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Nasal Intermittent Mandatory Ventilation Versus Nasal Continuous 845 Positive Airway Pressure: a Randomized Controlled Trial

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Nasal Intermittent Mandatory Ventilation Versus Nasal Continuous 845 Positive Airway Pressure: a Randomized Controlled Trial 1 2 Nasal Intermittent 3 4 Mandatory Ventilation 5 6 Versus Nasal Continuous Positive 7 Airway Pressure Before and After 8 9 Invasive Ventilatory Support 10 11 a, a 12 Osayame Ekhaguere, MBBS, MPH *, Shama Patel, MD , b 13 Haresh Kirpalani, BM, MSc Q2 Q3 14 15 16 KEYWORDS 17 Noninvasive respiratory support Continuous positive airway pressure 18 Noninvasive intermittent positive pressure ventilation Respiratory failure 19 Premature infants Intubation Heated humidified high-flow nasal cannula 20 21 22 KEY POINTS 23 Continuous positive airway pressure (CPAP), noninvasive intermittent positive pressure 24 ventilation (NIPPV), and heated humidified high-flow nasal cannula (HHFNC) are the main- 25 stays of primary and postextubation respiratory support in preterm infants. 26 The physiologic basis and practical application of CPAP and HHFNC are well delineated, 27 whereas those of NIPPV remain unsubstantiated and varied in the literature. 28 Available evidence suggests that NIPPV is superior to CPAP for primary and postextuba- 29 tion respiratory support in preterm infants. 30 Guidelines are needed on the practical application of NIPPV for preterm infants. 31 32 33 34 35 INTRODUCTION Q8 36 In current neonatal practice, a consensus now exists that avoidance or limitation of 37 invasive positive pressure ventilation in preterm infants when possible is of benefit.1 38 Clinical trials on noninvasive respiratory support for newborns began in the late 39 1960s.2,3 However, inadequate devices and interfaces and, serious complications 40 41 42 43 Disclosures: None. Q6 Q7 44 a Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Indiana University, Riley 45 Hospital for Children at Indiana University Health, 1030 West Michigan Street, C4600, Indian- b 46 apolis, IN 46202, USA; Department of Pediatrics, Division of Neonatology, The Children’s Q4 47 Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA 19104, USA * Corresponding author. Q5 48 E-mail address: [email protected] Clin Perinatol - (2019) -–- https://doi.org/10.1016/j.clp.2019.05.004 perinatology.theclinics.com 0095-5108/19/ª 2019 Elsevier Inc. All rights reserved. CLP1104_proof ■ 20 June 2019 ■ 12:31 pm 2 Ekhaguere et al 49 limited their adoption.4,5 Because invasive mechanical ventilation significantly 50 reduced neonatal mortality, focus on noninvasive support was limited. However, the Q9 51 association of invasive mechanical ventilation with bronchopulmonary dysplasia 52 (BPD),6 poor neurodevelopment,7 later mortality, and impacts on health care costs8 53 became more widely appreciated and stimulated further work to improve devices 54 and interfaces. Investigations into noninvasive respiratory support expanded in the 55 late 1980s after early observations raised hope of decreasing the incidence of 56 BPD.9 More systematic work then began on whether it would (1) obviate mechanical 57 ventilation, (2) prevent extubation failure, and (3) reduce the incidence of BPD. There 58 has been a significant increase in the use of noninvasive respiratory support in the last 59 2 decades.10 However, there is emerging evidence that the incidence of BPD has 60 remained unchanged in the same time period.10 Noninvasive respiratory support is 61 now available as continuous positive airway pressure (CPAP), nasal intermittent pos- 62 itive pressure ventilation (NIPPV), and heated humidified high-flow nasal cannula 63 (HHFNC). 64 This article focuses on 2 of the most extensively studied modes of noninvasive 65 respiratory support: CPAP and NIPPV. It reviews their mechanisms of action and 66 physiologic effects, and summarizes the evidence comparing their clinical use. Evi- 67 dence is drawn primarily from randomized controlled trials (RCTs). In brief, it also dis- 68 cusses HHFNC and a newer form of noninvasive support: noninvasive high-frequency 69 ventilation. 70 71 CONTINUOUS POSITIVE AIRWAY PRESSURE 72 Brief History 73 The physiologic consequences of laryngeal braking (grunting) sparked interest in 74 2,11 75 CPAP respiratory support. Teleologically, the goal seemed to be to overcome atel- 76 ectasis in spontaneously breathing newborns. Could this be used therapeutically? In the earliest publication of its use, there was an astonishing 55% increase in the ex- 77 2 78 pected survival. 79 Physiologic Principles of Continuous Positive Airway Pressure 80 81 Continuous positive airway pressure generates distending pressure that maintains 12 82 functional residual capacity. CPAP reduces elastic, flow-resistive, and inertial resis- 83 tance properties of the respiratory system and stabilizes the compliant premature 13–15 84 chest wall. Ultimately this reduces ventilation-perfusion mismatch and improves 16,17 85 oxygenation, work of breathing, and thoracoabdominal synchrony. Because atel- 86 ectasis leads to inflammation, unsurprisingly, CPAP reduces the inflammatory 18 87 response in the lower respiratory tract. In lamb studies, CPAP compared with me- 88 chanical ventilation reduced alveolar neutrophil influx, hydrogen peroxide production, 18,19 89 and protein accumulation, the hallmarks of lung injury that predispose preterm in- 19 90 fants to BPD. 91 Continuous Positive Airway Pressure Generating Devices 92 93 CPAP generating devices can be broadly classified into variable or continuous-flow 94 systems. 95 Variable-flow continuous positive airway pressure 96 These devices vary CPAP levels predominantly by varying gas flow rate. They entrain 97 gas flow and generate pressure during inspiration by the Bernoulli effect with the pres- 98 20 ence of an adaptive flip valve at the nasal interface (Fig. 1). The Infant Flow LP CPAP Q10 99 system (Care Fusion, Yorba Linda, CA) is an example of a variable-flow CPAP device. CLP1104_proof ■ 20 June 2019 ■ 12:31 pm Nasal Intermittent Mandatory Ventilation vs CPAP Q1 3 100 101 FPO 102 = 103 104 105 106 print & web 4C 107 Fig. 1. Design of nosepiece the medijet ª variable flow NCPAP. I. Diagram of the main com- 108 ponents: A, Breathing gas inlet with nozzle; B, Open gap of the Benvenisteprinciple; C, 109 Opening to the pressure chamber; D-Pressure/volume chamber; E-Expiration open; F, patient 110 interface. II. Breathing gas flows via the Benvenistevalve into the pressure chamber of the 111 Medijet. During inspiration, pressure in the patient’s airway decreases and breathing gas 112 flows in the direction of low resistance. III. During expiration, the expiratory flow (blue) 113 from the patient meets the incoming fresh gas flow (red) and is redirected out. (Courtesy 114 of medinMedical Innovations GmbH Olching, Germany) 115 Continuous-flow continuous positive airway pressure 116 These devices generate pressure by preventing gas egress from the circuit, which is 117 accomplished by an expiratory limb resistance or a titratable positive end-expiratory 118 pressure (PEEP) valve, depending on the specific device.20 Ventilator-derived 119 CPAP, and bubble CPAP (bCPAP) are both continuous-flow CPAP devices. The sub- 120 merged expiratory limb of the bCPAP system generates its pressure. Varying the sub- 121 mersion depth changes the pressure (Fig. 2). Some observational studies suggest that 122 bubbling from bCPAP further improves gas exchange by delivering low-amplitude, 123 high-frequency oscillations to the lungs, 21,22 but this is unsubstantiated in observa- 124 tional studies.23 125 126 Continuous Positive Airway Pressure Delivery Interfaces 127 Earlier CPAP systems used head and face chambers or endotracheal tubes to trans- 128 24 129 mit CPAP. In current practice, soft and less irritant binasal prongs and nasal masks 130 often made of silicone-based material are used. There is evidence of superiority of short binasal compared with single nasal and nasopharyngeal prongs in preventing 131 25 132 reintubation and improving oxygenation. Long nasopharyngeal tubes, which sit 133 134 135 136 137 138 139 140 141 142 143 FPO 144 = 145 146 147 148 149 print & web 4C Fig. 2. Bubble CPAP setup showing blended air source, heater humidification system, under- 150 water seal, and CPAP interface. (Courtesy of GaleMedCorporation, I-Lan, Taiwan) CLP1104_proof ■ 20 June 2019 ■ 12:31 pm 4 Ekhaguere et al 151 over the pharynx, are also used but are prone to obstruction. Binasal prongs and 152 masks may also result in complications. The major reported complication is nasal 153 septal injury, some requiring surgical intervention.26,27 However, dedicated nursing 154 care and barrier dressings (hydrocolloid and silicone gel sheeting) have been shown 155 to reduce significantly the risk of nasal injury.26,28–30 156 157 Comparative Studies 158 Continuous positive airway pressure versus supportive care for initial respiratory 159 support for preterm infants 160 Most trials in this category were in an era when antenatal steroids and surfactant were 161 still emerging therapies, which makes extrapolating their results to medically 162 advanced neonatal practice difficult. However, they still provide insight for low- 163 resource settings. 164 Two Cochrane meta-analyses examined CPAP versus supportive care for primary 165 respiratory support.31,32 Supportive care included head-box oxygen or regular nasal 166 cannula with thermoregulation and intravenous fluids. The first meta-analysis included 167 premature infants treated within the first 15 minutes of life, regardless of the respira- 168 tory status of the infant.31 Four trials that recruited 765 subjects were included. Failure 169 was determined as need for mechanical ventilation in 3 trials and need for CPAP in 1 170 trial. Individually, the older trials did not show any difference. However, in newer trials 171 dating from 2012, CPAP significantly decreased the failure rates. In the meta-analysis, 172 CPAP was superior to supportive care in reducing treatment failure (typical risk ratio 173 [RR] 0.66, 95% confidence interval [CI] 0.45 to 0.98; typical risk difference [RD] 174 À0.16, 95% CI À0.34 to –0.02).31 There was no reduction in BPD or mortality.31 175 The second meta-analysis evaluated continuous distending pressure compared 176 with supportive care in infants diagnosed with respiratory distress syndrome at any 177 time after birth.32 It included 6 trials with a total of 355 infants.
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