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.

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.

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.

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.

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.

Perioperative near-infrared spectroscopy cerebral oxygen saturation in symptomatic pediatric hydrocephalus patients at risk for intracranial hypertension.

OBJECTIVE: The lack of a continuous, noninvasive modality for monitoring intracranial pressure (ICP) is a major obstacle in the care of pediatric patients with hydrocephalus who are at risk for intracranial hypertension. Intracranial hypertension can lead to cerebral ischemia and brain tissue hypoxia. In this study, the authors evaluated the use of near-infrared spectroscopy (NIRS) to measure regional cerebral oxygen saturation (rSO2) in symptomatic pediatric patients with hydrocephalus concerning for elevated ICP. METHODS: The authors evaluated the NIRS rSO2 trends in pediatric patients presenting with acute hydrocephalus and clinical symptoms of intracranial hypertension. NIRS rSO2 values were recorded hourly before and after neurosurgical intervention. To test for significance between preoperative and postoperative values, the authors constructed a linear regression model with the rSO2 values as the outcome and pre- and postsurgery cohorts as the independent variable, adjusted for age and sex, and used the generalized estimating equation method to account for within-subject correlation. RESULTS: Twenty-two pediatric patients underwent NIRS rSO2 monitoring before and after CSF diversion surgery. The mean durations of NIRS rSO2 recording pre- and postoperatively were 13.95 and 26.82 hours, respectively. The mean pre- and postoperative rSO2 values were 73.84% and 80.65%, respectively, and the adjusted mean difference estimated from the regression model was 5.98% (adjusted p < 0.0001), suggestive of improved cerebral oxygenation after definitive neurosurgical CSF diversion treatment. Postoperatively, all patients returned to baseline neurological status with no clinical symptoms of elevated ICP. CONCLUSIONS: Cerebral oxygenation trends measured by NIRS in symptomatic pediatric hydrocephalus patients with intracranial hypertension generally improve after CSF diversion surgery.

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.