Anesthesiology Clin N Am 24 (2006) 145 – 161 Palliative Care and Pediatrics Doralina L. Anghelescu, MDa,T,Linda Oakes, RN, MSN, CCNSb, Pamela S. Hinds, RN, PhDc a Pain Management Service, Division of Anesthesia, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USAb Department of Patient Care Service, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA c Nursing Research, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA You matter because you are and you matter to the last moment of your life. We will do all we can, not only to help you die peacefully, but also to live until you die. Cicely Saunders Epidemiology of death in the pediatric setting Death in childhood is unnatural and unexpected; nevertheless, it is an un-questionable reality. More than 500,000 children live with complex chronic con-ditions, and approximately 55,000 children ages 0 to 19 years old die annually inthe United States [2,3]. One third of pediatric deaths occur in the neonatal period,half occur in the first year of life, and one fourth occurs among 15- to 19-year-oldadolescents . The epidemiology of childhood death is significantly differentfrom that of adult death. The causes of pediatric death are remarkable for theirdiversity. More than 30% of deaths are caused by injuries, whereas pediatriccancer has been identified as the cause of death in only 4% of cases. Among 5- to14-year-old children, cancer represents the second most frequent cause of death,whereas in the 1- to 4-year-old group, cancer represents the third most commoncause of death . Approximately 2200 children and adolescents die of cancer-related deaths each year in the United States. This work was supported in part by American Lebanese Syrian Associated Charities. T Corresponding author. E-mail address: firstname.lastname@example.org (D.L. Anghelescu).0889-8537/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved.doi:10.1016/j.atc.2005.11.001 anesthesiology.theclinics.com
146 anghelescu et al Palliative care should be considered for a variety of complex chronic con-ditions, even when a cure remains a possibility. Approximately one fourth of allchildhood deaths result from complex chronic conditions, defined as medicalconditions in which at least 12 months of survival is expected and that involveeither one or several organ systems severely enough to require specialty pediatriccare . Conditions in which patients may benefit from palliative care includecongenital anomalies incompatible with prolonged life, chromosomal disorders,metabolic disorders, complex chronic heart conditions, and neuromuscular con-ditions. Cancer and AIDS add to the list of medical conditions that prompt earlypalliative care interventions. Although deaths related to many pediatric cancersshow a downward trend, the number of deaths caused by noncancerous complexchronic conditions remains fairly constant over time . Four patterns of diseaseprogression for which palliative care is indicated have been identified [2,6,7]:conditions for which a potentially curative treatment has failed (cancer and severecongenital or acquired heart disease); conditions in which intensive long-termtreatment may prolong and enhance life but premature death is expected (cysticfibrosis, HIV infection, severe immune deficiencies, and muscular dystrophy);progressive conditions in which treatment is almost exclusively palliative butmay extend over many years (neurodegenerative diseases); and nonprogressiveneurologic conditions that result in high susceptibility to complications and pre-mature death (cerebral palsy, extreme prematurity, and hypoxic brain injury).Palliative care: goals and focus The World Health Organization’s definition of palliative care emphasizes theconcept of ‘‘active total care.’’ Palliative care is the active total care of patientswhose disease is not responsive to curative treatment. Control of pain, othersymptoms, and psychologic, social, and spiritual problems is paramount. Thegoal of palliative care is the achievement of the best possible quality of life forpatients and their families, consistent with their values, regardless of the locationof the patient [8,9]. The ultimate goal of pediatric palliative care is to embrace theunique needs of the suffering child and the family as well as those of the ‘‘familyof care-givers.’’ Ideally, palliative care is an early intervention instituted at thetime of diagnosis, which proceeds throughout the course of curative therapy. Inthis sense, palliative care is ‘‘about living until you die,’’ as Cicely Saunders ,the founder of the palliative care movement, eloquently defined it. When thedisease process is not amenable to curative interventions and extending the du-ration of life becomes a questionable goal, the focus of care shifts to maximizingthe quality of the time spent together by the child and the family, while mini-mizing suffering and pain. Early palliative intervention should be considered forall patients who have potentially life-threatening conditions. In caring for cancerpatients in particular, the relevant components of palliative care should beintroduced at the time of diagnosis. Importantly, the relationship between pal-liative care and curative care is not one of mutual exclusion; palliative care is notthe philosophy of care that replaces curative or life-extending efforts. Instead,
palliative care and pediatrics 147curative therapy and therapy aimed at maximizing comfort and quality of lifecare should overlap as concurrent components of care.Principles of pediatric palliative care The principles of pediatric palliative care are modeled after those for adultpalliative care but are adapted for the pediatric age group . The core idealsare open communication, intensive symptom management, timely access to care,flexibility in the implementation of interventions, ethical decision making, andattention to the quality of life of the patient, the parents, and the siblings. Theinterventions are child-focused and family oriented and can be modeled to fit‘‘any place, any time,’’ in the hospital or the home, with home-care and hos-pice support. The integrated model for providing palliative care for children with life-threatening or terminal conditions, as proposed by the American Academy ofPediatrics , is based on five principles: (1) respect for the dignity of patientsand families; (2) access to competent and compassionate palliative care; (3) sup-port for the caregivers; (4) improved professional and social support for pediat-ric palliative care; and (5) continued advancement of pediatric palliative carethrough research and education . Palliative care interventions should be basedon respect for the child and family’s preferences about monitoring, testing, andtreatment. Open communication between the child, the family, and the health careteam is crucial because it provides the foundation for decision making. Familysupport and bereavement care must be provided during the end of life and afterthe death of a child as integrated components of palliative care. The palliativecare approach is based on the understanding that a person is an indivisible entity,a physical and spiritual being. The interventions offered within the palliative carestructure address concerns at three levels: (1) physical concerns, such as symp-toms (pain, fatigue, dyspnea, agitation, nausea, vomiting, and pruritus); (2) psy-chosocial concerns, which include identifying and addressing the child andfamily’s fears and concerns, coping and communication skills, previous experi-ences and expectations, and sources of and needs for bereavement support; and(3) spiritual concerns . Respite care also should be considered throughout achild’s illness as a support measure for the family.Symptoms and suffering at the end of life There are a limited number of evidence-based interventions aimed at de-creasing physical symptoms and suffering at the end of life, reflecting the paucityof research on this topic. Interviews of parents of children who have died ofcancer reveal that children experience substantial suffering during the last monthof life. According to parental reports, 89% of the children experienced substan-tial suffering from at least one symptom; and the most common symptoms werefatigue, pain, dyspnea, and poor appetite . This study also found that treat-ment was seldom successful: fewer than 30% of parents reported that pain
148 anghelescu et altreatment was successful, and only 10% of parents reported that nausea andvomiting or constipation were controlled. Suffering may result in part from thefailure of the medical team to recognize it, as suggested by the discordancebetween parental reports and physician assessments. Other studies also haveidentified difficulties and limited success in managing pain for children withvarious chronic conditions at the end of life [11,12].Suffering among parents and siblings During the end-of-life period and after the death of a child, palliative careshould include family support care and bereavement care. Psychologic andphysical distress is common among parents and siblings after the death of achild. Psychologic distress, reported as depression, feelings of grief, guilt, or an-xiety, is common, as are elements of physical suffering such as insomnia, head-aches, and musculoskeletal pain. In one descriptive study , parents whoprovided home care for their dying child reportedly experienced better psycho-logic adjustment than parents whose child died in the hospital. Allowing familiesto choose their preferred location of end-of-life care (home versus hospital) isrecommended. Components of psychosocial distress reported by siblings afterthe death of a child include fears, sensations of isolation, school and socialdifficulties, and behavioral problems. One fourth to one third of parents reportsignificant marital distress, and one third of siblings report adjustment problems.Because parents of children who have died of cancer are themselves at risk forpremature death and the degree of suffering they perceive their child to experienceaffects the parents’ ability to function, the death of a child or adolescent is an issueof societal health.Caregiver suffering For the health care professional, suffering for and with the sick and dyingchild and the family is an integral part of caring . Caregiver suffering hasa multitude of dimensions that must be addressed within the meaning and pur-pose of palliative care. Human suffering results from a threat to the person’srelationship with the physical and psychologic self, with others, and with atranscendent source of meaning [15,16]. Suffering has its source in challengesthat threaten the intactness of the person as a complex physical, social, psycho-logic, and spiritual being [15,17]. When the physical, emotional, and spiritualdemands of caregiving exceed the caregiver’s resources and suffering becomes athreat to the caregiver’s sense of identity, integrity, and self-worth, the personalwell being of the caregiver and the quality of care will be endangered . Amultitude of factors can threaten the caregiver’s integrity: powerlessness andhopelessness in the face of suffering and death, competing demands, personalvalue conflicts, misplaced guilt, a struggle to meet the expectations of being a‘‘good’’ care provider, perceiving death as a failure to deliver ‘‘successful’’ care,and the subsequent erosion of self-esteem. Symptoms of caregiver suffering can
palliative care and pediatrics 149become manifest on a physical level (fatigue, weight changes, sleep disturbances,and susceptibility to illness), an emotional level (fear, guilt, resentment, depres-sion, anxiety, and feeling overwhelmed), a behavioral level (addictive behavior,controlling behavior, avoidance, and erosion of relationships), and a spirituallevel (crisis of faith and a loss of self-worth) . Strategies to address caregiversuffering aim to preserve or recover self-integrity and to honor the integrity ofothers. The first step toward healing is the acceptance and recognition of thesource and experience of suffering, which starts the dynamic process of sharedexperiences and reflections. The opportunity to express oneself in discussionforums (palliative care and ethics rounds and debriefing sessions after a childdies) and to listen to others’ experiences of suffering help in the search for mean-ing and significance in suffering and death.Barriers to providing optimal pediatric palliative care To ensure ‘‘competent, compassionate and consistent care to meet the chil-dren’s and their families’ physical, emotional and spiritual needs,’’ the 2003 In-stitute of Medicine Report ‘‘When Children Die’’  called for the provision andorganization of family and child-centered care, the restructuring of care financ-ing, policy reform, increased public awareness, enhanced education of health careprofessionals, and research focused on palliative care. Significant barriers to theoptimal care of dying children range from the individual educational level to theinstitutional and health care system level. Pediatric care providers often lack experience in dealing with death. In asurvey of attitudes and practices regarding the care of dying children, pediatriconcologists have reported a lack of formal education in pediatric palliative care;only 10% of pediatric oncologists had taken formal courses in pediatric terminalcare. They also have reported a high reliance on trial and error in learning toprovide end-of-life care (91.9%), learning from colleagues in clinical practice(85.4%), or learning from role models during their formative years . Beforepediatric palliative care can evolve as a well-defined area of clinical expertise,teaching, and research, pediatric palliative care specialists must be developedwho can take the lead as educators, clinical role models, and researchers andwho can expand educational programs to prepare all pediatric care providerswith basic competence in palliative, end-of-life, and bereavement care. The spe-cialty of palliative care medicine is advanced by the opportunity to obtainboard certification in hospice and palliative care medicine by both physiciansand nurses. At the institutional level, barriers to providing optimal palliative care can beovercome by developing and implementing clinical practice guidelines, institu-tional protocols, and procedures for palliative, end-of-life, and bereavement care.Palliative care ideally should be provided by an interdisciplinary care team, whichcould include palliative care physicians, advanced-practice nurses, social workers,patient care coordinators, child life specialists, and chaplains. Such team inter-ventions should promote the coordination and continuity of care.
150 anghelescu et al Other barriers to palliative care include financial and public policy limitations,as reflected by the lack of universal health care coverage for children, the lackof reimbursement for crucial services, and low daily reimbursement rates forhospice care. Although two thirds of children are covered by employment-basedor other private health insurance and one fifth are covered by state Medicaid orother public agencies, approximately 15% of children under the age of 19 haveno health insurance . Patient access to palliative care and hospice care canbe hindered by factors such as eligibility restrictions (eg, a life expectancy of6 months or less) and the family’s willingness to forgo further curative or life-prolonging care. There are various recommendations to improve access to hos-pice and palliative care, including enrollment criteria that are based on thediagnosis and severity of illness, rather than on life expectancy, and reimburse-ment for crucial services, such as palliative care consultations and counseling, aswell as bereavement services for the families.Pain and symptom management The importance of pain and symptom management at the end of life derivesfrom the high prevalence of symptoms and suffering [10,20] and the limitedsuccess of therapeutic interventions . During the last month of life, 89% ofchildren with cancer are reported to experience ‘‘a lot or a great deal’’ of sufferingfrom at least one symptom, and 51% of children suffer from three or moresymptoms. The most commonly treated symptoms are pain (76%) and dyspnea(65%). However, pain was successfully controlled in only 27% of cases anddyspnea in only 16% of cases . These data, based on parental reports, contrastsharply with the fact that 91% of pediatric oncologists report that they areproficient at treating the pain of dying children . Therefore, the dual nature ofour challenge is that symptom control at the end of life may be inadequate andthat providers may lack awareness of their limitations . Intensive symptommanagement is a priority of care and requires accurate symptom assessment,aggressive intervention, frequent reevaluation, and flexibility in refining andcombining therapeutic modalities. Major advances have been made in the assess-ment and control of pain in children. Misconceptions about the inability of chil-dren to feel or remember pain, the risk of opioid addiction in children, andthe desirability of ‘‘saving the stronger medication for later’’ have been overcome[22–24]. Several concepts and principles form the foundation of pediatricpain management. 1. Use developmentally appropriate assessment tools to ensure the con- sistency and accuracy of pain assessment. Behavioral pain scales are ap- propriate for young, nonverbal, or developmentally delayed children. Self-reporting is the gold standard for the older age group. 2. Follow a stepwise approach to the escalation of therapy, with an emphasis on drug selection based on the intensity of pain, ranging from acet-
palliative care and pediatrics 151 aminophen and nonsteroidal anti-inflammatory drugs for mild pain to opioids for moderate to severe pain. 3. Select the route of administration based on the criteria of simplicity, safety, convenience, and effectiveness; the oral route is preferred. 4. Titrate the dose to attain pain control while minimizing side effects and achieving a balance between satisfactory analgesia and acceptable side effects. 5. Evaluate and treat the cause of pain concomitantly with symptomatic pain management. 6. Determine the temporal characteristics of pain. Pain that is limited to intermittent, brief episodes may be controlled with as-needed doses; on- going pain is an indication for either an ‘‘around-the-clock’’ regimen or a strategy of delivering a long-acting opioid for constant pain plus a short- acting opioid for breakthrough episodes of pain. 7. Titrate the continuous hourly dose of opioid and the rescue doses for breakthrough pain according to the principle that the rescue dose should equal 50% to 200% of the hourly dose, or 5% to 10% of the total daily opioid requirement, and therefore both parameters should be adjusted proportionally [24,25]. 8. Select specific pharmacologic interventions based on the suspected pathophysiology of pain (eg, nociceptive pain versus neuropathic pain, inflammatory pain, or bone pain). 9. Follow a continuum of frequent pain reassessment, intervention adjust- ment, and assessment and treatment of side effects. 10. Multimodal interventions include nonpharmacologic modalities to com- plement and enhance the pharmacologic tools and the use of different classes of medications to target various pathophysiologic pathways. 11. Consider invasive treatment modalities for pain that is difficult to treat (epidural and intrathecal catheters and neurolytic nerve blocks). A number of factors may concur to limit the adequacy of pain control at theend of life. Parents’ misconceptions about the risk of respiratory depression,sedation, or addiction and practitioners’ underdosing of opioids are possiblescenarios that cause the undertreatment of pain. The distinction between theopioid-naRve and the opioid-tolerant patient is of paramount importance whenrefining pain management interventions. The recommended starting doses ofopioids are weight-based and are applicable to the opioid-naRve child, as indicatedin Table 1 [24,26–29]. This approach must be modified for the opioid-tolerantchild at the end of life. Titration to effect becomes a key strategy at the end oflife because the dosage required to achieve pain control may escalate tremen-dously. As in adults, there is no maximum acceptable dose of opioid; theappropriate dose is the dose that controls the child’s pain with the least sideeffects. The opioid response increases linearly with the log of the dose . Thus,strategies for opioid titration recommend a dose increment of 30% to 50% toimprove analgesia significantly for patients in moderate to severe pain [24,25].
152 anghelescu et alTable 1Analgesics for childrenDrug classification Medication Route and dosagea CommentOpioids Morphine PO: 0.15–0.3 mg/kg q 4 h Initial doses for opioid- Intermittent IV: 0.1 mg/kg q naRve children; titration to 3–4 h effect is often required for Continuous IV infusion: any opioid 0.03–0.06 mg/kg/h with an initial bolus of 0.05 mg/kg Hydromorphone Intermittent IV bolus: 0.015 mg/kg q 4–6 h Fentanyl Intermittent IV bolus: 1–2 mg/kg Continuous IV infusion: 1–3 mg/kg/hr Oxycodone PO: 0.1 mg/kg q 4 hNSAIDs Acetaminophen PO: 15 mg/kg q 4 h Limited anti-inflammatory (maximum 1000 mg/dose); effect maximum of 90 mg/kg/d in older children, 60 mg/kg/d in younger children (or 4000 mg/d) Naproxen PO: 5 mg/kg q 8–12 h; Side effects: anti-platelet, maximum dose of gastritis, renal toxicity 500 mg/dose or 1000 mg/d Ibuprofen PO: 5–10 mg/kg q 6–8 h; maximum dose of 800 mg/ dose or 3200 mg/d Ketorolac IV: 0. 5 mg q 6 h; limit to 48–72 hNeuropathic Gabapentin PO: 5 mg/kg or 100–300 mg Side effects: dizziness, co-analgesics up to 70 mg/kg/d or 1200 mg ataxia, somnolence, TID fatigue Amitriptyline PO: 0.1 mg/kg up to Side effects: dizziness, 1 mg/kg/d once per day somnolence, dry mouth, at bedtime cardiac dysrhythmiasAbbreviations: IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug; PO, oral; TID, threetimes per day. a Doses are for children older than 6 months of age.Experts report the need for high doses of opioids in pediatric palliative care[24,31,32], with doses of morphine as high as 500 mg/kg/h for children withterminal cancer . The selection of pharmacologic interventions for pain is dictated by the in-tensity of pain, with consideration of the pathophysiologic mechanisms involvedin the specific clinical situation and the child’s comorbidities and opioid history(side effects and preferred route). For mild pain, acetaminophen or nonsteroidalanti-inflammatory drugs are used as the first line of therapy. Acetaminophenhas the advantage of not causing gastrointestinal, renal, or platelet function side
palliative care and pediatrics 153effects, but its antipyretic action may mask fever in neutropenic patients. Non-steroidal anti-inflammatory drugs should be considered the agents of choice forbone pain (primary or metastatic bone tumors and leukemic infiltrates); however,they are contraindicated in children with thrombocytopenia, and their use may belimited by pharmacologic interactions with chemotherapeutic agents. Althoughselective cyclooxygenase-2 inhibitors have a better side-effect profile, they havenot been studied sufficiently in the pediatric population . If codeine is usedfor mild pain, the practitioner must consider that 10% of whites lack the enzymethat metabolizes codeine to its active form, morphine, and therefore these patientswill not experience the analgesic effect ; furthermore, the incidence of nau-sea, vomiting, and constipation may be higher than that caused by oxycodone orhydrocodone [21,35]. Morphine is an effective opioid for the treatment of moderate to severe noci-ceptive pain and is the gold standard with which all other opioids are compared.Pharmacokinetics studies suggest that younger children, when given an equiv-alent weight-based dose, are likely to have significantly lower plasma levels ofmorphine and its metabolites; therefore, a starting dose of oral morphine of 1.5 to2 mg/kg/d and a regimen of sustained-release oral morphine at 8-hour intervals,rather than the traditional twice-per-day regimen, is recommended for children[27,36]. The recommended pediatric dose for intravenous morphine is 0.02 to0.03 mg/kg/h. However, for infants in the first 3 months of life, morphine dosesshould be reduced by 25% to 30% because of the delayed clearance of opioids inthis age group. . For the child who has a pattern of continuous pain withintermittent exacerbation, morphine offers the advantage of several sustained-release preparations, some of which are available in capsules that can be openedand sprinkled on food or administered through a feeding tube. The immediate-release morphine solution can be concentrated to a maximum of 20 mg/mL,which makes it convenient for administration as sublingual drops for the childwho is unable to swallow at the end of life . If unacceptable side effects (pruritus, dysphoria, or myoclonus) occur withmorphine, an alternative opioid may be given using equianalgesic doses (Table 2)[30,37]. A hydromorphone-to-morphine equianalgesic ratio of 6 to 1 has beendetermined in a population of bone marrow transplant patients who had muco-sitis and were receiving patient-controlled analgesia . In the palliative caresetting, hydromorphone has the advantage that it can be administered subcuta-Table 2Opioid equianalgesic doses Equianalgesic dose (mg)Drug IV or IM POMorphine 10 30Hydromorphone 1.5 7.5Fentanyl 0.1–0.2 Not availableOxycodone Not available 15–30Abbreviations: IM, intramuscular; IV, intravenous; PO, oral.
154 anghelescu et alneously because of its high potency and high aqueous solubility. Fentanyl is anattractive alternative opioid for pain control at the end of life because it hasunique routes of administration, in addition to the traditional intravenous route.Oral transmucosal fentanyl has established indications in adult cancer palliativecare for control of breakthrough pain . The risks of hypoventilation, oxygendesaturation, and nausea and vomiting may limit the safety of its use in thepediatric population. Transdermal fentanyl has been evaluated for its usefulness,feasibility, and tolerability in a small study of children with cancer pain . Thismodality of opioid delivery is advantageous for treating stable levels of chronicpain at the end of life, and it offers the convenience of application only onceevery 72 hours. Nevertheless, it lacks flexibility and titratability because of the12- to 16-hour interval necessary to reach steady-state plasma concentrationsand the delayed dissipation of effect after removal of the patch because of con-tinued absorption from the subcutaneous reservoir. It can be useful for back-ground opioid delivery, while the need for rescue doses is met by using short-actingoral opioids. Opioid rotation is used to gain some analgesic benefit by taking advantageof the incomplete cross-tolerance between opioids. The indications for opioidrotation are dose-limiting toxicity (delivery of adequate analgesia is limited byside effects) or the development of tolerance that prevents adequate pain controlby dose escalation. The administration of 100% of the equianalgesic dose isunnecessary when rotating opioids and may lead to unacceptable side effects oroverdose [30,37]. For opioids with short half-lives, the conversion dose may beapproximately 50%, whereas for conversion to methadone, the required dose maybe only 10% to 20% of the equianalgesic dose of the opioid used previously . It is essential to anticipate and control opioid-related side effects to avoidadding to the patient’s discomfort and suffering. Interventions to control suchsymptoms are presented in Table 3 [28,37,42,43]. Patients may develop somedegree of tolerance to sedation, pruritus, nausea, and vomiting; however, childrendo not develop tolerance to constipation. A bowel regimen should be initiated atthe time of treatment with opioids, usually with a stool softener such as sodiumdocusate in combination with a stimulant such as senna. Additional factors suchas immobility and poor fluid and dietary intake may contribute to constipation,and interventions to attenuate them should be considered, if possible [21,44].Pruritus may be treated with antihistaminic drugs or low-dose naloxone infusionor by changing to another opioid. Sedation and somnolence can be bothersomeside effects of opioids and are controllable with both dextroamphetamine andmethylphenidate . Multimodal approaches that combine opioids with otheranalgesics (nonsteroidal anti-inflammatory drugs, anticonvulsants, and anti-depressants) and with nonpharmacologic interventions (Box 1) should be con-sidered in providing optimal pain relief with fewer side effects. Several principles guide the therapeutic approach to nausea and vomiting:(1) therapy should be mechanism-oriented; (2) the dose regimen of the first-linedrug should be optimized as tolerated; (3) combination therapy offers the benefitof different modes of action ; and (4) nonpharmacologic approaches should
palliative care and pediatrics 155Table 3Pharmacologic management of symptoms other than painSymptom Medication Route and dosageDyspnea Glycopyrrolate PO: 40–100 mg/kg/dose TID or QID IV: 4–10 mg/kg/dose q 3–4 h Opioids See Table 1Anxiety, agitation, Lorazepam PO or IV: 0.03–0.2 mg/kg q 4–6 h up to 2 mg/dose or delirium Midazolam IV: 0.025–0.05 mg/kg q 2–4 h Pentobarbital IV: 0.5–1 mg/kg, repeated q 5–10 min until desired effect Opioids See Table 1Nausea Ondansetron PO: 0.2 mg/kg q 8 h up to 8 mg/dose IV: 0.10–0.45 mg/kg q 8 h up to 8 mg/dose Lorazepam See anxiety above Promethazine PO or IV: 0.25–0.5 mg/kg q 4–6 h, with maximum 50 mg/dose Dexamethasone PO or IV: 0.1–0.2 mg/kg initially; then up to 1–1.5 mg/kg/day divided into doses q 6 h Metoclopramide PO or IV: 0.1 mg/kg up to 1–2 mg/kg q 6 h, with maximum 50 mg/dose Diphenhydramine PO or IV: 0.5–1 mg/kg q 4–6 h, with maximum 50 mg/dose Hydroxyzine PO: 0.5–1 mg/kg q 4–6 hPruritus Diphenhydramine See nausea above Hydroxyzine See nausea above Naloxone IV continuous infusion: 0.25 mg/kg/h; titrate up to 1 mg/kg/hConstipation Senna PO: 10–20 mg/kg or BID Docusate PO: 5 mg/dose (3–12y old) or 5–15 mg/dose ( N 12y old) BID or TID Bisacodyl PO: 5–10 mg/day (3–12y), 5–15 mg/day ( z12y) Naloxone PO: 1–3 mg TID, titrated to a maximum of 12 mg BIDExcessive sedation Methylphenidate PO: 0.3 mg/kg or 10–20 mg prior to breakfast and lunch; increase the dose up to 2 mg/kg/dAbbreviations: BID, twice per day; IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug;PO, oral; QID, four times per day; TID, three times per day.be included in the multimodal intervention . Nausea and vomiting havemultiple causes and contributing factors in the child receiving palliative care.Therapeutic interventions should be selected on the basis of the correspondingmechanism of action, and should target more than symptomatic relief, if possi-ble. Nausea and vomiting can be result from intestinal obstruction caused bytumor invasion or by impaction and chronic constipation. Opioid treatment,chemotherapy, and radiation therapy contribute to nausea and vomiting. Forsymptoms that are an expression of increased intracranial pressure, dexametha-sone may be beneficial. If triggered by movement, symptoms may respond to ananticholinergic-like scopolamine. Nausea and vomiting related to gastric stasismay respond to prokinetic agents such as metoclopramide. Anticipatory vomitingand anxiety-induced emesis are best treated with a benzodiazepine (eg, lor-azepam). Ondansetron and other 5-hydroxytryptamine antagonists are effective
156 anghelescu et al Box 1. Nonpharmacologic approaches to pain management Physical comfort measures Acupuncture Heat and cold Massage Pacifier Rocking Transcutaneous nerve stimulators Other Meditation and prayer Music and art therapy Behavioral and cognitive techniques Art and play therapy Biofeedback Controlled breathing, eg, blowing bubbles Desensitization Distraction Guided imagery Hypnotherapy Modeling Relaxation Thought stoppingfor nausea and vomiting in patients who have advanced cancer. Antihistaminesand phenothiazines are additional options. Anxiety and depression are prevalent among children at the end of life .Anxiety should be addressed by offering a caring, openly supportive environ-ment. Agitation and delirium require the consideration of potentially reversiblecauses, including pain, renal and hepatic failure, drug toxicity, sepsis, hypoxia,and brain metastases. The prolonged administration of benzodiazepines maybe associated with a decrease in anxiolytic effect and cumulative psychomotorimpairment; therefore, the recommendation is for short-term or intermittent use[21,45]. In the context of terminal restlessness and agitation at the end of life,the option of terminal sedation may be considered, with the intent to ensure com-fort [21,24]. Dyspnea or ‘‘air hunger’’ is a common source of suffering at the end of life and is intensely distressing to the child and the parents. A thorough eval-
palliative care and pediatrics 157uation of the underlying mechanism should direct the therapeutic interventions.The most frequent cause of respiratory distress in pediatric cancer patients ispulmonary metastases. Contributory reversible factors such as pneumonia, pleu-ral effusion, or volume overload should be considered and addressed with anti-biotics, thoracentesis, or diuresis, respectively. Beneficial supportive treatmentsinclude supplemental humidified oxygen for comfort and either systemic or in-haled opioids [46,47]. Fatigue is the most common symptom experienced by children and adoles-cents dying of cancer [10,48]. Treatment should be targeted toward the correctionof underlying causes, such as anemia, infection, pain, malnutrition, metabolicabnormalities, cardiac, renal, or hepatic compromise, or disrupted sleep [49,50].Prioritizing the activities of daily living, avoiding nonessential activities, andcareful planning for social interactions are useful strategies for families and healthcare providers when attempting to conserve the child’s energy. It also is helpfulfor family members to learn that fatigue can be an emotional or mental tiredness,rendering the dying child or adolescent unable to interact in a social situation,respond with expected emotions, or retain new information [49,51]. Altered sleeppatterns (such as prolonged naps or disrupted sleep) often accompany fatigue asdo negative thoughts, sadness, or even depression . Multiple distressing and burdensome symptoms that occur together are ref-erred to as symptom clusters. Sleep deprivation, pain, and anxiety tend to bepresent simultaneously in pediatric oncology patients and constitute a symptomcluster. Diminishing one symptom in the cluster may effectively diminish othersymptoms in the same cluster . The symptom management plan of careshould be individualized, acceptable to the child’s family, flexible, based on themost current research and evidence, and include both pharmacologic and non-pharmacologic interventions. Specific nonpharmacologic interventions shouldbe selected for children according to the type of symptom, the child’s age orcognitive level, and whether the intervention is focused on modifying the child’ssensory perception, behavior, or thoughts and coping abilities.Communication at the end of life Useful, effective and sensitive communication involving the terminally illchild and family and health care providers regarding the child’s prognosis, careoptions, and potential end-of-life experiences is critical for maintaining trustingrelationships that will be essential for preventing or diminishing the child andfamily’s suffering. In several reports, parents of terminally ill children describetheir perceptions of uncaring and insufficient communication from health careprofessionals and link that communication with their own lingering regrets andemotional distress [11,54–56]. Parents of terminally ill children tend to maintain hope for their child’s sur-vival, even when they have been told by trusted professionals that their child’sdeath is certain. When this need to maintain hope is respected by the health careprofessionals, parents tend to be more willing to participate in end-of-life care
158 anghelescu et aldecision making and to report higher satisfaction with end-of-life care . Cli-nicians experienced with pediatric end-of-life care generally recommend thatterminally ill children be informed about their prognosis because open com-munication can help to diminish certain fears [2,57–60]. Children differ in theamount and detail of information that they desire and a careful assessment ofwhat information is preferred needs to be ongoing. Effective, compassionatecommunication with the terminally ill child and the family may be the mostsignificant contribution that a health care professional can make to facilitate afamily’s adjustment to living without their child [9,55].Summary Such a systematic approach to symptoms and suffering, described step bystep in a problem-based approach, is insufficient and less than ideal, even whenit is based on good clinical evidence and sound science. It can only becomemeaningful and effective through a process of reintegration in which the patient’sgoals for care and ‘‘the big picture’’ are constantly reevaluated. Goal-orientedcare directs decision making toward integrated therapies and interventions thatkeep the child in the center as a whole human being, rather than the isolatedsymptoms. In this respect, pediatric palliative care involves conceptually a pro-cess of deconstruction into a series of discrete problems, only to reconstruct aholistic approach by which all dimensions, physical, psychosocial, and spiritual,are integrated in an attempt to relieve suffering and to preserve dignity, meaning,and value of life until the last moment.References  Saunders C. Care of the dying: 1. the problem of euthanasia. Nurs Times 1976;72(26):1003 – 5.  Himelstein BP, Hilden JM, Boldt AM, et al. Pediatric palliative care. N Engl J Med 2004; 350(17):1752 – 62.  Arias E, MacDorman MF, Strobino DM, et al. Annual summary of vital statistics–2002. Pediatrics 2003;112(6 Pt 1):1215 – 30.  Field M, Behrman R. When children die: improving palliative care and end-of-life care for children and their families. Washington (DC)7 National Academies Press; 2003.  Feudtner C, Hays RM, Haynes G, et al. Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services. Pediatrics 2001; 107(6):E99 – 103.  Hynson JL, Sawyer SM. Paediatric palliative care: distinctive needs and emerging issues. J Paediatr Child Health 2001;37(4):323 – 5.  Goldman A. ABC of palliative care: special problems of children. BMJ 1998;316(7124):49 – 52.  Levetown M. Compendium of pediatric palliative care: Children’s International Project on Palliative/Hospice Services (ChIPPS). Alexandria (VA)7 National Hospice and Palliative Care Organization; 2000.  American Academy of Pediatrics Committee on Bioethics and Committee on Hospital Care. Palliative care for children. Pediatrics 2000;106(Pt 1):351 – 7.
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