Respiratory alkalosis in children with febrile seizures

Abstract

SUMMARYPurpose: Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. Methods: We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco 2 were measured immediately on admission to the hospital. Key Findings: Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco 2 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco 2 37.7 ± 4.3 mmHg; p < 0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE-admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p < 0.005). Significance: The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid-base status.

Acid extrusion via blood–brain barrier causes brain alkalosis and seizures after neonatal asphyxia

“…A wide range of observations have shown that changes in extra- and intracellular pH exert a strong modulatory effect on brain excitability under normal and pathophysiological conditions, whereby an alkalosis enhances excitability while an acidosis has an opposite effect (Siesjö, 1985; Chesler, 1990; Kaku et al , 1993; Kaila, 1994; Casey et al , 2010; Enyedi and Czirjak, 2010; Ruusuvuori et al , 2010). This underscores the crucial role of brain pH regulation in seizure generation (Schuchmann et al , 2006, 2011; Ziemann et al , 2008; Tolner et al , 2011). …”

Recent Research on Febrile Seizures: A Review

“…A study of febrile seizures in Indian children found lower zinc levels in patients with FS compared to age matched febrile children without seizures [43]. Other studies have proposed that there is a link between FS and a systemic respiratory alkalosis, irrespective of the severity of the underlying infection [44]. These associations require large population studies to determine if they can be predictive or if they can ultimately be factors associated with prevention.…”

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

“…However, due to the short application time, effects on normal brain function and other side effects are expected to be minimal. Patients suffering from febrile seizures tend to hyperventilate during fever, which leads to a pathological reduction of pCO 2 in the blood (respiratory alkalosis) [22]. In these patients, carbogen inhalation would thus not lead to a pathological pCO 2 increase, but restore the physiological normal state.…”

“…They discovered that up to 2 hours after the febrile seizure the blood pH in children was significantly higher and the pCO 2 levels lower than in children admitted for other reasons (e.g. gastroenteritis, upper respiratory tract infection) [22]. Beyond that, individual uncontrolled therapeutic interventions have been reported, by which seizures could be stopped through elevation of the bood-pCO 2 either via re-breathing [23] or by carbogen inhalation [24].…”