Hospices and palliative care for children: converging stories.

INTRODUCTION: Children's hospices offer support to children and their families according to a model that is quite different from adult hospices and has evolved in parallel with specialist paediatric palliative medicine services. SOURCES OF DATA: Published research, Together for Short Lives. AREAS OF AGREEMENT: The services hospices offer are highly valued by families. AREAS OF CONTROVERSY: It is not always clear that hospices can be described as 'specialist', which can make it difficult for hospices to negotiate appropriate commissioning arrangements with the statutory sector. GROWING POINTS: Children's palliative care generally is poorly developed compared with the adult specialty, and local providers should work with hospices to help redress the inequity that children face in accessing specialist palliative care. AREAS TIMELY FOR DEVELOPING RESEARCH: If hospices are to continue to be important providers of palliative care in children they must develop robust and fair relationships with local healthcare providers. That would be facilitated by development of a funding formula for children that properly acknowledges the part hospices already play in palliative care.

Oral morphine versus transmucosal diamorphine for breakthrough pain in children: methods and outcomes: UK (DIPPER study) consensus.

OBJECTIVES: No randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility of conducting a prospective randomised controlled trial comparing oral and transmucosal administration of opioids for breakthrough pain. The aim of the current study was to achieve consensus on design aspects for a small-scale prospective study to inform a future randomised controlled trial of oral morphine, the current first-line treatment, versus transmucosal diamorphine. METHODS: The nominal group technique was used to achieve consensus on best practice for mode of administration, dose regimen and a range of suitable pain intensity outcome measures for transmucosal diamorphine in children and young people with breakthrough pain. An expert panel of ten clinicians in paediatric palliative care and three parent representatives participated. Consensus was achieved when agreement was reached and no further comments from participants were forthcoming. RESULTS: The panel favoured the buccal route of administration, with dosing according to the recommendations in the Association for Paediatric Palliative Medicine formulary (fifth Edition, 2020). The verbal Numerical Rating Scale was selected to measure pain in children 8 years old and older, the Faces Pain Scale-Revised for children between 4 and 8 years old, and Face, Legs, Activity, Cry and Consolability (FLACC)/FLACC-Revised as the observational tools. CONCLUSIONS: The nominal group technique allowed consensus to be reached for a small-scale, prospective, cohort study and provided information to inform the design of a randomised controlled trial.

Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancer.

The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.

'Total Pain' in Children with Severe Neurological Impairment.

Many children with palliative care needs experience difficulty in managing pain. Perhaps none more so than those with severe neurological impairment. For many years; behaviours in these children were misunderstood. As a result; pain was poorly recognised and inadequately managed. Significant advances have been made in the assessment and management of pain in this challenging group of patients. We summarise these advances; drawing on our own experience working with infants; children and young adults with palliative care needs within a UK tertiary paediatric palliative care service. We expand on the recent understanding of 'Total Pain'; applying a holistic approach to pain assessment and management in children with severe neurological impairment.

Morphine in children with cancer: impact of age, chemotherapy and other factors on protein binding.

The aim of this study was to contrast protein binding of morphine and morphine-6 glucuronide in cord blood and children with adults and examine impact of chemotherapy and other factors. Morphine binding was measured in spiked samples from 18 adults and 18 neonates (cord blood), and compared with six children with cancer receiving morphine. The influence of the following was examined: Human serum albumin (HSA), alpha-1 acid glycoprotein (AAG), non-esterified fatty acids (NEFA); palmitic acid and oleic acid, pH, vincristine, methotrexate, 6-mercaptopurine and M6G. binding correlated with concentrations of albumin and alpha1 acid glycoprotein. In vitro, binding was not altered by vincristine, 6-mercaptopurine, methotrexate or M6G. Compared with HSA alone, AAG increased binding, palmitic acid reduced it and oleic acid had no effect. Binding was unaffected by pH in samples from patients. Morphine binding was influenced by concentrations of albumin, AAG and morphine itself, but not by age.

Strong opioids in pediatric palliative medicine.

The management of pain in the palliative care of children is somewhat different from that in adults. It also differs in approach from the management of other types of acute and chronic pain in childhood. Whereas once opioids were thought to be highly dangerous drugs, unsuitable for use in children, they have now taken their place as the mainstay for provision of good analgesia to manage moderate-to-severe pain in both malignant and non-malignant life-limiting conditions. There are relatively little clinical or laboratory data regarding opioids specifically in children. However, much of what has been published regarding the management of pain in palliative medicine in adults can be extrapolated. On saying that, early research in children does suggest some significant differences in opioid pharmacokinetics, particularly with respect to morphine clearance, which seems to be faster in adults. Thus, the use of opioids in pediatric palliative care presents some unique challenges. Confident and rational use of opioids by pediatricians, illustrated by the WHO guidelines, is essential for the adequate management of pain complicating the palliative phase in children with life-limiting conditions.

Palliative care in children in Wales: a study of provision and need.

AIM: To establish incidence and prevalence of children needing palliative care in Wales. PATIENTS AND METHODS: Children were identified in three ways: (1) from paediatricians using the Welsh Paediatric Surveillance Unit (WPSU); (2) referrals to the specialist palliative medicine service based in Cardiff; and (3) children under the care of the two principal children's hospices serving Wales. All children referred or reported between January 2001 and December 2002 were included. RESULTS: A total of 226 children were identified. Fifty (22%) were identified by paediatricians, 58 (26%) were referred to the specialist paediatric palliative medicine service, 158 (70%) had been under the care of a children's hospice, and 34 (15%) were identified by more than one source. This study identified approximately 3.75 per 10000 children. This is about half the prevalence figures quoted in the ACT/ RCPCH document in 1997. CONCLUSIONS: The study may underestimate prevalence. Children needing palliative medicine are still under-recognized in Wales. The overlap between children's hospice care and specialist paediatric palliative medicine is relatively small.

Paediatric palliative medicine: a unique challenge.

For more than thirty years, adults suffering from life-threatening or terminal conditions have been able to access specialist skills in palliative medicine. It has taken much longer for children to start to have access to the same expertise. Paediatric palliative medicine adopts a robust and rational approach to symptom control, based on a thorough understanding of pathophysiology and therapeutics. At the same time, it recognises that physical issues are only one aspect of a child's quality of life and, by adopting a multi-dimensional approach, aims to address psychosocial and spiritual or existential concerns.

Complex chromosomal abnormalities in utero, 5 years before leukaemia.

Prenatal acquisition of leukaemia-associated gene rearrangements is a well-established phenomenon. This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero. Identical twin girls, aged 4 years, developed ETV6/AML1-positive acute lymphoblastic leukaemia (ALL) within 3 months of one another. Both demonstrated an identical four way, variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6 one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1 fusion and the associated complex chromosomal rearrangements occurred in utero. Clonal expansion of the abnormal cell in one twin was followed by metastasis to the other. There was a prolonged preleukaemic phase, which lasted well into childhood. The short time between the two diagnoses of ALL suggests a common precipitating event. The significance of the different secondary markers remains unclear.

Prophylaxis of acute chemotherapy-induced nausea and vomiting in children with cancer: what is the evidence?

BACKGROUND: Nausea and vomiting are preventable side effects of cancer chemotherapy for children. Antiemetics are essential, especially as treatment becomes more intensive. Many drugs are available, but adequate evidence-based recommendations are lacking. We aimed (1) to consider an evidence-based approach for pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in children, and (2) to compare this approach with antiemetic prescribing in two paediatric oncology centres. PROCEDURE: Relevant publications (Medline, Embase, CancerLit:1966-2002) were critically evaluated using pre-defined criteria. Evidence-based statements summarising their findings were formulated, and evidence basis proposed. Current prescribing practice was then compared with this evidence basis in Welsh children under 16 receiving chemotherapy at Llandough Hospital, Cardiff or Alder Hey Children's Hospital, Liverpool between 1 January 2001 and 31 December 2001. RESULTS: Of 213 studies retrieved, 82 provided evidence. Our evidence basis recommends combination 5HT3-antagonist/corticosteroid for highly emetogenic chemotherapy, 5HT3-antagonist alone for moderate emetogenicity, and no antiemetic for other chemotherapy. Forty-four children in Cardiff (0.6-16.9 yrs) and 14 in Liverpool (0.8-16.2 yrs) were included in the audit. Differences in prescribing practice between the centres were not significant. In 109/159 (69%) of chemotherapy courses (35, 87 and 100% of high, moderate and low emetogenicity, respectively), antiemetics were selected in accordance with evidence basis. Seventy percent of prescribed doses were as evidence basis recommended. CONCLUSIONS: We present an evidence basis for prescribing prophylactic antiemetics to children undergoing chemotherapy. Prescribing practices in these two centres treating Welsh children were similar. Both differed from the evidence basis we propose. Deviations were greatest for regimens of high emetogenicity, where effective emetic control is most crucial.