Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. METHOD: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Exploratory Outlier Detection for Acceleromyographic Neuromuscular Monitoring: Machine Learning Approach.

BACKGROUND: Perioperative quantitative monitoring of neuromuscular function in patients receiving neuromuscular blockers has become internationally recognized as an absolute and core necessity in modern anesthesia care. Because of their kinetic nature, artifactual recordings of acceleromyography-based neuromuscular monitoring devices are not unusual. These generate a great deal of cynicism among anesthesiologists, constituting an obstacle toward their widespread adoption. Through outlier analysis techniques, monitoring devices can learn to detect and flag signal abnormalities. Outlier analysis (or anomaly detection) refers to the problem of finding patterns in data that do not conform to expected behavior. OBJECTIVE: This study was motivated by the development of a smartphone app intended for neuromuscular monitoring based on combined accelerometric and angular hand movement data. During the paired comparison stage of this app against existing acceleromyography monitoring devices, it was noted that the results from both devices did not always concur. This study aims to engineer a set of features that enable the detection of outliers in the form of erroneous train-of-four (TOF) measurements from an acceleromyographic-based device. These features are tested for their potential in the detection of erroneous TOF measurements by developing an outlier detection algorithm. METHODS: A data set encompassing 533 high-sensitivity TOF measurements from 35 patients was created based on a multicentric open label trial of a purpose-built accelero- and gyroscopic-based neuromuscular monitoring app. A basic set of features was extracted based on raw data while a second set of features was purpose engineered based on TOF pattern characteristics. Two cost-sensitive logistic regression (CSLR) models were deployed to evaluate the performance of these features. The final output of the developed models was a binary classification, indicating if a TOF measurement was an outlier or not. RESULTS: A total of 7 basic features were extracted based on raw data, while another 8 features were engineered based on TOF pattern characteristics. The model training and testing were based on separate data sets: one with 319 measurements (18 outliers) and a second with 214 measurements (12 outliers). The F1 score (95% CI) was 0.86 (0.48-0.97) for the CSLR model with engineered features, significantly larger than the CSLR model with the basic features (0.29 [0.17-0.53]; P<.001). CONCLUSIONS: The set of engineered features and their corresponding incorporation in an outlier detection algorithm have the potential to increase overall neuromuscular monitoring data consistency. Integrating outlier flagging algorithms within neuromuscular monitors could potentially reduce overall acceleromyography-based reliability issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT03605225; https://clinicaltrials.gov/ct2/show/NCT03605225.

Predicting Intense Levels of Child Anxiety During Anesthesia Induction at Hospital Arrival.

In children, intense levels of anxiety during anesthetic induction are associated with a higher risk of pain, poor recovery, and emergence delirium. Therefore, it is important to identify these high-risk children at hospital arrival. The current study examined internalizing behavior (Child Behavior Checklist, CBCL) and state anxiety measures (modified Yale Preoperative Anxiety Scale, mYPAS, and State Trait Anxiety Inventory for Children, STAIC) at hospital arrival as predictors of anxiety during induction of anesthesia. One hundred children (aged 4 to 12 years) undergoing elective daycare surgery were included. The STAIC and mYPAS at hospital arrival were significant predictors of anxiety during induction, whereas CBCL was not. The STAIC state form at hospital arrival was the strongest predictor and could be used to identify children who will experience intense levels of anxiety during anesthetic induction, with sufficient to good diagnostic accuracy. Using the STAIC at hospital arrival allows targeted interventions to reduce anxiety in children.

Neuromuscular-blocking agents for tracheal intubation in pediatric patients (0-12 years): A systematic review and meta-analysis.

BACKGROUND: The benefit of using neuromuscular-blocking agents to facilitate tracheal intubation in pediatric patients remains unclear due to variations in design, treatments, and results among trials. By combining the available evidence, we aimed to establish whether scientific findings are consistent and can be generalized across various populations, settings, and treatments. METHODS: A systematic search for randomized controlled trials, related to the use of neuromuscular-blocking agents for tracheal intubation in American Society of Anesthesiologists class I-II participants (0-12 years), was performed. We considered all randomized controlled trials that studied whether intubation conditions and hemodynamics obtained by using neuromuscular-blocking agents were equivalent to those that were achieved without neuromuscular-blocking agents. We combined the outcomes in Review Manager 5.3 (RevMan, The Cochrane Collaboration) by pairwise random-effects meta-analysis using a risk ratio (RR) for intubation conditions and mean difference for hemodynamic values (mean [95% Confidence Intervals]). Heterogeneity among trials was explored using sensitivity analyses. RESULTS: We identified 22 eligible randomized controlled trials with 1651 participants. Overall, the use of a neuromuscular-blocking agent was associated with a clinically important increase in the likelihood of both excellent (RR = 1.41 [1.19-1.68], I2  = 76%) and acceptable (RR = 1.13 [1.07-1.19], I2  = 68%) intubating conditions. There is strong evidence that both unacceptable intubation conditions (RR = 0.35 [0.22-0.46], I2  = 23%) and failed first intubation attempts (RR = 0.25 [0.14-0.42], I2  = 0%) were less likely to occur when a neuromuscular-blocking agent was used compared with when it was not. Higher systolic or mean arterial pressures (mean difference = 13.3 [9.1-17.5] mm Hg, I2  = 69%) and heart rates (mean difference = 15.9 [11.0-20.8] beats/min, I2  = 75%) as well as a lower incidence of arrhythmias were observed when tracheal intubation was facilitated by neuromuscular-blocking agents. CONCLUSION: The use of a neuromuscular-blocking agent during light-to-moderate depth of anesthesia can improve the quality as well as the success rate of tracheal intubation and is associated with better hemodynamic stability during induction of anesthesia.

Systematic Review and Meta-analysis of Virtual Reality in Pediatrics: Effects on Pain and Anxiety.

BACKGROUND: Medical procedures often evoke pain and anxiety in pediatric patients. Virtual reality (VR) is a relatively new intervention that can be used to provide distraction during, or to prepare patients for, medical procedures. This meta-analysis is the first to collate evidence on the effectiveness of VR on reducing pain and anxiety in pediatric patients undergoing medical procedures. METHODS: On April 25, 2018, we searched EMBASE, MEDLINE, CENTRAL, PubMed, Web of Science, and PsycINFO with the keywords "VR," "children," and "adolescents." Studies that applied VR in a somatic setting with participants ≤21 years of age were included. VR was defined as a fully immersive 3-dimensional environment displayed in surround stereoscopic vision on a head-mounted display (HMD). We evaluated pain and anxiety outcomes during medical procedures in VR and standard care conditions. RESULTS: We identified 2889 citations, of which 17 met our inclusion criteria. VR was applied as distraction (n = 16) during venous access, dental, burn, or oncological care or as exposure (n = 1) before elective surgery under general anesthesia. The effect of VR was mostly studied in patients receiving burn care (n = 6). The overall weighted standardized mean difference (SMD) for VR was 1.30 (95% CI, 0.68-1.91) on patient-reported pain (based on 14 studies) and 1.32 (95% CI, 0.21-2.44) on patient-reported anxiety (based on 7 studies). The effect of VR on pediatric pain was also significant when observed by caregivers (SMD = 2.08; 95% CI, 0.55-3.61) or professionals (SMD = 3.02; 95% CI, 0.79-2.25). For anxiety, limited observer data were available. CONCLUSIONS: VR research in pediatrics has mainly focused on distraction. Large effect sizes indicate that VR is an effective distraction intervention to reduce pain and anxiety in pediatric patients undergoing a wide variety of medical procedures. However, further research on the effect of VR exposure as a preparation tool for medical procedures is needed because of the paucity of research into this field.

Virtual reality exposure before elective day care surgery to reduce anxiety and pain in children: A randomised controlled trial.

BACKGROUND: Pre-operative anxiety in children is very common and is associated with adverse outcomes. OBJECTIVE: The aim of this study was to investigate if virtual reality exposure (VRE) as a preparation tool for elective day care surgery in children is associated with lower levels of anxiety, pain and emergence delirium compared with a control group receiving care as usual (CAU). DESIGN: A randomised controlled single-blind trial. SETTING: A single university children's hospital in the Netherlands from March 2017 to October 2018. PATIENTS: Two-hundred children, 4 to 12 years old, undergoing elective day care surgery under general anaesthesia. INTERVENTION: On the day of surgery, children receiving VRE were exposed to a realistic child-friendly immersive virtual version of the operating theatre, so that they could get accustomed to the environment and general anaesthesia procedures. MAIN OUTCOME MEASURES: The primary outcome was anxiety during induction of anaesthesia (modified Yale Preoperative Anxiety Scale, mYPAS). Secondary outcomes were self-reported anxiety, self-reported and observed pain, emergence delirium, need for rescue analgesia (morphine) and parental anxiety. RESULTS: A total of 191 children were included in the analysis. During induction of anaesthesia, mYPAS levels (median [IQR] were similar in VRE, 40.0 [28.3 to 58.3] and CAU, 38.3 [28.3 to 53.3]; P = 0.862). No differences between groups were found in self-reported anxiety, pain, emergence delirium or parental anxiety. However, after adenoidectomy/tonsillectomy, children in the VRE condition needed rescue analgesia significantly less often (55.0%) than in the CAU condition (95.7%) (P = 0.002). CONCLUSION: In children undergoing elective day care surgery, VRE did not have a beneficial effect on anxiety, pain, emergence delirium or parental anxiety. However, after more painful surgery, children in the VRE group needed rescue analgesia significantly less often, a clinically important finding because of the side effects associated with analgesic drugs. Options for future research are to include children with higher levels of anxiety and pain and to examine the timing and duration of VRE. TRIAL REGISTRATION: Netherlands Trial Registry: NTR6116.

Development and validation of an android-based application for anaesthesia neuromuscular monitoring.

Quantitative neuromuscular block (NMB) assessment is an internationally recognised necessity in anesthesia care whenever neuromuscular blocking agents are administered. Despite this, the incidence of residual neuromuscular block and its associated major respiratory morbidity and mortality remain unacceptably high considering its preventable nature. Recent surveys show that quantitative NMB assessment is not consistently employed by anesthesiologists. Availability, price and practical concerns are some of the factors determining this phenomenon. Clinically assess and validate an Android cell phone application conceived specifically for NMB Monitoring in the anesthesia setting. Twenty-two adult ASA I to III patients scheduled to undergo elective surgical procedures under general anaesthesia requiring administration of a neuromuscular blocking agent were included. After anaesthesia induction, the grade of neuromuscular block was assessed at multiple independent time-points by paired comparison of the train of four (TOF) Ratios obtained by a Stimpod™ accelerometer and the currently developed application. Accelerometric measurements were made at the patient's hand after retrograde supramaximal stimulation of the ipsilateral ulnar nerve. TOF-ratios were subjected to bias analysis with 0.001 as the a priori established clinical significance cut-off. The difference between the two methods averaged 0.0004 (95% limits of agreement: ± 0.12), with 83.3% of the differences being under 0.05. This average inter-method difference was not significantly different than the a priori hypothesized difference cut-off of 0.001 (p = 0.78). Lin's concordance correlation coefficient and Pearson's correlation were both of 0.98. The custom developed Android application proved accurate for diagnosis of residual neuromuscular block.

Association between children's emotional/behavioral problems before adenotonsillectomy and postoperative pain scores at home.

BACKGROUND: Children undergoing adenotonsillectomy are at risk of severe postoperative pain and sleep problems. Little is known about the specific child risk factors for these problems. AIMS: The aim of this study was to assess the occurrence of postoperative pain, sleep problems, and medication adherence, and assess the influence of internalizing and externalizing problems on postoperative pain. METHODS: This prospective cohort study included 160 children, aged 1.5-5 years undergoing day-care adenotonsillectomy. Parents rated their child's pain with the Parents' Postoperative Pain Measure and their child's sleep problems with Vernon's Post Hospital Behavioral Questionnaire during the first 3 days and at day 10 postoperatively. Emotional/behavioral problems (ie, internalizing and externalizing behaviors) during the past 2 months were assessed using the Child Behavior Checklist. Regression analysis was used to assess whether children's pain intensity at home was associated with internalizing/externalizing problems, after controlling for age, preoperative child state anxiety, parental state anxiety, parental need for information, and socioeconomic status. RESULTS: Applying a threshold of ≥6 on the Parents' Postoperative Pain Measure, the incidence of moderate to severe pain was 57.6% at day 1, 53.5% at day 2, 35.4% at day 3, and 4.8% at day 10. During the first three postoperative nights, 37.1% of the children woke up. Internalizing problems (ß = 0.343; P = 0.001) and parental need for information (ß = 0.207; P = 0.011) were independently associated with higher pain scores at home during the first 3 days (R2 = 0.225). CONCLUSION: Following adenotonsillectomy, children often experienced moderate to severe pain and sleep problems during the first 3 days at home. Preoperative internalizing problems and parental need for information were independently associated with increased pain at home. Screening for these problems can help to identify vulnerable children and adapt the perioperative analgesic strategy accordingly (which includes preparation, information, and prescription of pain analgesics).

A Visual Analog Scale to assess anxiety in children during anesthesia induction (VAS-I): Results supporting its validity in a sample of day care surgery patients.

BACKGROUND: The modified Yale Preoperative Anxiety Scale is widely used to assess children's anxiety during induction of anesthesia, but requires training and its administration is time-consuming. A Visual Analog Scale, in contrast, requires no training, is easy-to-use and quickly completed. AIM: The aim of this study was to evaluate a Visual Analog Scale as a tool to assess anxiety during induction of anesthesia and to determine cut-offs to distinguish between anxious and nonanxious children. METHODS: Four hundred and one children (1.5-16 years) scheduled for daytime surgery were included. Children's anxiety during induction was rated by parents and anesthesiologists on a Visual Analog Scale and by a trained observer on the modified Yale Preoperative Anxiety Scale. Psychometric properties assessed were: (i) concurrent validity (correlations between parents' and anesthesiologists' Visual Analog Scale and modified Yale Preoperative Anxiety Scale scores); (ii) construct validity (differences between subgroups according to the children's age and the parents' anxiety as assessed by the State-Trait Anxiety Inventory); (iii) cross-informant agreement using Bland-Altman analysis; (iv) cut-offs to distinguish between anxious and nonanxious children (reference: modified Yale Preoperative Anxiety Scale ≥30). RESULTS: Correlations between parents' and anesthesiologists' Visual Analog Scale and modified Yale Preoperative Anxiety Scale scores were strong (0.68 and 0.73, respectively). Visual Analog Scale scores were higher for children ≤5 years compared to children aged ≥6. Visual Analog Scale scores of children of high-anxious parents were higher than those of low-anxious parents. The mean difference between parents' and anesthesiologists' Visual Analog Scale scores was 3.6, with 95% limits of agreement (-56.1 to 63.3). To classify anxious children, cut-offs for parents (≥37 mm) and anesthesiologists (≥30 mm) were established. CONCLUSIONS: The present data provide preliminary data for the validity of a Visual Analog Scale to assess children's anxiety during induction.

Audiovisual aid viewing immediately before pediatric induction moderates the accompanying parents' anxiety.

BACKGROUND: Parents accompanying their child during induction of anesthesia experience stress. The impact of audiovisual aid (AVA) on parental state anxiety and assessment of the child's anxiety at induction have been studied previously but need closer scrutiny. METHODS: One hundred and twenty parents whose children were scheduled for day-care surgery entered this randomized, controlled study. The intervention group (n = 60) was exposed to an AVA in the holding area. Parental anxiety was measured with the Spielberger State-Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information Scale (APAIS) at three time points: (i) on admission [T1]; (ii) in the holding area just before entering the operating theater [T2]; and (iii) after leaving [T3]. Additionally, at [T3], both parent and attending anesthetist evaluated the child's anxiety using a visual analogue scale. The anesthetist also filled out the Induction Compliance Checklist. RESULTS: On the state anxiety subscale, APAIS parental anxiety at T2 (P = 0.015) and T3 (P = 0.009) was lower in the AVA intervention group than in the control group. After induction, the child's anxiety rating by the anesthetist was significantly lower than by the parent, in both intervention and control groups. CONCLUSIONS: Preoperative AVA shown to parents immediately before induction moderates the increase in anxiety associated with the anesthetic induction of their child. Present results suggest that behavioral characteristics seem better predictors of child's anxiety during induction than anxiety ratings per se and that anesthetists are better than parents in predicting child's anxiety during induction.

Changes in sensory processing after anesthesia in toddlers.

BACKGROUND: Anesthesia and surgery may influence toddlers' sensory processing and consequently postoperative adjustment and behavior. This is the first study to: 1) test pre- to postoperative changes in sensory processing after pediatric anesthesia using the validated Infant/Toddler-Sensory Profile for 7-36 months (ITSP7-36); 2) identify putative predictors of these changes. METHODS: This prospective cohort study included 70 healthy boys (ASA I & II), aged 18-30 months, who underwent circumcision for religious reasons. Exclusion: boys with prior surgery and known developmental delay. PRIMARY OUTCOME: changes in sensory processing from the day of admission to day 14 postoperatively. The accompanying parent completed the ITSP7-36. Putative predictors: 1) child's preoperative emotional/behavioral problems; 2) child's state anxiety at induction; 3) postoperative pain at home. All children received standardized anesthesia and pain management. RESULTS: For 45 boys, assessments were completed at both time points. Significant changes in sensory processing (mean ITSP7-36 scores) were found on: low registration (47.5 to 49.8; P=0.015), sensory sensitivity (45.2 to 48.0; P=0.011), sensation avoiding (48.2 to 51.3; P=0.010), low threshold (93.4 to 99.4; P=0.007), auditory processing (39.3 to 43.3; P=0.000) and tactile processing (53.9 to 58.4; P=0.002). Higher scores on emotional/behavioral problems predicted changes on sensory processing. CONCLUSIONS: Sensory processing of these toddlers had changed after anesthesia. Children with more pre-existent emotional/behavioral problems are more vulnerable to these changes.

Development of a Virtual Reality Exposure Tool as Psychological Preparation for Elective Pediatric Day Care Surgery: Methodological Approach for a Randomized Controlled Trial.

BACKGROUND: Preoperative anxiety in children is highly prevalent and is associated with adverse outcomes. Existing psychosocial interventions to reduce preoperative anxiety are often aimed at distraction and are of limited efficacy. Gradual exposure is a far more effective way to reduce anxiety. Virtual reality (VR) provides a unique opportunity to gradually expose children to all aspects of the operating theater. OBJECTIVE: The aims of our study are (1) to develop a virtual reality exposure (VRE) tool to prepare children psychologically for surgery; and (2) to examine the efficacy of the VRE tool in a randomized controlled trial (RCT), in which VRE will be compared to care as usual (CAU). METHODS: The VRE tool is highly realistic and resembles the operating room environment accurately. With this tool, children will not only be able to explore the operating room environment, but also get accustomed to general anesthesia procedures. The PREoperative Virtual reality Intervention to Enhance Wellbeing (PREVIEW) study will be conducted. In this single-blinded RCT, 200 consecutive patients (aged 4 to 12 years) undergoing elective day care surgery for dental, oral, or ear-nose-throat problems, will be randomly allocated to the preoperative VRE intervention or CAU. The primary outcome is change in child state anxiety level between baseline and induction of anesthesia. Secondary outcome measures include child's postoperative anxiety, emergence delirium, postoperative pain, use of analgesics, health care use, and pre- and postoperative parental anxiety. RESULTS: The VRE tool has been developed. Participant recruitment began March 2017 and is expected to be completed by September 2018. CONCLUSIONS: To our knowledge, this is the first RCT evaluating the effect of a VRE tool to prepare children for surgery. The VRE intervention is expected to significantly diminish preoperative anxiety, postoperative pain, and the use of postoperative analgesics in pediatric patients. The tool could create a less stressful experience for both children and their parents, in line with the modern emphasis on patient- and family-centered care. TRIAL REGISTRATION: Netherlands Trial Registry: NTR6116; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6116 (Archived by WebCite at http://www.webcitation.org/6ryke7aep).