Five percent CO₂ is a potent, fast-acting inhalation anticonvulsant.
OBJECTIVE
CO₂ has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO₂ can be used to suppress seizures in epilepsy patients. The effect of CO₂ on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans.


METHODS
In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. Five percent CO₂ was applied for 5 min, 3 min before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO₂ in medical carbogen shortly after electrographic seizure onset.


RESULTS
In rats, 5% CO₂ strongly suppressed cortical afterdischarges, by approximately 75%, whereas responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO₂) from 37 to 44-45 mm Hg (corresponding to inhalation of 5% CO₂ or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by approximately 25%. In a pilot trial carried out in seven patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO₂ was started after seizure generalization.


CONCLUSIONS
Five percent CO₂ has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO₂ can be used for acute treatment to suppress seizures in epilepsy patients.
Tolner
Else A
EA
Department of Biosciences, University of Helsinki, Helsinki, Finland.
Hochman
Daryl W
DW
Hassinen
Pekka
P
Otáhal
Jakub
J
Gaily
Eija
E
Haglund
Michael M
MM
Kubová
Hana
H
Schuchmann
Sebastian
S
Vanhatalo
Sampsa
S
Kaila
Kai
K
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000737:chemistry; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005260:Female; D006801:Humans; D008254:Macaca nemestrina; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors; D055815:Young Adult
D000927:Anticonvulsants; D002245:Carbon Dioxide