1. 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, USA
b
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 [1]
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 in
the 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-old
adolescents [4]. The epidemiology of childhood death is significantly different
from that of adult death. The causes of pediatric death are remarkable for their
diversity. More than 30% of deaths are caused by injuries, whereas pediatric
cancer has been identified as the cause of death in only 4% of cases. Among 5- to
14-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 common
cause of death [4]. 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: doralina.anghelescu@stjude.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

2. 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 all
childhood deaths result from complex chronic conditions, defined as medical
conditions in which at least 12 months of survival is expected and that involve
either one or several organ systems severely enough to require specialty pediatric
care [5]. Conditions in which patients may benefit from palliative care include
congenital 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 early
palliative care interventions. Although deaths related to many pediatric cancers
show a downward trend, the number of deaths caused by noncancerous complex
chronic conditions remains fairly constant over time [5]. Four patterns of disease
progression for which palliative care is indicated have been identified [2,6,7]:
conditions for which a potentially curative treatment has failed (cancer and severe
congenital or acquired heart disease); conditions in which intensive long-term
treatment may prolong and enhance life but premature death is expected (cystic
fibrosis, HIV infection, severe immune deficiencies, and muscular dystrophy);
progressive conditions in which treatment is almost exclusively palliative but
may extend over many years (neurodegenerative diseases); and nonprogressive
neurologic 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 the
concept of ‘‘active total care.’’ Palliative care is the active total care of patients
whose disease is not responsive to curative treatment. Control of pain, other
symptoms, and psychologic, social, and spiritual problems is paramount. The
goal of palliative care is the achievement of the best possible quality of life for
patients and their families, consistent with their values, regardless of the location
of the patient [8,9]. The ultimate goal of pediatric palliative care is to embrace the
unique needs of the suffering child and the family as well as those of the ‘‘family
of care-givers.’’ Ideally, palliative care is an early intervention instituted at the
time of diagnosis, which proceeds throughout the course of curative therapy. In
this sense, palliative care is ‘‘about living until you die,’’ as Cicely Saunders [1],
the founder of the palliative care movement, eloquently defined it. When the
disease process is not amenable to curative interventions and extending the du-
ration of life becomes a questionable goal, the focus of care shifts to maximizing
the quality of the time spent together by the child and the family, while mini-
mizing suffering and pain. Early palliative intervention should be considered for
all patients who have potentially life-threatening conditions. In caring for cancer
patients in particular, the relevant components of palliative care should be
introduced at the time of diagnosis. Importantly, the relationship between pal-
liative care and curative care is not one of mutual exclusion; palliative care is not
the philosophy of care that replaces curative or life-extending efforts. Instead,

3. palliative care and pediatrics 147
curative therapy and therapy aimed at maximizing comfort and quality of life
care should overlap as concurrent components of care.
Principles of pediatric palliative care
The principles of pediatric palliative care are modeled after those for adult
palliative care but are adapted for the pediatric age group [8]. The core ideals
are open communication, intensive symptom management, timely access to care,
flexibility in the implementation of interventions, ethical decision making, and
attention to the quality of life of the patient, the parents, and the siblings. The
interventions 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 of
Pediatrics [9], is based on five principles: (1) respect for the dignity of patients
and 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 care
through research and education [9]. Palliative care interventions should be based
on respect for the child and family’s preferences about monitoring, testing, and
treatment. Open communication between the child, the family, and the health care
team is crucial because it provides the foundation for decision making. Family
support and bereavement care must be provided during the end of life and after
the death of a child as integrated components of palliative care. The palliative
care approach is based on the understanding that a person is an indivisible entity,
a physical and spiritual being. The interventions offered within the palliative care
structure 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 and
family’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 [2]. Respite care also should be considered throughout a
child’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 paucity
of research on this topic. Interviews of parents of children who have died of
cancer reveal that children experience substantial suffering during the last month
of life. According to parental reports, 89% of the children experienced substan-
tial suffering from at least one symptom; and the most common symptoms were
fatigue, pain, dyspnea, and poor appetite [10]. This study also found that treat-
ment was seldom successful: fewer than 30% of parents reported that pain

4. 148 anghelescu et al
treatment was successful, and only 10% of parents reported that nausea and
vomiting or constipation were controlled. Suffering may result in part from the
failure of the medical team to recognize it, as suggested by the discordance
between parental reports and physician assessments. Other studies also have
identified difficulties and limited success in managing pain for children with
various 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 care
should include family support care and bereavement care. Psychologic and
physical distress is common among parents and siblings after the death of a
child. 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 [13], parents who
provided home care for their dying child reportedly experienced better psycho-
logic adjustment than parents whose child died in the hospital. Allowing families
to choose their preferred location of end-of-life care (home versus hospital) is
recommended. Components of psychosocial distress reported by siblings after
the death of a child include fears, sensations of isolation, school and social
difficulties, and behavioral problems. One fourth to one third of parents report
significant marital distress, and one third of siblings report adjustment problems.
Because parents of children who have died of cancer are themselves at risk for
premature death and the degree of suffering they perceive their child to experience
affects the parents’ ability to function, the death of a child or adolescent is an issue
of societal health.
Caregiver suffering
For the health care professional, suffering for and with the sick and dying
child and the family is an integral part of caring [14]. Caregiver suffering has
a 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’s
relationship with the physical and psychologic self, with others, and with a
transcendent source of meaning [15,16]. Suffering has its source in challenges
that threaten the intactness of the person as a complex physical, social, psycho-
logic, and spiritual being [15,17]. When the physical, emotional, and spiritual
demands of caregiving exceed the caregiver’s resources and suffering becomes a
threat to the caregiver’s sense of identity, integrity, and self-worth, the personal
well being of the caregiver and the quality of care will be endangered [18]. A
multitude of factors can threaten the caregiver’s integrity: powerlessness and
hopelessness in the face of suffering and death, competing demands, personal
value 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

5. palliative care and pediatrics 149
become 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 spiritual
level (crisis of faith and a loss of self-worth) [14]. Strategies to address caregiver
suffering aim to preserve or recover self-integrity and to honor the integrity of
others. The first step toward healing is the acceptance and recognition of the
source and experience of suffering, which starts the dynamic process of shared
experiences and reflections. The opportunity to express oneself in discussion
forums (palliative care and ethics rounds and debriefing sessions after a child
dies) 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’’ [4] called for the provision and
organization of family and child-centered care, the restructuring of care financ-
ing, policy reform, increased public awareness, enhanced education of health care
professionals, and research focused on palliative care. Significant barriers to the
optimal care of dying children range from the individual educational level to the
institutional and health care system level.
Pediatric care providers often lack experience in dealing with death. In a
survey of attitudes and practices regarding the care of dying children, pediatric
oncologists have reported a lack of formal education in pediatric palliative care;
only 10% of pediatric oncologists had taken formal courses in pediatric terminal
care. They also have reported a high reliance on trial and error in learning to
provide end-of-life care (91.9%), learning from colleagues in clinical practice
(85.4%), or learning from role models during their formative years [19]. Before
pediatric palliative care can evolve as a well-defined area of clinical expertise,
teaching, and research, pediatric palliative care specialists must be developed
who can take the lead as educators, clinical role models, and researchers and
who can expand educational programs to prepare all pediatric care providers
with basic competence in palliative, end-of-life, and bereavement care. The spe-
cialty of palliative care medicine is advanced by the opportunity to obtain
board certification in hospice and palliative care medicine by both physicians
and nurses.
At the institutional level, barriers to providing optimal palliative care can be
overcome 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, which
could 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.

6. 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 lack
of reimbursement for crucial services, and low daily reimbursement rates for
hospice care. Although two thirds of children are covered by employment-based
or other private health insurance and one fifth are covered by state Medicaid or
other public agencies, approximately 15% of children under the age of 19 have
no health insurance [4]. Patient access to palliative care and hospice care can
be hindered by factors such as eligibility restrictions (eg, a life expectancy of
6 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 the
diagnosis and severity of illness, rather than on life expectancy, and reimburse-
ment for crucial services, such as palliative care consultations and counseling, as
well as bereavement services for the families.
Pain and symptom management
The importance of pain and symptom management at the end of life derives
from the high prevalence of symptoms and suffering [10,20] and the limited
success of therapeutic interventions [10]. During the last month of life, 89% of
children with cancer are reported to experience ‘‘a lot or a great deal’’ of suffering
from at least one symptom, and 51% of children suffer from three or more
symptoms. The most commonly treated symptoms are pain (76%) and dyspnea
(65%). However, pain was successfully controlled in only 27% of cases and
dyspnea in only 16% of cases [10]. These data, based on parental reports, contrast
sharply with the fact that 91% of pediatric oncologists report that they are
proficient at treating the pain of dying children [19]. Therefore, the dual nature of
our challenge is that symptom control at the end of life may be inadequate and
that providers may lack awareness of their limitations [21]. Intensive symptom
management is a priority of care and requires accurate symptom assessment,
aggressive intervention, frequent reevaluation, and flexibility in refining and
combining 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, and
the desirability of ‘‘saving the stronger medication for later’’ have been overcome
[22–24]. Several concepts and principles form the foundation of pediatric
pain 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-

7. 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 the
end of life. Parents’ misconceptions about the risk of respiratory depression,
sedation, or addiction and practitioners’ underdosing of opioids are possible
scenarios that cause the undertreatment of pain. The distinction between the
opioid-naRve and the opioid-tolerant patient is of paramount importance when
refining pain management interventions. The recommended starting doses of
opioids are weight-based and are applicable to the opioid-naRve child, as indicated
in Table 1 [24,26–29]. This approach must be modified for the opioid-tolerant
child at the end of life. Titration to effect becomes a key strategy at the end of
life because the dosage required to achieve pain control may escalate tremen-
dously. As in adults, there is no maximum acceptable dose of opioid; the
appropriate dose is the dose that controls the child’s pain with the least side
effects. The opioid response increases linearly with the log of the dose [30]. Thus,
strategies for opioid titration recommend a dose increment of 30% to 50% to
improve analgesia significantly for patients in moderate to severe pain [24,25].

8. 152 anghelescu et al
Table 1
Analgesics for children
Drug classification Medication Route and dosagea Comment
Opioids 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 h
NSAIDs 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 h
Neuropathic 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 dysrhythmias
Abbreviations: IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug; PO, oral; TID, three
times 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 with
terminal cancer [33].
The selection of pharmacologic interventions for pain is dictated by the in-
tensity of pain, with consideration of the pathophysiologic mechanisms involved
in the specific clinical situation and the child’s comorbidities and opioid history
(side effects and preferred route). For mild pain, acetaminophen or nonsteroidal
anti-inflammatory drugs are used as the first line of therapy. Acetaminophen
has the advantage of not causing gastrointestinal, renal, or platelet function side

9. palliative care and pediatrics 153
effects, but its antipyretic action may mask fever in neutropenic patients. Non-
steroidal anti-inflammatory drugs should be considered the agents of choice for
bone pain (primary or metastatic bone tumors and leukemic infiltrates); however,
they are contraindicated in children with thrombocytopenia, and their use may be
limited by pharmacologic interactions with chemotherapeutic agents. Although
selective cyclooxygenase-2 inhibitors have a better side-effect profile, they have
not been studied sufficiently in the pediatric population [21]. If codeine is used
for mild pain, the practitioner must consider that 10% of whites lack the enzyme
that metabolizes codeine to its active form, morphine, and therefore these patients
will not experience the analgesic effect [34]; furthermore, the incidence of nau-
sea, vomiting, and constipation may be higher than that caused by oxycodone or
hydrocodone [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 of
morphine and its metabolites; therefore, a starting dose of oral morphine of 1.5 to
2 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 to
0.03 mg/kg/h. However, for infants in the first 3 months of life, morphine doses
should be reduced by 25% to 30% because of the delayed clearance of opioids in
this age group. [27]. For the child who has a pattern of continuous pain with
intermittent exacerbation, morphine offers the advantage of several sustained-
release preparations, some of which are available in capsules that can be opened
and 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 child
who is unable to swallow at the end of life [21].
If unacceptable side effects (pruritus, dysphoria, or myoclonus) occur with
morphine, an alternative opioid may be given using equianalgesic doses (Table 2)
[30,37]. A hydromorphone-to-morphine equianalgesic ratio of 6 to 1 has been
determined in a population of bone marrow transplant patients who had muco-
sitis and were receiving patient-controlled analgesia [38]. In the palliative care
setting, hydromorphone has the advantage that it can be administered subcuta-
Table 2
Opioid equianalgesic doses
Equianalgesic dose (mg)
Drug IV or IM PO
Morphine 10 30
Hydromorphone 1.5 7.5
Fentanyl 0.1–0.2 Not available
Oxycodone Not available 15–30
Abbreviations: IM, intramuscular; IV, intravenous; PO, oral.

10. 154 anghelescu et al
neously because of its high potency and high aqueous solubility. Fentanyl is an
attractive alternative opioid for pain control at the end of life because it has
unique routes of administration, in addition to the traditional intravenous route.
Oral transmucosal fentanyl has established indications in adult cancer palliative
care for control of breakthrough pain [39]. The risks of hypoventilation, oxygen
desaturation, and nausea and vomiting may limit the safety of its use in the
pediatric population. Transdermal fentanyl has been evaluated for its usefulness,
feasibility, and tolerability in a small study of children with cancer pain [40]. This
modality of opioid delivery is advantageous for treating stable levels of chronic
pain at the end of life, and it offers the convenience of application only once
every 72 hours. Nevertheless, it lacks flexibility and titratability because of the
12- to 16-hour interval necessary to reach steady-state plasma concentrations
and 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-acting
oral opioids.
Opioid rotation is used to gain some analgesic benefit by taking advantage
of the incomplete cross-tolerance between opioids. The indications for opioid
rotation are dose-limiting toxicity (delivery of adequate analgesia is limited by
side effects) or the development of tolerance that prevents adequate pain control
by dose escalation. The administration of 100% of the equianalgesic dose is
unnecessary when rotating opioids and may lead to unacceptable side effects or
overdose [30,37]. For opioids with short half-lives, the conversion dose may be
approximately 50%, whereas for conversion to methadone, the required dose may
be only 10% to 20% of the equianalgesic dose of the opioid used previously [41].
It is essential to anticipate and control opioid-related side effects to avoid
adding to the patient’s discomfort and suffering. Interventions to control such
symptoms are presented in Table 3 [28,37,42,43]. Patients may develop some
degree of tolerance to sedation, pruritus, nausea, and vomiting; however, children
do not develop tolerance to constipation. A bowel regimen should be initiated at
the time of treatment with opioids, usually with a stool softener such as sodium
docusate in combination with a stimulant such as senna. Additional factors such
as 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 infusion
or by changing to another opioid. Sedation and somnolence can be bothersome
side effects of opioids and are controllable with both dextroamphetamine and
methylphenidate [21]. Multimodal approaches that combine opioids with other
analgesics (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-line
drug should be optimized as tolerated; (3) combination therapy offers the benefit
of different modes of action [24]; and (4) nonpharmacologic approaches should

11. palliative care and pediatrics 155
Table 3
Pharmacologic management of symptoms other than pain
Symptom Medication Route and dosage
Dyspnea Glycopyrrolate PO: 40–100 mg/kg/dose TID or QID
IV: 4–10 mg/kg/dose q 3–4 h
Opioids See Table 1
Anxiety, 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 1
Nausea 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 h
Pruritus Diphenhydramine See nausea above
Hydroxyzine See nausea above
Naloxone IV continuous infusion: 0.25 mg/kg/h; titrate up to
1 mg/kg/h
Constipation 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 BID
Excessive sedation Methylphenidate PO: 0.3 mg/kg or 10–20 mg prior to breakfast and
lunch; increase the dose up to 2 mg/kg/d
Abbreviations: 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 [21]. Nausea and vomiting have
multiple causes and contributing factors in the child receiving palliative care.
Therapeutic interventions should be selected on the basis of the corresponding
mechanism of action, and should target more than symptomatic relief, if possi-
ble. Nausea and vomiting can be result from intestinal obstruction caused by
tumor invasion or by impaction and chronic constipation. Opioid treatment,
chemotherapy, and radiation therapy contribute to nausea and vomiting. For
symptoms that are an expression of increased intracranial pressure, dexametha-
sone may be beneficial. If triggered by movement, symptoms may respond to an
anticholinergic-like scopolamine. Nausea and vomiting related to gastric stasis
may respond to prokinetic agents such as metoclopramide. Anticipatory vomiting
and anxiety-induced emesis are best treated with a benzodiazepine (eg, lor-
azepam). Ondansetron and other 5-hydroxytryptamine antagonists are effective

12. 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 stopping
for nausea and vomiting in patients who have advanced cancer. Antihistamines
and phenothiazines are additional options.
Anxiety and depression are prevalent among children at the end of life [10].
Anxiety should be addressed by offering a caring, openly supportive environ-
ment. Agitation and delirium require the consideration of potentially reversible
causes, including pain, renal and hepatic failure, drug toxicity, sepsis, hypoxia,
and brain metastases. The prolonged administration of benzodiazepines may
be associated with a decrease in anxiolytic effect and cumulative psychomotor
impairment; 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
[10] and is intensely distressing to the child and the parents. A thorough eval-

13. palliative care and pediatrics 157
uation of the underlying mechanism should direct the therapeutic interventions.
The most frequent cause of respiratory distress in pediatric cancer patients is
pulmonary 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 treatments
include 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 correction
of underlying causes, such as anemia, infection, pain, malnutrition, metabolic
abnormalities, cardiac, renal, or hepatic compromise, or disrupted sleep [49,50].
Prioritizing the activities of daily living, avoiding nonessential activities, and
careful planning for social interactions are useful strategies for families and health
care providers when attempting to conserve the child’s energy. It also is helpful
for 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 sleep
patterns (such as prolonged naps or disrupted sleep) often accompany fatigue as
do negative thoughts, sadness, or even depression [52].
Multiple distressing and burdensome symptoms that occur together are ref-
erred to as symptom clusters. Sleep deprivation, pain, and anxiety tend to be
present simultaneously in pediatric oncology patients and constitute a symptom
cluster. Diminishing one symptom in the cluster may effectively diminish other
symptoms in the same cluster [53]. The symptom management plan of care
should be individualized, acceptable to the child’s family, flexible, based on the
most current research and evidence, and include both pharmacologic and non-
pharmacologic interventions. Specific nonpharmacologic interventions should
be selected for children according to the type of symptom, the child’s age or
cognitive level, and whether the intervention is focused on modifying the child’s
sensory perception, behavior, or thoughts and coping abilities.
Communication at the end of life
Useful, effective and sensitive communication involving the terminally ill
child and family and health care providers regarding the child’s prognosis, care
options, and potential end-of-life experiences is critical for maintaining trusting
relationships that will be essential for preventing or diminishing the child and
family’s suffering. In several reports, parents of terminally ill children describe
their perceptions of uncaring and insufficient communication from health care
professionals and link that communication with their own lingering regrets and
emotional 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’s
death is certain. When this need to maintain hope is respected by the health care
professionals, parents tend to be more willing to participate in end-of-life care

14. 158 anghelescu et al
decision making and to report higher satisfaction with end-of-life care [54]. Cli-
nicians experienced with pediatric end-of-life care generally recommend that
terminally ill children be informed about their prognosis because open com-
munication can help to diminish certain fears [2,57–60]. Children differ in the
amount and detail of information that they desire and a careful assessment of
what information is preferred needs to be ongoing. Effective, compassionate
communication with the terminally ill child and the family may be the most
significant contribution that a health care professional can make to facilitate a
family’s adjustment to living without their child [9,55].
Summary
Such a systematic approach to symptoms and suffering, described step by
step in a problem-based approach, is insufficient and less than ideal, even when
it is based on good clinical evidence and sound science. It can only become
meaningful and effective through a process of reintegration in which the patient’s
goals for care and ‘‘the big picture’’ are constantly reevaluated. Goal-oriented
care directs decision making toward integrated therapies and interventions that
keep the child in the center as a whole human being, rather than the isolated
symptoms. In this respect, pediatric palliative care involves conceptually a pro-
cess of deconstruction into a series of discrete problems, only to reconstruct a
holistic 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
[1] Saunders C. Care of the dying: 1. the problem of euthanasia. Nurs Times 1976;72(26):1003 – 5.
[2] Himelstein BP, Hilden JM, Boldt AM, et al. Pediatric palliative care. N Engl J Med 2004;
350(17):1752 – 62.
[3] Arias E, MacDorman MF, Strobino DM, et al. Annual summary of vital statistics–2002.
Pediatrics 2003;112(6 Pt 1):1215 – 30.
[4] 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.
[5] 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.
[6] Hynson JL, Sawyer SM. Paediatric palliative care: distinctive needs and emerging issues.
J Paediatr Child Health 2001;37(4):323 – 5.
[7] Goldman A. ABC of palliative care: special problems of children. BMJ 1998;316(7124):49 – 52.
[8] 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.
[9] American Academy of Pediatrics Committee on Bioethics and Committee on Hospital Care.
Palliative care for children. Pediatrics 2000;106(Pt 1):351 – 7.

15. palliative care and pediatrics 159
[10] Wolfe J, Grier HE, Klar N, et al. Symptoms and suffering at the end of life in children with
cancer. N Engl J Med 2000;342(5):326 – 33.
[11] Contro N, Larson J, Scofield S, et al. Family perspectives on the quality of pediatric palliative
care. Arch Pediatr Adolesc Med 2002;156(1):14 – 9.
[12] Hunt AM. A survey of signs, symptoms and symptom control in 30 terminally ill children.
Dev Med Child Neurol 1990;32(4):341 – 6.
[13] Mulhern RK, Lauer ME, Hoffmann RG. Death of a child at home or in the hospital: subsequent
psychological adjustment of the family. Pediatrics 1983;71(5):743 – 7.
[14] Rushton C. The other side of caring: caregiver suffering. In: Carter B, Levetown M, editors.
Palliative care for infants, children, and adolescents. Baltimore (MD)7 The Johns Hopkins Uni-
versity Press; 2004. p. 220 – 46.
[15] Kane JR, Hellsten MB, Coldsmith A. Human suffering: the need for relationship-based re-
search in pediatric end-of-life care. J Pediatr Oncol Nurs 2004;21(3):180 – 5.
[16] Brenneis JM. Spirituality and suffering. In: Parris WC, editor. Cancer pain management. Boston7
Butterworth-Heinemann; 1997. p. 551.
[17] Cassel EJ. The nature of suffering and the goals of medicine. N Engl J Med 1982;306(11):
639 – 45.
[18] Rushton CH. The baby K case: ethical challenges of preserving professional integrity. Pediatr
Nurs 1995;21(4):367 – 72.
[19] Hilden JM, Emanuel EJ, Fairclough DL, et al. Attitudes and practices among pediatric on-
cologists regarding end-of-life care: results of the 1998 American Society of Clinical Oncology
survey. J Clin Oncol 2001;19(1):205 – 12.
[20] Collins JJ, Byrnes ME, Dunkel IJ, et al. The measurement of symptoms in children with cancer.
J Pain Symptom Manage 2000;19(5):363 – 77.
[21] Wolfe J, Friebert S, Hilden J. Caring for children with advanced cancer integrating pallia-
tive care. Pediatr Clin North Am 2002;49(5):1043 – 62.
[22] Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia
and postoperative analgesia in neonatal cardiac surgery. N Engl J Med 1992;326(1):1 – 9.
[23] Taddio A, Katz J, Ilersich AL, et al. Effect of neonatal circumcision on pain response during
subsequent routine vaccination. Lancet 1997;349(9052):599 – 603.
[24] Frager G. Palliative care and terminal care of children. Child Adolesc Psychiatr Clin N Am
1997;6(4):889 – 909.
[25] Cherny NI, Portenoy RK. Cancer pain management. Current strategy. Cancer 1993;72(Suppl 11):
3393 – 415.
[26] McGrath P. Pain control. In: Doyle D, Hanks G, McDonald N, editors. Oxford textbook of
palliative medicine. 2nd edition. Oxford (UK)7 Oxford University Press; 1998. p. 1013 – 28.
[27] Collins J. Palliative care and the child with cancer. Hematol Oncol Clin North Am 2002;16:
657 – 70.
[28] Weisman S. Supportive care in children with cancer. In: Berger A, Portenoy RK, Weissman DE,
editors. Principles and practices of supportive oncology. Philadelphia7 Lippincott-Raven; 1998.
p. 845 – 52.
[29] Anghelescu D, Oakes L. Working toward better cancer pain management for children. Cancer
Pract 2002;10(Suppl 1):S52–7.
[30] Yaster M. Clinical pharmacology. In: Schechter N, Berde CB, Yaster M, editors. Pain in infants,
children, and adolescents. 2nd edition. Philadephia7 Lippincott, Williams Wilkins; 2003.
p. 71 – 83.
[31] Hooke C, Hellsten MB, Stutzer C, et al. Pain management for the child with cancer in end-of-life
care: APON position paper. J Pediatr Oncol Nurs 2002;19(2):43 – 7.
[32] Siden H, Nalewajek BS. High dose opioids in pediatric palliative care. J Pain Symptom Manage
2003;25(5):397 – 9.
[33] Collins JJ, Grier HE, Kinney HC, et al. Control of severe pain in children with terminal
malignancy. J Pediatr 1995;126(4):653 – 7.
[34] Caraco Y, Sheller J, Wood AJ. Pharmacogenetic determination of the effects of codeine and
prediction of drug interactions. J Pharmacol Exp Ther 1996;278(3):1165 – 74.

16. 160 anghelescu et al
[35] Schecter N, Weisman SJ. Management of pain in childhood cancer. In: Patt R, editor. Cancer
pain. Philadelphia7 JB Lippincott; 1993. p. 509.
[36] Hunt A, Joel S, Dick G, et al. Population pharmacokinetics of oral morphine and its glucuro-
nides in children receiving morphine as immediate-release liquid or sustained-release tablets for
cancer pain. J Pediatr 1999;135(1):47 – 55.
[37] Galloway KS, Yaster M. Pain and symptom control in terminally ill children. Pediatr Clin
North Am 2000;47(3):711 – 46.
[38] Collins JJ, Geake J, Grier HE, et al. Patient-controlled analgesia for mucositis pain in children:
a three-period crossover study comparing morphine and hydromorphone. J Pediatr 1996;129(5):
722 – 8.
[39] Payne R, Coluzzi P, Hart L, et al. Long-term safety of oral transmucosal fentanyl citrate for
breakthrough cancer pain. J Pain Symptom Manage 2001;22(1):575 – 83.
[40] Collins JJ, Dunkel IJ, Gupta SK, et al. Transdermal fentanyl in children with cancer pain:
feasibility, tolerability, and pharmacokinetic correlates. J Pediatr 1999;134(3):319 – 23.
[41] Portenoy RK. Opioid tolerance and responsiveness: research findings and clinical observations.
In: Gebhart GF, Hammond DJ, Jensen TS, editors. Progress in pain research and management.
Seattle (WA)7 JASP Press; 1994. p. 615 – 9.
[42] Berde CB, Collins JJ. Cancer pain and palliative care in children. In: Wall P, Melzack R, editors.
Textbook of pain. Edinburgh (UK)7 Churchill Livingstone; 1999. p. 967 – 89.
[43] Levetown M. Treatment of symptoms other than pain in pediatric palliative care. In: Portenoy
R, Bruera E, editors. Topics in palliative care. New York7 Oxford University Press; 1998.
p. 51 – 69.
[44] Fallon M, O’Neill B. ABC of palliative care: constipation and diarrhoea. BMJ 1997;315(7118):
1293 – 6.
[45] Barraclough J. ABC of palliative care: depression, anxiety, and confusion. BMJ 1997;315(7119):
1365 – 8.
[46] Bruera E, MacEachern T, Ripamonti C, et al. Subcutaneous morphine for dyspnea in cancer
patients. Ann Intern Med 1993;119(9):906 – 7.
[47] Bruera E, Schoeller T, MacEachern T. Symptomatic benefit of supplemental oxygen in
hypoxemic patients with terminal cancer: the use of the N of 1 randomized controlled trial.
J Pain Symptom Manage 1992;7(6):365 – 8.
[48] Kutner JS, Kassner CT, Nowels DE. Symptom burden at the end of life: hospice providers’
perceptions. J Pain Symptom Manage 2001;21(6):473 – 80.
[49] Hinds PS, Hockenberry-Eaton M, Gilger E, et al. Comparing patient, parent, and staff
descriptions of fatigue in pediatric oncology patients. Cancer Nurs 1999;22(4):277 – 88 [quiz:
288–9].
[50] National Comprehensive Cancer Network. Clinical practice guidelines in oncology v.2.2005.
Cancer related fatigue. Available at: http://www.nccn.org. Accessed January 5, 2006.
[51] Hinds PS, Hockenberry-Eaton M, Quargnenti A, et al. Fatigue in 7- to 12-year-old patients
with cancer from the staff perspective: an exploratory study. Oncol Nurs Forum 1999;26(1):
37 – 45.
[52] Hockenberry MJ, Hinds PS, Barrera P, et al. Three instruments to assess fatigue in children with
cancer: the child, parent and staff perspectives. J Pain Symptom Manage 2003;25(4):319 – 28.
[53] Hinds PS, Oakes LL, Hicks J, et al. End-of-life care for children and adolescents. Semin Oncol
Nurs 2005;21(1):53 – 62.
[54] Wolfe J, Klar N, Grier HE, et al. Understanding of prognosis among parents of children who
died of cancer: impact on treatment goals and integration of palliative care. JAMA 2000;284(19):
2469 – 75.
[55] De Graves SD, Aranda S. Exploring documentation of end-of-life care of children with cancer.
Int J Palliat Nurs 2002;8(9):435 – 43.
[56] Meyer EC, Burns JP, Griffith JL, et al. Parental perspectives on end-of-life care in pediatric
intensive care unit. Crit Care Med 2002;30(1):226 – 31.
[57] A statement from the Work Group on Palliative Care for Children of the International Work

17. palliative care and pediatrics 161
Group on Death, Dying, and Bereavement: Children, adolescents, and death; myths, realities,
and challenges. Death Stud 1999;23(5):443 – 63.
[58] Faulkner KW. Talking about death with a dying child. Am J Nurs 1997;97(6):64, 6, 8, 9.
[59] Freyer DR. Care of the dying adolescent: special considerations. Pediatrics 2004;113(2):381 – 8.
[60] Nitschke R, Meyer WH, Sexauer CL, et al. Care of terminally ill children with cancer. Med
Pediatr Oncol 2000;34(4):268 – 70.