developed that is intended to provide clinical and spiritual care, psychosocial and ethical support, advice and mediation for children, families and staff, and to address the latters educational and training needs.

An Overview of Paediatric Palliative Care

The approach to managing symptoms, including pain and psychological symptoms, needs to be systematic and careful. For pain, the details of its cause, severity, timing, nature and interference with daily life should be identified. After careful assessment, treatment approaches can be devised which take into consideration the broadest picture and include an appropriate combination of pharmacological and holistic treatments. Regular review ensures that treatment is adjusted as the situation alters.