Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials.

BACKGROUND: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications. METHODS: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates. RESULTS: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty). CONCLUSION: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine.

Optimal Dose of Intranasal Dexmedetomidine for Laceration Repair in Children: A Phase II Dose-Ranging Study.

STUDY OBJECTIVE: To determine the optimal sedative dose of intranasal dexmedetomidine for children undergoing laceration repair. METHODS: This dose-ranging study employing the Bayesian Continual Reassessment Method enrolled children aged 0 to 10 years with a single laceration (<5 cm), requiring single-layer closure, who received topical anesthetic. Children were administered 1, 2, 3, or 4 mcg/kg intranasal dexmedetomidine. The primary outcome was the proportion with adequate sedation (Pediatric Sedation State Scale score of 2 or 3 for ≥90% of the time from sterile preparation to tying of the last suture). Secondary outcomes included the Observational Scale of Behavior Distress-Revised (range: 0 [no distress] to 23.5 [maximal distress]), postprocedure length of stay, and adverse events. RESULTS: We enrolled 55 children (35/55 [64%] males; median [interquartile range {IQR}] age 4 [2, 6] years). At 1, 2, 3, and 4 mcg/kg intranasal dexmedetomidine, respectively, the proportion of participants "adequately" sedated was 1/3 (33%), 2/9 (22%), 13/21 (62%), and 12/21 (57%); the posterior mean (95% equitailed credible intervals) for the probability of adequate sedation was 0.38 (0.04, 0.82), 0.25 (0.05, 0.54), 0.61 (0.41, 0.80), and 0.57 (0.36, 0.76); the median (IQR) Observational Scale of Behavior Distress-Revised scores during suturing was 2.7 (0.3, 3), 0 (0, 3.8), 0.6 (0, 5), and 0 (0, 3.7); the median (IQR) postprocedure length of stay was 67 (60, 78), 76 (60, 100), 89 (76, 109), and 113 (76, 150) minutes. There was 1 adverse event, a decrease in oxygen saturation at 4 mcg/kg, which resolved with head repositioning. CONCLUSION: Despite limitations, such as our limited sample size and subjectivity in Pediatric Sedation State Scale scoring, sedation efficacy for 3 and 4 mcg/kg were similarly based on equitailed credible intervals suggesting either could be considered optimal.

Hands-On Workshops Improve Emergency Department Physicians' Self-Reported Understanding of Pediatric Hand Injuries.

OBJECTIVES: The aims of this study were to assess emergency department (ED) physician perception of hand injuries and improve their understanding and confidence in treating these injuries. METHODS: Combined didactic and hands-on workshops for ED physicians were developed and run by a team of medical students, plastic surgeons, and ED physicians. The workshops consisted of a short review by a hand surgeon followed by hands-on sessions involving radiograph assessment, administration of local anesthetic, closed reduction, and splinting. Two sessions, 6 months apart, were provided. The workshops were evaluated using preworkshop and postworkshop questionnaires to assess the following domains: confidence and competence in treating hand injuries, knowledge of basic hand injury care, and feedback on the intervention itself. RESULTS: Fifty physicians participated in the workshops. After the workshops, physician recognition of hand fracture reduction as a critical skill increased. Self-efficacy ratings of fracture assessment, administration of local anesthetic, performing a reduction, and applying postreduction immobilization increased. Median scores on knowledge-testing questions also increased postintervention from 73.3% (95% confidence interval, 70.2-78.5) to 86.7% (95% confidence interval, 79.3-86.2) (P < 0.05). Finally, physicians reported that they found the intervention educational, useful, and important, and approximately 90% of participants indicated they intended to change their practice based on this intervention. CONCLUSIONS: Knowledge sharing between specialists and generalists through combined didactic and hands-on workshops is an effective and well-received method of refining physician knowledge and increasing confidence in treating subspecialty-specific clinical presentations.

Innovative virtual care delivery in a Canadian paediatric tertiary-care centre.

Health care systems and providers have rapidly adapted to virtual care delivery during this unprecedented time. Clinical programs initiated a variety of virtual care delivery models to maintain access to care, preserve personal protective equipment, and minimize infectious disease spread. Herein, we first describe the context within paediatric health delivery during the COVID-19 pandemic in Canada that fueled the rise of virtual care delivery. We then summarize the development, implementation, and beneficial impact of the innovative virtual care delivery programs currently in use at Children's Hospital of Eastern Ontario (CHEO) for both inpatient and outpatient care, specifically in our ambulatory clinics, emergency department, and mental health program. We highlight the transferable unique ways CHEO has integrated virtual care delivery through our governance structure, stakeholder engagement including patient, caregivers and health care providers and staff, development, and use of eHealth tools and novel approaches for patient care requiring physical assessment. We conclude with our vision for the future of virtual care, one component of paediatric care delivery in the post-COVID-19 era, which requires a common framework for virtual care evaluation. Importantly, rapid implementation of a primarily virtual care model at CHEO sustained high volume quality paediatric care. We believe many of these programs should and will remain in the post-pandemic era. A comprehensive, unified approach to evaluation is essential to yield meaningful results that inform sustainable care delivery models that integrate virtual care, and ultimately help ensure the best health outcomes for our patients.

XyloFUNS: Xylocaine to freeze during unpleasant nasopharyngeal swabs in children-a randomized controlled trial.

Objectives: To evaluate the efficacy of intranasal vaporized lidocaine in reducing pain for children undergoing a nasopharyngeal (NP) swab in the Emergency Department (ED). Study Design: A randomized blinded clinical trial was conducted in a paediatric ED. Both participants and the researcher evaluating the primary outcome were blinded. Children aged 6 to 17 years old requiring a NP swab were eligible. Participants were randomly allocated to receive intranasal lidocaine or a sham treatment prior to their NP swab. The primary outcome measure was pain during the swab as assessed by the visual analog scale. Secondary outcome measures were pain using the verbal numeric rating scale, fear using the children fear scale, and adverse effects of the intervention. Results: Eighty-eight participants were enrolled-45 in the lidocaine group and 43 controls. The mean visual analog scale scores for pain were 46 mm in the lidocaine group and 53 mm in the control group (mean difference 7 mm; 95% CI: -5 to 19 mm). No serious adverse events were observed. Conclusions: Intranasal lidocaine administered prior to NP swabs in the ED failed to show an improvement in pain scores for school-aged children and youth.

Impact of young age on outcomes of emergency department procedural sedation.

OBJECTIVES: Relatively little is known about outcomes of procedural sedation in very young children. Our objective was to examine the association between procedural sedation in young children (≤ 2 years) and the incidence of sedation-related adverse events. METHODS: This is a secondary analysis of a prospective cohort study of children 0 to 18 years undergoing parenteral procedural sedation in six Canadian pediatric emergency departments (ED). The primary risk factor was age ≤ 2 years. Secondary risk factors were sex, procedure type, pre-procedure and sedation medications. The outcomes examined were: serious adverse events (SAE), significant interventions, oxygen desaturation and vomiting. RESULTS: Of the 6295 patients included, 946 (15%) were ≤2 years. Children 13-24 months comprised 90% of the young age group. Children ≤ 2 years were sedated most commonly for laceration repair (n = 450; 47.6%), while orthopedic reduction was most common in children > 2 (n = 3983; 74.5%). Ketamine was the most common medication in both groups, but was used more frequently in children ≤ 2 years (80.9% vs 58.9%; p < 0.001). There was no difference in the odds of SAE (OR 0.83, 95% Confidence Interval (CI) 0.4 to 1.9), significant intervention (OR 0.82, 95% CI 0.4 to 1.7) or oxygen desaturation (OR 0.95, 95% CI 0.7 to 1.3) between age groups, however children ≤ 2 years vomited less frequently (OR 0.24, 95% CI 0.1 to 0.6). CONCLUSIONS: Young age, specifically between 13 and 24 months, was not associated with a significant difference in the incidence of adverse events.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Intravenous ketamine for emergency department treatment of suicidal ideation in a paediatric population: protocol for a double-blind, randomised, placebo-controlled, parallel-arm pilot trial (KSI study).

INTRODUCTION: Suicidal ideation (SI) is a common and severe cause of morbidity in adolescents. Patients frequently present to the emergency department (ED) for care, yet there is no acute therapeutic intervention for SI. A single dose of intravenous ketamine has demonstrated efficacy in rapidly reducing SI in adults; however, ketamine has not been studied in paediatrics. We aim to determine the feasibility of a trial of a single intravenous ketamine dose to reduce SI for patients in the paediatric ED. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, placebo-controlled, parallel-arm pilot trial of intravenous ketamine for ED treatment of SI in a paediatric population. INTERVENTION: one intravenous dose of 0.5 mg/kg of ketamine (max 50 mg), over 40 min. Placebo: one intravenous dose of 0.5 mL/kg (max 50 mL) of normal saline, over 40 min. Participants will be randomised in a 1:1 ratio. SI severity will be measured at baseline, 40 min, 80 min, 120 min, 24 hours and 7 days. We aim to recruit 20 participants. The primary feasibility outcome is the proportion of eligible patients who complete the study protocol. We will pilot three SI severity tools and explore the efficacy, safety and tolerability of the intervention. ETHICS AND DISSEMINATION: This study will be conducted according to Canadian Biomedical Research Tutorial, international standards of Good Clinical Practice and the Health Canada, Food and Drug Act, Part C, Division 5. The study documents have been approved by the CHEO Research Institute Research Ethics Board (CHEO REB (23/02E)). Participants must provide free and informed consent to participate. If incapable due to age, assenting participants with parental/legal guardian consent may participate. On completion, we will endeavour to present results at international conferences, and publish the results in a peer-reviewed journal. Participants will receive a results letter. TRIAL REGISTRATION NUMBER: NCT05468840.

Rates of pediatric emergency department visits vary according to neighborhood marginalization in Ottawa, Canada.

OBJECTIVES: To determine the association between neighborhood marginalization and rates of pediatric ED visits in Ottawa, Ontario. Secondary objectives investigated if the association between neighborhood marginalization and rates varied by year, acuity, and distance to hospital. METHODS: We calculated rates of pediatric ED visits per 1000 person-years for census dissemination areas within 100 km of the Children's Hospital of Eastern Ontario for patients < 18 years old from January 2018 through December 2020. The 2016 Ontario Marginalization Index categorized neighborhoods along quintiles of residential instability, material deprivation, ethnic concentration, and dependency. Generalized mixed-effects models determined the incidence rate ratios of pediatric ED visits for each quintile of marginalization; multivariate models were used to control for year of presentation and distance to hospital. Analysis was repeated for low versus high acuity ED visits. RESULTS: There were 154,146 ED visits from patients in 2055 census dissemination areas within 100 km of CHEO from 2018 to 2020. After controlling for year and distance from hospital in multivariate analyses, there were higher rates of pediatric ED visits for dissemination areas with high residential instability, high material deprivation, and low ethnic concentration. These findings did not change according to visit acuity. CONCLUSIONS: Neighborhood residential instability and material deprivation should be considered when locating alternatives to emergency care.

RéSUMé: OBJECTIFS: Déterminer l'association entre la marginalisation du quartier et les taux de visites aux urgences pédiatriques à Ottawa, en Ontario. Les objectifs secondaires visaient à déterminer si l'association entre la marginalisation du quartier et les taux variait selon l'année, l'acuité et la distance à l'hôpital. MéTHODES: Nous avons calculé les taux de visites aux urgences pédiatriques par tranche de 1000 années-personnes dans les aires de diffusion du recensement à moins de 100 km du Centre hospitalier pour enfants de l'est de l'Ontario pour les patients de moins de 18 ans de janvier 2018 à décembre 2020. L'Indice de marginalisation de l'Ontario de 2016 classait les quartiers selon des quintiles d'instabilité résidentielle, de privation matérielle, de concentration ethnique et de dépendance. Les modèles à effets mixtes généralisés ont déterminé les ratios des taux d'incidence des visites aux urgences pédiatriques pour chaque quintile de marginalisation; des modèles multivariés ont été utilisés pour contrôler l'année de présentation et la distance à l'hôpital. L'analyse a été répétée pour les visites à l'urgence de faible acuité par rapport à haute acuité. RéSULTATS: Il y a eu 154 146 visites aux urgences de patients dans 2 055 aires de diffusion du recensement à moins de 100 km du CHEO de 2018 à 2020. Après avoir tenu compte de l'année et de la distance par rapport à l'hôpital dans les analyses multivariées, on a constaté des taux plus élevés de visites aux urgences pédiatriques dans les zones de diffusion présentant une instabilité résidentielle élevée, une privation matérielle élevée et une faible concentration ethnique. Ces résultats n'ont pas changé selon l'acuité de la visite. CONCLUSIONS: L'instabilité résidentielle du quartier et la privation matérielle doivent être prises en compte lors de la recherche de solutions de rechange aux soins d'urgence.

Hybrid immunity after BNT162b2 Covid-19 vaccine administration in children aged 5 to 11 years.

BACKGROUND: The immune response to coronavirus disease 2019 (COVID-19) vaccination is stronger among adults with prior infection (hybrid immunity). It is important to understand if children demonstrate a similar response to better inform vaccination strategies. Our study investigated the humoral response after BNT162b2 COVID-19 vaccine doses in SARS-CoV-2 naïve and recovered children (5-11 years). METHODS: A multi-institutional, longitudinal, prospective cohort study was conducted. Children were enrolled in a case-ascertained antibody surveillance study in Ottawa, Ontario from September/2020-March/2021; at least one household member was severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive on RT-PCR. In November 2021, BNT162b2 COVID-19 vaccine was authorized for children aged 5-11 in Canada. Children enrolled in the surveillance study intending to receive two vaccine doses were invited to participate in this study from November 2021-April 2022. Main exposure was prior SARS-CoV-2 infection, defined by positive RT-PCR or SARS-CoV-2 anti-N IgG antibody presence. Primary outcome was spike IgG antibody levels measured following the first vaccine dose (2-3 weeks) and second vaccine dose (3-4 weeks). RESULTS: Of the 153 eligible children, 75 participants (median age 8.9 IQR (7.4, 10.2) years; 38 (50.7 %) female; 59 (78.7 %) Caucasian) had complete follow-up. Fifty-four (72 %) children had prior SARS-COV-2 infection. Spike IgG antibody levels are significantly higher in SARS-CoV-2 recovered participants after receiving the first dose (p < 0.001) and the second (p = 0.01) compared to infection naïve children. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 recovered children (5-11 years) demonstrated higher antibody levels following first BNT162b2 vaccine dose compared with naïve children. Most reached antibody saturation two to three weeks after the first dose; a second dose didn't change the saturation level. A single vaccine dose in SARS-CoV-2 recovered children may be equivalent or superior to a 2-dose primary series in naïve children. Further research is needed on the durability and quality of a single vaccine dose in this population.

Accuracy of point-of-care SARS-CoV-2 detection using buccal swabs in pediatric emergency departments.

To optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and the laboratory approach is simple, accurate, and rapid. In this prospective cohort study we evaluated the accuracy of a point-of care nucleic acid device using caregiver/patient self-collected buccal swabs. Participants were recruited in 14 Canadian tertiary care pediatric emergency departments. Children <18 years of age deemed to require SARS-CoV-2 testing were eligible. Caregivers or the patient-collected buccal swabs which were tested on the ABBOTT ID NOW. The reference standard was nasopharyngeal swab specimens collected by a healthcare provider tested via laboratory reverse transcription PCR (RT-PCR). We enrolled 2,640 study participants and 14.4% (381/2,640) were SARS-CoV-2 RT-PCR-positive. Eight percent (223/2,640) and 85.0% (2,244/2,640) were concordant test-positive and concordant test-negative, respectively. Sensitivity and specificity of the investigational approach were 58.5% [95% confidence interval (CI): 53.4, 63.5] and 99.3% (95% CI: 98.9, 99.6), respectively. Cycle threshold values were lower among concordant [median 17 (15, 21)] relative to discordant [median 30 (22, 35)] swabs (P < 0.001). Sensitivity was greatest among children <4 years of age, when caregivers performed the swabs, among unvaccinated children, and those with shorter symptom duration. Across multiple pain measures, less pain was associated with buccal swab testing. Although accuracy of the buccal swab point-of-care SARS-CoV-2 test was good and negative agreement was excellent, sensitivity was only 58.5%. Concordance was greater among those with higher viral loads, and the approach involving buccal swabs was less painful.IMPORTANCETo optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and laboratory approach is simple, accurate, and rapid. We evaluated the accuracy and pain associated with buccal swab specimen collection by caregivers or children themselves who were tested using a point-of-care isothermal nucleic acid amplification SARS-CoV-2 test. This novel approach was compared to nasopharyngeal swab specimens tested using laboratory-based PCR tests. While negative agreement was excellent, positive percent agreement was less than 60%. Concordance was greater among those with higher viral loads, and thus, sensitivity is excellent when transmissibility is more likely to occur. Importantly, the approach involving buccal swabs was significantly less painful, and thus, children and their caregivers are more likely to agree to testing using such an approach.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT05040763).

Types of diagnostic errors reported by paediatric emergency providers in a global paediatric emergency care research network.

BACKGROUND: Diagnostic errors, reframed as missed opportunities for improving diagnosis (MOIDs), are poorly understood in the paediatric emergency department (ED) setting. We investigated the clinical experience, harm and contributing factors related to MOIDs reported by physicians working in paediatric EDs. METHODS: We developed a web-based survey in which physicians participating in the international Paediatric Emergency Research Network representing five out of six WHO regions, described examples of MOIDs involving their own or a colleague's patients. Respondents provided case summaries and answered questions regarding harm and factors contributing to the event. RESULTS: Of 1594 physicians surveyed, 412 (25.8%) responded (mean age=43 years (SD=9.2), 42.0% female, mean years in practice=12 (SD=9.0)). Patient presentations involving MOIDs had common undifferentiated symptoms at initial presentation, including abdominal pain (21.1%), fever (17.2%) and vomiting (16.5%). Patients were discharged from the ED with commonly reported diagnoses, including acute gastroenteritis (16.7%), viral syndrome (10.2%) and constipation (7.0%). Most reported MOIDs (65%) were detected on ED return visits (46% within 24 hours and 76% within 72 hours). The most common reported MOID was appendicitis (11.4%), followed by brain tumour (4.4%), meningitis (4.4%) and non-accidental trauma (4.1%). More than half (59.1%) of the reported MOIDs involved the patient/parent-provider encounter (eg, misinterpreted/ignored history or an incomplete/inadequate physical examination). Types of MOIDs and contributing factors did not differ significantly between countries. More than half of patients had either moderate (48.7%) or major (10%) harm due to the MOID. CONCLUSIONS: An international cohort of paediatric ED physicians reported several MOIDs, often in children who presented to the ED with common undifferentiated symptoms. Many of these were related to patient/parent-provider interaction factors such as suboptimal history and physical examination. Physicians' personal experiences offer an underexplored source for investigating and mitigating diagnostic errors in the paediatric ED.

Inhaled nitrous oxide for painful procedures in children and youth: a systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to synthesize indication-based evidence for N2O for distress and pain in children. STUDY DESIGN: We included trials of N2O in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting N2O or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively. RESULTS: We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% N2O (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I2 = 0%) and 50% N2O plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I2 = 43%) were superior to EMLA. 50% N2O was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I2 = 15%). For distress and pain during laceration repair, N2O was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), N2O was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), N2O was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), N2O was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), N2O plus EMLA was "favorable" versus N2O and EMLA alone. Common adverse effects of N2O included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with N2O alone (278/1147 (24.2%)) versus N2O plus midazolam (48/52 (92.3%)) and N2O plus fentanyl (123/201 (61.2%)). CONCLUSIONS: There is sufficient evidence to recommend N2O plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.

RéSUMé: OBJECTIFS: Synthétiser les données probantes fondées sur l'indication pour le N2O pour la détresse et la douleur chez les enfants. Plan d'étude : Nous avons inclus des essais de N2O chez des participants âgés de 0 à 21 ans, signalant une détresse ou une douleur pour les procédures des services d'urgence. Le critère de jugement principal était la détresse procédurale. Lorsqu'une méta-analyse n'était pas possible, nous avons utilisé la classification de Tricco et al. "neutre" (p>0,05), "favorable" ou "défavorable" (p<0,05, en faveur de la N2O ou du comparateur, respectivement). Nous avons utilisé l'outil risque de biais de la Collaboration Cochrane et le système Grading of Recommendations Assessment, Development, and Evaluation pour évaluer respectivement le risque de biais et la qualité des preuves. RéSULTATS: Nous avons inclus 30 essais. Pour la douleur sur l'échelle visuelle analogique (0-100 mm) pendant l'insertion IV, 70 % de N2O (delta : -16,5 ; IC à 95% : -28,6 à -4,4 ; p = 0,008 ; trois essais ; I2 = 0 %) et 50 % de N2O plus un mélange eutectique d'anesthésiques locaux (EMLA) (delta : -1,2 ; IC à 95 % : -2,1 à -0,3 ; p = 0,007 ; deux essais ; I2 = 43 %) étaient supérieurs à l'EMLA. La N2O à 50 % n'était pas supérieure à l'EMLA (delta : -0,4 ; IC à 95 % : -1,2 à 0,3 ; p = 0,26 ; deux essais ; I2 = 15 %). En ce qui concerne la détresse et la douleur pendant la réparation des lacérations, le N2O était "favorable" par rapport à la lidocaïne SC, à l'oxygène et au midazolam oral, mais "neutre" par rapport à la kétamine IV (cinq essais). Pour la détresse et la douleur pendant la réduction des fractures (trois essais), le N2O était « neutre ¼ par rapport à la mépéridine IM plus prométhazine, l'anesthésie régionale et la kétamine IV plus midazolam. Pour la détresse et la douleur lors de la ponction lombaire (un essai), le N2O était "favorable" par rapport à l'oxygène. Pour la détresse et la douleur pendant le cathétérisme urétral (un essai), N2O était "neutre" par rapport au midazolam oral. Pour la douleur pendant l'injection intramusculaire (un essai), le N2O plus EMLA était « favorable ¼ par rapport au N2O et à l'EMLA seuls. Les effets indésirables les plus fréquents de la N2O étaient les nausées (4,4 %), l'agitation (3,7 %) et les vomissements (3,6 %). Les EI étaient moins fréquents avec la N2O seule (278/1147 (24,2 %)) par rapport au N2O plus midazolam (48/52 (92,3 %)) et le N2O plus fentanyl (123/201 (61,2 %)). CONCLUSIONS: Il existe suffisamment de preuves pour recommander le N2O plus un anesthésique topique pour l'insertion intraveineuse et la réparation des lacérations. Les effets indésirables sont plus importants lorsqu'ils sont combinés avec d'autres agents sédatifs.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Epinephrine and dexamethasone in children with bronchiolitis.

BACKGROUND: Although numerous studies have explored the benefit of using nebulized epinephrine or corticosteroids alone to treat infants with bronchiolitis, the effectiveness of combining these medications is not well established. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial in which 800 infants (6 weeks to 12 months of age) with bronchiolitis who were seen in the pediatric emergency department were randomly assigned to one of four study groups. One group received two treatments of nebulized epinephrine (3 ml of epinephrine in a 1:1000 solution per treatment) and a total of six oral doses of dexamethasone (1.0 mg per kilogram of body weight in the emergency department and 0.6 mg per kilogram for an additional 5 days) (the epinephrine-dexamethasone group), the second group received nebulized epinephrine and oral placebo (the epinephrine group), the third received nebulized placebo and oral dexamethasone (the dexamethasone group), and the fourth received nebulized placebo and oral placebo (the placebo group). The primary outcome was hospital admission within 7 days after the day of enrollment (the initial visit to the emergency department). RESULTS: Baseline clinical characteristics were similar among the four groups. By the seventh day, 34 infants (17.1%) in the epinephrine-dexamethasone group, 47 (23.7%) in the epinephrine group, 51 (25.6%) in the dexamethasone group, and 53 (26.4%) in the placebo group had been admitted to the hospital. In the unadjusted analysis, only the infants in the epinephrine-dexamethasone group were significantly less likely than those in the placebo group to be admitted by day 7 (relative risk, 0.65; 95% confidence interval, 0.45 to 0.95, P=0.02). However, with adjustment for multiple comparisons, this result was rendered insignificant (P=0.07). There were no serious adverse events. CONCLUSIONS: Among infants with bronchiolitis treated in the emergency department, combined therapy with dexamethasone and epinephrine may significantly reduce hospital admissions. (Current Controlled Trials number, ISRCTN56745572.)