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Propofol-based total intravenous anesthesia (TIVA) is gaining popularity for pediatric surgical procedures. 1 While TIVA has been popular for many years in adult ambulatory surgery and pediatric radiological imaging, inhalational anesthesia has remained the mainstay for pediatric surgical anesthesia, especially in infants. Nevertheless, TIVA is the preferred technique for selecting infant surgical populations, including those at risk of malignant hyperthermia or emergence delirium and those requiring neurophysiological monitoring (spine,

BACKGROUND: In infants and young children, anesthetic dosing is based on population pharmacokinetics and patient hemodynamics not on patient-specific brain activity. Electroencephalography (EEG) provides insight into brain activity during anesthesia. The primary goal of this prospective observational pilot study was to assess the prevalence of isoelectric EEG events—a sign of deep anesthesia—in infants and young children undergoing general anesthesia using sevoflurane or propofol infusion for maintenance. METHODS: Children 0–37 months of age requiring general anesthesia for surgery excluding cardiac, intracranial, and emergency cases were enrolled by age: 0–3, 4–6, 7–12, 13–18, and 19–37 months. Anesthesia was maintained with sevoflurane or propofol infusion. EEG was recorded from induction to extubation. Isoelectric EEG events (amplitude <20 µV, lasting ≥2 seconds) were characterized by occurrence, number, duration, and percent of isoelectric EEG time over anesthetic time. Associations with patient demographics, anesthetic, and surgical factors were determined. RESULTS: Isoelectric events were observed in 63% (32/51) (95% confidence interval [CI], 49–76) of patients. The median (interquartile range [IQR]) number of isoelectric events per patient was 3 (0–31), cumulative isoelectric time per patient was 12 seconds (0–142 seconds), isoelectric time per event was 3 seconds (0–4 seconds), and percent of total isoelectric over anesthetic time was 0.1% (0%–2.2%). The greatest proportion of isoelectric events occurred between induction and incision. Isoelectric events were associated with higher American Society of Anesthesiologists (ASA) physical status, propofol bolus, endotracheal tube use, and lower arterial pressure during surgical phase. CONCLUSIONS: Isoelectric EEG events were common in infants and young children undergoing sevoflurane or propofol anesthesia. Although the clinical significance of these events remains uncertain, they suggest that dosing based on population pharmacokinetics and patient hemodynamics is often associated with unnecessary deep anesthesia during surgical procedures.

Background Propofol total intravenous anesthesia (TIVA) is increasingly popular in pediatric anesthesia, but education on its use is variable and over‐dosage adverse events are not uncommon. Recent work suggests that electroencephalogram (EEG) parameters can guide propofol dosing in the pediatric population. This education quality improvement project aimed to implement a standardized EEG TIVA training program over 12 months in a large pediatric anesthesia division. Methods The division consisted of 63 faculty, 11 clinical fellows, 32 residents, and 28 nurse anesthetists at the Children's Hospital of Philadelphia. The program was assessed for effectiveness (a significant improvement in EEG knowledge scores), scalability (training 50% of fellows and staff), and sustainability (recurring EEG lectures for 80% of rotating residents and 100% of new fellows and staff). The key drivers included educational content development (lectures, articles, and hand‐outs), training a cohort of EEG TIVA trainers, intraoperative teaching (teaching points and dosing tables), decision support tools (algorithms and anesthesia electronic record pop‐ups), and knowledge tests (written exam and verbal quiz during cases). Results Over 12 months, 78.5% of the division (62/79) completed EEG training and test scores improved (mean score 38% before training vs 59% after training, p < .001). Didactic lectures were given to 100% of the fellows, 100% (11/11) of new staff, and 80% (4/5 blocks) of rotating residents. Conclusion This quality improvement education project successfully trained pediatric anesthesia faculty, staff, residents, and fellows in EEG‐guided TIVA. The training program was effective, scalable, and sustainable over time for newly hired faculty staff and rotating fellows and residents.

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. We 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 for surgery using sevoflurane or propofol anesthetic. Frontal 4-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life (PedsQL) variables were analyzed for association with isoelectric events. Results. Isoelectric events occurred in 32% (206/648) of patients, varied significantly among sites (9-88%), and were most prevalent during pre-incision (117/628, 19%) and surgical maintenance (117/643, 18%). Isoelectric events were more likely with [odds ratio-OR (95% confidence interval-CI)] infants &lt; 3 months [4.4 (2.57-7.4) p&lt;0.001], endotracheal tube use [1.78 (1.16-2.73) p=0.008], propofol bolus for airway placement after sevoflurane induction [2.92 (1.78-4.8) p&lt;0.001], and less likely with use of muscle relaxant for intubation [0.67 (0.46-0.99) p=0.046]. Expired sevoflurane was higher in patients with isoelectric events [mean difference (95% CI)] during pre-incision [0.2% (0.1, 0.4) p=0.005] and surgical maintenance [0.2% (0.1, 0.3) p=0.002]. Isoelectric events were associated with moderate (8/12, 67%) and severe hypotension (11/18, 61%) during pre-incision [OR: 4.6 (1.30-16.1) p=0.018; 3.54 (1.27, 9.9) p=0.015] and surgical maintenance [OR: 3.64 (1.71-7.8) p=0.001; 7.1 (1.78- 28.1) p=0.005], and lower PedsQL scores [median of differences (95% CI)] at baseline in patients 0-12 [-3.5 (-6.2, -0.7) p=0.008] and 25-36 months [-6.3 (-10.4, -2.1) p=0.003] and 30-day follow-up in 0-12 months [-2.8 (-4.9, 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.

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.

Introduction Pain assessment is challenging in neonates. Behavioral and physiological pain scales do not assess neocortical nociception, essential to pain encoding and central pain pathway development. Functional near‐infrared spectroscopy (fNIRS) can assess neocortical activation to noxious stimuli from changes in oxy‐(HbO) and total‐hemoglobin concentrations (HbT). This study aims to assess fNIRS nociceptive functional activation in the prefrontal cortex of neonates undergoing circumcision through changes in HbO and HbT, and the correlation between changes in fNIRS and Neonatal Infant Pain Scale (NIPS), a behavioral pain assessment scale. Methods In healthy term neonates, HbO, HbT, and NIPS were recorded during sequential circumcision events 1‐Prep before local anesthetic injection; 2‐Local anesthetic injection; 3‐Prep before incision; 4‐Oral sucrose; 5‐Incision; 6‐Gomco (hemostatic device) attached; 7‐Gomco twisted on; and 8‐Gomco removed. fNIRS and NIPS changes after each event were assessed with Wilcoxon signed‐rank test and summarized as median and interquartile range (IQR). Changes in fNIRS vs. NIPS were correlated with Spearman coefficient. Results In 31 neonates fNIRS increased (median [IQR] µmol/L) with noxious events: Local injection (HbO: 1.1 [0.5, 3.1], p < .001; HbT: 2.3 [0.2, 7.6], p < .001), Gomco attached (HbO: 0.7 [0.1, 1.7], p = .002; HbT: 0.7 [−0.2, 2.9], p = .02), and Gomco twisted on (HbO: 0.5 [−0.2, 1.7], p = .03; HbT: 0.8 [−0.1, 3.3], p = .02). fNIRS decreased with non‐noxious event: Prep before incision (HbO: −0.6 [−1.2, −0.2] p < .001; HbT: −1 [−1.8, −0.4], p < .001). Local anesthetic attenuated fNIRS increases to subsequent sharp stimuli. NIPS increased with subsequent sharp stimuli despite local anesthetic. Although fNIRS and NIPS changed in the same direction, there was not a strong correlation between them. Conclusions During neonatal circumcision, changes in fNIRS differed between different types of painful stimuli, which was not the case for NIPS, suggesting that fNIRS may complement NIPS to assess the quality of pain.

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