Automated digital technologies for supporting sepsis prediction in children: a scoping review protocol.

INTRODUCTION: While there have been several literature reviews on the performance of digital sepsis prediction technologies and clinical decision-support algorithms for adults, there remains a knowledge gap in examining the development of automated technologies for sepsis prediction in children. This scoping review will critically analyse the current evidence on the design and performance of automated digital technologies to predict paediatric sepsis, to advance their development and integration within clinical settings. METHODS AND ANALYSIS: This scoping review will follow Arksey and O'Malley's framework, conducted between February and December 2022. We will further develop the protocol using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. We plan to search the following databases: Association of Computing Machinery (ACM) Digital Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Google Scholar, Institute of Electric and Electronic Engineers (IEEE), PubMed, Scopus and Web of Science. Studies will be included on children >90 days postnatal to <21 years old, predicted to have or be at risk of developing sepsis by a digitalised model or algorithm designed for a clinical setting. Two independent reviewers will complete the abstract and full-text screening and the data extraction. Thematic analysis will be used to develop overarching concepts and present the narrative findings with quantitative results and descriptive statistics displayed in data tables. ETHICS AND DISSEMINATION: Ethics approval for this scoping review study of the available literature is not required. We anticipate that the scoping review will identify the current evidence and design characteristics of digital prediction technologies for the timely and accurate prediction of paediatric sepsis and factors influencing clinical integration. We plan to disseminate the preliminary findings from this review at national and international research conferences in global and digital health, gathering critical feedback from multidisciplinary stakeholders. SCOPING REVIEW REGISTRATION: https://osf.io/veqha/?view_only=f560d4892d7c459ea4cff6dcdfacb086.

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.

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.

Pediatric pulse oximetry-based OSA screening at different thresholds of the apnea-hypopnea index with an expression of uncertainty for inconclusive classifications.

BACKGROUND: Assessments of pediatric obstructive sleep apnea (OSA) are underutilized across Canada due to a lack of resources. Polysomnography (PSG) measures OSA severity through the average number of apnea/hypopnea events per hour (AHI), but is resource intensive and requires a specialized sleep laboratory, which results in long waitlists and delays in OSA detection. Prompt diagnosis and treatment of OSA are crucial for children, as untreated OSA is linked to behavioral deficits, growth failure, and negative cardiovascular consequences. We aim to assess the performance of a portable pediatric OSA screening tool at different AHI cut-offs using overnight smartphone-based pulse oximetry. MATERIAL AND METHODS: Following ethics approval and informed consent, children referred to British Columbia Children's Hospital for overnight PSG were recruited for two studies including 160 and 75 children, respectively. An additional smartphone-based pulse oximeter sensor was used in both studies to record overnight pulse oximetry [SpO2 and photoplethysmogram (PPG)] alongside the PSG. Features characterizing SpO2 dynamics and heart rate variability from pulse peak intervals of the PPG signal were derived from pulse oximetry recordings. Three multivariate logistic regression screening models, targeted at three different levels of OSA severity (AHI ≥ 1, 5, and 10), were developed using stepwise-selection of features using the Bayesian information criterion (BIC). The "Gray Zone" approach was also implemented for different tolerance values to allow for more precise detection of children with inconclusive classification results. RESULTS: The optimal diagnostic tolerance values defining the "Gray Zone" borders (15, 10, and 5, respectively) were selected to develop the final models to screen for children at AHI cut-offs of 1, 5, and 10. The final models evaluated through cross-validation showed good accuracy (75%, 82% and 89%), sensitivity (80%, 85% and 82%) and specificity (65%, 79% and 91%) values for detecting children with AHI ≥ 1, AHI ≥ 5 and AHI ≥ 10. The percentage of children classified as inconclusive was 28%, 38% and 16% for models detecting AHI ≥ 1, AHI ≥ 5, and AHI ≥ 10, respectively. CONCLUSIONS: The proposed pulse oximetry-based OSA screening tool at different AHI cut-offs may assist clinicians in identifying children at different OSA severity levels. Using this tool at home prior to PSG can help with optimizing the limited resources for PSG screening. Further validation with larger and more heterogeneous datasets is required before introducing in clinical practice.

A Postoperative Pain Management Mobile App (Panda) for Children at Home After Discharge: Usability and Feasibility.

BACKGROUND: Emphasis on outpatient pediatric surgical procedures places the burden of responsibility for postoperative pain management on parents or guardians. Panda is a mobile phone app that provides scheduled medication alerts and allows parents to track their child's pain and medication administration. We have previously tested and optimized the usability and feasibility of Panda within the hospital setting. OBJECTIVE: The purpose of this study was to evaluate and optimize the usability and feasibility of Panda for use at home based on alert response adherence (response to any medication notification within 1 hour) and parents' satisfaction. METHODS: Parents or guardians of children aged 3 to 18 years undergoing day surgery were recruited to use Panda at home for 1 to 7 days to manage their scheduled medications and to assess their child's pain. After the surgical procedure, a research assistant guided parents through app setup before independent use at home. We aimed to recruit 10 child-caregiver pairs in each of three rounds of evaluation. Each user's adherence with the recommended medication alerts was analyzed through audit-trail data generated during the use of the app. We used the Computer System Usability Questionnaire and a poststudy phone interview to evaluate the app's ease of use and identify major barriers to adoption. Suggestions provided during the interviews were used to improve the app between each round. RESULTS: Twenty-nine child-caregiver pairs participated in three rounds, using the app for 1 to 5 days. Alert response adherence (response to any medication notification within 1 hour) improved as the study progressed: participants responded to a median 30% (interquartile range [IQR] 22%-33%) of alerts within 1 hour in round 1, and subsequently to median 60% (IQR 44%-64%) in round 2 and median 64% (IQR 56%-72%) in round 3 (P=.005). Similarly, response times decreased from median 131 (IQR 77-158) minutes in round 1 to median 31 (IQR 18-61) minutes in round 2 and median 10 (IQR 2-14) minutes in round 3 (P=.002). Analysis of interview feedback from the first two rounds revealed usability issues, such as complaints of too many pages and trouble hearing app alerts, which were addressed to streamline app function, as well as improve visual appearance and audible alerts. CONCLUSIONS: It is feasible for parents or guardians to use Panda at home to manage their child's medication schedule and track their pain. Simple modifications to the app's alert sounds and user interface improved response times.

Night to night pulse oximetry variability in children with suspected sleep apnea.

Obstructive Sleep Apnea (OSA) is the most common form of sleep-disordered breathing in children. The gold standard to screen for OSA, polysomnography (PSG), requires an overnight stay in the hospital and is resource intensive. The Phone Oximeter is a non-invasive smartphone-based tool to record pulse oximetry. This portable device is able to measure patients over multiple nights while at home, causing less sleep disturbance than PSG and is able to measure night to night variability in sleep. This study analyzed the Screen My Sleep children (SMS) dataset, in which 74 children were monitored over multiple nights with the Phone Oximeter, including one night simultaneously with PSG in the hospital and two nights at home. In this study, we aim to investigate the night to night variability and assess the accuracy of the oxygen desaturation index (ODI) screening for children with significant OSA. In order to assess the performance of the ODI calculation in children, we implemented different ODIs at different desaturation levels and time durations. The variability was studied using a one-way ANOVA, and ODI's performance screening for OSA using the area under the ROC curve (AUC). The implemented ODIs provide similar OSA screening results, using different apnea/hypopnea index (AHI) thresholds, as the ODI recommended for adults by the American academy of sleep medicine (AASM). The ODI provides an AUC of around 0.77, 0.76, 0.94 and 0.97 classifying children with an AHI > 1, AHI > 5 AHI > 10 and AHI > 15, respectively. The SMS dataset shows no significant night to night variability between the two nights at home. However, when comparing with the night at the hospital, both nights at home show a decrease in the lowest SpO2 value as well as overall SpO2 signal quality percentage. This study shows that there is variability in SpO2 signal between at-home versus in hospital settings.

Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System.

BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I-III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for 127 patients, of median (range) age 64 (22-86) years, undergoing surgical procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6-90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions.

The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured Review.

OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) mortality prediction model in pregnant and recently pregnant women receiving critical care in low-, middle-, and high-income countries during the study period (1985-2015), using a structured literature review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based Medicine Reviews, searched for articles published between 1985 and 2015. STUDY SELECTION: Twenty-five studies (24 publications), of which two were prospective, were included in the analyses. Ten studies were from high-income countries (HICs), and 15 were from low- and middle-income countries (LMICs). Median study duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU admission complicates 0.48% of deliveries, and pregnant and recently pregnant women account for 1.49% of ICU admissions. One quarter were admitted while pregnant, three quarters of these for an obstetric indication and for a median of three days. The median APACHE II score was 10.9, with a median APACHE II-predicted mortality of 16.6%. Observed mortality was 4.6%, and the median standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were more frequently admitted with a medical comorbidity but were less likely to die than were women in LMICs. CONCLUSION: The APACHE II score consistently overestimates mortality risks for pregnant and recently pregnant women receiving critical care, whether they reside in HICs or LMICs. There is a need for a pregnancy-specific outcome prediction model for these women.

Developing an objective method for analyzing vital signs changes in neonates during general anesthesia.

BACKGROUND: Commonly used general anesthetics are considered to be neurotoxic to the developing rodent brain, leading to poor long-term outcome. However, it is unclear whether these rodent studies can be extrapolated to the human neonate. Given that anesthesia for urgent neonatal surgery cannot be avoided, it is vitally important to assess other factors that may impact neurological outcome following anesthesia and surgery. OBJECTIVE: The purpose of this study is to identify thresholds for detecting vital sign deviations, which may have the potential for affecting neurological outcome following anesthesia and surgery in neonates. These data may be suitable to identify targets for prospective quality improvement projects and guide future research for strategies to reduce detrimental neurocognitive outcomes. METHODS: A retrospective analysis of vital sign data was performed for neonates (age ≤28 days), undergoing noncardiac surgery over a 4-year period (2010-2013). Thresholds for detecting bradycardia, tachycardia, hypothermia, hyperthermia, hypertension, hypotension, hypocarbia, hypoxemia, significant changes in mean arterial blood pressure, and periods of high inspired oxygen concentration, were proposed. Selected chart review, to identify additional risk factors, and identify sources of data artifact, was performed for 224 cases. RESULTS: Data from 435 procedures in neonates, with median (IQR [range]) ages of 6 (2-16 [0-28]) days were available for analysis. Five (3-6 [0-12]) rule deviations per case were observed; only 11 cases had no rule deviations. Hypothermia was observed in 285/435 (70%), moderate hypocapnia in 298/430 (69%), and severe hypotension in 270/435 (62%) cases. CONCLUSION: An objective method of comparing cases has been created with a method to automatically identify neonatal vital sign deviations. With further validation the method has the potential to be a powerful tool to drive future quality improvement projects in neonatal anesthesia.

A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation.

The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions.

An Ethnographic Observational Study to Evaluate and Optimize the Use of Respiratory Acoustic Monitoring in Children Receiving Postoperative Opioid Infusions.

BACKGROUND: Respiratory depression in children receiving postoperative opioid infusions is a significant risk because of the interindividual variability in analgesic requirement. Detection of respiratory depression (or apnea) in these children may be improved with the introduction of automated acoustic respiratory rate (RR) monitoring. However, early detection of adverse events must be balanced with the risk of alarm fatigue. Our objective was to evaluate the use of acoustic RR monitoring in children receiving opioid infusions on a postsurgical ward and identify the causes of false alarm and optimal alarm thresholds. METHODS: A video ethnographic study was performed using an observational, mixed methods approach. After surgery, an acoustic RR sensor was placed on the participant's neck and attached to a Rad87 monitor. The monitor was networked with paging for alarms. Vital signs data and paging notification logs were obtained from the central monitoring system. Webcam videos of the participant, infusion pump, and Rad87 monitor were recorded, stored on a secure server, and subsequently analyzed by 2 research nurses to identify the cause of the alarm, response, and effectiveness. Alarms occurring within a 90-second window were grouped into a single-alarm response opportunity. RESULTS: Data from 49 patients (30 females) with median age 14 (range, 4.4-18.8) years were analyzed. The 896 bedside vital sign threshold alarms resulted in 160 alarm response opportunities (44 low RR, 74 high RR, and 42 low SpO2). In 141 periods (88% of total), for which video was available, 65% of alarms were deemed effective (followed by an alarm-related action within 10 minutes). Nurses were the sole responders in 55% of effective alarms and the patient or parent in 20%. Episodes of desaturation (SpO2 < 90%) were observed in 9 patients: At the time of the SpO2 paging trigger, the RR was >10 bpm in 6 of 9 patients. Based on all RR samples observed, the default alarm thresholds, to serve as a starting point for each patient, would be a low RR of 6 (>10 years of age) and 10 (4-9 years of age). CONCLUSIONS: In this study, the use of RR monitoring did not improve the detection of respiratory depression. An RR threshold, which would have been predictive of desaturations, would have resulted in an unacceptably high false alarm rate. Future research using a combination of variables (e.g., SpO2 and RR), or the measurement of tidal volumes, may be needed to improve patient safety in the postoperative ward.

A smartphone version of the Faces Pain Scale-Revised and the Color Analog Scale for postoperative pain assessment in children.

BACKGROUND: Effective pain assessment is essential during postoperative recovery. Extensive validation data are published supporting the Faces Pain Scale-Revised (FPS-R) and the Color Analog Scale (CAS) in children. Panda is a smartphone-based application containing electronic versions of these scales. OBJECTIVES: To evaluate agreement between Panda and original paper/plastic versions of the FPS-R and CAS and to determine children's preference for either Panda or original versions of these scales. METHODS: ASA I-III children, 4-18 years, undergoing surgery were assessed using both Panda and original versions of either the FPS-R or CAS. Pain assessments were conducted within 10 min of waking from anesthesia and 30 min later. RESULTS: Sixty-two participants, median (range) age 7.5 (4-12) years, participated in the FPS-R trial; Panda scores correlated strongly with the original scores at both time points (Pearson's r > 0.93) with limits of agreement within clinical significance (80% CI). Sixty-six participants, age 13 (5-18) years, participated in the CAS trial. Panda scores correlated strongly with the original scores at both time points (Pearson's r > 0.87); mean pain scores were higher (up to +0.47 out of 10) with Panda than with the original tool, representing a small systematic bias, but limits of agreement were within clinical significance. Most participants who expressed a preference preferred Panda over the original tool (81% of FPS-R, 76% of CAS participants). CONCLUSION: The Panda smartphone application can be used in lieu of the original FPS-R and CAS for assessment of pain in children. Children's preference for Panda may translate to improved cooperation with self-report of pain.

A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial.

PURPOSE: Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65 µg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization. METHODS: In this randomized controlled trial, children meeting the inclusion criteria (aged 8-18 yr, American Society of Anesthesiologists physical status I-III, normal developmental profile and prescribed COI/PCA morphine for postoperative analgesia) were randomized to receive an infusion containing a naloxone, opioid, and saline admixture (NOSA) of 12 µg naloxone per 1 mg morphine per 1 mL normal saline or morphine only (control). The severity of opioid-induced pruritus was assessed by self-report using a modified colour analogue scale (mCAS; score 0-10). The groups were also compared for opioid utilization, pain scores, and administration of antipruritic medications, which were recorded for up to 48 hr or until the COI/PCA was discontinued. RESULTS: Ninety-two participants were enrolled in the study. The median [interquartile range] dose of naloxone administered to the NOSA participants was 0.37 [0.30-0.48] µg·kg(-1)·hr(-1). The incidence of OIP, determined by self-report and treatment, was not different between groups: 22% in the NOSA group vs 36% in the control group (mean difference, -15%; 95% confidence interval [CI], -33 to 4; P = 0.164). The severity of opioid-induced pruritus was similar in the two groups, with a median difference in the participants' mean mCAS score of -0.29 (95% CI, -0.75 to 0.26; P = 0.509). Opioid utilization did not differ between groups, with a median difference of -1.35 µg·kg(-1)·hr(-1) (95% CI, -5.85 to 7.55; P = 0.518), and pain scores did not differ, with a median difference of 0.0 (95% CI, -1.0 to 1.5; P = 0.659). CONCLUSION: This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).

Identifying a rapid bolus dose of dexmedetomidine (ED50) with acceptable hemodynamic outcomes in children.

BACKGROUND: Dexmedetomidine is a highly sensitive, specific α2 adrenoceptor agonist with anxiolytic, sedative, and analgesic effects. Administration is recommended as a loading dose infused over 10 min. Clinical experience and a previous study suggested a shorter time frame might be used without causing adverse hemodynamic effects. OBJECTIVE: To determine the dexmedetomidine dose that can be given as a rapid 5 s bolus to healthy children during total intravenous anesthesia (TIVA) without causing significant hemodynamic effects. METHODS: ASA I-II children, aged 5-9 years, having elective surgery under TIVA were recruited. The up-and-down sequential study design was employed to determine the effective dose of dexmedetomidine, starting at 0.3 mcg·kg(-1) with 0.1 mcg·kg(-1) intervals, which caused no hemodynamic response in half the subjects (ED50). Positive responses were defined as mean blood pressure (MAP) and/or heart rate (HR) changes ≥30% from baseline. Three parametric estimators and one nonparametric estimator were used to determine the ED50. RESULTS: Twenty-one subjects with median age 7.1 (range 5.4-9.5) years and median weight 23.6 (range 16.2-36.7) kg were recruited. A maximum median HR decrease of 20 b·min(-1) occurred at 50 s and a maximum median MAP increase of 12.5 mmHg occurred at 100 s after bolus dose administration. Fifteen subjects (71%) had a HR <60 b·min(-1) while one subject had a HR <40 b·min(-1) (minimum 35 b·min(-1)) for 60 s following the dexmedetomidine bolus. Four estimators led to an ED50 estimate for dexmedetomidine of 0.49 mcg·kg(-1) [95% CI 0.26-0.80 mcg·kg(-1)]. CONCLUSION: The ED50 of dexmedetomidine administered over 5 s without significant hemodynamic compromise is 0.49 mcg·kg(-1). Further work is needed to determine the 'safe' (ED5 or less) and effective dose for desired perioperative clinical outcomes.

Real-time cardiorespiratory coherence is blind to changes in respiration during general anesthesia.

PURPOSE: A novel real-time cardiorespiratory coherence (CRC) algorithm has been developed to monitor nociception during general anesthesia. CRC uses custom designed filters to track and analyze the respiratory sinus arrhythmia (RSA) as it moves in time and frequency. CRC is a form of sensor fusion between heart rate and respiration, estimating the strength of linear coupling between the two signals. The aim of this study was to estimate the effect of changes in respiration rate (RR) and peak airway pressure (PPaw) on CRC. The response of CRC was compared to a prior offline wavelet-based algorithm (WTCRC) as well as traditional univariate heart rate variability (HRV) measures. A nociception index was created for each algorithm, ranging from 0 (no nociception) to 100 (strong nociception). METHODS: Following ethics approval and informed consent, data were collected from 48 children receiving general anesthesia during dental surgery. The times of change in RR and PPaw events were noted in real-time. A total of 43 RR and 35 PPaw change events were analyzed post hoc in pseudo real-time. The nociception index averages were compared between a baseline period and a response period around each event. A Wilcoxon rank-sum test was used to compare changes. RESULTS: The change in RR changed the CRC nociception index by an average of -2.2 [95% CI from -10 to 4.7] (P > 0.3), and the change in PPaw changed the CRC nociception index by an average of 5.4 [-1.0 to 11] (P > 0.1). The changes were smaller than those of many traditional HRV measures. CONCLUSIONS: Real-time CRC was blind to the changes in respiration, and was less sensitive than many of the traditional HRV measures. A nociception index based on CRC can thus function across a wider range of respiratory conditions than can many traditional univariate HRV measures. The real-time CRC algorithm shows promise for monitoring nociception during general anesthesia.

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.

A systematic review and meta-analysis of caudal blockade versus alternative analgesic strategies for pediatric inguinal hernia repair.

BACKGROUND: The optimal analgesic strategy for pediatric inguinal hernia repair (IHR) remains undefined. We evaluated the available evidence comparing caudal blockade to alternative analgesic strategies in achieving post-operative analgesia. METHODS: A systematic review of prospective studies comparing analgesic practices for open unilateral pediatric IHR was performed by searching Medline, Embase, and the Cochrane library from 1950-2011. Articles were critically appraised and included if adequate description of experimental (caudal) and control (nerve blockade or wound infiltration) groups were performed. Pain scores were standardized and evaluated 1 hour after procedure as was the need for rescue analgesia using REVMAN. RESULTS: Three hundred and seventy articles were identified via our search strategy, thirteen of which were included for analysis. Articles identified were all single-institution, generally small (mean N=29 subjects/arm) and of poor quality (median Jadad score: 2). There was no significant difference in pain scores (-0.09, 95% CI: -0.32, 0.13, p=0.41) or the need for rescue analgesia (0.80, 95% CI: 0.56, 1.13, p=0.46). CONCLUSION: There is no demonstrable difference in post-operative pain scores or rescue analgesia when comparing caudal blockade with alternative pain management strategies after pediatric IHR. This equipoise suggests that caudal blockade may be obviated for lower risk and less time-consuming maneuvers in patients barring supplementary indications for pain control.

Monitoring nociception during general anesthesia with cardiorespiratory coherence.

A novel wavelet transform cardiorespiratory coherence (WTCRC) algorithm has been developed to measure the autonomic state. WTCRC may be used as a nociception index, ranging from 0 (no nociception, strong coherence) to 100 (strong nociception, low coherence). The aim of this study is to estimate the sensitivity of the algorithm to nociception (dental dam insertions) and antinociception (bolus doses of anesthetic drugs). WTCRC's sensitivity is compared to mean heart rate (HRmean) and mean non-invasive blood pressure (NIBPmean), which are commonly used clinical signs. Data were collected from 48 children receiving general anesthesia during dental surgery. The times of dental dam insertion and anesthetic bolus events were noted in real-time during surgeries. 42 dental dam insertion and 57 anesthetic bolus events were analyzed. The change in average WTCRC, HRmean, and NIBPmean was calculated between a baseline period before each event and a response period after. A Wilcoxon rank-sum test was used to compare changes. Dental dam insertion changed the WTCRC nociception index by an average of 14 (82 %) [95 % CI from 7.4 to 19], HRmean by 7.3 beats/min (8.1 %) [5.6-9.6], and NIBPmean by 8.3 mmHg (12 %) [4.9-13]. A bolus dose of anesthetics changed the WTCRC by -15 (-50 %) [-21 to -9.3], HRmean by -4.8 beats/min (4.6 %) [-6.6 to -2.9], and NIBPmean by -2.6 mmHg (3.4 %) [-4.7 to -0.50]. A nociception index based on cardiorespiratory coherence is more sensitive to nociception and antinociception than are HRmean or NIBPmean. The WTCRC algorithm shows promise for noninvasively monitoring nociception during general anesthesia.

Identification by families of pediatric adverse events and near misses overlooked by health care providers.

BACKGROUND: Identifying adverse events and near misses is essential to improving safety in the health care system. Patients are capable of reliably identifying and reporting adverse events. The effect of a patient safety reporting system used by families of pediatric inpatients on reporting of adverse events by health care providers has not previously been investigated. METHODS: Between Nov. 1, 2008, and Nov. 30, 2009, families of children discharged from a single ward of British Columbia's Children's Hospital were asked to respond to a questionnaire about adverse events and near misses during the hospital stay. Rates of reporting by health care providers for this period were compared with rates for the previous year. Family reports for specific incidents were matched with reports by health care providers to determine overlap. RESULTS: A total of 544 familes responded to the questionnaire. The estimated absolute increase in reports by health care providers per 100 admissions was 0.5% (95% confidence interval -1.8% to 2.7%). A total of 321 events were identified in 201 of the 544 family reports. Of these, 153 (48%) were determined to represent legitimate patient safety concerns. Only 8 (2.5%) of the adverse events reported by families were also reported by health care providers. INTERPRETATION: The introduction of a family-based system for reporting adverse events involving pediatric inpatients, administered at the time of discharge, did not change rates of reporting of adverse events and near misses by health care providers. Most reports submitted by families were not duplicated in the reporting system for health care providers, which suggests that families and staff members view safety-related events differently. However, almost half of the family reports represented legitimate patient safety concerns. Families appeared capable of providing valuable information for improving the safety of pediatric inpatients.