Forsyth, R 
ORCID: 0000-0002-5657-4180, Allen, M, Bedson, E ORCID: 0000-0001-5209-1854, Downes, A, Gough, C, Hartshorn, S, Lawton, K, Lyttle, MD, Messahel, S, Mullen, N et al (show 6 more authors)
(2024)
Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT))
Trials, 25 (1).
349-.
ISSN 1745-6215, 1745-6215
Abstract
Background: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment. Methods: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as ‘carbogen’. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality. Discussion: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff. Trial registration: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Convulsive status epilepticus, Acid-base, pH, Respiratory acidosis, Paediatrics, Deferred consent |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Population Health |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 04 Jun 2024 09:41 |
| Last Modified: | 28 Feb 2026 01:35 |
| DOI: | 10.1186/s13063-024-08188-5 |
| Open Access URL: | https://link.springer.com/article/10.1186/s13063-0... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3181992 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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