Accepted Article
Article Type: Regular Article
High-flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants
Running Title: Diaphragm activation during non-invasive respiratory support
Nehad Nasef1, Enas El-Gouhary1, Patti Schurr1, Maureen Reilly1, Jennifer Beck2, Michael Dunn1,3, Eugene Ng1,3
1
Women and Babies Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
2
Keenan Research Centre for Biomedical Science, Department of Critical Care, St. Michael's Hospital, Toronto, Ontario, Canada
3
Division of Neonatology, Department of Paediatrics, University of Toronto, Ontario, Canada
Corresponding Author Eugene Ng, MD, FRCPC, FAAP Department of Newborn & Developmental Paediatrics Sunnybrook Health Sciences Centre
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/apa.12998 This article is protected by copyright. All rights reserved.
Accepted Article
2075 Bayview Avenue, Toronto Ontario M4N 3M5, CANADA Tel: +1 (416) 480-6100 ext. 87781 Fax: +1 (416) 480-5612 Email: [email protected]
ABSTRACT Aim High-flow nasal cannulae (HFNC) are increasingly used for respiratory management of preterm infants. However, their ability to provide support compared to nasal continuous positive airway pressure (CPAP) has been questioned. We compared the effect of HFNC versus nasal CPAP on diaphragm electrical activity (EAdi) in preterm infants. Methods Preterm infants ≤1,500g were randomised in a crossover design to receive two hours of either Infant Flow® CPAP (IF-CPAP) at 5-6cmH2O or HFNC with the flow rate adjusted to achieve an equivalent pharyngeal pressure. A feeding catheter with miniaturised sensors was inserted for continuous EAdi measurement. Results The study comprised 10 infants. Physiologic parameters and oxygen requirements were not different between the two modes. However, seven infants demonstrated a
This article is protected by copyright. All rights reserved.
Accepted Article
48 hours, treated with methylxanthines for apnoea of prematurity and required less than 35% oxygen. Exclusion criteria were: congenital or acquired anomaly of the gastrointestinal tract, diaphragmatic paralysis, congenital or acquired neurological condition, congenital heart disease including symptomatic patent ductus arteriosus, congenital or acquired anomaly of the respiratory tract including lung infections, treatment of sepsis and on muscle relaxants or narcotic analgesics at the time of enrolment.
Study Design A prospective, un-blinded randomised crossover study was performed comparing respiratory support provided by either IF-CPAP or HFNC. IF-CPAP nasal prongs are 6mm long and come in three sizes (4, 4.5 and 5mm). Flow from the IF-CPAP system was adjusted in order to deliver pressures between 5-6cmH2O. The HFNC system consists of a gas source, air-oxygen blender and a heated humidifier (Fisher & Paykel Healthcare Limited, Laval, QC, Canada) delivering air/oxygen via a nasal cannula with an outer diameter size of 0.28cm tapered (Salter Labs-Nasal Cannula [Infant]). To provide comparable end expiratory pressure, the flow rate was adjusted according to the targeted pharyngeal pressure in cmH2O, calculated as 0.7 + (1.1 x Flow [L/min/kg]) (9). Following the parents’ or guardians’ consent, infants were randomised, by sealed envelopes, to start on one of the two crossover protocols. In the first protocol, EAdi was recorded continuously while infants were on IF-CPAP for two hours followed by HFNC for another two hours. In the second protocol, EAdi was recorded while infants were on HFNC for two hours followed by IF-CPAP for another two hours. A single
This article is protected by copyright. All rights reserved.
Accepted Article
Nte
Neural expiratory time
Nrr
Neural respiratory rate
PEEP
Positive end-expiratory pressure
SaO2
Oxygen saturation
VLBW
Very low birth weight
Competing interests Dr. Jennifer Beck has a commercial relationship with Maquet Critical Care, including the licensing of patented inventions.
REFERENCES 1.
Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev 2003;CD000143.
2.
Liptsen E, Aghai ZH, Pyon KH, Saslow JG, Nakhla T, Long J, et al. Work of breathing during nasal continuous positive airway pressure in preterm infants: a comparison of bubble vs variable-flow devices. J Perinatol 2005; 25:453-8.
This article is protected by copyright. All rights reserved.
Accepted Article
29.
Lavizzari A, Veneroni C, Colnaghi M, Ciuffini F, Zannin E, Fumagalli M, et al. Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures. Arch Dis Child Fetal Neonatal Ed 2014;99:F315-20.
30.
Daish H, Badurdeen S. Question 2: Humidified heated high flow nasal cannula versus nasal continuous positive airway pressure for providing respiratory support following extubation in preterm newborns. Arch Dis Child 2014;99:880-2.
This article is protected by copyright. All rights reserved.
Accepted Article
Table 1 Baseline characteristics of preterm infants Characteristics
Protocol 1 Protocol 2
p value
n=5
n=5
Gestational Age at birth (weeks)
26.5±1.4
26.7±1.4
0.7
Corrected gestational age at enrolment (weeks)
30.4±0.9
31.4±1.5
0.3
Female sex
4 (80%)
5 (100%)
0.5
Birth weight (gm)
894±166
916±247
0.8
Weight at enrolment (gm)
1229±248
1326±235
0.5
Surfactant
3 (60%)
3 (60%)
0.7
Days on mechanical ventilation
10.6±13
7.6±9.7
0.7
Data expressed as mean ± SD or number & percentage Paired-t test for continuous variables and the chi-square test with Fisher’s Exact for categorical variables
This article is protected by copyright. All rights reserved.
Accepted Article
patient use size six French specialised feeding catheter (Maquet Critical Care AB, Solna, Sweden), with an array of miniaturised stainless steel electrodes mounted for monitoring EAdi signals, was orally inserted into the oesophagus. The first 45 minutes of EAdi recording on each respiratory support modality were designated for adaptation and were not used for analysis (Figure 1). Fraction of inspired oxygen (FiO2) was adjusted to keep oxygen saturation (SaO2) between 88 and 92%, in line with our unit protocol. Upon completion or termination of the protocol, the infant was returned to the originally prescribed treatment as determined by the medical team. The protocol was terminated if a study infant exhibited any of the followings: increased respiratory distress, sustained increase in heart rate by more than 20bpm from baseline for over 10 minutes or more than three significant apnoea episodes during any of the 30 minutes on each respiratory support modality.
Primary outcome was the difference in EAdi between IF-CPAP and HFNC as measured by EAdi tonic, EAdi peak, neural inspiratory time (NTi), neural expiratory time (NTe) and neural respiratory rate (Nrr). The methodology of data acquisition and analysis of the EAdi signal was described in details by Emeriaud et al (10). Other secondary outcomes included: difference in the number of apnoea episodes defined as periods of flat EAdi tracing for five to 10, 10 to 15 and more than 15 seconds, episodes of clinically significant apnoea defined by pause of breathing >20 seconds or >10 seconds if associated with heart rate < 80 per minute or SaO2 < 80%. Clinical data including infant's SaO2, heart rate and respiratory rate were continuously monitored (Philips Intellivue® MP70 monitors). Data for statistical analysis were
This article is protected by copyright. All rights reserved.
Accepted Article
collected from the monitor at the same time of EAdi recording. This study protocol was approved by the research ethics board at Sunnybrook Health Sciences Centre.
Data acquisition and Analysis EAdi signals were captured via the neurally adjusted ventilatory assist (NAVA) module of the Maquet® Servo-i ventilation platform and recorded by a study laptop computer (11). This ventilator was not used to deliver any assist, but was used because of the monitoring and acquisition capabilities for EAdi. The catheter was positioned at the level of the crural diaphragm based on the on-line feedback from the EAdi signals displayed on the ventilator (12). Once the position was confirmed, the catheter was secured by tape, with catheter position marked on the catheter. EAdi was measured and recorded continuously throughout the entire study period. However, analysis was performed on the 30-minute epoch at the middle of each respiratory support modality, allowing for a pre-analysis interval for adaptation of 45 minutes and a post-analysis interval of 45 minutes to the next handling with feeding.
Sample size calculation and Statistical Analysis: Previous data (8) showed that mean EAdi tonic of preterm infants with mild respiratory distress was 8.7 ± 3.8 arbitrary units (au). In a case report of a preterm infant at 26 weeks of gestation, increasing the flow rate of the high-flow nasal cannula from 2 to 8L/min was associated with a 70% reduction in EAdi levels (13). We hypothesised that adequate flow on the HFNC would be associated with a 50%
This article is protected by copyright. All rights reserved.
Accepted Article
reduction in EAdi tonic to a mean of about 4.4au. A sample size of nine infants was required to test our hypothesis with a power of 0.8 and a significant p-value of
Article Type: Regular Article
High-flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants
Running Title: Diaphragm activation during non-invasive respiratory support
Nehad Nasef1, Enas El-Gouhary1, Patti Schurr1, Maureen Reilly1, Jennifer Beck2, Michael Dunn1,3, Eugene Ng1,3
1
Women and Babies Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
2
Keenan Research Centre for Biomedical Science, Department of Critical Care, St. Michael's Hospital, Toronto, Ontario, Canada
3
Division of Neonatology, Department of Paediatrics, University of Toronto, Ontario, Canada
Corresponding Author Eugene Ng, MD, FRCPC, FAAP Department of Newborn & Developmental Paediatrics Sunnybrook Health Sciences Centre
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/apa.12998 This article is protected by copyright. All rights reserved.
Accepted Article
2075 Bayview Avenue, Toronto Ontario M4N 3M5, CANADA Tel: +1 (416) 480-6100 ext. 87781 Fax: +1 (416) 480-5612 Email: [email protected]
ABSTRACT Aim High-flow nasal cannulae (HFNC) are increasingly used for respiratory management of preterm infants. However, their ability to provide support compared to nasal continuous positive airway pressure (CPAP) has been questioned. We compared the effect of HFNC versus nasal CPAP on diaphragm electrical activity (EAdi) in preterm infants. Methods Preterm infants ≤1,500g were randomised in a crossover design to receive two hours of either Infant Flow® CPAP (IF-CPAP) at 5-6cmH2O or HFNC with the flow rate adjusted to achieve an equivalent pharyngeal pressure. A feeding catheter with miniaturised sensors was inserted for continuous EAdi measurement. Results The study comprised 10 infants. Physiologic parameters and oxygen requirements were not different between the two modes. However, seven infants demonstrated a
This article is protected by copyright. All rights reserved.
Accepted Article
48 hours, treated with methylxanthines for apnoea of prematurity and required less than 35% oxygen. Exclusion criteria were: congenital or acquired anomaly of the gastrointestinal tract, diaphragmatic paralysis, congenital or acquired neurological condition, congenital heart disease including symptomatic patent ductus arteriosus, congenital or acquired anomaly of the respiratory tract including lung infections, treatment of sepsis and on muscle relaxants or narcotic analgesics at the time of enrolment.
Study Design A prospective, un-blinded randomised crossover study was performed comparing respiratory support provided by either IF-CPAP or HFNC. IF-CPAP nasal prongs are 6mm long and come in three sizes (4, 4.5 and 5mm). Flow from the IF-CPAP system was adjusted in order to deliver pressures between 5-6cmH2O. The HFNC system consists of a gas source, air-oxygen blender and a heated humidifier (Fisher & Paykel Healthcare Limited, Laval, QC, Canada) delivering air/oxygen via a nasal cannula with an outer diameter size of 0.28cm tapered (Salter Labs-Nasal Cannula [Infant]). To provide comparable end expiratory pressure, the flow rate was adjusted according to the targeted pharyngeal pressure in cmH2O, calculated as 0.7 + (1.1 x Flow [L/min/kg]) (9). Following the parents’ or guardians’ consent, infants were randomised, by sealed envelopes, to start on one of the two crossover protocols. In the first protocol, EAdi was recorded continuously while infants were on IF-CPAP for two hours followed by HFNC for another two hours. In the second protocol, EAdi was recorded while infants were on HFNC for two hours followed by IF-CPAP for another two hours. A single
This article is protected by copyright. All rights reserved.
Accepted Article
Nte
Neural expiratory time
Nrr
Neural respiratory rate
PEEP
Positive end-expiratory pressure
SaO2
Oxygen saturation
VLBW
Very low birth weight
Competing interests Dr. Jennifer Beck has a commercial relationship with Maquet Critical Care, including the licensing of patented inventions.
REFERENCES 1.
Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev 2003;CD000143.
2.
Liptsen E, Aghai ZH, Pyon KH, Saslow JG, Nakhla T, Long J, et al. Work of breathing during nasal continuous positive airway pressure in preterm infants: a comparison of bubble vs variable-flow devices. J Perinatol 2005; 25:453-8.
This article is protected by copyright. All rights reserved.
Accepted Article
29.
Lavizzari A, Veneroni C, Colnaghi M, Ciuffini F, Zannin E, Fumagalli M, et al. Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures. Arch Dis Child Fetal Neonatal Ed 2014;99:F315-20.
30.
Daish H, Badurdeen S. Question 2: Humidified heated high flow nasal cannula versus nasal continuous positive airway pressure for providing respiratory support following extubation in preterm newborns. Arch Dis Child 2014;99:880-2.
This article is protected by copyright. All rights reserved.
Accepted Article
Table 1 Baseline characteristics of preterm infants Characteristics
Protocol 1 Protocol 2
p value
n=5
n=5
Gestational Age at birth (weeks)
26.5±1.4
26.7±1.4
0.7
Corrected gestational age at enrolment (weeks)
30.4±0.9
31.4±1.5
0.3
Female sex
4 (80%)
5 (100%)
0.5
Birth weight (gm)
894±166
916±247
0.8
Weight at enrolment (gm)
1229±248
1326±235
0.5
Surfactant
3 (60%)
3 (60%)
0.7
Days on mechanical ventilation
10.6±13
7.6±9.7
0.7
Data expressed as mean ± SD or number & percentage Paired-t test for continuous variables and the chi-square test with Fisher’s Exact for categorical variables
This article is protected by copyright. All rights reserved.
Accepted Article
patient use size six French specialised feeding catheter (Maquet Critical Care AB, Solna, Sweden), with an array of miniaturised stainless steel electrodes mounted for monitoring EAdi signals, was orally inserted into the oesophagus. The first 45 minutes of EAdi recording on each respiratory support modality were designated for adaptation and were not used for analysis (Figure 1). Fraction of inspired oxygen (FiO2) was adjusted to keep oxygen saturation (SaO2) between 88 and 92%, in line with our unit protocol. Upon completion or termination of the protocol, the infant was returned to the originally prescribed treatment as determined by the medical team. The protocol was terminated if a study infant exhibited any of the followings: increased respiratory distress, sustained increase in heart rate by more than 20bpm from baseline for over 10 minutes or more than three significant apnoea episodes during any of the 30 minutes on each respiratory support modality.
Primary outcome was the difference in EAdi between IF-CPAP and HFNC as measured by EAdi tonic, EAdi peak, neural inspiratory time (NTi), neural expiratory time (NTe) and neural respiratory rate (Nrr). The methodology of data acquisition and analysis of the EAdi signal was described in details by Emeriaud et al (10). Other secondary outcomes included: difference in the number of apnoea episodes defined as periods of flat EAdi tracing for five to 10, 10 to 15 and more than 15 seconds, episodes of clinically significant apnoea defined by pause of breathing >20 seconds or >10 seconds if associated with heart rate < 80 per minute or SaO2 < 80%. Clinical data including infant's SaO2, heart rate and respiratory rate were continuously monitored (Philips Intellivue® MP70 monitors). Data for statistical analysis were
This article is protected by copyright. All rights reserved.
Accepted Article
collected from the monitor at the same time of EAdi recording. This study protocol was approved by the research ethics board at Sunnybrook Health Sciences Centre.
Data acquisition and Analysis EAdi signals were captured via the neurally adjusted ventilatory assist (NAVA) module of the Maquet® Servo-i ventilation platform and recorded by a study laptop computer (11). This ventilator was not used to deliver any assist, but was used because of the monitoring and acquisition capabilities for EAdi. The catheter was positioned at the level of the crural diaphragm based on the on-line feedback from the EAdi signals displayed on the ventilator (12). Once the position was confirmed, the catheter was secured by tape, with catheter position marked on the catheter. EAdi was measured and recorded continuously throughout the entire study period. However, analysis was performed on the 30-minute epoch at the middle of each respiratory support modality, allowing for a pre-analysis interval for adaptation of 45 minutes and a post-analysis interval of 45 minutes to the next handling with feeding.
Sample size calculation and Statistical Analysis: Previous data (8) showed that mean EAdi tonic of preterm infants with mild respiratory distress was 8.7 ± 3.8 arbitrary units (au). In a case report of a preterm infant at 26 weeks of gestation, increasing the flow rate of the high-flow nasal cannula from 2 to 8L/min was associated with a 70% reduction in EAdi levels (13). We hypothesised that adequate flow on the HFNC would be associated with a 50%
This article is protected by copyright. All rights reserved.
Accepted Article
reduction in EAdi tonic to a mean of about 4.4au. A sample size of nine infants was required to test our hypothesis with a power of 0.8 and a significant p-value of
