To Compare the Efficacy of Heated Humidified High-Flow Nasal Cannula and Continuous Positive Airway Pressure in Post-Extubation Period in VLBW Infants

To Compare the Efficacy of Heated Humidified High-Flow Nasal Cannula and Continuous Positive... Abstract Objective The objective of this study was to compare efficacy of continuous positive airway pressure (CPAP) and heated humidified high-flow nasal cannula (HHHFNC) as noninvasive respiratory support in post-extubation period in very low birth weight (VLBW) infants. Method This retrospective study enrolled 136 neonates, ≤32 weeks gestation and ≤1500 grams birth weight, requiring noninvasive respiratory support during post-extubation period. Results There was no significant difference in post-extubation failure in HHHFNC group when compared with CPAP group (p > 0.05) but post-extubation complication was significantly higher in CPAP group (p < 0.05) including nasal septal trauma and pneumothorax. Conclusions In neonates ≤32 weeks of gestational age, HHHFNC showed similar efficacy, and better safety profile than nasal-CPAP when used during post-extubation period for respiratory support. heated humidified high-flow nasal cannula (HHHFNC), continuous positive airway pressure (CPAP), respiratory support, post-extubation period, complications INTRODUCTION Respiratory failure remains a major problem in the neonatal intensive care unit (NICU), especially in preterm infants. The past decade has seen dramatic changes in respiratory care of preterm infants with the implementation of labor room continuous positive airway pressure (CPAP), selective use of surfactant for respiratory distress syndrome (RDS), caffeine for early extubation and noninvasive ventilation with the objective of minimizing the lung injury. To avoid ventilator-induced lung injury, ventilator support is minimized by early application of noninvasive respiratory support [1]. Nasal CPAP, nasal intermittent positive pressure ventilation and bi-level positive airway pressure (BiPAP) are three most commonly used noninvasive respiratory supports [2, 3]. Nasal CPAP is associated with complicated fixation techniques, positional problem, nasal trauma and apparent neonatal agitation [4, 5], whereas high flow through nasal cannula has inadequately warmed and humidified gas, which increases the risk of mucosal injury and nosocomial infection [6–8]. Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity in clinical practice owing to technical ease of its use without sealing. Retrospective and observational studies suggest that HHHFNC can be used as noninvasive respiratory support of premature infant with respiratory distress [7, 9–11]. Various randomized controlled trials (RCTs) demonstrated no significant difference in HHHFNC and CPAP during post-extubation respiratory support [12–16]. A recent systematic review revealed HHHFNC has similar rates of efficacy to other forms of noninvasive respiratory support in preterm infant as post-extubation support and was also associated with less complications like nasal trauma [17]. HHHFNC has gained popularity in developed countries but still there is no concrete evidence over its use in low- and middle-income countries, as there are less trials that have sought the role of HHHFNC in these countries like India. Hence, we conducted this study to see the efficacy of HHHFNC in comparison with CPAP for post-extubation respiratory support and thus generating evidence over the use of HHHFNC in low- and middle-income countries. MATERIAL AND METHODS This retrospective and prospective observational cohort study was conducted at a tertiary level NICU of Deep Hospital, Ludhiana, North India. Routine use of HHHFNC in infants commenced in our unit from 1 July 2013. Infants were eligible if they were born at a gestational age of <32 weeks or birth weight ≤1500 g either in our hospital or transferred in our unit before 48 h of post-natal age and needed noninvasive respiratory support after a period of mechanical ventilation with an endotracheal tube. Infants placed on CPAP between 1 January 2013 and 30 June 2013 were assigned to the CPAP group, and infants placed on HHHFNC from 1 July 2013 to 30 December 2013 were assigned to the HHHFNC group. We compared the safety and efficacy of the CPAP and HHHFNC in both the groups. Infants with lethal congenital anomalies/malformations (Pierre-Robin, Treacher Collins, Goldenhar, choanal atresia, cleft lip/palate), fatal chromosomal anomalies, gastrointestinal malformation (intestinal atresia, omphalocele, gastroschisis or diaphragmatic hernia), severe asphyxia (hypoxic ischemic encephalopathy stage III) and cyanotic congenital heart disease were excluded from the study. The records of infants admitted in Deep hospital have their medical information recorded in medical records. This information was used for retrospective data collection. The neonates who fulfilled predefined extubation criteria (requiring minimal ventilator settings on Synchronised intermittent mandatory ventilation/Pressure support ventilation mode [peak inspiratory pressure = 10–12 mmH2O, FiO2 = 0.25–0.30% with SPO2 = 92–95%, Rate = 20–25] for at least 12 h, clinically stable, maintaining perfusion, normal metabolic milieu) were extubated to either HHHFNC (1 July to 30 December 2013) or CPAP (1 January to 30 June 2013) or room air as per the discretion of the treating physician during the study period duration. We used AIRVOTM 2 high flow system (Fisher and Paykel) as HHHFNC and Fischer and Paykel HHHFNC prongs, and the diameter of the nasal prongs was <50% of the neonate nares, thus allowing leak. In HHHFNC group, initial flow rate was started at 5 l/min and initial FiO2 was 30%. FiO2 was titrated to maintain SpO2 between 90% and 95%. Flow rate was increased to a maximum of 7 l/min above the starting flow rate. In CPAP group, infants were started on a bubble CPAP generator (Fisher and Paykel Healthcare, Inc.) using short bi-nasal prongs (Hudson). Initial CPAP pressure was 5 cm of H2O and FiO2 of 30%. FiO2 was adjusted to maintain SpO2 between 90% and 95%. Flow rate or CPAP pressure was increased by 1 (maximum flow of 7 l/min or CPAP pressure of 7 cmH2O) if FiO2 increased by 10% above the starting FiO2 or pCO2, increased by 10 mmHg above the baseline value or increased respiratory distress score (Silverman Anderson score) by 2 from the baseline or >5 over a duration of 1 h or decreased lung expansion on the chest radiograph. Infants who were ventilated >7 days or who were intubated more than three times during the ventilation period owing to any sentinel events were given peri-extubation single dose of injection dexamethasone 0.15 mg/kg. Injection caffeine (loading dose at 20 mg/kg/dose of caffeine citrate and 5–7.5 mg/kg/dose as a maintenance dose) was used as a standard practice in unit to facilitate extubation and for prevention of apnea of prematurity. Infants who required reintubation within 48 h were considered to have extubation failure (criteria for reintubation were recurrent or severe apnea, more than four episodes per hour or need for bag and mask ventilation for any apnea, FiO2 requirement >60% with Silverman score >6, pH < 7.20 and PaCO2 > 60 mmHg, severe metabolic acidosis, arterial base deficit >−10 and shock requiring inotropic support). Baseline characteristics of the study population were recorded in predesigned proforma. Late onset sepsis (after 72 h of life) was defined by (a) positive blood, Cerebrospinal fluid or urine culture or (b) clinical signs of sepsis with C reactive protein > 10 mg/l. Infant was considered to have antenatal steroid (ANS) exposure if mother was administered at least one dose of steroid 12 h before delivery. Definitions of small for gestational age, prolonged preterm premature rupture of membranes, chorioamnionitis, gestational diabetes mellitus, pregnancy-induced hypertension, RDS, patent ductus arteriosus, early onset sepsis (<72 h of life) and indications for surfactant, early rescue surfactant (within 2 h of life), late rescue surfactant (after 2 h of life) and ibuprofen/paracetamol were as per standard protocol. Post-extubation complications defined were air leak, nasal septal trauma, CPAP belly or nasal bridge damage. STUDY OUTCOMES The primary outcome of this study was extubation failure within 48 h after extubation. Secondary outcomes were incidence of pneumothorax, predefined post-extubation complications and requirement of post-extubation respiratory support up to 72 h. STATISTICAL METHODS All the data were entered in excel sheet and analyzed. Chi-square and Fisher exact test were used to compare categorical data. Continuous variables were analyzed by Student’s two-sample t-test and Mann–Whitney U-test as appropriate. p value < 0.05 was considered as statistically significant. All p values are two sided and have not been adjusted for multiple comparison. Data were analyzed by using IBM SPSS V.18 software. RESULTS In this study, 136 infants in both the group fulfilled the inclusion criteria of the study, 56 infants were in the CPAP group and rest were in the HHHFNC group. In this study, baseline characteristics of the included infants during 6 month period of first and second half of the year were compared. There was no difference in the baseline characteristics between the two groups (Table 1). Table 1 Baseline characteristics of the study population Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Table 1 Baseline characteristics of the study population Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 There was no difference in the incidence of post-extubation failure in both the groups (p > 0.05). The incidence of post-extubation complication was significantly higher in CPAP group when compared with HHHFNC group (p < 0.001). Of 12 infants, eight infants developed nasal septal damage and four infants landed up with pneumothorax. There was no significant difference in the duration of post-extubation respiratory support up to 72 h in both the groups (Table 2). Table 2 Primary and secondary outcomes Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Table 2 Primary and secondary outcomes Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 DISCUSSION The results of our study show that HHHFNC is equally efficacious to CPAP for post-extubation. There was also significant reduction in post-extubation complications with application of HHHFNC including nasal trauma and pneumothorax. The results of our study are similar to published RCTs [13, 14, 18]. This observation further supports the early retrospective and observational studies and recent systematic review [7, 9–11, 17]. According to these studies, HHHFNC can be applied safely and effectively as noninvasive respiratory management of premature infant. A recent randomized noninferiority trial revealed HHHFNC had efficacy and safety similar to Nasal continuous positive airway pressure (n-CPAP)/BiPAP when used as a primary approach in mild to moderate RDS [19]. In our study, duration of post-extubation respiratory support up to 72 h was not statistically significantly different in the groups, whereas in others conducted, RCT infants who were on CPAP had significantly shorter duration of post-extubation respiratory support [13, 14, 18]. In our study, overall adverse events were higher in CPAP group compared with HHHFNC group in contrast to adverse events similar in both groups in multi-centric trial [18]. The results of adverse events were similar to recently published meta-analysis that showed HHHFNC resulted in significant reduction in incidence of nasal trauma when compared with CPAP [20]. In this study, we reported that CPAP leads to increase in pneumothorax in post-extubation period. The results of the study are similar to recently published Cochrane meta-analysis [17]. The strength of the study includes adequate sample size and strict study protocol and limitation of our study includes its retrospective nature. Thus, HHHFNC group had similar efficacy and less adverse events during post-extubation period in very low birth weight (VLBW) infants. However, additional prospective research is needed to better define the utility and safety of HHFNC compared with NCPAP. CONCLUSION The results of our study clearly demonstrated the efficacy and safety of HHHFNC in VLBW preterm infants in post-extubation period. Owing to limited evidence from low- and middle-income countries, a large and well-designed multi-centric RCT from these countries will give good evidence for use of HHHFNC in these countries because neonatal population and NICU care of the developing countries is different from developed countries, thus making generalization of results from developed countries difficult. REFERENCES 1 DiBlasi RM. Neonatal noninvasive ventilation techniques: do we really need to intubate? Respir Care 2011 ; 56 : 1273 – 94 . Google Scholar CrossRef Search ADS PubMed 2 Roberts CT , Davis PG , Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013 . Neonatology 2013 ; 104 : 203 – 9 . Google Scholar CrossRef Search ADS PubMed 3 Amatya S , Rastogi D , Bhutada A , et al. Weaning of nasal CPAP in preterm infants: who, when and how? A systematic review of the literature . World J Pediatr 2015 ; 11 : 7 – 13 . Google Scholar CrossRef Search ADS PubMed 4 Bonner KM , Mainous RO. The nursing care of the infant receiving bubble CPAP therapy . Adv Neonatal Care 2008 ; 8 : 78 – 95 . quiz 96–97. Google Scholar CrossRef Search ADS PubMed 5 McCoskey L. Nursing care guidelines for prevention of nasal breakdown in neonates receiving nasal CPAP . Adv Neonatal Care 2008 ; 8 : 116 – 24 . Google Scholar CrossRef Search ADS PubMed 6 Waugh JB , Granger WM. An evaluation of 2 new devices for nasal high-flow gas therapy . Respir Care 2004 ; 49 : 902 – 6 . Google Scholar PubMed 7 Woodhead DD , Lambert DK , Clark JM , et al. Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial . J Perinatol 2006 ; 26 : 481 – 5 . Google Scholar CrossRef Search ADS PubMed 8 Kopelman AE , Holbert D. Use of oxygen cannulas in extremely low birthweight infants is associated with mucosal trauma and bleeding, and possibly with coagulase negative staphylococcal sepsis . J Perinatol 2003 ; 23 : 94 – 7 . Google Scholar CrossRef Search ADS PubMed 9 Holleman-Duray D , Kaupie D , Weiss MG. Heated humidified high flow nasal cannula: use and a neonatal early extubation protocol . J Perinatol 2007 ; 27 : 776 – 81 . Google Scholar CrossRef Search ADS PubMed 10 Miller SM , Dowd SA. High flow nasal cannula and extubation success in the premature infant: a comparison of two modalities . J Perinatol 2010 ; 30 : 805 – 8 . Google Scholar CrossRef Search ADS PubMed 11 Shoemaker MT , Pierce MR , Yoder BA , et al. High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study . J Perinatol 2007 ; 27 : 85 – 91 . Google Scholar CrossRef Search ADS PubMed 12 Campbell DM , Shah PS , Shah V , et al. Nasal continuous positive airway pressure from high flow cannula versus infant flow for preterm infants . J Perinatol 2006 ; 26 : 546 – 9 . Google Scholar CrossRef Search ADS PubMed 13 Collins CL , Holberton JR , Barfield C , et al. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants . J Pediatr 2013 ; 162 : 949 – 54 . Google Scholar CrossRef Search ADS PubMed 14 Manley BJ , Owen LS , Doyle LW , et al. High-flow nasal cannulae in very preterm infants after extubation . N Engl J Med 2013 ; 369 : 1425 – 33 . Google Scholar CrossRef Search ADS PubMed 15 Collaborative Group for the Multicenter Study on Heated Humidified High flow Nasal Cannula Ventilation . Efficacy and safety of heated humidified high flow nasal cannula for prevention of extubation failure in neonates , [in Chinese]. Zhonghua Er Ke Za Zhi 2014 ; 52 : 271 – 6 . PubMed 16 Mostafa-Gharehbaghi M , Mojabi H. Comparing the effectiveness of nasal continuous positive airway pressure (NCPAP) and high flow nasal cannula (HFNC) in prevention of post extubation assisted ventilation . Zahedan J Res Med Sci 2015 ; 17 : e984 . Google Scholar CrossRef Search ADS 17 Wilkinson D , Andersen C , O'Donnell CP , et al. High flow nasal cannula for respiratory support in preterm infants . Cochrane Database Syst Rev 2016 ; 2 : CD006405 . Google Scholar PubMed 18 Yoder BA , Stoddard RA , Li M , et al. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates . Pediatrics 2013 ; 131 : e1482 – 90 . Google Scholar CrossRef Search ADS PubMed 19 Lavizzari A , Colnaghi M , Ciuffini F , et al. Heated, humidified high flow nasal cannula v/s nasal continuous positive airway pressure for respiratory distress syndrome: a randomised clinical non inferiority trial . JAMA Pediatrics 2017 , in press. 20 Fleeman N , Mahon J , Bates V , et al. The clinical effectiveness and cost-effectiveness of heated humidified high flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation . Health Technol Assess 2016 ; 20 : 1 – 68 . Google Scholar CrossRef Search ADS PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

To Compare the Efficacy of Heated Humidified High-Flow Nasal Cannula and Continuous Positive Airway Pressure in Post-Extubation Period in VLBW Infants

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© The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Abstract

Abstract Objective The objective of this study was to compare efficacy of continuous positive airway pressure (CPAP) and heated humidified high-flow nasal cannula (HHHFNC) as noninvasive respiratory support in post-extubation period in very low birth weight (VLBW) infants. Method This retrospective study enrolled 136 neonates, ≤32 weeks gestation and ≤1500 grams birth weight, requiring noninvasive respiratory support during post-extubation period. Results There was no significant difference in post-extubation failure in HHHFNC group when compared with CPAP group (p > 0.05) but post-extubation complication was significantly higher in CPAP group (p < 0.05) including nasal septal trauma and pneumothorax. Conclusions In neonates ≤32 weeks of gestational age, HHHFNC showed similar efficacy, and better safety profile than nasal-CPAP when used during post-extubation period for respiratory support. heated humidified high-flow nasal cannula (HHHFNC), continuous positive airway pressure (CPAP), respiratory support, post-extubation period, complications INTRODUCTION Respiratory failure remains a major problem in the neonatal intensive care unit (NICU), especially in preterm infants. The past decade has seen dramatic changes in respiratory care of preterm infants with the implementation of labor room continuous positive airway pressure (CPAP), selective use of surfactant for respiratory distress syndrome (RDS), caffeine for early extubation and noninvasive ventilation with the objective of minimizing the lung injury. To avoid ventilator-induced lung injury, ventilator support is minimized by early application of noninvasive respiratory support [1]. Nasal CPAP, nasal intermittent positive pressure ventilation and bi-level positive airway pressure (BiPAP) are three most commonly used noninvasive respiratory supports [2, 3]. Nasal CPAP is associated with complicated fixation techniques, positional problem, nasal trauma and apparent neonatal agitation [4, 5], whereas high flow through nasal cannula has inadequately warmed and humidified gas, which increases the risk of mucosal injury and nosocomial infection [6–8]. Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity in clinical practice owing to technical ease of its use without sealing. Retrospective and observational studies suggest that HHHFNC can be used as noninvasive respiratory support of premature infant with respiratory distress [7, 9–11]. Various randomized controlled trials (RCTs) demonstrated no significant difference in HHHFNC and CPAP during post-extubation respiratory support [12–16]. A recent systematic review revealed HHHFNC has similar rates of efficacy to other forms of noninvasive respiratory support in preterm infant as post-extubation support and was also associated with less complications like nasal trauma [17]. HHHFNC has gained popularity in developed countries but still there is no concrete evidence over its use in low- and middle-income countries, as there are less trials that have sought the role of HHHFNC in these countries like India. Hence, we conducted this study to see the efficacy of HHHFNC in comparison with CPAP for post-extubation respiratory support and thus generating evidence over the use of HHHFNC in low- and middle-income countries. MATERIAL AND METHODS This retrospective and prospective observational cohort study was conducted at a tertiary level NICU of Deep Hospital, Ludhiana, North India. Routine use of HHHFNC in infants commenced in our unit from 1 July 2013. Infants were eligible if they were born at a gestational age of <32 weeks or birth weight ≤1500 g either in our hospital or transferred in our unit before 48 h of post-natal age and needed noninvasive respiratory support after a period of mechanical ventilation with an endotracheal tube. Infants placed on CPAP between 1 January 2013 and 30 June 2013 were assigned to the CPAP group, and infants placed on HHHFNC from 1 July 2013 to 30 December 2013 were assigned to the HHHFNC group. We compared the safety and efficacy of the CPAP and HHHFNC in both the groups. Infants with lethal congenital anomalies/malformations (Pierre-Robin, Treacher Collins, Goldenhar, choanal atresia, cleft lip/palate), fatal chromosomal anomalies, gastrointestinal malformation (intestinal atresia, omphalocele, gastroschisis or diaphragmatic hernia), severe asphyxia (hypoxic ischemic encephalopathy stage III) and cyanotic congenital heart disease were excluded from the study. The records of infants admitted in Deep hospital have their medical information recorded in medical records. This information was used for retrospective data collection. The neonates who fulfilled predefined extubation criteria (requiring minimal ventilator settings on Synchronised intermittent mandatory ventilation/Pressure support ventilation mode [peak inspiratory pressure = 10–12 mmH2O, FiO2 = 0.25–0.30% with SPO2 = 92–95%, Rate = 20–25] for at least 12 h, clinically stable, maintaining perfusion, normal metabolic milieu) were extubated to either HHHFNC (1 July to 30 December 2013) or CPAP (1 January to 30 June 2013) or room air as per the discretion of the treating physician during the study period duration. We used AIRVOTM 2 high flow system (Fisher and Paykel) as HHHFNC and Fischer and Paykel HHHFNC prongs, and the diameter of the nasal prongs was <50% of the neonate nares, thus allowing leak. In HHHFNC group, initial flow rate was started at 5 l/min and initial FiO2 was 30%. FiO2 was titrated to maintain SpO2 between 90% and 95%. Flow rate was increased to a maximum of 7 l/min above the starting flow rate. In CPAP group, infants were started on a bubble CPAP generator (Fisher and Paykel Healthcare, Inc.) using short bi-nasal prongs (Hudson). Initial CPAP pressure was 5 cm of H2O and FiO2 of 30%. FiO2 was adjusted to maintain SpO2 between 90% and 95%. Flow rate or CPAP pressure was increased by 1 (maximum flow of 7 l/min or CPAP pressure of 7 cmH2O) if FiO2 increased by 10% above the starting FiO2 or pCO2, increased by 10 mmHg above the baseline value or increased respiratory distress score (Silverman Anderson score) by 2 from the baseline or >5 over a duration of 1 h or decreased lung expansion on the chest radiograph. Infants who were ventilated >7 days or who were intubated more than three times during the ventilation period owing to any sentinel events were given peri-extubation single dose of injection dexamethasone 0.15 mg/kg. Injection caffeine (loading dose at 20 mg/kg/dose of caffeine citrate and 5–7.5 mg/kg/dose as a maintenance dose) was used as a standard practice in unit to facilitate extubation and for prevention of apnea of prematurity. Infants who required reintubation within 48 h were considered to have extubation failure (criteria for reintubation were recurrent or severe apnea, more than four episodes per hour or need for bag and mask ventilation for any apnea, FiO2 requirement >60% with Silverman score >6, pH < 7.20 and PaCO2 > 60 mmHg, severe metabolic acidosis, arterial base deficit >−10 and shock requiring inotropic support). Baseline characteristics of the study population were recorded in predesigned proforma. Late onset sepsis (after 72 h of life) was defined by (a) positive blood, Cerebrospinal fluid or urine culture or (b) clinical signs of sepsis with C reactive protein > 10 mg/l. Infant was considered to have antenatal steroid (ANS) exposure if mother was administered at least one dose of steroid 12 h before delivery. Definitions of small for gestational age, prolonged preterm premature rupture of membranes, chorioamnionitis, gestational diabetes mellitus, pregnancy-induced hypertension, RDS, patent ductus arteriosus, early onset sepsis (<72 h of life) and indications for surfactant, early rescue surfactant (within 2 h of life), late rescue surfactant (after 2 h of life) and ibuprofen/paracetamol were as per standard protocol. Post-extubation complications defined were air leak, nasal septal trauma, CPAP belly or nasal bridge damage. STUDY OUTCOMES The primary outcome of this study was extubation failure within 48 h after extubation. Secondary outcomes were incidence of pneumothorax, predefined post-extubation complications and requirement of post-extubation respiratory support up to 72 h. STATISTICAL METHODS All the data were entered in excel sheet and analyzed. Chi-square and Fisher exact test were used to compare categorical data. Continuous variables were analyzed by Student’s two-sample t-test and Mann–Whitney U-test as appropriate. p value < 0.05 was considered as statistically significant. All p values are two sided and have not been adjusted for multiple comparison. Data were analyzed by using IBM SPSS V.18 software. RESULTS In this study, 136 infants in both the group fulfilled the inclusion criteria of the study, 56 infants were in the CPAP group and rest were in the HHHFNC group. In this study, baseline characteristics of the included infants during 6 month period of first and second half of the year were compared. There was no difference in the baseline characteristics between the two groups (Table 1). Table 1 Baseline characteristics of the study population Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Table 1 Baseline characteristics of the study population Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 Baseline Characteristics CPAP group (n=56) HHHFNC group (n=80) p value Mean birth weight (g) 1263.2±224.7 1187.00±219.4 0.870 Mean birth gestational age (weeks) 28.7±2.0 28.8±1.9 0.331 Infants <28 weeks 16 (28.5%) 20 (25%) 1.000 Extremely low birth weight 8 (14.2%) 20 (20%) 0.672 Extramural 28 (50%) 38 (47.5%) 0.247 Male 44 (78.6%) 56 (70%) 0.704 Caesarean section 28 (50%) 32 (40%) 0.728 ANS 50 (89.2%) 72 (90%) 0.892 Early onset sepsis 20 (35.7%) 44 (55%) 0.315 Early rescue surfactant 32 (57.1%) 38 (47.5%) 0.268 Any sentinel events(Air leak, accidental extubation, tube block) 0 (0%) 0 (0%) – Late-onset sepsis 28 (50%) 60 (75%) 0.163 Hemodynamic significant PDA requiring treatment 24 (42.8%) 24 (30.0%) 0.487 There was no difference in the incidence of post-extubation failure in both the groups (p > 0.05). The incidence of post-extubation complication was significantly higher in CPAP group when compared with HHHFNC group (p < 0.001). Of 12 infants, eight infants developed nasal septal damage and four infants landed up with pneumothorax. There was no significant difference in the duration of post-extubation respiratory support up to 72 h in both the groups (Table 2). Table 2 Primary and secondary outcomes Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Table 2 Primary and secondary outcomes Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 Outcomes CPAP group (n = 56) HHHFNC group (n = 80) p value Post-extubation failure 2 (3.5%) 0 (0%) 0.088 Post-extubation complications 12 (21.4%) 0 (0%) <0.001 Nasal trauma 8 (14.28%) 0 (0%) 0.0005 Pneumothorax 4 (7.14%) 0 (0%) 0.015 Post-extubation respiratory support up to 72 h 40 (71.4%) 60 (75%) 0.642 DISCUSSION The results of our study show that HHHFNC is equally efficacious to CPAP for post-extubation. There was also significant reduction in post-extubation complications with application of HHHFNC including nasal trauma and pneumothorax. The results of our study are similar to published RCTs [13, 14, 18]. This observation further supports the early retrospective and observational studies and recent systematic review [7, 9–11, 17]. According to these studies, HHHFNC can be applied safely and effectively as noninvasive respiratory management of premature infant. A recent randomized noninferiority trial revealed HHHFNC had efficacy and safety similar to Nasal continuous positive airway pressure (n-CPAP)/BiPAP when used as a primary approach in mild to moderate RDS [19]. In our study, duration of post-extubation respiratory support up to 72 h was not statistically significantly different in the groups, whereas in others conducted, RCT infants who were on CPAP had significantly shorter duration of post-extubation respiratory support [13, 14, 18]. In our study, overall adverse events were higher in CPAP group compared with HHHFNC group in contrast to adverse events similar in both groups in multi-centric trial [18]. The results of adverse events were similar to recently published meta-analysis that showed HHHFNC resulted in significant reduction in incidence of nasal trauma when compared with CPAP [20]. In this study, we reported that CPAP leads to increase in pneumothorax in post-extubation period. The results of the study are similar to recently published Cochrane meta-analysis [17]. The strength of the study includes adequate sample size and strict study protocol and limitation of our study includes its retrospective nature. Thus, HHHFNC group had similar efficacy and less adverse events during post-extubation period in very low birth weight (VLBW) infants. However, additional prospective research is needed to better define the utility and safety of HHFNC compared with NCPAP. CONCLUSION The results of our study clearly demonstrated the efficacy and safety of HHHFNC in VLBW preterm infants in post-extubation period. Owing to limited evidence from low- and middle-income countries, a large and well-designed multi-centric RCT from these countries will give good evidence for use of HHHFNC in these countries because neonatal population and NICU care of the developing countries is different from developed countries, thus making generalization of results from developed countries difficult. REFERENCES 1 DiBlasi RM. Neonatal noninvasive ventilation techniques: do we really need to intubate? Respir Care 2011 ; 56 : 1273 – 94 . Google Scholar CrossRef Search ADS PubMed 2 Roberts CT , Davis PG , Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013 . Neonatology 2013 ; 104 : 203 – 9 . Google Scholar CrossRef Search ADS PubMed 3 Amatya S , Rastogi D , Bhutada A , et al. Weaning of nasal CPAP in preterm infants: who, when and how? A systematic review of the literature . World J Pediatr 2015 ; 11 : 7 – 13 . Google Scholar CrossRef Search ADS PubMed 4 Bonner KM , Mainous RO. The nursing care of the infant receiving bubble CPAP therapy . Adv Neonatal Care 2008 ; 8 : 78 – 95 . quiz 96–97. Google Scholar CrossRef Search ADS PubMed 5 McCoskey L. Nursing care guidelines for prevention of nasal breakdown in neonates receiving nasal CPAP . Adv Neonatal Care 2008 ; 8 : 116 – 24 . Google Scholar CrossRef Search ADS PubMed 6 Waugh JB , Granger WM. An evaluation of 2 new devices for nasal high-flow gas therapy . Respir Care 2004 ; 49 : 902 – 6 . Google Scholar PubMed 7 Woodhead DD , Lambert DK , Clark JM , et al. Comparing two methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation: a prospective, randomized, masked, crossover trial . J Perinatol 2006 ; 26 : 481 – 5 . Google Scholar CrossRef Search ADS PubMed 8 Kopelman AE , Holbert D. Use of oxygen cannulas in extremely low birthweight infants is associated with mucosal trauma and bleeding, and possibly with coagulase negative staphylococcal sepsis . J Perinatol 2003 ; 23 : 94 – 7 . Google Scholar CrossRef Search ADS PubMed 9 Holleman-Duray D , Kaupie D , Weiss MG. Heated humidified high flow nasal cannula: use and a neonatal early extubation protocol . J Perinatol 2007 ; 27 : 776 – 81 . Google Scholar CrossRef Search ADS PubMed 10 Miller SM , Dowd SA. High flow nasal cannula and extubation success in the premature infant: a comparison of two modalities . J Perinatol 2010 ; 30 : 805 – 8 . Google Scholar CrossRef Search ADS PubMed 11 Shoemaker MT , Pierce MR , Yoder BA , et al. High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study . J Perinatol 2007 ; 27 : 85 – 91 . Google Scholar CrossRef Search ADS PubMed 12 Campbell DM , Shah PS , Shah V , et al. Nasal continuous positive airway pressure from high flow cannula versus infant flow for preterm infants . J Perinatol 2006 ; 26 : 546 – 9 . Google Scholar CrossRef Search ADS PubMed 13 Collins CL , Holberton JR , Barfield C , et al. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants . J Pediatr 2013 ; 162 : 949 – 54 . Google Scholar CrossRef Search ADS PubMed 14 Manley BJ , Owen LS , Doyle LW , et al. High-flow nasal cannulae in very preterm infants after extubation . N Engl J Med 2013 ; 369 : 1425 – 33 . Google Scholar CrossRef Search ADS PubMed 15 Collaborative Group for the Multicenter Study on Heated Humidified High flow Nasal Cannula Ventilation . Efficacy and safety of heated humidified high flow nasal cannula for prevention of extubation failure in neonates , [in Chinese]. Zhonghua Er Ke Za Zhi 2014 ; 52 : 271 – 6 . PubMed 16 Mostafa-Gharehbaghi M , Mojabi H. Comparing the effectiveness of nasal continuous positive airway pressure (NCPAP) and high flow nasal cannula (HFNC) in prevention of post extubation assisted ventilation . Zahedan J Res Med Sci 2015 ; 17 : e984 . Google Scholar CrossRef Search ADS 17 Wilkinson D , Andersen C , O'Donnell CP , et al. High flow nasal cannula for respiratory support in preterm infants . Cochrane Database Syst Rev 2016 ; 2 : CD006405 . Google Scholar PubMed 18 Yoder BA , Stoddard RA , Li M , et al. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates . Pediatrics 2013 ; 131 : e1482 – 90 . Google Scholar CrossRef Search ADS PubMed 19 Lavizzari A , Colnaghi M , Ciuffini F , et al. Heated, humidified high flow nasal cannula v/s nasal continuous positive airway pressure for respiratory distress syndrome: a randomised clinical non inferiority trial . JAMA Pediatrics 2017 , in press. 20 Fleeman N , Mahon J , Bates V , et al. The clinical effectiveness and cost-effectiveness of heated humidified high flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation . Health Technol Assess 2016 ; 20 : 1 – 68 . Google Scholar CrossRef Search ADS PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Journal of Tropical PediatricsOxford University Press

Published: Aug 1, 2018

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