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National Guideline Alliance (UK). Cerebral palsy in under 25s: assessment and management. London: National Institute for Health and Care Excellence (NICE); 2017 Jan. (NICE Guideline, No. 62.)
Review question: In children and young people with cerebral palsy, which interventions are effective in managing sleep disturbances arising from no identifiable cause?
23.1. Introduction
Adequate sleep is recognised as a vital element in normal health and development. As such, sleep disturbances can lead to a reduction in the quality of life, potentiating negative outcomes in children and young people with cerebral palsy and also directly and indirectly their parents and families.
There are a wide variety of reasons for underlying sleep disturbances in children and young people with cerebral palsy. These include the presence of increased or decreased nocturnal movements and comorbidities such as obstructive sleep apnoea or other sleep-related breathing disorders, pain, epilepsy and behavioural problems. Any approach to improving sleep should start with recognising and managing these factors before focusing on specific behavioural and pharmacological approaches used in wider population groups that help sleep initiation and maintenance.
Appropriate interventions can potentially help physical and psychological wellbeing as well as individual development, function and participation. This review aims to determine which interventions are more clinically and cost effective for reducing sleep disturbances.
23.2. Description of clinical evidence
A systematic search was conducted to retrieve evidence on the clinical and cost effectiveness of interventions for reducing sleep disturbances in children and young people with cerebral palsy.
The Committee in the review protocol prioritised the following pharmacological and nonpharmacological interventions:
- melatonin
- sleep systems and/or sleep positioning (postural devices, wedges and supports)
- age-appropriate behavioural sleep routine (termed as sleep hygiene programmes)
- sedatives:
- alimemazine/Vallergan
- chloral hydrate
- clonidine.
Five studies have been included in this evidence review (Appleton 2012, Coppola 2004, Dodge & Wilson 2001, Lloyd 2014, Wasdell 2008). One study is a Cochrane systematic review on sleep-positioning systems in children with cerebral palsy (Lloyd 2014); and 4 studies are randomised controlled trials on the use of melatonin (Appleton 2012, Coppola 2004, Dodge & Wilson 2001, Wasdell 2008).With regards to the evidence retrieved for the use of sleep-positioning systems, Lloyd and colleagues conducted a systematic review that included children and young people up to 18 years of age with cerebral palsy. Sleep patterns and sleep quality were part of the secondary outcomes analysed in this Cochrane review, as well as quality of life of the child and the family. Only 2 crossover trials met the inclusion criteria with regards to population and outcomes considered. Sleep quality was measured by both polysomnography and video recording, or by Actigraph.
In relation to the clinical effectiveness of melatonin, no studies were identified that only looked at children and young people with cerebral palsy. However, 4 studies comparing melatonin with placebo in populations of children and young people with neurodevelopmental disorders (including cerebral palsy) were included, of which 3 were crossover (Coppola 2004, Dodge & Wilson 2001, Wasdell 2008), and 1 was a health-technology assessment (Appleton 2012). All trials were double-blinded and placebo-controlled. Sample sizes ranged from 20 to 143, and participants were aged between 1 and 18 years.
Participants received melatonin or placebo each day during 10 days (Wasdell 2008), 4 weeks (Coppola 2004), 6 weeks (Dodge & Wilson 2001) or 12 weeks (Appleton 2012). Two studies used a fixed dose of melatonin of 5 mg (Dodge & Wilson 2001, Wasdell 2008); in 1 study, treatment with melatonin was initiated at a daily dose of 3 mg and parents were allowed to increase the dosage up to 9 mg/day during the following 2 weeks in case of inefficacy (Coppola 2004); in 1 study (Appleton 2012), the starting dose was 0.5 mg and the dosage could be increased through 2 mg and 6 mg to 12 mg during the first 4 weeks. Time of administration of the intervention differed slightly across studies, being fixed in 1 case at 8pm (Dodge & Wilson 2001), 45 minutes before bedtime (Appleton 2012), 20 to 30 minutes before the child’s most desirable bedtime (Wasdell 2008), or even at bedtime (Coppola 2004).
With regards to the outcomes, all the included studies reported on:
- Total night sleep time measured either by sleep diaries (Appleton 2012, Coppola 2004, Dodge & Wilson 2001, Wasdell 2008) or actigraphy (Appleton 2012, Wasdell 2008).
- Sleep latency measured either by sleep diaries (Appleton 2012, Coppola 2004, Dodge & Wilson 2001, Wasdell 2008) or actigraphy (Appleton 2012, Wasdell 2008).
- Night wakes measured either by sleep diaries (Appleton 2012, Coppola 2004, Dodge & Wilson 2001, Wasdell 2008) or actigraphy and Composite Sleep Disturbance Index (CSDI) score (Appleton 2012, Wasdell 2008).
- Quality of life of the parents measured using Family Impact Module of the Pediatric Quality of Life Inventory (PedsQL) (Appleton 2012).
GRADE methodology was used for this question and GRADE profiles were produced.
Data for these outcomes were meta-analysed where possible.
Appleton 2012 also reported on adverse effects, but no formal statistical evaluation was conducted.
For full details, see the review protocol in Appendix D. See also the study selection flow chart in Appendix F, forest plots in Appendix I, study evidence tables in Appendix J and the exclusion list in Appendix K.
23.3. Clinical evidence profile
Table 97
evidence profile summary for sleep positioning systems.
Table 98
evidence profile sumary for melatonin versus placebo.
23.4. Economic evidence
No economic evaluations of interventions relevant to managing discomfort and/or pain and distress were identified in the literature search conducted for this guideline. Full details of the search and economic article selection flow chart can be found in Appendix E and Appendix F, respectively.
This review question was not prioritised for de novo economic modelling. To aid consideration of cost effectiveness, relevant resource and cost-use data are presented in Appendix G.
23.5. Evidence statements
23.5.1. Sleep-positioning systems
23.5.1.1. Sleep latency
A systematic review including 2 crossover trials with 21 participants found no significant difference in sleep latency between sleeping in the sleep-positioning system or not.
23.5.1.2. Sleep efficiency
A systematic review including 2 crossover trials with 21 participants found no significant difference in sleep efficiency between sleeping in the sleep-positioning system or not.
23.5.1.3. Quality of life of child and family
No studies were found for this outcome.
23.5.2. Melatonin versus placebo
23.5.2.1. Total night sleep time measured by sleep diaries
High-quality evidence from 4 studies with 205 participants found no clinically significant difference between melatonin and placebo for total night sleep time when measured with sleep diaries.
23.5.2.2. Total night sleep time measured by actigraphy
Moderate-quality evidence from 2 studies with 109 participants found no clinically significant difference between melatonin and placebo for total night sleep time when measured with actigraphy.
23.5.2.3. Sleep latency measured by sleep diaries
Moderate-quality evidence from 4 studies with 205 participants found a clinically significant beneficial effect of melatonin compared with placebo for sleep latency.
23.5.2.4. Sleep latency measured by actigraphy
Low-quality evidence from 2 studies with 99 participants found a clinically significant beneficial effect of melatonin compared with placebo for sleep latency.
23.5.2.5. Night wakes measured by sleep diaries
High-quality evidence from 3 studies with 95 participants found no clinically significant difference between melatonin and placebo for number of night wakes when measured with sleep diaries
23.5.2.6. Night wakes measured by actigraphy
Moderate-quality evidence from 1 study with 50 participants found no clinically significant difference between melatonin and placebo for number of night wakes when measured with actigraphy.
23.5.2.7. Night wakes measured by CSDI
High-quality evidence from 1 study with 125 participants found no clinically significant difference between melatonin and placebo for number of night wakes when measured with CSDI score.
23.5.2.8. Quality of life of the parents measured by using Family Impact Module of the PedsQL
High-quality evidence from 1 study with 133 participants found no clinically significant difference between melatonin and placebo on the quality of life of the parents.
23.5.2.9. Adverse events
No formal statistical analysis was done by the included studies; however no difference between the intervention and the control groups with regards to adverse events was reported.
23.6. Evidence to recommendations
23.6.1. Relative value placed on the outcomes considered
The aim of this review is to determine which interventions are more clinically and cost effective for managing sleep disturbance in children and young people with cerebral palsy.
The following outcomes were identified by the Committee as most useful in decision-making:
- Sleep quality, measured for example, by polysomnography (gold standard) or by other methods such as wrist actigraphy, sleep diaries and/or Sleep Habits Questionnaire
- Health-related quality of life (for example, Peds-QL, Pediatric QOL-CP module or EQ-5D)
- Other important outcomes were: adverse events, and daytime emotional wellbeing and/or lability.
23.6.2. Consideration of clinical benefits and harms
The Committee noted that the first and most important aspect of sleep management of any sleep disorder in children and young people with cerebral palsy is the maintenance of ‘sleep hygiene’. Simple steps to manage a normal sleep routine are vital to help sleep latency and maintenance.
The Committee reflected on the close correlation between pain and/or discomfort and sleep disturbance. In individuals with cerebral palsy there are a number of potential factors around tone, musculo-skeletal comfort, positioning, nutrition and comorbidity that can directly affect the quality of sleep.
As such, the Committee recommended that the second step of any sleep management plan should be to consider and manage treatable causes of any sleep disturbance, in particular consideration of sleep-disordered breathing patterns, potential epilepsy and movement difficulties, behavioural aspects and optimising physical and psychological comfort.
The Committee noted that the evidence provided showed that sleep systems should not be used to solely manage primary sleep disorders or if there are concerns about epilepsy. However, as outlined in NICE spasticity guidelines, they can be useful for hip placement and thereby potentially reduce pain and discomfort. They could, therefore, be of benefit to help in some secondary sleep disorders. Regular review of their individual applicability and tolerance is advised.
The evidence identified gave no specific backing to sedative use, though these are frequently used in primary, secondary and tertiary medical practice. A trial of sedative medication is often used in primary and secondary care to see if this helps recover an appropriate diurnal: nocturnal sleep pattern. However, as their side-effect profile is marked particularly in children or young people with respiratory or ear, nose or throat difficulties, the Committee agreed their continued use should not routinely be considered without seeking specialist advice.
The Committee agreed that a trial of melatonin could be considered to manage difficulties in sleep initiation and/or latency. However, they also agreed that it is not routinely used to manage problems of sleep duration or episodes of waking through the night. The Committee noted that ‘slow release’ formulations are considered as working long-term through the duration of sleep but the efficacy of these preparations is not proven.
The Committee noted an increasing use of chloral hydrate and/or clonidine to help with sleep initiation and maintenance, particularly in dystonic children in particular, however there was as yet no evidence base to support this.
It was noted that in adults with cerebral palsy and sleep disturbances the most common forms of management are psychological wellbeing interventions and sometimes chlorpheniramine as a sedative.
The Committee agreed that if there were ongoing sleep disturbances, the child or young person should be referred to specialist sleep services for multidisciplinary team assessment and management.
Because of the lack of clarity of the effectiveness of sedatives in managing sleep disorders in children and young people with cerebral palsy, the Committee agreed to develop a research recommendation assessing the clinical and cost effectiveness of interventions (sleep hygiene, sedatives and/or melatonin) to improve sleep disturbances.
23.6.3. Consideration of economic benefits and harms
The Committee acknowledged that the cost of sleep systems varies depending on the type of equipment needed. Following this discussion the Committee believed that sleep systems would not be considered cost effective relative to the other interventions included in this review because they are not primarily used to reduce sleep disturbance. However, the Committee highlighted that interventions aimed at reducing pain, including on occasion the use of sleep systems, can reduce sleep disturbance indirectly.
The first-line intervention recommended by the Committee was modifications to the patient’s sleep routine (sleep hygiene programmes) that would be implemented by the family and/or carer at home without employing NHS resources. This programme should be put in place together with consideration of management of any potential comorbidity that could affect sleep initiation and maintenance.
Following unsuccessful modifications to the patient’s sleep routine, the Committee considered a trial of melatonin to help manage problems sleep initiation and/or latency. However the Committee did not feel melatonin would be considered cost effective to manage problems of sleep maintenance or waking.
The Committee noted that the brand of melatonin used in the UK (Circadin) is a tablet preparation, but shorter-release oral solutions are available from specialist order manufacturers at a higher cost. However, the Committee stated that the tablet preparation is often crushed, evading the need for oral solutions that are more expensive. Advice regarding this should be provided via specialist paediatric pharmacy groups.
In the event of lack of efficacy of melatonin, the Committee advised that specialist advice should be sought to initiate a trial of sedatives, with a defined end point. The Committee was surprised chloral hydrate incurred such a high cost (143.3mg/5ml oral solution BP, 150ml, £244.26 [BNF June 2016]) when presented with a cost description of the pharmacological treatments (Appendix G); leading to a recommendation that patients should be seen by a specialist before sedatives are received to ensure the most appropriate and cost-effective treatment is administered.
Even though chloral hydrate is associated with a high cost it is important to reiterate that the cost effectiveness of any sedative included in this review cannot be ascertained in the absence of clinical-effectiveness data. For this reason, the research recommendation from the Committee to consider the clinical and cost effectiveness of interventions to improve sleep disorders in children and young people with cerebral palsy will assess if benefits can justify the costs to mitigate current uncertainty in this area.
23.6.4. Quality of evidence
One systematic review and 4 RCTs were included in this review. The quality of the evidence ranged from high to low, and main reasons for bias were because of imprecision or study design.
23.6.5. Other considerations
The recommendations related to this evidence review were based on the evidence and the Committee’s clinical experience.
23.6.6. Key conclusions
The Committee concluded that the evidence pointed to the act that sleep positioning systems seem not to have a clinically significant effect on sleep quality in children and young people with cerebral palsy who experience sleep disturbance. With regards to the use of melatonin, the intervention has a clinically beneficial effect on sleep initiation and/or latency, but no clinically significant difference was found for all the other outcomes related to both sleep quality and quality of life.
23.7. Recommendations
- 100.
Optimise sleep hygiene for children and young people with cerebral palsy.
- 101.
Manage treatable causes of sleep disturbances that are identified in children and young people with cerebral palsy.
- 102.
If no treatable cause is found, consider a trial of melatonino to manage sleep disturbances for children and young people with cerebral palsy, particularly for problems with falling asleep.
- 103.
Do not offer regular sedative medication to manage primary sleep disorders in children with cerebral palsy without seeking specialist advice.
- 104.
Do not offer sleep positioning systems solely to manage primary sleep disorders in children and young people with cerebral palsy.
- 105.
Refer the child or young person to specialist sleep services for multidisciplinary team assessment and management if there are ongoing sleep disturbances.
23.8. Research recommendations
- 7.
What is the clinical and cost effectiveness of interventions (sleep hygiene, sedatives, melatonin) to improve sleep disturbance in children and young people with cerebral palsy?
Table 99
Research recommendation rationale.
Table 100
Research recommendation statements.
Footnotes
- o
At the time of publication (Janaury 2017), melatonin did not have a UK marketing authorisation for use in children and young people under 18 for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.
- Management of sleep disturbances - Cerebral palsy in under 25s: assessment and m...Management of sleep disturbances - Cerebral palsy in under 25s: assessment and management
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