Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial.

OBJECTIVES: In children with septic shock, guidelines recommend resuscitation with 40-60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock. DESIGN: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days. SETTING: Four pediatric Emergency Departments in Queensland, Australia. PATIENTS: Children between 28 days and 18 years old with septic shock. INTERVENTIONS: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23). MEASUREMENTS AND MAIN RESULTS: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9-12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12-26 min) in the intervention group, and 49 minutes (IQR, 29-63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0-10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6-28.6 mL/kg) in the standard group (difference, -20.0; 95% CI, -28.0 to -12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26-27 d) versus 26 days (IQR, 25-27 d). There were no adverse events reported associated with the intervention. CONCLUSIONS: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.

Measuring Physical Function in the PICU: Development and Testing of a Children's Version (Age 2-18 yr) of the Chelsea Critical Care Physical Assessment Tool.

OBJECTIVES: To adapt and develop a reliable and easily administered outcome measure of physical and respiratory function in critically ill children in the PICU. DESIGN: Modified Delphi study to adapt the Chelsea Critical Care Physical Assessment (CPAx) tool for use in children 2-18 years old, with subsequent prospective testing in a single-center cohort. SETTING: Single-center tertiary PICU. SUBJECTS: Delphi process in 27 panelists (including physiotherapists, occupational therapists, and pediatric intensivists from seven countries from January 2018 to March 2018). Cohort study in 54 patients admitted to PICU for greater than 24 hours over a 3-month period (April 2018 to June 2018), with median age 5.5 years (interquartile range [IQR], 3-12.75 yr), 33 of 54 male, and 38 of 54 invasively ventilated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three Delphi iterations were required to reach greater than or equal to 80% consensus in all the children's CPAx (cCPAx) items. In the subsequent cohort study, six physiotherapists used the cCPAx tool and scored 54 participants, with a total 106 observations. The median cCPAx tool score was 14.50 (IQR, 3-25) out of a possible total of 50. Inter-rater reliability for 30 randomly selected participants was excellent (intraclass correlation coefficient, 0.998). Completion rate of cCPAx in the 54 patients occurred in 78 of 106 occasions (74%). CONCLUSIONS: The cCPAx tool content that was developed using Delphi methodology provided a feasible and clinically relevant tool for use in assessing physical morbidity in PICU patients 2-18 years old. Overall, the cCPAx scores were low, demonstrating low levels of physical function and high levels of immobility during PICU care.

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study.

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29-120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0-26.0) days in the intervention and 21.0 (0.0-25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5-11.3) days in the intervention group versus 6.9 (3.0-11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6-101.2) hours in the intervention group versus 47.3 (22.4-106.8) hours in the standard care group (median difference -12 hr; 95% CI, -56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT.

Long-term outcomes after paediatric sepsis (LOTUS)-A protocol for an Australian cohort study.

BACKGROUND: Globally, sepsis has been identified as one of the leading causes of preventable childhood mortality and morbidity. Previous studies on intensive care patients estimated that approximately 30% of children with sepsis experience some form of disability at discharge. Development of care has seen growing numbers of children treated for sepsis not requiring a PICU admission; however, outcomes in this population are yet to be understood. Further focus is required to understand sepsis survivorship across the wider population to address knowledge gaps and morbidity burden in the broader surviving population. AIMS: To assess the cognitive, physical, emotional and social health of children surviving sepsis 2 years after hospital discharge. STUDY DESIGN: A prospective, observational cohort study. RESULTS: Two hundred and thirty-two children will be screened, 2 years after their hospital admission, and approached for participation in this study. Children who are <18 years of age at follow-up, treated for sepsis-related organ dysfunction or septic shock in Queensland between October 2018 and December 2019, will be included. Children who are deceased at follow-up, under care of the state, or require English interpreters will be excluded from participation. Data will be collected through an online follow-up survey comprising validated caregiver-reported questionnaires covering the four Post Intensive Care Syndrome-paediatrics (PICS-p) domains (cognitive, physical, emotional and social health; Manning et al. Pediatr Crit Care Med, 2018, 19, 298-300). The primary outcome is an adaptive behaviour of the participants assessed using the Vinelands-3 tool. Secondary outcomes will include neurodevelopment, quality of life, child distress, overall function, executive function, caregiver's distress and caregiver's stress. Analysis of variance (ANOVA), Kruskal-Wallis and Fisher's exact test/chi-squared tests will be used for statistical analyses. No adjustments will be made for multiple comparisons but it is acknowledged that comparisons made in this study are exploratory. RELEVANCE TO CLINICAL PRACTICE: With more children surviving sepsis, there is a need for a more comprehensive assessment of patient and family outcomes to allow support structures for families leaving the hospital after sepsis. This study is expected to inform clinicians and stakeholders of patient and family well-being after sepsis survivorship.

Long-term outcomes after paediatric sepsis: A narrative review.

OBJECTIVES: Sepsis is one of the leading causes of mortality in the paediatric population. However, knowledge is limited around morbidity in childhood sepsis survivors. The aim of this review is to identify and critically appraise the evidence for long-term outcomes in paediatric survivors of sepsis using the Post Intensive Care Syndrome - paediatrics (PICS-p) framework. METHODS: A search for studies was undertaken in the electronic databases PubMed and Cumulative Index to Nursing and Allied Health Literature from 2010. Criteria for inclusion are as follows: participants >28 d adjusted age, diagnosed with sepsis, and follow-up after hospital discharge using a validated outcome measure. The PICS-p subdomains (cognitive, physical, emotional, and social) guided thematic synthesis of current literature. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: In total, nine studies, involving 2136 children, using 13 different outcome measures were included in the review. Mean follow-up time was 28 d after hospital discharge with a range of 7 d to 12 m across the PICS-p domains. Physical functioning was the most examined domain explored in six studies that used four outcome measures. Morbidity in physical, cognitive, and emotional domains was still evident at 9-12 m. No literature identified explored social health. CONCLUSION(S): Overall, we identified a wide range of measures, administered at various time points in studies of sepsis survivorship in childhood. Variation in follow-up timepoints, validated tools, and restricted outcome measures highlighted the lack in understanding of this priority area. Furthermore, long-term outcome research and a cohesive understanding across all the PICS-p domains are needed to better understand this population. REGISTRATION: Not registered.

Post-traumatic stress and health-related quality of life after admission to paediatric intensive care: Longitudinal associations in mother-child dyads.

OBJECTIVE: Elevated post-traumatic stress symptoms (PTSS) and reduced health-related quality of life (HRQoL) are commonly experienced in both children and their parent's following admission to the paediatric intensive care unit (PICU). Previous research has demonstrated a conflict in the directionality between PTSS and HRQoL in children and their parents. Our study sought to explore the interconnection and transmission between PTSS and HRQoL in children and their mothers following an admission to the PICU. DESIGN: Prospective longitudinal design. SETTING: Two tertiary care PICUs in Brisbane, Australia. PATIENTS: Two hundred eighty-two mother-child dyads of children aged 2-16 years admitted to the PICU for >8 h. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Four waves of dyadic data (n = 282 mother-child dyads) over a 12-month period from the PICU post-traumatic stress study were used. Cross-lagged panel modelling was used to examine the link between maternal-rated PTSS and HRQoL across children and their mothers. Actor-partner interdependence modelling was then used to examine the interconnections between mothers and children over time. In the dyadic model, partner effects were only present from mother to their child (i.e., higher maternal PTSS was predictive of higher child PTSS at subsequent time points). Higher maternal PTSS predicted lower maternal mental HRQoL but not lower child psychosocial HRQoL. Actor effects were also present with lower child psychosocial HRQoL, predicting higher child PTSS at subsequent time points. Findings indicated that a unidirectional transmission process from mother to child may be present after a child's life-threatening illness. CONCLUSIONS: This study provides evidence for a long-term negative influence of maternal PTSS on child PTSS in families who have experienced a paediatric critical illness or injury. This highlights the important role of maternal wellbeing in children's mental health outcomes following PICU admission. Further research needs to explore the temporal and dyadic relationships of PTSS and HRQoL.

Neurodevelopmental outcome and quality of life in children admitted to the paediatric intensive care unit: A single-centre Australian cohort study.

BACKGROUND: The development of new morbidities has become increasingly identified in paediatric critical care medicine. To date, there has been limited research of long-term outcomes following paediatric critical illness in Australia. OBJECTIVES: The objective of this study was to quantify neurodevelopmental impairments in children following paediatric intensive care unit (PICU) discharge and their association with health-related quality of life (HRQoL). METHODS: A single-centre ambidirectional cohort study at an Australian hospital. Parents of children admitted to the PICU between 2015 and 2017 were invited to participate. Neurodevelopmental outcome and HRQoL was prospectively evaluated, using the Ages and Stages Questionnaire (<5 years), Strengths and Difficulties Questionnaire (≥5 years), and Pediatric Quality of Life Inventory™, respectively. RESULTS: A total of 230 parents of critically ill children participated. Children were 1.9 years old (median, interquartile range [IQR]: 0.2, 7.5), male (59.6%), and ventilated (49.1%) at PICU admission. The median time to follow-up was 24.4 months (IQR: 16.3, 36.7). Parent respondents were more likely to be female (85.5%), White (88.3%), and partnered (81.1%). The incidence of overall neurodevelopmental impairment was 30% (33% in children aged <5 years; 24% in children aged ≥5 years). The incidence of poor HRQoL was 37.9%. History of developmental delay was independently associated with overall neurodevelopmental impairment (adjusted odds ratio [aOR]: 4.21, 95% confidence interval: 2.05, 8.63) and poor HRQoL (aOR: 7.29, 95% confidence interval: 3.26, 16.27). Two or more PICU admissions (aOR: 4.10, IQR: 1.82, 9.26) was also associated with poor HRQoL. CONCLUSIONS: This is the first contemporary view of PICU long-term outcomes conducted in Australia and significantly informs ongoing research in this area. Approximately one-third of PICU survivors demonstrate neurodevelopmental impairment and reduced quality of life. Multiple domains of post-intensive care syndrome-paediatrics must be considered to have a comprehensive understanding of child outcomes. Assessment of baseline/premorbid functioning is also essential in order to understand the true impact of illness and PICU admission.

Implementing paediatric appropriate use criteria for endotracheal suction to reduce complications in mechanically ventilated children with respiratory infections.

BACKGROUND: Endotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections. OBJECTIVE: The objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions. METHODS: A mixed-method, pre-implementation-post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models. RESULTS: Data from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use. CONCLUSIONS: Implementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections.

Measuring Social Health Following Pediatric Critical Illness: A Scoping Review and Conceptual Framework.

OBJECTIVE: Social health is an important component of recovery following critical illness as modeled in the pediatric Post-Intensive Care Syndrome framework. We conducted a scoping review of studies measuring social outcomes (measurable components of social health) following pediatric critical illness and propose a conceptual framework of the social outcomes measured in these studies. DATA SOURCES: PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Registry. STUDY SELECTION: We identified studies evaluating social outcomes in pediatric intensive care unit (PICU) survivors or their families from 1970-2017 as part of a broader scoping review of outcomes after pediatric critical illness. DATA EXTRACTION: We identified articles by dual review and dual-extracted study characteristics, instruments, and instrument validation and administration information. For instruments used in studies evaluating a social outcome, we collected instrument content and described it using qualitative methods adapted to a scoping review. DATA SYNTHESIS: Of 407 articles identified in the scoping review, 223 (55%) evaluated a social outcome. The majority were conducted in North America and the United Kingdom, with wide variation in methodology and population. Among these studies, 38 unique instruments were used to evaluate a social outcome. Specific social outcomes measured included individual (independence, attachment, empathy, social behaviors, social cognition, and social interest), environmental (community perceptions and environment), and network (activities and relationships) characteristics, together with school and family outcomes. While many instruments assessed more than one social outcome, no instrument evaluated all areas of social outcome. CONCLUSIONS: The full range of social outcomes reported following pediatric critical illness were not captured by any single instrument. The lack of a comprehensive instrument focused on social outcomes may contribute to under-appreciation of the importance of social outcomes and their under-representation in PICU outcomes research. A more comprehensive evaluation of social outcomes will improve understanding of overall recovery following pediatric critical illness.

Adaptive Clinical Trials in Pediatric Critical Care: A Systematic Review.

OBJECTIVES: This systematic review investigates the use of adaptive designs in randomized controlled trials (RCTs) in pediatric critical care. DATA SOURCES: PICU RCTs, published between 1986 and 2020, stored in the www.PICUtrials.net database and MEDLINE, EMBASE, CENTRAL, and LILACS databases were searched (March 9, 2022) to identify RCTs published in 2021. PICU RCTs using adaptive designs were identified through an automated full-text screening algorithm. STUDY SELECTION: All RCTs involving children (< 18 yr old) cared for in a PICU were included. There were no restrictions to disease cohort, intervention, or outcome. Interim monitoring by a Data and Safety Monitoring Board that was not prespecified to change the trial design or implementation of the study was not considered adaptive. DATA EXTRACTION: We extracted the type of adaptive design, the justification for the design, and the stopping rule used. Characteristics of the trial were also extracted, and the results summarized through narrative synthesis. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. DATA SYNTHESIS: Sixteen of 528 PICU RCTs (3%) used adaptive designs with two types of adaptations used; group sequential design and sample size reestimation. Of the 11 trials that used a group sequential adaptive design, seven stopped early due to futility and one stopped early due to efficacy. Of the seven trials that performed a sample size reestimation, the estimated sample size decreased in three trials and increased in one trial. CONCLUSIONS: Little evidence of the use of adaptive designs was found, with only 3% of PICU RCTs incorporating an adaptive design and only two types of adaptations used. Identifying the barriers to adoption of more complex adaptive trial designs is needed.

Patient blood management in critically ill children undergoing cardiac surgery: A cohort study.

OBJECTIVE: The objective of this study was to audit current patient blood management practice in children throughout cardiac surgery and paediatric intensive care unit (PICU) admission. DESIGN: This was a prospective observational cohort study. SETTING: This was a single-centre study in the cardiac operating room (OR) and PICU in a major tertiary children's hospital in Australia. PATIENTS: Children undergoing corrective cardiac surgery and requiring admission to PICU for postoperative recovery were included in the study. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients and 1779 blood sampling episodes were audited over a 7-month period. The median age was 9 months (interquartile range [IQR] = 1-102), with the majority (n = 30 [54%]) younger than 12 months. The median number of blood sampling episodes per patient per day was 6.6 (IQR = 5.8-8.0) in total, with a median of 5.0 (IQR = 4.0-7.5) episodes in the OR and 5.0 (IQR = 3.4-6.2) episodes per day throughout PICU admission. The most common reason for blood tests across both OR and PICU settings was arterial blood gas analysis (total median = 86%, IQR = 79-96). The overall median blood sampling volume per kg of bodyweight, patient, and day was 0.63 mL (IQR = 0.20-1.14) in total. Median blood loss for each patient was 3.5 mL/kg per patient per day (IQR = 1.7-5.6) with negligible amounts in the OR and a median of 3.6 mL/kg (IQR = 1.7-5.7) in the PICU. The median Cell Saver® transfusion volume was 9.9 mL/kg per patient per day (IQR = 4.0-19.1) in the OR. The overall median volume of other infusion products (albumin 4%, albumin 20%, packed red blood cells) received by each patient was 20.1 mL/kg (IQR = 10.7-36.4) per day. Sampling events and blood loss were positively associated with PICU stay. CONCLUSIONS: Patient blood management practices observed in this study largely conform to National Blood Authority guidelines. Further implementation projects and research are needed to accelerate implementation of known effective blood conservation strategies within paediatric critical care environments.

General practitioner perspectives on a shared-care model for paediatric patients post-intensive care: A cross-sectional survey.

INTRODUCTION: While paediatric critical illness mortality rates in Australia are declining, the growing cohort of paediatric intensive care unit (PICU) survivors means an increasing number of children facing substantial health challenges after their discharge from intensive care. General practitioners (GPs) play a key role in provision of comprehensive health care to children and families and are ideally positioned to provide developmental surveillance and support the care of both the child and family following critical illness. METHODS: An anonymous, cross-sectional survey of 60 GPs, reached via private invitation (19% response) or via social media weblink, was conducted where the GPs were asked about their current confidence and knowledge in managing children post PICU. This included awareness of short- and long-term problems, of paediatric intensive care syndrome in paediatrics (PICS-p), and of educational materials. Lastly, a parent-completed screening questionnaire and shared-care pathway were proposed to GPs for their feedback on perceived benefit and willingness to participate. Data were analysed using frequency distributions and chi-square statistics. RESULTS: Ninety-three percent of GPs had some level of confidence in caring for a child post PICU admission and low confidence in their knowledge of potential short- and long-term complications. Eighty percent of GPs had not heard of PICS-p, and 93% were unaware of educational materials available on this topic. Ninety-five percent of GPs perceived that the proposed patient-screening tool and shared-care pathways would be beneficial, and 70% predicted that they would definitely use educational materials if accessible through GP central repositories. CONCLUSION: To reduce ongoing health problems for children recovering from critical illness, the family GP plays a pivotal role in providing community-level developmental care, particularly in Australia. Increasing GP confidence and knowledge through education is essential, and using a parent-completed screening questionnaire and shared-care pathway to improve care may be beneficial. GPs must also be involved in the implementation stages of future shared-care models.

Ventilator weaning and extubation practices in critically ill children: An Australian and New Zealand survey of practice.

OBJECTIVES: We aimed to (i) describe current weaning and extubation practices in children (protocols to identify weaning candidates, spontaneous breathing trials, and other aspects of care such as sedation weaning) and (ii) understand responsibilities for ventilation weaning decisions across Australia and New Zealand (ANZ). METHODS: A cross-sectional survey of ANZ intensive care units who routinely intubate and ventilate children (<18 years) was conducted. We worked with the Australian and New Zealand Intensive Care Society Paediatric Study Group to identify units and potential respondents (senior nurse representative per unit) and to administer questionnaires. Survey questions (n = 35) examined current protocols, practices, unit staffing, and decision-making responsibilities for ventilation weaning and extubation. Open-ended questions examined respondents' experiences of weaning and extubation. RESULTS: A senior nursing respondent from 18/22 intensive care units (82%) completed the survey. Across units, most used sedation assessment tools (88%), and less often, sedation weaning tools (55%). Spontaneous awakening protocols were not used; one unit (5%) reported the use of a spontaneous breathing protocol. Two respondents reported that ventilation weaning protocols (11%) were in use, with 44% of units reporting the use of extubation protocols. Weaning and extubation practices were largely perceived as medically driven, with qualitative data demonstrating a desire from most respondents for greater shared decision-making. CONCLUSION: In ANZ, ventilation weaning and extubation practices are largely medically driven with variation in the use of protocols to support mechanical ventilation weaning and extubation in children. Our findings highlight the importance of future research to determine the impact of greater collaboration of the multidisciplinary team on weaning practices.

Quality measurement and surveillance platforms in critically ill children: A scoping review.

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)-non-inferiority (peripheral arterial catheter) trial.

BACKGROUND: The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters. METHODS: We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete. FINDINGS: Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events. INTERPRETATION: Infusion set use can be safely extended to 7 days with resultant cost and workload reductions. FUNDING: Australian National Health and Medical Research Council.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation). Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease. Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021. Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685). Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels. Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups. Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.

Midazolam exposure in the paediatric intensive care unit predicts acute post-traumatic stress symptoms in children.

BACKGROUND: Clinically significant post-traumatic stress symptoms (PTSS) have been reported in up to a quarter of paediatric intensive care unit (PICU) survivors. Ongoing PTSS negatively impacts children's psychological development and physical recovery. However, few data regarding associations between potentially modifiable PICU treatment factors, such as analgosedatives and invasive procedures, and children's PTSS have been reported. OBJECTIVES: We sought to investigate the medical treatment factors associated with children's PTSS after PICU discharge. METHODS: A prospective longitudinal cohort study was conducted in two Australian tertiary referral PICUs. Children aged 2-16 y admitted to the PICU between June 2008 and January 2011 for >8 h and <28 d were eligible for participation. Biometric and clinical data were obtained from medical records. Parents reported their child's PTSS using the Trauma Symptom Checklist for Young Children at 1, 3, 6, and 12 months after discharge. Logistic regression was used to assess potential associations between medical treatment and PTSS. RESULTS: A total of 265 children and their parents participated in the study. In the 12-month period following PICU discharge, 24% of children exhibited clinically elevated PTSS. Median risk of death (Paediatric Index of Mortality 2 [PIM2]) score was significantly higher in the PTSS group (0.31 [IQR 0.14-1.09] v 0.67 [IQR 0.20-1.18]; p = 0.014). Intubation and PICU and hospital length of stay were also significantly associated with PTSS at 1 month, as were midazolam, propofol, and morphine. After controlling for gender, reason for admission, and PIM2 score, only midazolam was significantly and independently associated with PTSS and only at 1 month (adjusted odds ration (aOR) 3.63, 95% CI 1.18, 11.12, p = 0.024). No significant relationship was observed between the use of medications and PTSS after 1 month. CONCLUSIONS: Elevated PTSS were evident in one quarter (24%) of children during the 12 months after PICU discharge. One month after discharge, elevated PTSS were most likely to occur in children who had received midazolam therapy.

Appropriate use criteria for endotracheal suction interventions in mechanically ventilated children: The RAND/UCLA development process.

OBJECTIVES: Endotracheal suction is an invasive airway clearance technique used in mechanically ventilated children. This article outlines the methods used to develop appropriate use criteria for endotracheal suction interventions in mechanically ventilated paediatric patients. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop paediatric appropriate use criteria. This included the following sequential phases of defining scope and key terms, a literature review and synthesis, expert multidisciplinary panel selection, case scenario development, and appropriateness ratings by an interdisciplinary expert panel over two rounds. The panel comprised experts in the fields of paediatric and neonatal intensive care, respiratory medicine, infectious diseases, critical care nursing, implementation science, retrieval medicine, and education. Case scenarios were developed iteratively by interdisciplinary experts and derived from common applications or anticipated intervention uses, as well as from current clinical practice guidelines and results of studies examining interventions efficacy and safety. Scenarios were rated on a scale of 1 (harm outweighs benefit) to 9 (benefit outweighs harm), to define appropriate use (median: 7 to 9), uncertain use (median: 4 to 6), and inappropriate use (median: 1 to 3) of endotracheal suction interventions. Scenarios were than classified as a level of appropriateness. CONCLUSIONS: The RAND Corporation/University of California, Los Angeles Appropriateness Method provides a thorough and transparent method to inform development of the first appropriate use criteria for endotracheal suction interventions in paediatric patients.

The Paediatric AirWay Suction (PAWS) appropriateness guide for endotracheal suction interventions.

BACKGROUND/OBJECTIVE: Endotracheal suction is an invasive and potentially harmful technique used for airway clearance in mechanically ventilated children. Choice of suction intervention remains a complex and variable process. We sought to develop appropriate use criteria for endotracheal suction interventions used in paediatric populations. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop the Paediatric AirWay Suction appropriateness guide. This included defining key terms, synthesising current evidence, engaging an expert multidisciplinary panel, case scenario development, and two rounds of appropriateness ratings (weighing harm with benefit). Indications (clinical scenarios) were developed from common applications or anticipated use, current practice guidelines, clinical trial results, and expert consultation. RESULTS: Overall, 148 (19%) scenarios were rated as appropriate (benefit outweighs harm), 542 (67%) as uncertain, and 94 (11%) as inappropriate (harm outweighs benefit). Disagreement occurred in 24 (3%) clinical scenarios, namely presuction and postsuction bagging across populations and age groups. In general, the use of closed suction was rated as appropriate, particularly in the subspecialty population 'patients with highly infectious respiratory disease'. Routine application of 0.9% saline for nonrespiratory indications was more likely to be inappropriate/uncertain than appropriate. Panellists preferred clinically indicated suction versus routine suction in most circumstances. CONCLUSION: Appropriate use criteria for endotracheal suction in the paediatric intensive care have the potential to impact clinical decision-making, reduce practice variability, and improve patient outcomes. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.