Background: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. Methods: Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. Results: Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95% CI, 2.57 to 7.4; P < 0.001), endotracheal tube use (odds ratio, 1.78; 95% CI, 1.16 to 2.73; P = 0.008), and propofol bolus for airway placement after sevoflurane induction (odds ratio, 2.92; 95% CI, 1.78 to 4.8; P < 0.001), and less likely with use of muscle relaxant for intubation (odds ratio, 0.67; 95% CI, 0.46 to 0.99; P = 0.046]. Expired sevoflurane was higher in patients with isoelectric events during preincision (mean difference, 0.2%; 95% CI, 0.1 to 0.4; P = 0.005) and surgical maintenance (mean difference, 0.2%; 95% CI, 0.1 to 0.3; P = 0.002). Isoelectric events were associated with moderate (8 of 12, 67%) and severe hypotension (11 of 18, 61%) during preincision (odds ratio, 4.6; 95% CI, 1.30 to 16.1; P = 0.018) (odds ratio, 3.54; 95% CI, 1.27 to 9.9; P = 0.015) and surgical maintenance (odds ratio, 3.64; 95% CI, 1.71 to 7.8; P = 0.001) (odds ratio, 7.1; 95% CI, 1.78 to 28.1; P = 0.005), and lower Pediatric Quality of Life scores at baseline in patients 0 to 12 months (median of differences, –3.5; 95% CI, –6.2 to –0.7; P = 0.008) and 25 to 36 months (median of differences, –6.3; 95% CI, –10.4 to –2.1; P = 0.003) and 30-day follow-up in 0 to 12 months (median of differences, –2.8; 95% CI, –4.9 to 0; P = 0.036). Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs. propofol). Conclusions: Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New:

Biomedical research has been struck with the problem of study findings that are not reproducible. With the advent of large databases and powerful statistical software, it has become easier to find associations and form conclusions from data without forming an a‐priori hypothesis. This approach may yield associations without clinical relevance, false positive findings, or biased results due to “fishing” for the desired results. To improve reproducibility, transparency, and validity among clinical trials, the National Institute of Health recently updated its grant application requirements, which mandates registration of clinical trials and submission of the original statistical analysis plan (SAP) along with the research protocol. Many leading journals also require the SAP as part of the submission package. The goal of this article and the companion article detailing the SAP of an actual research study is to provide a practical guide on writing an effective SAP. We describe the what, why, when, where, and who of a SAP, and highlight the key contents of the SAP.

Intraoperative electroencephalography (EEG) monitoring under pediatric anesthesia has begun to attract increasing interest, driven by the availability of pediatric-specific EEG monitors and the realization that traditional dosing methods based on patient movement or changes in hemodynamic response often lead to imprecise dosing, especially in younger infants who may experience adverse events (e.g., hypotension) due to excess anesthesia. EEG directly measures the effects of anesthetics on the brain, which is the target end-organ responsible for inducing loss of consciousness. Over the past ten years, research on anesthesia and computational neuroscience has improved our understanding of intraoperative pediatric EEG monitoring and expanded the utility of EEG in clinical practice. We now have better insights into neurodevelopmental changes in the developing pediatric brain, functional connectivity, the use of non-proprietary EEG parameters to guide anesthetic dosing, epileptiform EEG changes during induction, EEG changes from spinal/regional anesthesia, EEG discontinuity, and the use of EEG to improve clinical outcomes. This review article summarizes the recent literature on EEG monitoring in perioperative pediatric anesthesia, highlighting several of the topics mentioned above.