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.

A survey of practice in the anesthetic management of adolescent idiopathic scoliosis spine fusion by the North American Pediatric Spine Anesthesiologists Collaborative.

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) affects 2%-4% of the general pediatric population. While surgical correction remains one of the most common orthopedic procedures performed in pediatrics, limited consensus exists on the perioperative anesthetic management. AIMS: To examine the current state of anesthetic management of typical AIS spine fusions at institutions which have a dedicated pediatric orthopedic spine surgeon. METHODS: A web-based survey was sent to all members of the North American Pediatric Spine Anesthesiologists (NAPSA) Collaborative. This group included 34 anesthesiologists at 19 different institutions, each of whom has a Harms Study Group surgeon performing spine fusions at their hospital. RESULTS: Thirty-one of 34 (91.2%) anesthesiologists completed the survey, with a missing response rate from 0% to 16.1% depending on the question. Most anesthesia practices (77.4%; 95% confidence interval [CI], 67.7-93.4) do not have patients come for a preoperative visit prior to the day of surgery. Intravenous induction was the preferred method (74.2%; 95% CI 61.3-89.9), with the majority utilizing two peripheral IVs (93.5%; 95% CI 90.3-100) and an arterial line (100%; 95% CI 88.8-100). Paralytic administration for intubation and/or exposure was divided (51.6% rocuronium/vecuronium, 45.2% no paralytic, and 3.2% succinylcholine) amongst respondents. While tranexamic acid was consistently utilized for reducing blood loss, dosing regimens varied. When faced with neuromonitoring signal issues, 67.7% employ a formal protocol. Most anesthesiologists (93.5%; 95% CI 78.6-99.2) extubate immediately postoperatively with patients admitted to an inpatient floor bed (77.4%; 95% CI 67.7-93.3). CONCLUSION: Most anesthesiologists (87.1%; 95% CI 80.6-99.9) report the use of some form of an anesthesia-based protocol for AIS fusions, but our survey results show there is considerable variation in all aspects of perioperative care. Areas of agreement on management comprise the typical vascular access required, utilization of tranexamic acid, immediate extubation, and disposition to a floor bed. By recognizing the diversity of anesthetic care, we can develop areas of research and improve the perioperative management of AIS.

Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial.

BACKGROUND: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on blood glucose and serum potassium concentrations, which are relevant due to the associations of derangements of both parameters with undesired outcomes. We investigated the effects of 3 different doses of dexmedetomidine on these outcomes in a randomized controlled trial in children undergoing elective surgery. METHODS: Sixty-four American Society of Anesthesiologists I-II children were randomized to receive either dexmedetomidine 0.25 µg/kg, dexmedetomidine 0.5 µg/kg, dexmedetomidine 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds after induction of anesthesia. Changes in plasma glucose and serum potassium concentrations were measured in venous blood sampled before and at 15 and 30 minutes after study drug administration. Data were plotted within and between groups and analyzed using a constrained longitudinal data approach. RESULTS: Forty-nine children completed the study. Mean glucose levels at 15 and 30 minutes were elevated with estimated changes from baseline of 0.37 mmol/L (95% CI, 0.29-0.45 mmol/L) and 0.05 mmol/L (95% CI, 0.00-0.10 mmol/L), respectively. At 15 minutes, there was a linear dose-response relationship (1.07 mmol/L/µg/kg [95% CI, 0.57-1.58 mmol/L/µg/kg]), but there was no appreciable effect of dexmedetomidine at 30 minutes (0.15 mmol/L/µg/kg [95% CI, -0.40 to 0.70 mmol/L/µg/kg]). Potassium levels were depressed relative to baseline, with a mean difference at 15 minutes of -0.20 mEq/L (95% CI, -0.28 to -0.12 mEq/L) and at 30 minutes of -0.12 mEq/L (95% CI, -0.15 to -0.08 mEq/L), but there was no appreciable effect of dexmedetomidine at either time. CONCLUSIONS: Small elevations in glucose and decreases in potassium were observed after induction of anesthesia in children. The elevation in glucose at 15 minutes depended on the dose of dexmedetomidine administered. These preliminary data warrant further investigation.

Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on myocardial repolarization, which is important given that the drug is listed as a possible risk factor for torsades de pointes. We investigated the effect of 3 different doses of dexmedetomidine on myocardial repolarization and transmural dispersion in children undergoing elective surgery with total IV anesthesia. METHODS: Sixty-four American Society of Anesthesiologists I-II children 3-10 years of age were randomized to receive dexmedetomidine 0.25 µg/kg, 0.5 µg/kg, 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds, after induction of anesthesia. Pre- and postintervention 12-lead electrocardiograms were recorded. The interval between the peak and the end of the electrocardiogram T wave (Tp-e; transmural dispersion) and heart rate-corrected QT intervals (myocardial repolarization) were measured by a pediatric electrophysiologist blinded to group allocation. Data were analyzed using an analysis of covariance regression model. The study was powered to detect a 25-millisecond difference in Tp-e. RESULTS: Forty-eight children completed the study, with data analyzed from 12 participants per group. There were no instances of dysrhythmias. Tp-e values were unaffected by dexmedetomidine administration at any of the studied doses (F = 0.09; P = .96). Mean (99% CI) within-group differences were all <2 milliseconds (-5 to 8). Postintervention, corrected QT interval increased in the control group, but decreased in some dexmedetomidine groups (F = 7.23; P < .001), specifically the dexmedetomidine 0.5 and 0.75 µg/kg doses. Within groups, the mean (99% CI) differences between pre- and postintervention corrected QT interval were 12.4 milliseconds (-5.8 to 30.6) in the control group, -9.0 milliseconds (-24.9 to 6.9) for dexmedetomidine 0.25 µg/kg, -18.6 milliseconds (-33.7 to -3.5) for dexmedetomidine 0.5 µg/kg, and -14.1 milliseconds (-27.4 to -0.8) for dexmedetomidine 0.75 µg/kg. CONCLUSIONS: Of the bolus doses of dexmedetomidine studied, none had an effect on Tp-e and the dexmedetomidine 0.5 and 0.75 µg/kg doses shortened corrected QT intervals when measured at 1 minute after dexmedetomidine bolus injection during total IV anesthesia. There is no evidence for an increased risk of torsades de pointes in this context.

Integrating intraoperative physiology data into outcome analysis for the ACS Pediatric National Surgical Quality Improvement Program.

BACKGROUND: The Pediatric National Surgical Quality Improvement Program (P-NSQIP) samples surgical procedures for benchmarking and quality improvement. While generally comprehensive, P-NSQIP does not collect intraoperative physiologic data, despite potential impact on outcomes. AIMS: The aims of this study were (a) to describe a methodology to augment P-NSQIP with vital signs data and (b) demonstrate its utility by exploring relationships that intraoperative hypothermia and hypotension have with P-NSQIP outcomes. METHODS: Vital signs from 2012 to 2016 were available in a research databank. Episodes of hypotension and hypothermia were extracted and recorded alongside local P-NSQIP data. Multivariable regression analyses were performed to explore associations with undesired outcomes, including: surgical site infection, wound disruption, unplanned return to the operating room, and blood transfusion. Model variables were selected with the Akaike information criterion using 2012-2014 as the training set and validated with receiver operating characteristics analysis using 2015-2016 as the testing set. RESULTS: Data from 6737 patients were analyzed, with 43.9% female, median [interquartile range] age 5.8 [1.3-12.4] years, undergoing procedures lasting 118 [75-193] minutes. Hypothermia, observed in 45% of cases, was associated with wound disruption (odds ratio 1.75, 95% CI 1.1-2.83). Hypotension, observed in 60% of cases, was associated with unplanned returns (odds ratio 1.58, 95% CI 1.02-2.51), and transfusions (odds ratio 1.95, 95% CI 1.14-3.52). Surgical site infection, wound disruption, unplanned return, and transfusion models had areas under the receiver operating characteristic curve of 0.69/0.67, 0.59/0.63, 0.78/0.79, and 0.92/0.93 for validation models including hypothermia/hypotension respectively. CONCLUSION: Adding intraoperative vital signs to P-NSQIP data allowed identification of two modifiable risk factors: hypothermia was associated with increased wound disruption, and hypotension with increased blood transfusions and unplanned returns to the operating room. These findings may motivate prospective studies and prompt other centers and P-NSQIP to augment outcome data with intraoperative physiological data.

Using physiological monitoring data for performance feedback: an initiative using thermoregulation metrics.

BACKGROUND: Feedback of performance data can improve professional practice and outcomes. Vital signs are not routinely used for quality improvement because of their limited access. Intraoperative hypothermia has been associated with deleterious effects, including surgical site infections and bleeding. We speculated that providing feedback could help keep temperature monitoring and management a priority in the anesthesiologist's mind, thereby improving perioperative temperature management. We hypothesized that feedback on thermoregulation metrics, without changes in policy, could reduce temperature-monitoring delays at the start of scoliosis correction surgery. METHODS: Although our tertiary pediatric centre does not have an anesthesia information management system, vital signs for all surgical cases are recorded in real time. Temperature data from children undergoing spine surgery are extracted from a vital signs databank and analyzed using MATLAB. Spine team anesthesiologists are provided with both team and individualized feedback regarding two variables: the percentage of time that patients are hypothermic and the time delay from the start of the case to the first temperature monitoring (our primary outcome). These data are shared every six months as run charts for the entire group and as anonymized (coded) box-and-whisker plots for each anesthesiologist. RESULTS: This feedback of temperature-delay data reduced the median [interquartile range] delay from 39.0 [18.7-61.5] min to 14.4 [10.8-22.9] min (median reduction, 21.8 min; 95% confidence interval, 14.9 to 28.2; P < 0.001). It did not, however, further reduce the percentage of time patients remained hypothermic beyond the improvements already achieved with prewarming. CONCLUSION: Feedback of intraoperative thermoregulation management improved both group and individual performances as measured by significant, sustained reductions in temperature-monitoring delays. Thus, intraoperative vital signs data may improve the quality of, and reduce the variability in, anesthetic practice.

Preoperative warming and undesired surgical and anesthesia outcomes in pediatric spinal surgery-a retrospective cohort study.

BACKGROUND: Underbody forced air warming is a method commonly used for intraoperative temperature maintenance in children. We previously reported that preoperative forced air warming of children undergoing spinal surgery substantially reduces the incidence and duration of intraoperative hypothermia (<36°C). OBJECTIVE: The aim of this study was to evaluate the effects of preoperative warming before spinal deformity surgery on surgical site infection rate, length of hospitalization, and bleeding (estimated blood loss and incidence of cell salvaged and/or allogeneic packed red blood cell transfusions). METHODS: Demographic, anesthetic, and surgical data of all patients who underwent spinal deformity surgery between December 2009 and December 2012 were obtained by retrospective chart review. Temperature data were abstracted from an existing repository; the incidence and duration of hypothermic episodes were identified. For each outcome, logistic regression models and propensity score analysis were used to estimate the effect of prewarming, adjusted for potential confounders. The issue of missing data was handled by a multiple imputation method. Data from 334 procedures were used in modeling and propensity score stratification. RESULTS: Adjusted odds ratios for the effects of prewarming were 0.47 (95% CI 0.15-1.49) for surgical site infections; 0.89 (95% CI 0.55-1.41) for cell salvaged blood transfusion; 0.43 (95% CI 0.22-0.83) for allogeneic packed red blood cell transfusion; and 1.24 (95% CI 0.77-1.99) for a length of hospitalization >6 days. Adjusted mean decrease in estimated blood loss for prewarming was 72 (95% CI -29 to 173) ml. CONCLUSION: In this study, prewarming was associated with a reduction in allogeneic packed red blood cell transfusion. However, no causal relationship between prewarming and reduced allogeneic blood transfusion should be assumed. Prewarming was not associated with reductions in estimated blood loss, length of hospitalization, or the incidence of surgical site infection.

Changes in QTc associated with a rapid bolus dose of dexmedetomidine in patients receiving TIVA: a retrospective study.

BACKGROUND: Clinical indications for the perioperative use of dexmedetomidine in pediatric anesthesia are accumulating. However, in 2013, dexmedetomidine was added to the list of medications with possible risk of prolonging the QT interval and/or inducing Torsades de Pointes. Unfortunately, current evidence for dexmedetomidine-induced QT prolongation is sparse and somewhat contradictory. OBJECTIVE: The purpose of this study was to evaluate temporal changes in corrected QT interval (QTc) after a rapid bolus administration of dexmedetomidine under total intravenous anesthesia (TIVA) with a standardized propofol and remifentanil administration. METHODS: Electrocardiography (ECG) and corresponding trend data were extracted from automated electronic data capture of physiological monitoring. Ten-second epochs of ECG data were extracted in 1-min intervals for 12 min, starting 1 min before dexmedetomidine bolus administration, and ending 10 min after. QT intervals were extracted using an automated routine in MATLAB, and corrected for heart rate (HR) using Bazett's (QTcB) and Fridericia's formulas (QTcF). QTcB and QTcF were compared using Wilcoxon signed-rank test between baseline measurements and the subsequent four interval values. RESULTS: Data from 21 subjects (17 male) with median (range) age 7.1 (5.4-9.5) yr, weight 23.6 (16.2-36.7) kg, and height 121 (103-140) cm were analyzed. Bolus administration of dexmedetomidine reduced HR in all subjects (median 22%), and caused transient reduction of QT interval, with its peak at 1-min postbolus administration: QTcB (median reduction 30.7 ms, P < 0.001) or QTcF (median reduction 15.4 ms, P = 0.001); QT shortening became statistically insignificant 4 min following dexmedetomidine bolus administration for QTcB and 2 min for QTcF. CONCLUSION: In this study, a rapid bolus of dexmedetomidine transiently shortened corrected QT intervals. However, these effects are confounded by dexmedetomidine-induced bradycardia. These findings should be confirmed in pediatric studies without concomitant TIVA administration and with optimized correction of baseline HR.

The safety of modern anesthesia for children with long QT syndrome.

BACKGROUND: Patients with long QT syndrome (LQTS) may experience a clinical spectrum of symptoms, ranging from asymptomatic, through presyncope, syncope, and aborted cardiac arrest, to sudden cardiac death. Arrhythmias in LQTS are often precipitated by autonomic changes. This patient population is believed to be at high risk for perioperative arrhythmia, specifically torsades de pointes (TdP), although this perception is largely based on limited literature that predates current anesthetic drugs and standards of perioperative monitoring. We present the largest multicenter review to date of anesthetic management in children with LQTS. METHODS: We conducted a multicentered retrospective chart review of perioperative management of children with clinically diagnosed LQTS, aged 18 years or younger, who received general anesthesia (GA) between January 2005 and January 2010. Data from 8 institutions were collated in an anonymized database. RESULTS: One hundred three patients with LQTS underwent a total of 158 episodes of GA. The median (interquartile range) age and weight of the patients at the time of GA was 9 (3-15) years and 30.3 (15.4-54) kg, respectively. Surgery was LQTS-related in 81 (51%) GA episodes (including pacemaker, implantable cardioverter-defibrillator, and loop recorder insertions and revisions and lead extractions) and incidental in 77 (49%). ß-blocker therapy was administered to 76% of patients on the day of surgery and 47% received sedative premedication. Nineteen percent of patients received total IV anesthesia, 30% received total inhaled anesthesia, and the remaining 51% received a combination. No patient received droperidol. There were 5 perioperative episodes of TdP, all in neonates or infants, all in surgery that was LQTS-related, and none of which was overtly attributable to anesthetic regimen. Thus the incidence (95% confidence interval) of perioperative TdP in incidental versus LQTS-related surgery was 0/77 (0%; 0%-5%) vs 5/81 (6.2%; 2%-14%). CONCLUSIONS: With optimized perioperative management, modern anesthesia for incidental surgery in patients with LQTS is safer than anecdotal case report literature might suggest. Our series suggests that the risk of perioperative TdP is concentrated in neonates and infants requiring urgent interventions after failed first-line management of LQTS.

Usability and performance characteristics of the pediatric air-Q® intubating laryngeal airway.

PURPOSE: The air-Q® intubating laryngeal airway (ILA) is a supraglottic device (SGD) designed specifically to function as both a primary airway and a bridging device and conduit for fibreoptic intubation in difficult airway scenarios. This observational study evaluated the usability and performance characteristics of pediatric air-Q ILA sizes 1.0, 1.5, 2.0, and 2.5 when used as a primary airway. METHODS: One hundred ten children, American Society of Anesthesiologists physical status I-III and undergoing elective surgery, received a weight-appropriate air-Q ILA following induction of anesthesia. The evaluation criteria included ease of insertion, quality of ventilation, presence of gastric insufflation, oropharyngeal leak pressures (OLPs) and maximum tidal volumes (VT max) in five different head positions, and fibreoptic view of the glottis. RESULTS: For sizes 1.0, 1.5, 2.0, and 2.5, the median [P25,P75] neutral OLPs (cm H2O) were 23.0 [20.0,30.0], 16.5 [15.0,20.8], 14.0 [10.0,17.8], and 14.0 [11.3,16.8], respectively. The median [P25,P75] neutral VT max values (mL · kg(-1)) were 17.4 [14.3,19.7], 20.3 [16.8,25.5], 17.8 [14.5,22.1], and 14.0 [11.6,16.0], respectively. Median [P25,P75] ease of insertion scores (0-10; 0 = easiest ever, 10 = most difficult ever) were 1 [1,2], 2 [2,3], 2 [1,2.8], and 2 [2,3] respectively. Ventilation was adequate in 108/110 cases, and a fibreoptic view of the vocal cords was obtained in 102/110 cases. CONCLUSIONS: The air-Q ILA functions acceptably as a primary SGD in infants and children. The OLPs are lower than published values for the ProSeal laryngeal mask airway (LMA ProSeal™), the current pediatric SGD of choice, but adequate tidal volumes are readily achievable. The fibreoptic views of the glottis portend well for fibreoptic intubation through the device. (This trial was registered at clinicaltrials.gov number, NCT00885911).

A retrospective audit to examine the effectiveness of preoperative warming on hypothermia in spine deformity surgery patients.

BACKGROUND: Hypothermia (core body temperature <36°C) during surgery has been associated with surgical site infection, a major risk in all spine deformity surgeries. Forced air warming is an important method of intraoperative temperature maintenance in children. In mid-2010, we empirically introduced preoperative warming as a strategy to reduce intraoperative hypothermia. OBJECTIVE: We report the prevalence and extent of hypothermia during spine deformity surgeries at our institution and evaluate the effect of the introduction of preoperative warming. METHODS: We performed a retrospective audit of temperature data in children who underwent spine deformity surgeries during two-seven-month periods: November 2011 to June 2012 and 2 years prior to this period (before preoperative warming implementation). Specifically, the following data were obtained: (i) case duration; (ii) first measured temperature; (iii) last measured temperature; (iv) percentage of case spent hypothermic; (v) number of hypothermic episodes per case, and (vi) delay between case start and time of first temperature measured. Data were compared visually and using the Mann-Whitney U-test. Confidence intervals (CI) were obtained using the Hodges-Lehmann estimator. RESULTS: Preoperative warming reduced the percentage of case duration spent hypothermic by a median of 111.1 min (P < 0.001, 95% CI 77.1-139.9 min). Additionally, it increased the first measured temperature by a median of 0.5°C (P < 0.001, 95% CI 0.3-0.7°C). The last temperature at the end of the case remained unchanged (P = 0.57, 95% CI -0.2-0.1°C). CONCLUSION: Preoperative warming of children undergoing spine deformity surgery significantly reduces the percentage of case spent hypothermic, thereby potentially reducing risk of perioperative complications.

An Individualized Postoperative Pain Risk Communication Tool for Use in Pediatric Surgery: Co-Design and Usability Evaluation.

BACKGROUND: Risk identification and communication tools have the potential to improve health care by supporting clinician-patient or family discussion of treatment risks and benefits and helping patients make more informed decisions; however, they have yet to be tailored to pediatric surgery. User-centered design principles can help to ensure the successful development and uptake of health care tools. OBJECTIVE: We aimed to develop and evaluate the usability of an easy-to-use tool to communicate a child's risk of postoperative pain to improve informed and collaborative preoperative decision-making between clinicians and families. METHODS: With research ethics board approval, we conducted web-based co-design sessions with clinicians and family participants (people with lived surgical experience and parents of children who had recently undergone a surgical or medical procedure) at a tertiary pediatric hospital. Qualitative data from these sessions were analyzed thematically using NVivo (Lumivero) to identify design requirements to inform the iterative redesign of an existing prototype. We then evaluated the usability of our final prototype in one-to-one sessions with a new group of participants, in which we measured mental workload with the National Aeronautics and Space Administration (NASA) Task Load Index (TLX) and user satisfaction with the Post-Study System Usability Questionnaire (PSSUQ). RESULTS: A total of 12 participants (8 clinicians and 4 family participants) attended 5 co-design sessions. The 5 requirements were identified: (A) present risk severity descriptively and visually; (B) ensure appearance and navigation are user-friendly; (C) frame risk identification and mitigation strategies in positive terms; (D) categorize and describe risks clearly; and (E) emphasize collaboration and effective communication. A total of 12 new participants (7 clinicians and 5 family participants) completed a usability evaluation. Tasks were completed quickly (range 5-17 s) and accurately (range 11/12, 92% to 12/12, 100%), needing only 2 requests for assistance. The median (IQR) NASA TLX performance score of 78 (66-89) indicated that participants felt able to perform the required tasks, and an overall PSSUQ score of 2.1 (IQR 1.5-2.7) suggested acceptable user satisfaction with the tool. CONCLUSIONS: The key design requirements were identified, and that guided the prototype redesign, which was positively evaluated during usability testing. Implementing a personalized risk communication tool into pediatric surgery can enhance the care process and improve informed and collaborative presurgical preparation and decision-making between clinicians and families of pediatric patients.

Identification of Requirements for a Postoperative Pediatric Pain Risk Communication Tool: Focus Group Study With Clinicians and Family Members.

BACKGROUND: Pediatric surgery is associated with a risk of postoperative pain that can impact the family's quality of life. Although some risk factors for postoperative pain are known, these are often not consistently communicated to families. In addition, although tools for risk communication exist in other domains, none are tailored to pediatric surgery. OBJECTIVE: As part of a larger project to develop pain risk prediction tools, we aimed to design an easy-to-use tool to effectively communicate a child's risk of postoperative pain to both clinicians and family members. METHODS: With research ethics board approval, we conducted virtual focus groups (~1 hour each) comprising clinicians and family members (people with lived surgical experience and parents of children who had recently undergone surgery/medical procedures) at a tertiary pediatric hospital to understand and evaluate potential design approaches and strategies for effectively communicating and visualizing postoperative pain risk. Data were analyzed thematically to generate design requirements and to inform iterative prototype development. RESULTS: In total, 19 participants (clinicians: n=10, 53%; family members: n=9, 47%) attended 6 focus group sessions. Participants indicated that risk was typically communicated verbally by clinicians to patients and their families, with severity indicated using a descriptive or a numerical representation or both, which would only occasionally be contextualized. Participants indicated that risk communication tools were seldom used but that families would benefit from risk information, time to reflect on the information, and follow-up with questions. In addition, 9 key design requirements and feature considerations for effective risk communication were identified: (1) present risk information clearly and with contextualization, (2) quantify the risk and contextualize it, (3) include checklists for preoperative family preparation, (4) provide risk information digitally to facilitate recall and sharing, (5) query the family's understanding to ensure comprehension of risk, (6) present the risk score using multimodal formats, (7) use color coding that is nonthreatening and avoids limitations with color blindness, (8) present the most significant factors contributing to the risk prediction, and (9) provide risk mitigation strategies to potentially decrease the patient's level of risk. CONCLUSIONS: Key design requirements for a pediatric postoperative pain risk visualization tool were established and guided the development of an initial prototype. Implementing a risk communication tool into clinical practice has the potential to bridge existing gaps in the accessibility, utilization, and comprehension of personalized risk information between health care professionals and family members. Future iterative codesign and clinical evaluation of this risk communication tool are needed to confirm its utility in practice.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

BACKGROUND: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. METHODS: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. RESULTS: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10-4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10-7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10-7). CONCLUSIONS: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication.

The effects of droperidol and ondansetron on dispersion of myocardial repolarization in children.

OBJECTIVES: To compare the effects of droperidol and ondansetron on electrocardiographic indices of myocardial repolarization in children. AIM: To refine understanding of the torsadogenic risk to children exposed to anti-emetic prophylaxis in the perioperative period. BACKGROUND: QT interval prolongation is associated with torsades des pointes (TdP), but is a poor predictor of drug torsadogenicity. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall, rather than QT interval prolongation per se. TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T wave (Tp-e). Tp-e may therefore provide a readily available, noninvasive assay of drug torsadogenicity. The perioperative period is one of high risk for TdP in children with or at risk of long QT syndromes. Droperidol and ondansetron are two drugs commonly administered perioperatively, for prophylaxis of nausea and vomiting, which can prolong the QT interval. This study investigated their effects on myocardial repolarization. METHODS: One hundred and eight ASA1-2 children undergoing elective day-case surgery were randomized to receive droperidol, ondansetron, both or neither. Pre- and post-administration 12-lead electrocardiogram (ECGs) were recorded. QT and Tp-e intervals were measured and compared within and between groups, for the primary endpoint of a 25 ms change in Tp-e. RESULTS: Eighty children completed the study. There were no demographic or baseline ECG differences between groups. QT intervals lengthened by 10-17 ms after allocated treatments, with no between-group differences. Values remained within normal limits for all groups. Tp-e intervals increased by 0-7 ms, with no between-group differences. There were no instances of dysrhythmia. CONCLUSIONS: Droperidol and ondansetron, in therapeutic anti-emetic doses, produce equivalent, clinically insignificant QT prolongation and negligible Tp-e prolongation, suggesting that neither is torsadogenic in healthy children at these doses.

Caudal and Intravenous Anesthesia Without Airway Instrumentation for Laparoscopic Inguinal Hernia Repair in Infants: A Case Series.

We report a series of 20 neonates and infants (18 born preterm) who underwent laparoscopic inguinal hernia repair with caudal anesthesia, oxygen via nasal cannula, and intravenous anesthesia. Surgery was successful in all cases without airway instrumentation or intraoperative complications. Sedation was provided with dexmedetomidine, propofol, and remifentanil. Two patients had apnea in the following 24 hours. There were no unplanned intensive care admissions. Laparoscopy allowed unplanned bilateral repair in 2 cases. Caudal with intravenous anesthesia without airway instrumentation is a viable technique for laparoscopic inguinal hernia repair. Avoiding general endotracheal anesthesia may reduce perioperative complications and influence postoperative disposition.

The effect of propofol concentration on dispersion of myocardial repolarization in children.

BACKGROUND: QT interval prolongation on the electrocardiogram (ECG) may be drug-induced and is traditionally associated with torsades des pointes. A better predictor of torsades des pointes is the time interval between the peak and the end of the T-wave (Tp-e). Older studies of propofol's effect on the corrected interval (QTc) are conflicting and confounded by polypharmacy. It was recently shown that target-controlled infusion of propofol at 3 microg/mL has no effect on QTc or Tp-e. This plasma concentration of propofol is at the extreme lower end of the range for surgical anesthesia. In this randomized, double-blind, clinical study, we investigated the dose-response relationship between propofol, QTc, and Tp-e in a range of doses clinically relevant for surgical anesthesia. METHODS: Sixty healthy unpremedicated children, aged 3-10 yr, were recruited. Subjects were randomized to receive target-controlled infusions of propofol, to achieve 1 of 3 plasma concentrations: 3, 4.5, and 6 microg/mL. A preoperative 12 lead ECG was performed and repeated 5 min after induction. Two investigators, blinded to group allocation and to the timing of the ECG traces, independently measured QTc and Tp-e within and between each group. Paired t-tests were used to compare QTc and Tp-e within groups. One-way analysis of variance was used for intergroup analysis. The primary outcome measure was a change of >25 ms in Tp-e both within and between groups. RESULTS: ECG recordings were obtained in 51 children. There were no demographic or ECG differences at baseline, at which time QTc and Tp-e values were within normal limits. There were no differences in QTc or Tp-e after induction within or between the three different groups. DISCUSSION: Propofol has no effect on myocardial repolarization in healthy children at clinically relevant doses. This suggests that propofol would be a rational choice for children with a preexisting repolarization abnormality.

A comparison of the effect on dispersion of repolarization of age-adjusted MAC values of sevoflurane in children.

BACKGROUND: QT interval prolongation is associated with torsades des pointes (TdP), but is a poor predictor of drug torsadogenicity. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall, rather than QT interval prolongation per se. TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T-wave (Tp-e). Thus Tp-e is a readily measured assay of drug torsadogenicity. Several anesthetic drugs prolong the QT interval, but their effect on TDR is largely unknown. METHODS: We investigated the effects of sevoflurane on corrected QT (QTc) and Tp-e intervals in 54 unpremedicated ASA I-II children, aged 3-10 yr, who were randomized to receive sevoflurane 1, 1.25, or 1.5 MAC, age-adjusted. Twelve-lead electrocardiograms were recorded before and after sevoflurane exposure. QTc and Tp-e were compared within and among groups using 2-way analysis of variance. Change in Tp-e after sevoflurane exposure was the primary outcome measure. RESULTS: Sevoflurane significantly prolonged preoperative QTc at all doses (P < 0.005), with no dose-response relationship, but had no effect on preoperative Tp-e. CONCLUSION: Sevoflurane markedly prolongs the QTc in healthy children, but does not increase dispersion of repolarization as measured by the Tp-e interval, indicating low or no torsadogenicity, and making it unlikely to increase predisposition to TdP.

The effects of propofol and sevoflurane on the QT interval and transmural dispersion of repolarization in children.

Prolongation of the QT interval is associated with torsades de pointes (TdP), especially in children or young adults with long QT syndromes. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall. Several anesthetic drugs prolong the QT interval, but their effect on TDR is unknown. TDR can be measured on the electrocardiograph (ECG) as the time interval between the peak and end of the T wave (Tp-e). We investigated the effects of propofol and sevoflurane on the corrected QT (QTc) and Tp-e intervals in 50 unpremedicated ASA physical status I-II children, aged 1-16 yr, who were randomized to receive propofol (group P) or sevoflurane (group S). Twelve-lead ECGs were recorded preoperatively and intraoperatively. Sevoflurane significantly prolonged the preoperative QTc; propofol did not. Neither anesthetic had any significant effect on the preoperative Tp-e. Sevoflurane increases the duration of myocardial repolarization in children to a larger extent than does propofol, but as the dispersion of repolarization appears unaffected, the risk of TdP is likely to be minimal with either anesthetic.