Context Breath-holding spells (BHS) are a non-epileptic event where the child involuntarily stops breathing, typically for less than one minute, varying from several times daily to a few times a month.¹ There are two types of BHS: cyanotic and pallid; cyanotic occurs in response to fear or anger, causing oxygen desaturation and loss of consciousness, and pallid can be triggered by pain or fear, causing pallor, oxygen desaturation, and seizure-like movements.¹ The child is a 7-year-old girl with Cornelia de Lange syndrome and a past medical history of respiratory infections and gastroesophageal reflux disease. She was diagnosed with BHS with up to 120 episodes daily. Her electrolytes, renal function, ferritin and haemoglobin levels were within normal ranges. There is no evidence of epilepsy, iron-deficiency anaemia, or abnormal neurological findings. Due to her severe BHS, her case was discussed at the British Paediatric Sleep Society videoconference by her consultant, resulting in the suggestion of a piracetam trial. This is a nootropic drug which works by restoring cell membrane fluidity and neurotransmission with anticonvulsant properties, improving neuronal function.² Piracetam is currently licensed for post-anoxic myoclonus in adults, with very little evidence of use in BHS.

Pharmacist Contribution There are currently no national, international, or local guidelines on treatment of BHS. A literature review was conducted using MEDLINE and EMBASE, resulting in two randomised-controlled trials (RCTs) being analysed: one demonstrated a 77% complete response of BHS with piracetam compared to 6% in placebo group, which was statistically significant (p <0.05)³, and another demonstrated a reduction in median overall number of attacks/month of 1 in the piracetam group, compared to 5 in the placebo group (p <0.001).⁴ NHS Networks was used to contact other centres for advice, with no responses. The patient had comparable characteristics to those in the studies, so piracetam was initiated at a starting dose of 40 mg/kg/day as recommended in the two RCTs. A licensed liquid formulation was available for use in adults which was used off-label. A risk assessment was carried out to ensure safe use and approval sought from the medicines committee.

Outcome The incidence of BHS initially improved with a reduction in desaturations, however increased again which coincided with teething pain. After an MDT discussion, the dose was increased in line with the clinical trials, with no reported adverse effects.

Lessons Learned Drugs used in adults are often extrapolated for use in children, either on an unlicensed or off-label basis. A thorough literature review was required, especially regarding dosing and safe administration, and exploring appropriate formulations. To ensure safe use, a risk assessment with the MDT is required to ensure benefits outweigh risks, and increased monitoring is in place to assess any adverse effects.

Conclusion Our experience of piracetam in one patient with BHS shows that it can be used safely; however, this should be used on an individual case basis after discussion with the MDT. Further research is required in BHS and, in particular, the need for treatment guidelines.

References

1. Flodine T, Mendez M. Breath Holding Spells [Internet]. 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539782/ [Accessed March 2022]

2. Winblad B. Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Reviews 2006;11:169–182.

3. Abbaskhanian A, Ehteshami S, Sajjadi S, Rezai M. Effects of piracetam on pediatric breath holding spells: a randomized double blind controlled trial. Iran J Child Neurology 2012;6:9–15.

4. Sawires H, Botrous O. Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells. European Journal of Pediatrics 2012;171:1063–1067.