Role of lactate measurement in predicting recurrence of seizure within 24 hours in simple febrile seizure patients

Pediatric febrile seizure (FS) is classified into two types, simple febrile seizures (SFSs) and complex febrile seizures (CFSs). The prognosis of CFS and SFS is distinct from each other. Even after diagnosis of SFS, patients with recurrence of seizure within 24 hours are defined as CFS. And it is crucial to predict the recurrence of seizure in SFS patients. The purpose of this study was to investigate the role of lactate levels in predicting recurrence of seizure within 24 hours in SFS patients. This retrospective study was conducted on patients who visited the emergency department with FS from January 2017 to February 2020 at a single tertiary university hospital. They were divided into the recurrence group and the SFS group according to the recurrence of seizures. Multivariable analysis was performed to confirm whether lactate levels could be an independent factor in predicting recurrence of seizure within 24 hours in SFS patients. Of the 177 patients, 38 patients were classified into the recurrence group. High lactate levels (odds ratio = 1.45; 95%confidence interval: 1.04–2.03, p = 0.031) were found to be a significant factor in predicting recurrence of seizure within 24 hours in SFS patients. The areas under the ROC curve for lactate was 0.733. In patients with FS, high lactate levels were shown to be a useful and independent factor in predicting recurrence of seizure within 24 hours in SFS patients.

Lactate; Seizures; Febrile; Recurrence; Pediatric patient

[1] Waruiru C, Appleton R. Febrile seizures: an update. Archives of Disease in Childhood. 2004; 89: 751–756.

[2] Shinnar S, Glauser TA. Febrile seizures. Journal of Child Neurology. 2002; 17: S44–S52.

[3] Berg AT, Shinnar S. Complex febrile seizures. Epilepsia. 1996; 37: 126–133.

[4] Natsume J, Hamano S, Iyoda K, Kanemura H, Kubota M, Mimaki M, et al. New guidelines for management of febrile seizures in Japan. Brain and Development. 2017; 39: 2–9.

[5] Bakker J, De Lima AP. Increased blood lacate levels: an important warning signal in surgical practice. Critical Care. 2004; 8: 1–3.

[6] Jansen TC, van Bommel J, Mulder PG, Rommes JH, Schieveld SJ, Bakker J. The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study. Critical Care. 2008; 12: R160.

[7] Song YJ, Kim A, Kim GT, Yu HY, Lee ES, Park MJ, et al. Inhibition of lactate dehydrogenase a suppresses inflammatory response in RAW 264.7 macrophages. Molecular Medicine Reports. 2019; 19: 629–637.

[8] Kwon A, Kwak BO, Kim K, Ha J, Kim S, Bae SH, et al. Cytokine levels in febrile seizure patients: a systematic review and meta-analysis. Seizure. 2018; 59: 5–10.

[9] Goksugur S, Kabakus N, Bekdas M, Demircioglu F. Neutrophil-to-lymphocyte ratio and red blood cell distribution width is a practical predictor for differentiation of febrile seizure types. European Review for Medical and Pharmacological Sciences. 2014; 18: 3380–3385.

[10] Liu Z, Li X, Zhang M, Huang X, Bai J, Pan Z, et al. The role of mean platelet volume/platelet count ratio and neutrophil to lymphocyte ratio on the risk of febrile seizure. Scientific Reports. 2018; 8: 15123.

[11] Yigit Y, Yilmaz S, Akdogan A, Halhalli H, Ozbek A, Gencer E. The role of neutrophil-lymphocyte ratio and red blood cell distribution width in the classification of febrile seizures. European Review for Medical and Pharmacological Sciences. 2017; 21: 554–559.

[12] Kruse O, Grunnet N, Barfod C. Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: a systematic review. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2011; 19: 74.

[13] French JA. Febrile seizures about febrile seizures and epilepsy: possible outcomes. Neurology. 2012; 79: e80–e82.

[14] Jan MM, Girvin JP. Febrile seizures. Update and controversies. Neurosciences Journal. 2004; 9: 235–242.

[15] Huang W-X, Yu F, Sanchez RM, Liu Y-Q, Min J-W, Hu J-J, et al. TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain. Brain, Behavior, and Immunity. 2015; 48: 68–77.

[16] Virta M, Hurme M, Helminen M. Increased plasma levels of pro‐ and anti‐inflammatory cytokines in patients with febrile seizures. Epilepsia. 2002; 43: 920–923.

[17] Azab SF, Abdalhady MA, Ali A, Amin EK, Sarhan DT, Elhindawy EM, et al. Interleukin-6 gene polymorphisms in Egyptian children with febrile seizures: a case-control study. Italian Journal of Pediatrics. 2016; 42: 31.

[18] Choi J, Min HJ, Shin J. Increased levels of HMGB1 and pro-inflammatory cytokines in children with febrile seizures. Journal of Neuroinflammation. 2011; 8: 135.

[19] Tomoum HY, Badawy NM, Mostafa AA, Harb MY. Plasma interleukin-1β levels in children with febrile seizures. Journal of Child Neurology. 2007; 22: 689–692.

[20] Haspolat S, Mihçi E, Coşkun M, Gümüslü S, Özbenm T, Yegin O. Interleukin-1β, tumor necrosis factor-α, and nitrite levels in febrile seizures. Journal of Child Neurology. 2002; 17: 749–751.

[21] Evans TC, Jehle D. The red blood cell distribution width. The Journal of Emergency Medicine. 1991; 9: 71–74.

[22] Gontko-Romanowska K, Żaba Z, Panieński P, Steinborn B, Szemień M, Łukasik-Głębocka M, et al. The assessment of laboratory parameters in children with fever and febrile seizures. Brain and Behavior. 2017; 7: e00720.

[23] Consoli A, Nurjhan N, Reilly JJ, Bier DM, Gerich JE. Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans. American Journal of Physiology-Endocrinology and Metabolism. 1990; 259: E677–E684.

[24] van Hall G. Lactate kinetics in human tissues at rest and during exercise. Acta Physiologica. 2010; 199: 499–508.

[25] Samuvel DJ, Sundararaj KP, Nareika A, Lopes-Virella MF, Huang Y. Lactate boosts TLR4 signaling and NF-κB pathway-mediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation. Journal of Immunology. 2009; 182: 2476–2484.

[26] Pucino V, Bombardieri M, Pitzalis C, Mauro C. Lactate at the crossroads of metabolism, inflammation, and autoimmunity. European Journal of Immunology. 2017; 47: 14–21.

[27] Lipka K, Bülow HH. Lactic acidosis following convulsions. Acta Anaesthesiologica Scandinavica. 2003; 47: 616–618.

[28] Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures: A model for the study of an anion-gap acidosis not associated with hyperkalemia. New England Journal of Medicine. 1977; 297: 796–799.

[29] Hesdorffer DC, Shinnar S, Lax DN, Pellock JM, Nordli DR, Seinfeld S, et al. Risk factors for subsequent febrile seizures in the FEBSTAT study. Epilepsia. 2016; 57: 1042–1047.

[30] Brody EI, Genuini M, Auvin S, Lodé N, Brunet SR. Prehospital capillary lactate in children differentiates epileptic seizure from febrile seizure, syncope, and psychogenic nonepileptic seizure. Epilepsy & Behavior. 2022; 127: 108551.

[31] Costea RM, Maniu I, Dobrota L, Neamtu B. Stress hyperglycemia as predictive factor of recurrence in children with febrile seizures. Brain Sciences. 2020; 10: 131.

[32] Legouis D, Ricksten S, Faivre A, Verissimo T, Gariani K, Verney C, et al. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nature Metabolism. 2020; 2: 732–743.