Framework for Research Gaps in Pediatric Ventilator Liberation.

BACKGROUND: The 2023 international pediatric ventilator liberation clinical practice guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, due to the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence. RESEARCH QUESTION: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines? STUDY DESIGN: and Methods: We conducted systematic reviews of the literature in 8 pre-defined PICO areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) meeting in Spring 2022 for open discussion, feedback was incorporated, and final evaluation of research gaps are summarized in this document. While randomized trials trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs may also be appropriate, given challenges with conducting large multi-center RCTs in children. RESULTS: Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multi-center RCTs to provide definitive results, while other gaps can be addressed with multi-center observational studies or quality improvement initiatives. Furthermore, there remains a need for some physiologic studies in several areas, particularly regarding newer diagnostic methods to improve identification of patients at high-risk of extubation failure. INTERPRETATION: While pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and there are multiple research gaps which should be filled through high quality RCTs, and multi-center observational studies and quality improvement initiatives.

How to follow the guidelines, when the appropriate fluid is missing?

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution.

Nurses' decision-making around gastric residual volume measurement in UK adult intensive care: A four-centre survey.

BACKGROUND: Despite increasing evidence of the potential inaccuracy and unwarranted practice of regular GRV measurement in critically in adults, this practice persists within the United Kingdom. AIM: To explore adult intensive care nurses' decision-making around the practice of GRV measurement to guide enteral feeding. METHODS: A cross-sectional 16 item electronic survey in four adult intensive care units (ICUs) in England and Wales. RESULTS: Two hundred and seventy-three responses were obtained across four ICUs with acceptable response rates for most [Unit 1 74 /127 = 58.2%; Unit 2 87/129 = 67.4%; Unit 3 77/120 = 64.1%; Unit 4 35/168 = 20.8%]. Most (243/273 (89%) reported measuring GRV 4-6 hourly, with most (223/273 82%) reporting that the main reason was to assess feed tolerance or intolerance and 37/273 (13.5%) saying their unit protocol required it. In terms of factors affecting decision-making, volume obtained was the most important factor, followed by the condition of the patient, with aspirate colour and appearance less important. When asked how they would feel about not measuring GRV routinely, the majority (78.2%) of nurses felt worried (140/273 = 51.2%) or very worried (74/273 = 27%). CONCLUSIONS: Factors affecting the nurses' decision-making around GRV were based largely on fear of risk (around vomiting and pulmonary aspiration) and compliance with unit protocols. RELEVANCE TO CLINICAL PRACTICE: Despite increasing evidence suggesting it is unnecessary, nurses' beliefs around the value of this practice persist and it continues to be embedded into unit protocols around feeding.

Association between protein intake and muscle wasting in critically ill children: A prospective cohort study.

BACKGROUND: Survival from pediatric critical illness in high-income countries is high, and the focus now must be on optimizing the recovery of survivors. Muscle mass wasting during critical illness is problematic, so identifying factors that may reduce this is important. Therefore, the aim of this study was to examine the relationship between quadricep muscle mass wasting (assessed by ultrasound), with protein and energy intake during and after pediatric critical illness. METHODS: A prospective cohort study in a mixed cardiac and general pediatric intensive care unit in England, United Kingdom. Serial ultrasound measurements were undertaken at day 1, 3, 5, 7, and 10. RESULTS: Thirty-four children (median age 6.65 [0.47-57.5] months) were included, and all showed a reduction in quadricep muscle thickness during critical care admission, with a mean muscle wasting of 7.75%. The 11 children followed-up had all recovered their baseline muscle thickness by 3 months after intensive care discharge. This muscle mass wasting was not related to protein (P = 0.53, ρ = 0.019) (95% CI: -0.011 to 0.049) or energy intake (P = 0.138, ρ = 0.375 95% CI: -0.144 to 0.732) by 72 h after admission, nor with severity of illness, highest C-reactive protein, or exposure to intravenous steroids. Children exposed to neuromuscular blocking drugs exhibited 7.2% (95% CI: -0.13% to 14.54%) worse muscle mass wasting, but this was not statistically significant (P = 0.063). CONCLUSION: Our study did not find any association between protein or energy intake at 72 h and quadricep muscle mass wasting.

Use of selective gut decontamination in critically ill children: PICnIC a pilot RCT and mixed-methods study.

Background: Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population. Objectives: To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control. Design: Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study. Setting: Six paediatric intensive care units in England. Participants: Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study. Interventions: The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation. Main outcome measures: The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures. Results: A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival. Limitations: The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training. Conclusions: PICnIC's findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised. Future work: A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted. Trial registration: This trial is registered as ISRCTN40310490. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections.

Intravenous maintenance fluid therapy in acutely and critically ill children: state of the evidence.

Intravenous maintenance fluid therapy (IV-MFT) is one of the most prescribed, yet one of the least studied, interventions in paediatric acute and critical care settings. IV-MFT is not typically treated in the same way as drugs with specific indications, contraindications, compositions, and associated adverse effects. In the last decade, societies in both paediatric and adult medicine have issued evidence-based practice guidelines for the use of intravenous fluids in clinical practice. The main objective of this Viewpoint is to summarise and compare the rationales on which these international expert guidelines were based and how these recommendations affect IV-MFT practices in paediatric acute and critical care. Although these guidelines recommend the use of isotonic fluids as a standard in IV-MFT, some discrepancies and uncertainties remain regarding the systematic use of balanced fluids, glucose and electrolyte requirements, and appropriate fluid volume. IV-MFT should be considered in the same way as any other prescription drug and none of the components of IV-MFT prescription should be overlooked (ie, choice of drug, dosing rate, duration of treatment, and de-escalation). Furthermore, most evidence that was used to inform the guidelines comes from high-income countries. Although some principles of IV-MFT are universal, the direct relevance to and feasibility of implementing the guidelines in low-income and middle-income countries is uncertain.

Development and application of a 2-step methodology to select a reference society providing Dietary Reference Values for national implementation.

OBJECTIVE: To describe and discuss a 2-step methodology developed to select a reference society that provides Dietary Reference Values (DRV) for national implementation and to illustrate its application in Switzerland with one macronutrient and one micronutrient. DESIGN: During Step 1, we searched and compared DRV and methodologies used to define DRV from eight European societies for seven selected nutrients. We repeated this procedure during Step 2 for DRV from two preselected societies for forty-four nutrients. SETTING: The 2-step methodology applied here for Switzerland may be used in other countries. PARTICIPANTS: The research team commissioned six external experts from three linguistic regions of Switzerland, who provided their opinions through two online surveys, individual interviews and a focus group. RESULTS: After Step 1, we excluded five societies because of old publication dates, irrelevant publication languages for Switzerland, difficulty in accessing documents, or because their DRV were mainly based on another society. After Step 2, the two societies were qualified based on the analysis of the values and methodologies used. The need for free and easily accessible scientific background information favoured the European Food Safety Authority (EFSA). We chose alternative societies for nine nutrients for the overall population or subgroups and for the elderly. CONCLUSIONS: To manage heterogeneous and complex data from several societies, adopting a 2-step methodology including fewer nutrients and more societies during Step 1, and fewer societies but all nutrients in Step 2, was very helpful. With some exceptions, we selected EFSA as the main society to provide DRV for Switzerland.

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial.

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020.

Mechanical insufflation-exsufflation to promote extubation success in critically ill adults on intensive care: protocol for a randomised controlled feasibility trial.

BACKGROUND: Extubation failure, defined as reintubation within 48 h, is associated with increased intensive care unit (ICU) length of stay and higher mortality risk. One cause of extubation failure is secretion retention, resulting from an inability to cough effectively. Mechanical insufflation-exsufflation (MI-E) simulates a cough aiding secretion clearance. However, MI-E is not routinely used in the ICU for invasively ventilated patients. This study aims to determine feasibility and acceptability of a randomised controlled trial (RCT) examining MI-E use to promote extubation success in intubated, ventilated adults. METHODS: It is a single-centre, feasibility RCT with semi-structured interviews, economic scoping, and exploratory physiology study. The feasibility RCT (n = 50) will compare standard care to a MI-E protocol including a minimum of two MI-E sessions via the endotracheal tube prior to extubation. Post-extubation, MI-E will be delivered via facemask or mouthpiece up to two times/day for 48 h. MI-E settings will be individualised. All patients will receive standard care (no MI-E) in relation to mechanical ventilation, weaning, rehabilitation, physiotherapy techniques such as positioning, manual airway clearance techniques, manual/ventilator hyperinflation, endotracheal suctioning, and nebulisation. Clinical data collection will occur before, on completion, and 5-min post-physiotherapy sessions (intervention/control arms). Resource use will be calculated for each 24-h period. Analyses will be descriptive and address feasibility outcomes including participant recruitment and attrition, proportion of MI-E treatment sessions completed, dataset completeness, and frequency of adverse events and acceptability. Semi-structured online interviews informed by the Theoretical Framework of Acceptability (TFA) with patients, clinicians, and family members will explore the acceptability of the MI-E intervention and study processes. Interview data will be analysed using reflexive thematic analysis based on TFA domains through first-level coding. The embedded physiology study will use electrical impedance tomography and lung ultrasound to explore lung recruitment and de-recruitment during MI-E in a subset of 5-10 patients. DISCUSSION: This study will examine feasibility and acceptability of a RCT protocol of MI-E to promote extubation success. Study findings will inform design modification and conduct of a future adequately powered trial. Furthermore, the study will contribute and advance the understanding of MI-E use in critically ill intubated adults. TRIAL REGISTRATION: ISRCTN 24603037; IRAS 303674.

Association between enteral feeding and gastrointestinal complications in children receiving extracorporeal life support: A retrospective cohort study.

BACKGROUND: Extracorporeal life support is an accepted treatment modality for children with severe cardiac and/or respiratory dysfunction. However, after a period of inadequate gut perfusion, clinicians are often reluctant to initiate enteral nutrition. METHODS: This was a retrospective cohort study in a single large pediatric intensive care unit in North West England over 5.5 years (2017-2022). RESULTS: One hundred fifty-six children, who had a median age of 2 months (IQR, 0.3-15) and a mean weight-for-age z score of -1.50 (SD, 1.7), were included. Indications for extracorporeal life support were respiratory failure (31%), cardiac arrest (28%), low cardiac output state (27%), and inability to separate from cardiopulmonary bypass (12%). Most (75%) children were fed during extracorporeal life support, with a median time to initiate feeding of 24 h (IQR, 12.2-42.7). More gastrointestinal complications were associated with being enterally fed (86% vs 14%; P < 0.001), but complications were predominantly feed intolerance (46%), which was associated with receiving formula feeds rather than maternal (breast) milk (P < 0.001). Overall, the proportion of children's median energy targets achieved by 72 h was 38% (IQR, 10.7%-76%), but this varied by support indication. CONCLUSIONS: Our findings suggest most children tolerated enteral feeding within 24 h after extracorporeal life support initiation, with only mild gastrointestinal complications.

Effectiveness of high vs lower enteral protein intake, considering energy intake, on clinical outcomes in critically ill children: a systematic review protocol.

OBJECTIVE: The objective of this review is to evaluate the effectiveness of high vs lower enteral protein intake, considering energy intake, on clinical and nutritional outcomes in critically ill children hospitalized in the pediatric intensive care unit. INTRODUCTION: Over- and undernutrition increases the risk of morbidity and mortality in critically ill children. The impact of high vs lower enteral protein intake on clinical outcomes, considering energy intake, still needs to be investigated in children of different ages. INCLUSION CRITERIA: This review will consider studies of critically ill children (aged between ≥ 37 weeks gestational age and < 18 years) admitted to the pediatric intensive care unit for a minimum of 48 hours and receiving enteral nutrition. Randomized controlled trials comparing high vs lower enteral protein intake, considering energy intake, will be eligible. Primary outcomes will include clinical and nutritional outcomes, such as length of stay in the pediatric intensive care unit and nitrogen balance. METHODS: Using the JBI methodology for systematic reviews of effectiveness, we will search for randomized controlled trials published in English, French, Italian, Spanish, and German in electronic databases, including MEDLINE, CINAHL Complete, Embase, and the Cochrane Library, from database inception until the present. We will also search clinical trial registers and, if required, contact authors. Two independent reviewers will screen and select studies for inclusion, data extraction, and assessment of methodological quality. A third reviewer will be consulted if necessary. A statistical meta-analysis will be performed if feasible. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022315325.

Is bolus or continuous enteral feeding better in critically ill children: An evidence-based review.

Inadequate nutrition can lead to increased morbidity and mortality for mechanically ventilated children in the paediatric intensive care unit (PICU). Enteral feeding can either be delivered by gravity bolus (intermittent) feeding or continuously via a pump and in UK PICUs variable practice exists. This evidence-based review therefore aimed to examine the evidence surrounding the two feeding methods for ventilated children, to determine whether one provides better enteral nutrition. Four papers were included, three randomized controlled trials and a systematic review, which provide conflicting evidence. There is some suggestion that bolus feeding may be superior in medical children on PICU to achieve their energy and protein goals faster, however, the clinical significance of the results is questionable and further research is needed to identify whether one method of feeding can impact on patient outcomes.

Using the TIDieR checklist to describe the intervention of the Sedation and Weaning in Children (SANDWICH) trial.

BACKGROUND: Published reports of complex interventions in randomized controlled trials often lack sufficient detail to allow trial replication and adoption into practice. AIM: The aim of this paper is to describe our experience of using the Template for Intervention Description and Replication (TIDieR) checklist in reporting a recent trial of sedation and ventilation weaning in critically ill children (the Sedation and Weaning in Children [SANDWICH] trial). METHODS: The TIDieR 12-point checklist has been used to detail and describe the specific SANDWICH trial intervention and methods of implementation. RESULTS/DISCUSSION: Overall, we found the checklist a useful tool to direct and ensure consistency of reporting of our complex intervention used in a multi-centre clinical trial. We experienced some minor limitations in classifying training materials and delivery mode into one item because of the overlapping nature of this component. CONCLUSION: Using the TIDieR checklist to report complex interventions tested in trials provides a structured, systematic way of describing necessary detail. This allows clinicians to understand the theory behind the intervention, how it should be delivered, and the resources required. RELEVANCE TO CLINICAL PRACTICE: The SANDWICH intervention had a significant beneficial effect on reducing time on ventilation for children. The detailed description of the team-based intervention will aid replication, implementation and monitoring of fidelity in other paediatric intensive care units.

Operational Definitions Related to Pediatric Ventilator Liberation.

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. INTERPRETATION: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.