Anesthetic-sparing effect of dexmedetomidine during total intravenous anesthesia for children undergoing dental surgery: A randomized controlled trial.

BACKGROUND: Dexmedetomidine, an α2-adrenergic agonist, reduces propofol and remifentanil requirements when used as an adjunct to total intravenous anesthesia in adults, but studies in a pediatric population are sparse. This study investigates the magnitude of dose-sparing effects of a postinduction dexmedetomidine bolus on propofol and remifentanil requirements during pediatric surgery. METHODS: In this randomized, double-blind, controlled trial, children aged 2-10 years undergoing elective dental surgery were assigned to one of four groups: placebo, 0.25 mcg/kg dexmedetomidine, 0.5 mcg/kg dexmedetomidine, and 1 mcg/kg dexmedetomidine. Maintenance with fixed-ratio propofol and remifentanil total intravenous anesthesia followed a bispectral index (BIS)-guided algorithm designed to maintain a stable depth of anesthesia. The primary outcomes were time-averaged maintenance infusion rates of propofol and remifentanil. Secondary outcomes in the postanesthetic care unit included sedation scores, pain scores, and time to discharge. RESULTS: Data from 67 patients were available for analysis. The median [interquartile range] propofol infusion rate was lower in the 1 mcg/kg dexmedetomidine group (180 [164-185] mcg/kg/min) versus placebo (200 [178-220] mcg/kg/min): percent change -10.0%; 95% CI -2.4 to -19.8; p = 0.013. The remifentanil infusion rate was also lower in the 1 mcg/kg dexmedetomidine group (0.089 [0.080, 0.095] mcg/kg/min) versus placebo (0.103 [0.095, 0.106] mcg/kg/min): percent change, -13.7%; 95% CI -5.47 to -21.0; p = .022. However, neither propofol nor remifentanil infusion rates were significantly different in the 0.25 or 0.5 mcg/kg dexmedetomidine groups. In the postanesthesia care unit, there were no differences in pain or sedation scores, and time to discharge was not significantly prolonged in any dexmedetomidine group. CONCLUSION: Dexmedetomidine 1 mcg/kg reduced the propofol and remifentanil requirements during maintenance of anesthesia in children when administered as a postinduction bolus. TRIALS REGISTRATION: ClinicalTrials.gov: NCT03422978, date of registration 2018-02-06.

Prediction Model Performance With Different Imputation Strategies: A Simulation Study Using a North American ICU Registry.

OBJECTIVES: To evaluate the performance of pragmatic imputation approaches when estimating model coefficients using datasets with varying degrees of data missingness. DESIGN: Performance in predicting observed mortality in a registry dataset was evaluated using simulations of two simple logistic regression models with age-specific criteria for abnormal vital signs (mentation, systolic blood pressure, respiratory rate, WBC count, heart rate, and temperature). Starting with a dataset with complete information, increasing degrees of biased missingness of WBC and mentation were introduced, depending on the values of temperature and systolic blood pressure, respectively. Missing data approaches evaluated included analysis of complete cases only, assuming missing data are normal, and multiple imputation by chained equations. Percent bias and root mean square error, in relation to parameter estimates obtained from the original data, were evaluated as performance indicators. SETTING: Data were obtained from the Virtual Pediatric Systems, LLC, database (Los Angeles, CA), which provides clinical markers and outcomes in prospectively collected records from 117 PICUs in the United States and Canada. PATIENTS: Children admitted to a participating PICU in 2017, for whom all required data were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Simulations demonstrated that multiple imputation by chained equations is an effective strategy and that even a naive implementation of multiple imputation by chained equations significantly outperforms traditional approaches: the root mean square error for model coefficients was lower using multiple imputation by chained equations in 90 of 99 of all simulations (91%) compared with discarding cases with missing data and lower in 97 of 99 (98%) compared with models assuming missing values are in the normal range. Assuming missing data to be abnormal was inferior to all other approaches. CONCLUSIONS: Analyses of large observational studies are likely to encounter the issue of missing data, which are likely not missing at random. Researchers should always consider multiple imputation by chained equations (or similar imputation approaches) when encountering even only small proportions of missing data in their work.

Blood pressure nomograms for children undergoing general anesthesia, stratified by age and anesthetic type, using data from a retrospective cohort at a tertiary pediatric center.

Reference values for non-invasive blood pressure (NIBP) are available for children undergoing general anesthesia, but have not been analyzed by type of anesthetic. This study establishes age-specific pediatric NIBP reference values, stratified by anesthetic type: inhalational anesthesia (IHA), total intravenous anesthesia (TIVA), and mostly intravenous anesthesia (MIVA, an inhalational induction followed by intravenous maintenance of anesthesia). NIBP measurements were extracted from a de-identified vital signs database for children < 19 years undergoing anesthesia between Jan/2013-Dec/2016, excluding cardiac surgery. We automatically rejected artifacts and randomly sampled 20 NIBP values per case. Anesthetic phase (induction/maintenance) was identified using operating room booking times for procedure start, and anesthetic types were identified based on intraoperative minimum alveolar concentration values in the different phases of the anesthetic. From 36,347 cases in our operating room booking system, we matched 24,457 cases with available vital signs. Of these, 20,613 (84%) had valid NIBP data and could be assigned to one anesthetic type: TIVA 11,819 [57%], IHA 4,752 [23%], and MIVA 4,042 [20%]. Mean NIBP during anesthesia increased with age, from median values of 48 mmHg (TIVA), 45 mmHg (IHA), and 41 mmHg (MIVA) in neonates, to 70 mmHg (TIVA), 68 mmHg (IHA), and 64 mmHg (MIVA) in 18-year-olds, respectively. In children < 1 year, mean NIBP values were 4 mmHg higher with TIVA than IHA (p < 0.001). These pediatric NIBP reference values contribute to ongoing debate about alarm limits based on age and anesthetic type, and may motivate prospective studies into the effects of different anesthesia regimes on vital signs.

The Effect of Carbetocin Dose on Transmural Dispersion of Myocardial Repolarization in Healthy Parturients Scheduled for Elective Cesarean Delivery Under Spinal Anesthesia: A Prospective, Randomized Clinical Trial.

BACKGROUND: QT interval prolongation is associated with torsade de pointes but remains a poor predictor of drug torsadogenicity. Increased transmural dispersion of myocardial repolarization (TDR), measured as the time interval between the peak and end of the T wave (Tp-e), is a more reliable predictor. Carbetocin is recommended as an uterotonic in patients undergoing cesarean delivery (CD), but its effect on Tp-e is unknown. We evaluated the effect of carbetocin dose on Tp-e and Bazett-corrected QT intervals (QTc) during elective CD under spinal anesthesia. METHODS: On patient consent, 50 healthy parturients undergoing elective CD with a standardized spinal anesthetic and phenylephrine infusion were randomized to receive an intravenous (IV) bolus of carbetocin 50 µg (C50) or 100 µg (C100) via an infusion pump over 1 minute. A 12-lead electrocardiogram (ECG) was obtained at baseline, 5 minutes after spinal anesthesia, then 5 and 10 minutes after carbetocin administration. A cardiologist blinded to group and timing of ECGs measured QTc and Tp-e using Emori's criteria. Primary outcome was the change in Tp-e at 5 minutes after carbetocin administration between the C50 and C100 groups and within each group compared to baseline values. Secondary outcomes included occurrence of arrhythmias, changes in QTc at 5 and 10 minutes after carbetocin, changes in both QTc and Tp-e after spinal anesthesia compared to baseline between and within groups. RESULTS: Data from 41 parturients with a mean (standard deviation [SD]) age of 39.0 (0.7) years and weight of 75.0 (12.0) kg were analyzed. Between groups, at 5 minutes after carbetocin administration, Tp-e in C100 was 4.1 milliseconds longer compared to C50 (95% confidence interval [CI], 0.8-7.5; P = .01). Within groups, at 5 minutes after carbetocin administration, C50 did not significantly increase Tp-e compared to baseline (mean difference [MD] 1.9 milliseconds; 95% CI, -0.95 to 4.81 milliseconds; P = .42) but C100 did (MD 5.1 milliseconds; 95% CI, 2.1-8.1; P = .003). QTc increased significantly within C50 and C100 groups at 5 and 10 minutes after carbetocin administration (all P < .001), with no between-group differences. There were no arrhythmias. CONCLUSIONS: Tp-e was unaffected by C50 IV given after CD in healthy parturients under spinal anesthesia, but minimally prolonged by C100. The increase in QTc after carbetocin administration was statistically significant, but with no apparent dose-dependent effect. The minimal Tp-e prolongation at the higher dose is unlikely to have any clinically significant impact on TDR and therefore the risk of inducing torsade de pointes is low.

The Effect of Low-Dose Intraoperative Ketamine on Closed-Loop-Controlled General Anesthesia: A Randomized Controlled Equivalence Trial.

BACKGROUND: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine. METHODS: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I-II patients aged 19-54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg-1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg-1·min-1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist's discretion. An equivalence range of ±8.99% was assumed for comparing controller performance. RESULTS: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] -3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg-1·min-1; 95% CI, 6.5-43.1; P = .005). CONCLUSIONS: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS.

Characteristics and Timing of Mortality in Children Dying With Infections in North American PICUs.

OBJECTIVES: To investigate the characteristics and timing of death of children with severe infections who die during PICU admission. DESIGN: We analyzed demographics, timing of death, diagnoses, and common procedures in a large cohort obtained from the Virtual Pediatrics Systems database, focusing on early deaths (< 1 d). SETTING: Clinical records were prospectively collected in 130 PICUs across North America. PATIENTS: Children admitted between January 2009 and December 2014 with at least one infection-related diagnosis at time of death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis included data from 106,464 children admitted to PICUs. The 4,240 children (4%) who died were older than PICU survivors. The median (interquartile range) duration in PICU prior to death was 7.1 days (2.1-21.3 d), with 635 children (15%) dying early (< 1 d of PICU admission). Children who died early were older, more likely to have septic shock, and more likely to have received cardiopulmonary resuscitation than those who died later. Withdrawal of care was less likely in early deaths compared with later deaths. After adjusting for age, sex, sepsis severity, procedures (including cardiopulmonary resuscitation and heart, lung, and renal support), and number of admissions contributed per PICU, it was found that children admitted from the emergency department, inpatient floors, or referring hospitals had significantly greater risk of early death compared with children admitted from the operating room. CONCLUSIONS: A substantial proportion of children admitted to PICU with severe infections die early and differ from those dying later in diagnoses, procedures, and admitting location. The emergency department is a key source of critically ill patients. Understanding characteristics of early deaths may yield recruitment considerations for clinical trials enrolling children at high risk of early death.

Anesthesia in the modern world of apps and technology: Implications and impact on wellness.

Recent decades have seen an unprecedented leap in digital innovation, with far-reaching implications in healthcare. Anesthesiologists have historically championed the adoption of new technologies. However, the rapid evolution of these technologies has outpaced attempts at studying their potential impact on healthcare providers' well-being. This document introduces several categories of workplace technologies commonly encountered by the anesthesiologist. We examine examples of novel technology and the impact of these digital interventions on the anesthesiologist's well-being. We also review popular personalized technology aimed at improving wellness and the impact on well-being examined. Finally, technology acceptance models are introduced to improve technology adoption, which, when appropriately applied, may minimize the negative impacts of technology on anesthesiologists' well-being. Incorporating quantitative, serial assessments of well-being as part of technology implementation are proposed as a future direction for examining the wellness impact of technology on anesthesiologists.

Association of dexmedetomidine with recovery room and hospital discharge times: A retrospective cohort analysis.

BACKGROUND: Dexmedetomidine is a useful anesthetic adjunct, increasingly popular during pediatric surgery and procedural sedation. Its half-life of 2-3 hours might prolong recovery and discharge times when compared with an un-supplemented propofol anesthetic. This may create an additional burden in a busy post-anesthetic care unit (PACU). AIM: To investigate whether intraoperative adjuvant dexmedetomidine delays PACU discharge in patients undergoing propofol anesthesia for day surgery or procedural investigations with minimal anticipated post-procedural pain. METHODS: We conducted a retrospective review of outpatient procedures performed during a six-month period including pediatric patients, ASA physical status I-III, who underwent intravenous anesthesia with propofol and remifentanil for magnetic resonance imaging (MRI), strabismus repair, upper gastrointestinal endoscopy, or combined upper/lower gastrointestinal endoscopy. Patients receiving a sedative premedication, long-acting opioids, or volatile anesthetics for maintenance of anesthesia, were excluded. Duration of PACU stay was compared for patients who did or did not receive intraoperative dexmedetomidine in the four procedure groups. RESULTS: Charts were reviewed for 359 patients; 130 (36%) received dexmedetomidine. Median differences in duration of PACU stay for dexmedetomidine versus non-dexmedetomidine cases were: 5 minutes (95%CI 0 to 10, p=0.037) for MRI; 5 minutes (95%CI -3 to 15, p=0.258) for strabismus surgery; 7 minutes (95%CI 3 to 10, p<0.001) for upper endoscopy; and 5 minutes (95%CI 1 to 12, p=0.021) for combined upper/lower endoscopy. Linear regression (F=61.1, adjusted R2 =0.40) indicated a significant relationship between dexmedetomidine dose (estimate 14.6 minutes per µg/kg, 95%CI 8.2 to 21.1, p<0.001) and duration of PACU stay. CONCLUSION: We found evidence for a small association of intraoperative dexmedetomidine with duration of recovery from propofol anesthesia for a set of common outpatient procedures, with a potential dose relationship equivalent to approximately 15 minutes delay per µg/kg dexmedetomidine administered. Future research into the benefits of dexmedetomidine in pediatric anesthesia should further evaluate this relationship.

Effect of ketamine on the NeuroSENSE WAVCNS during propofol anesthesia; a randomized feasibility trial.

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAVCNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAVCNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg-1 initial bolus, 10 mcg kg-1 min-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg-1 remifentanil over 30 s, then 1.5 mg kg-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAVCNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAVCNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAVCNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAVCNS. This effect should be considered when using the WAVCNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.

The effect of ketamine on depth of hypnosis indices during total intravenous anesthesia-a comparative study using a novel electroencephalography case replay system.

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg-1 bolus followed by a 10 mcg kg-1 min-1 infusion], Group 0.25 [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland-Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ2 = 8.01, p = 0.018; SE, χ2 = 11.44, p = 0.003; WAV, χ2 = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.