Automated Adjustments of Inspired Fraction of Oxygen to Avoid Hypoxemia and Hyperoxemia in Neonates – A Systematic Review on Clinical Studies

 

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Abstract

Supplemental oxygen is commonly provided during transition of neonates immediately after birth. Whereas an initial FiO₂ of 0.21 is now recommended to stabilize full-term infants in the delivery room, the best FiO₂ to start resuscitation of the very low birth weight infant (VLBWI) immediately after delivery is currently not known. Recent recommendations include the use of pulse oximetry to titrate the use of supplemental oxygen. As reference values for pulse oximetry during the first minutes of life have become available, automated FiO₂-adjustments are feasible and may be very useful for delivery room care to limit oxygen exposure. Beyond neonatal transition, preterm infants in the neonatal intensive care unit (NICU) commonly require supplemental oxygen to avoid hypoxemia, especially VLBWI receiving respiratory support because of poor respiratory drive and/or lung disease. For respiratory care of newborn infants in the NICU automated FiO₂-adjustment systems have been developed and have been studied in preterm infants for limited time frames using short-term physiological outcomes. These studies could demonstrate short-term benefits such as more stable arterial oxygen saturation. Recent clinical trials have shown that oxygen targeting may significantly affect mortality and morbidity. Therefore, randomized controlled trials are needed to study the effects of automated FiO₂-adjustment on long-term outcomes to prove possible benefits on survival, the rate of retino­pathy of prematurity and on neuro-development­al outcome.

Zusammenfassung

Bei Neugeborenen wird unmittelbar nach der Geburt häufig zusätzlich Sauerstoff verabreicht, um deren Anpassung zu unterstützen. Während für die Stabilisierung von reifen Neugeborenen im Kreißsaal ein initialer FiO₂ von 0,21 empfohlen wird, ist die bestmögliche Sauerstofffraktion für sehr untergewichtige Frühgeborene (VLBWI) unmittelbar nach der Geburt derzeit unbekannt. Derzeit wird für Frühgeborene empfohlen, den FiO₂ nach der pulsoximetrisch gemessenen arteriellen Sauerstoffsättigung zu steuern. Da inzwischen Referenzwerte für die Pulsoximetrie für die ersten Lebensminuten verfügbar sind, ist eine automatische FiO₂-Anpassung technisch machbar und könnte helfen, die Verabreichung von Sauerstoff im Kreißsaal zu limitieren. Jenseits der Phase der Anpassung unmittelbar nach der Geburt benötigen Frühgeborene in der Neugeborenenintensivstation häufig zusätzlichen Sauerstoff um Hypoxämien zu vermeiden. Dies ist insbesondere bei VLBWI aufgrund des häufig reduzierten Atemantriebs und/oder aufgrund einer vorhandenen Lungenerkrankung notwendig. Inzwischen wurden automatische FiO₂-Regler entwickelt und bei Frühgeborenen in Kurzzeitstudien mit physiologischen Zielkriterien klinisch untersucht. Diese Studien fanden günstige Effekte bei kurzfristigen Zielkriterien wie z. B. eine stabilere arterielle Sauerstoffsättigung innerhalb eines vorgewählten Zielbereichs. Neuere klinische Studien haben gezeigt, dass das Anstreben bestimmter Sauerstoffsättigungszielbereiche einen signifikanten Einfluss auf die Mortalität oder Morbidität hat. Daher sind randomisierte Studien notwendig, um die Effekte einer automatisierten FiO₂-Anpassung auf langfristige Zielkriterien und deren Einfluss auf die Überlebensrate, auf die Rate an Frühgeborenenretinopathie oder auf die neurologische Entwicklung zu untersuchen.

• References

• 1 American Heart Association, American Academy of Pediatrics . 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: neonatal resuscitation guidelines. Pediatrics. 2006. 117. e1029-e1038
  Google Scholar
• 2 Bancalari E, Claure N. Control of oxygenation during mechanical ventilation in the premature infant. Clin Perinatol 2012; 39: 563-572
  CrossrefPubMedGoogle Scholar
• 3 Barker SJ. “Motion-resistant” pulse oximetry: a comparison of new and old models. Anesth Analg 2002; 95: 967-972
  PubMedGoogle Scholar
• 4 Bhutani VK, Taube JC, Antunes MJ et al. Adaptive control of inspired oxygen delivery to the neonate. Pediatr Pulmonol 1992; 14: 110-117
  CrossrefPubMedGoogle Scholar
• 5 Bohnhorst B, Peter CS, Poets CF. Pulse oximeters’ reliability in detecting hypoxemia and bradycardia: comparison between a conventional and two new generation oximeters. Crit Care Med 2000; 28: 1565-1568
  CrossrefPubMedGoogle Scholar
• 6 Bohnhorst B, Poets CF. Major reduction in alarm frequency with a new pulse oximeter. Intensive Care Med 1998; 24: 277-278
  CrossrefPubMedGoogle Scholar
• 7 Bolivar JM, Gerhardt T, Gonzalez A et al. Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation. J Pediatr 1995; 127: 767-773
  CrossrefPubMedGoogle Scholar
• 8 BOOST II United Kingdom Collaborative Group, BOOST II Australia Collaborative Group, BOOST II New Zealand Collaborative Group . Oxygen saturation and outcomes in preterm infants. N Engl J Med 2013; 368: 2094-2104
  CrossrefPubMedGoogle Scholar
• 9 Burns KEA, Meade MO, Lessard MR et al. Wean Earlier and Automatically with New Technology (The WEAN Study): A Multicentre, Pilot Randomized Controlled Trial. Am J Respir Crit Care Med 2013; 187: 1203-1211
  CrossrefPubMedGoogle Scholar
• 10 Chow LC, Wright KW, Sola A. CSMC Oxygen Administration Study Group . Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants?. Pediatrics 2003; 111: 339-345
  CrossrefPubMedGoogle Scholar
• 11 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: 640–5.e1-640–5.e2
  PubMedGoogle Scholar
• 12 Claure N, Gerhardt T, Everett R et al. Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia. Pediatrics 2001; 107: 1120-1124
  CrossrefPubMedGoogle Scholar
• 13 Claure N, Gerhardt T, Hummler H et al. Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation. J Pediatr 1997; 131: 910-913
  CrossrefPubMedGoogle Scholar
• 14 Claure N, Bancalari E, D’Ugard C et al. Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants. Pediatrics 2011; 127: e76-e83
  CrossrefPubMedGoogle Scholar
• 15 Claure N, Bancalari E. Automated closed loop control of inspired oxygen concentration. Respir Care 2013; 58: 151-161
  CrossrefPubMedGoogle Scholar
• 16 Claure N, Bancalari E. Role of automation in neonatal respiratory support. J Perinat Med 2012;
  PubMedGoogle Scholar
• 17 Coleman RJ, Beharry KDA, Brock RS et al. Effects of brief, clustered versus dispersed hypoxic episodes on systemic and ocular growth factors in a rat model of oxygen-induced retinopathy. Pediatr Res 2008; 64: 50-55
  CrossrefPubMedGoogle Scholar
• 18 Costarino AT, Davis DA, Keon TP. Falsely normal saturation reading with the pulse oximeter. Anesthesiology 1987; 67: 830-831
  CrossrefPubMedGoogle Scholar
• 19 Dawson JA, Kamlin COF, Vento M et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics 2010; 125: e1340-e1347
  CrossrefPubMedGoogle Scholar
• 20 Di Fiore JM, Bloom JN, Orge F et al. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr 2010; 157: 69-73
  Google Scholar
• 21 Di Fiore JM, Walsh M, Wrage L et al. SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network . Low Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia. J Pediatr 2012; 161: 1047.e1-1052.e1
  PubMedGoogle Scholar
• 22 Fauchère J-C, Schulz G, Haensse D et al. Near-infrared spectroscopy measurements of cerebral oxygenation in newborns during immediate postnatal adaptation. J Pediatr 2010; 156: 372-376
  CrossrefPubMedGoogle Scholar
• 23 Finer N, Leone T. Oxygen saturation monitoring for the preterm infant: the evidence basis for current practice. Pediatr Res 2009; 65: 375-380
  CrossrefPubMedGoogle Scholar
• 24 Frank L, Sosenko IR. Development of lung antioxidant enzyme system in late gestation: possible implications for the prematurely born infant. J Pediatr 1987; 110: 9-14
  CrossrefPubMedGoogle Scholar
• 25 Frank L, Sosenko IR. Prenatal development of lung antioxidant enzymes in four species. J Pediatr 1987; 110: 106-110
  CrossrefPubMedGoogle Scholar
• 26 Fuchs H, Lindner W, Buschko A et al. Brain oxygenation monitoring during neonatal resuscitation of very low birth weight infants. J Perinatol 2012; 32: 356-362
  CrossrefPubMedGoogle Scholar
• 27 Fuchs H, Lindner W, Buschko A et al. Cerebral oxygenation in very low birth weight infants supported with sustained lung inflations after birth. Pediatr Res 2011; 70: 176-180
  PubMedGoogle Scholar
• 28 Gozal E, Row BW, Schurr A et al. Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat. Neurosci Lett 2001; 305: 197-201
  CrossrefPubMedGoogle Scholar
• 29 Hagadorn JI, Furey AM, Nghiem T-H et al. Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study. Pediatrics 2006; 118: 1574-1582
  CrossrefPubMedGoogle Scholar
• 30 Hallenberger A, Poets CF, Horn W et al. Closed-Loop Automatic Oxygen Control (CLAC) in Preterm Infants: A Randomized Controlled Trial. Pediatrics 2014; 133: e379-e385
  CrossrefPubMedGoogle Scholar
• 31 Harris AP, Sendak MJ, Donham RT. Changes in arterial oxygen saturation immediately after birth in the human neonate. J Pediatr 1986; 109: 117-119
  CrossrefPubMedGoogle Scholar
• 32 Hibbs AM, Johnson NL, Rosen CL et al. Prenatal and neonatal risk factors for sleep disordered breathing in school-aged children born preterm. J Pediatr 2008; 153: 176-182
  CrossrefPubMedGoogle Scholar
• 33 House JT, Schultetus RR, Gravenstein N. Continuous neonatal evaluation in the delivery room by pulse oximetry. J Clin Monit 1987; 3: 96-100
  CrossrefPubMedGoogle Scholar
• 34 Hummler HD, Pohlandt F, Franz AR. Pulse oximetry during low perfusion caused by emerging pneumonia and sepsis in rabbits. Crit Care Med 2002; 30: 2501-2508
  CrossrefPubMedGoogle Scholar
• 35 Jain A, Mehta T, Auld PA et al. Glutathione metabolism in newborns: evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures. Pediatr Pulmonol 1995; 20: 160-166
  CrossrefPubMedGoogle Scholar
• 36 Jouvet P, Farges C, Hatzakis G et al. Weaning children from mechanical ventilation with a computer-driven system (closed-loop protocol): a pilot study. Pediatr Crit Care Med 2007; 8: 425-432
  CrossrefPubMedGoogle Scholar
• 37 Kamlin COF, O’Donnell CPF, Davis PG et al. Oxygen saturation in healthy infants immediately after birth. J Pediatr 2006; 148: 585-589
  CrossrefPubMedGoogle Scholar
• 38 Kattwinkel J, Perlman JM, Aziz K et al. Neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010; e1400-e1413
  PubMedGoogle Scholar
• 39 Lellouche F, Mancebo J, Jolliet P et al. A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation. Am J Respir Crit Care Med 2006; 174: 894-900
  CrossrefPubMedGoogle Scholar
• 40 Mariani G, Dik PB, Ezquer A et al. Pre-ductal and post-ductal O₂ saturation in healthy term neonates after birth. J Pediatr 2007; 150: 418-421
  CrossrefPubMedGoogle Scholar
• 41 Martin RJ, Wang K, Köroğlu O et al. Intermittent hypoxic episodes in preterm infants: do they matter?. Neonatology 2011; 100: 303-310
  CrossrefPubMedGoogle Scholar
• 42 Maxwell LG, Harris AP, Sendak MJ et al. Monitoring the resuscitation of preterm infants in the delivery room using pulse oximetry. Clin Pediatr (Phila) 1987; 26: 18-20
  CrossrefPubMedGoogle Scholar
• 43 McEvoy C, Durand M, Hewlett V. Episodes of spontaneous desaturations in infants with chronic lung disease at two different levels of oxygenation. Pediatr Pulmonol 1993; 15: 140-144
  CrossrefPubMedGoogle Scholar
• 44 Meier-Stauss P, Bucher HU, Hürlimann R et al. Pulse oximetry used for documenting oxygen saturation and right-to-left shunting immediately after birth. Eur J Pediatr 1990; 149: 851-855
  CrossrefPubMedGoogle Scholar
• 45 Morozoff EP, Smyth JA. Evaluation of three automatic oxygen therapy control algorithms on ventilated low birth weight neonates. Conf Proc IEEE Eng Med Biol Soc 2009; 2009: 3079-3082
  PubMedGoogle Scholar
• 46 Morozoff PE, Evans RW. Closed-loop control of SaO₂ in the neonate. Biomed Instrum Technol 1992; 26: 117-123
  PubMedGoogle Scholar
• 47 O’Donnell CPF, Kamlin COF, Davis PG et al. Clinical assessment of infant colour at delivery. Arch Dis Child Fetal Neonatal Ed 2007; 92: F465-F467
  CrossrefPubMedGoogle Scholar
• 48 Perlman JM, Wyllie J, Kattwinkel J et al. Neonatal Resuscitation Chapter Collaborators. Part 11: Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2010; S516-S538
  PubMedGoogle Scholar
• 49 Pichler G, Binder C, Avian A et al. Reference ranges for regional cerebral tissue oxygen saturation and fractional oxygen extraction in neonates during immediate transition after birth. J Pediatr 2013; 163: 1558-1563
  CrossrefPubMedGoogle Scholar
• 50 Pillekamp F, Hermann C, Keller T et al. Factors influencing apnea and bradycardia of prematurity – implications for neurodevelopment. Neo­natology 2007; 91: 155-161
  PubMedGoogle Scholar
• 51 Rabi Y, Yee W, Chen SY et al. Oxygen saturation trends immediately after birth. J Pediatr 2006; 148: 590-594
  CrossrefPubMedGoogle Scholar
• 52 Ratner V, Kishkurno SV, Slinko SK et al. The contribution of intermittent hypoxemia to late neurological handicap in mice with hyperoxia-induced lung injury. Neonatology 2007; 92: 50-58
  CrossrefPubMedGoogle Scholar
• 53 Sami HM, Kleinman BS, Lonchyna VA. Central venous pulsations associated with a falsely low oxygen saturation measured by pulse oximetry. J Clin Monit 1991; 7: 309-312
  CrossrefPubMedGoogle Scholar
• 54 Saugstad OD. Oxygen saturations immediately after birth. J Pediatr 2006; 148: 569-570
  CrossrefPubMedGoogle Scholar
• 55 Schmid MB, Hopfner RJ, Lenhof S et al. Cerebral desaturations in preterm infants: a crossover trial on influence of oxygen saturation target range. Arch Dis Child Fetal Neonatal Ed 2013; 98: F392-F398
  CrossrefPubMedGoogle Scholar
• 56 Sink DW, Hope SAE, Hagadorn JI. Nurse:patient ratio and achievement of oxygen saturation goals in premature infants. Arch Dis Child Fetal Neonatal Ed 2011; 96: F93-F98
  CrossrefPubMedGoogle Scholar
• 57 Sun Y, Kohane IS, Stark AR. Computer-assisted adjustment of inspired oxygen concentration improves control of oxygen saturation in newborn infants requiring mechanical ventilation. J Pediatr 1997; 131: 754-756
  CrossrefPubMedGoogle Scholar
• 58 SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network . Carlo WA, Finer NN et al. N Engl J Med 2010; 362: 1959-1969
  CrossrefPubMed
• 59 Stichtenoth G, Demmert M, Bohnhorst B et al. Major contributors to hospital mortality in very-low-birth-weight infants: data of the birth year 2010 cohort of the German Neonatal Network. Klin Padiatr 2012; 224: 276-281
  Article in Thieme ConnectPubMedGoogle Scholar
• 60 Tan A, Schulze A, O’Donnell CPF et al. Air versus oxygen for resuscitation of infants at birth. Cochrane Database Syst Rev 2005; CD002273
  PubMedGoogle Scholar
• 61 Urlesberger B, Grossauer K, Pocivalnik M et al. Regional oxygen saturation of the brain and peripheral tissue during birth transition of term infants. J Pediatr 2010; 157: 740-744
  CrossrefPubMedGoogle Scholar
• 62 Urschitz MS, Horn W, Seyfang A et al. Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial. Am J Respir Crit Care Med 2004; 170: 1095-1100
  CrossrefPubMedGoogle Scholar
• 63 Vento M. Tailoring oxygen needs of extremely low birth weight infants in the delivery room. Neonatology 2011; 99: 342-348
  CrossrefPubMedGoogle Scholar
• 64 Vento M, Aguar M, Brugada M et al. Oxygen saturation targets for preterm infants in the delivery room. J Matern Fetal Neonatal Med 2012; 25 (Suppl. 01) 45-46
  PubMedGoogle Scholar
• 65 Vento M, Moro M, Escrig R et al. Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 2009; 124: e439-e449
  CrossrefPubMedGoogle Scholar
• 66 Viña J, Vento M, García-Sala F et al. L-cysteine and glutathione metabolism are impaired in premature infants due to cystathionase deficiency. Am J Clin Nutr 1995; 61: 1067-1069
  PubMedGoogle Scholar
• 67 Wyllie J, Perlman JM, Kattwinkel J et al. Neonatal Resuscitation Chapter Collaborators. Part 11: Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation 2010; e260-e287
  PubMedGoogle Scholar