Abstract
Background:
Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome.
Methods:
Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis.
Results:
Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBF
Conclusion:
In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted.
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References
Mercier CE, Soll RF. Clinical trials of natural surfactant extract in respiratory distress syndrome. Clin Perinatol 1993;20:711–35.
Sandri F, Plavka R, Ancora G, et al.; CURPAP Study Group. Prophylactic or early selective surfactant combined with nCPAP in very preterm infants. Pediatrics 2010;125:e1402–9.
Stevens TP, Finer NN, Carlo WA, et al.; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT). J Pediatr 2014;165:240–249.e4.
Göpel W, Kribs A, Ziegler A, et al.; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011;378:1627–34.
Dargaville PA, Aiyappan A, De Paoli AG, et al. Minimally-invasive surfactant therapy in preterm infants on continuous positive airway pressure. Arch Dis Child Fetal Neonatal Ed 2013;98:F122–6.
Schipper JA, Mohammad GI, van Straaten HL, Koppe JG. The impact of surfactant replacement therapy on cerebral and systemic circulation and lung function. Eur J Pediatr 1997;156:224–7.
Murdoch E, Kempley ST. Randomized trial examining cerebral haemodynamics following artificial or animal surfactant. Acta Paediatr 1998;87:411–5.
Rey-Santano C, Mielgo VE, Andres L, Ruiz-del-Yerro E, Valls-i-Soler A, Murgia X. Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome. Pediatr Res 2013;73:639–46.
Lewis JF, Ikegami M, Jobe AH, Tabor B. Aerosolized surfactant treatment of preterm lambs. J Appl Physiol (1985) 1991;70:869–76.
Henry MD, Rebello CM, Ikegami M, Jobe AH, Langenback EG, Davis JM. Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs. Am J Respir Crit Care Med 1996;154:366–75.
Ellyett KM, Broadbent RS, Fawcett ER, Campbell AJ. Surfactant aerosol treatment of respiratory distress syndrome in the spontaneously breathing premature rabbit. Pediatr Res 1996;39:953–7.
Dijk PH, Heikamp A, Bambang Oetomo S. Surfactant nebulisation prevents the adverse effects of surfactant therapy on blood pressure and cerebral blood flow in rabbits with severe respiratory failure. Intensive Care Med 1997;23:1077–81.
Fok TF, al-Essa M, Dolovich M, Rasid F, Kirpalani H. Nebulisation of surfactants in an animal model of neonatal respiratory distress. Arch Dis Child Fetal Neonatal Ed 1998;78:F3–9.
Jorch G, Hartl H, Roth B, et al. Surfactant aerosol treatment of respiratory distress syndrome in spontaneously breathing premature infants. Pediatr Pulmonol 1997;24:222–4.
Berggren E, Liljedahl M, Winbladh B, et al. Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome. Acta Paediatr 2000;89:460–4.
Finer NN, Merritt TA, Bernstein G, Job L, Mazela J, Segal R. An open label, pilot study of Aerosurf® combined with nCPAP to prevent RDS in preterm neonates. J Aerosol Med Pulm Drug Deliv 2010;23:303–9.
Lewis JF, Tabor B, Ikegami M, Jobe AH, Joseph M, Absolom D. Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant. J Appl Physiol (1985) 1993;74:1256–64.
Lewis J, Ikegami M, Higuchi R, Jobe A, Absolom D. Nebulized vs. instilled exogenous surfactant in an adult lung injury model. J Appl Physiol (1985) 1991;71:1270–6.
Li WZ, Chen WM, Kobayashi T. Aerosolized surfactant reverses respiratory failure in lung-lavaged rats. Acta Anaesthesiol Scand 1994;38:82–8.
Schermuly R, Schmehl T, Günther A, Grimminger F, Seeger W, Walmrath D. Ultrasonic nebulization for efficient delivery of surfactant in a model of acute lung injury. Impact on gas exchange. Am J Respir Crit Care Med 1997;156:445–53.
Wagner MH, Amthauer H, Sonntag J, Drenk F, Eichstädt HW, Obladen M. Endotracheal surfactant atomization: an alternative to bolus instillation? Crit Care Med 2000;28:2540–4.
Dellacá RL, Milesi I. Method and system for the administration of a pulmonary surfactant by atomization. European patent 2012016523420120423, WO2013160129 A1, 2013 (patent pending).
Leonhardt S, Lachmann B. Electrical impedance tomography: the holy grail of ventilation and perfusion monitoring? Intensive Care Med 2012;38:1917–29.
Frerichs I, Dargaville PA, van Genderingen H, Morel DR, Rimensberger PC. Lung volume recruitment after surfactant administration modifies spatial distribution of ventilation. Am J Respir Crit Care Med 2006;174:772–9.
Dargaville PA, Rimensberger PC, Frerichs I. Regional tidal ventilation and compliance during a stepwise vital capacity manoeuvre. Intensive Care Med 2010;36:1953–61.
Tingay DG, Bhatia R, Schmölzer GM, Wallace MJ, Zahra VA, Davis PG. Effect of sustained inflation vs. stepwise PEEP strategy at birth on gas exchange and lung mechanics in preterm lambs. Pediatr Res 2014;75:288–94.
Tingay DG, Mills JF, Morley CJ, Pellicano A, Dargaville PA. The deflation limb of the pressure-volume relationship in infants during high-frequency ventilation. Am J Respir Crit Care Med 2006;173:414–20.
De Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH. Lung recruitment using oxygenation during open lung high-frequency ventilation in preterm infants. Am J Respir Crit Care Med 2006;174:639–45.
Miedema M, de Jongh FH, Frerichs I, van Veenendaal MB, van Kaam AH. Changes in lung volume and ventilation during surfactant treatment in ventilated preterm infants. Am J Respir Crit Care Med 2011;184:100–5.
Dassieu G, Brochard L, Agudze E, Patkaï J, Janaud JC, Danan C. Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results. Intensive Care Med 1998;24:1076–82.
Frizzola M, Miller TL, Rodriguez ME, et al. High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol 2011;46:67–74.
Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med 2009;103:1400–5.
Lu KW, Pérez-Gil J, Taeusch H. Kinematic viscosity of therapeutic pulmonary surfactants with added polymers. Biochim Biophys Acta 2009;1788:632–7.
Mallol J, Rattray S, Walker G, Cook D, Robertson CF. Aerosol deposition in infants with cystic fibrosis. Pediatr Pulmonol 1996;21:276–81.
Zannin E, Ventura ML, Dellacà RL, et al. Optimal mean airway pressure during high-frequency oscillatory ventilation determined by measurement of respiratory system reactance. Pediatr Res 2014;75:493–9.
Tingay DG, Wallace MJ, Bhatia R, et al. Surfactant before the first inflation at birth improves spatial distribution of ventilation and reduces lung injury in preterm lambs. J Appl Physiol (1985) 2014;116:251–8.
Bhatia R, Schmölzer GM, Davis PG, Tingay DG. Electrical impedance tomography can rapidly detect small pneumothoraces in surfactant-depleted piglets. Intensive Care Med 2012;38:308–15.
Tingay DG, Copnell B, Grant CA, Dargaville PA, Dunster KR, Schibler A. The effect of endotracheal suction on regional tidal ventilation and end-expiratory lung volume. Intensive Care Med 2010;36:888–96.
Tingay DG, Polglase GR, Bhatia R, et al. Pressure-limited sustained inflation vs. gradual tidal inflations for resuscitation in preterm lambs. J Appl Physiol (1985) 2015;118:890–7.
Adler A, Amyot R, Guardo R, Bates JH, Berthiaume Y. Monitoring changes in lung air and liquid volumes with electrical impedance tomography. J Appl Physiol (1985) 1997;83:1762–7.
Polglase GR, Tingay DG, Bhatia R, et al. Pressure- versus volume-limited sustained inflations at resuscitation of premature newborn lambs. BMC Pediatr 2014;15:14–43.
Lauzon AM, Bates JH. Estimation of time-varying respiratory mechanical parameters by recursive least squares. J Appl Physiol (1985) 1991;71:1159–65.
Hepponstall JM, Tingay DG, Bhatia R, Loughnan PM, Copnell B. Effect of closed endotracheal tube suction method, catheter size, and post-suction recruitment during high-frequency jet ventilation in an animal model. Pediatr Pulmonol 2012;47:749–56.
Marquis F, Coulombe N, Costa R, Gagnon H, Guardo R, Skrobik Y. Electrical impedance tomography’s correlation to lung volume is not influenced by anthropometric parameters. J Clin Monit Comput 2006;20:201–7.
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Milesi, I., Tingay, D., Zannin, E. et al. Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome. Pediatr Res 80, 92–100 (2016). https://doi.org/10.1038/pr.2016.39
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DOI: https://doi.org/10.1038/pr.2016.39
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