Downloaded from fn.bmj.com on June 15, 2014 - Published by group.bmj.com
Original article
Changes in ventilator strategies and outcomes in preterm infants Valentina Vendettuoli,1 Roberto Bellù,2 Rinaldo Zanini,2 Fabio Mosca,1 Luigi Gagliardi,3 for the Italian Neonatal Network ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ archdischild-2013-305165). 1
NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy 2 Neonatal Intensive Care Unit, Ospedale ‘A Manzoni’, Lecco, Italy 3 Pediatrics and Neonatology Division, Woman and Child Health Department, Ospedale Versilia, Viareggio, Italy Correspondence to Dr Valentina Vendettuoli, NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via della Commenda 12, Milano 20122, Italia, valentina.vendettuoli@ mangiagalli.it Received 31 August 2013 Revised 18 April 2014 Accepted 24 April 2014 Published Online First 20 May 2014
ABSTRACT Background Although life-saving, intubation and mechanical ventilation can lead to complications including bronchopulmonary dysplasia (BPD). In order to reduce the incidence of BPD, non-invasive ventilation (NIV) is increasingly used. Objective The aim of our study was to describe changes in ventilator strategies and outcomes between 2006 and 2010 in the Italian Neonatal Network (INN). Design Multicentre cohort study. Settings 31 tertiary level neonatal units participating in INN in 2006 and 2010. Patients 2465 preterm infants 23–30 weeks gestational age (GA) without congenital anomalies. Main outcomes measures Death, BPD and other variables defined according to Vermont Oxford Network. Logistic regressions, adjusting for confounders and clustering for hospitals, were used. Results Similar numbers of infants were studied between 2006 and 2010 (1234 in 2006 and 1231 in 2010). The baseline risk of populations studied (GA, birth weight and Vermont Oxford Network Risk-Adjustment score) did not change. After adjusting for confounding variables, infants receiving invasive mechanical ventilation decreased (OR=0.72, 95% CI 0.58 to 0.89) while NIV increased (OR=1.75, 95% CI 1.39 to 2.21); intubation in delivery room decreased (OR=0.64, 95% CI 0.51 to 0.79). Considering outcomes, there was a significant reduction in mortality (OR=0.73, 95% CI 0.55 to 0.96) and in the combined outcome mortality or BPD (OR=0.76, 95% CI 0.62 to 0.94). Conclusions Despite a stable baseline risk, from 2006 to 2010, we observed a lower level of invasiveness, a reduction of mechanical ventilation and an increase of NIV use, and this was accompanied by a decrease in riskadjusted mortality and BPD.
INTRODUCTION
To cite: Vendettuoli V, Bellù R, Zanini R, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F321–F324.
Between 2000 and 2009, the rates of mortality and major neonatal morbidities including chronic lung disease1 in survivors decreased for infants with a birth weight (BW) of 501–1500 g. However, pulmonary disorders are responsible of over 50% of neonatal deaths in very preterm infants,2 3 and are associated with morbidities that have severe longterm consequences.1 2 Several different methods for providing respiratory support can be applied in the care of preterm infants. In previous decades, it was common to initiate endotracheal intubation and mechanical ventilation in neonates with moderate to severe respiratory distress syndrome (RDS).4 These procedures can be life-saving, but may have adverse effects on the respiratory system.4 Bronchopulmonary dysplasia
What is already known on this topic ▸ Ventilator assistance remains one of the most important and most used procedures in very preterm infants. ▸ Different techniques, both invasive (with endotracheal intubation) and non-invasive, are available.
What this study adds ▸ In a large cohort of preterm infants, in last 5 years we observed a reduction of invasive mechanical ventilation and an increase of non-invasive ventilation. ▸ Changes in ventilator practices were accompanied by a reduction in both mortality and bronchopulmonary dysplasia.
(BPD) represents one of the most significant pulmonary complications. It is a multifactorial disease, its pathogenesis being linked to immature lung tissue, barotrauma, volutrauma5 and prolonged mechanical ventilation.6 Nasal continuous positive airway pressure (nCPAP) has been used to wean preterm infants off mechanical ventilation and, more recently, as a primary mode of respiratory support for preterm infants with respiratory insufficiency.7 8 Nowadays, improvements in the measurement of volume and flow in modern neonatal ventilators have led to a variety of alternative non-invasive ventilation (NIV) procedures, in addition to the well-known nCPAP.9 NIV refers to any technique that uses constant or variable pressure to provide ventilator support, but without tracheal intubation such as continuous positive airway pressure, nasal intermittent mandatory ventilation (nIMV), nasal intermittent positive pressure ventilation and high flow nasal cannula. Currently, NIV is widely used in neonatal intensive care units;9 however, there are few data on how these techniques have been taken up by neonatologists, resulting in actual changes in ventilator strategies in very preterm infants, and if these changes have been associated with changes in respiratory outcomes, such as BPD.5 6 Neonatal networks allow the collection of large multicentre databases and are an ideal tool to answer these scientific questions.10 11
Vendettuoli V, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F321–F324. doi:10.1136/archdischild-2013-305165
F321
Downloaded from fn.bmj.com on June 15, 2014 - Published by group.bmj.com
Original article We undertook this study to identify changes in respiratory procedures and outcomes for preterm infants enrolled in the Italian Neonatal Network (INN) 5 years apart (between 2006 and 2010).
METHODS A cohort of neonates 23–30 weeks gestational age (GA), born in 2006 and 2010, and assisted in tertiary level neonatal intensive care units adhering to the INN was analysed. INN is a voluntary collaboration of neonatal units in Italy, with the purpose of coordinating national data collection, adhering to the Vermont Oxford Network (VON). In 2006, 31 hospitals participated, and in the following years the number of hospitals progressively grew to 86 in 2012; however, for the purpose of this study we only considered infants assisted in the 31 hospitals participating in both 2006 and 2010. We excluded from the study infants dying in the delivery room and those with congenital anomalies. All the variables were defined according to VON (http://www. vtoxford.org). All data undergo automated data checks for quality, and completeness is verified and certified at the time of submission as part of participation in the VON. Concerning ventilator support, for each infant the database collects data on such procedures as oxygen supplementation; use of nCPAP, and use of nCPAP before intubation; use of high flow nasal cannula; use of nIMV/synchronised intermittent mandatory ventilation; use of conventional ventilation; use of high frequency ventilation; and surfactant administration during initial resuscitation in delivery room or at any time. The outcomes analysed for this study are mortality before discharge from the hospital, or BPD, defined according to the VON.12 Briefly, BPD is defined as being present if the infant received any supplemental oxygen at 36 weeks postmenstrual age; infants discharged or transferred between 34 and 36 weeks were classified based on their oxygen status at discharge (see online supplementary appendix).
Data analysis In order to obtain unbiased estimates, we tried to ensure comparability of populations analysed between years by taking the following steps: first, we restricted the inclusion criteria only to infants admitted to hospitals that participated in the INN in both 2006 and 2010. Second, we compared infants in both years for variables known to influence both ventilation procedures and outcomes, and that could act as confounders such as GA, BW, antenatal steroids, sex, being inborn, mode of delivery, being twins, intubation in delivery room and RDS. We also calculated for each infant the severity of illness by using the Vermont Oxford Network Risk-Adjustment (VON-RA) score, which takes into consideration GA, BW for GA, mode of delivery, multiple pregnancy, 1-min Apgar score, race, being inborn, and sex (coefficients kindly provided by J Horbar and E Edwards, VON), a validated infant severity score.13 14 Finally, we estimated changes in frequencies in procedures (NIV, mechanical ventilation, any respiratory support, etc) and outcomes (death, BPD, death or BPD) between years by using random-effects logistic models which took into account clustering for hospitals. Results are expressed as ORs and 95% CI. Estimates were adjusted for severity of illness of infant and antenatal steroid prophylaxis. Missing data never exceeded 2.4%, except for BPD (6.1%). Analyses were performed using STATA (V.11) statistical software. F322
Table 1 Characteristics of infants in the 2 years considered expressed as means and SD or per cent
GA BW Sex (male) SGA Multiple gestation Antenatal steroids Inborn Apgar at 1 min Died in delivery room Caesarean section RDS VON-RA score
2006
2010
p Value
27.5±2.0 1007±278 53.9% 10.1% 26.7% 79.3% 90.9% 5.4±2.3 0.80% 76.1% 82.6% 0.12±0.05
27.5±2.0 998±287 49.9% 11.7% 31.9% 85.3% 91.4% 5.6±2.2 0.65% 80.1% 85.2% 0.12±0.05
0.70 0.45 0.05 0.21 0.01
Original article
Changes in ventilator strategies and outcomes in preterm infants Valentina Vendettuoli,1 Roberto Bellù,2 Rinaldo Zanini,2 Fabio Mosca,1 Luigi Gagliardi,3 for the Italian Neonatal Network ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ archdischild-2013-305165). 1
NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy 2 Neonatal Intensive Care Unit, Ospedale ‘A Manzoni’, Lecco, Italy 3 Pediatrics and Neonatology Division, Woman and Child Health Department, Ospedale Versilia, Viareggio, Italy Correspondence to Dr Valentina Vendettuoli, NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via della Commenda 12, Milano 20122, Italia, valentina.vendettuoli@ mangiagalli.it Received 31 August 2013 Revised 18 April 2014 Accepted 24 April 2014 Published Online First 20 May 2014
ABSTRACT Background Although life-saving, intubation and mechanical ventilation can lead to complications including bronchopulmonary dysplasia (BPD). In order to reduce the incidence of BPD, non-invasive ventilation (NIV) is increasingly used. Objective The aim of our study was to describe changes in ventilator strategies and outcomes between 2006 and 2010 in the Italian Neonatal Network (INN). Design Multicentre cohort study. Settings 31 tertiary level neonatal units participating in INN in 2006 and 2010. Patients 2465 preterm infants 23–30 weeks gestational age (GA) without congenital anomalies. Main outcomes measures Death, BPD and other variables defined according to Vermont Oxford Network. Logistic regressions, adjusting for confounders and clustering for hospitals, were used. Results Similar numbers of infants were studied between 2006 and 2010 (1234 in 2006 and 1231 in 2010). The baseline risk of populations studied (GA, birth weight and Vermont Oxford Network Risk-Adjustment score) did not change. After adjusting for confounding variables, infants receiving invasive mechanical ventilation decreased (OR=0.72, 95% CI 0.58 to 0.89) while NIV increased (OR=1.75, 95% CI 1.39 to 2.21); intubation in delivery room decreased (OR=0.64, 95% CI 0.51 to 0.79). Considering outcomes, there was a significant reduction in mortality (OR=0.73, 95% CI 0.55 to 0.96) and in the combined outcome mortality or BPD (OR=0.76, 95% CI 0.62 to 0.94). Conclusions Despite a stable baseline risk, from 2006 to 2010, we observed a lower level of invasiveness, a reduction of mechanical ventilation and an increase of NIV use, and this was accompanied by a decrease in riskadjusted mortality and BPD.
INTRODUCTION
To cite: Vendettuoli V, Bellù R, Zanini R, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F321–F324.
Between 2000 and 2009, the rates of mortality and major neonatal morbidities including chronic lung disease1 in survivors decreased for infants with a birth weight (BW) of 501–1500 g. However, pulmonary disorders are responsible of over 50% of neonatal deaths in very preterm infants,2 3 and are associated with morbidities that have severe longterm consequences.1 2 Several different methods for providing respiratory support can be applied in the care of preterm infants. In previous decades, it was common to initiate endotracheal intubation and mechanical ventilation in neonates with moderate to severe respiratory distress syndrome (RDS).4 These procedures can be life-saving, but may have adverse effects on the respiratory system.4 Bronchopulmonary dysplasia
What is already known on this topic ▸ Ventilator assistance remains one of the most important and most used procedures in very preterm infants. ▸ Different techniques, both invasive (with endotracheal intubation) and non-invasive, are available.
What this study adds ▸ In a large cohort of preterm infants, in last 5 years we observed a reduction of invasive mechanical ventilation and an increase of non-invasive ventilation. ▸ Changes in ventilator practices were accompanied by a reduction in both mortality and bronchopulmonary dysplasia.
(BPD) represents one of the most significant pulmonary complications. It is a multifactorial disease, its pathogenesis being linked to immature lung tissue, barotrauma, volutrauma5 and prolonged mechanical ventilation.6 Nasal continuous positive airway pressure (nCPAP) has been used to wean preterm infants off mechanical ventilation and, more recently, as a primary mode of respiratory support for preterm infants with respiratory insufficiency.7 8 Nowadays, improvements in the measurement of volume and flow in modern neonatal ventilators have led to a variety of alternative non-invasive ventilation (NIV) procedures, in addition to the well-known nCPAP.9 NIV refers to any technique that uses constant or variable pressure to provide ventilator support, but without tracheal intubation such as continuous positive airway pressure, nasal intermittent mandatory ventilation (nIMV), nasal intermittent positive pressure ventilation and high flow nasal cannula. Currently, NIV is widely used in neonatal intensive care units;9 however, there are few data on how these techniques have been taken up by neonatologists, resulting in actual changes in ventilator strategies in very preterm infants, and if these changes have been associated with changes in respiratory outcomes, such as BPD.5 6 Neonatal networks allow the collection of large multicentre databases and are an ideal tool to answer these scientific questions.10 11
Vendettuoli V, et al. Arch Dis Child Fetal Neonatal Ed 2014;99:F321–F324. doi:10.1136/archdischild-2013-305165
F321
Downloaded from fn.bmj.com on June 15, 2014 - Published by group.bmj.com
Original article We undertook this study to identify changes in respiratory procedures and outcomes for preterm infants enrolled in the Italian Neonatal Network (INN) 5 years apart (between 2006 and 2010).
METHODS A cohort of neonates 23–30 weeks gestational age (GA), born in 2006 and 2010, and assisted in tertiary level neonatal intensive care units adhering to the INN was analysed. INN is a voluntary collaboration of neonatal units in Italy, with the purpose of coordinating national data collection, adhering to the Vermont Oxford Network (VON). In 2006, 31 hospitals participated, and in the following years the number of hospitals progressively grew to 86 in 2012; however, for the purpose of this study we only considered infants assisted in the 31 hospitals participating in both 2006 and 2010. We excluded from the study infants dying in the delivery room and those with congenital anomalies. All the variables were defined according to VON (http://www. vtoxford.org). All data undergo automated data checks for quality, and completeness is verified and certified at the time of submission as part of participation in the VON. Concerning ventilator support, for each infant the database collects data on such procedures as oxygen supplementation; use of nCPAP, and use of nCPAP before intubation; use of high flow nasal cannula; use of nIMV/synchronised intermittent mandatory ventilation; use of conventional ventilation; use of high frequency ventilation; and surfactant administration during initial resuscitation in delivery room or at any time. The outcomes analysed for this study are mortality before discharge from the hospital, or BPD, defined according to the VON.12 Briefly, BPD is defined as being present if the infant received any supplemental oxygen at 36 weeks postmenstrual age; infants discharged or transferred between 34 and 36 weeks were classified based on their oxygen status at discharge (see online supplementary appendix).
Data analysis In order to obtain unbiased estimates, we tried to ensure comparability of populations analysed between years by taking the following steps: first, we restricted the inclusion criteria only to infants admitted to hospitals that participated in the INN in both 2006 and 2010. Second, we compared infants in both years for variables known to influence both ventilation procedures and outcomes, and that could act as confounders such as GA, BW, antenatal steroids, sex, being inborn, mode of delivery, being twins, intubation in delivery room and RDS. We also calculated for each infant the severity of illness by using the Vermont Oxford Network Risk-Adjustment (VON-RA) score, which takes into consideration GA, BW for GA, mode of delivery, multiple pregnancy, 1-min Apgar score, race, being inborn, and sex (coefficients kindly provided by J Horbar and E Edwards, VON), a validated infant severity score.13 14 Finally, we estimated changes in frequencies in procedures (NIV, mechanical ventilation, any respiratory support, etc) and outcomes (death, BPD, death or BPD) between years by using random-effects logistic models which took into account clustering for hospitals. Results are expressed as ORs and 95% CI. Estimates were adjusted for severity of illness of infant and antenatal steroid prophylaxis. Missing data never exceeded 2.4%, except for BPD (6.1%). Analyses were performed using STATA (V.11) statistical software. F322
Table 1 Characteristics of infants in the 2 years considered expressed as means and SD or per cent
GA BW Sex (male) SGA Multiple gestation Antenatal steroids Inborn Apgar at 1 min Died in delivery room Caesarean section RDS VON-RA score
2006
2010
p Value
27.5±2.0 1007±278 53.9% 10.1% 26.7% 79.3% 90.9% 5.4±2.3 0.80% 76.1% 82.6% 0.12±0.05
27.5±2.0 998±287 49.9% 11.7% 31.9% 85.3% 91.4% 5.6±2.2 0.65% 80.1% 85.2% 0.12±0.05
0.70 0.45 0.05 0.21 0.01
