Conflict of Interest Declaration
The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: None.
The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees:
One author (GMW) was co-author of one of the included observational studies. He was excluded from bias assessment of this study.
One author (DT) was co-author of 3 included randomized trials and both included observational studies. He was excluded from bias assessment of these studies.
Both acknowledged their potential intellectual conflicts of interest and participated in the Task Force discussion of the consensus on science and treatment recommendations.
CoSTR Citation
Yamada NK, McKinlay CJD, Quek BH, Rabi Y, Costa-Nobre DT, de Almeida MF, Davis PG, El-Naggar W, Fabres JG, Fawke J, Foglia EE, Guinsburg R, Hosono S, Isayama T, Kapadia VS, Kawakami MD, Kim HS, Lee H, Liley HG, Madar RJ, Nakwa FL, Perlman JM, Roehr CC, Rüdiger M, Schmölzer GM, Sugiura T, Trevisanuto D, Wyckoff MH, Wyllie JP, Weiner GM. Supraglottic airways for neonatal resuscitation (NLS#618/5340 [Internet] Brussels, Belgium. International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, Available from http://ilcor.org
Methodological Preamble (and Link to Published Systematic Review)
This PICOST was prioritized by the Neonatal Life Support Task Force because the question had not been updated since 2015, the previous CoSTR had focused on the use of supraglottic airways compared with endotracheal intubation, and the Task Force was interested in evaluating the use of a supraglottic airway as the initial device for positive-pressure ventilation because of the high risk of leak and obstruction when using a face mask. The Task Force was aware that additional randomized trials comparing a supraglottic device and face mask as the initial device for positive-pressure ventilation had been completed since the previous review. The continuous evidence process for the creation of Consensus of Science and Treatment Recommendations (CoSTR) started with a systematic review of supraglottic devices (Yamada, 2021 PROSPERO 2021 CRD42021230722) conducted by Nicole Yamada, Christopher McKinlay, Bin Huey Quek, and Gary Weiner. Evidence from neonatal literature was sought and considered by the Neonatal Life Support Task Force and clinical content experts. These data were taken into account when formulating the Treatment Recommendations.
Systematic Review
Reference not yet available
PICOST
The PICOST (Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame)
Population: Newborn infants 34 0/7 weeks’ or more gestation receiving intermittent positive-pressure ventilation during resuscitation immediately after birth
Intervention: Supraglottic airway
Comparator: Face mask
Outcomes: Failure to improve with the device (as defined by authors), intubation during initial resuscitation, time to heart rate >100 beats per minute (bpm) during initial resuscitation, duration of positive pressure ventilation during initial resuscitation, time to cessation of positive pressure ventilation, chest compressions or epinephrine (adrenaline) administration during initial resuscitation, soft tissue injury (as defined by authors), admission to neonatal intensive care unit (NICU), air leak during the initial hospital stay (presence of pneumothorax, pneumomediastinum, pulmonary interstitial emphysema, or pneumopericardium), survival to hospital discharge, neurodevelopmental impairment at ≥ 18 months (abnormal motor, sensory or cognitive function, or low educational achievement at ≥18 months of age using an appropriate, standardized test or examination).
Outcomes ratings using the GRADE classifications of critical or important were based on a consensus for international neonatal resuscitation guidelines (range 1-3 low importance for decision-making, 4-6 important but not critical for decision-making, 7-9 critical for decision-making). {Strand 2020 328} Potential subgroups (late preterm and cuffless supraglottic device) were defined a priori. Outcomes were converted into main outcomes and additional outcomes for submission to PROSPERO. All included randomized controlled trials (RCTs) and quasi-randomized RCTs (quasi-RCTs) allowed cross-over between devices if the subject did not respond to the initial randomized device. If cross-over occurred, outcomes were measured and assigned to the initial device (intent-to-treat principle). If necessary, study authors were contacted to request missing data. Missing standard deviations (SD) were either imputed following the guidelines outlined in the Cochrane Handbook or estimated. {Wan 2014 135}
Study Designs: RCTs, quasi-RCTs, and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) were eligible for inclusion. Quasi-RCTs were included with RCTs in meta-analyses. Unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Outcomes from observational studies were assessed if there were fewer than 2 included RCTs/quasi-RCTs or if the certainty of evidence from RCTs/quasi-RCTs was scored very low.
Timeframe: All years and all languages were included as long as there was an English abstract. The literature search was updated to December 9, 2021.
PROSPERO registration:
The review was registered with PROSPERO CRD42021230722.
Risk of Bias:
Risk of bias (RoB) was assessed by outcome using the Cochrane ROB2 tool {Sterne 2019 366} for RCTs and quasi-RCTs, and the ROBINS-I tool {Sterne 2016 355} for observational studies. RoB for each outcome was summarized across studies. Statistical heterogeneity was considered present if the I2 statistic was >50%. We attempted to explain statistical heterogeneity using sensitivity analyses. Imprecision was considered present if the total number of participants included was less than optimal information size (OIS) for the outcome under consideration. OIS was calculated as the sample size required for a single, adequately powered RCT (alpha 0.05, beta 0.80, control event rate equal to the pooled event rate in the face mask group, effect size = relative risk 0.75 or 1 SD). {Dupont 1974 274}
Overall, study-level RoB was high. All studies were at high RoB for lack of blinding of participants and personnel due to the nature of the intervention and for lack of blinding of outcome assessors for many outcomes.
All outcomes selected for GRADE assessment, except failure to improve with the device, were rated as low or very low certainty evidence. For most outcomes, this uncertainty was attributable to high RoB and imprecision.
Consensus on Science
COMPARISON: Supraglottic airway compared with face mask ventilation for positive-pressure ventilation during resuscitation immediately after birth
The systematic review identified 5 RCTs {Feroze 2008 148; Pejovic 2018 255; Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286} and 1 quasi-RCT {Zhu 2011 1405} involving a total of 1857 newborn infants, and 2 retrospective cohort studies {Trevisanuto 2004 151; Zanardo 2010 327} involving 218 newborn infants. An additional study {Pejovic 2021 pg # pending} reported secondary outcomes from a subset of newborn infants enrolled in an included RCT {Pejovic 2020 2138}.
For the important outcome of failure to improve with the device, evidence of moderate certainty (downgraded for risk of bias and imprecision, upgraded for strong association) from 6 trials {Feroze 2008 148; Pejovic 2018 255; Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286; Zhu 2011 1405} involving 1823 newborn infants showed probable benefit from receiving positive-pressure ventilation with a supraglottic airway compared to a face mask (risk ratio (RR) 0.24; 95% confidence interval (CI) 0.17 to 0.36; p <0.001; I2 = 35%; Absolute risk difference (ARD) -11%, 95% CI -13% to -8%; NNT= 10).
For the important outcome of endotracheal intubation during resuscitation, evidence of low certainty (downgraded for risk of bias, inconsistency, and imprecision; upgraded for strong association) from 4 trials {Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286; Zhu 2011 1405} involving 1715 newborn infants showed possible benefit from receiving positive-pressure ventilation with a supraglottic airway compared to a face mask (RR 0.34, 95% CI 0.20 to 0.56; p <0.001; I2=78%; ARD -5%, 95% CI -6% to -3%; NNT 20). In sensitivity analysis, heterogeneity was not significantly decreased and the benefit remained (RR 0.19, 95% CI 0.09 to 0.37; p < 0.001; I2 = 63%) after removing the study {Pejovic 2020 2138} where intubation was only possible if a physician was available during the resuscitation. Heterogeneity was decreased and the risk reduction was no longer statistically significant (RR 0.65, 95% CI 0.36 to 1.19; p=0.17; I2 =45%) when the single quasi-RCT {Zhu 2011 1405} was removed.
For the critical outcome of chest compressions during resuscitation, evidence of low certainty (downgraded for risk of bias and imprecision) from 3 trials {Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286} involving 1346 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.97, 95% CI 0.57 to 1.65; p=0.91; I2=0%; ARD 1/1000 fewer newborn infants with chest compressions when receiving positive-pressure ventilation with a supraglottic airway, 95% CI 17/1000 fewer to 26/1000 more).
For the critical outcome of epinephrine (adrenaline) administration during resuscitation, evidence of low certainty (downgraded for risk of bias and imprecision) from 2 trials {Singh 2005 303; Trevisanuto 2015 286} involving 192 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.67, 95% CI 0.11 to 3.87; p=0.65; I2 not applicable; ARD 10 /1000 fewer newborn infants receive epinephrine (adrenaline) when receiving positive-pressure ventilation with a supraglottic airway, 95% CI 28/1000 fewer to 90/1000 more). Statistical heterogeneity could not be calculated because events occurred in only one trial {Trevisanuto 2015 286}.
For the important outcome of time to heart rate >100 bpm, evidence of low certainty (downgraded for risk of bias and imprecision) from 1 trial {Pejovic 2021 pg # pending} involving a subset of 46 newborn infants enrolled in a previously reported RCT {Pejovic 2020 2138} showed possible benefit from receiving positive-pressure ventilation with a supraglottic airway compared to a face mask (mean difference -66 s, 95% CI -100 s to -31 s; p<0.001)
For the important outcome of duration of positive-pressure ventilation, evidence of low certainty (downgraded for risk of bias and inconsistency) from 4 trials {Pejovic 2018 255; Singh 2005 303; Trevisanuto 2015 286; Zhu 2011 1405} involving 610 newbor infnats showed possible benefit from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (mean difference -18 s, 95% CI -24 s to -13 s; p < 0.001; I2 = 94%. In sensitivity analysis, all of the heterogeneity was attributed to one study {Trevisanuto 2015 286}. This may reflect a different protocol or policy, in this single center trial, for when to remove the supraglottic airway and discontinue positive-pressure ventilation. When removing this study, the beneficial effect was retained and statistical heterogeneity was significantly reduced (mean difference -30s, 95% CI -36 s to -24 s; p < 0.001; I2 = 0%).
For the important outcome of admission to the NICU, evidence of very low certainty (downgraded for risk of bias, inconsistency, indirectness, and imprecision) from 4 trials {Pejovic 2018 255; Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286} involving 1314 newborn infants showed possible benefit and no likely harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.97, 95% CI 0.94 to 1.00; p=0.07; I2=82%; ARD -3%, 95% CI -5% to 0%; NNT 34). In sensitivity analysis, all of the heterogeneity was attributed to the high rate of admission to the NICU (96% in both groups) in one study {Pejovic 2020. 2138}. This may reflect heterogeneity in the population studied (sicker newborns) or in the policies/protocols for intensive care admission in this single center trial. When this study was removed, the treatment effect was increased and heterogeneity was significantly decreased (RR 0.60, 95% CI 0.40 to 0.90, p=0.01; I2 =0%).
For the important outcome of admission to the NICU, evidence of very low certainty (downgraded for risk of bias, indirectness, and imprecision) from 2 retrospective cohort studies {Trevisanuto 2004 151; Zanardo 2010 327} involving 218 newborn infants showed possible benefit and no likely harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.65, 95% CI 0.43 to 1.00; p=0.05; I2 =36%; ARD -13%; 95% CI -25% to 0%).
For the important outcome of air leak during initial hospital stay, evidence of very low certainty (downgraded for risk of bias, indirectness, and imprecision) from 2 trials {Singh 2005 303; Trevisanuto 2015 286} involving 192 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR not estimable due to no events; I2=0%; ARD 0%, 95% CI -3% to 3%).
For the important outcome of air leak during initial hospital stay, evidence of very low certainty (downgraded for risk of bias, indirectness, and imprecision) from 2 retrospective cohort studies {Trevisanuto 2004 151; Zanardo 2010 327} involving 218 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.32, 95% CI 0.05 to 1.99; p=0.22; I2=0%; ARD -3%, 95% CI -7% to 1%).
For the important outcome of soft tissue injury, evidence of low certainty (downgraded for risk of bias and imprecision) from 4 trials {Pejovic 2020 2138; Singh 2005 303; Trevisanuto 2015 286; Zhu 2011 1405} involving 1724 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 1.05, 95% CI 0.15 to 7.46; p=0.96; I2 not applicable; ARD 0/1000 fewer newborn infants with soft tissue injury when receiving positive-pressure ventilation with a supraglottic airway, 95% CI 2/1000 fewer to 15/1000 more). Statistical heterogeneity could not be calculated for this outcome because there were no events recorded in 3 of 4 included studies. Soft tissue injury (2 events in each group) only occurred in one study {Pejovic 2020 2138}.
For the critical outcome of survival to hospital discharge, evidence of low certainty (downgraded for risk of bias and imprecision) from 1 trial {Singh 2005 303} involving 50 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 1.00; 95% CI 0.93 to 1.08; p=1.0; I2 not applicable; ARD, 0/1000 fewer newborn infants survive when receiving positive-pressure ventilation with a supraglottic airway, 95% CI 70/1000 fewer to 80/1000 more).
For the critical outcome of survival to hospital discharge, evidence of low certainty (downgraded for risk of bias and imprecision) from 2 retrospective cohort studies {Trevisanuto 2004 151; Zanardo 2010 327} involving 218 newborn infants could not exclude benefit or harm from providing positive-pressure ventilation with a supraglottic airway compared with a face mask (RR 0.99; 95% CI 0.96 to 1.02; p=0.58; I2=0%; ARD 10/1000 fewer newborn infants survive when receiving positive pressure ventilation with a supraglottic airway, 95% CI 40/1000 fewer to 20/1000 more).
For the critically important outcome of neurodevelopmental impairment at ≥18 months of age, no data were reported in the included studies.
Subgroup Analyses:
No data were reported to perform prespecified subgroup analyses by gestational age (term vs. late preterm).
For the planned subgroup analysis based on device design (cuffed device vs. uncuffed (i-Gel™) device), “failure to improve with the device” was the only outcome with sufficient data to analyze, and there was no evidence of an interaction (p = 0.29, I2 = 10%).
Treatment Recommendations
Where resources and training permit, we suggest that a supraglottic airway may be used in place of a face mask for newborn infants 34 0/7 weeks’ or more gestation receiving intermittent positive pressure ventilation during resuscitation immediately after birth (weak recommendation, low certainty of evidence).
Justification and Evidence to Decision Framework Highlights
In making these recommendations, the Neonatal Life Support Task Force acknowledges the following:
Supraglottic airways compared with face masks may be more effective in achieving successful resuscitation of late preterm and term newborn infants who receive positive pressure ventilation immediately after birth.
Although “failure to improve with device” was variously defined by authors, and often included cross-over to the alternative device, there was a strong inverse association between the use of a supraglottic airway and risk of endotracheal intubation. This may reflect a greater likelihood of achieving effective ventilation using the supraglottic airway. Nevertheless, given that the interventions were not blinded, and ability to intubate in the largest trial was dependent on physician availability, there are risks of differential co-interventions and other biases. Furthermore, optimal information size was not achieved for any of the critical or important pre-specified outcomes except duration of positive-pressure ventilation. Therefore, further trials are needed before stronger recommendations can be made about use of supraglottic airways as the initial device for positive pressure ventilation.
Balancing factors in the Task Force recommendation include the training required for supraglottic airway insertion and the safety of the supraglottic airway compared with face mask ventilation. Although the training provided was incompletely documented in several studies {Feroze 2008 148; Singh 2005 303; Zhu 2011 1405} and no study compared the effectiveness of different training programs, successful insertion of the supraglottic airway was high despite apparently short-duration training with a manikin. In the largest trial {Pejovic 2020 2138}, participating midwives received brief didactic training for insertion of a cuffless supraglottic device as part of a Helping Babies Breathe course and were required to demonstrate 3 successful insertions in a maninkin before participating in the study. Only 2 RCTs {Singh 2005 303; Trevisanuto 2015 286} indicated that successful insertion in a newborn infant was a prerequisite to study participation. While the individual studies had limited power to establish the safety of the supraglottic airway, the Task Force was encouraged by the relatively large number of newborn infants reported across all studies and the small number of adverse events.
Neither the cost of supplying supraglottic airways in the delivery room nor the cost-effectiveness of providing positive-pressure ventilation with a supraglottic airway compared with a face mask has been studied. In 5 of the included studies {Pejovic 2018 255; Pejovic 2020 2138; Trevisanuto 2015 286; Zhu 2011 1405}, the authors indicated that the device was provided as part of the study. The availability of resources and economic considerations may influence the decision whether to use a supraglottic airway or face mask. Given the large number of infants worldwide who receive positive pressure ventilation after birth, it is important to evaluate the cost-effectiveness of the supraglottic airway as the initial device for positive pressure ventilation.
Knowledge Gaps
The training requirements to achieve and maintain competency with supraglottic airway insertion, including different types of devices.
The effectiveness and safety of supraglottic airways as the initial device for positive-pressure ventilation in high resource settings.
The effectiveness and safety of supraglottic airways compared with face masks during chest compressions.
The effectiveness and safety of supraglottic airways compared with face masks for newborn infants with orofacial anomalies.
The effectiveness and safety of different supraglottic airway designs.
The effectiveness and safety of supraglottic airways for positive-pressure ventilation among newborn infants less than 34 weeks’ gestation.
The resource utilization and cost-effectiveness of using supraglottic airways compared with face masks as the initial device for positive-pressure ventilation in different settings.
Attachments: NLS 5340 Supgraglottic airway Et D
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