In establishing that a given intervention is in the child’s best interest, it is clearly necessary to be aware of the existing evidence. In an age where evidence-based medicine is a professional requirement,² it is important that practice is not just based on anecdotes and experience, but also is justified with research. Critical appraisal and clinical reasoning must underpin practice. Systematic reviews or meta-analyses, where they exist, are authoritative sources of such evidence. Individual carefully designed double-blind trials are also powerful evidence. Anecdote and case history, however, are not indicators of effectiveness. They are important signposts to studies that should take place, but should not result in an uncritical change of practice by themselves.

The literature pertaining to non-pharmacological approaches to the management of neurological symptoms is particularly sparse. A rational and logical approach does not, however, mean that practice should be limited only to that rather narrow range of therapeutic options that have been subjected to study in children. It is often necessary to extrapolate from evidence in the adult specialty, or from related disciplines such as acute pain management. Sometimes, professionals working in pediatric palliative care need to be therapeutically creative, using a sound knowledge of pharmacology and therapeutics to develop an approach that, while it may not be fully supported by evidence, is nevertheless rational.

Complementary and alternative medicine (CAM) ap- proaches should be used in conjunction with conventional medicine to aim to provide better symptom control and meet the cultural, spiritual, and psychosocial needs of the child and family.³ Many neurological symptoms are exacerbated by depression, anxiety, and/or fatigue. There is evidence to suggest these are ameliorated by some CAM approaches, including massage,⁴^–¹² acupuncture,^8,^10,¹³^–¹⁶ and transcutaneous electrical stimulation (TENS)^8,¹⁷ can offer some assistance with this. The effectiveness of TENS is unclear^18,¹⁹ but it is well tolerated by most patients. Music therapy and hydrotherapy are naturally enjoyable interventions for children (Fig. 27-1).

Fig. 27-1 Child’s depiction of successful family-centered interdisciplinary care of child with neurological symptoms.

Symptoms

For a summary of doses and indications of medications in this chapter, see Table 27-1.

TABLE 27-1 Doses and Indications for Medications Mentioned in This Chapter

Medication	Indication	Dosage
Midazolam	Status epilepticus and terminal seizure control. Breakthrough anxiety, such as panic attacks. Adjuvant for pain of cerebral irritation. Dyspnea	For status epilepticus: By buccal administration, Neonate 300 micrograms/kg as a single dose Child 1-6 mo, 300 micrograms/kg (max. 2.5 mg), repeated once if necessary Child 6 mo-1 yr, 2.5 mg, repeated once if necessary Child 1-5 yrs, 5 mg, repeated once if necessary Child 5-10 yrs, 7.5 mg, repeated once if necessary Child 10-18 yrs, 10 mg, repeated once if necessary For terminal seizure control: By subcutaneous or intravenous infusion over 24 hrs, 50-300 mcg/kg/hour up to maxi. 160 mg For anxiety or dyspnea: Approximately 50% above doses
Diamorphine	As for morphine. Useful where large doses need to be dissolved in small volume	Relative potency parenteral preparations 3x that of oral morphine.
Phenobarbital	Adjuvant in pain of cerebral irritation. Control of terminal seizures. Sedation	By mouth: Neonates, loading dose by slow intravenous injection, then 2.5-5 mg/kg by mouth once a day Child 1 mo-12 yrs, 1-1.5 mg/kg twice a day, increased by 2 mg/kg daily as required (usual maintenance dose 2.5-4 mg/kg once or twice a day) Child 12-18 yrs, 60-180 mg once a day.
Diazepam	Short-term anxiety relief. Relief of muscle spasm. Treatment of status epilepticus	Short-term anxiety relief: By mouth: Child 2-12 yrs, 2-3 mg three times a day Child 12-18 yrs, 2-10 mg three times a day Relief of muscle spasm: By mouth: Child 1-12 mo, initially 250 mcg/kg twice a day Child 1-5 yrs, initially 2.5 mg twice a day Child 5-12 yrs, initially 5 mg twice a day Child 12-18 yrs, initially 10 mg twice a day, maxi. Total daily dose 40 mg Status epilepticus: By intravenous injection over 3-5 min: Neonate, 300-400 mcg/kg repeated after 10 min if necessary Child 1 mo-12 yrs, 300-400 mcg/kg repeated after 10 min if necessary Child 12-18 yrs, 10-20 mg repeated after 10 min if necessary By rectum: Neonate, 1.25-2.5 mg repeated after 10 min if necessary Child 1 mo-2 yrs, 5 mg repeated after 10 min if necessary Child 2-12 yrs, 5-10 mg repeated after 10 min if necessary Child 12-18 yrs, 10 mg repeated after 10 min if necessary
Levomepromazine	Antiemetic where cause is unclear, or where probably multifactorial. Secondary effects include sedation and analgesia	Antiemetic: By mouth: Child 2-12 yrs, starting dose 0.1-1 mg/kg, max 25 mg Child greater than 12 yrs, 6.25-25 mg by mouth once or twice daily By continuous intravenous or subcutaneous infusion over 24 hrs: Child 1 mo-12 yrs, 100-400 mcg/kg over 24 hrsChild greater than 12-18 yrs, 5-25 mg over 24 hrs For sedation: By subcutaneous infusion over 24 hrs: Child 1 yr-12 yrs, 0.35-3 mg/kg over 24 hrs Child over 12-18 yrs, 12.5-200 mg over 24 hrs Analgesic: May be of benefit in a very distressed patient with severe pain unresponsive to other measures Stat dose 0.5 mg/kg by mouth or subcutaneously. Titrate dose according to response; usual maximum daily dose in adult 100 mg subcutaneous or 200 mg by mouth
Fentanyl	Severe pain (synthetic opioid analgesic), particularly as rotation from morphine or if patch formulation desirable	By transmucosal application (lozenge with oromucosal applicator): Child 2-18 yrs, 15-20 mcg/kg as a single dose, max. dose 400 mcg By transdermal patch: Based on oral morphine dose-equivalent Product monogram, Oral morphine 60-134 mg = 25 mcg/h patch of fentanyl Oral morphine 180-224 mg = 50 mcg/h patch of fentanyl Oral morphine 27-314 mg = 75 mcg/h patch of fentanyl
Hydromorphone	Severe pain (opioid analgesic) especially if diamorphine unavailable and solubility is an issue	By mouth: Child 12-18 yrs, initially 1.3 mg every 4 hrs, increasing as required
Tizanidine	Muscle spasm	By mouth: Adult dose, initially 2 mg increasing in increments of 2 mg at intervals of 3 to 4 days. Give total daily dose in divided doses up to 3-4 times daily. Usual total daily dose 24 mg. Maximum total daily dose 36 mg
Baclofen	Chronic severe spasticity of voluntary muscle	By mouth: Initially, Child 1-10 yrs 0.75-2 mg/kg daily or 2.5 mg 4 times daily. Increased gradually to maintenance: Child 1-2 yrs, 10-20 mg daily in divided doses Child 2-6 yrs, 20-30 mg daily in divided doses Child 6-10 yrs, 30-60 mg in divided doses
Melatonin	Sleep disturbance caused by disruption of circadian rhythm (not anxiolytic)	By mouth: Dose unknown, initially 2-3 mg, increasing every 1-2 wk dependent on effectiveness up to maximum 10 mg (higher doses have been used)

Seizures

Management of seizures outside the terminal phase is beyond the scope of this chapter. The palliative care professional should continue to liaise carefully with colleagues in neurology, even as death approaches. Potentially, this can achieve several important objectives:

• Rationalization of anticonvulsant medications

Children with life-limiting conditions in ACT categories III and IV (Table 27-2), which are often chronic neurological conditions, are likely to have seizures that have been difficult to control for some time. The result is typically that, at the time it is clear a palliative phase has been entered, children are on a large number of different anticonvulsants.

TABLE 27-2 Life-Limiting Conditions

The long-term management of seizures requires a neurologist to balance carefully immediate benefit with long-term side effects. In the palliative phase, such a balance may no longer be necessary. Discussion with neurology colleagues may allow:

• Discontinuation of some anticonvulsants,

• Reduction in the number of anticonvulsants,

• Substitution of specific anticonvulsants with broader range ones with additional desirable benefits such as anxiolysis or activity against neuropathic pain.

Management of breakthrough seizures usually requires a parenteral approach. This presents a conflict with one of the aims of palliative care, which is to offer the family the choice of locations, typically home, hospital, or hospice, for death to occur. The intravenous and subcutaneous routes may not be appropriate, because they are not usually available except to professionals who may not be immediately on hand.

The solution to this is to use the buccal route. Small volumes of water soluble drugs such as midazolam and diamorphine can be administered between the cheek and the gum. They are absorbed rapidly through the oral mucosa, effectively providing an alternative parenteral route without needles. This is increasingly used for management of breakthrough seizures in neurology ²⁰ and is ideally suited to their management in the terminal phase.

• Management of terminal seizures

The two mainstays of seizure management in the terminal stages are phenobarbital and midazolam. Both may be given as continuous subcutaneous infusion, though phenobarbital must be given separately from other medications. The decision as to which of these should be first-line use is largely up to the clinician; there is little evidence to suggest which is likely to be more effective, and it may depend on the individual circumstances and patient.

• Phenobarbital

Phenobarbital is rarely used in seizure disorders because of the risk of adverse effect in long-term use. In the palliative phase, however, where these are unlikely to be a significant consideration, it has a number of potential advantages over many other anticonvulsants, though not all are proved. It is anxiolytic, rather than simply sedative,²¹ effective against cerebral irritation; is sedating it may have some activity against neuropathic pain.²² It can also be given orally or through a gastrostomy tube.

It does, however, also have some disadvantages:

It induces its own metabolism, so the dose may need to be kept under review; and its long half-life means it cannot easily be titrated against its effect, particularly if given orally.

• Midazolam

Midazolam is a short-acting benzodiazepine. It is often used by neurologists for breakthrough seizures, but rarely for background control because of its short half-life. In the palliative phase, Midazolam is usually given by continuous subcutaneous infusion although there is no reason in principle why it should not also be given intravenously. It can be mixed with other medications in the same syringe driver, including diamorphine, morphine, levomepromazine, and other medications commonly used in the final days of life. It is easy to titrate against symptoms due to its short half-life; ²³ powerfully anxiolytic, amnestic and sedating; and has a broad range of anticonvulsant activity. Midazolam is widely used in pediatric palliative care, so it has reasonable clinical experience and evidence base. Also, it is highly soluble so can be given by buccal route.

Midazolam’s disadvantages are that paradoxical agitation can occur in some children ²⁴ and its short half-life makes it inappropriate for background control of seizures except by parenteral infusion. The drug can cause confusion; and in cognitively aware children, loss of memory may be a disadvantage, particularly if it impairs family relationships.

The decision as to which is the better first-line approach will depend largely on individual circumstances. For a child who has otherwise no need for parenteral access, phenobarbital given orally may be preferable. For a child needing benzodiazepines for other reasons, midazolam may be the logical choice. For many children, adequate control of seizures in the terminal phase will in practice require both drugs to be given parenterally as the swallowing reflex becomes lost.