Palliative Care in Pediatrics

Liza-Marie Johnson

Melissa DeLario

Justin N. Baker

Javier R. Kane

Palliative medicine for children is the art and science of family-centered care aimed at enhancing quality of life, promoting healing, and attending to suffering. Inherent in this definition is the possibility of delivering palliative care in partnership with curative care for children with life-limiting illness or for children who may not die. Many principles already reviewed in other sections of this book are universally applicable across the age spectrum of the dying, so this chapter provides an overview of issues specific to the care of the life-threatened child.

Each year in the United States, approximately 53,000 children die, compared with approximately 2.4 million adults. National Vital Statistics for 2007, published in 2010, demonstrate that accidents remain the number one cause of death in children aged 1 to 19 (1). The second leading cause of death for children for ages 1 to 4 is congenital malformations, deformations, and chromosomal abnormalities; ages 5 to 14 is malignancy; and for ages 15 to 19 is homicide. For infants, the leading causes of death are congenital malformations, deformations, and chromosomal abnormalities, disorders related to short gestation and low birth weight, sudden infant death syndrome, and newborns affected by maternal complications of pregnancy such as uterine rupture. Hundreds of thousands more children are living with life-threatening conditions. Goldman (2) estimated that 50/100,000 children were living with life-threatening illness. Feudtner et al. (3) have done extensive research characterizing the epidemiology of childhood death. They have defined a group of complex chronic conditions (CCCs) “that can be reasonably expected to last at least 12 months (unless death intervenes) and to involve either several different organ systems or one organ system severely enough to require specialty pediatric care and probably some period of hospitalization in a tertiary care center.” National data demonstrated that of 1.75 million deaths occurring in the 0 to 24-year-old population from 1979 to 1997, 5% were attributable to cancer CCCs, 16% to non-cancer CCCs, 43% to injuries, and 37% to all other death causes. Non-cancer CCCs accounted for approximately 25% of infant deaths, 20% of childhood deaths, and 7% of adolescent deaths. Death rates from CCCs are declining slowly due to advances in medical care for ill children. Feudtner estimates that each year approximately 15,000 infants, children, adolescents, and young adults might benefit from supportive care services delivered both at home and in the hospital, and that on any given day, approximately 5,000 are living in the last 6 months of their lives, many of whom die in hospitals after prolonged periods of inpatient care and artificial life-sustaining therapies (4,5). A recent retrospective observational study examined hospitalizations in the United States for children with CCCs and found that over time, the use of inpatient resources has increased (6). Additionally, Burns et al. (7) showed consistent increases in hospitalizations for children with CCCs from 1991 to 2005. Children at risk for chronic physical, developmental, behavioral, or emotional conditions account for about 18% of all children but represent 10% of pediatric hospital admissions and 70% of healthcare expenditures (8,9,10). The results of these studies suggest that more efforts should be focused on ongoing care of these children on both outpatient and inpatient bases. The diseases of childhood which might be appropriate for palliative care are many and include the following:

Conditions for which curative or life-prolonging treatment is possible but may fail, such as advanced or progressive malignancy or malignancy with a poor prognosis, or complex and severe congenital or acquired heart disease.
Conditions requiring long periods of intensive treatment aimed at prolonging quality of life such as human immunodeficiency virus, cystic fibrosis, severe gastrointestinal disorders, or malformations such as gastroschisis, severe epidermolysis bullosa, severe immunodeficiencies, renal failure when dialysis and/or transplantation are not available or indicated, chronic or severe respiratory failure, or muscular dystrophy.
Progressive conditions in which treatment is exclusively palliative from diagnosis such as mucopolysaccharidoses or other storage disorders, progressive metabolic disorders, certain chromosomal abnormalities such as Trisomy 13 or Trisomy 18, or severe forms of osteogenesis imperfecta.
Conditions with severe, non-progressive disability, causing extreme vulnerability to health complications such as severe cerebral palsy, extreme prematurity, severe neurologic impairments due to illness or injury, or severe brain malformations. Given the uncertainty of prognosis, many children with these conditions will not fit eligibility criteria for hospice care in the United States, which generally requires a life expectancy of 6 months or less (11).

SUFFERING

Suffering results from a threat to one’s physical and psychological self, from a threat to one’s relationships with others, and from a threat to one’s relationship with a transcendent
source of meaning (12). Suffering is a profoundly personal experience and is endurable, and at times even fulfilling, when it becomes meaningful (13). Despite best efforts, children living with chronic, life-threatening, and terminal illnesses experience substantial suffering. The extent, as well type, of suffering has broad-ranging implications in the child’s life as a whole and in the family as a functional unit. Understanding the illness experience of patient and families is essential. Parents who recognize that their children have a poor prognosis and believe that their children are suffering from the illness and its treatment are more likely to put greater value on comfort and quality of life as they make care decisions.

Serious illness threatens children’s sense of personal integrity and shatters all aspects of their lives. Physical pain and other symptoms cause fear, depression, and isolation. Illness affects their daily activities, sense of well-being, physical strength and agility, and the motives and quality of their relationships. Disease crushes their sense of security and brings fears of the unknown, rejection, and punishment. Children also become confused by the experience of a mixed variety of emotions of anger, anxiety, sadness, loneliness, and isolation in the presence of a threatening situation (14). Children are highly vulnerable to the stress inherent to the experience of severe illness. They have an egocentric view of the world and lack a fully developed repertoire of coping mechanisms, such as problem solving or decision making, which are influenced by age-dependent behavior and cognitive abilities.

Within the physical realm, the published experience speaks best to those with malignant diseases. Recent studies by Wolfe et al. (15) and Collins et al. (16,17) point to the wide variety and high prevalence of symptoms from which children with life-threatening illness suffer. There appears to be significant discrepancies between the reports of parents and physicians regarding the children’s symptoms in the last month of life, with parents reporting each symptom more than the physicians. Furthermore, currently available treatments may not be successful in easing suffering associated with these symptoms that can cause significant distress. For children with nonmalignant diseases, some of the more troublesome symptoms might include gastroesophageal reflux, neuroirritability, immobility, incontinence, seizures, muscle spasms, pressure ulcers, contractures, recurrent infections, increased secretions, restlessness, sleep disturbance, and edema. There are few valid and reliable tools available to assess these symptoms and little data to substantiate the use of many of the interventions currently prescribed.

Suffering, for the parents of a child with a life-threatening illness, can also be a multidimensional experience of pain, fear, failure, despair, powerlessness, hopelessness, purposelessness, and vulnerability. Parental anxiety is due in part to the changing parent-child structure, the need to understand the illness experience, become familiar with the hospital environment, adapt to the changing relationships with their child and other family members, and negotiate with professionals about their care (18,19). Parents must also deal not only with the immediate threat of disease on their child’s life but also with important additional family stressors during treatment such as lifestyle changes, marital tension, financial strain, loss of self-esteem, and even loss of sleep (20). Furthermore, when confronted with the suffering and possible death of their child, parents frequently recognize their own limitations and mortality. Their perception of life, death, and the world around them is changed dramatically by the reality of the loss of their child. In addition, parents must also satisfy the emotional needs of other children in the family which many times parallel those of the seriously ill child (21). Finally, children and their families may also suffer spiritually. This may be manifested as a sense of isolation and abandonment, a sense of hopelessness and uncertainty about the meaning and ultimate purpose of life.

The American Academy of Pediatrics supports an integrated model of palliative care in which the components of palliative care are offered at diagnosis and continued throughout the course of illness, whether the outcome ends in cure or death (22). Basic principles of pediatric palliative care include the following:

All children suffering from chronic, life-threatening, and terminal illnesses are eligible.
Care is patient and family centered and is based on continued healing relationships.
Care focuses on attending to suffering and enhancing quality of life for the child and family.
Care is provided for the child as a unique individual and the family as a functional unit.
Care is incorporated into the mainstream of medical care regardless of the curative intent of therapy.
Care is not directed at shortening life.
Care is coordinated and continuous throughout the illness trajectory and across all settings in which the child receives services.
Care is goal directed and consistent with the beliefs and values of the child and his or her caregivers.
Care is interdisciplinary and addresses all levels of the patient’s and family’s illness experience.
Advocacy for participation of the child and caregivers in decision making is paramount.
Facilitation and documentation of communication are critical tasks of the team.
Respite care and support are essential for families and caregivers.
Bereavement care should be provided for surviving family members including parents and siblings, for as long as needed.
Prognosis for short-term survival and a “Do Not Resuscitate” order are not required for eligibility.

These essentials do not mandate a particular structure for care delivery other than to suggest the function of an interdisciplinary team of health care and allied health care professionals to provide care coordination and to facilitate the delivery of services with the goal to attend suffering, promote healing, and improve quality of life.

INDIVIDUALIZED ADVANCED CARE PLANNING AND COORDINATION

Seriously ill patients and their families must often make difficult care decisions. Healthcare providers must empower them in this process through expert communication, information sharing, and support in the context of a therapeutic alliance. Care providers must communicate openly and honestly about the child’s condition and prognosis and help identify realistic goal-directed treatment options. In the presence of advancing illness parents often have an overwhelming desire to continue cure-directed interventions while emphasizing comfort and quality of life (23). Families often need assistance in balancing these dual goals of care and with implementing a care plan that reflects their personal beliefs and values within the framework provided by a complex healthcare system. Much of the fragmentation of services that occurs in modern healthcare systems results from the lack of a coordinating entity. The loss of continuity may be addressed by providing a medical home for these children along with the services of an advanced-illness care coordinator supported by a physician with palliative care experience. Pediatric practices that act as the medical home for children with chronic conditions and provide care coordination are associated with fewer hospitalizations and improved care quality (24). Care coordination may be facilitated by a registered nurse whose primary responsibilities are to enhance communication across settings, facilitate the participation of the patient and family in the decision-making process, ensure that healthcare providers adhere to the goals and principles of palliative care, and honor the patient and family’s wishes. The coordinator may advocate for change in the nature of the palliative care interventions according to the stage of disease and the patient and family’s expectations, hopes, values, and concerns. The coordinator may also be responsible for ensuring access to proper management of pain and other symptoms, as well as to optimize physical function, and facilitate psychosocial and spiritual support. In our experience, provision of a trained advanced illness care coordinator to facilitate end-of-life communication can help the medical team and family embrace the reality of imminent death, provide effective anticipatory guidance about what to expect as the illness progresses, increase utilization of and length of stay in end-of-life services, facilitate completion of advance directives, and honor the families’ preferences for the location of death. The roles provided by a physician advocate and the integration of services facilitated by the advanced care coordinator are essential for maintaining a patient and family centered, relationship-based approach and promotion of palliative care goals (25,26).

ETHICAL ISSUES

Although palliative care is becoming increasingly integrated in the care of children at the end of life, the process of caring for children at this stage is not always without conflict. Conflict may occur between family members, between staff, or between family members and staff when disagreements arise over the goals of care and on what treatments or limitations of treatment are in the best interests of the child. Conflicts may be highly emotional and may result in moral distress. Clinical ethics consultation may be helpful when agreements cannot be achieved on the goals of care. In difficult cases, institutional ethics committees can help resolve conflicts about treatment decisions, provide a forum for discussion of hospital policies, and educate the healthcare community about ethical concepts (27).

Decision-making capacity (DMC) includes the ability to understand and appreciate the risks, benefits, and outcomes of a medical decision as well as understanding the consequences of alternative decisions. Children are considered to have an evolving sense of DMC and thus parents or guardians are considered the best surrogate decision makers to make decisions on behalf of the child (28). As they mature, children form opinions about their health care, particularly children with a significant illness history, and these opinions should be included and valued in the discussion. Whenever possible, caregivers must make an effort to invite children to participate in medical decision making and honor their end-of-life care wishes. This is particularly important for any child, regardless of age, who can understand his or her medical condition, who can communicate his or her preferences, and who is able to reach a reasonable decision and can understand its consequences (28). Children ≥ age 14 should provide assent whenever possible (29,30).

Clinicians assisting families with treatment decisions in palliative care have valuable expertise with these decisions and can provide recommendations among therapies to families, while making it clear that families who select an alternative therapy will not be abandoned. Decision making should be shared and driven by communication between child, parent, and physician (31). Understanding the illness experience from the perspective of the child and family, establishing accurate prognosis and communicating it effectively, setting reasonable goals and establishing a comprehensive advancedillness care plan are indispensable steps in this process.

Foregoing life-sustaining medical therapies through withholding or withdrawal of artificial life-sustaining interventions is often ethically permissible, but this is a possible source of conflict within a family or with medical staff. Family care conferences and interdisciplinary team meetings to facilitate communication and clarify goals of care are often helpful at resolving conflicts. The ability to provide an intervention (such as artificial nutrition and hydration) is not an obligation to provide that intervention, particularly if the burdens of the therapy are greater than the benefits to the patient and family (32,33). When the risk-benefit ratio of an intervention is unclear, shared decision making may result in a time-limited trial to assess if the intervention is beneficial and compatible with the goals of care. Although some find one morally more distressing than the other, the withholding and withdrawing of an intervention are ethically equivalent and therefore it is permissible to withdraw medical therapies not felt to be compatible with the goals of care, even
if withdrawal leads to the patient’s natural death (such as removal of a ventilator) (33). In making these difficult decisions the right to self-determination, or autonomy, allows individuals and families to make risk-benefit determinations specific to their personal experiences and value systems. The discontinuation of non-beneficial interventions is within the scope of parental decision-making authority and should not be viewed as inconsistent with a child’s best interests. Clinicians should seek to override family wishes only when those wishes clearly conflict with the best interests of a child. Clinical ethics consultation is always advisable in these cases.

Imminently dying children should not be allowed to experience suffering at the end of life. Clinicians have a fiduciary responsibility to their patients and should control symptoms with appropriate medical interventions. The principles that guide the rule of double effect and sedation of highly symptomatic patients with pain or dyspnea in adults also apply in the care of children (34). The goal of therapy is to relieve distressing symptoms and not to hasten death. Consultation with palliative care and pain teams can aid clinicians with symptom management at the end of life and is recommended.

Unfortunately, a small number of children will experience intractable physical suffering that is refractory to traditional medical interventions. Parents of seriously ill children may be willing to try a variety of approaches, some of which may be potentially harmful, hoping for benefit in a desperate situation, particularly when the condition imposes a heavy burden for which mainstream therapies are insufficient (35). Of note, although some alternative medicine practices in the care of seriously ill children may be justified, there are no published guidelines for the use of these practices in children (36). In these rare circumstances, palliative sedation therapy (PST) with medications achieving continuous deep sedation (CDS) can be ethically permissible and numerous case series have demonstrated efficacy in patients for refractory suffering. Propofol is an example of one such medication and has been demonstrated to reduce pain and suffering in pediatric patients (37,38,39). The indications for PST at the end of life include two core components: the presence of severe suffering refractory to standard palliative management and the primary aim of relief of distress (40). We recommend that traditional therapies be maximized under a time-limited trial and ethics consultation be obtained prior to the initiation of PST in pediatric patients. Used appropriately, PST does not hasten death (41). The use of sedation for existential (emotional) suffering is discouraged (42). Figure 63.1 provides guidelines for clinicians considering PST in an imminently dying patient (Fig. 63.1).

SYMPTOM CONTROL

Pain Assessment and Management

Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (43). Several outstanding and more comprehensive resources are available for pain management in children (44,45,46,47,48,49). Pain is subjective in nature. The experience of pain can be modulated by environmental, developmental, behavioral, psychological, familial, and cultural factors. Unrelieved pain for the child can produce fear, mistrust, irritability, impaired coping, and posttraumatic stress symptoms. Parents feel guilt and anger when pain is undertreated and may even lead them to consider euthanasia as a treatment alternative (50). Many children have pain at some time during their course with life-threatening illness; it can be disease related, treatment related, and/or related to psychological distress. Incidental, or traumatic, pain can still occur in a life-threatened child as well.

Pain assessment must be age-appropriate and requires a careful history and physical examination, determination of the primary cause(s) of pain, and evaluation of secondary causes and modulating features. Pain complaints should always be taken seriously; severe pain for a child is a medical emergency. Elements of the pain assessment should include the quality of the pain, region and radiation, severity, temporal factors, and provocative and palliative factors. Additional historical elements include disease stage and context, fear of pain, ability to take medication, prior analgesic use, potential role of diseasespecific treatment, reactions of parents and family context, and other nonpain symptoms, including depression and/or anxiety, sleep disturbance, and most important, interference with activities of daily life, including play. Methods of pain assessment must be appropriate to the child’s age, situation, emotional resources, developmental level and context, and wishes of the child and family. Ideally, pain assessment, being subjective, should be by self-report in verbal children able to communicate. For children >7 years of age, visual analog or verbal response scales that rate the pain on a horizontal or numeric scale are appropriate. For children aged 3 to 7, several validated, self-report tools are available, including Faces Scale, Oucher, poker chip tool, body maps, and pain thermometers, but more research is needed in this population of young children. The Bieri modification of the Faces Scale has improved morphometrics and score distribution (51,52,53,54,55,56,57).

For infants, toddlers, and preverbal children, several observation assessment scales exist, including the r-FLACC, NCCPC-PV, and the Pediatric Pain Profile Tools for the numeric assessment of pain in the cognitively impaired child have also been described (58,59,60,61). In general, pain management for children should follow the World Health Organization analgesic ladder (62). Table 63.1 lists some of the more commonly used and available medications for mild, moderate, and severe pain. Particularly for children who cannot swallow pills, the long half-life, low cost, and availability in concentrated liquid formulation make methadone a good choice for long-term analgesia and for preventing opioid withdrawal symptoms (63,64). A short initial and long terminal half-life requires judicious titration to prevent oversedation. Given the toxic metabolite accumulation and the availability of several alternatives, meperidine cannot be recommended and is excluded from the table. Medications for pain should be administered according to a regular schedule. Rescue doses should be provided for intermittent or more severe breakthrough pain. Effective management of procedural pain is as critical as expert anticipation,
prevention, and treatment of medication side effects (65,66). Depending on the etiology of the pain being treated, there are many nonopiate adjunct therapies available. Table 63.2 lists some of the more commonly used medications and their indications. For children, in particular, choose the simplest, most effective, least painful route which for most will be oral or sublingual or for those with central venous access, parenteral. Intramuscular injections should be avoided if possible. Rectal administration is possible, and many medications, including nonopiates and opiates as well as medication for nonpain symptoms, can be absorbed rectally. Subcutaneous infusion, popular in adult hospice and palliative medicine, is possible in children but may be inadvisable for needlephobic children. Transdermal and inhalational routes may also be used in children, but little pharmacokinetic data are available regarding their use; anecdotally, absorption and/or metabolism of transdermal fentanyl may be faster in children, requiring patch changes every 2 days if breakthrough pain occurs. Promotion of good psychosocial and spiritual care must be partnered with appropriate pharmacology (67). Children should be given choices as often as possible. Behavioral methods, such as deep breathing (blowing bubbles), progressive relaxation, and biofeedback, have a role in pain management for children. Physical methods, such as
touch therapies, including massage, transcutaneous electrical nerve stimulation, physical therapy, heat/cold, and acupuncture and/or acupressure, for example, are helpful adjuncts. Cognitive modalities, including distraction, music, art, play, imagery, and hypnosis, are also effective in children. Studies have demonstrated efficacy of many of these modalities alone or in combination with pharmacologic therapies (68,69).

Figure 63.1. Algorithm for possible initiation of palliative sedation therapy (PST) with continuous deep sedation (CDS).

1. Consider ethics consultation if staff cannot agree with prognosis, intolerable suffering, or goals of care and this is causing staff or patient distress.

2. CDS is a rarely utilized intervention. Opportunity for controversy exists if its purpose is misunderstood or if used inappropriately. For this reason we strongly recommend ethics consultation in pediatric patients prior to initiation of PST with CDS.

TABLE 63.1 Opioid and nonopioid analgesics

Drug	Initial Dose (mg/kg/dose)	Route	Interval	Maximum Dose	Formulation
Acetaminophen	10-15	p.o./p.r.	q4h	1 g/dose; 4 g/d	T, CT, L, D, S
Ibuprofen	5-10	p.o.	q6h	2.4 g/d; 3.4 g/d (adults)	T, CT, L, D
Choline magnesium trisalicylate	7.5-20	p.o.	b.i.d.-t.i.d.	1.5 g/dose	T, L
Naproxen	5-7	p.o.	q8-12h	1 g/d	T, L
Ketorolac	0.5	p.o., i.v., i.m.	q6h	30 mg/dose i.v., 10 mg/dose p.o.	I, T
Codeine	0.5-1	p.o., s.q., i.m.	q3-4h	60 mg/dose	T, L, I
Tramadol	1-2	p.o.	q6h	100 mg/dose, 400 mg/d	T
Morphine	0.2-0.5	p.o., s.l., p.r.	q3-4h	Titrate	T, L, D, S
	0.1	i.v., s.q., i.m.	q2-4h	Titrate	I
	0.3-0.6 (long-acting)	p.o.	q8-12h	Titrate	SRT
Hydromorphone	0.03-0.08	p.o., p.r.	q3-4h	Titrate	T, L, S
	0.015	i.v., s.q., i.m.	q2-4h	Titrate	I
Methadone	0.2	p.o.	q8-12h	Titrate	T, L
	0.1	i.v., s.q., i.m.	q8-12h	Titrate	I
Fentanyl	0.5-1 µg/kg/h	Transdermal	q48-72h	Titrate	P
	5-15 µg/kg (sedative)	t.m.	q4-6h	Titrate	LO
	1-2 µg/kg	i.v., s.q.	q1-2h	Titrate	I
Oxycodone	0.05-0.15	p.o.	q6h	Titrate	T, L
	0.1-0.3 (long-acting)	p.o.	q12h	Titrate	SRT
CT, chewable tablet; D, drops; I, injection; L, liquid; LO, lozenge; P, patch; S, suppository; SRT, sustained-release tablet; T, tablet or capsule.

These therapies should be approached from a familycentered perspective; parents can easily be taught many of these techniques. Providing effective tools for parental involvement in symptom management should increase feelings of control in an often uncontrollable situation.

Respiratory Symptoms

Dyspnea is a term used to describe a feeling of breathlessness. It is a distressing symptom for children and families; it can be a major detriment to comfort and quality of life in advanced disease. In many cases, it is also associated with shorter survival. Possible causes include tumor metastases, pneumonia, effusions, or neuromuscular problems that impair breathing. Measurement of dyspnea is difficult as it is subjective and does not correlate well with respiratory rate, work of breathing, or oxygen level. The Dalhousie Dyspnea Scales have been validated for use in children aged 6 to 18 years (70). In older children, the modified Borg scale or 15-count breathlessness score may be useful (71). Care of patients with dyspnea typically involves treatment of the underlying cause, if possible, oxygen, oral and/or parenteral opiates, and/or benzodiazepines (72). Nebulized morphine does not appear to be superior to other routes of administration in the treatment of dyspnea (73). Some patients may benefit from using a fan with cold air blowing on the face, pulmonary rehabilitation, and chest physiotherapy to mobilize secretions (74,75,76). Interestingly, the use of supplemental oxygen has not been found to be more beneficial than air inhalation in adults

with end-stage dyspnea (77). There are no studies to support the use of supplemental oxygen in children at the end of life although practical experience suggests that this treatment may have additional psychological benefits for the parents of the sick child.

TABLE 63.2 Adjuvant drugs useful in pediatric pain management

Drug	Initial Dose (mg/kg/dose)	Route	Interval	Maximum Dose	Formulation	Indication
Amitriptyline	0.1	p.o.	q.h.s.	2 mg/kg/d	T, I	Neuropathic pain, depression, sleep disturbance
Nortriptyline	0.2-0.5	p.o.	q.h.s.	3 mg/kg/d	T, L	Neuropathic pain, depression, sleep disturbance
Paroxetine	10 mg/dose	p.o.	q.a.m.	60 mg/d	T, L, SRT	Neuropathic pain, depression
Fluoxetine	0.2	p.o.	q.a.m.	80 mg/d	T, L, SRT, 90 mg/q/wk	Neuropathic pain, depression
Carbamazepine	2.5-5	p.o., p.r.	b.i.d.-q.i.d.	2400 mg/d	T, L, SRT, CT	Neuropathic pain
Valproic acid	5	p.o.	q.d.-t.i.d.	60 mg/kg/d	T, L, SRT	Neuropathic pain
	5	i.v.	q6-8h		I
	10-15	p.r.	q8h		L
Clonazepam	0.003-0.01	p.o.	t.i.d.-q.i.d.	0.2 mg/kg/d	T	Neuropathic pain
Gabapentin	5	p.o.	b.i.d.-t.i.d.	2400 mg/d	T, L	Neuropathic pain
Methylphenidate	0.1	p.o.	q4h-q24	60 mg/d	T, SRT	Coanalgesia, decreased sedation with opiates
Dextroamphetamine	0.1	p.o.	q4h-q24	40 mg/d	T, SRT	Coanalgesia, decreased sedation with opiates
Diazepam	0.1-0.2	i.v., i.m.	q2-4h	10 mg/dose	T, L, I	Anxiety, muscle spasm
	0.2-0.3	p.o.	q4-6h	10 mg/dose	T, L
	0.3-0.5	p.r.	q2-4h	20 mg/dose	I, S
Midazolam	0.05-0.1	i.v., s.q., i.m.	q2-4h	2.5 mg/dose	I	Anxiety, muscle spasm
	0.2-0.3	Intranasal			I
	0.25-0.5	p.o.			L
Lorazepam	0.05	p.o., s.l., p.r., i.v., i.m.	q4-6h	2 mg/dose	T, L, I	Anxiety, muscle spasm
Dexamethasone	Varies by indication	p.o., i.v., i.m., s.q.	q6-12h	10 mg/dose	T, L, I	Bone pain, increased intracranial pressure
CT, chewable tablet; I, injection; L, liquid; S, suppository; SRT, sustained release tablet or capsule; T, tablet or capsule.