Sevoflurane and seizures
Jerry Y. Chao MD and Elissa G. Yozawitz MD
Original article
Jerry Y Chao, Alan D Legatt, Elissa G Yozawitz, David C Adams, Ellise S Delphin, Shlomo Shinnar. Electroencephalographic Findings and Clinical Behavior During Induction of Anesthesia With Sevoflurane in Human Infants: A Prospective Observational Study. Anesth Analg . 2020 Jun;130(6):e161-e164. doi: 10.1213/ANE.0000000000004380.
PMID: 31453873
Original article
Jerry Y Chao, Matthew Tam, Alexander Ferrera, Daria Ivenitsky, Luciana Gizzo, Rachel Schwartz, Alan D Legatt, Elissa G Yozawitz, Yungtai Lo, Guohua Li, Shlomo Shinnar. Epileptiform discharges, electrographic seizures, and electroclinical seizures during paediatric sevoflurane anaesthesia: a systematic review and proposal for standard definitions. Br J Anaesth. 2023 Jan;130(1):e18-e21. doi: 10.1016/j.bja.2022.09.021. PMID: 36333161
Have you ever been curious about the funny movements kids sometimes make during inhalational induction with sevoflurane? Do the movements just reflect the fact that the kids are “fighting” or “resisting” the mask induction? And as they reach an increased depth of general anesthesia, what are the involuntary movements that are sometimes seen? Are the movements worrisome with jerking movements sometimes resembling what appear to be “seizure-like” behaviors? Could some of these behaviors represent actual seizures, which may have clinical implications?
These observations and questions have been raised by pediatric anesthesiologists since sevoflurane was first used in pediatric patients in the late 90s and early 00s.(1) Building on this prior research, Drs. Jerry Chao, Elissa Yozawitz (the neonatal neurologist whose paper from the NEJM(2) was featured in a recent PAAD on pediatric seizures) and colleagues studied the epileptogenicity of sevoflurane further and estimated the incidence of seizure-like movements, seizures, and abnormal video-electroencephalogram (EEG) patterns in a cohort of full term infants undergoing noncardiac surgery.(3) The central research question was to assess – using a full head montage EEG – whether clinical or electrographic seizures would be identifiable during sevoflurane induction when high doses of sevoflurane are administered during the course of routine clinical care. The investigators observed that no infants developed seizures during sevoflurane induction, but abnormal EEG changes were observed 4/54 infants (estimated incidence of 7.4%; 95% confidence interval [2.1% - 17.9%]) in their sample cohort, suggesting that epileptiform EEG changes are not uncommon and may occur in otherwise healthy infants presenting for anesthesia with no history of neurological disorders.
Drs. Chao, Yozawitz and colleagues then performed a systematic review of the literature(4,5) and found that the estimated prevalence of abnormal EEG patterns during pediatric sevoflurane anesthesia in prior studies was 30.9%; 95% confidence interval [27.3% - 34.5%] in a pooled sample size of 621 subjects, but the precision of the estimate was affected by heterogeneity and bias that exists within and between studies. For example, there was heterogeneity with regard to (1) whether midazolam was administered (which is known to affect the development of epileptiform EEG changes), (2) subject age, and (3) phase of anesthesia studied. Importantly, the individual studies had great variability in the numbers of EEG electrodes used and did not use consistent terminology for epileptiform and other EEG changes.
The investigators conclude that in order to improve the rigor and reproducibility of future pediatric EEG research, a standard set of definitions and classifications of abnormal EEG findings is necessary. The team – including neonatal and pediatric neurologists, electrophysiologists, and epidemiologists/biostatisticians – propose a simplified version of the International League Against Epilepsy (ILAE) and the American Clinical Neurophysiology Society (ACNS) classifications to help introduce a standard approach to classifying abnormal EEG that could be useful for future research, systematic reviews, and meta-analyses.
The proposed classification system would be as follows:
1) No epileptiform discharges or electrographic seizures.
a. Normal EEG.
b. Focal or generalized slowing, including rhythmic delta activity. Focal slowing is defined as abnormal slower frequencies occurring over part of the head and abnormal generalized slowing, including non-evolving rhythmic delta (0-3 Hz) activity have been classified as epileptiform findings in some studies. However, this is not the case and these patterns should not be classified as epileptiform discharges.
2) Interictal epileptiform discharges, defined as spikes, polyspikes, sharp waves, or spike and wave complexes, reflecting possible areas of cortical irritability and potential epileptogenicity that are
a. Isolated/sporadic epileptiform discharges, meaning they occur singly without repetition or periodic recurrence, or
b. Repetitive/periodic epileptiform discharges, meaning they occur repetitively, sometimes regularly at a specific frequency
c. Electrographic seizures or electroclinical seizures, with electrographic seizure referring to observed salient EEG findings alone without clinical manifestations (e.g., no convulsions or other motor behaviors), in contrast to electroclinical seizures, which are characterized by both salient EEG features and clinical manifestations such as tonic or clonic movements. Despite this distinction, electrographic and electroclinical findings are included in the same category because both entities ultimately describe seizure activity, regardless of whether obvious clinical manifestations are present.
PS from Myron: How do you treat patients with known seizure disorders perioperatively? Specifically do you avoid sevoflurane? Do you avoid other anesthetic drugs that may or may not be epileptogenic (ketamine? propofol? local anesthetics?) Send me your thoughts and I will post in the Friday Reader Response.
References
1. Constant I, Seeman R, Murat I. Sevoflurane and epileptiform EEG changes. PaediatrAnaesth 2005;15:266-74.
2. Yozawitz E. Neonatal Seizures. N Engl J Med 2023;388:1692-700.
3. Chao JY, Legatt AD, Yozawitz EG, Adams DC, Delphin ES, Shinnar S. Electroencephalographic Findings and Clinical Behavior During Induction of Anesthesia With Sevoflurane in Human Infants: A Prospective Observational Study. Anesth Analg 2020;130:e161-e4.
4. Chao JY, Tam M, Ferrera A, Ivenitsky D, Gizzo L, Schwartz R, Legatt AD, Yozawitz EG, Lo Y, Li G, Shinnar S. Epileptiform discharges, electrographic seizures, and electroclinical seizures during paediatric sevoflurane anaesthesia: a systematic review and proposal for standard definitions. Br J Anaesth 2023;130:e18-e21.
5. Chao JY, Yozawitz EG, Legatt AD, Schwartz R, Lo Y, Li G, Shinnar S. Epileptiform discharges, electrographic seizures, and electroclinical seizures during paediatric sevoflurane anaesthesia. Response to Br J Anaesth 2023; 130: e423-4. Br J Anaesth 2023.