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Research JAMA Pediatrics | Original Investigation Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children A Systematic Review and Network Meta-Analysis Narayan Prabhu Iyer, MBBS, MD; Alexandre T. Rotta, MD; Sandrine Essouri, MD, PhD; Jose Roberto Fioretto, MD, PhD; Hannah J. Craven, MLIS; Elizabeth C. Whipple, MLS, AHIP; Padmanabhan Ramnarayan, MBBS, MD; Samer Abu-Sultaneh, MD; Robinder G. Khemani, MD, MsCI Supplemental content IMPORTANCE Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown. OBJECTIVE To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT). DATA SOURCES MEDLINE, Embase, and CINAHL Complete through May 2022. STUDY SELECTION Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS. DATA EXTRACTION AND SYNTHESIS Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA). MAIN OUTCOMES AND MEASURES The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury. RESULTS A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension. CONCLUSIONS AND RELEVANCE The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF. Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Author: Narayan Prabhu Iyer, MBBS, MD, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, 4650 Sunset JAMA Pediatr. doi:10.1001/jamapediatrics.2023.1478 Blvd, MS#31, Los Angeles, CA 91301 Published online June 5, 2023. (niyer@chla.usc.edu). (Reprinted) E1 Research Original Investigation Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children xtubation failure (EF) is an important event that is as- sociated with poor clinical outcomes in pediatric inten- Key Points 1-3 E sive care units (PICUs). Postextubation noninvasive Question What is the most effective postextubation noninvasive respiratory support (NRS), including high-flow nasal cannula respiratory support modality in children? (HFNC), continuous positive airway pressure (CPAP), and bi- Findings In this systematic review and network meta-analysis, level positive airway pressure (BiPAP), is frequently used in extubation failure and treatment failure rates were lower with PICUs in an attempt to reduce the risk of EF. Several random- continuous positive airway pressure (CPAP), high-flow nasal ized clinical trials and observational studies have tried to evalu- cannula (HFNC), and bilevel positive airway pressure (BiPAP) ate the efficacy of various modes of NRS, but based on the cur- compared to conventional oxygen therapy (COT). Based on rent evidence, it is unclear whether NRS is superior to bayesian ranking probabilities, CPAP was reported to be the most effective of the evaluated noninvasive respiratory support modes conventional oxygen therapy (COT) in preventing EF and which for the prevention of extubation failure and treatment failure. type of NRS is the most effective. Pooling of evidence from randomized clinical trials and or Meaning The results suggest that CPAP, HFNC, and BiPAP were observational studies using a meta-analytic model is consid- more effective than COT for providing postextubation NRS in a pediatric population. ered the highest form of evidence. However, a standard pair- wise meta-analysis is limited when there is a high degree of heterogeneity among studies, particularly when the interven- cluded liberation from NRS, total duration of NRS, number of tions and comparators differ (ie, different forms of NRS). There- ventilator-free days, hospital length of stay, and pressure in- fore, we designed a systematic review and network meta- juries. One outcome of limited importance was included, analysis to study the relative efficacy reported for different namely, abdominal distension. modes of NRS in preventing EF and other patient-centered out- comes among critically ill children. Literature Search and Data Collection Comprehensive search strategies were composed and con- ducted by 1 of 2 medical librarians (H.J.C. or E.C.W.) in MEDLINE, Embase, and CINAHL Complete on March 10, 2021, Methods and run again on May 12, 2022, for all human studies includ- To prepare this report, we used the Preferred Reporting Items ing children 18 years and younger. There were no language or for Systematic Reviews and Meta-analyses (PRISMA) reporting date limitations. Only randomized clinical trials were in- guideline (eTable 1 in Supplement 1). This review was cluded in the review. Further details of the literature search conducted as part of a project to develop clinical practice are provided in the eMethods in Supplement 1, and the com- 6,7 guidelines for ventilator liberation in children. The protocol plete search strategy is provided in eTable 2 in Supplement 1. for the systematic review is registered in PROSPERO Data abstraction was done by a pair of independent review- (CRD42021228702). Details of the protocol for the systematic ers using a standardized data collection form in REDCap, and review can be accessed at https://www.crd.york.ac.uk/ discrepancies between the 2 reviewers were resolved by a third PROSPERO/display_record.php?ID=CRD42021228702. reviewer. Risk of bias of included studies was assessed using the Cochrane tool for the assessment of risk of bias in random- ized trials (RoB version 2.0). Population, Interventions, and Outcomes This systematic review and network meta-analysis was de- signed to answer the following questions. In children who are Statistical Analysis hospitalized in the short term, is postextubation NRS more ef- HFNC, CPAP, and BiPAP were the experimental nodes (inter- fective than COT in preventing EF? What is the reported rela- ventions in a network plot), and COT was considered the refer- tive efficacy of different modes of NRS in preventing EF? The ence node in the network meta-analysis. We performed the population in included studies comprised critically ill children analysis using a bayesian analytic framework. A bayesian ap- from birth (born at 37 weeks’ gestation or later) to age 18 years proach has been preferred for network meta-analyses since it is receivinginvasivemechanicalventilationformorethan24hours better able to handle studies with very few events and produce and being supported by postextubation NRS either as rescue or probability and ranking outputs that are intuitive to end users. planned prior to extubation. The different modes of NRS in- Abayesianrandom-effectsmodelfornetworkmeta-analysiswas cluded HFNC, CPAP, and BiPAP using any patient interface. adopted because it assumes and accounts for unexplained Outcomes were selected prior to the literature search and heterogeneity across studies (eMethods in Supplement 1). rated for their patient centeredness and importance using the Different interventions were ranked using the rank prob- Grading of Recommendations Assessment, Development and abilities generated by the bayesian approach. We also used the Evaluation (GRADE) approach. The panel of experts catego- surface under the cumulative ranking curve (SUCRA) to de- rized the outcomes as follows. Critical outcomes included mor- scribe the relative ranking of interventions. SUCRA is ex- tality, failure to liberate from invasive mechanical ventilation pressed as a fraction and provides the relative probability of (ie, EF, ,defined as reintubation within 48 to 72 hours), PICU an intervention being the best among all options. SUCRA of length of stay, escalation of care or crossover to other treat- 1 for an intervention indicates that the intervention is certain ments, and treatment failure (TF; reintubation or escalation/ to be the best among all the interventions tested, while a SU- crossover to another NRS mode). Important outcomes in- CRA of 0 indicates that the intervention is certain to be the E2 JAMA Pediatrics Published online June 5, 2023 (Reprinted) jamapediatrics.com Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children Original Investigation Research Figure 1. Effect Estimates and Grading of Recommendations Assessment, Development, and Evaluation Certainty of Evidence Rating for Reintubation and Treatment Failure Extubation failure, OR (95% CrI) Treatment failure, OR (95% CrI) COT CPAP HFNC BiPAP COT CPAP HFNC BiPAP 0.43 0.49 0.63 0.26 0.33 0.45 COT (0.17-1.02) (0.24-1.01) (0.24-1.64) COT (0.10-0.56) (0.15-0.65) (0.17-1.16) Low Low Low High High Low 1.14 1.47 1.26 1.72 CPAP (0.62-2.09) (0.64-3.48) CPAP (0.74-2.26) (0.75-4.22) Low Low Moderate Low 1.28 1.36 (0.54-3.13) (0.57-3.38) HFNC HFNC Low Low BiPAP BiPAP Grade certainty of evidence High Moderate Low Odds ratios (ORs) and 95% credible intervals (CrIs) are presented. Comparisons positive airway pressure; COT, conventional oxygen therapy; CPAP, continuous between treatments should be read from left to right. ORs less than 1 favor the positive airway pressure; HFNC, high-flow nasal cannula. column-defining treatment for the network estimates. BiPAP indicates bilevel worst among the treatments tested. It is recommended that maining 174 records were reviewed for eligibility. A total of 9 the ranks be interpreted in the context of the certainty of evi- randomized clinical trials fulfilled the eligibility criteria and dence and the absolute risk reduction of the pairwise were included in the analysis. eFigure 1 in Supplement 1 shows 13,14 comparisons. the reasons for exclusion of records during the full text Using the bayesian framework, we performed a meta- review. regression analysis to explore the association of age with the The 9 included studies had a total sample size of 1421 21-29 effectiveness of NRS on reducing EF (reintubation) and TF. In participants. Characteristics of the studies included in this our model, we assumed a common study-level covariate ef- review along with the details of NRS equipment and the in- fect vs the baseline treatment (COT). We chose to divide stud- terfaces used are provided in eTable 3 in Supplement 1.Five ies into 2 groups, those with a mean age 6 months and younger studies compared COT with NRS; 3 compared COT with 21,26,27 25 and those with a mean age older than 6 months based on epi- HFNC, 1 compared COT with CPAP, and 1 compared 22 23,24 demiologic data suggesting higher rates of EF in younger COT with BiPAP. Two trials compared HFNC and CPAP, 16 28 children. Modelcomparisonswerebasedoncomparingmodel 1 compared HFNC and BiPAP, and 1 compared CPAP and fit in addition to the deviance information criterion (DIC). DIC BiPAP. NRS (HFNC, CPAP, and BiPAP) was initiated imme- 21,22,26-29 is the combination of the penalty incurred for complexity of a diately after extubation (planned NRS) in 6 studies, model and the deviance for a model. Models with smaller DIC while 1 study used NRS only with the onset of respiratory dis- are preferred to models with larger DIC, and a difference in DIC tress (rescue NRS). Two studies allowed both planned and 17 23,24 greater than 7 is considered substantial. rescue NRS. The primary outcome varied between the For outcomes with only 2 interventions, we performed studies, but all studies reported EF (defined as reintubation standard pairwise meta-analysis with a random-effects model within 48 to 72 hours). using RevMan version 5.4 (Cochrane Collaboration). The net- The risk of bias profiles for EF is shown in eFigure 2 in work meta-analysis was conducted using the GeMTC pack- Supplement 1. None of the trials were blinded because of the age of R version 3.5.3 (RStudio), and the network plots were impracticality of blinding NRS. Concealment of the alloca- created using the multinma package in R version 4.2.2 (R tion sequence was poorly reported. In the context of lack of Foundation). We assessed certainty of evidence using re- blinding, 2 studies were considered to have high risk of bias cently published guidance by the GRADE working group because they allowed crossover of COT to the other arm. De- 19,20 (eMethods in Supplement 1). tails of the risk of bias profiles for other outcomes is provided in supplemental figures (eFigures 3-11 in Supplement 1). Estimates of Interventions Results In the network meta-analysis, all 9 trials reported outcomes A total of 11 615 records were screened, 11 441 of which were for EF and TF. Figure 1 describes the relative effect estimates excluded after reviewing the abstracts. Full texts of the re- and absolute estimates reported for EF and TF of COT, HFNC, jamapediatrics.com (Reprinted) JAMA Pediatrics Published online June 5, 2023 E3 Research Original Investigation Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children Figure 2. Cumulative Ranks and Surface Under the Cumulative Rank Curve (SUCRA) for Extubation Failure and Treatment Failure Treatment BiPAP CPAP COT HFNC A Extubation failure B Treatment failure 1.00 1.00 Cumulative probability curves and 0.75 0.75 SUCRA values for different noninvasive respiratory support modes. For each mode, the cumulative probability of being 0.50 0.50 ranked first through fourth is displayed. The more the curve for a certain regimen is located toward the SUCRA: SUCRA: 0.25 0.25 upper left corner, the higher its CPAP (0.829) CPAP (0.912) SUCRA value and the better its HFNC (0.669) HFNC (0.644) BiPAP (0.426) BiPAP (0.426) effectiveness. BiPAP indicates bilevel COT (0.0748) COT (0.017) positive airway pressure; COT, 0 0 1 2 3 4 1 2 3 4 conventional oxygen therapy; CPAP, Rank Rank continuous positive airway pressure; HFNC, high-flow nasal cannula. CPAP, and BiPAP. HFNC, CPAP, and BiPAP were associated with of stay was shorter for HFNC (−8.7 days; 95% CrI, −19.0 to 1.1) lower rates of EF compared to COT. The largest absolute risk and CPAP (−9 days; 95% CrI, −20.0 to 2.4) (eTable 4 in Supple- reduction (6%), with a baseline risk of EF of 12%, was seen with ment 1), and the estimates were similar to COT for HFNC (0.03 CPAP (number needed to treat = 17 per 1000 patients). CPAP days; 95% CrI, −1.6 to 1.7) and CPAP (−0.3 days; 95% CrI, −3.2 had the highest probability of being the best intervention with to 2.6) for PICU length of stay (eTable 5 in Supplement 1). 23,24,27,28 28 a SUCRA of 0.83. HFNC, CPAP, and BiPAP appeared to be even PICU mortality was reported in 4 trials. One trial more effective with the outcome of reducing TF. Compared to had 0 events for the HFNC arm, and this study was not in- COT, both HFNC (11% reduction) and CPAP (12% reduction) cluded in the network meta-analysis, as there is no standard were associated with large absolute reductions in TF with the methodology in bayesian network analyses for dealing with 31,32 baseline TF rate of 18%. Like for EF, CPAP had the highest prob- studies with 0 events. COT (3.9% mortality), CPAP (1.2% ability of being the best intervention to prevent TF with a SU- mortality), and HFNC (2.2% mortality in all studies and 2.5% CRA of 0.91. HFNC was the second ranked intervention and mortality in studies included in the analysis) had similar rates BiPAP the third ranked intervention for both EF and TF. The of PICU mortality (eTable 6 in Supplement 1). 30 26,27 cumulative ranking curves for EF and TF are shown in Two trials comparing HFNC and COT had 0 events re- Figure 2. The summary absolute effect sizes of all the com- lated to nasal injury, and these were excluded from the analy- parisons along with the GRADE certainty of evidence esti- sis. Incidence of nasal injury was modestly elevated for CPAP mates is provided in Figure 3 (EF) and Figure 4 (TF). (3.8%) and HFNC (1.3%) and moderately elevated for BiPAP Age-adjusted subgroup forest plots derived using a meta- (8.7%) compared to COT. Compared to HFNC, CPAP (OR, 2.7; regression analysis for EF and TF are shown in Figure 5. The 95% CrI, 0.84-13) and BiPAP (OR, 3.1; 95% CrI, 0.80-20) had a effect estimates appear similar for EF, whereas for TF, NRS ap- nonsignificant trend for increased incidence of nasal injury peared to be more effective in infants 6 months and younger. (eTable 7 in Supplement 1). The interaction coefficient B (log odds ratio [OR] with 95% CrI) COT had 0 events of abdominal distension in 2 trials. The for EF was 0.25 (−1.60 to 2.06) with a DIC of 31.7. The interac- mean incidence of abdominal distension was similar for all NRS tion coefficient for TF was −1.21 (−2.91 to 0.25) with a DIC of modes but modestly higher than COT (HFNC, 2.4%; CPAP, 31.4. Thus, the covariate-adjusted models did not offer no- 2.8%; and BiPAP, 3.2%) with no difference between the NRS table improvement in DIC compared with the unadjusted mod- modes in the network meta-analysis (eTable 8 in Supple- els (DIC = 30.4), and the 95% CrI of the interaction coeffi- ment 1). Analysis for all the outcomes reached convergence and cient includes the possibility of no interaction for both the none of network loops showed inconsistency. outcomes. The 95% CrI of the interaction coefficient for TF was Three outcomes—hospital mortality, aspiration, and se- close to the level of significance, suggesting that all 3 inter- dation use—were only reported in 2 studies comparing CPAP 23,24 ventions (HFNC, CPAP, and BiPAP) may be more effective than and HFNC (eTable 9 and eFigures 9-11 in Supplement 1). COT in infants. In this age-adjusted model, CPAP remained the In a pairwise analysis, hospital mortality was lower with CPAP best ranked treatment, with a SUCRA of 0.82 for EF and 0.89 compared to HFNC with an OR of 0.38 (95% CI, 0.15-0.97). This for TF. difference in mortality was largely due to unexplained differ- A detailed summary of other findings can be found in ence in 1 study where most deaths in the HFNC group (ie, 8 of eTable 4 in Supplement 1 and risk of bias profiles are in eFig- 13) happened after PICU discharge. The rates of aspiration ures 3-8 in Supplement 1). Compared to COT, hospital length (OR, 1.00; 95% CI, 0.21-4.73) and sedation use (OR, 0.95; 95% E4 JAMA Pediatrics Published online June 5, 2023 (Reprinted) jamapediatrics.com Cumulative percentage (1=100%) Cumulative percentage (1=100%) Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children Original Investigation Research Figure 3. Summary of Findings for Extubation Failure Studies, No. HFNC COT Population: critically ill children intubated and mechanically ventilated for at least 24 h Interventions: HFNC Total sample size CPAP BiPAP Reference treatment: COT Outcomes: extubation failure Setting: PICU, CICU CPAP BiPAP Outcome: extubation failure. Rate in reference population: 12.3% (123 per 1000) Anticipated absolute effect (95% Crl) Intervention, total Odds ratio (95% Crl) Certainty of evidence Ranking (SUCRA) studies, total participants Without intervention With intervention Difference 58 Fewer per 1000 a HFNC, 6 trials, 1080 Low 0.669 123 per 1000 0.50 (0.23-1.02) 65 per 1000 91 (fewer to 2 more) participants CPAP, 4 trials, 843 66 Fewer per 1000 Low 0.829 123 per 1000 0.43 (0.17-1.01) 57 per 1000 participants (99 fewer to 2 more) BiPAP, 3 trials, 418 42 Fewer per 1000 Low 0.426 0.64 (0.24-1.64) 123 per 1000 81 per 1000 participants (92 fewer to 64 more) COT, 5 trials, 501 Reference 0.074 Reference Reference Reference Reference participants Compared with COT Odds ratio (95% Crl) BiPAP 0.64 (0.24-1.60) Relative effects with CPAP 0.43 (0.17-1.01) reference to COT HFNC 0.50 (0.23-1.01) 0.1 1.0 2.0 BiPAP indicates bilevel positive airway pressure; COT, conventional oxygen therapy; CPAP, continuous positive airway pressure; CrI, credible interval; HFNC, high-flow nasal cannula. Downgraded due to serious risk of bias and imprecision. CI, 0.83-1.09) were not different between the HFNC and CPAP venting EF and TF in the 9 included trials. CPAP was likely the groups (eFigure 12 in Supplement 1). Length of invasive me- best modality for preventing EF and TF. HFNC was likely the chanical ventilation prior to extubation was not reported in all second best modality for preventing EF and TF, with an effec- the studies, and we could not analyze its impact on NRS tiveness only modestly lower than that of CPAP. efficacy. The results of the meta-regression analysis did not show a statistically significant interaction with age and should be considered exploratory. Nevertheless, our results suggest a trend of improved efficacy of NRS in children 6 months and Discussion younger compared to those older than 6 months. CPAP re- There is increasing recognition of potential harms with pro- mained the best NRS mode in infants 6 months and younger. 33,34 longed use of invasive mechanical ventilation in children. We used TF as a composite outcome (escalation or cross- Early liberation from invasive mechanical ventilation, often over of respiratory support plus EF) to describe the real- with the use of postextubation NRS, has been attempted with world practice in which escalation or change to other forms of the aim of reducing the duration of invasive mechanical ven- NRS are often tried before reintubation. Trials that allowed es- tilation without increasing the rates of EF. Many modes of NRS calation reflect a practice that is closer to real-world postex- have been studied in children but the optimal mode for postex- tubation care but obscure the true difference in EF rates be- tubation respiratory support remains uncertain. Using a net- tween the trial arms. In this systematic review and network work meta-analysis model, our study results suggest that meta-analysis, we found a large reduction in TF both with CPAP HFNC, CPAP, and BiPAP appeared to be better than COT in pre- (12.5% less) and HFNC (11.2% less) compared to COT. jamapediatrics.com (Reprinted) JAMA Pediatrics Published online June 5, 2023 E5 Research Original Investigation Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children Figure 4. Summary of Findings for Treatment Failure Studies, No. HFNC COT Population: critically ill children intubated and mechanically ventilated for at least 24 h Interventions: HFNC CPAP Total sample size BiPAP Reference treatment: COT Outcomes: treatment failure Setting: PICU, CICU CPAP BiPAP Outcome: treatment failure (escalation/crossover plus reintubation). Rate in reference population: 18% (183 per 1000) Anticipated absolute effect (95% Crl) Intervention, total Certainty of evidence Ranking (SUCRA) studies, total Odds ratio (95% Crl) participants Without intervention With intervention Difference 112 Fewer per 1000 HFNC, 6 trials, 1084 High 0.644 180 per 1000 0.33 (0.16-0.65) 68 per 1000 147 (fewer to 55 fewer) participants CPAP, 4 trials, 847 125 Fewer per 1000 High 0.912 180 per 1000 0.266 (0.11-0.56) 55 per 1000 participants (157 fewer to 70 fewer) BiPAP, 3 trials, 418 90 Fewer per 1000 Low 0.426 0.46 (0.17-1.20) 180 per 1000 113 per 1000 participants (144 fewer to 23 more) COT, 5 trials, 501 Reference 0.017 Reference Reference Reference Reference participants Compared with COT Odds ratio (95% Crl) BiPAP 0.46 (0.17-1.20) Relative effects with CPAP 0.26 (0.11-0.56) reference to COT HFNC 0.33 (0.16-0.65) 0.1 1.0 2.0 BiPAP indicates bilevel positive airway pressure; CICU, cardiac intensive care unit; COT, conventional oxygen therapy; CPAP, continuous positive airway pressure; CrI, credible interval; HFNC, high-flow nasal cannula. Downgraded due to serious risk of bias and imprecision. Our report illustrates the trade-offs involved when choos- dominal distension), CPAP and HFNC would typically be pref- ing a NRS modality for postextubation support. Compared to erable to COT for postextubation support, especially in chil- COT, CPAP and HFNC showed large reductions in EF (approxi- dren at high risk of EF. EF rates vary across regions and health 36,37 mately6%reduction)andTF(approximately12%reduction)and care settings ; the absolute risk reduction in EF associated possibly hospital length of stay (approximately 9 days reduc- with NRS use will likely increase in settings where the baseline tion). On the other hand, CPAP and BiPAP were associated with EF rate is higher and where NRS modes can be effectively imple- high rates of nasal trauma compared to COT (3% to 8% in- mented. A recent network meta-analysis including adult trials crease)andHFNC(approximately1%increase).HFNC,CPAP,and studying the efficacy of postextubation NRS suggested in- BiPAP also had an approximate 2% increase in the incidence of creased effectiveness with NRS in patients at higher risk of EF. abdominal distension compared to COT. Comparing CPAP and We could not perform a similar analysis due to a lack of suffi- HFNC,bothmodalitieshadsimilarreportedeffectivenessinpre- cientnumberofrandomizedclinicaltrialsamongchildrenathigh venting EF and TF, although CPAP was ranked higher for both risk of EF. the outcomes. PICU and hospital length of stay, aspiration risk, and sedation use were similar between CPAP and HFNC. CPAP Limitations had reduced hospital mortality compared to HFNC, although There are several limitations to our study. The risk of bias as- most of the difference in mortality was after discharge from the sociated with studies resulted in low to very low certainty of PICU, and the cause of the difference is unclear. As most pa- evidence in most comparisons and therefore the study re- tients, families, and clinicians are likely to value preventing EF sults should be interpreted with caution. The generalizability over the potential adverse outcomes (eg, pressure injury and ab- of our analysis is affected by the characteristics of the popu- E6 JAMA Pediatrics Published online June 5, 2023 (Reprinted) jamapediatrics.com Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children Original Investigation Research Figure 5. Meta-Regression Analysis for Extubation Failure and Treatment Failure Using Age as an Effect Modifier A Extubation failure B Treatment failure ≤6 mo >6 mo HFNC HFNC Forest plot of effect estimates and 95% credible intervals (CrIs) derived CPAP CPAP from the meta-regression network meta-analysis exploring the impact of age (6 months vs >6 months) on the effectiveness of noninvasive BiPAP BiPAP respiratory support for preventing extubation failure and treatment failure. BiPAP indicates bilevel positive airway pressure; CICU, 0.12 0.25 0.50 1.0 2.0 4.0 0.02 0.04 0.09 0.18 0.35 0.71 1.41 cardiac intensive care unit; CPAP, Odds ratio, 95% CrI Odds ratio, 95% CrI continuous positive airway pressure; HFNC, high-flow nasal cannula. lation included in the trials. Only 2 studies had a mean age older relative efficacy of different NRS modes. Most trials did not in- than 1 year, and the mean age in these was younger than 48 clude outcomes or data related to resource utilization or cost. months, which might limit generalization of these results to Costs of different NRS modes are not standard across coun- older patients. None of the studies with CPAP or BiPAP had a tries and health systems; sometimes overall costs associated mean or median age older than 1 year. Further, patients with with a specific NRS mode become the decisive issue in the certain noncardiac congenital abnormalities (eg, congenital dia- choice of NRS to be used in an institution. phragmatic hernia and facial abnormalities) and neurologic or neuromuscular impairment were excluded from 7 and 5 stud- ies, respectively. Thus, the results of this analysis may only be Conclusion applicable to younger children without such abnormalities. Similarly, CPAP and BiPAP interfaces were varied and in- Despite its limitations, this systematic review and network cluded nonocclusive nasal cannulas, which are likely less ef- meta-analysis provides evidence of better reported effective- fective in providing predictable pressures compared to leak- ness with CPAP, HFNC, and BiPAP compared to COT in pre- free interfaces. When choosing a NRS mode, considerations of venting EF and TF with modest increases in complications such equipment availability, associated costs to patients and the as abdominal distension and nasal injury. CPAP was likely to health care system, and the need for a high level of nursing care be the best intervention to prevent EF and TF. Future studies are also important. These factors vary across health systems are needed in children older than 2 years and in specific popu- and geographic regions and are likely to have an impact on the lations at higher risk of EF. ARTICLE INFORMATION (Ramnarayan); Department of Pediatrics, Division Administrative, technical, or material support:Iyer, of Pediatric Critical Care, Riley Hospital for Children Craven, Whipple, Khemani. Accepted for Publication: April 5, 2023. at Indiana University Health and Indiana University Supervision: Iyer, Ramnarayan, Abu-Sultaneh, Published Online: June 5, 2023. School of Medicine, Indianapolis (Abu-Sultaneh); Khemani. doi:10.1001/jamapediatrics.2023.1478 Department of Anesthesiology and Critical Care, Conflict of Interest Disclosures: Dr Iyer reported Open Access: This is an open access article Children’s Hospital Los Angeles, Los Angeles, grants from Eunice Kennedy Shriver National distributed under the terms of the CC-BY License. California (Khemani); Children’s Hospital Los Institute of Child Health and Human Development ©2023IyerNPetal. JAMA Pediatrics. Angeles, University of Southern California Keck National Heart, Lung, and Blood Institute during the Author Affiliations: Division of Neonatology, Fetal School of Medicine, Los Angeles (Khemani). conduct of the study. Dr Rotta reported personal and Neonatal Institute, Children’s Hospital Los Author Contributions: Dr Iyer had full access to all fees from Breas for clinical advisory board Angeles, Los Angeles, California (Iyer); Department the data in the study and takes responsibility for the participation outside the submitted work and of Pediatrics, Keck School of Medicine, University of integrity of the data and the accuracy of the data royalties from Elsevier for editorial work on a Southern California, Los Angeles (Iyer); Department analysis. textbook and personal fees from Vapotherm for of Pediatrics, Division of Pediatric Critical Care Concept and design: Iyer, Rotta, Essouri, Fioretto, lecturing and development of educational materials Medicine, Duke University, Durham, North Carolina Whipple, Ramnarayan, Abu-Sultaneh, Khemani. outside the submitted work. Dr Ramnarayan (Rotta); Department of Pediatrics, Sainte-Justine Acquisition, analysis, or interpretation of data:Iyer, reported grants from National Institute for Health Hospital, Université de Montréal, Montreal, Rotta, Essouri, Craven, Whipple, Ramnarayan, and Care Research during the conduct of the study Quebec, Canada (Essouri); Department of Abu-Sultaneh, Khemani. and consultancy fees from Sanofi outside the Pediatrics, Pediatric Critical Care Division, Botucatu Drafting of the manuscript: Iyer, Fioretto, Craven, submitted work. Dr Abu-Sultaneh reported grants Medical School - UNESP-Sao Paulo State University, Ramnarayan, Khemani. from Eunice Kennedy Shriver National Institute of Botucatu, Sao Paulo, Brazil (Fioretto); Ruth Lilly Critical revision of the manuscript for important Child Health, the National Heart, Lung, and Blood Medical Library, Indiana University School of intellectual content: Iyer, Rotta, Essouri, Craven, Institute, and Indiana University School of Medicine Medicine, Indianapolis (Craven, Whipple); Faculty Whipple, Abu-Sultaneh, Khemani. during the conduct of the study. Dr Khemani of Medicine, Department of Surgery and Cancer, Statistical analysis: Iyer, Khemani. reported grants from the National Institutes of Imperial College London, London, United Kingdom Obtained funding: Abu-Sultaneh, Khemani. Health during the conduct of the study and jamapediatrics.com (Reprinted) JAMA Pediatrics Published online June 5, 2023 E7 Research Original Investigation Association of Extubation Failure Rates With HFNC, CPAP, and BiPAP vs COT in Children personal fees from Nihon Kohden OrangeMed and 12. Salanti G, Ades AE, Ioannidis JP. Graphical for post-extubation laryngitis in pediatric patients. Bayer outside the submitted work. No other methods and numerical summaries for presenting Article in Spanish. Arch Bronconeumol. 2002;38 results from multiple-treatment meta-analysis: an (10):463-467. doi:10.1016/s0300-2896(02) disclosures were reported. overview and tutorial. J Clin Epidemiol. 2011;64(2): 75266-6 Funding/Support: The project was funded by 163-171. doi:10.1016/j.jclinepi.2010.03.016 26. Testa G, Iodice F, Ricci Z, et al. Comparative Eunice Kennedy Shriver National Institute of Child 13. Mbuagbaw L, Rochwerg B, Jaeschke R, et al. evaluation of high-flow nasal cannula and Health and Human Development National Heart, Approaches to interpreting and choosing the best conventional oxygen therapy in paediatric cardiac Lung, and Blood Institute of the National Institutes treatments in network meta-analyses. Syst Rev. surgical patients: a randomized controlled trial. of Health (R13HD102137), in addition to funds from 2017;6(1):79. doi:10.1186/s13643-017-0473-z Interact Cardiovasc Thorac Surg. 2014;19(3):456-461. the Department of Pediatrics at Indiana University doi:10.1093/icvts/ivu171 14. Murad MH, Montori VM, Ioannidis JP, et al. How School of Medicine, Indianapolis, Indiana. to read a systematic review and meta-analysis and 27. Wijakprasert P, Chomchoey J. High-flow nasal Role of the Funder/Sponsor: The funders had no apply the results to patient care: users’ guides to cannula versus conventional oxygen therapy in role in the design and conduct of the study; the medical literature. JAMA. 2014;312(2):171-179. post-extubation pediatric patients: a randomized collection, management, analysis, and doi:10.1001/jama.2014.5559 controlled trial. J Med Assoc Thai. 2018;101(10): interpretation of the data; preparation, review, or 1331-1335. http://www.jmatonline.com/index.php/ 15. Dias S, Sutton AJ, Welton NJ, Ades AE. Evidence approval of the manuscript; and decision to submit jmat/article/view/9504 synthesis for decision making 3: heterogeneity– the manuscript for publication. subgroups, meta-regression, bias, and 28. Li XQ, Zhao WL, Li DY, Lei L, Luo LL, Qiao LN. bias-adjustment. 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Ramnarayan P, Richards-Belle A, Drikite L, et al; Crit Care. 2022;38(1). doi:10.7196/SAJCC.2022. research informatics support. J Biomed Inform. FIRST-ABC Step-Up RCT Investigators and the v38i1.513 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 Paediatric Critical Care Society Study Group. Effect 38. Fernando SM, Tran A, Sadeghirad B, et al. of high-flow nasal cannula therapy vs continuous 10. Sterne JAC, Savović J, Page MJ, et al. RoB 2: Noninvasive respiratory support following positive airway pressure therapy on liberation from a revised tool for assessing risk of bias in extubation in critically ill adults: a systematic review randomised trials. BMJ. 2019;366:l4898. doi:10. respiratory support in acutely ill children admitted and network meta-analysis. Intensive Care Med. to pediatric critical care units: a randomized clinical 1136/bmj.l4898 2022;48(2):137-147. doi:10.1007/s00134-021- trial. JAMA. 2022;328(2):162-172. doi:10.1001/jama. 11. Dias S, Caldwell DM. Network meta-analysis 06581-1 2022.9615 explained. Arch Dis Child Fetal Neonatal Ed. 2019; 104(1):F8-F12. doi:10.1136/archdischild-2018-315224 25. Rodríguez JA, Von Dessauer B, Duffau G. Non-invasive continuous positive airways pressure E8 JAMA Pediatrics Published online June 5, 2023 (Reprinted) jamapediatrics.com Supplemental Online Content Iyer NP, Rotta AT, Essouri S, et al. Association of extubation failure rates with high-flow nasal cannula, continuous positive airway pressure, and bilevel positive airway pressure vs conventional oxygen therapy in infants and young children: a systematic review and network meta-analysis. JAMA Pediatr. Published online June 5, 2023. doi:10.1001/jamapediatrics.2023.1478 eMethods. Details of Bayesian network analysis and Assessment of certainty of evidence eTable 1. PRISMA NMA Checklist of Items to Include When Reporting A Systematic Review Involving a Network Meta-analysis eTable 2. Search strategies for MEDLINE, Embase, and CINAHL eTable 3. Characteristics of included studies. eTable 4. Summary of findings: Hospital length of stay eTable 5. Summary of findings: PICU length of stay eTable 6. Summary of findings: PICU Mortality eTable 7. Summary of findings: Nasal Injury eTable 8. Summary of findings: Abdominal distension eTable 9. Summary of findings for pair-wise analysis between CPAP and HFNC eFigure 1. PRISMA Flow of information eFigure 2. Risk of bias. Extubation failure eFigure 3. Risk of bias: Treatment failure eFigure 4. Risk of bias: Abdominal distension eFigure 5. Risk of bias: Hospital length of stay eFigure 6. Risk of bias: PICU mortality eFigure 7. Risk of bias: Nasal injury eFigure 8. Risk of bias: PICU LOS © 2023 Iyer NP et al. JAMA Pediatrics. eFigure 9. Risk of bias: Hospital mortality eFigure 10. Risk of bias: Sedation use eFigure 11. Risk of bias: Aspiration eFigure 12. Forest plot of effect estimates and 95% confidence intervals of the pairwise metanalysis comparing CPAP and HFNC. This supplemental material has been provided by the authors to give readers additional information about their work. © 2023 Iyer NP et al. JAMA Pediatrics. eMethods Literature search Pairs of reviewers independently screened the title and abstracts and performed full text review. Any conflicts were resolved by a third reviewer. Title, abstract screening and full text review were performed using the systematic review software, Covidence (Covidence systematic review software, Veritas Health Innovation, Melbourne, Vic, Australia. (www.covidence.org). We used the following eligibility criteria: a) Patients: We included studies conducted in the PICU or the pediatric cardiac intensive care unit (CICU) that were performed on critically ill children up to age 18 years, receiving IMV for more than 24 hours who underwent or were scheduled for planned ventilator liberation. We excluded studies that included preterm infants (37 weeks or less gestation at birth) and where data for older infants and children were not included. We also excluded studies where extubation occurred in the neonatal intensive care unit (NICU) or outside the intensive care units (e.g. operating rooms). b) Study type: We included randomized trials evaluating the use of post-extubation NRS. We aimed to include all NRS modes using any patient interface. Details of Bayesian model For both the main analysis and the meta-regression analysis, we used Bayesian methods with informative priors for the between-trials heterogeneity. An empirical study conducted by Turner et al. provides the basis for choosing a plausible prior for the between-studies variance parameter [in our analysis a log normal distribution (-2.89, 1.91)], which is assumed to be equal across comparisons. © 2023 Iyer NP et al. JAMA Pediatrics. 2 The analysis was conducted with the Markov Chain Monte Carlo methods. Four Markov chains, yielding 400 000 iterations (100,000 iterations per chain after an initial burn-in of 10,000 and a thinning of 10) generating the posterior distributions of the model parameters, were carried out. Convergence was checked by using the Brooks-Gelman-Rubin diagnostic. The goodness of fit 2 2 of the model was assessed with residual deviance. The I statistic was used to assess statistical heterogeneity. Inconsistency was determined by the Bayesian p-value calculated using the node splitting approach. The effect of the intervention for dichotomous outcomes was summarized as odds ratio and 95% credible intervals (CrI); for continuous measures data was summarized as mean difference and 95% CrI. Assessment of certainty of evidence We assessed certainty of evidence using recently published guidance by the GRADE working 5,6 group. For this analysis, we used a minimally contextualized approach which only considers if the credible intervals include the null effect. Thresholds for ARR were determined by a survey of authors. The authors considered a difference of >3% (>30 per 1000 ARR) in extubation failure, a difference of >6% (>100 per 1000 ARR) in treatment failure (assuming half of patients with treatment failure get reintubated), a difference in PICU LOS of >24 hours and a difference in length of IMV of >12 hours as clinically significant. © 2023 Iyer NP et al. JAMA Pediatrics. eTable 1. PRISMA NMA Checklist of Items to Include When Reporting A Systematic Review Involving a Network Meta-analysis Section/Topic Item Checklist Item Reported # on Page # TITLE Title 1 Identify the report as a systematic review 1 incorporating a network meta-analysis (or related form of meta-analysis). ABSTRACT Structured 2 Provide a structured summary including, as 5-6 summary applicable: Background: main objectives Methods: data sources; study eligibility criteria, participants, and interventions; study appraisal; and synthesis methods, such as network meta- analysis. Results: number of studies and participants identified; summary estimates with corresponding confidence/credible intervals; treatment rankings may also be discussed. Authors may choose to summarize pairwise comparisons against a chosen treatment included in their analyses for brevity. Discussion/Conclusions: limitations; conclusions and implications of findings. Other: primary source of funding; systematic review registration number with registry name. INTRODUCTION Rationale 3 Describe the rationale for the review in the context 7 of what is already known, including mention of why a network meta-analysis has been conducted. Objectives 4 Provide an explicit statement of questions being 7 addressed, with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). METHODS Protocol and 5 Indicate whether a review protocol exists and if and 7-8 registration where it can be accessed (e.g., Web address); and, if available, provide registration information, including registration number. © 2023 Iyer NP et al. JAMA Pediatrics. Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of 8-9 follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. Clearly describe eligible treatments included in the treatment network, and note whether any have been clustered or merged into the same node (with justification). Information 7 Describe all information sources (e.g., databases 9 sources with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. Search 8 Present full electronic search strategy for at least eTable2 one database, including any limits used, such that it could be repeated. Study selection 9 State the process for selecting studies (i.e., eMethods screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). Data collection 10 Describe method of data extraction from reports 9 process (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. Data items 11 List and define all variables for which data were 8-9 sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. Geometry of the S1 Describe methods used to explore the geometry of Table 2, network the treatment network under study and potential Table 3 biases related to it. This should include how the evidence base has been graphically summarized for presentation, and what characteristics were compiled and used to describe the evidence base to readers. Risk of bias within 12 Describe methods used for assessing risk of bias of 9 individual studies individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. Summary measures 13 State the principal summary measures (e.g., risk 9-10 ratio, difference in means). Also describe the use of additional summary measures assessed, such as treatment rankings and surface under the cumulative ranking curve (SUCRA) values, as well as modified approaches used to present summary findings from meta-analyses. Planned methods 14 Describe the methods of handling data and 9-10 of analysis combining results of studies for each network meta- eMethods © 2023 Iyer NP et al. JAMA Pediatrics. analysis. This should include, but not be limited to: Handling of multi-arm trials; Selection of variance structure; Selection of prior distributions in Bayesian analyses; and Assessment of model fit. Assessment of S2 Describe the statistical methods used to evaluate the eMethods Inconsistency agreement of direct and indirect evidence in the treatment network(s) studied. Describe efforts taken to address its presence when found. Risk of bias across 15 Specify any assessment of risk of bias that may 9 studies affect the cumulative evidence (e.g., publication bias, selective reporting within studies). Additional 16 Describe methods of additional analyses if done, 9 analyses indicating which were pre-specified. This may include, but not be limited to, the following: Sensitivity or subgroup analyses; Meta-regression analyses; Alternative formulations of the treatment network; and Use of alternative prior distributions for Bayesian analyses (if applicable). RESULTS Study selection 17 Give numbers of studies screened, assessed for 11-12 eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. Presentation of S3 Provide a network graph of the included studies to Table 2, 3 network structure enable visualization of the geometry of the treatment network. Summary of S4 Provide a brief overview of characteristics of the Table 2,3 network geometry treatment network. This may include commentary on the abundance of trials and randomized patients for the different interventions and pairwise comparisons in the network, gaps of evidence in the treatment network, and potential biases reflected by the network structure. Study 18 For each study, present characteristics for which eTable3 characteristics data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. © 2023 Iyer NP et al. JAMA Pediatrics. Risk of bias within 19 Present data on risk of bias of each study and, if eFigure 2- studies available, any outcome level assessment. 11 Results of 20 For all outcomes considered (benefits or harms), 11-14 individual studies present, for each study: 1) simple summary data for each intervention group, and 2) effect estimates and confidence intervals. Modified approaches may be needed to deal with information from larger networks. Synthesis of results 21 Present results of each meta-analysis done, 11-14 including confidence/credible intervals. In larger networks, authors may focus on comparisons versus a particular comparator (e.g. placebo or standard care), with full findings presented in an appendix. League tables and forest plots may be considered to summarize pairwise comparisons. If additional summary measures were explored (such as treatment rankings), these should also be presented. Exploration for S5 Describe results from investigations of 14 inconsistency inconsistency. This may include such information as measures of model fit to compare consistency and inconsistency models, P values from statistical tests, or summary of inconsistency estimates from different parts of the treatment network. Risk of bias across 22 Present results of any assessment of risk of bias eFigure 2- studies across studies for the evidence base being studied. 11 and Summary of findings table Results of 23 Give results of additional analyses, if done (e.g., 12-13 additional analyses sensitivity or subgroup analyses, meta-regression analyses, alternative network geometries studied, alternative choice of prior distributions for Bayesian analyses, and so forth). DISCUSSION Summary of 24 Summarize the main findings, including the 14-15 evidence strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy-makers). Limitations 25 Discuss limitations at study and outcome level (e.g., 16-17 risk of bias), and at review level (e.g., incomplete retrieval of identified research, reporting bias). Comment on the validity of the assumptions, such as transitivity and consistency. Comment on any concerns regarding network geometry (e.g., avoidance of certain comparisons). © 2023 Iyer NP et al. JAMA Pediatrics. Conclusions 26 Provide a general interpretation of the results in the 17 context of other evidence, and implications for future research. FUNDING 2-3 Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. This should also include information regarding whether funding has been received from manufacturers of treatments in the network and/or whether some of the authors are content experts with professional conflicts of interest that could affect use of treatments in the network. PICOS = population, intervention, comparators, outcomes, study design. * Text in italics indicateS wording specific to reporting of network meta-analyses that has been added to guidance from the PRISMA statement. Authors may wish to plan for use of appendices to present all relevant information in full detail for items in this section. © 2023 Iyer NP et al. JAMA Pediatrics. eTable 2. Search strategies for MEDLINE, Embase, and CINAHL MEDLINE (Ovid) Databases selected: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions(R) Line Query 1 Continuous Positive Airway Pressure/ 2 Continuous Positive Airway Pressure*.mp. 3 CPAP.mp. 4 1 or 2 or 3 5 exp Sleep Apnea Syndromes/ 6 sleep apnea*.mp. 7 5 or 6 8 4 not 7 9 (extubation* adj2 (readiness or failure* or outcome*)).mp. 10 ((face or nasal) adj mask ventilat*).mp. 11 helmet ventilat*.mp. 12 ((High-flow or highflow) adj3 nasal cannula*).mp. 13 ((high-flow or highflow or humidified) adj3 oxygen*).mp. 14 (negative pressure adj2 ventilator*).mp. 15 NIV.mp. 16 Noninvasive Ventilation/ 17 Noninvasive Ventilation*.mp. 18 Non invasive Ventilation*.mp. 19 Oxygen Inhalation Therapy/ 20 Oxygen inhalat* therap*.mp. 21 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 22 Adolescent/ 23 Adolescen*.mp. 24 Teen*.mp. 25 Youth*.mp. 26 exp Child/ 27 Child*.mp. 28 Infant/ 29 Infant, Newborn/ 30 Infant*.mp. 31 Infanc*.mp. 32 Newborn*.mp. 33 Neonat*.mp. 34 Pediatrics/ 35 P?ediatric*.mp. 36 Hospitals, Pediatric/ © 2023 Iyer NP et al. JAMA Pediatrics. 37 Intensive Care Units, Pediatric/ 38 PICU*.mp. 39 (Kid or kids).mp. 40 Toddler*.mp. 41 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 42 (Adaptive adj2 Support Ventilat*).mp. 43 Airway Extubation/ 44 Airway extubat*.mp. 45 Artificial Respirati*.mp. 46 ((intubation or extubation*) adj3 (airway or tracheal or intratracheal or endotracheal)).mp. 47 exp Intermittent Positive-Pressure Breathing/ 48 Intermittent Positive-Pressure Breathing.mp. 49 exp Intermittent Positive-Pressure Ventilation/ 50 Intermittent Positive-Pressure Ventilat*.mp. 51 Intubation, Intratracheal/ 52 Mechanical Ventilat*.mp. 53 Neurally Adjusted Ventilatory Assist*.mp. 54 open lung ventilat*.mp. 55 Peep.mp. 56 Positive End Expiratory Pressure*.mp. 57 exp Positive-Pressure Respiration/ 58 Positive-Pressure Ventilat*.mp. 59 pressure controlled ventilat*.mp. 60 Proportional Assist Ventilat*.mp. 61 Reintubat*.mp. 62 Respiration, Artificial/ 63 Respirator Weaning*.mp. 64 Ventilator*.mp. 65 (Ventilat* adj3 Liberation*).mp. 66 exp Ventilators, Mechanical/ 67 exp Ventilator Weaning/ 68 Ventilator* Weaning*.mp. 69 Ventilation Weaning*.mp. 70 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 71 21 and 41 and 70 Embase (Elsevier) Line Query © 2023 Iyer NP et al. JAMA Pediatrics. #84 #22 AND #44 AND #83 #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #83 #75 OR #76 OR #77 OR #78 OR #79 OR #80 OR #81 OR #82 #82 'artificial respirati*' #81 'volume controlled ventilation'/exp #80 'ventilation weaning*' #79 'ventilator* weaning*' #78 'ventilator weaning'/de #77 'mechanical ventilator'/de #76 ventilat* NEAR/3 liberation* #75 ventilator* #74 'ventilator'/de #73 'tracheal extubation'/de #72 'respirator weaning*' #71 'artificial ventilation'/de #70 reintubat* #69 'protective ventilation'/exp #68 'proportional assist ventilat*' #67 'pressure support ventilation'/de #66 'pressure controlled ventilat*' #65 'pressure controlled ventilation'/de #64 'positive-pressure ventilat*' #63 'positive pressure ventilation'/de #62 'positive end expiratory pressure*' #61 'positive end expiratory pressure ventilation'/exp #60 peep © 2023 Iyer NP et al. JAMA Pediatrics. #59 'open lung ventilat*' #58 'noninvasive positive pressure ventilation'/exp #57 'neurally adjusted ventilatory assist*' #56 'mechanical ventilat*' #55 'inverse ratio ventilation'/de #54 'invasive ventilation'/exp #53 'endotracheal intubation'/exp #52 'intermittent positive-pressure ventilat*' #51 'intermittent positive pressure ventilation'/exp #50 'intermittent positive-pressure breathing' #49 'intermittent mandatory ventilation'/exp (intubation* OR extubation*) NEAR/3 (airway OR tracheal OR intratracheal OR #48 endotracheal) #47 'airway extubat*' #46 'extubation'/de #45 adaptive NEAR/2 support NEXT/1 ventilat* #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #44 #43 #43 toddler* #42 'toddler'/exp #41 kid OR kids #40 picu* #39 'pediatric intensive care unit'/de #38 p$ediatric* #37 'pediatrics'/de #36 neonat* #35 newborn* © 2023 Iyer NP et al. JAMA Pediatrics. #34 infanc* #33 infant* #32 'newborn'/exp #31 'infancy'/exp #30 'infant'/exp #29 child* #28 'child'/exp #27 youth* #26 teen* #25 adolescen* #24 'adolescence'/de #23 'adolescent'/exp #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #22 #15 OR #16 OR #21 #21 #19 NOT #20 #20 #17 OR #18 #19 #1 OR #2 OR #3 #18 'sleep apnea*' #17 'sleep disordered breathing'/exp #16 'oxygen inhalat* therap*' #15 'non-invasive ventilat*' #14 'noninvasive ventilat*' #13 'noninvasive ventilation'/de #12 niv #11 'negative pressure' NEAR/2 ventilat* #10 ('high flow' OR highflow OR humidified) NEAR/3 oxygen* #9 'high flow oxygen therapy'/de #8 ('high flow' OR highflow OR humidified) NEAR/3 'nasal cannula*' © 2023 Iyer NP et al. JAMA Pediatrics. #7 'helmet ventilat*' #6 'heated humidifier'/de #5 (face OR nasal) NEXT/1 'mask ventilat*' #4 extubation* NEAR/2 (readiness OR failure* OR outcome*) #3 cpap #2 'continuous positive airway pressure*' #1 'continuous positive airway pressure'/de CINAHL Complete (EBSCO) Line Query S73 S20 AND S71 AND S72 S70 OR S69 OR S68 OR S67 OR S66 OR S65 OR S64 OR S63 OR S62 OR S61 OR S60 OR S59 OR S58 OR S57 OR S56 OR S55 OR S54 OR S53 OR S52 OR S51 OR S72 S50 OR S49 OR S48 OR S47 OR S46 OR S45 OR S44 OR S43 OR S42 OR S41 OR S40 OR S39 S38 OR S37 OR S36 OR S35 OR S34 OR S33 OR S32 OR S31 OR S30 OR S29 OR S71 S28 OR S27 OR S26 OR S25 OR S24 OR S23 OR S22 OR S21 S70 adaptive N2 support ventilat* S69 (MH "Extubation") S68 airway extubat* S67 artificial respirati* (intubation* OR extubation*) N3 (airway OR tracheal OR intratracheal OR S66 endotracheal) S65 (MH "Intermittent Positive Pressure Breathing") S64 Intermittent Positive-Pressure Breathing S63 (MH "Intermittent Positive Pressure Ventilation") S62 Intermittent Positive-Pressure Ventilat* © 2023 Iyer NP et al. JAMA Pediatrics. S61 (MH "Intubation, Intratracheal") S60 (MH "Inverse Ratio Ventilation") S59 (MH "Mandatory Minute Volume Ventilation") S58 mechanical ventilat* S57 neurally adjusted ventilatory assist* S56 open lung ventilat* S55 peep S54 (MH "Positive End-Expiratory Pressure") S53 Positive End Expiratory Pressure* S52 (MH "Positive Pressure Ventilation") S51 positive-pressure ventilat* S50 pressure controlled ventilat* S49 (MH "Pressure Support Ventilation") S48 proportional assist ventilat* S47 reintubat* S46 (MH "Respiration, Artificial") S45 'respirator weaning*' S44 ventilator* S43 ventilat* N3 liberation* S42 (MH "Ventilators, Mechanical") S41 (MH "Ventilator Weaning") S40 ventilator* weaning* S39 Ventilation Weaning* S38 (MH "Adolescence+") © 2023 Iyer NP et al. JAMA Pediatrics. S37 Adolescen* S36 Teen* S35 Youth* (MH "Child") OR (MH "Child, Hospitalized") OR (MH "Child, Medically Fragile") S34 OR (MH "Child, Preschool") S33 Child* S32 (MH "Infant") OR (MH "Infant, Hospitalized") OR (MH "Infant, High Risk") S31 (MH "Infant, Newborn") S30 Infant* S29 Infanc* S28 Newborn* S27 Neonat* S26 (MH "Pediatrics") S25 P#ediatric* S24 (MH "Intensive Care Units, Pediatric") S23 PICU* S22 Kid OR kids S21 Toddler* S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 S20 OR S19 S19 (MH "Ventilation, Negative Pressure") S18 "oxygen inhalat* therap*" S17 "non invasive ventilat*" S16 "noninvasive ventilat*" S15 niv © 2023 Iyer NP et al. JAMA Pediatrics. S14 "negative pressure" N2 ventilat* S13 ("high flow" OR highflow OR humidified) N3 oxygen* S12 ("high flow" OR highflow OR humidified) N3 "nasal cannula*" S11 "helmet ventilat*" S10 (face OR nasal) N1 "mask ventilat*" S9 Extubation* N2 (readiness OR failure* OR outcome*) S8 S6 NOT S7 S7 S4 OR S5 S6 S1 OR S2 OR S3 S5 "sleep apnea*" S4 (MH "Sleep Apnea Syndromes+") S3 CPAP S2 "continuous positive airway pressure*" S1 (MH "Continuous Positive Airway Pressure") eTable 3. Characteristics of included studies. Study Sample Population Prophylactic Treatment arms size or Rescue Akyildiz, 100 Pediatric patients intubated for Prophylactic HFNC 1-2L/kg to 2018 more than 24 hours, a max 25L/min. redominantly medical subjects. COT was Subjects with cyanotic heart delivered by either © 2023 Iyer NP et al. JAMA Pediatrics. disease and those who failed nasal cannula or a spontaneous breathing trial simple face mask (SBT) excluded. Average age with the same was 27 and 52 months for saturation (SpO2) High Flow Nasal Cannula target. (HFNC) and Conventional Oxygen Therapy (COT) groups respectively. Patients with diaphragmatic hernia or paralysis, cyanotic congenital heart disease with unrepaired or palliated right to left intracardiac shunt, and presence of a tracheostomy tube were excluded. Fioretto, 108 Age 1mo-3 years, passed SBT Noninvasive 2015 and high risk of extubation ventilation group: failure [a) Invasive Mechanical EPAP 5 cm H2O ventilation (IMV) for more and IPAP 15 than 15 days; b) use of Prophylactic cmH2O, PS 10 cm inotropic agents for more than H2O. EPAP was 48 hours; c) continuous titrated up to 10 intravenous administration of cm H2O, IPAP sedatives/analgesics d) age was titrated up to between 1 and 3 month; e) 20 cmH2O, and mean airway pressure (Paw) FiO2 was titrated greater than 8.5; f) Inspired up to 0.6, as oxygen (FiO2) greater than 0.4 needed. Nasal or and oxygenation index (OI) face mask used. greater than 4.5 immediately Oxygen therapy: before extubation; g) standard nasal underlying cardiac or catheter to pulmonary disease; h) maintain congestive heart failure; i) SpO22>92% hypercapnia. Patients with neuromuscular disease, or those with contraindications for NIV (coma or the inability to protect the airway, nonacceptance of NIV by the patient, hemodynamic instability, shock, cardiac arrhythmia, cranial or facial trauma or surgery that could prevent NIV use, abdominal © 2023 Iyer NP et al. JAMA Pediatrics. distention, nausea or vomiting, recent gastric or esophageal surgery, active gastrointestinal hemorrhage, and undrained pneumothorax) were excluded from the study. Ramnarayan, 84 Patients age between > 36 Prophylactic 2L/kg/min 2018 weeks corrected for (62%) and (<10kg), HFNC gestation and < 16 years. Rescue rate weight based Predominantly medical (38%) up to 50L/min in subjects (including patient with >60kg. different upper and lower CPAP: 6- respiratory, cardiac, 8cmH2O. No neurological, and restrictions on type neuromuscular disease). of interface- any of Subjects in Rescue group the following needed to also satisfy one or could be used: more of the following criteria mask, nasal prong, a) hypoxia (oxygen saturation helmet. < 92% in FiO2 > 0.40, or equivalent); b) acute respiratory acidosis (pH < 7.3 with a concomitant partial pressure of carbon dioxide (pCO2) > 6.5 kPa); c) moderate respiratory distress (use of accessory muscles, subcostal and intercostal recession, tachypnoea for age, grunting). ~55% in both groups <1 yr age. Patients with mid- facial/craniofacial anomalies (Unrepaired cleft palate, choanal atresia) or recent craniofacial surgery were excluded from the study. Ramnarayan, 553 Patient age from birth (>36 Prophylactic 2L/kg/min 2022 weeks corrected gestational (63%) and (<12kg), HFNC age) up to 15 years. Median rescue (37%) rate weight based ag 3mo in both groups. Mixed up to 50L/min in indications for IMV(medical >50kg. and postoperative). CPAP: 6- Bronchiolitis overrepresented 8cmH2O. No in CPAP (44.9%) vs HFNC restrictions on type (34.5%) and Cardiac of interface- any of © 2023 Iyer NP et al. JAMA Pediatrics. indications overrepresented in the following HFNC (28.8%) vs CPAP could be used: (20.2%). mask, nasal prong, Patients with tracheostomy in helmet. place, on home non-invasive ventilation prior to admission, midfacial/craniofacial anomalies (unrepaired cleft palate, choanal atresia), or recent craniofacial surgery were excluded. Rodriguez, 25 Predominantly medical Rescue Control: L- 2002 subjects. Only those with signs adrenaline every of post-extubation laryngeal 15-60 minutes, edema (using modified oxygen. Downes and Raphaelys CPAP 5-12 score). 4 and 3.5 mo median cmH2O using ages of COT and CPAP. nasal cannula in Patients with a history of children <2 years anatomical or acquired age and nasal abnormalities of upper airway masks in older were excluded. children. Testa, 2014 89 < 18 months, elective cardiac Prophylactic HFNC: 2L/kg/min surgery (cyanotic and Oxygen therapy: acyanotic) with CPB and a max 2L/min Risk Adjustment for Congenital Heart Surgery (RACHS) score of 2 and above. Patients with major congenital malformations or neuromuscular disease were excluded. Wijakprasert, 152 Predominantly medical Prophylactic HFNC: 1L/kg/min 2018 subjects intubated for at least initially, titrated 24 hours. Pediatric patients upwards COT: 10L/min between 29 days and 15 years of age, mean age of 42 mo and 32 mo for HFNC and COT groups. Patient with neuromuscular disease, tracheostomy, and nasal abnormalities were excluded. Li Xiaoqing, 102 Predominantly medical causes Prophylactic BiPAP using nasal 2022 of IMV for >24 hours- severe cannula in children © 2023 Iyer NP et al. JAMA Pediatrics. pneumonia, heart failure and <15 kg and nasal sepsis. Ages between 1 month masks in bigger to 14 years old were enrolled children. and randomly assigned to HFNC: 1-2L/kg treatment group 1, Bilevel for infants and Positive Airway Pressure toddlers, pre- (BPAP) (n=55) and treatment school children. group 2, HFNC (n=47). For older children, Patient with central respiratory initial setting of failure and neuromuscular 20L/min. diseases were excluded. Zheng, 186 High-risk infants < 6 months Prophylactic The initial BiPAP 2022 of age with stable setting hemodynamic status after 36 cm H2O (low) cardiac surgery. High risk and 810 cm H2O factors included pulmonary (high), rate 20 hypertension, pneumonia, 30/min. Initial preoperative or postoperative nasal CPAP respiratory failure, setting was 36 cm oxygenation index > 8, PaO2 H2O; the oxygen /FIO2 < 200 mm Hg, and flow was 68 ARDS. After extubation, all L/min. Both infants were intravenously applied using injected with silicone binasal methylprednisolone sodium prongs. succinate 1 mg/kg for the prevention of laryngeal edema. Subjects with excessive secretions were given an intravenous infusion of ambroxol hydrochloride to facilitate mucociliary clearance and chest physical therapy. Patients with congenital thoracic and abdominal malformations, those who received postoperative extracorporeal membrane oxygenation support or preoperative tracheotomy and intubation were excluded. © 2023 Iyer NP et al. JAMA Pediatrics. eTable 4. Summary of findings: Hospital length of stay Effects of estimates and certainty of evidence for post extubation noninvasive respiratory support © 2023 Iyer NP et al. JAMA Pediatrics. Population: Critically ill children intubated and mechanically ventilated for at least 24 hours. Setting: PICU, CICU Interventions: High Flow Nasal Cannula (HFNC) Continuous Positive Airway Pressure (CPAP) Reference treatment: Conventional Oxygen Therapy (COT) Outcomes: Hospital length of stay (LOS) Outcome: Hospital LOS. Hospital LOS in reference population: 26.5 days Intervention, Mean Anticipated absolute effect (95% CrI) Certainty of Ranking Total studies, difference evidence (SUCRA) Without With Difference Total participants (95% intervention intervention Credible Interval, CrI) HFNC 8.7 ( 19, 26.5 days 17.8 days 8.7 days less Low 0.683 3 trials, 740 1.1) (19 days less participants to 1.1 days more) CPAP 9.0 ( 20, 26.5 days 17.5 days 9.0 days less Low 0.708 2 trials, 588 2.4) (20 days less to participants 2.4 days more) COT Reference Reference Reference Reference Reference 0.108 1 trial, 152 participants Relative effects with reference to COT Downgraded due to serious imprecision Hospital LOS, Effect estimates of all comparisons (mean difference, days): COT CPAP HFNC b b COT 9.06 ( 20.8, 2.4) 8.7 ( 19, 1.1) CPAP 0.29 ( 5.5, 6.0) HFNC b c Low certainty of effect estimate, Very low certainty of effect estimate eTable 5. Summary of findings: PICU length of stay © 2023 Iyer NP et al. JAMA Pediatrics. Effects of estimates and certainty of evidence for post extubation noninvasive respiratory support Population: Critically ill children intubated and mechanically ventilated for at least 24 hours. Setting: PICU, CICU Interventions: High Flow Nasal Cannula (HFNC) Continuous Positive Airway Pressure (CPAP) Reference treatment: Conventional Oxygen Therapy (COT) Outcomes: PICU length of stay Outcome: PICU LOS. PICU LOS in reference population: 5.85 days Intervention, Mean Anticipated absolute effect (95% CrI) Certainty of Ranking Total studies, difference evidence (SUCRA) Without With Difference Total (95% Credible intervention intervention participants Interval, CrI) HFNC 0.04 ( 1.6, 5.85 days 5.88 days 0.03 days more Low 0.494 4 trials, 829 1.7) (1.6 days less to participants 1.7 days more) CPAP 0.30 ( 3.2, 5.85 days 5.35 days 0.3 days less Low 0.596 2 trials, 588 2.6) (3.2 days less to participants 2.6 days more) COT Reference Reference Reference Reference Reference 0.409 2 trials, 241 participants Relative effects with reference to COT Downgraded due to serious imprecision PICU LOS, Effect estimates of all comparisons (mean difference, days): COT CPAP HFNC b b COT 0.30 ( 3.2, 2.6) 0.04 ( 1.5, 1.7) CPAP 0.32 ( 2.1, 2.7) HFNC Low certainty of effect estimate eTable 6. Summary of findings: PICU Mortality © 2023 Iyer NP et al. JAMA Pediatrics. Effects of estimates and certainty of evidence for post extubation noninvasive respiratory support Population: Critically ill children intubated and mechanically ventilated for at least 24 hours. Setting: PICU, CICU Interventions: High Flow Nasal Cannula (HFNC) Continuous Positive Airway Pressure (CPAP) Bi Level Positive Airway Pressure (BiPAP) Reference treatment: Conventional Oxygen Therapy (COT) Outcomes: PICU Mortality Outcome: PICU Mortality. Rate in reference population: 3.9% (39 per 1000) Intervention, Odds ratio Anticipated absolute effect (95% CrI) Certainty Ranking Total studies, (95% of (SUCRA) Without With Difference Total participants Credible intervention intervention evidence Interval, CrI) HFNC 1.3 (0.26, 39 per 1000 50 per 1000 11 more per Very low 0.459 3 trials with non zero 7.7) 1000 events, 780 (29 fewer to 199 participants more) CPAP 0.96 (0.11, 39 per 1000 37 per 1000 2 fewer per Very low 0.883 1 trial, 544 8.5) 1000 participants (35 fewer to 217 more) COT. Reference Reference Reference Reference Reference 0.618 1 trial, 152 participants Relative effects with reference to COT (sensitivity analysis) Downgraded due to serious risk of bias and serious imprecision. PICU mortality, Effect estimates of all comparisons (Odds ratio, 95% Crl): COT CPAP HFNC b b COT 0.96 (0.11, 8.5) 1.34 (0.26, 7.7) CPAP 1.38 (0.32, 6.2) HFNC Very low certainty of effect estimates eTable 7. Summary of findings: Nasal Injury © 2023 Iyer NP et al. JAMA Pediatrics. Effects of estimates and certainty of evidence for post extubation noninvasive respiratory support Population: Critically ill children intubated and mechanically ventilated for at least 24 hours. Setting: PICU, CICU Interventions: Continuous Positive Airway Pressure (CPAP) Bi Level Positive Airway Pressure (BiPAP) Reference treatment: High Flow Nasal Cannula (HFNC) Outcomes: Nasal injury Outcome: Nasal injury. Rate in reference population: 1.8% (18 per 1000) Intervention, Odds ratio Anticipated absolute effect (95% CrI) Certainty of Ranking Total studies, (95% Without With Difference evidence (SUCRA) Total participants Credible interventio intervention Interval, CrI) HFNC Reference Reference Reference Reference Reference 0.925 3 trials, 768 participants. CPAP 2.7 (0.84, 18 per 1000 47 per 1000 29 more per Very low 0.319 3 trials, 852 15) 1000 participants (3 fewer to 180 more) BiPAP 3.1 (0.78, 18 per 1000 54 per 1000 36 more per Very low 0.254 2 trials, 284 21) 1000 participants (4 fewer to 250 more) Relative effects with reference to HFNC Downgraded due to serious risk of bias and serious imprecision. Nasal injury, Effect estimates for all comparisons (Odds ratio, 95% Crl): HFNC CPAP BiPAP HFNC 2.69 (0.8, 13) CPAP b b 3.1 (0.80, 20) 1.15 (0.26, 5.0) BiPAP Very low certainty of effect estimate eTable 8. Summary of findings: Abdominal distension © 2023 Iyer NP et al. JAMA Pediatrics. Effects of estimates and certainty of evidence for post extubation noninvasive respiratory support Population: Critically ill children intubated and mechanically ventilated for at least 24 hours. Setting: PICU, CICU Interventions: Continuous Positive Airway Pressure (CPAP) Bi Level Positive Airway Pressure (BiPAP) Reference treatment: High Flow Nasal Cannula (HFNC) Outcomes: Abdominal distension Outcome: Abdominal distension. Rate in reference population: 2.3% (23 per 1000) Intervention, Odds ratio Anticipated absolute effect (95% CrI) Certainty Ranking Total studies, (95% Without With Difference of (SUCRA) Total participants Credible evidence intervention intervention Interval, CrI) HFNC Reference Reference Reference Reference Reference 0.446 2 trials with non zero events, 666 participants CPAP 0.99 (0.31, 23 per 1000 23 per 1000 0 fewer per 1000 Very low 0.435 3 trials, 852 3.3) (16 fewer to 49 participants more) BiPAP 0.78 (0.09, 23 per 1000 18 per 1000 5 fewer per 1000 Very low 0.618 1 trial, 182 6.5) (21 fewer to 106 participants more) COT. 2 trials, 241 Zero events Zero events Zero events Zero events participants Relative effects with reference to HFNC Downgraded due to serious risk of bias and serious imprecision. Abdominal distension, Effect estimates of all comparisons (Odds ratio, 95% Crl): HFNC CPAP BiPAP HFNC 0.99 (0.31, 3.25) CPAP b b 0.78 (0.09, 6.5) 1.25 (0.22, 7.37) BiPAP Very low certainty of effect estimate eTable 9. Summary of findings for pair wise analysis between CPAP and HFNC © 2023 Iyer NP et al. JAMA Pediatrics. CPAP compared to HFNC for post-extubation non-invasive respiratory support Patient or population: post extubation non invasive respiratory support Setting: PICU Intervention: CPAP Comparison: HFNC Anticipated absolute of Certainty effects Relative participants of the Outcomes effect Risk (studies) evidence Risk with (95% CI) difference Follow-up (GRADE) HFNC with CPAP 30 fewer per 635 OR 0.38 1,000 Mortality, hospital 50 per 1,000 a,c Low (0.15 to 0.97) (42 fewer to 1 (2 RCTs) fewer) 0 fewer per 666 OR 1.00 1,000 Aspiration 9 per 1,000 a,b (2 RCTs) Very low (0.21 to 4.73) (7 fewer to 32 more) 13 fewer per 589 OR 0.95 1,000 Sedation use 580 per 1,000 a,b Low (2 RCTs) (0.83 to 1.09) (46 fewer to 21 more) *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; OR: odds ratio GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. a. Lack of blinding and allocation not blinded to some participants. Crossover to other intervention permitted. b. Wide 95% CI that includes benefit to either intervention c. Wide 95% CI that includes lack of clinically meaningful benefit eFigure 1. PRISMA Flow of information © 2023 Iyer NP et al. JAMA Pediatrics. 8 16 eFigure 2. Risk of bias. Extubation failure © 2023 Iyer NP et al. JAMA Pediatrics. 8 16 eFigure 3. Risk of bias: Treatment failure © 2023 Iyer NP et al. JAMA Pediatrics. © 2023 Iyer NP et al. JAMA Pediatrics. 10,11,13,14,16 eFigure 4. Risk of bias: Abdominal distension © 2023 Iyer NP et al. JAMA Pediatrics. 10,11,14 eFigure 5. Risk of bias: Hospital length of stay © 2023 Iyer NP et al. JAMA Pediatrics. 10,11,14,15 eFigure 6. Risk of bias: PICU mortality 10,11,13-16 eFigure 7. Risk of bias: Nasal injury © 2023 Iyer NP et al. JAMA Pediatrics. 10,11,13,14 eFigure 8. Risk of bias: PICU LOS © 2023 Iyer NP et al. JAMA Pediatrics. 10,11 eFigure 9. Risk of bias: Hospital mortality © 2023 Iyer NP et al. JAMA Pediatrics. 10,11 eFigure 10. Risk of bias: Sedation use © 2023 Iyer NP et al. JAMA Pediatrics. 10,11 eFigure 11. Risk of bias: Aspiration © 2023 Iyer NP et al. JAMA Pediatrics. Figure 12a. Pairwise metanalysis: Forest plot of comparison: HFNC versus CPAP, outcome: 10,11 Mortality, Hospital © 2023 Iyer NP et al. JAMA Pediatrics. Figure 12b. Pairwise metanalysis: Forest plot of comparison: HFNC versus CPAP, outcome: 10,11 Aspiration Figure 12c. Pairwise metanalysis: Forest plot of comparison: HFNC versus CPAP, outcome: 10,11 Sedation use References: © 2023 Iyer NP et al. JAMA Pediatrics. 1. Turner RM, Jackson D, Wei Y, Thompson SG, Higgins JP. Predictive distributions for between study heterogeneity and simple methods for their application in Bayesian meta analysis. Stat Med. 2015;34(6):984 998. 2. Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta analysis of randomized controlled trials. Med Decis Making. 2013;33(5):607 617. 3. Brooks SP, Gelman A. General Methods for Monitoring Convergence of Iterative Simulations. Journal of Computational and Graphical Statistics. 1998;7(4):434 455. 4. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making. 2013;33(5):641 656. 5. Brignardello Petersen R, Bonner A, Alexander PE, et al. Advances in the GRADE approach to rate the certainty in estimates from a network meta analysis. J Clin Epidemiol. 2018;93:36 44. 6. Brignardello Petersen R, Mustafa RA, Siemieniuk RAC, et al. GRADE approach to rate the certainty from a network meta analysis: addressing incoherence. J Clin Epidemiol. 2019;108:77 7. Hultcrantz M, Rind D, Akl EA, et al. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017;87:4 13. 8. Akyõldõz B, Öztürk S, Ülgen Tekerek N, Do anay S, Görkem SB. Comparison between high flow nasal oxygen cannula and conventional oxygen therapy after extubation in pediatric intensive care unit. Turk J Pediatr. 2018;60(2):126 133. 9. Fioretto JR, Ribeiro CF, Carpi MF, et al. Comparison between noninvasive mechanical ventilation and standard oxygen therapy in children up to 3 years old with respiratory failure after extubation: a pilot prospective randomized clinical study. Pediatr Crit Care Med. 2015;16(2):124 10. Ramnarayan P, Lister P, Dominguez T, et al. FIRST line support for Assistance in Breathing in Children (FIRST ABC): a multicentre pilot randomised controlled trial of high flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care. Crit Care. 2018;22(1):144. 11. Ramnarayan P, Richards Belle A, Drikite L, et al. 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. JAMA. 2022;327(16):1555 1565. 12. Rodriguez JA, Von Dessauer B, Duffau G. [Non invasive continuous positive airways pressure for post extubation laryngitis in pediatric patients]. Archivos de bronconeumologia. 2002;38(10):463 467. 13. Testa G, Iodice F, Ricci Z, et al. Comparative evaluation of high flow nasal cannula and conventional oxygen therapy in paediatric cardiac surgical patients: a randomized controlled trial. Interact Cardiovasc Thorac Surg. 2014;19(3):456 461. 14. Wijakprasert P, Chomchoey J. High flow nasal cannula versus conventional oxygen therapy in post extubation pediatric patients: A randomized controlled trial. Journal of the Medical Association of Thailand. 2018;101(10):1331 1335. 15. Li XQ, Zhao WL, Li DY, Lei L, Luo LL, Qiao LN. Clinical Study on Early Extubation and Sequential Non Invasive Respiratory Support for Children with Acute Respiratory Failure Receiving Invasive Mechanical Ventilation. Sichuan da xue xue bao Yi xue ban = Journal of Sichuan University Medical science edition. 2022;53(2):321 326. 16. Zheng YR, Lin WH, Lin SH, Xu N, Cao H, Chen Q. Bi level Positive Airway Pressure Versus Nasal CPAP for the Prevention of Extubation Failure in Infants After Cardiac Surgery. Respir Care. 2022;67(4):448 454. © 2023 Iyer NP et al. JAMA Pediatrics. © 2023 Iyer NP et al. JAMA Pediatrics.
JAMA Pediatrics – American Medical Association
Published: Jun 5, 2023
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