Electroencephalographic Indices for Clinical Endpoints during Propofol Anesthesia in Infants: An Early-phase Propofol Biomarker-finding Study.

BACKGROUND: Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. METHODS: This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. RESULTS: Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 µg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) µg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). CONCLUSIONS: SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

The Utility of Electroencephalograhy in Guiding General Anesthesia in Children.

Traditional pediatric anesthetic dosing using pharmacokinetic estimates based on age and weight is often imprecise, frequently leading to oversedation. Intraoperative electroencephalography (EEG) allows visualization of the brain's response to anesthetic agents in real time, facilitating precise titration of anesthetic drug doses optimized for the individual child. The goal of EEG-guided anesthesia management is to maintain an optimal state of hypnosis during various stages of the procedure while minimizing hemodynamic instability and other adverse effects of anesthesia. This is especially important in children with less predictable anesthetic requirements, such as children with atypical neurodevelopment, altered levels of consciousness before anesthesia, or those receiving total intravenous anesthesia, neuromuscular blockers, or a combination of anesthetic agents with different mechanisms of actions. Children with limited cardiorespiratory reserves and those undergoing high-risk procedures such as cardiopulmonary bypass also benefit from EEG guidance as they have a narrower therapeutic window for optimal anesthetic dosing. Various processed EEG (pEEG) monitors are available for intraoperative monitoring in children. These monitors display a pEEG index based on the manufacturer's algorithm, purportedly indicating the patient's hypnotic state. Due to differences in developmental neurophysiology and EEG dynamics in children, pEEG indices may not always reliably indicate the hypnotic state, especially in neonates and infants. Learning to interpret nonproprietary EEG parameters including the raw EEG, spectral-edge frequency 95% (SEF95), and density spectral array can prevent overreliance on pEEG indices. This review provides an overview of the advantages of EEG guidance during clinical anesthesia, including potential reduction in anesthetic dosage, prevention of EEG suppression, and reduction in peri-operative adverse events. We describe the use of nonproprietary EEG parameters in guiding anesthesia in children for various clinical end points including laryngoscopy, surgical incision, and maintenance of anesthesia, as well as sedation. We illustrate these principles with various case examples commonly encountered during pediatric anesthesia. Lastly, we discuss strategies to expand intraoperative EEG monitoring in children through education and training programs, as well as advocate for further research to assess clinical outcomes associated with EEG guidance to support its routine use in clinical care.

γ-Aminobutyric Acid-Ergic Development Contributes to the Enhancement of Electroencephalogram Slow-Delta Oscillations Under Volatile Anesthesia in Neonatal Rats.

BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.

The Nurse-Implemented Chronotherapeutic Bundle in Critically Ill Children, RESTORE Resilience (R2): Pilot Testing in a Two-Phase Cohort Study, 2017-2021.

OBJECTIVES: Pilot test the nurse-led chronotherapeutic bundle in critically ill children, RESTORE Resilience (R2). DESIGN: A two-phase cohort study was carried out from 2017 to 2021. SETTING: Two similarly sized and organized PICUs in the United States. PATIENTS: Children 6 months to 17 years old who were mechanically ventilated for acute respiratory failure. INTERVENTIONS: R2 seven-item chronotherapeutic bundle, including: 1) replication of child's pre-hospital daily routine (i.e., sleep/wake, feeding, activity patterns); 2) cycled day-night light/sound modulation; 3) minimal effective sedation; 4) night fasting with bolus enteral daytime feedings; 5) early progressive mobility; 6) nursing care continuity; and 7) parent diaries. MEASUREMENTS AND MAIN RESULTS: Children underwent environmental (light, sound) and patient (actigraphy, activity log, salivary melatonin, electroencephalogram) monitoring. Parents completed the Child's Daily Routine and Sleep Survey (CDRSS) and Family-Centered Care Scale. The primary outcome was post-extubation daytime activity consolidation (Daytime Activity Ratio Estimate [DARE]). Twenty baseline-phase (2017-2019) and 36 intervention-phase (2019-2021) participants were enrolled. During the intervention phase, nurses used the CDRSS to construct children's PICU schedules. Overall compliance with nurse-implemented R2 elements 1-5 increased from 18% (interquartile range, 13-30%) at baseline to 63% (53-68%) during the intervention phase (p < 0.001). Intervention participants were exposed to their pre-hospitalization daily routine (p = 0.002), cycled day-night light/sound modulation (p < 0.001), and early progressive mobility on more PICU days (p = 0.02). Sedation target identification, enteral feeding schedules, and nursing care continuity did not differ between phases. Parent diaries were seldom used. DARE improved during the intervention phase and was higher pre-extubation (median 62% vs. 53%; p = 0.04) but not post-extubation (62% vs. 57%; p = 0.56). CONCLUSIONS: In the PICU, implementation of an individualized nurse-implemented chronotherapeutic bundle is feasible. Children who received the R2 bundle had increased pre-extubation daytime activity consolidation compared to children receiving usual care. Given variation in protocol adherence, further R2 testing should include interprofessional collaboration, pragmatic trial design, and implementation science strategies.

Implementation of an electroencephalogram-guided propofol anesthesia practice in a large academic pediatric hospital: A quality improvement project.

BACKGROUND: Propofol-based total intravenous anesthesia is gaining popularity in pediatric anesthesia. Electroencephalogram can be used to guide propofol dosing to the individual patient to mitigate against overdosing and adverse events. However, electroencephalogram interpretation and propofol pharmacokinetics are not sufficiently taught in training programs to confidently deploy electroencephalogram-guided total intravenous anesthesia. AIMS: We conducted a quality improvement project with the smart aim of increasing the percentage of electroencephalogram-guided total intravenous anesthesia cases in our main operating room from 0% to 80% over 18 months. Balancing measures were number of total intravenous anesthesia cases, emergence times, and perioperative emergency activations. METHODS: The project key drivers were education, equipment, and electronic health record modifications. Plan-Do-Study-Act cycles included: (1) providing journal articles, didactic lectures, intraoperative training, and teaching documents; (2) scheduling electroencephalogram-guided total intravenous anesthesia teachers to train faculty, staff, and fellows for specific cases and to assess case-based knowledge; (3) adding age-based propofol dosing tables and electroencephalogram parameters to the electronic health record (EPIC co, Verona, WI); (4) procuring electroencephalogram monitors (Sedline, Masimo Inc). Electroencephalogram-guided total intravenous anesthesia cases and balancing measures were identified from the electronic health record. The smart aim was evaluated by statistical process control chart. RESULTS: After the four Plan-Do-Study-Act cycles, electroencephalogram-guided total intravenous anesthesia increased from 5% to 75% and was sustained at 72% 9 months after project completion. Total intravenous anesthesia cases/mo and number of perioperative emergency activations did not change significantly from start to end of the project, while emergence time for electroencephalogram-guided total intravenous anesthesia was greater statistically but not clinically (total intravenous anesthesia without electroencephalogram [16 ± 10 min], total intravenous anesthesia with electroencephalogram [18 ± 9 min], sevoflurane [17 ± 9 min] p < .001). CONCLUSION: Quality improvement methods may be deployed to adopt electroencephalogram-guided total intravenous anesthesia in a large academic pediatric anesthesia practice. Keys to success include education, in operating room case training, scheduling teachers with learners, electronic health record modifications, and electroencephalogram devices and supplies.

A Narrative Review of Multiinstitutional Data Registries of Pediatric Congenital Heart Disease in Pediatric Cardiac Anesthesia and Critical Care Medicine.

Congenital heart disease (CHD) is one of the most common birth anomalies. While the care of children with CHD has improved over recent decades, children with CHD who undergo general anesthesia remain at increased risk for morbidity and mortality. Electronic health record systems have enabled institutions to combine data on the management and outcomes of children with CHD in multicenter registries. The application of descriptive analytics methods to these data can improve clinicians' understanding and care of children with CHD. This narrative review covers efforts to leverage multicenter data registries relevant to pediatric cardiac anesthesia and critical care to improve the care of children with CHD.

Reducing the environmental impact of mask inductions in children: A quality improvement report.

BACKGROUND: Inhalational anesthetic agents are potent greenhouse gases with global warming potential that far exceed that of carbon dioxide. Traditionally, pediatric inhalation inductions are achieved with a volatile anesthetic delivered to the patient in oxygen and nitrous oxide at high fresh gas flows. While contemporary volatile anesthetics and anesthesia machines allow for a more environmentally conscious induction, practice has not changed. We aimed to reduce the environmental impact of our inhalation inductions by decreasing the use of nitrous oxide and fresh gas flows. METHODS: Through a series of four plan-do-study-act cycles, the improvement team used content experts to demonstrate the environmental impact of the current inductions and to provide practical ways to reduce this, by focusing on nitrous oxide use and fresh gas flows, with visual reminders introduced at point of delivery. The primary measures were the percentage of inhalation inductions that used nitrous oxide and the maximum fresh gas flows/kg during the induction period. Statistical process control charts were used to measure improvement over time. RESULTS: 33 285 inhalation inductions were included over a 20-month period. nitrous oxide use decreased from 80% to <20% and maximum fresh gas flows/kg decreased from a rate of 0.53 L/min/kg to 0.38 L/min/kg, an overall reduction of 28%. Reduction in fresh gas flows was greatest in the lightest weight groups. Induction times and behaviors remained unchanged over the duration of this project. CONCLUSIONS: Our quality improvement group decreased the environmental impact of inhalation inductions and created cultural change within our department to sustain change and foster the pursuit of future environmental efforts.

Co-administration of Ketamine in Pediatric Patients with Neurologic Conditions at Risk for Intracranial Hypertension.

BACKGROUND: Ketamine has traditionally been avoided as an induction agent for tracheal intubation in patients with neurologic conditions at risk for intracranial hypertension due to conflicting data in the literature. The objective of this study was to evaluate and compare the effects of ketamine versus other medications as the primary induction agent on peri-intubation neurologic, hemodynamic and respiratory associated events in pediatric patients with neurologic conditions at risk for intracranial hypertension. METHODS: This retrospective observational study enrolled patients < 18 years of age at risk for intracranial hypertension who were admitted to a quaternary children's hospital between 2015 and 2020. Associated events included neurologic, hemodynamic and respiratory outcomes comparing primary induction agents of ketamine versus non-ketamine for tracheal intubation. RESULTS: Of 143 children, 70 received ketamine as the primary induction agent prior to tracheal intubation. Subsequently after tracheal intubation, all the patients received adjunct analgesic and sedative medications (fentanyl, midazolam, and/or propofol) at doses that were inadequate to induce general anesthesia but would keep them comfortable for further diagnostic workup. There were no significant differences between associated neurologic events in the ketamine versus non-ketamine groups (p = 0.42). This included obtaining an emergent computed tomography scan (p = 0.28), an emergent trip to the operating room within 5 h of tracheal intubation (p = 0.6), and the need for hypertonic saline administration within 15 min of induction drug administration for tracheal intubation (p = 0.51). There were two patients who had clinical and imaging evidence of herniation, which was not more adversely affected by ketamine compared with other medications (p = 0.49). Of the 143 patients, 23 had pre-intubation and post-intubation intracranial pressure values recorded; 11 received ketamine, and 3 of these patients had intracranial hypertension that resolved or improved, whereas the remaining 8 children had intracranial pressure within the normal range that was not exacerbated by ketamine. There were no significant differences in overall associated hemodynamic or respiratory events during tracheal intubation and no 24-h mortality in either group. CONCLUSIONS: The administration of ketamine as the primary induction agent prior to tracheal intubation in combination with other agents after tracheal intubation in children at risk for intracranial hypertension was not associated with an increased risk of peri-intubation associated neurologic, hemodynamic or respiratory events compared with those who received other induction agents.

Quantitative electroencephalogram in term neonates under different sleep states.

Electroencephalogram (EEG) can be used to assess depth of consciousness, but interpreting EEG can be challenging, especially in neonates whose EEG undergo rapid changes during the perinatal course. EEG can be processed into quantitative EEG (QEEG), but limited data exist on the range of QEEG for normal term neonates during wakefulness and sleep, baseline information that would be useful to determine changes during sedation or anesthesia. We aimed to determine the range of QEEG in neonates during awake, active sleep and quiet sleep states, and identified the ones best at discriminating between the three states. Normal neonatal EEG from 37 to 46 weeks were analyzed and classified as awake, quiet sleep, or active sleep. After processing and artifact removal, total power, power ratio, coherence, entropy, and spectral edge frequency (SEF) 50 and 90 were calculated. Descriptive statistics were used to summarize the QEEG in each of the three states. Receiver operating characteristic (ROC) curves were used to assess discriminatory ability of QEEG. 30 neonates were analyzed. QEEG were different between awake vs asleep states, but similar between active vs quiet sleep states. Entropy beta, delta2 power %, coherence delta2, and SEF50 were best at discriminating awake vs active sleep. Entropy beta had the highest AUC-ROC ≥ 0.84. Entropy beta, entropy delta1, theta power %, and SEF50 were best at discriminating awake vs quiet sleep. All had AUC-ROC ≥ 0.78. In active sleep vs quiet sleep, theta power % had highest AUC-ROC > 0.69, lower than the other comparisons. We determined the QEEG range in healthy neonates in different states of consciousness. Entropy beta and SEF50 were best at discriminating between awake and sleep states. QEEG were not as good at discriminating between quiet and active sleep. In the future, QEEG with high discriminatory power can be combined to further improve ability to differentiate between states of consciousness.

Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study.

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.

Functional near-infrared spectroscopy to assess pain in neonatal circumcisions.

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.

Implementation of an electroencephalogram-guided propofol anesthesia education program in an academic pediatric anesthesia practice.

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.

Decadron, Diamox, and Zantac: A Novel Combination for Ventricular Shunt Failure in Pediatric Neurosurgical Patients.

OBJECTIVE: Cerebral ventricular shunt failure is common and presents with symptoms that range from headaches to death. The combination of Diamox (acetazolamide), Decadron (dexamethasone), and Zantac (ranitidine) (DDZ) is used at our institution to medically stabilize pediatric patients presenting with symptomatic shunt failure before shunt revision. We describe our experience of this drug combination as a temporizing measure to decrease symptoms associated with shunt failure. METHODS: We performed a single-center retrospective chart review of patients younger than 18 years with ventricular shunt failure who underwent a shunt revision between January 2015 to October 2017 and received DDZ before surgery. The outcome variables evaluated included pre-DDZ and post-DDZ clinical symptoms, pain scores, and vital signs. RESULTS: There were 112 cases that received DDZ before shunt revision. The 4 most commonly reported symptoms were analyzed. Headache was observed in 42 cases pre-DDZ, and post-DDZ there was a 71% reduction in headache (P < 0.0001); emesis was reported pre-DDZ in 76 cases, and post-DDZ there was an 83% reduction (P < 0.0001); irritability was noted pre-DDZ in 30 cases, and post-DDZ there was a 77% reduction (P = 0.0003); lethargy pre-DDZ was observed in 60 cases, and post-DDZ 73% demonstrated improvement (P < 0.0001). Maximum pain scores significantly decreased post-DDZ (P < 0.0001). Heart rate, systolic, and diastolic blood pressures significantly decreased post-DDZ (P < 0.0001, P < 0.0001, P = 0.0002, respectively). CONCLUSIONS: The combination of Decadron, Diamox, and Zantac is a novel treatment for ventricular shunt failure that may temporarily improve symptoms in patients awaiting shunt revision. Future studies could compare efficacy with other medical treatments.

Prevalence of Isoelectric Electroencephalography Events in Infants and Young Children Undergoing General Anesthesia.

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.

An approach to using pharmacokinetics and electroencephalography for propofol anesthesia for surgery in infants.

Safe and effective techniques for propofol total intravenous anesthesia (TIVA) in infants are not well imbedded into clinical practice, resulting in practitioner unfamiliarity and potential for over- and under-dosing. In this education article, we describe our approach to TIVA dosing in infants and toddlers (birth to 36 months) which combines the use of pharmacokinetic models with EEG multi-parameter analysis. Pharmacokinetic models describe propofol and remifentanil effect site concentrations (Ce) over time in different age groups for a given dosing regimen. These models display substantial biological variability between individuals within age groups, impeding their application to clinical practice. Nevertheless, they reveal that younger infants require a higher propofol loading dose, a lower propofol maintenance dose, and a higher remifentanil dose compared with older infants. Proprietary EEG indices (eg, Bispectral Index) can serve as a biomarker of propofol Ce in adults and children to guide dosing to the individual patient; however, they are not recommended for infants as their validity remains uncertain this population. In our experience, EEG waveforms and processed parameters can reflect propofol Ce in infants, reflected by spectral edge frequency (SEF), density spectral array (DSA), and waveform patterns. In our practice, we use a "lookup table" of age-based dosing regimens or target-controlled infusion (TCI) based on the pharmacokinetic models to deliver a target propofol Ce and co-administer remifentanil and/or regional technique for analgesia. We analyze Electroencephalogram (EEG) waveforms, SEF, and DSA to adjust the propofol dose or TCI target concentration to the individual infant. EEG analysis mitigates against biological variability inherent in the pharmacokinetic models and has improved our experience with TIVA for infants.

Guide to the statistical analysis plan.

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.

Statistical Analysis Plan for "An international multicenter study of isoelectric electroencephalography events in infants and young children during anesthesia for surgery".

This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background; (b) Definitions of protocol violations; (c) Definitions of objectives and other terms; (d) Variables for analyses; (e) Handling of missing data and study bias; (f) Statistical analysis of the primary and secondary study outcomes; (g) Reporting of study results; and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan.