Volume Studies
Introduction
NB: Studies briefly referenced in this introduction are fully referenced within the main body ‘Volume Studies 2003 – 2022’ further below.
“The main goal for the neonatologist is to facilitate the adaptation to extra-uterine life during transition, while minimising lung injury, opening and protecting the premature lung from the first breath onwards”. Lista G Et al. ‘Achieving and maintaining lung volume in the preterm infant: from the first breath to the Neonatal Intensive Care Unit (NICU)”
Tragically, lung and brain injury can be inflicted in the Delivery Room (DR) before arrival in the NICU.
“The initiation of ventilation in the delivery room is one of the most important but least controlled interventions a preterm infant will face. Tidal volumes (VT) used in the neonatal intensive care unit (NICU) are carefully measured and adjusted. However, the Volumes that an infant receives (in the Delivery Room) during resuscitation are usually unmonitored and highly variable…”
“Inappropriate VTs delivered to preterm infants during respiratory support substantially increase the risk of injury and inflammation to the lungs and brain. These may cause cerebral blood flow instability and initiate a cerebral inflammatory cascade. The two pathways increase the risk of brain injury and potential life-long adverse neurodevelopmental outcomes” Samantha K. Barton Et al. ‘Unravelling the Links Between the Initiation of Ventilation and Brain Injury in Preterm Infants’ https://www.frontiersin.org/articles/10.3389/fped.2015.00097/full
Reflecting the need for volume control in the Delivery Room, this study attracted over 500 views in its first 6 weeks and has since attracted over 7,000 views, more than 78% of all Frontiers articles, ever. http://loop-impact.frontiersin.org/impact/article/165314#totalviews/views
Two published studies have compared Volume Control NextStep™ prototypes with leading SIB and T-Piece Resuscitators.
Both studies, the first with a simulated ET tube, the second with a face mask, showed consistent outcomes and demonstrated the unique ability of the NextStep™ to accurately control volume through changes in lung compliance, potentially mitigating the risk of Volutrauma, IVH and BPD whilst leading SIB and T-Piece resuscitators delivered multiple times target, safe volume.
Please see the studies below: 2016 “Routinely-used ventilation devices for newborn resuscitation can triple intended VT and requires further investigation.” And 2017 ”All devices, except the Next Step™ delivered a too high VT, up to sixfold the target at the 2.0mL/cmH2O compliance.”
Volume Studies 2003 - 2022
2003
“Ten million newborns worldwide each year need resuscitation assistance. More than 1 million babies die annually from complications of birth asphyxia” Thomas E Wiswell MD. ’Neonatal Resuscitation’ Respiratory Care March 2003, 48 (3) 288-295 http://rc.rcjournal.com/content/48/3/288
2005
“Neonatal chronic lung disease (CLD) is the major long-term pulmonary complication of preterm birth affecting about 20% of infants who need respiratory assistance” (>2 million) Sweet, David G, Halliday, Henry ‘Treatments in Respiratory Medicine.’ 4(5):347-359, 2005. https://link.springer.com/article/10.2165%2F00151829-200504050-00006
2006
“Initially, barotrauma was seen as being of major importance… however, increasing evidence has suggested that excessive volume, leading to over-expansion (volutrauma) and inadequate volume, leading to under-expansion/collapse, are more important aetiologically.”A Grover, Neonatal Unit, Leicester Royal Infirmary, Leicester, UK, D Field Department of Health Sciences, University of Leicester, Leicester, UK. ‘Volume-targeted ventilation in the neonate: time to change?’ https://pubmed.ncbi.nlm.nih.gov/17768158/
“Accumulating evidence from animal models 1 as well as adult human studies 2 indicates that excessive tidal volume (volutrauma) rather than high inspiratory pressure is the primary determinant of lung injury.” Peter G. Davis, MD, FRACP, Colin J. Morley, MD. ‘Volume Control: A logical Solution to Volutrauma?’ https://doi.org/10.1016/j.jpeds.2006.06.032
2008
“Volutrauma is High Tidal Volume (VT) that causes over-distension of the lung and plays a key role in Ventilator Induced Lung Injury (VILI)”
“Lung injury can occur during resuscitation with just a few large manual inflations. (Dreyfus et al and Hernandez et al animal studies)”
“Lung injury is caused mainly by high Tidal Volume (Vt) ventilation, not by high pressure”
“Many lesions occur within 2 minutes of starting ventilation”
“When Tidal Volume was controlled so as to avoid lung over-distension, little or no injury occurred” Georg M. Schmölzer, MD, Arjan B. Te Pas, MD, Peter G. Davis, MD, Colin J. Morley, MD. ‘Reducing Lung Injury during Neonatal Resuscitation of Preterm Infants.’ Journal of pediatrics 153(6):741-5 August 2008. https://www.jpeds.com/article/S0022-3476(08)00689-6/fulltext
2011
“A recent systematic review and meta-analysis shows that volume-targeted ventilation (VTV) compared with pressure-limited ventilation (PLV) reduces death and bronchopulmonary dysplasia, pneumothorax, hypocarbia and severe cranial ultrasound abnormalities.”
“As high VT (volutrauma), and not pressure per se, causes lung injury, controlling VT rather than PIP is a logical strategy for ventilating preterm infants” C Klingenberg, K I Wheeler, P G Davis, C J Morley ‘A Practical Guide to Neonatal Volume Guarantee Ventilation.’ Journal of Perinatology : Official Journal of the California Perinatal Association 2011; 31(9):575-585. https://www.ncbi.nlm.nih.gov/pubmed/21760587
2012
“This study highlights the critical role that the initial respiratory support has on the development of brain inflammation and injury, and the requirement for better monitoring of delivered tidal volumes to preterm infants in the delivery room.”
Graeme R. Polglase,* Suzanne L. Miller, Samantha K. Barton, Ana Baburamani, Flora Y. Wong, James D. S. Aridas, Andrew W. Gill, Timothy J. M. Moss, Mary Tolcos, Martin Kluckow and Stuart B. Hooper. ‘Initiation of Resuscitation with High Tidal Volumes Causes Cerebral Hemodynamic Disturbance, Brain Inflammation and Injury in Preterm Lambs’. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382197/
2015
“The initiation of ventilation in the delivery room is one of the most important but least controlled interventions a preterm infant will face. Tidal volumes (VT) used in the neonatal intensive care unit (NICU) are carefully measured and adjusted. However, the Volumes that an infant receives (in the delivery room) during resuscitation are usually unmonitored and highly variable…”
“Inappropriate VTs delivered to preterm infants during respiratory support substantially increase the risk of injury and inflammation to the lungs and brain. These may cause cerebral blood flow instability and initiate a cerebral inflammatory cascade. The two pathways increase the risk of brain injury and potential life-long adverse neurodevelopmental outcomes” Samantha K. Barton, Mary Tolcos, Suzie L. Miller, Charles C. Roehr, Georg M. Schmölzer, Peter G. Davis, Timothy J. M. Moss, Domenic A. LaRosa, Stuart B. Hooper and Graeme R. Polglase. ‘Unravelling the Links Between the Initiation of Ventilation and Brain Injury in Preterm Infants’ Frontiers in Pediatrics 10 November 2015 https://doi.org/10.3389/fped.2015.00097 http://loop-impact.frontiersin.org/impact/article/165314#totalviews/views
2016
“Preterm birth complications are the leading cause of death among children unde 5 years of age, responsible for approximately 1 million deaths in 2015” Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al.‘Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals.’ Lancet. 2016;388(10063):3027-35 https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)31593-8.pdf
“Routinely-used ventilation devices for newborn resuscitation can triple intended VT and requires further investigation.” Solevåg AL, Haemmerle E, van Os S, Bach KP, Cheung PY, Schmölzer GM.
‘Comparison of positive pressure ventilation devices in a newborn manikin’ OBJECTIVE: To compare tidal volume (VT) delivery and ventilation rate between devices for positive pressure ventilation (PPV) during newborn resuscitation.’ J Maternal Fetal Neonatal Med. 2016;30(5):595-599
https://www.tandfonline.com/doi/abs/10.1080/14767058.2016.1180360?journalCode=ijmf20
2017
“The main goal for the neonatologist is to facilitate the adaptation to extra-uterine life during transition, while minimising lung injury, opening and protecting the premature lung from the first breath onwards” Lista G, Maturana A, Moya FR. ‘Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU’ European Journal of Paediatrics Eur J Pediatr. 2017;176 (10):1287-9 https://link.springer.com/article/10.1007/s00431-017-2984-y
”All devices, except the Next Step™ delivered a too high VT, up to sixfold the target at the 2.0mL/cmH2O compliance.” Anne Lee Solevåg, Enrico Haemmerle, Sylvia van Os, Katinka P. Bach, Po-Yin Cheung, Georg M. Schmölzer. ‘A Novel Prototype Neonatal Resuscitator That Controls Tidal Volume and Ventilation Rate: A Comparative Study of Mask Ventilation in a Newborn Manikin.’ Front. Pediatr., 2017 https://www.frontiersin.org/articles/10.3389/fped.2016.00129/full
Reflecting the level of interest in finding a solution to Volutrauma, this study attracted over 500 views in its first 4 weeks and has since attracted over 5,300 views, more than 73% of all Frontiers articles, ever.
http://loop-impact.frontiersin.org/impact/article/226151#totalviews/views
“It’s possible! Resuscitation with volume ventilation after delivery” “…I think volume resuscitation will be the future.” Michael Narvey All things Neonatal’ http://allthingsneonatal.com/2017/08/
2018
“A controlled bench test was undertaken to determine the performance variability among a range of neonatal self-inflating bags (SIB) compliant with current International Standards Organisation. No (previous) systematic study has evaluated variance in different models of neonatal SIB.”
“RESULTS: Ten out of the 20 models of SIB failed our testing methodology. Two models could not provide safe minimum tidal volumes (2.5-5 mL); six models exceeded safety inflation pressure limit >45 cm H2O, representing 6% of their inflations; five models had excessive coefficient of variation (>30% averaged across compression distances) and three models did not deliver inflation volumes >2.5 mL until approximately 50% of maximum bag compression distance was reached. The study also found significant intrabatch variability and forward leakage.”
“CONCLUSION: Compliance of SIBs with ISO standards may not guarantee acceptable or safe performance to resuscitate newborn infants.” Tracy MB, Halliday R, Tracy SK, Hinder MK. ‘Newborn self-inflating manual resuscitators: precision robotic testing of safety and reliability.’ Arch Dis Child Fetal Neonatal Ed. 2018 Oct 18. pii: fetalneonatal-2018-315391. doi: 10.1136/archdischild-2018-315391.
https://fn.bmj.com/content/fetalneonatal/early/2018/10/18/archdischild-2018-315391.full.pdf
“Intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) are major complications of premature birth.”
“Avoidance of high tidal volumes and hypocarbia in the delivery suite might reduce Intraventricular Haemorrhage (IVH) development.” Pahuja A, Hunt K, Murthy V, Bhat P, Bhat R, Milner AD, Greenough A. ‘Relationship of resuscitation, respiratory function monitoring data and outcomes in preterm infants.’ Eur J Pediatr. 2018 Nov https://link.springer.com/article/10.1007/s00431-018-3222-y
“Every year, an estimated 15 million babies are born preterm (before 37 completed weeks of gestation) and this number is rising” World Health Organization. ‘Preterm Birth’ 2018 https://www.who.int/en/news-room/fact-sheets/detail/preterm-birth
“The T-piece resuscitator (TPR) has seen increased use as a primary resuscitation device with newborns.”
” Results show important variation in delivered ventilation from set values due to inherent TPR device design characteristics with a range of lung compliances expected at birth. Significant differences were seen in tidal volumes across devices particularly at higher Compliance.
Device-generated inadvertent PEEP and over delivery of PIP may be clinically deleterious for term and preterm newborns or infants with larger Compliance during resuscitation.” Murray Hinder, Alistair McEwan, Thomas Drevhammer, Snorri Donaldson, Mark Brian Tracy. ‘T-piece Resuscitators: How do they compare?’ Correspondence to Murray Hinder, Neonatal Intensive Care Unit, Westmead Hospital, Westmead, NSW 2145, Australia; murray.hinder@health.nsw.gov.au May 2018 BMJ Archives of Disease in Childhood – Fetal and Neonatal Edition https://fn.bmj.com/content/104/2/F122
”Faced with level 1 evidence of important benefits of VTV, it is hard to justify continuing to expose infants to pressure-controlled ventilation. The way forward is for us to be willing to abandon our comfort zone and embrace the paradigm shift that VTV represents.” Keszler M. ‘Volume-targeted ventilation: One size does not fit all. Evidence-based recommendations for successful use.’ Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F5. https://relaped.com/wp-content/uploads/2018/08/Volume-targeted-ventilation.pdf
2019
“Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants with multiple factors affected from prenatal to postnatal periods. Despite the great advances in neonatal care over almost 50 years, the rates of BPD are not decreased and may even have risen.” Tae-Jung Sung. Korean J Pediatr.‘Bronchopulmonary dysplasia; what should we do to improve its outcomes?’ https://www.kjp.or.kr/journal/view.php?doi=10.3345/kjp.2019.0017
“Delivery of inadvertent high tidal volume (VT) during positive pressure ventilation (PPV) in the delivery room is common.”
“High VT delivery during PPV has been associated with haemodynamic brain injury in animal models.”
“High VT delivery during mask Positive Pressure ventilation (PPV) at birth was associated with brain injury.” Mian Q, Cheung PY, O’Reilly M, Barton SK, Polglase GR, Schmölzer GM. ‘Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room.’ Arch Dis Child Fetal Neonatal Ed. 2019;104(1):F57-F62 https://fn.bmj.com/content/104/1/F57
“Despite major improvements in the care and outcome of extremely preterm infants over the last few decades, BPD (especially severe BPD) remains a challenging disease to treat and presents several challenges to clinicians. Its effects can be seen not only in the lungs of these infants but also in many other organ systems. BPD is a risk factor for the development of Cerebral Palsy, with a significant increase in rates of CP in patients with severe BPD.”
“Reducing the rate of BPD and identifying new specific targeted therapies for established BPD remains one of the biggest challenges for neonatologists and pediatric pulmonologists.” Frances Flanagan and Anita Bhandari.‘Bronchopulmonary Dysplasia and Cerebral Palsy’. Springer Nature Switzerland AG 2019 Cerebral Palsy. https://doi.org/10.1007/978-3-319-50592-3_67-1
”Tidal volume delivery. Several animal studies reported that high VT delivery during PPV causes lung and brain injury. However, when VT is controlled little or no lung injury occurs. Delivery room studies have reported large variation in VT delivery with high tidal volumes as large as 30 ml/kg.” Georg M Schmoelzer MD, PhD, Colin J. Morley, Omar C.O.F. Kamlin, ‘Enhanced monitoring during neonatal resuscitation, Seminars in Perinatology’ https://doi.org/10.1053/j.semperi.2019.08.006
”VTV should be the primary mode of ventilation as it minimises volutrauma and atelectotrauma.” Anna Rodgers1, Cheentan Singh2 “Specialist neonatal respiratory care for babies born preterm (NICE guideline 124): a review’ (UK) National Institute for Health and Care Excellence (NICE).3 http://dx.doi.org/10.1136/archdischild-2019-317461
“High tidal volume during Positive Pressure Ventilation for infants <29 weeks GA linked to Intraventricular Haemorrhage.”
“One could ask if there is harm in using a volume targeted strategy in the delivery room? I think we would be hard pressed to say that keeping the volumes under 6 mL/kg is a bad idea.”
“The challenge as I see it now is whether we rig up devices to accomplish this or do the large medical equipment providers develop an all-in-one system to accomplish this? I think the time has come to do so and will be first in line to try it out if there is a possibility to do a trial.” Michael Narvey, MD, FAAP, RCPSC Pediatrics, Michael has an account Committee Chair at Canadian Pediatric Society: Fetus & Newborn Committee ‘All Things Neonatal’ June 5, 2019 http://allthingsneonatal.com/2019/06/
2020
“Importantly, despite the high requirement of PPV in the delivery room, it is likely the least controlled respiratory support a neonate will ever receive, and this has proven to be inadvertently injurious to the immature brain (11, 13, 21).”
“Excessively high VT causes volutrauma—a major cause of lung inflammation and injury (16, 29–32). Together, these factors contribute to a suboptimal ventilation situation that leads to injury of the lung and, consequently, the brain. Indeed, the use of excessive VT has dire consequences on the immature brain. Preterm infants <29 weeks GA who received unintentional high VT ventilation (>6 ml/kg, where median normal VT is 4.2–5.8 ml/kg) in the delivery room had a nearly 4-fold higher incidence of IVH than infants who received normal VT (<6 ml/kg; 51% vs. 13%) (21, 33).”
Kyra Y. Y. Chan,1,2 Suzanne L. Miller,1,2 Georg M. Schmölzer,3,4 Vanesa Stojanovska,1,2,† and Graeme R. Polglase1,2,*† ‘Respiratory Support of the Preterm Neonate: Lessons About Ventilation-Induced Brain Injury From Large Animal Models’ Frontiers in Neurology https://www.frontiersin.org/articles/10.3389/fneur.2020.00862/full
“Evidence suggests that volume-targeted ventilation modes result in lower rates of death or bronchopulmonary dysplasia (BPD) compared with traditional pressure-limited ventilation.”…“Judicious use of mechanical ventilation, and the use of lung-protective strategies when mechanical ventilation is needed, reduces the risk of bronchopulmonary dysplasia (BPD) an ongoing cause of major morbidity for very preterm survivors.” Kate Hodgson, Peter Davis, Louise Owen .The Royal Women’s Hospital, VIC. ‘Emerging Topics and Controversies in Neonatology’ pp 195-209 Mechanical Ventilation of the Preterm Infant 2020
https://link.springer.com/chapter/10.1007/978-3-030-28829-7_11
“…patients with BPD and resulting complications will incur over CAD$700,000 in lifetime health systems costs” van Katwyk, S., Augustine, S., Thébaud, B. et al. ‘Lifetime patient outcomes and healthcare utilization for Bronchopulmonary dysplasia (BPD) and extreme preterm infants: a microsimulation study.’ BMC Pediatr 20, 136 (2020).
https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-020-02037-5
2021
“The bag-and-mask or T-piece circuits commonly used for neonatal resuscitation provide no feedback information on the delivered TV, hence it is poorly controlled and can potentially expose the preterm neonate to volutrauma [6]. Ventilation with targeted TV is an accepted ventilator management in many NICUs to minimize lung damage [27], but DR (Delivery Room) practice continues to focus on PLV.”
”It was striking that in our study 19.1% of times subject received TV >10 ml/kg, even though the T-piece resuscitators were set at the recommended PIP and positive end expiratory pressure.” NB: Even when using a Respiratory Function Monitor (RFM) – very rarely used during Deliver Room Resuscitation.
“In conclusion, we report that measurement of delivered TV via ETT in the DR is feasible in preterm infants using a RFM. There is a high degree of intra- and inter-subject variability in delivered TV with potential to cause volutrauma.”
Vaidya, R., Visintainer, P. & Singh, R. ‘Tidal volume measurements in the delivery room in preterm infants requiring positive pressure ventilation via endotracheal tube-feasibility study’. J Perinatol 41 https://doi.org/10.1038/s41372-021-01113-7
“During the first day of life, episodes of hypocapnia defined as PaCO2<4.5 kPa were less frequent in infants ventilated by VTV (64% vs. 32%). We also found that the lowest detected PaCO2 per infant was higher in the VTV-group compared with the PLV-group (4.9 ± 1.1 and 4.3 ± 0.6 kPa, p < .01). The known association between hypocapnia and IVH makes these findings important.3” Linda Wallström MD, Amanda Sjöberg MD, Richard Sindelar MD PhD ‘Early volume targeted ventilation in preterm infants born at 22–25 weeks of gestational age’ https://pubmed.ncbi.nlm.nih.gov/33611849/
“Today, non-invasive respiratory support has been adopted even in the tiniest babies with the highest risk of lung injury. …can we enhance (iii) success of non-invasive respiratory support and (iv) better prevent ultimate harm to the developing lung? With increased survival of infants at the highest risk of developing lung injury and an unchanging burden of bronchopulmonary dysplasia, we should question indiscriminate use of non-invasive respiratory support and address the above issues.” Glaser K.a Wright C.J.b ‘Indications for and Risks of Non-invasive Respiratory Support’ https://www.karger.com/Article/Abstract/515818
“Volume Targeted Ventilation (VTV) is available on most modern neonatal ventilators, and its use is supported by physiologic considerations and human trials showing improvement in several important clinical outcomes with no adverse effects compared with Pressure Limited Ventilation (PLV).”
“Volume Targeted Ventilation (VTV) should be the default neonatal ventilation mode.” Belteki G, Morley CJ. ‘Volume-Targeted Ventilation.’ Clinics in Perinatology. 2021 Dec 1;48(4):825-41. https://www.journals.elsevier.com/clinics-in-perinatology/recent-articles
“Despite advances in neonatal intensive care, more than half of surviving infants born extremely preterm (EP; <28 weeks’ gestation) develop bronchopulmonary dysplasia (BPD). Prevention of BPD is critical because of its associated mortality and morbidity, including adverse neurodevelopmental outcomes and respiratory health in later childhood and beyond.” Louise SOwenMD123Brett JManleyPhD123Kate A Hodgson MBBS(Hons)12Calum TRobertsPhD456 ‘Impact of early respiratory care for extremely preterm infants’ https://www.sciencedirect.com/science/article/abs/pii/S0146000521000926
2022
”Animal and observational human studies report that delivery of excessive tidal volume (VT) at birth is associated with lung and brain injury. Using a respiratory function monitor (RFM) to guide VT delivery might reduce injury and improve outcomes.” de Medeiros SM, Mangat A, Polglase GR, et al ‘Respiratory function monitoring to improve the outcomes following neonatal resuscitation: a systematic review and meta-analysis’ Archives of Disease in Childhood – Fetal and Neonatal Edition Published Online First: 20 January 2022. doi:10.1136/archdischild-2021-323017 https://fn.bmj.com/content/early/2022/01/20/archdischild-2021-323017
”Bronchopulmonary dysplasia (BPD) is a serious respiratory complication in premature infants and moderate-to-severe BPD may affect the long-term quality of life and lack of specific treatment once it (has) happened. Therefore, it is necessary to identify early diagnostic biomarkers for moderate-to-severe BPD” YuchenYang, JuanLi, JianMao ‘Early diagnostic value of C-reactive protein as an inflammatory marker for moderate-to-severe bronchopulmonary dysplasia in premature infants with birth weight less than 1500 g’ https://www.sciencedirect.com/science/article/pii/S1567576921010985#!
