Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants: The SAIL Randomized Clinical Trial

Haresh Kirpalani, Sarah J. Ratcliffe, Martin Keszler, Peter G. Davis, Elizabeth E. Foglia, Arjan Te Pas, Melissa Fernando, Aasma Chaudhary, Russell Localio, Anton H. Van Kaam, Wes Onland, Louise S. Owen, Georg M. Schmölzer, Anup Katheria, Helmut Hummler, Gianluca Lista, Soraya Abbasi, Daniel Klotz, Burkhard Simma, Vinay NadkarniFrancis R Poulain, Steven M. Donn, Han Suk Kim, Won Soon Park, Claudia Cadet, Juin Yee Kong, Alexandra Smith, Ursula Guillen, Helen G. Liley, Andrew O. Hopper, Masanori Tamura

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H 2 O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P =.29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P =.002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions.

Original languageEnglish (US)
Pages (from-to)1165-1175
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume321
Issue number12
DOIs
StatePublished - Mar 26 2019

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Extremely Premature Infants
Intermittent Positive-Pressure Ventilation
Bronchopulmonary Dysplasia
Economic Inflation
Randomized Controlled Trials
Resuscitation
Ventilation
Premature Infants
Gestational Age
Neonatal Intensive Care Units
Bradycardia
Masks
Respiration
Outcome Assessment (Health Care)
Parturition

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants : The SAIL Randomized Clinical Trial. / Kirpalani, Haresh; Ratcliffe, Sarah J.; Keszler, Martin; Davis, Peter G.; Foglia, Elizabeth E.; Te Pas, Arjan; Fernando, Melissa; Chaudhary, Aasma; Localio, Russell; Van Kaam, Anton H.; Onland, Wes; Owen, Louise S.; Schmölzer, Georg M.; Katheria, Anup; Hummler, Helmut; Lista, Gianluca; Abbasi, Soraya; Klotz, Daniel; Simma, Burkhard; Nadkarni, Vinay; Poulain, Francis R; Donn, Steven M.; Kim, Han Suk; Park, Won Soon; Cadet, Claudia; Kong, Juin Yee; Smith, Alexandra; Guillen, Ursula; Liley, Helen G.; Hopper, Andrew O.; Tamura, Masanori.

In: JAMA - Journal of the American Medical Association, Vol. 321, No. 12, 26.03.2019, p. 1165-1175.

Research output: Contribution to journalArticle

Kirpalani, H, Ratcliffe, SJ, Keszler, M, Davis, PG, Foglia, EE, Te Pas, A, Fernando, M, Chaudhary, A, Localio, R, Van Kaam, AH, Onland, W, Owen, LS, Schmölzer, GM, Katheria, A, Hummler, H, Lista, G, Abbasi, S, Klotz, D, Simma, B, Nadkarni, V, Poulain, FR, Donn, SM, Kim, HS, Park, WS, Cadet, C, Kong, JY, Smith, A, Guillen, U, Liley, HG, Hopper, AO & Tamura, M 2019, 'Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants: The SAIL Randomized Clinical Trial', JAMA - Journal of the American Medical Association, vol. 321, no. 12, pp. 1165-1175. https://doi.org/10.1001/jama.2019.1660
Kirpalani, Haresh ; Ratcliffe, Sarah J. ; Keszler, Martin ; Davis, Peter G. ; Foglia, Elizabeth E. ; Te Pas, Arjan ; Fernando, Melissa ; Chaudhary, Aasma ; Localio, Russell ; Van Kaam, Anton H. ; Onland, Wes ; Owen, Louise S. ; Schmölzer, Georg M. ; Katheria, Anup ; Hummler, Helmut ; Lista, Gianluca ; Abbasi, Soraya ; Klotz, Daniel ; Simma, Burkhard ; Nadkarni, Vinay ; Poulain, Francis R ; Donn, Steven M. ; Kim, Han Suk ; Park, Won Soon ; Cadet, Claudia ; Kong, Juin Yee ; Smith, Alexandra ; Guillen, Ursula ; Liley, Helen G. ; Hopper, Andrew O. ; Tamura, Masanori. / Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants : The SAIL Randomized Clinical Trial. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 321, No. 12. pp. 1165-1175.
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title = "Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants: The SAIL Randomized Clinical Trial",
abstract = "Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H 2 O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2{\%} female), 426 infants (92.6{\%}) completed the trial. In the sustained inflation group, 137 infants (63.7{\%}) died or survived with BPD vs 125 infants (59.2{\%}) in the standard resuscitation group (adjusted risk difference [aRD], 4.7{\%} [95{\%} CI, -3.8{\%} to 13.1{\%}]; P =.29). Death at less than 48 hours of age occurred in 16 infants (7.4{\%}) in the sustained inflation group vs 3 infants (1.4{\%}) in the standard resuscitation group (aRD, 5.6{\%} [95{\%} CI, 2.1{\%} to 9.1{\%}]; P =.002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions.",
author = "Haresh Kirpalani and Ratcliffe, {Sarah J.} and Martin Keszler and Davis, {Peter G.} and Foglia, {Elizabeth E.} and {Te Pas}, Arjan and Melissa Fernando and Aasma Chaudhary and Russell Localio and {Van Kaam}, {Anton H.} and Wes Onland and Owen, {Louise S.} and Schm{\"o}lzer, {Georg M.} and Anup Katheria and Helmut Hummler and Gianluca Lista and Soraya Abbasi and Daniel Klotz and Burkhard Simma and Vinay Nadkarni and Poulain, {Francis R} and Donn, {Steven M.} and Kim, {Han Suk} and Park, {Won Soon} and Claudia Cadet and Kong, {Juin Yee} and Alexandra Smith and Ursula Guillen and Liley, {Helen G.} and Hopper, {Andrew O.} and Masanori Tamura",
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TY - JOUR

T1 - Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death among Extremely Preterm Infants

T2 - The SAIL Randomized Clinical Trial

AU - Kirpalani, Haresh

AU - Ratcliffe, Sarah J.

AU - Keszler, Martin

AU - Davis, Peter G.

AU - Foglia, Elizabeth E.

AU - Te Pas, Arjan

AU - Fernando, Melissa

AU - Chaudhary, Aasma

AU - Localio, Russell

AU - Van Kaam, Anton H.

AU - Onland, Wes

AU - Owen, Louise S.

AU - Schmölzer, Georg M.

AU - Katheria, Anup

AU - Hummler, Helmut

AU - Lista, Gianluca

AU - Abbasi, Soraya

AU - Klotz, Daniel

AU - Simma, Burkhard

AU - Nadkarni, Vinay

AU - Poulain, Francis R

AU - Donn, Steven M.

AU - Kim, Han Suk

AU - Park, Won Soon

AU - Cadet, Claudia

AU - Kong, Juin Yee

AU - Smith, Alexandra

AU - Guillen, Ursula

AU - Liley, Helen G.

AU - Hopper, Andrew O.

AU - Tamura, Masanori

PY - 2019/3/26

Y1 - 2019/3/26

N2 - Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H 2 O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P =.29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P =.002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions.

AB - Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H 2 O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P =.29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P =.002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions.

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