Association of delayed adequate antimicrobial treatment and organ dysfunction in pediatric bloodstream infections.

BACKGROUND: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. METHODS: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. RESULTS: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). CONCLUSIONS: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. IMPACT: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.

Designing a national pediatric critical care database: a Delphi consensus study.

PURPOSE: We sought to describe the processes undertaken for the systematic selection and consensus determination of the common data elements for inclusion in a national pediatric critical care database in Canada. METHODS: We conducted a multicentre Delphi consensus study of Canadian pediatric intensive care units (PICUs) participating in the creation of a national database. Participants were PICU health care professionals, allied health professionals, caregivers, and other stakeholders. A dedicated panel group created a baseline survey of data elements based on literature, current PICU databases, and expertise in the field. The survey was then used for a Delphi iterative consensus process over three rounds, conducted from March to June 2021. RESULTS: Of 86 invited participants, 68 (79%) engaged and agreed to participate as part of an expert panel. Panel participants were sent three rounds of the survey with response rates of 62 (91%), 61 (90%) and 55 (81%), respectively. After three rounds, 72 data elements were included from six domains, mostly reflecting clinical status and complex medical interventions received in the PICU. While race, gender, and home region were included by consensus, variables such as minority status, indigenous status, primary language, and ethnicity were not. CONCLUSION: We present the methodological framework used to select data elements by consensus for a national pediatric critical care database, with participation from a diverse stakeholder group of experts and caregivers from all PICUs in Canada. The selected core data elements will provide standardized and synthesized data for research, benchmarking, and quality improvement initiatives of critically ill children.

RéSUMé: OBJECTIF: Nous avons cherché à décrire les processus entrepris pour la sélection systématique et la détermination consensuelle des éléments de données communs à inclure dans une base de données nationale sur les soins intensifs pédiatriques au Canada. MéTHODE: Nous avons mené une étude multicentrique de consensus selon la méthode Delphi sur les unités de soins intensifs pédiatriques (USIP) canadiennes participant à la création d'une base de données nationale. Les personnes participant à l'étude étaient des professionnel·les de la santé de l'USIP, du personnel paramédical, des soignant·es et d'autres intervenant·es. Un groupe de travail spécialisé a créé une enquête de base des éléments de données sur la littérature, les bases de données actuelles portant sur les USIP et l'expertise dans le domaine. L'enquête a ensuite été utilisée pour créer un processus de consensus itératif Delphi sur trois cycles, mené de mars à juin 2021. RéSULTATS: Sur les 86 personnes invitées à participer, 68 (79 %) se sont engagées et ont accepté de participer à un groupe d'experts. Les membres du panel ont reçu trois rondes du sondage, avec des taux de réponse de 62 (91 %), 61 (90 %) et 55 (81 %), respectivement. Après trois cycles, 72 éléments de données provenant de six domaines ont été inclus, reflétant principalement l'état clinique et les interventions médicales complexes reçues à l'USIP. Alors que la race, le genre et la région d'origine ont été inclus par consensus, des variables telles que le statut de minorité, le statut d'autochtone, la langue principale parlée et l'origine ethnique ne l'ont pas été. CONCLUSION: Nous présentons le cadre méthodologique utilisé pour sélectionner des éléments de données consensuels destinés à une base de données nationale sur les soins intensifs pédiatriques, avec la participation d'un groupe diversifié d'expert·es et de soignant·es de toutes les USIP au Canada. Les éléments de données de base sélectionnés fourniront des données normalisées et synthétisées pour la recherche, l'analyse comparative et les initiatives d'amélioration de la qualité pour les enfants gravement malades.

Association between leukoreduced red blood cell transfusions and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

BACKGROUND AND OBJECTIVES: Hospital-acquired infections (HAIs) are an important problem in critically ill children. Studies show associations between the transfusion of non-leukoreduced red blood cell units (RBC) and increased HAI incidence rates (IRs). We hypothesize that transfusing pre-storage leukoreduced RBC is also associated with increased HAI IR. We aim to evaluate the associations between (1) a leukoreduced RBC restrictive transfusion strategy and HAI IR, (2) leukoreduced RBC transfusions and HAI IR, and (3) the number or volume of leukoreduced RBC transfusions and HAI IR in critically ill children. MATERIALS AND METHODS: This post hoc secondary analysis of the "Transfusion Requirement in Paediatric Intensive Care Units" (TRIPICU) randomized controlled trial (637 patients) used quasi-Poisson multivariable regression models to estimate HAI incidence rate ratios (IRRs) and 95% confidence intervals (CI). RESULTS: A restrictive transfusion strategy yielded an IRR of 0.88 (95% CI 0.67, 1.16). The association between transfusing leukoreduced RBCs (IRR 1.25; 95% CI 0.73, 2.13) and HAI IR was not statistically significant. However, we observed significant associations between patients who received >20 cc/kg volume of leukoreduced RBC transfusions (IRR 2.14; 95% CI 1.15, 3.99) and ≥3 leukoreduced RBC transfusions (IRR 2.40; 95% CI 1.15, 4.99) and HAI IR. CONCLUSION: Exposing critically ill children to >20 cc/kg or ≥3 leukoreduced RBC transfusions were associated with higher HAI IR, suggesting dose-response patterns.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Clinical Reasoning Behind Antibiotic Use in PICUs: A Qualitative Study.

OBJECTIVES: To describe the reasoning processes used by pediatric intensivists to make antibiotic-related decisions. DESIGN: Grounded theory qualitative study. SETTING: Three Canadian university-affiliated tertiary medical, surgical, and cardiac PICUs. PATIENTS: Twenty-one PICU physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted field observation during morning rounds followed by semistructured interviews with participants to examine the clinical reasoning behind antibiotic-related decisions (starting/stopping antibiotics, or treatment duration) made for patients with a suspected/proven bacterial infection. We used a grounded theory approach for data collection and analysis. Thematic saturation was reached after 21 interviews. Of the 21 participants, 10 (48%) were female, 15 (71%) were PICU attending staff, and 10 (48%) had greater than 10 years in clinical practice. Initial clinical reasoning involves using an analytical approach to determine the likelihood of bacterial infection. In case of uncertainty, an assessment of patient safety is performed, which partly overlaps with the use of intuitive clinical reasoning. Finally, if uncertainty remains, physicians tend to consult infectious diseases experts. Factors that override this clinical reasoning process include disease severity, pressure from consultants, and the tendency to continue antibiotic treatment initiated by colleagues. CONCLUSIONS: Antibiotic-related decisions for critically ill children are complex, and pediatric intensivists use several clinical reasoning strategies to decrease the uncertainty around the bacterial etiology of infections. However, disease severity and patient safety concerns may overrule decisions based on clinical evidence and lead to antibiotic use. Several cognitive biases were identified in the clinical reasoning processes.

Antimicrobial Stewardship in Bronchiolitis: A Retrospective Cohort Study of Three PICUs in Canada.

OBJECTIVES: To determine the association between the implementation of an antimicrobial stewardship program at a local PICU and to determine the association between the presence of an antimicrobial stewardship programs and antimicrobial use across three Canadian PICUs, among critically ill children with bronchiolitis. DESIGN: A multicenter retrospective cohort study. SETTING: Three Canadian PICUs over two winter seasons. INTERVENTIONS: An antimicrobial stewardship program was implemented at PICU 1 at the end of season 1. PATIENTS: Patients less than or equal to 2 years old admitted with bronchiolitis. MEASUREMENTS AND MAIN RESULTS: We used regression models with an interaction term between site (PICU 1 and PICU 2) and season (1 and 2) as the primary analysis to determine the association between implementation of an antimicrobial stewardship program at PICU 1 and 1) the proportion of antimicrobials discontinued 72 hours after hospital admission (logistic regression), 2) antimicrobial treatment duration (negative binomial regression), and 3) antimicrobial prescriptions within 48 hours of hospital admission (logistic regression). As a secondary analysis, we determined the association between having an antimicrobial stewardship program present and the aforementioned outcomes across the three PICUs. A total of 372 patients were included. During seasons 1 and 2, median age was 2.2 months (interquartile range, 1.2-6.2 mo) and 2.1 months (interquartile range, 1.3-6.8 mo), respectively. Among patients with viral bronchiolitis, implementation of an antimicrobial stewardship program at PICU 1 was associated with increased odds of discontinuing antimicrobials (odds ratio, 25.63; 95% CI, 2.86-326.29), but not with antimicrobial duration (odds ratio, 0.56; 95% CI, 0.31-1.02) or antimicrobial prescriptions (odds ratio, 0.33; 95% CI, 0.10-1.04). The presence of an antimicrobial stewardship program was similarly associated with antimicrobial discontinuation among patients with viral bronchiolitis (odds ratio, 20.79; 95% CI, 2.46-244.92), but not with antimicrobial duration (odds ratio, 0.57; 95% CI, 0.32-1.03) or antimicrobial prescriptions (odds ratio, 0.37; 95% CI, 0.12-1.11). CONCLUSIONS: Antimicrobial stewardship programs were associated with increased likelihood of discontinuing antimicrobial treatments in the PICU patients with viral bronchiolitis. However, larger studies are needed to further determine the role of an antimicrobial stewardship programs in reducing unnecessary antimicrobial use in this patient population.

Antimicrobial treatment duration for uncomplicated bloodstream infections in critically ill children: a multicentre observational study.

BACKGROUND: Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. METHODS: We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. RESULTS: Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11-25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11-24), respiratory 15 (IQR 11-26), intra-abdominal 20 (IQR 14-26), skin/soft tissue 17 (IQR 15-33), urinary 17 (IQR 15-35), central nervous system 33 (IQR 15-46) and other sources 29.5 (IQR 15-55) days. When sources of infection were unclear, the median duration was 13 (IQR 10-16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. CONCLUSIONS: Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.

Association between the length of storage of transfused leukoreduced red blood cell units and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

OBJECTIVE: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. BACKGROUND: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. METHODS: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). RESULTS: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). CONCLUSION: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.

Compliance With an Antibiotic Guideline for Suspected Ventilator-Associated Infection: The Ventilator-Associated INfection (VAIN2) Study.

OBJECTIVES: To evaluate a guideline for antibiotic decisions in children with suspected ventilator-associated infection. DESIGN: Prospective, observational cohort study conducted in 22 PICUs in the United States and Canada. SETTING: PICUs in 22 hospitals from April 2017 to January 2019. SUBJECTS: Children less than 3 years old on mechanical ventilation greater than 48 hours who had respiratory secretions cultured and antibiotics initiated for suspected ventilator-associated infection. INTERVENTIONS: After baseline data collection in children with suspected ventilator-associated infection (Phase 1), a consensus guideline was developed for advising antibiotic continuation or stopping at 48-72 hours (Phase 2) and implemented (Phase 3). Guideline-based antibiotic recommendations were provided to the treating clinicians once clinical and microbiologic data were available. Demographic and outcome data were collected, and guideline compliance and antibiotic utilization evaluated for Phase 1 and Phase 3. MEASUREMENTS AND MAIN RESULTS: Despite education and implementation efforts, guideline-concordant antibiotic management occurred in 158 of 227 (70%) Phase 3 subjects compared with 213 of 281 (76%) in Phase 1. Illness severity and positive respiratory cultures were the primary determinants of antibiotic continuation. For subjects with a positive respiratory culture but a score for which antibiotic discontinuation was recommended (score ≤ 2), only 27% of Phase 3 subjects had antibiotics discontinued. Antibiotic continuation was not associated with improved outcomes in these subjects and was associated with significantly longer duration of ventilation (median 5.5 d longer) and PICU stay (5 d longer) in the overall study population. Positive respiratory cultures were not associated with outcomes irrespective of antibiotic treatment. CONCLUSIONS: Antibiotic guideline efficacy and safety remain uncertain due to clinician failure to follow the guideline, instead primarily relying on respiratory culture results. Strategies to overcome clinician perceptions of respiratory cultures and other barriers will be vital for improving guideline adherence and antibiotic use in suspected ventilator-associated infection in future studies.

Prevalence of Acute Rehabilitation for Kids in the PICU: A Canadian Multicenter Point Prevalence Study.

OBJECTIVES: To evaluate mobilization practices, barriers, and mobility-related adverse events in Canadian PICUs. DESIGN: National 2-day point prevalence study. SETTING: Thirteen PICUs across Canada. PATIENTS: Children with a minimum 72-hour PICU length of stay on the allocated study day. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes of interest were the prevalence and nature of mobilization activities, rehabilitation resources, adverse events, and factors associated with out-of-bed mobility and therapist-provided mobility. Two PICUs (15%) had early mobilization practice guidelines, and one PICU (8%) reported a formal process for engaging families in the mobilization of patients. The prevalence of mobilization was 110 of 137 patient-days (80%). The commonest activity was out-of-bed mobility (87/137; 64% patient-days); there was no active mobilization on 46 patient-days (34%). Therapists provided mobility on 33% of patient-days. Mobility was most commonly facilitated by nurses (74% events) and family (49% events). Family participation was strongly associated with out-of-bed mobility (odds ratio 6.4; p = 0.001). Intubated, mechanically ventilated patients were mobilized out-of-bed on 18 of 50 patient-days (36%). However, the presence of an endotracheal tube, vasoactive infusions, and age greater than or equal to 3 years were independently associated with not being mobilized out-of-bed. Barriers were reported on 58 of 137 patient-days (42%), and adverse events occurred in 22 of 387 mobility events (6%). CONCLUSIONS: Mobilization is common and safe, and the majority of children in Canadian PICUs are being mobilized out-of-bed, even when mechanically ventilated. Family engagement in PICU-based rehabilitation is increasing. This study provides encouraging evidence that common barriers can be overcome in order to safely mobilize children in PICUs.

Associations Between Postoperative Management in the Critical Care Unit and Adolescent Developmental Outcomes Following Cardiac Surgery in Infancy: An Exploratory Study.

OBJECTIVES: Children with congenital heart disease are at high risk for developmental sequelae. Most studies focus on preoperative and intraoperative predictors of developmental impairment, with less attention to the postoperative period. The relationship between patient-related factors specific to the postoperative course in the PICU following cardiac surgery with long-term neurodevelopmental outcomes in adolescence was examined. DESIGN: Retrospective chart review of patients previously recruited to a study describing their developmental outcomes in adolescence. SETTING: Single tertiary care pediatric hospital in Canada. PATIENTS: Eighty adolescents, born between 1991 and 1999, with congenital heart disease who required open-heart surgery before 2 years old. MEASUREMENTS AND MAIN RESULTS: Several variables related to acuity of illness and complexity of postoperative course in the PICU were collected. Outcome measures included the Movement-Assessment Battery for Children-2 (motor), Leiter Brief Intelligence Quotient (cognition), and Strength and Difficulties Questionnaire (behavior). Analyses examined associations between PICU variables and long-term outcomes. Longer mechanical ventilation (ß = -0.49; p = 0.013) and dopamine use (ß = -14.41; p = 0.012) were associated with lower motor scores. Dopamine use was associated with lower cognitive scores (ß = -14.02; p = 0.027). Longer PICU stay (ß = 0.18; p = 0.002), having an open chest postoperatively (ß = 3.83; p = 0.017), longer mechanical ventilation (ß = 0.20; p = 0.001), longer inotrope support (ß = 0.27; p = 0.002), hours on dopamine (ß = 0.01; p = 0.007), days to enteral feeding (ß = 0.22; p = 0.012), lower hemoglobin (ß = -0.11; p = 0.004), and higher creatinine (ß = 0.05; p = 0.014) were all associated with behavioral difficulties. CONCLUSIONS: Several important developmental outcomes in adolescents were associated with factors related to their postoperative course in the PICU as infants. Findings may highlight those children at highest risk for neurodevelopmental sequelae and suggest new approaches to critical care management following open-heart surgery, with the aim of mitigating or preventing adverse long-term outcomes.

International Survey on Determinants of Antibiotic Duration and Discontinuation in Pediatric Critically Ill Patients.

OBJECTIVES: We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries. DESIGN: Cross-sectional survey. SETTING: PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries. CONCLUSIONS: Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.

Early fluid overload was associated with prolonged mechanical ventilation and more aggressive parameters in critically ill paediatric patients.

AIM: We evaluated the influence of early fluid overload on critically ill children admitted to a paediatric intensive care unit by examining mechanical ventilation (MV), mortality, length of stay and renal replacement therapy. METHODS: This retrospective cohort study covered January 2015 to December 2016 and focused on all episodes of MV support that exceeded 24 hours. The fluid overload percentage (FO%) was calculated daily for the first 72 hours and we estimated its effect on outcomes. RESULTS: We included 186 MV episodes in 154 patients. The median age was 13.8 months, with an interquartile range (IQR) of 3.8-34.0 months, and the mortality rate was 12.4%. The median FO% in the first 72 hours was 8.0% (IQR 3.6%-11.2%). An FO% of ≥10% was associated with higher ventilatory parameters, namely peak inspiratory pressure (P = .023) and positive end expiratory pressure (P = .003), and renal replacement therapy (P = .02) and higher mortality (8.8% vs 19.7%). In a multivariate Cox regression model, FO ≥ 10% at 72 hours was independently associated with longer MV support, but not mortality (P = .001). CONCLUSION: In a heterogeneous paediatric population given MV, an early cumulative FO of ≥10% was associated with more aggressive ventilatory parameters and prolonged length of MV, but not mortality.

The impact of a quality improvement project to standardize pain, agitation, and withdrawal assessments on the use of morphine and midazolam in the Pediatric Intensive Care Unit.

BACKGROUND: This study aims to assess the impact of a quality improvement initiative to increase assessments of pain, agitation, and iatrogenic withdrawal syndrome, on the use of sedative and analgesic medication in a pediatric intensive care unit. METHODS: This is a retrospective pre and post, observational, quality improvement study conducted in an 18-bed medical-surgical-cardiac, tertiary intensive care unit. We included patients consecutively admitted from October 1 to March 31 (pre-period 2015-2016, post-period 2016-2017) who were mechanically ventilated beyond 48 hours. A multidisciplinary team, including a family advisor, implemented the following interventions using rapid "Plan-Do-Study-Act cycles:" (a) standardized pain and sedation assessments, (b) standardized sedation goal setting, and (c) non-pharmacological strategies to manage pain and agitation. We did not implement any specific sedation protocol. We used audit and feedback to reinforce change. RESULTS: The post-intervention phase started once sedation scores were documented q12h for >60% of patients. The groups (n = 45 per group) were similar regarding demographics, severity of illness, and mechanical ventilation duration, but different in length of intensive care stay. The cumulative dose of midazolam equivalent was significantly lower in the post-intervention period (3.71 vs 2.65 mg/kg/mechanical ventilation day, P = 0.009, 95% CI: -1.12 (-1.89, -0.31)). Morphine equivalent usage went from 3.51 to 2.57 mg/kg/mechanical ventilation day (P = 0.066, 95% CI: -0.67 [-1.44, 0.05]). There were no significant pre-post-differences in the use of other sedative agents, rates of iatrogenic withdrawal syndrome or severe pain, nor medication cost. CONCLUSION: Implementation of a multifaceted QI project was successful at increasing standardized assessments of pain and agitation, and was associated with a significant reduction in midazolam use. We also observed a decrease in morphine use without increasing rates of severe pain. Incidence of iatrogenic withdrawal syndrome and cost were unchanged.

Can biomarkers improve the rational use of antibiotics?

PURPOSE OF REVIEW: We aim to review recent literature about the use of biomarkers to guide the initiation and duration of antibiotic treatments for suspected bacterial infections. RECENT FINDINGS: Several good quality meta-analyses show that procalcitonin can be safely used to guide antibiotic-related decisions, especially for respiratory infections, thereby decreasing unnecessary antibiotic exposure. Furthermore, the use of CRP-based algorithms to guide antibiotic initiation in primary care patients with acute respiratory infections is associated with a reduction in antibiotic use without an increase in adverse events. Regarding neutrophil CD64 and serum amyloid A, more good-quality evidence is needed to assess their utility as biomarkers to tailor antibiotic use. Finally, transcriptomics, metabolomics and proteomics are promising tools for the development of tests to differentiate specific host responses to viral, bacterial and noninfectious stimuli, but such tests still need further validation. SUMMARY: Evidence shows that the use of biomarkers, procalcitonin and CRP, can safely reduce unnecessary antibiotic prescriptions in certain infectious syndromes. The clinical utility of host-based strategies such as transcriptomics, metabolomics and proteomics for the diagnosis of infectious diseases has yet to be evaluated, as well as considerations such as costs, technical complexity and result turnaround time.

Determinants of Antibiotic Tailoring in Pediatric Intensive Care: A National Survey.

OBJECTIVES: To describe the criteria that currently guide empiric antibiotic treatment in children admitted to Canadian PICUs. DESIGN: Cross-sectional survey. SETTING: Canadian PICUs. SUBJECTS: Pediatric intensivists and pediatric infectious diseases specialists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used focus groups and literature review to design the survey questions and its four clinical scenarios (sepsis, pneumonia, meningitis, and intra-abdominal infections). We analyzed our results using descriptive statistics and multivariate linear regression. Our response rate was 60% for pediatric intensivists (62/103) and 36% for pediatric infectious diseases specialists (37/103). Variables related to patient characteristics, disease severity, pathogens, and clinical, laboratory, and radiologic infection markers were associated with longer courses of antibiotics, with median increment ranging from 1.75 to 7.75 days. The presence of positive viral polymerase chain reaction result was the only variable constantly associated with a reduction in antibiotic use (median decrease from, -3.25 to -8.25 d). Importantly, 67-92% of respondents would still use a full course of antibiotics despite positive viral polymerase chain reaction result and marked clinical improvement for patients with suspected sepsis, pneumonia, and intra-abdominal infection. Clinical experience was associated with shorter courses of antibiotics for meningitis and sepsis (-1.3 d [95% CI, -2.4 to -0.2] and -1.8 d [95% CI, -2.8 to -0.7] per 10 extra years of clinical experience, respectively). Finally, site and specialty also influenced antibiotic practices. CONCLUSIONS: Decisions about antibiotic management for PICU patients are complex and involve the assessment of several different variables. With the exception of a positive viral polymerase chain reaction, our findings suggest that physicians rarely consider reducing the duration of antibiotics despite clinical improvement. In contrast, they will prolong the duration when faced with a nonreassuring characteristic. The development of objective and evidence-based criteria to guide antibiotic therapy in critically ill children is crucial to ensure the rational use of these agents in PICUs.

Clinical Outcomes of Rapid Respiratory Virus Testing in Emergency Departments: A Systematic Review and Meta-Analysis.

Importance: Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear. Objective: To determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) was associated with decreased antibiotic use, ancillary tests, ED length of stay, and ED return visits and hospitalization and increased influenza antiviral treatment. Data Sources: Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022. Study Selection: Randomized clinical trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Two independent reviewers (T.S. and K.W.) extracted data and assessed risk of bias using the Cochrane Risk of Bias, version 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Main Outcomes and Measures: Antibiotic use and secondary outcomes were pooled separately as risk ratios (RRs) and risk difference estimates with 95% CIs. Results: Of 7157 studies identified, 11 (0.2%; n = 6068 patients) were included in pooled analyses. Routine rapid viral testing was not associated with antibiotic use (RR, 0.99; 95% CI, 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR, 1.33; 95% CI, 1.02-1.75; moderate certainty) and lower use of chest radiography (RR, 0.88; 95% CI, 0.79-0.98; moderate certainty) and blood tests (RR, 0.81; 95% CI, 0.69-0.97; moderate certainty). There was no association with urine testing (RR, 0.95; 95% CI, 0.77-1.17; low certainty), ED length of stay (0 hours; 95% CI, -0.17 to 0.16; moderate certainty), return visits (RR, 0.93; 95%, CI 0.79-1.08; moderate certainty) or hospitalization (RR, 1.01; 95% CI, 0.95-1.08; high certainty). Adults represented 963 participants (16%). There was no association of viral testing with antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, or industry funding. Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that there are limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted.

A survey of preventive measures used and their impact on central line-associated bloodstream infections (CLABSI) in intensive care units (SPIN-BACC).

BACKGROUND: The Quebec central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates in most ICUs. Given the surveillance trends observed in recent years, we aimed to determine what preventive measures have been implemented, if compliance to measures was monitored and its impact on CLABSI incidence rates. METHODS: All hospitals participating in the Quebec healthcare-associated infections surveillance program (SPIN-BACC - n = 48) received a 77-question survey about preventive measures implemented and monitored in their ICU. The questionnaire was validated for construct, content, face validity, and reliability. We used Poisson regression to measure the association between compliance monitoring to preventive measures and CLABSI rates. RESULTS: Forty-two (88%) eligible hospitals completed the survey. Two components from the maximum barrier precautions were used less optimally: cap (88%) and full sterile body drape (71%). Preventive measures reported included daily review of catheter need (79%) and evaluation of insertion site for the presence of inflammation (90%). Two hospitals rewired lines even if an infection was suspected or documented.In adult ICUs, there was a statistically significant greater decrease in CLABSI rates in ICUs that monitored compliance to preventive insertion measures, after adjusting for teaching status and the number of hospital beds (p = 0.036). CONCLUSIONS: Hospitals participating to the SPIN-BACC program follow recommendations for CLABSI prevention, but only a minority locally monitor their application. Compliance monitoring of preventive measures for catheter insertion was associated with a decrease in CLABSI incidence rates.