Pediatric Palliative Care and Neurologic Conditions

Pediatric palliative care teams are commonly consulted to see children who have diseases and impairments of the nervous system. Of children enrolled in a pediatric palliative care project, 44% were categorized with a primary neurologic condition (24% of those were deemed progressive neurologic, 20% were CNS damage) and 15% frequently have associated neurologic impairment (10% with congenital anomalies and 5% with metabolic).¹ Recent data for the Pediatric Advanced Care Team (PACT) at Children’s Hospital Boston and Dana Farber Cancer Institute categorized 37% neurologic and 10% genetic or metabolic.² Unfortunately, little has been written about palliative care as it pertains to children with neurologic impairment (NI) and their families.

Families of such children face many challenges, including: lifelong conditions, living with hope and uncertainty, experiencing the sorrow of what is not possible along with the joy of small victories, difficulty in assessing and managing symptoms, and navigating through the care of many specialists. Palliative care teams are well suited to address the myriad psychosocial, spiritual, and physical needs experienced by these children and their families.

The personal challenges experienced by children and their families exist within the larger context of societal debates regarding medical decision making for such children. These discussions are guided and influenced by ethics, morality, religion, personal values, justice, resource usage, and quality of life. Case reports in the literature highlight the variability of this debate with examples of doing everything, possibly so as to not create the impression of discrimination based on disability³ and not offering treatment out of an assumption of poor quality of life.⁴ As society wrestles with these challenges, we must avoid bringing this debate to the bedside and instead be guided by legal and ethical knowledge while providing compassion and support.

Patient Population

There are a broad range of conditions with NI that benefit from pediatric palliative care.⁵ The conditions may be:

Conditions and suggested timing of palliative care consultation are summarized in Table 39-2; assistance with symptom management can occur at any point in time.

TABLE 39-2 Neurologic Conditions and Timing of Palliative Care Consults

Unique experiences and challenges

There are a number of unique themes experienced by children with NI and their families, including the lifelong nature of such conditions, limitations in acquiring independence, bereavement that includes loss of the intensive care provider role, lack of evidence for medical decision making, and challenges with symptom management. Support from interdisciplinary teams includes anticipating and exploring how each area affects an individual child and family. This section focuses on the themes that cross psychosocial and spiritual areas of need.

Loss is a recurrent theme, starting from the time of diagnosis. This theme is often repeated when what the child cannot do and the ongoing problems that cannot be fixed are reviewed at medical appointments. This journey often includes chronic sorrow, a phrase used to describe sorrow over time in response to ongoing loss.⁶ Examples may include loss of functional ability, loss of ability to meet nutritional and fluid needs through eating, and loss of health. Families are also simultaneously exploring meaning and hope in the context of their values, beliefs, relationships, and supportive networks. They may find joy in little victories, outcomes that were not expected, as they navigate hope, meaning, loss, and uncertainty.

Loss of function often includes lifelong dependence on others for physical care and may include the same for decision making. Parents may have unspoken worries, such as what will happen if the child outlives his or her parents, and wonder how to factor this future worry into current decisions. As a child ages, questions of who will provide care, the location of this care, and who will make decisions for the child become relevant. Parents may worry about this child being a burden to another sibling while worrying about the quality of care at other facilities. For children living in facilities, such as medical foster homes, group homes, and long-term medical care facilities, another challenge is created when the legal decision maker is removed from the range of daily experiences, including suffering of the child. This can create conflicts when the child’s care provider, with a set of values, beliefs, and direct experience with the child, may judge a decision differently than the recognized decision maker. Other conflicting interests that often go unrecognized include financial interests of care facilities and personal interests of care providers, even when the best care for the child is the goal.

The care needs of children with NI often dominates a parents’ day, which may lead to limited emotional, spiritual, and physical reserves. This often leaves little energy to reflect and may result in decisions that are made during a time of crisis. The intensity of the care provider’s role can naturally result in this role becoming a prominent part of a parents’ identity. This may later impact bereavement when a parent experiences the loss of this role and loss of membership in parent support groups. In addition, being a long-term care provider can create a heightened sense of responsibility over outcome and loss of perspective over the intensive efforts being used to maintain the child’s level of health.

In the context of these challenges are the themes of hope and joy. It is not uncommon to identify a family saying, “I wouldn’t choose this, but I wouldn’t have it any other way” as they share the lessons learned through their child and the important role of this child in their family. Such families often experience simultaneous joy and sorrow that allows us to worry and celebrate with them as we join them and assist them on their journey.

Pediatric palliative care teams provide expertise through knowledge of themes that are universal to all children with life-threatening conditions, along with experience of themes that are unique to certain populations. This expertise allows teams to explore supportive approaches to healing and hope, meaning and values, relationships and connections, and grief and loss. Resiliency is an essential component of this process when a child and family live with a condition that is both lifelong, often experienced over years, and will result in an early death.

What to Expect: Life Expectancy Literature

Life expectancy data for children with NI, whether that data is related to the disability label, such as cerebral palsy, or related to a specific diagnosis that explains the disability, such as a genetic disorder, congenital syndrome, or metabolic disorder, provides a context but is of limited use for individual prognosis. Health problems that are life threatening can be divided into those related to the severity of the motor disability regardless of the cause, such as oral motor dysfunction and recurrent pulmonary aspiration, or related to the specific diagnosis that explains the disability, such as a genetic disorder with an associated cardiac defect or central apnea.

Information about life expectancy demonstrates a wide variation. The more severe the motor disability, such as the inability to lift the head up when prone, the more likely the child will not survive to adulthood.^7–12 Survival for individuals with CP that includes severe impairment in cognitive function, motor ability, vision and hearing was 50% at 13 years and 25% at 30 years.⁹ It is beneficial to understand that CP is not a diagnosis but a developmental label indicating impairment of motor control as a result of non-progressive impairment of the central nervous system acquired at an early age. Information and experience from CP is relevant to any disease that results in severe motor impairment.

Even progressive diseases where decline occurs early in life, such as Tay-Sachs disease, often have a range of survival that may vary by several years. Prognostic information for specific diagnoses often lags the expanded survival from routine pulmonary management that assists with mobilization of secretions and treatment of acute respiratory illnesses. Worry over prognosis is further heightened when there is identification of neurologic impairment with no diagnosis. As palliative care clinicians we can assist through knowledge of the limitations of information that may be provided to families, use our knowledge and experience from all disorders with NI, and help anticipate and prepare for future events.

Framework for Approaching Prognosis, Uncertainty, and Decision Making

Literature and experience demonstrates a wide range in life expectancy, yet has provided limited information on how families approach this uncertainty. Studies^13,14 of the experience of families with children dying from neurodegenerative conditions identify how they navigate uncharted territory and use strategies such as seeking and sharing information, focusing on the child, reframing the experience, and promoting the child’s health. Factors influencing parental decisions to limit or discontinue medical interventions include perception of their child’s suffering, likelihood of improvement, perception of their child’s will to survive, quality of life, previous experience with end-of-life decision making for others, and financial resources.^15,16

Illness trajectory as a guide to decision making

Adult literature describes illness trajectories for cancer, organ failure, and frailty.^17,18 Using the latter two trajectories and experience, Fig. 39-1 provides a hypothetical framework for reflecting on and anticipating the trajectory of a child with NI. The figure is intended to guide families through decision making by using a reflection on the past benefit of interventions to anticipating the probable and possible future benefit by hoping for the best, preparing for the worst.¹⁹

Fig. 39-1 Prognosis and uncertainty—hope for the best, prepare for the rest.

The hypothetical disease trajectory highlights that many health issues in children with NI progress gradually with initial benefit and return to health and functional baseline with treatment available. Over time, less return to baseline will occur from the interventions available, reflecting the inability to fix the problems that are secondary to the permanent NI. Predicting outcome at the beginning of the trajectory before any decline in health status is seen can result in pressure of past success²⁰ when the outcome is better than predicted. Asking a parent of a child with NI to make a decision to limit interventions before the child has had any significant decline in health may feel as if the emphasis is on limiting interventions because of the disability. By identifying associated health problems, monitoring for changes in health status, and noting any decreased benefit from treatments, we can identify individuals with NI who are at risk for life-threatening events.

Anticipating benefit also requires knowledge of how offered interventions will alter the clinical course. Some of the more common interventions for children with severe NI include anti-reflux surgery, tracheotomy, and spinal surgery. Most of the information in the literature is case reports or small series without rigorous evidence to indicate which patient is likely to experience benefit, morbidity greater than the intended benefit, or no alteration in the clinical course. In addition, these interventions are often approached as needed and required for the problems identified, rather than interventions to offer and consider. Fortunately, relevant information can be gained from the literature; a summary of information for these interventions is provided later in this chapter.

Support for the process of decision making is best done through a reflection of the child’s history in the context of emotional and spiritual needs that impact this process. Outlined are questions to consider and review with parents and care providers. It is helpful to acknowledge that some may be difficult to answer but help frame what parents are often already worrying about and considering. Such discussions should include opportunities to reflect on the successes and experiences that are enjoyed by the child. In addition, a comprehensive review of emotional coping, sources of stress, spiritual beliefs, and support networks, as examples, should be sought.

Starting the conversation:

• Please share with us what the past few months or years have been like and what you understand about your child’s health status.

• What are you worrying about?

• What are you anticipating?

• What are your hopes for your child?

• What do you consider most important for your child as your consider decisions?

Reflective questions with parents and care providers:

• How does a typical day for your child look now compared to the start of these problems and/or symptoms?

• When did you first start worrying about these problems and/or symptoms?

• How does your child’s health compare this month to the start of these problems?

• Where would you estimate your child’s health baseline to be now compared with 2 years ago?

• Is your child’s health baseline 75%, 50%, or less than 50% of where it was? Has your child’s health declined by 25%, 50%, or more than 50%?

• How often in a month is your child sick now compared to 12 months ago? Has illness been increasing in frequency?

• What percentage of time in a typical week would you estimate that your child enjoys now compared to 12 months ago? Has this declined over time?

• Are you seeing less benefit from chronic and acute treatments over time with less return to prior baseline, longer duration with each illness, or a shorter time between each illness?

• How much reserve do you estimate for your child?

• Do you worry that your child is suffering?

• What percentage of each day or week is there suffering?

Here are some further questions for families and medical teams after goals have been identified and the child’s health trajectory has been reviewed:

• What is the likelihood of the identified interventions bringing an improvement or recovery of the current health and functional baseline? To meeting the goals identified such as improving comfort and quality of life? To prolonging the suffering identified?

• How will the course look with or without the treatment available?

• Are there treatment strategies for the symptoms that are causing distress?

Documenting, Communicating, and Coordinating Plans of Care

Great care is possible only when information is identified, documented, and communicated to those involved in the child’s care. This can ensure that previously defined care plans are carried out, which protects the child from interventions that are anticipated to cause potential harm without long-term benefit. It can be beneficial to others to summarize why certain interventions have been limited. This can lessen a sense of giving up and help direct those involved with the child to what we can do; that there is always care to provide.

Information to consider documenting includes: goals of care and how these goals guide decisions, heathcare and symptom management plans that meet these goals, naming the legal decision maker, the location for acute illness, resuscitation status, care plans for home and school in the event of a life-threatening event, and contact information for individuals with expertise and availability to assist at times of acute events. Those who should receive this information include the family, healthcare proxy or legal decision maker, home care nurses, providers of care in foster care or group homes, school nurses and teachers, respite care providers, bus drivers, healthcare team members, and palliative care and/or hospice teams.

Symptom Management

Children with NI experience pain more frequently than the general pediatric population.^26–29 Caregivers of children with severe cognitive impairment reported 44% experiencing pain each week over a 4-week interval. Pain frequency was higher in the most impaired group of children.²⁷ In a study of nonverbal cognitively impaired children, caregivers reported that 62% experienced five or more separate days of pain and 24% experienced pain almost daily.²⁹ In addition, children with severe-to-profound cognitive impairment were found to have elevated pain scores at baseline on two pain assessment scales.³⁰

Other distressing symptoms commonly encountered in children with NI include: ^31–33

In addition, depression and anxiety may be experienced at an increased rate by children with a muscular dystrophy (MD) such as Duchenne MD.³⁴ Unfortunately, few studies have explored symptom management in children with NI both during life and at the end of life.

General approach

This section will outline management of distressing symptoms for children with NI (Fig. 39-2). This allows the healthcare provider to consider interventions that may benefit several problems. This can be helpful because it is not always possible to determine which symptoms or problems are the primary source of distress and which ones are the secondary manifestations in these children. Is the nonverbal neurologically impaired child irritable and in distress because of spasticity or is the spasticity secondary to underlying pain? Are the signs and symptoms of dysautonomia caused by pain, mimic the appearance of pain, or do the associated problems of dysautonomia contribute to pain? Given these challenges, it is helpful to focus on all potential sources of distressing symptoms, including neuropathy. The focus of this section will be on nonverbal children with NI given the inherent challenge with this group.

Fig. 39-2 Multidimensional symptom assessment and management.

(These symptoms are sources of agitation, distress, and irritability in neurologically impaired children.)

There is regional and international variation in medication selection for the variety of problems and distressing symptoms encountered. Medications provided in the tables indicate mechanisms of action so that medications with similar properties available in different countries can be identified.

Nonpharmacologic management

A critical part of symptom management in children with NI is nonpharmacologic pain management. Parents often become very adept at identifying and sharing tricks through parental support groups. One key area is assistance with identifying supportive equipment that minimizes positional pain. This can include seating systems and supportive pillows. Use of a pool is often found to be very relaxing for such children. Cuddling and physical therapy are commonly used. Although massage has not been studied in this population, many families report significant benefit for their child. Other modalities for consideration include aromatherapy and acupuncture.

Spasticity

Spasticity is an involuntary, velocity-dependent, increase to muscle tone that results in resistance to movement. Spinal and cortical injury can alter inhibitory and excitatory messages to the motor neuron, resulting in spasticity. Spasticity may be mistaken for seizure activity but is typically not as rhythmic or symmetrical. Factors that can exacerbate spasticity include acute illness, discomfort such as from constipation, and pain. For this reason, neuropathy may be a poorly recognized contributing factor to spasticity in children with NI.

Treatment is intended to reduce the excessive muscle tone, with the goal of improving a patient’s functional capacity and comfort. Various therapeutic interventions are available, including physical therapy, medications, and surgery. There are few randomized controlled trials of oral drugs, especially in children. There is weak evidence demonstrating the efficacy of medications such as benzodiazepines, baclofen, dantrolene, and α2-adrenergic agonists of clonidine and tizanidine.^64,65 There have been only two trials comparing drugs, tizanidine vs. diazepam and tizanidine vs. baclofen, with no significant differences noted between medications in either trial.^66,67 Adverse drug reactions are common, and highest with dantrolene (64% to 91%).⁶⁴ Side effects commonly seen with all medications include sedation, drowsiness, and muscle weakness. Side effects tend to be dose related and disappear when doses are reduced. In patients with multiple sclerosis, evidence identifies benefits of treating spasticity with gabapentin without experiencing sedation.⁶⁸ This may indicate benefit to children with demyelinating or other neurodegenerative conditions but warrants further study.

Typically, children with NI referred to palliative care are commonly on one of these medications or have an intrathecal baclofen pump. The role of palliative care clinicians can be to search for factors that can exacerbate spasticity, such as pain, and offer therapeutic symptom management trials, rather than increasing or adding other interventions for spasticity.

Autonomic Dysfunction

Autonomic dysfunction, also called dysautonomia, is common in children with NI. Other terms used include autonomic storm, sympathetic storm, paroxysmal sympathetic hyperactivity, and paroxysmal autonomic instability with dystonia. In children with NI, dysautonomia typically reflects hypothalamic impairment. Autonomic dysreflexia is used most commonly to describe autonomic dysfunction seen in patients with spinal cord injury above the splanchnic sympathetic outflow, which is at or above T6, though T6-T10 may be susceptible.

The autonomic nervous system regulates body temperature, respiratory rate, heart rate, blood pressure, intestinal motility, urination, salivation, perspiration, and pupillary size. Symptoms that are more commonly seen in children with NI and associated dysautonomia include: tachycardia or bradycardia; hypertension; hyperthermia, or hypothermia; skin changes including pallor, flushing and redness of the face, and/or body; vomiting, retching, bowel dysmotility, and constipation; urinary retention; abnormal sweating; increased salivation; posturing; and agitation.

As with other symptoms, evaluation should include a search for factors that may exacerbate the features of dysautonomia, including a review of potential sources of pain. Treatment for dysautonomia in neurologically impaired children has been poorly studied. Treatment options include benzodiazepines, bromocriptine, clonidine, oral and intrathecal baclofen, beta agonists such as metoprolol, and morphine sulfate. Literature is limited to case reports, predominantly in patients with traumatic brain injury. In a review of case reports of hypothalamic dysfunction, cyproheptadine was identified to benefit 4 individuals, including minimizing or eliminating symptoms of temperature instability, diaphoresis, vomiting, and abdominal pain.⁶⁹ Other interventions used in patients in this review without benefit included antiepileptics, haloperidol, diazepam, and clonidine. A recent case series of 6 patients following traumatic brain injury identified improvement with gabapentin when symptoms of agitation, dysautonomia, and spasticity persisted despite treatment with bromocriptine, clonidine, ITB pump, metoprolol, morphine, and benzodiazepine.⁷⁰ Finally, 13 out of 15 individuals with familial dysautonomia experienced a decrease in symptoms of nausea, retching, tachycardia, and flushing on pregabalin.⁷¹ Most patients were already using clonidine and a benzodiazepine. In children with NI, a therapeutic trial for pain should be considered because it is difficult to determine when features of dysautonomia are indicating underlying pain. In addition to scheduled medications, children with intermittent autonomic storms, often manifested by an acute onset of facial flushing, sweating, tachycardia, retching, agitation, and stiffening, may benefit from use of clonidine, diazepam, and morphine sulfate as needed during these episodes.

Medication Toxicities

Although uncommon, the features of serotonin syndrome and neuroleptic malignant syndrome include autonomic dysfunction and can be a result of medications used in this population. Awareness and monitoring for changes from a child’s baseline can alert us to these possible drug effects. Features of serotonin syndrome include tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, increased bowel sounds, hyperreflexia, clonus, agitation, and rigidity.⁷² Drugs commonly implicated include selective serotonin reuptake inhibitors (SSRIs). Other drugs reported, often when used in combination, include: trazadone, fentanyl, tramadol, risperidone, ondansetron, metoclopramide, and valproate. Management includes removal of causative medications, use of cyproheptadine as a 5HT2 antagonist, and supportive care for other associated problems. Features of neuroleptic malignant syndrome are similar and include muscle rigidity, autonomic dysfunction, and altered mental status, most commonly caused by dopamine antagonists such as haloperidol. It has also been associated with tricyclic antidepressants and some anticonvulsants.⁷³

Agitation and Delirium

Agitation is considered an unpleasant state of arousal. It may present as loud speech, crying, increased motor activity, increased autonomic arousal of diaphoresis or increased heart rate, inability to relax, or disturbed sleep-rest pattern. Symptoms in agitation overlap with anxiety though are noted to have more motor rather than psychological manifestations. In contrast, delirium is a disturbance of consciousness with an acute onset over hours to days. Associated features include fluctuating course, disordered thinking, a change in cognition, inattention, altered sleep-wake cycle, perceptual disturbances, and psychomotor disturbances.^74,75 Causes include opioid or anticholinergic medications; metabolic disturbances of infection, dehydration, renal, liver, or electrolyte; pain; and impairment of vision or hearing.

Management of agitation and delirium involves evaluating for treatable medical causes, including medications, metabolic disturbances, and sources of discomfort such as pain, dyspnea, muscle spasms, position, and constipation. It is also helpful to consider conditions that mimic the appearance of agitation, such as akathisia from antidopaminergic medications, myoclonus, withdrawal from opioids, and paradoxical reactions. Medications that can help manage the symptoms include benzodiazepines and neuroleptics.

Seizures

Seizures are frequently identified in children with NI. Such children are typically followed by a pediatric neurologist. Palliative care physicians can assist them through knowledge of side effects with medications and the ketogenic diet such as risk of renal stones. Other events may masquerade as a seizure such as myoclonus, which is a brief, involuntary twitching of a muscle or a group of muscles, and episodes of arching or posturing. We can also assist by working with the child’s neurologist to determine a plan for breakthrough seizures using rescue medications. This may include diazepam rectal gel, Diastat, or midazolam, which can be given sublingual and intranasal. There is increasing evidence that midazolam may be more effective than diazepam.^76–78 Finally, we can assist parents if they are experiencing changes in their child’s health status occurring in conjunction with refractory epilepsy.

Abnormal Movements: Dystonia and Posturing

Dystonia is a movement disorder that causes the muscles to contract and spasm involuntarily resulting in twisting, repetitive movements and abnormal postures. Dystonia may be a primary disorder of movement, it may be secondary to diseases and insults that injure the central nervous system, or it may be a result of medications such as neuroleptics. Interventions include physical therapy, medications, and botulinum toxin for focal muscle groups. There have been few studies evaluating the effectiveness of medications for secondary dystonia. Those considered include benzodiazepines, baclofen, dopaminergic agents such as bromocriptine and levodopa (Sinemet), and anticholinergics such as trihexyphenidyl (Artane). Palliative care physicians can assist by assessing for distressing symptoms such as pain that can worsen the movement disorder.

Posturing is a term used to describe both findings of abnormal position, such as arching of the back, and clinical exam findings, such as decorticate, decerebrate, and opisthotonos. Lack of nomenclature, assessment tools, and the variability of neurologic impairment results in a variation of assessment, should the movement be labeled dystonia, posturing, or autonomic storm, and approaches to management, as evident by the large number of medications for consideration. Again, palliative care teams can assist by bringing a comprehensive approach to assessment including a thorough consideration of neuropathy as a source of symptoms.

In addition, clinical findings of posturing can be informative as pre-terminal signs of progressive injury to the central nervous system in children with neurodegenerative conditions, indicating loss of inhibitory control. These findings can include: decorticate posturing as indicated by rigid extension of the arms and legs, downward pointing of the toes, and backward arching of the head; decerebrate posturing with rigidity, flexion of the arms, clenched fists, and extended legs; and opisthotonos with rigidity and severe arching of the back, with the head thrown backward. These can also be intermittent findings in children with severe injury of the CNS.

Sleep Disturbance

Treating sources of distress will often improve sleep in children with NI. Pharmacologic treatments to consider include melatonin,^79,80 antidepressants such as tricyclic antidepressants and trazodone,^81–83 clonidine,⁸⁴ and antipsychotics, especially for patients with delirium.⁸⁵ When using melatonin for children with NI, some advocate that as the severity of disability increases, higher doses, occasionally even up to 15 mg, may be beneficial.⁸⁰ Benzodiazepines tend to be overused, leading to dependency and tolerance, and should only be used in a time-limited manner and discontinued or weaned following short-term use.⁸⁶ Nonpharmacologic interventions include a consistent bedtime and routine, quiet, a dark environment, and stimulus control.⁸⁵ When sleep problems are linked to symptoms such as pain or dyspnea, or correlated with an underlying problem such as obstructive apnea, treatment of the underlying condition may improve sleep.

Benzodiazpines

Common considerations in benzodiazepine use include spasticity, dystonia, dysautonomia, seizures, agitation, irritability, sleep, and dyspnea. They are generally safe and effective in the short term, although cognitive impairments and paradoxical effects such as behavioral disinhibition occasionally occur. Limitations of chronic use are a result of tolerance with a decrease of benzodiazepine-binding sites. This can be prevented by keeping dosages minimal, courses ideally less than four weeks, or intermittent use. Sudden cessation with long-term use can result in a withdrawal syndrome. Ideally, benzodiazepines are used intermittently, such as for a prolonged seizure or autonomic crisis, or as a bridge when other interventions are initiated, such as treating increasing spasticity that is potentially secondary to pain while waiting for titration up to a final dose of gabapentin or nortriptyline. Finally, a few case reports identify clonazepam as a useful adjuvant for neuropathic pain, though these reports are of short duration.

Methadone

Methadone is the only opioid with a prolonged effect that is available as a liquid, a beneficial option for children with NI. The main disadvantages are its biphasic elimination and effect of other medications on metabolism. The initial rapid distribution phase, with a half-life of 2 to 3 hours, followed by a slow elimination phase with a half-life of 4.2 to 130 hours, can result in drug accumulation and toxicity 2 to 5 days after starting or increasing methadone. For this reason, dose adjustments should not occur more often than every 72 hours. Potential drug interactions that may be relevant to children with NI include:

Methadone is a beneficial option for symptom management in children with NI. Given some of the complexity, there may be benefit in initiating other medication trials first, such as gabapentin, given its safety and no interactions with other drugs, if suboptimal benefit initiate nortriptyline next, with methadone used as a third-line symptom management intervention. Another reason for this order is the greater benefit with the combination of gabapentin and nortriptyline for neuropathic pain over either one given solely.⁸⁷

Respiratory Health in Children with NI

Children with severe neurologic impairment have a high incidence of respiratory problems.⁸⁸ Recurrent respiratory illness leading to respiratory failure is the most common cause of mortality in children with severe cerebral palsy.^10,11 Aspiration is a frequent factor, identified in 31% to 68% of children with cerebral palsy.^89–91 Aspiration pneumonia in neurologically impaired children is best understood as an acute exacerbation resulting from chronic contributing factors. Those factors include:

In children with severe NI and recurrent respiratory illnesses, it is misleading to parents to label respiratory exacerbations as pneumonia or aspiration pneumonia because this can give the impression of a reversible problem. Instead, it can be helpful to acknowledge that the goal of chronic and acute treatment is to minimize the effect of these factors and maximize recovery and maintenance of health while we prepare for diminishing benefit.

Other factors that are considered to contribute to a decline in respiratory function include gastroesophageal reflux disease (GERD) and neuromuscular (NM) scoliosis. Evidence for the benefit of interventions is unfortunately limited, but includes:

Dyspnea

Dyspnea is the experience of shortness of breath, difficulty breathing, or uncomfortable breathing. It is a common symptom of numerous medical disorders. Included are diseases of the lung parenchyma and obstruction of the airway, which can occur from repeated micro-aspiration with resulting infection, inflammation, bronchiectasis, and lung scarring over time.

Measures of respiratory rate, oxygen saturation, blood gas levels, and family perception do not necessarily correlate with the patient’s perception of breathlessness. Instruments such as the Respiratory Distress Observational Scale (RDOS) are being evaluated for use in adults unable to report about dyspnea.¹⁰⁶ When assisting parents in assessing for dyspnea in a nonverbal child, strategies are similar to those used in pain assessment of such children. Assessment can include asking a parent if he or she has observed the child to be in distress or appear anxious during a respiratory exacerbation. Behaviors indicating distress may include facial expression, appearing restlessness, or becoming withdrawn. It can also be helpful to instruct parents and care providers to breathe along with the child for 1 minute as an indirect indicator of the child’s effort of breathing.

Treating dyspnea is typically focused on identifying and aggressively treating the underlying cause. Evidence is established in adults for using interventions to alleviate dyspnea that persists despite maximum medical management of identified causes. These interventions include an oxygen trial, cool air from a fan or open window, repositioning, lorezepam for associated anxiety, and morphine sulfate. A recent review from the American College of Physicians identified strong evidence for treating adults with dyspnea from chronic lung disease with short-term opioids.^107,108 Evidence includes demonstration of significant improvement in refractory dyspnea in participants completing a randomized, double blind, placebo-controlled crossover study with no significant episodes of sedation.¹⁰⁹ Several studies have demonstrated the safety of using morphine sulfate for management of dyspnea that occurs despite maximum treatment of the underlying cause without development of respiratory depression.^110–112 A suggested starting dose for an opioid naive patient is 25% to 30% of the dose used for pain with a maximum starting dose of 5 mg orally. If the patient is already on an opioid, increase the dose by 30%.

As a decline in respiratory status occurs despite management of these contributing factors, respiratory distress during exacerbations is likely an under-recognized symptom in children with NI. Using evidence for managing dyspnea in adults, children deserve symptom management of respiratory distress incorporated into medical care plans (Table 39-4). ¹¹³ For example, the table identifies antibiotics that provide coverage of anaerobic bacteria along with other oral bacteria when treating children who chronically aspirate oral secretions.^114–118 Morphine sulfate is included in Table 39-4 to remind us to ask if there is distress during respiratory exacerbations and to include that information in care plans when distress is identified. This allows integration of symptom management into acute medical care plans in advance of seeing limited benefit from chronic and acute medical interventions. Overall, this will assist with future decisions by assuring that comfort is part of the care plan and avoid decisions to use interventions offered being made solely out of fear of suffering.

TABLE 39-4 Respiratory Home Management: Medical and Symptom Treatment Strategies

* Symptoms include increased coughing, secretions, congestion, respiratory rate and breathing effort.

† Use when respiratory symptoms persist or worsen despite an increase in chronic interventions.

‡ Include with third or fourth exacerbation, sooner if symptoms return within two months of antibiotic course.

§ Features suggesting respiratory distress include facial expression such as grimacing, appearing restlessness, having an anxious look, stiffening, tears, or becoming withdrawn.

Adapted from Hauer JM. Respiratory symptom management in a child with severe neurologic impairment. J Palliat Med 2007; 10(5):1201-1207. Table 39-1. Reprinted with permission from Journal of Palliative Medicine.

For such reasons, we likely underuse morphine sulfate when managing respiratory distress, instead reserving its use for comfort at the end of life. Integrating symptom management earlier can minimize interventions being pursued out of fear of the patient suffering without the intervention. There is a need to study the integration of morphine sulfate into the care plans of neurologically impaired children with recurrent respiratory exacerbations. Waiting until the goal is comfort care rather than treatment focused delays initiation of comfort strategies.

Secretions

Secretions occur for various reasons in children with NI. It is helpful to consider sialorrhea separately from thicker respiratory secretions. Sialorrhea involves thin, watery secretions that can pool out of the mouth as a result of diminished oral sensation of saliva. There is ample evidence of the benefit of medications such as glycopyrrolate and botox or surgical ligation of the salivary ducts in diminishing sialorrhea. In contrast, an increase in respiratory secretions in such children is likely due to multiple factors, including an increase in pulmonary secretions as a result of inflammation from aspiration of oral secretions and mucous that is difficult to mobilize. Management is directed at minimizing the development of such secretions through use of inhaled steroids and assistance with clearance through bronchial drainage techniques and devices such as the pulmonary vest and cough assist. Medications are available to decrease secretions but should be used with caution in this population because they can result in thicker secretions that are more difficult to mobilize. They may have a more beneficial role when comfort is the primary goal of care. Medications with anticholinergic properties that have been used for management of secretions at the end-of-life include scopolamine, hyoscyamine, and atropine, tertiary amines that may cause sedation and delirium as they cross the blood brain barrier. Glycopyrrolate is another option, which may be less sedating. No evidence exists indicating that one is more beneficial than another. Decreasing total fluid intake by 25% or more is another simple intervention to consider for management of excessive respiratory secretions.

Nausea, Retching, Vomiting, and Feeding Intolerance

Gastrointestinal symptoms are common in children with severe NI.^27–29 This includes pain localized to the gut as noted in the pain section. Vomiting in these children is commonly attributed to GERD.¹¹⁹ Alternatively, stimulation of the emetic reflex is likely an under-reported source of symptoms in these patients.^100,120 Experience and limited evidence suggests the benefit of considering sources beyond GERD. Considerations include visceral hyperalgesia, activation of the emetic reflex, and dysautonomia (Table 39-5).

TABLE 39-5 Medications for Retching, Vomiting, Feeding Intolerance in Children with NI

Persistent Feeding Intolerance

Feeding intolerance can be a source of distress for children with severe NI who are receiving fluid and nutrition through a feeding tube. As with recurrent respiratory exacerbations as a result of chronic pulmonary aspiration, the initial benefit from treatment interventions may lessen over time. At such times it can be beneficial to integrate symptom management strategies into medical care plans.

Management includes treating contributing problems such as constipation. As reviewed previously, some children benefit from an empiric trial of gabapentin or nortriptyline for visceral hyperalgesia, cyproheptadine for retching, and ondansetron, or hyoscyamine for vomiting, being mindful of which medication targets which receptor so as to avoid duplication. Because there is limited evidence to guide in such patients, one must be careful from introducing too many trial options. Other intervention strategies include an empiric trial of an elemental formula, an empiric trial of metronidazole or rifaximine for small bowel bacterial overgrowth in children with persistent diarrhea, and a trial of J-tube feedings. Experience shows that J-tube feedings often do not improve pain associated with vomiting. This may reflect irreversible changes in the nervous system with resulting autonomic dysfunction and visceral hyperalgesia.

Some of these children will have persistent problems despite using these options. At such times, some children will benefit from a decrease by 25% or more in the total amount of nutrition and fluids provided by feeding tube. Families benefit at such times from a reflection on primary goals and determining approaches that meet these goals such as feeding to comfort rather than feeding to a required amount, and withholding feedings that are resulting in pain and discomfort.

Medical Nutrition and Hydration

Forgoing medical nutrition and hydration remains one of the more difficult areas given the symbolic significance of nutrition, the myths about dehydration and starvation, and under-recognition of the complications of artificial hydration and nutrition.¹³² The American Academy of Pediatrics policy statement recognizes that “Life-sustaining medical treatment encompasses all interventions that may prolong the life of patients. …includes less technically demanding measures such as antibiotics, insulin, chemotherapy, and nutrition and hydration provided intravenously or by tube.”¹³³ It is permissible to discontinue medical nutrition and hydration when it is prolonging or contributing to suffering.^134–137

Children with NI receiving medical nutrition and fluids through a feeding tube are vulnerable to complications as health continues to decline. This can include progressive feeding intolerance, development of edema, and increasing oral secretions. It is important to combine knowledge of reversible sources of these problems with an understanding of features that are part of progressive, irreversible decline. This can be challenging in children with NI who live chronically with impairment that is considered static and who often experience decline over a long period, increasing the likelihood of aggressive evaluation and treatment at the end of life. It is helpful to recognize that even children with static conditions experience irreversible decline in organ function, likely a result of ongoing apoptosis in the setting of baseline impairment of the nervous system. This may account for why some children with NI develop feeding intolerance later in life that is not amenable to medical interventions.

It can be helpful to recognize with parents the years of benefit provided by a feeding tube as we consider development of harm from this intervention. This is a time to inform without expecting a decision; educating on the role of feeding tubes as life-sustaining technology in the same sense as a ventilator and the benefit of considering when technology is becoming more burdensome, even when that technology has been routine and is easy to use. The previous sections are a critical part of this process, by creating a context for understanding the goals of the child and family and through knowledge of the child’s health trajectory. It is helpful to estimate for families the length of time that may pass following discontinuation of medical nutrition and hydration until death occurs, often 10 to 14 days, but can be much longer by several weeks when small amounts of fluid are used to flush a feeding tube after medications have been given.

Care Teams to Meet the Complexity of Needs

The goal of palliative care and hospice teams is to meet the needs in the location of care, whether in the hospital, clinic, school, or home. Given the multiple challenges that families of children with NI experience, they benefit from as much anticipation of needs as possible: care in the school setting, symptom management at home, financial planning, and preparing for end-of-life care. One challenge is how to incorporate home-based palliative and/or hospice care into home care plans while preserving established blocks of home care nursing. Some states are eliminating this challenge through waivers that allow both resources to be used, allowing established home nurses to continue. This is of critical importance given the practical day-to-day care needs of such children along with the benefit of early integration of palliative care for such children and their families.

End-of-Life Care

Autopsy, Brain and Tissue Bank, and Organ Donation

The option of autopsy or tissue donation to the Brain and Tissue Bank is ideally discussed with the family by a trusted physician before death. Some families may feel that the child has been through enough while others may feel that this is a way to advance science and help other children who may suffer from the same condition.

The goal of the Brain and Tissue Bank is to advance research on developmental disorders. It serves the critical purpose of collecting, preserving, and distributing human tissues to scientific investigators who are dedicated to the improved understanding, care and treatment of developmental disorders, offering hope to others. The procedure to recover tissue at time of death will not interfere with open casket viewing. The Brain and Tissue Bank covers all expenses related to the recovery of tissue. All donor information remains anonymous and anyone who registers holds the right to withdraw at any time. Further information for families can be found at www.btbankfamily.org.

Increasingly, pediatric hospitals are developing policies that support donation after cardiac death programs. There is increasing awareness of this approach as noted by the number of cases that were initiated by the family.^138,139 Organ donor programs that include donation after cardiac death may have benefit by providing an opportunity for legacy building. Further review is needed on how this impacts end-of-life care and bereavement.

Bereavement

Bereavement often starts before the child’s death. Support from palliative care teams can link families to assistance from extended family, friends, or community providers, including faith communities and grief counselors, as families prepare to transition from the specialized healthcare system. Bereavement care also guides the family through the legal requirements and decisions for the care and relinquishment of the body.

Unique areas of bereavement are seen in parents of children with NI. The limited research has not found differences on measures of grief between parents of children with developmental impairment and other parents.¹⁴⁰ Themes identified that are unique to parents of children with NI include: working through two difficult transitions, first when the child was diagnosed with NI and second when the child died; a need to justify their love of their child to others; parents’ lack of opportunity to share their grief, resulting in a socially imposed silent grief; loss of an intensive caregiver role and support group membership; conflicting feelings of sadness; and relief over prior fears about the child’s future. Bereavement is an essential part of supportive care with importance in attending to the experiences unique to families of children with NI.

Future Directions and Ongoing Challenges

There are many opportunities to better understand how palliative care, as an interdisciplinary team, and palliative medicine, as a medical specialty, can best assist this population. Areas of need include symptom assessment and management and improved understanding of how interventions alter outcomes for these children. There is benefit in exploring how parents approach decision making that is both similar and unique to other groups of children with life- threatening conditions.

Acknowledgments

With gratitude to Melissa Connelly, Elayne Sommers, and Jean Stansbury, members of the palliative care team at Gillette Children’s Specialty Healthcare. Through their work they have benefitted countless families and are a source of inspiration to others.