Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine Comparison of Non Synchronized Nasal Intermittent Positive Pressure Ventilation versus Nasal Continuous Positive Airway Pressure as Post-Extubation Respiratory Support in Preterm Infants with Respiratory Distress Syndrome: A Randomized Controlled Trial. Bonny Jasani MD, DM, Ruchi Nanavati MD, Nandkishor Kabra MD, DM, Shankar Rajdeo DNB, Vineet Bhandari MD, DM doi: 10.3109/14767058.2015.1059809 Abstract
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Objective To determine whether post extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to NCPAP in preterm infants with RDS. Methods In this randomized, controlled, open, prospective, single-center clinical trial we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation. Results A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in 6 (19.3%) of nsNIPPV group compared with 9 (28.12%) of NCPAP group and was statistically not significant (P = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.35±39.34 hours versus 111.83±116.39 hours, P = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.86±92.05 hours versus 90.10±140.48 hours, P = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (P = 0.02). Conclusions Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.
© 2014 Informa UK Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Title: Comparison of Non Synchronized Nasal Intermittent Positive Pressure Ventilation versus Nasal Continuous Positive Airway Pressure as Post-Extubation Respiratory Support in Preterm Infants with Respiratory Distress Syndrome: A Randomized Controlled Trial. Authors: 1. Bonny Jasani MD, DM
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
2. Ruchi Nanavati MD 3. Nandkishor Kabra MD, DM 4. Shankar Rajdeo DNB 5. Vineet Bhandari MD, DM Institutional affiliations: 1,2,3,4
Department of Neonatology, Seth G S Medical College and KEM Hospital, Mumbai,
Pincode: 400012, India. 5
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Corresponding Author: Dr Bonny Jasani, Department of Neonatology, 10th Floor, Multi Storey Building, KEM Hospital, Parel, Mumbai, Maharashtra, India. Pincode: 400012. Phone No: +912224107035. Email: [email protected]. Short running title: nsNIPPV versus NCPAP: Post-extubation support in preterm infants. Conflict of interest and source of funding: None Site of the registry and the registration number: ctri.nic.in, CTRI/2014/01/004284 Keywords: NIPPV, NCPAP, mechanical ventilation, non-invasive ventilation, preterm infants.
Abstract Objective To determine whether post extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to NCPAP in preterm infants with RDS.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Methods In this randomized, controlled, open, prospective, single-center clinical trial we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation. Results A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in 6 (19.3%) of nsNIPPV group compared with 9 (28.12%) of NCPAP group and was statistically not significant (P = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.35±39.34 hours versus 111.83±116.39 hours, P = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.86±92.05 hours versus 90.10±140.48 hours, P = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (P = 0.02). Conclusions Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.
Introduction The initiation of mechanical ventilation (MV) in the first days of a preterm infant is a major factor for development of bronchopulmonary dysplasia (BPD) and ventilator-associated morbidities [1, 2]. Non-invasive ventilation (NIV) has been increasingly used to reduce the need for invasive MV in preterm infants and subsequently lower the incidence of BPD [3, 4].
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Nasal continuous positive airway pressure (NCPAP) has been the initial respiratory support for preterm infants with respiratory distress syndrome (RDS) and has become an established practice in many centers [5, 6]. Extubation to NCPAP compared to no respiratory support has been associated with lower incidence of respiratory failure, risk of developing BPD and need for mechanical ventilation in preterm infants [7]. Furthermore, post-extubation support with NCPAP in these infants has been associated with a 40% failure rate at 1 week [8] which has encouraged the use of nasal intermittent positive-pressure ventilation (NIPPV) to reduce these failure rates even further. NIPPV is a form of NIV assistance using a nasal interface to provide respiratory support [9]. It can be used in a synchronized (SNIPPV) or non-synchronized (nsNIPPV) manner to supplement the infants own breathing efforts [10]. Meta analyses has shown that use of SNIPPV reduces the incidence of symptoms of extubation failure more effectively than NCPAP with absence of the gastrointestinal side effects [11]. The drawback pertaining to this mode is it requires special expensive equipment to deliver SNIPPV. Since the phasing out of the ventilator used to deliver SNIPPV, neonatal intensive care units (NICUs) across the world have started using nsNIPPV through conventional neonatal ventilators, for which the evidence is limited. Therefore, we undertook this study to determine whether post-extubation of respiratory support via nsNIPPV would result in improved rates of successful extubation when compared with NCPAP in preterm infants with RDS.
Methods Subjects This single-center randomized clinical trial (RCT) was conducted from September 2010 to September 2012 at a Level III NICU of a tertiary teaching hospital. The study was approved by the institutional ethics committee. Preterm very low birth weight (VLBW) infants with
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
respiratory distress and chest X-ray suggestive of RDS on mechanical ventilation were included in the trial. Infants with suspected upper airway obstruction, congenital airway malformations, or major cardiopulmonary malformations were excluded.
Study Intervention Eligible infants were enrolled after obtaining written informed consent from parents or guardians. The randomization codes were generated by a statistician by using randomization software. The randomization method used was stratified, balanced permuted block procedure for two birth weight strata: 500 to 999 grams and 1000 to 1500 grams. These codes were placed in sequentially numbered opaque sealed envelopes. Preterm ventilated infants, when deemed eligible for extubation, were assigned randomly either to nsNIPPV or NCPAP group. The physician on-call opened sequentially numbered sealed opaque envelopes and randomized infants to respective groups. Access to envelopes was restricted to designated physicians. Blinding of intervention and outcome measurement was not feasible because of the nature of intervention. The diagnosis and severity of RDS were based on clinical signs along with Kero’s and Makinen’s radiologic classification [12]. All infants received a loading dose of 20 mg/kg caffeine citrate and a maintenance dose of 5 mg/kg/day until 34 completed weeks of gestation. Infants were initiated on time-cycled, pressure limited, and continuous-flow neonatal ventilator (Bearcub 750 PSV infant ventilator, Bear Medical Systems, Inc,
Riverside, CA). If indicated by severity of RDS, as per unit policy, natural surfactant [Survanta® or Neosurf (bovine lipid extract surfactant), Cipla, India] was administered if infants had moderate or severe RDS on the chest X-ray and/or fraction of inspired oxygen (FiO2) requirement >0.3. The criteria for extubation were peak inspiratory pressure (PIP) ≤ 15 cm H2O, positive end
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
expiratory pressure (PEEP) ≤ 5 cm H2O, rate of 15 to 25, FiO2 of ≤0.35 and hematocrit of >35% [9]. The devices used for NCPAP were either variable flow CPAP (Infant flow driver, Viasys Healthcare) or ventilator CPAP (BearCub 750 PSV infant ventilator) and nsNIPPV was administered through the BearCub ventilator. Infants randomized to NCPAP were put on CPAP of 5 to 6 cm H2O while those randomized to nsNIPPV, PIP was increased by 4 cm H2O from the pre-extubation value to attempt to compensate for the leak in this open system, PEEP was kept at ≤ 5 cm H2O and rate the same as was being given before extubation; FiO2 was adjusted in all infants to maintain oxygen saturation between 88 to 93% on pulse oximetry. The flow rate was kept at 8 to 10 L/min in both modes of respiratory support. nsNIPPV and NCPAP delivered through ventilator was administered by appropriately sized Hudson prongs and variable flow NCPAP by Infant Flow driver short binasal prongs. All babies on nsNIPPV/NCPAP had an appropriate sized orogastric tube placed kept open to air, to avoid distension of the stomach. A blood gas was obtained 1 hour after extubation. Thereafter, blood gas was sent at least once every 6-12 hours in the first 24 hours post-extubation; subsequent blood gases were obtained as clinically indicated. After careful evaluation of the infant’s respiratory status, the infant was weaned from nsNIPPV/NCPAP to oxyhood, nasal cannula or room air by the attending neonatologist with the use of the following guidelines: in the nsNIPPV group, once the infant had ventilator settings of PIP/PEEP 12/4 cm H2O, rate of 10% of daily feed volume), or the presence of abdominal distension or bloody stools, which precluded the continuation of feeds in the absence of culture positive sepsis or radiographic evidence of NEC. Full feeds were defined as feeds that reached 150 mL/kg per day and sustained for 3 consecutive days.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Sample size calculation On the basis of previous data from our NICU, 46% of our preterm infants administered NCPAP as post extubation support needed intubation and MV within the first 72 hours of extubation. We hypothesized that by using nsNIPPV as post extubation support would reduce the need for intubation and MV to 15% (an absolute reduction of 30%). With a two sided alpha error of 0.05 and beta error of 0.2 (power 80%), the estimated sample size was 62 (31 in each group).
Statistical Analyses Baseline characteristics and outcome measures on continuous scales were analyzed by using two sample t test or Mann Whitney U test as appropriate. Baseline characteristics and outcome measures on nominal scales were analyzed by chi square test or Fisher exact test as appropriate. Statistical significance was considered if the p value was
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Objective To determine whether post extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to NCPAP in preterm infants with RDS. Methods In this randomized, controlled, open, prospective, single-center clinical trial we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation. Results A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in 6 (19.3%) of nsNIPPV group compared with 9 (28.12%) of NCPAP group and was statistically not significant (P = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.35±39.34 hours versus 111.83±116.39 hours, P = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.86±92.05 hours versus 90.10±140.48 hours, P = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (P = 0.02). Conclusions Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.
© 2014 Informa UK Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Title: Comparison of Non Synchronized Nasal Intermittent Positive Pressure Ventilation versus Nasal Continuous Positive Airway Pressure as Post-Extubation Respiratory Support in Preterm Infants with Respiratory Distress Syndrome: A Randomized Controlled Trial. Authors: 1. Bonny Jasani MD, DM
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
2. Ruchi Nanavati MD 3. Nandkishor Kabra MD, DM 4. Shankar Rajdeo DNB 5. Vineet Bhandari MD, DM Institutional affiliations: 1,2,3,4
Department of Neonatology, Seth G S Medical College and KEM Hospital, Mumbai,
Pincode: 400012, India. 5
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Corresponding Author: Dr Bonny Jasani, Department of Neonatology, 10th Floor, Multi Storey Building, KEM Hospital, Parel, Mumbai, Maharashtra, India. Pincode: 400012. Phone No: +912224107035. Email: [email protected]. Short running title: nsNIPPV versus NCPAP: Post-extubation support in preterm infants. Conflict of interest and source of funding: None Site of the registry and the registration number: ctri.nic.in, CTRI/2014/01/004284 Keywords: NIPPV, NCPAP, mechanical ventilation, non-invasive ventilation, preterm infants.
Abstract Objective To determine whether post extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to NCPAP in preterm infants with RDS.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Methods In this randomized, controlled, open, prospective, single-center clinical trial we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation. Results A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n = 31) or NCPAP (n = 32). Extubation failure occurred in 6 (19.3%) of nsNIPPV group compared with 9 (28.12%) of NCPAP group and was statistically not significant (P = 0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.35±39.34 hours versus 111.83±116.39 hours, P = 0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.86±92.05 hours versus 90.10±140.48 hours, P = 0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (P = 0.02). Conclusions Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.
Introduction The initiation of mechanical ventilation (MV) in the first days of a preterm infant is a major factor for development of bronchopulmonary dysplasia (BPD) and ventilator-associated morbidities [1, 2]. Non-invasive ventilation (NIV) has been increasingly used to reduce the need for invasive MV in preterm infants and subsequently lower the incidence of BPD [3, 4].
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Nasal continuous positive airway pressure (NCPAP) has been the initial respiratory support for preterm infants with respiratory distress syndrome (RDS) and has become an established practice in many centers [5, 6]. Extubation to NCPAP compared to no respiratory support has been associated with lower incidence of respiratory failure, risk of developing BPD and need for mechanical ventilation in preterm infants [7]. Furthermore, post-extubation support with NCPAP in these infants has been associated with a 40% failure rate at 1 week [8] which has encouraged the use of nasal intermittent positive-pressure ventilation (NIPPV) to reduce these failure rates even further. NIPPV is a form of NIV assistance using a nasal interface to provide respiratory support [9]. It can be used in a synchronized (SNIPPV) or non-synchronized (nsNIPPV) manner to supplement the infants own breathing efforts [10]. Meta analyses has shown that use of SNIPPV reduces the incidence of symptoms of extubation failure more effectively than NCPAP with absence of the gastrointestinal side effects [11]. The drawback pertaining to this mode is it requires special expensive equipment to deliver SNIPPV. Since the phasing out of the ventilator used to deliver SNIPPV, neonatal intensive care units (NICUs) across the world have started using nsNIPPV through conventional neonatal ventilators, for which the evidence is limited. Therefore, we undertook this study to determine whether post-extubation of respiratory support via nsNIPPV would result in improved rates of successful extubation when compared with NCPAP in preterm infants with RDS.
Methods Subjects This single-center randomized clinical trial (RCT) was conducted from September 2010 to September 2012 at a Level III NICU of a tertiary teaching hospital. The study was approved by the institutional ethics committee. Preterm very low birth weight (VLBW) infants with
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
respiratory distress and chest X-ray suggestive of RDS on mechanical ventilation were included in the trial. Infants with suspected upper airway obstruction, congenital airway malformations, or major cardiopulmonary malformations were excluded.
Study Intervention Eligible infants were enrolled after obtaining written informed consent from parents or guardians. The randomization codes were generated by a statistician by using randomization software. The randomization method used was stratified, balanced permuted block procedure for two birth weight strata: 500 to 999 grams and 1000 to 1500 grams. These codes were placed in sequentially numbered opaque sealed envelopes. Preterm ventilated infants, when deemed eligible for extubation, were assigned randomly either to nsNIPPV or NCPAP group. The physician on-call opened sequentially numbered sealed opaque envelopes and randomized infants to respective groups. Access to envelopes was restricted to designated physicians. Blinding of intervention and outcome measurement was not feasible because of the nature of intervention. The diagnosis and severity of RDS were based on clinical signs along with Kero’s and Makinen’s radiologic classification [12]. All infants received a loading dose of 20 mg/kg caffeine citrate and a maintenance dose of 5 mg/kg/day until 34 completed weeks of gestation. Infants were initiated on time-cycled, pressure limited, and continuous-flow neonatal ventilator (Bearcub 750 PSV infant ventilator, Bear Medical Systems, Inc,
Riverside, CA). If indicated by severity of RDS, as per unit policy, natural surfactant [Survanta® or Neosurf (bovine lipid extract surfactant), Cipla, India] was administered if infants had moderate or severe RDS on the chest X-ray and/or fraction of inspired oxygen (FiO2) requirement >0.3. The criteria for extubation were peak inspiratory pressure (PIP) ≤ 15 cm H2O, positive end
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
expiratory pressure (PEEP) ≤ 5 cm H2O, rate of 15 to 25, FiO2 of ≤0.35 and hematocrit of >35% [9]. The devices used for NCPAP were either variable flow CPAP (Infant flow driver, Viasys Healthcare) or ventilator CPAP (BearCub 750 PSV infant ventilator) and nsNIPPV was administered through the BearCub ventilator. Infants randomized to NCPAP were put on CPAP of 5 to 6 cm H2O while those randomized to nsNIPPV, PIP was increased by 4 cm H2O from the pre-extubation value to attempt to compensate for the leak in this open system, PEEP was kept at ≤ 5 cm H2O and rate the same as was being given before extubation; FiO2 was adjusted in all infants to maintain oxygen saturation between 88 to 93% on pulse oximetry. The flow rate was kept at 8 to 10 L/min in both modes of respiratory support. nsNIPPV and NCPAP delivered through ventilator was administered by appropriately sized Hudson prongs and variable flow NCPAP by Infant Flow driver short binasal prongs. All babies on nsNIPPV/NCPAP had an appropriate sized orogastric tube placed kept open to air, to avoid distension of the stomach. A blood gas was obtained 1 hour after extubation. Thereafter, blood gas was sent at least once every 6-12 hours in the first 24 hours post-extubation; subsequent blood gases were obtained as clinically indicated. After careful evaluation of the infant’s respiratory status, the infant was weaned from nsNIPPV/NCPAP to oxyhood, nasal cannula or room air by the attending neonatologist with the use of the following guidelines: in the nsNIPPV group, once the infant had ventilator settings of PIP/PEEP 12/4 cm H2O, rate of 10% of daily feed volume), or the presence of abdominal distension or bloody stools, which precluded the continuation of feeds in the absence of culture positive sepsis or radiographic evidence of NEC. Full feeds were defined as feeds that reached 150 mL/kg per day and sustained for 3 consecutive days.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of Otago on 07/15/15 For personal use only.
Sample size calculation On the basis of previous data from our NICU, 46% of our preterm infants administered NCPAP as post extubation support needed intubation and MV within the first 72 hours of extubation. We hypothesized that by using nsNIPPV as post extubation support would reduce the need for intubation and MV to 15% (an absolute reduction of 30%). With a two sided alpha error of 0.05 and beta error of 0.2 (power 80%), the estimated sample size was 62 (31 in each group).
Statistical Analyses Baseline characteristics and outcome measures on continuous scales were analyzed by using two sample t test or Mann Whitney U test as appropriate. Baseline characteristics and outcome measures on nominal scales were analyzed by chi square test or Fisher exact test as appropriate. Statistical significance was considered if the p value was
