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JAMA Apr 2022The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children: A Randomized Clinical Trial.
IMPORTANCE
The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known.
OBJECTIVE
To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support.
DESIGN, SETTING, AND PARTICIPANTS
This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom. Six hundred children aged 0 to 15 years clinically assessed to require noninvasive respiratory support within 72 hours of extubation were recruited between August 8, 2019, and May 18, 2020, with last follow-up completed on November 22, 2020.
INTERVENTIONS
Patients were randomized 1:1 to start either HFNC at a flow rate based on patient weight (n = 299) or CPAP of 7 to 8 cm H2O (n = 301).
MAIN OUTCOMES AND MEASURES
The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio (HR) of 0.75. There were 6 secondary outcomes, including mortality at day 180 and reintubation within 48 hours.
RESULTS
Of the 600 children who were randomized, 553 children (HFNC, 281; CPAP, 272) were included in the primary analysis (median age, 3 months; 241 girls [44%]). HFNC failed to meet noninferiority, with a median time to liberation of 50.5 hours (95% CI, 43.0-67.9) vs 42.9 hours (95% CI, 30.5-48.2) for CPAP (adjusted HR, 0.83; 1-sided 97.5% CI, 0.70-∞). Similar results were seen across prespecified subgroups. Of the 6 prespecified secondary outcomes, 5 showed no significant difference, including the rate of reintubation within 48 hours (13.3% for HFNC vs 11.5 % for CPAP). Mortality at day 180 was significantly higher for HFNC (5.6% vs 2.4% for CPAP; adjusted odds ratio, 3.07 [95% CI, 1.1-8.8]). The most common adverse events were abdominal distension (HFNC: 8/281 [2.8%] vs CPAP: 7/272 [2.6%]) and nasal/facial trauma (HFNC: 14/281 [5.0%] vs CPAP: 15/272 [5.5%]).
CONCLUSIONS AND RELEVANCE
Among critically ill children requiring noninvasive respiratory support following extubation, HFNC compared with CPAP following extubation failed to meet the criterion for noninferiority for time to liberation from respiratory support.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN60048867.
Topics: Adolescent; Airway Extubation; Cannula; Child; Child, Preschool; Continuous Positive Airway Pressure; Critical Illness; Female; Humans; Infant; Infant, Newborn; Male; Oxygen Inhalation Therapy
PubMed: 35390113
DOI: 10.1001/jama.2022.3367 -
Ugeskrift For Laeger Dec 2023Home oxygen therapy is an acknowledged treatment for patients suffering from chronic hypoxaemia, due to pulmonary or cardiac disease, and may have positive effects on... (Review)
Review
Home oxygen therapy is an acknowledged treatment for patients suffering from chronic hypoxaemia, due to pulmonary or cardiac disease, and may have positive effects on survival and quality of life. The risks and side effects of the treatment are usually mild, and the equipment has developed to become relatively affordable, accessible and easy to transport. Adjustments in the oxygen settings can be necessary when travelling by airplane or during physical effort or sleep. Prescription and follow-ups are usually best maintained by hospital departments with expertise in pulmonary medicine, as argued in this review.
Topics: Humans; Quality of Life; Oxygen Inhalation Therapy; Lung; Oxygen; Denmark; Hypoxia
PubMed: 38078470
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2021High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review.
OBJECTIVES
To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches.
SELECTION CRITERIA
We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO/FiO) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO/FiO may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma.
AUTHORS' CONCLUSIONS
HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.
Topics: Acute Disease; Adult; Barotrauma; Bias; Critical Care; Hospital Mortality; Humans; Intubation; Length of Stay; Masks; Nasal Mucosa; Noninvasive Ventilation; Oxygen Inhalation Therapy; Patient Reported Outcome Measures; Pneumonia; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Insufficiency; Treatment Failure
PubMed: 33661521
DOI: 10.1002/14651858.CD010172.pub3 -
Critical Care (London, England) Dec 2020The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO clearance after 2 h of treatment.
METHODS
We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes.
RESULTS
Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis.
CONCLUSIONS
HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD.
TRIAL REGISTRATION
The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).
Topics: Aged; Cannula; Equivalence Trials as Topic; Female; Humans; Italy; Male; Middle Aged; Noninvasive Ventilation; Oxygen Inhalation Therapy; Pulmonary Disease, Chronic Obstructive; Symptom Flare Up
PubMed: 33317579
DOI: 10.1186/s13054-020-03409-0 -
JAMA Jul 2022The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Therapy on Liberation From Respiratory Support in Acutely Ill Children Admitted to Pediatric Critical Care Units: A Randomized Clinical Trial.
IMPORTANCE
The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known.
OBJECTIVE
To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support.
DESIGN, SETTING, AND PARTICIPANTS
Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022.
INTERVENTIONS
Patients were randomized 1:1 to commence either HFNC at a flow rate based on patient weight (n = 301) or CPAP of 7 to 8 cm H2O (n = 299).
MAIN OUTCOMES AND MEASURES
The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which a participant was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio of 0.75. Seven secondary outcomes were assessed, including mortality at critical care unit discharge, intubation within 48 hours, and use of sedation.
RESULTS
Of the 600 randomized children, consent was not obtained for 5 (HFNC: 1; CPAP: 4) and respiratory support was not started in 22 (HFNC: 5; CPAP: 17); 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis (median age, 9 months; 226 girls [39%]). The median time to liberation in the HFNC group was 52.9 hours (95% CI, 46.0-60.9 hours) vs 47.9 hours (95% CI, 40.5-55.7 hours) in the CPAP group (absolute difference, 5.0 hours [95% CI -10.1 to 17.4 hours]; adjusted hazard ratio 1.03 [1-sided 97.5% CI, 0.86-∞]). This met the criterion for noninferiority. Of the 7 prespecified secondary outcomes, 3 were significantly lower in the HFNC group: use of sedation (27.7% vs 37%; adjusted odds ratio, 0.59 [95% CI, 0.39-0.88]); mean duration of critical care stay (5 days vs 7.4 days; adjusted mean difference, -3 days [95% CI, -5.1 to -1 days]); and mean duration of acute hospital stay (13.8 days vs 19.5 days; adjusted mean difference, -7.6 days [95% CI, -13.2 to -1.9 days]). The most common adverse event was nasal trauma (HFNC: 6/295 [2.0%]; CPAP: 18/278 [6.5%]).
CONCLUSIONS AND RELEVANCE
Among acutely ill children clinically assessed to require noninvasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support.
TRIAL REGISTRATION
ISRCTN.org Identifier: ISRCTN60048867.
Topics: Administration, Inhalation; Cannula; Continuous Positive Airway Pressure; Critical Care; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Oxygen Inhalation Therapy; Respiratory Insufficiency
PubMed: 35707984
DOI: 10.1001/jama.2022.9615 -
Minerva Anestesiologica Sep 2019The role of spontaneous breathing among patients with acute hypoxemic respiratory failure and ARDS is debated: while avoidance of intubation with noninvasive ventilation... (Review)
Review
The role of spontaneous breathing among patients with acute hypoxemic respiratory failure and ARDS is debated: while avoidance of intubation with noninvasive ventilation (NIV) or high-flow nasal cannula improves clinical outcome, treatment failure worsens mortality. Recent data suggest patient self-inflicted lung injury (P-SILI) as a possible mechanism aggravating lung damage in these patients. P-SILI is generated by intense inspiratory effort yielding: (A) swings in transpulmonary pressure (i.e. lung stress) causing the inflation of big volumes in an aerated compartment markedly reduced by the disease-induced aeration loss; (B) abnormal increases in transvascular pressure, favouring negative-pressure pulmonary edema; (C) an intra-tidal shift of gas between different lung zones, generated by different transmission of muscular force (i.e. pendelluft); (D) diaphragm injury. Experimental data suggest that not all subjects are exposed to the development of P-SILI: patients with a PaO2/FiO2 ratio below 200 mmHg may represent the most at risk population. For them, current evidence indicates that high-flow nasal cannula alone may be superior to intermittent sessions of low-PEEP NIV delivered through face mask, while continuous high-PEEP helmet NIV likely promotes treatment success and may mitigate lung injury. The optimal initial noninvasive treatment of hypoxemic respiratory failure/ARDS remains however uncertain; high-flow nasal cannula and high-PEEP helmet NIV are promising tools to enhance success of the approach, but the best balance between these techniques has yet to be identified. During noninvasive support, careful clinical monitoring remains mandatory for prompt detection of treatment failure, in order not to delay intubation and protective ventilation.
Topics: Acute Lung Injury; Cannula; Humans; Hypoxia; Monitoring, Physiologic; Noninvasive Ventilation; Oxygen Inhalation Therapy; Positive-Pressure Respiration; Pulmonary Edema; Respiration; Respiratory Distress Syndrome; Respiratory Insufficiency; Respiratory Mechanics; Self-Injurious Behavior; Treatment Failure; Unnecessary Procedures; Ventilator-Induced Lung Injury; Work of Breathing
PubMed: 30871304
DOI: 10.23736/S0375-9393.19.13418-9 -
Respiratory Care Oct 2019Oxygen is the most commonly used drug in critical care. However, because it is a gas, most clinicians and most patients do not regard it as a drug. For this reason, the... (Review)
Review
Oxygen is the most commonly used drug in critical care. However, because it is a gas, most clinicians and most patients do not regard it as a drug. For this reason, the use of medical oxygen over the past century has been driven by custom, practice, and "precautionary principles" rather than by scientific principles. Oxygen is a life-saving drug for patients with severe hypoxemia, but, as with all other drugs, too much can be harmful. It has been known for many decades that the administration of supplemental oxygen is hazardous for some patients with COPD and other patients who are vulnerable to retention of carbon dioxide (ie, hypercapnia). It has been recognized more recently that excessive oxygen therapy is associated with significantly increased mortality in critically ill patients, even in the absence of risk factors for hypercapnia. This paper provides a critical overview of past and present oxygen use for critically ill patients and will provide guidance for safer oxygen use in the future.
Topics: Critical Illness; Emergency Medical Services; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Intensive Care Units; Oxygen; Oxygen Inhalation Therapy; Practice Patterns, Physicians'; Respiration, Artificial
PubMed: 31409632
DOI: 10.4187/respcare.07044 -
Current Opinion in Anaesthesiology Jun 2022Apneic oxygenation is increasingly used in pediatric anesthesia. Its benefit for specific applications depends on the effect of apneic oxygenation on safe apnea time and... (Review)
Review
PURPOSE OF REVIEW
Apneic oxygenation is increasingly used in pediatric anesthesia. Its benefit for specific applications depends on the effect of apneic oxygenation on safe apnea time and carbon dioxide (CO2) elimination, on differences between low and high flow oxygen delivery, and on possible adverse effects. The present review summarizes current evidence on these pathophysiological aspects of apneic oxygenation as well as its applications in pediatric anesthesia.
RECENT FINDINGS
Apneic oxygenation with both low flow and high flow nasal oxygen increases the safe apnea time, but does not lead to increased CO2 elimination. Airway pressures and adverse effects like atelectasis formation, oxidative stress and aerosol generation under apneic oxygenation are not well studied in pediatric anesthesia. Data from adults suggest no important effect on airway pressures when the mouth is open, and no significant formation of atelectasis, oxidative stress or aerosol generation with high flow nasal oxygen.
SUMMARY
Apneic oxygenation in pediatric anesthesia is mainly used during standard and difficult airway management. It is sometimes used for airway interventions, but CO2 accumulation remains a major limiting factor in this setting. Reports highlight the use of high flow nasal oxygen in spontaneously breathing rather than in apneic children for airway interventions.
Topics: Adult; Anesthesia; Apnea; Carbon Dioxide; Child; Humans; Oxygen; Oxygen Inhalation Therapy; Pulmonary Atelectasis
PubMed: 35671025
DOI: 10.1097/ACO.0000000000001127 -
The European Respiratory Journal Sep 2021
Topics: Humans; Oximetry; Oxygen; Oxygen Inhalation Therapy
PubMed: 34598975
DOI: 10.1183/13993003.01023-2021 -
Nature Reviews. Cardiology Nov 2023Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular... (Review)
Review
Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have questioned the excessive use of oxygen therapy and have identified specific cardiovascular diseases in which a more conservative approach to oxygen therapy could be beneficial compared with a more liberal approach. In this Review, we provide numerous perspectives on systemic and molecular oxygen homeostasis and the pathophysiological consequences of excessive oxygen use. In addition, we provide an overview of findings from clinical studies on oxygen therapy for myocardial ischaemia, cardiac arrest, heart failure and cardiac surgery. These clinical studies have prompted a shift from liberal oxygen supplementation to a more conservative and vigilant approach to oxygen therapy. Furthermore, we discuss the alternative therapeutic strategies that target oxygen-sensing pathways, including various preconditioning approaches and pharmacological HIF activators, that can be used regardless of the level of oxygen therapy that a patient is already receiving.
Topics: Animals; Humans; Cardiovascular Diseases; Hypoxia; Oxygen; Oxygen Inhalation Therapy; Gene Expression Regulation; Mammals
PubMed: 37308571
DOI: 10.1038/s41569-023-00886-y