Background: Oxygen saturation (SpO2) targeting in the preterm infant may be improved with a better understanding of the SpO2 responses to changes in inspired oxygen (FiO2). Objective: We investigated the first-order FiO2-SpO2 relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. Methods: In recordings of FiO2 and SpO2 from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO2 adjustments and mapped the subsequent SpO2 responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. Results: In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO2 adjustments followed by a first-order SpO2 response. All response parameters differed between FiO2 increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p < 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO2 instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. Conclusions: First-order SpO2 responses show variable gain, influenced by the direction of FiO2 adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO2 for SpO2 targeting in preterm infants.

Keywords:
Oxygen inhalation therapy, Preterm infant, Arterial oxygen saturation, Automated control, Fraction of inspired oxygen
1.
Silverman WA: A cautionary tale about supplemental oxygen: the albatross of neonatal medicine. Pediatrics 2004;113:394-396.
2.
Stenson BJ: Oxygen targets for preterm infants. Neonatology 2013;103:341-345.
3.
Saugstad OD, Aune D: Optimal oxygenation of extremely low birth weight infants: a meta-analysis and systematic review of the oxygen saturation target studies. Neonatology 2014;105:55-63.
4.
Hagadorn JI, Furey AM, Nghiem T-H, Schmid CH, Phelps DL, Pillers D-AM, et al: Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study. Pediatrics 2006;118:1574-1582.
5.
Laptook A, Salhab W, Allen J, Saha S, Walsh M: Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range? J Perinatol 2006;26:337-341.
6.
Lim K, Wheeler KI, Gale TJ, Jackson HD, Kihlstrand JF, Sand C, et al: Oxygen saturation targeting in preterm infants receiving continuous positive airway pressure. J Pediatr 2014;164:730-736.e1.
7.
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, et al: Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 2010;362:1959-1969.
8.
Schmidt B, Whyte RK, Roberts RS: Trade-off between lower or higher oxygen saturations for extremely preterm infants: the first benefits of oxygen saturation targeting (BOOST) II trial reports its primary outcome. J Pediatr 2014;165:6-8.
9.
Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, et al: Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA 2013;309:2111-2120.
10.
Clarke A, Yeomans E, Elsayed K, Medhurst A, Berger P, Skuza E, et al: A randomised crossover trial of clinical algorithm for oxygen saturation targeting in preterm infants with frequent desaturation episodes. Neonatology 2015;107:130-136.
11.
Claure N, Gerhardt T, Everett R, Musante G, Herrera C, Bancalari E: Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia. Pediatrics 2001;107:1120-1124.
12.
Claure N, D'Ugard C, Bancalari E: Automated adjustment of inspired oxygen in preterm infants with frequent fluctuations in oxygenation: a pilot clinical trial. J Pediatr 2009;155:640-645.e1-2.
13.
Zapata J, Gómez JJ, Araque Campo R, Matiz Rubio A, Sola A: A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation. Acta Paediatr 2014;103:928-933.
14.
Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS: Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial. Pediatrics 2014;133:e379-e385.
15.
Cakar N, Tuğrul M, Demirarslan A, Nahum A, Adams A, Akıncı Ö, et al: Time required for partial pressure of arterial oxygen equilibration during mechanical ventilation after a step change in fractional inspired oxygen concentration. Intensive Care Med 2001;27:655-659.
16.
Weinreich UM, Thomsen LP, Hansen A, Kjærgaard S, Wagner PD, Rees SE: Time to steady state after changes in FiO2 in patients with COPD. COPD 2013;10:405-410.
17.
Sano A, Kikucki M: Adaptive-control of arterial oxygen-pressure of newborn-infants under incubator oxygen treatments. IEE Proc D 1985;132:205-211.
18.
Keim T, Amjad R, Fales R: Modelling and feedback control of inspired oxygen for premature infants. ASME Dynamic Systems and Control Conference, Arlington, 2011, pp 501-508.
19.
Versmold H, Linderkamp O, Stuffer K, Holzmann M, Riegel K: In vivo vs. in vitro response time of trancutaneous PO2 electrodes. A comparison of four devices in newborn infants. Acta Anaesthesiol Scand Suppl 1978;22:40-48.
20.
Fathabadi OS, Gale T, Lim K, Salmon B, Wheeler K, Olivier J, et al: Assessment of validity and predictability of the FiO2-SpO2 transfer-function in preterm infants. Physiol Meas 2014;35:1425-1437.
21.
Yu C, He WG, So JM, Roy R, Kaufman H, Newell JC: Improvement in arterial oxygen control using multiple-model adaptive-control procedures. IEEE Trans Biomed Eng 1987;34:567-574.
22.
Lopez JA, Araque Campo R, Rubio M: Auto-mixer: equipment for the reduction of risks associated with inadequate oxygen supply. Ingenieria Investigacion 2014;34:60-65.
23.
Luepschen H, Zhu L, Leonhardt S: Robust closed-loop control of the inspired fraction of oxygen for the online assessment of recruitment maneuvers. Conf Proc IEEE Eng Med Biol Soc 2007;2007:495-498.
24.
Quine D, Wong CM, Boyle EM, Jones JG, Stenson BJ: Non-invasive measurement of reduced ventilation: perfusion ratio and shunt in infants with bronchopulmonary dysplasia: a physiological definition of the disease. Arch Dis Child Fetal Neonatal Ed 2006;91:F409-F414.
25.
Feinstein AR: Principles of Medical Statistics. Boca Raton, CRC Press, 2001, p 712.
26.
Aliverti A, Pennati F, Salito C, Woods JC: Regional lung function and heterogeneity of specific gas volume in healthy and emphysematous subjects. Eur Respir J 2013;41:1179-1188.
27.
Severinghaus JW: Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol 1979;46:599-602.
28.
Karbing DS, Kjærgaard S, Smith BW, Espersen K, Allerød C, Andreassen S, et al: Variation in the PaO2/FiO2 ratio with FiO2: mathematical and experimental description, and clinical relevance. Crit Care 2007;11:R118.
29.
Tehrani FT, Bazar AR: A feedback controller for supplemental oxygen treatment of newborn-infants - a simulation study. Med Eng Phys 1994;16:329-333.
30.
Morozoff EP, Saif M: Oxygen therapy control of neonates: part II - evaluating manual, PID and fuzzy logic controller designs. Control Int Syst 2008;36:238-249.
31.
Lim K, Wheeler KI, Jackson HD, Fathabadi OS, Gale TJ, Dargaville PA: Lost without trace: oximetry signal dropout in preterm infants. Arch Dis Child Fetal Neonatal Ed 2015;100:F436-F438.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.