Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V Ts) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V Ts at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V T. EEL and V T were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENTRL1−VENTRL8) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V T and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p<0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V

Measurement of ventilation and cardiac related impedance changes with electrical impedance tomography

Introduction Electrical impedance tomography (EIT) has been shown to be able to distinguish both ventilation and perfusion. With adequate filtering the regional distributions of both ventilation and perfusion and their relationships could be analysed. Several methods of separation have been suggested previously, including breath holding, electrocardiograph (ECG) gating and frequency filtering. Many of these methods require interventions inappropriate in a clinical setting. This study therefore aims to extend a previously reported frequency filtering technique to a spontaneously breathing cohort and assess the regional distributions of ventilation and perfusion and their relationship. Methods Ten healthy adults were measured during a breath hold and while spontaneously breathing in supine, prone, left and right lateral positions. EIT data were analysed with and without filtering at the respiratory and heart rate. Profiles of ventilation, perfusion and ventilation/perfusion related impedance change were generated and regions of ventilation and pulmonary perfusion were identified and compared. Results Analysis of the filtration technique demonstrated its ability to separate the ventilation and cardiac related impedance signals without negative impact. It was, therefore, deemed suitable for use in this spontaneously breathing cohort. Regional distributions of ventilation, perfusion and the combined ΔZV/ΔZQ were calculated along the gravity axis and anatomically in each position. Along the gravity axis, gravity dependence was seen only in the lateral positions in ventilation distribution, with the dependent lung being better ventilated regardless of position. This gravity dependence was not seen in perfusion. When looking anatomically, differences were only apparent in the lateral positions. The lateral position ventilation distributions showed a difference in the left lung, with the right lung maintaining a similar distribution in both lateral positions. This is likely caused by more pronounced anatomical changes in the left lung when changing positions. Conclusions The modified filtration technique was demonstrated to be effective in separating the ventilation and perfusion signals in spontaneously breathing subjects. Gravity dependence was seen only in ventilation distribution in the left lung in lateral positions, suggesting gravity based shifts in anatomical structures. Gravity dependence was not seen in any perfusion distributions

Efficacy and safety of normal saline instillation and paediatric endotracheal suction: an integrative review

To synthesise research findings regarding the efficacy and safety of normal saline instillation (NSI) during endotracheal suction in the paediatric intensive care unit.The Cochrane Library, PROSPERO, the National Health Service Centre for Reviews and Dissemination, PubMed and Cumulative Index to Nursing and Allied Health (CINAHL) databases were systematically searched. Subject headings included "suctioning, endotracheal", "suction", "sodium chloride", "normal saline" and "paediatrics". Additional references were sourced from hand searches of journal article reference lists and Google Scholar.An integrative, systematic approach was used to qualitatively synthesise study results in the context of paediatric intensive care nursing practice. Data were extracted using a standardised data extraction form. Quality assessment was performed independently by two reviewers.Three studies met pre-defined inclusion criteria. Quality of all study methods was 75% on the Mixed Method Appraisal Tool, although reporting quality varied. Overall, there was a scarcity of high quality evidence examining NSI and paediatric endotracheal suction. Outcome measures included oxygen saturation (SpO2), serious adverse events (author/s defined) and ventilation parameters (author/s defined). Endotracheal suction with NSI was associated with a transient decrease in blood oxygen saturation; research protocols did not include interventions to mitigate alveolar derecruitment. Studies were not powered to detect differences in endotracheal tube (ETT) occlusion or ventilator associated pneumonia (VAP).NSI was associated with a transient decrease in oxygen saturation. In children with obstructive mucous, NSI may have a positive effect. Practices which maximise secretion removal and mitigate the negative physiological interactions of ETS have been poorly evaluated in the paediatric population. High quality, powered, clinical trials are needed to determine the safety and efficacy of normal saline instillation and to inform clinical practice

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children

Objectives: Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children. Design: Functional residual capacity and lung clearance index, ameasure of ventilation homogeneity, were calculated using asulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax). Setting: Pediatric anesthesia unit of university hospital. Patients and participants: Thirty preschool children without cardiopulmonary disease undergoing elective surgery. Measurements and results: Mean (range) age was 48.5 (24-80) months, weight 17.2 (10.5-26.9) kg, functional residual capacity (mean ± SD) 22.9 ± 6.2 ml.kg−1 in the supine position and 23.3 ± 5.6 ml.kg−1 in the flat prone position, while lung clearance indices were 8.1 ± 2.3 vs. 7.9 ± 2.3, respectively. In contrast, functional residual capacity increased to 27.6 ± 6.5 ml.kg−1 (p< 0.001) in the augmented prone position while at the same time the lung clearance index decreased to 6.7 ± 0.9 (p< 0.001). Conclusions: Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary functio

Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A Paediatric Acute Respiratory Intervention Study (PARIS)

Background Bronchiolitis imposes the largest health care burden on non-elective paediatric hospital admissions worldwide, with up to 15 % of cases requiring admission to intensive care. A number of previous studies have failed to show benefit of pharmaceutical treatment in respect to length of stay, reduction in PICU admission rates or intubation frequency. The early use of non-invasive respiratory support devices in less intensive scenarios to facilitate earlier respiratory support may have an impact on outcome by avoiding progression of the disease process. High Flow Nasal Cannula (HFNC) therapy has emerged as a new method to provide humidified air flow to deliver a non-invasive form of positive pressure support with titratable oxygen fraction. There is a lack of high-grade evidence on use of HFNC therapy in bronchiolitis. Methods/Design Prospective multi-centre randomised trial comparing standard treatment (standard subnasal oxygen) and High Flow Nasal Cannula therapy in infants with bronchiolitis admitted to 17 hospitals emergency departments and wards in Australia and New Zealand, including 12 non-tertiary regional/metropolitan and 5 tertiary centres. The primary outcome is treatment failure; defined as meeting three out of four pre-specified failure criteria requiring escalation of treatment or higher level of care; i) heart rate remains unchanged or increased compared to admission/enrolment observations, ii) respiratory rate remains unchanged or increased compared to admission/enrolment observations, iii) oxygen requirement in HFNC therapy arm exceeds FiO2 ≥ 40 % to maintain SpO2 ≥ 92 % (or ≥94 %) or oxygen requirement in standard subnasal oxygen therapy arm exceeds >2L/min to maintain SpO2 ≥ 92 % (or ≥94 %), and iv) hospital internal Early Warning Tool calls for medical review and escalation of care. Secondary outcomes include transfer to tertiary institution, admission to intensive care, length of stay, length of oxygen treatment, need for non-invasive/invasive ventilation, intubation, adverse events, and cost. Discussion This large multicenter randomised trial will allow the definitive assessment of the efficacy of HFNC therapy as compared to standard subnasal oxygen in the treatment of bronchiolitis

High-flow nasal cannula (HFNC) support in interhospital transport of critically ill children

Purpose: Optimal respiratory support for interhospital transport of critically ill children is challenging and has been scarcely investigated. High-flow nasal cannula (HFNC) therapy has emerged as a promising support mode in the paediatric intensive care unit (PICU), but no data are available on HFNC used during interhospital transport. We aimed to assess the safety of HFNC during retrievals of critically ill children and its impact on the need for invasive ventilation (IV). Methods: This was a retrospective, single-centre study of children under 2years old transported by a specialized paediatric retrieval team to PICU. We compared IV rates before (2005-2008) and after introduction of HFNC therapy (2009-2012). Results: A total of 793 infants were transported. The mean transport duration was 1.4h (range 0.25-8), with a mean distance of 205km (2-2,856). Before introduction of HFNC, 7% (n=23) were retrieved on non-invasive ventilation (NIV) and 49% (n=163) on IV. After introduction of HFNC, 33% (n=150) were retrieved on HFNC, 2% (n=10) on NIV, whereas IV decreased to 35% (n=162, p<0.001). No patients retrieved on HFNC required intubation during retrieval, or developed pneumothorax or cardiac arrest. Using HFNC was associated with a significant reduction in IV initiated by the retrieval team (multivariate OR 0.51; 95% CI 0.27-0.95; p=0.032). Conclusions: We report on a major change of practice in transport of critically ill children in our retrieval system. HFNC therapy was increasingly used and was not inferior to low-flow oxygen or NIV. Randomized trials are needed to assess whether HFNC can reduce the need for IV in interhospital transport of critically ill children

Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): Protocol for a Randomized Controlled Trial

Background Extracorporeal membrane oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children in whom the predicted mortality risk remains very high. The inevitable host inflammatory response and activation of the coagulation cascade due to the extracorporeal circuit contribute to additional morbidity and mortality in these patients. Mixing nitric oxide (NO) into the sweep gas of ECMO circuits may reduce the inflammatory and coagulation cascade activation during ECMO support. Objective The purpose of this study is to test the feasibility and safety of mixing NO into the sweep gas of ECMO systems and assess its effect on inflammation and coagulation system activation through a pilot randomized controlled trial. Methods The Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR) trial is an open-label, parallel-group, pilot randomized controlled trial to be conducted at a single center. Fifty patients who require ECMO support will be randomly assigned to receive either NO mixed into the sweep gas of the ECMO system at 20 ppm for the duration of ECMO or standard care (no NO) in a 1:1 ratio, with stratification by support type (veno-venous vs veno-arterial ECMO). Results Outcome measures will focus on feasibility (recruitment rate and consent rate, and successful inflammatory marker measurements), the safety of the intervention (oxygenation and carbon dioxide control within defined parameters and methemoglobin levels), and proxy markers of efficacy (assessment of cytokines, chemokines, and coagulation factors to assess the impact of NO on host inflammation and coagulation cascade activation, clotting of ECMO components, including computer tomography scanning of oxygenators for clot assessments), bleeding complications, as well as total blood product use. Survival without ECMO and the length of stay in the pediatric intensive care unit (PICU) are clinically relevant efficacy outcomes. Long-term outcomes include neurodevelopmental assessments (Ages and Stages Questionnaire, Strength and Difficulties Questionnaire, and others) and quality of life (Pediatric Quality of Life Inventory and others) measured at 6 and 12 months post ECMO cannulation. Analyses will be conducted on an intention-to-treat basis. Conclusions The NECTAR study investigates the safety and feasibility of NO as a drug intervention during extracorporeal life support and explores its efficacy. The study will investigate whether morbidity and mortality in patients treated with ECMO can be improved with NO. The intervention targets adverse outcomes in patients who are supported by ECMO and who have high expected mortality and morbidity. The study will be one of the largest randomized controlled trials performed among pediatric patients supported by ECMO. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619001518156; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376869 International Registered Report Identifier (IRRID) DERR1-10.2196/4376

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial

Introduction Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol. Methods and analysis The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery. Ethics and dissemination The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12617000821392.</p

A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis

BACKGROUND: High-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTS: The analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, −11 percentage points; 95% confidence interval, −15 to −7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. CONCLUSIONS: Among infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. (Funded by the National Health and Medical Research Council and others; Australian and New Zealand Clinical Trials Registry number, ACTRN12613000388718.