Dear Sirs, We read with interest the recent work by Dr Tracy and colleagues: "The effectiveness of Ambu neonatal self-inflating bag to provide consistent positive end-expiratory pressure", doi:10.1136/ archdischild-2015-308649 ADC FN&N Ed. 2016.

We would like to comment on the statement and findings by Tracy et al. Firstly, a strong point of the paper is that the authors have systematically investigated the reliability of single and multiple use SIBs and valves. Also, the observation that PEEP provision varies within differently compliant systems is particularly noteworthy, especially when using SIBs on newborn infants who are known to portray rapidly changing lung mechanics. For instance, the well-known work by Bjoerklund et al. and Dreyfuss et al. highlighted the importance of tight PIP control when ventilating newborn lungs (Bjoerklund 1996; Dreyfuss 1997). We further read with interest that Tracy et al. found the strongest correlation between inflations per minute (IPM) and accuracy of PEEP provision when IPM was 60min-1. Authors thereby replicated previous results by Morley et al. and Kelm et al. and others (Morley 2010, Kelm 2009).

Conversely, we are surprised to read that Tracy and co-authors suggest that a) the Ambu SIB/PEEP-valve combination, used together with the Ambu manometer, has not been previously studied. This is not correct; several investigators have researched the reliability of manual ventilation devices, incl. SIB/ PEEP-valve combinations. And b) we believe that the author's concluding strong statement on the safety of the Ambu SIB/PEEP-valve combination needs to be revisited in the light of findings by other authors, as outlined below.

The Ambu SIB/PEEP-valve combination, with or without the attachable manometer, has been studied in detail by several groups of investigators (Hartung et al. 2012, 2013, 2014 & 2016; Thio et al. 2010 & 2014; Kelm et al. 2012). As an example, Hartung and colleagues recently investigated the reliability of the delivered end-expiratory pressures from the Ambu SIB, together with Ambu 10-PEEP-valves, both with single use and multiple use PEEP-valves (Hartung 2013 & Hartung 2014 & Hartung 2016). However, much different to Tracy and colleagues' findings, these studies showed significant variation in their PEEP provision, even when factory new Ambu-10-PEEP-valves were tested on a new Ambu Mark IV SIB (Ambu Ballerup, Denmark) under highly standardized conditions: PEEPs ranged from 2.0 cmH2O to 5.15 cmH2O when set at 5 cmH2O, and 5.0 to 9.08 when set at 10cmH2O, respectively. Hartung et al. further found that repeated thermo sterilization continued to decrease the reliability of the tested Ambu multi-use PEEP-valves (Hartung 2013).

It is common to most in vitro-studies on the provision of PIP/ PEEP that these, for obvious advantages such as repeatability of the tests etc., are conducted under controlled circumstances, including the use of leak free models. However, as shown by both Wood et al. and Schilleman et al., large mask leaks constantly occur during manual ventilation of babies, which impact significantly on the efficiency of manual ventilation (Wood 2008, Schilleman 2010). Accordingly, previous work by Hartung et al. investigated how leak affected the provision of PIP/ PEEP when using the SIB. The findings were that increased leak correlated with decreased PIP and PEEP provision when using a SIB/PEEP-valve combination, whereas the tested T-piece resuscitator (Neopuff, Fisher and Paykel Healthcare, Auckland, NZ), a continuous flow device, steadily compensated for leaks up to 85% (Hartung 2012). But, we believe that recommendations for real life, clinical scenarios, even when based on convincing laboratory data, need to be made with considerably caution, when the results stem from highly controlled laboratory studies.

Lastly, Tracy et al. studied a lung model which was ventilated by a human operator, whereas the aforementioned studies by Hartung et al. were performed using a standardized plunger-driver to exclude variations in pressures as seen in manually delivered inflations (Hartung 2012 & 2013 & 2016). Therefore, we would like to strongly caution against Tracy et al.'s statement, which, based on their findings from only three investigators, confidently states that it would be possible to consistently deliver a required PIP by hand when using an Ambu SIB/PEEP- valve combination with manometer. The concept of the "educated hand" has long been refuted, for instance in studies by Bennett et al. (Bennett 2005), Hartung et al. (Hartung 2014), van Vonderen et al. (van Vonderen 2014) or Roehr and colleagues (Roehr 2012). They, as well as other authors, proved the highly significant variation in the delivery of positive pressure ventilation by human operators when using SIB/ PEEP- valve combinations. Reassuringly, and not dissimilar to Tracy's observations, Kelm et al. were able to show that specific training in target PIP delivery improved PIP provision in neonatal practitioners (Kelm 2010) and Hartung et al. showed that use of the Ambu pressure manometer helped with adherence to target PIPs, when compared to no manometer use (Hartung 2014). However, worryingly we read the very recent reports from Japan, in which an increased incidence of pneumothoraces in resuscitated term born infants (by use of SIB) has been lamented since the 2010 change in neonatal resuscitation guidelines, as featured in ADC F&N, together with an accompanying editorial by Ruediger and Poets (Hishikawa 2015; Ruediger 2015).

To conclude, our current understanding of the limited body of literature on SIB use in neonates suggests that the safest means to provide safe and effective manual ventilation for preterm infants requiring resuscitation still remains to be established. Given the discrepancy between the available in-vitro and in-vivo studies, and in keeping with Tracy's final conclusion, we strongly caution that before sound conclusions about the reliability and safety of any SIB device are made, further research is needed. More efforts need to be made to establish in order to determine the safest and most effective way of in delivering manual ventilation to babies during neonatal resuscitation.

Charles C Roehr, Gerd Schmalisch, Julia C Hartung March 2nd 2016

References: Tracy M, Shah D, Priyadarshi A, Hinder M. The effectiveness of Ambu neonatal self-inflating bag to provide consistent positive end-expiratory pressure. Arch Dis Child Fetal Neonatal Ed. 2016 Jan 19. pii: fetalneonatal-2015-308649. doi: 10.1136/archdischild-2015-308649. [Epub ahead of print]

Bjoerklund LJ, Vilstrup CT, Larsson A, Svenningsen NW, Werner O. Changes in lung volume and static expiratory pressure-volume diagram after surfactant rescue treatment of neonates with established respiratory distress syndrome. Am J Respir Crit Care Med. 1996; 154: 918-23.

Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998; 157: 294-323.

Morley CJ, Dawson JA, Stewart MJ, Hussain F, Davis PG. The effect of a PEEP valve on a Laerdal neonatal self-inflating resuscitation bag. J Paediatr Child Health. 2010; 46: 51-6.

Kelm M, Proquitte H, Schmalisch G, Roehr CC. Reliability of two common PEEP-generating devices used in neonatal resuscitation. Klin Padiatr. 2009; 221: 415-8.

Wood FE, Morley CJ, Dawson JA, Davis PG. A respiratory function monitor improves mask ventilation. Arch Dis Child Fetal Neonatal Ed. 2008; 93: F380-1.

Schilleman K, Witlox RS, Lopriore E, Morley CJ, Walther FJ, te Pas AB. Leak and obstruction with mask ventilation during simulated neonatal resuscitation. Arch Dis Child Fetal Neonatal Ed. 2010; 95: F398-402.

Hartung JC, te Pas AB, Fischer H, Schmalisch G, Roehr CC. Leak during manual neonatal ventilation and its effect on the delivered pressures and volumes: an in vitro study. Neonatology. 2012; 102: 190-5.

Hartung JC, Schm?lzer G, Schmalisch G, Roehr CC. Repeated thermo- sterilisation further affects the reliability of positive end-expiratory pressure valves. J Paediatr Child Health. 2013; 49: 741-5.

Hartung JC, Dold SK, Thio M, tePas A, Schmalisch G, Roehr CC. Time to adjust to changes in ventilation settings varies significantly between different T-piece resuscitators, self-inflating bags, and manometer equipped self-inflating bags. Am J Perinatol. 2014; 31: 505-12.

Hartung JC, Wilitzki S, Thio-Lluch M, Te Pas AB, Schmalisch G, Roehr CC. Reliability of Single-Use PEEP-Valves Attached to Self-Inflating Bags during Manual Ventilation of Neonates - An In Vitro Study. PLoS One. 2016;11(2):e0150224.

Bennett S, Finer NN, Rich W, Vaucher Y. A comparison of three neonatal resuscitation devices. Resuscitation. 2005; 67: 113-8.

van Vonderen JJ, Kamar R, Schilleman K, Walther FJ, Hooper SB, Te Pas AB. Influence of the hand squeeze and mask distensibility on tidal volume measurements during neonatal mask ventilation. Neonatology. 2013; 104: 216 -21.

Roehr CC, Kelm M, Fischer HS, B?hrer C, Schmalisch G, Proquitt? H. Manual ventilation devices in neonatal resuscitation: tidal volume and positive pressure-provision. Resuscitation. 2010; 81: 202-5.

Thio M, Dawson JA, Moss TJ, Galinsky R, Rafferty A, Hooper SB, Davis PG. Self-inflating bags versus T-piece resuscitator to deliver sustained inflations in a preterm lamb model. Arch Dis Child Fetal Neonatal Ed. 2014; 99: F274-7.

Thio M, Bhatia R, Dawson JA, Davis PG. Oxygen delivery using neonatal self-inflating resuscitation bags without a reservoir. Arch Dis Child Fetal Neonatal Ed. 2010; 95: F315-9.

Kelm M, Dold SK, Hartung J, Breckwoldt J, Schmalisch G, Roehr CC. Manual neonatal ventilation training: a respiratory function monitor helps to reduce peak inspiratory pressures and tidal volumes during resuscitation. J Perinat Med. 2012; 40: 583-6.

Hishikawa K, Goishi K, Fujiwara T, Kaneshige M, Ito Y, Sago H. Pulmonary air leak associated with CPAP at term birth resuscitation. Arch Dis Child Fetal Neonatal Ed. 2015; 100: F382-7.

Poets CF, Ruediger M. Mask CPAP during neonatal transition: too much of a good thing for some term infants? Arch Dis Child Fetal Neonatal Ed. 2015; 100: F378-9.

Conflict of Interest:

None declared

We read with great interest the recent article by Shetty et al (Arch Dis Child Fetal Neonatal Ed 2016;0:F1-F4) who showed that continuous positive airway pressure (CPAP) and humidified high-flow nasal cannula (HHFNC) in infants with evolving or established bronchopulmonary dysplasia (BPD) have similar effects on work of breathing (WOB).1 Like many other articles in this field, Shetty's paper unfortunately suffers from inconsistencies in defining WOB, which we wish to clarify. The definition "WOB" used throughout the paper, as a proxy for respiratory effort, seems misleading insofar Shetty et al actually assessed not WOB but the pressure time product (PTP) of the diaphragm (PTPdi). WOB and PTP, expressed either as esophageal pressure PTP or PTPdi, are two independent physical variables that address distinctly different features related to respiratory effort. In physics, the term "WOB" refers to the work done during each respiratory cycle and is mathematically expressed as WOB = ? Ppl x dVt. The Campbell diagram depicts the dynamic relationship between these two variables.2 In respiratory physiology, WOB describes the energy required as inspiratory flow begins to perform the task of ventilation. The term WOB might therefore be inaccurate to indicate the actual effort necessary for the patient to breathe, because it overlooks the energy expended during the isometric phase of respiration (muscle contraction without volume displacement). More properly, Shetty et al determined PTP, a variable that directly measures energy expenditure during the dynamic and isometric respiratory phases. PTP comprises the average inspiratory pressure starting from the onset of respiratory effort and the end of inspiration (Pavg): PTP = Pavg ? Ti.3 Because research into respiratory mechanics in spontaneously breathing infants is an exciting new field of study that increasingly attracts students, researchers, and physicians we need a concerted effort to clarify terminology that they might find confusing. Especially confusing is the tendency to use WOB as a proxy for respiratory effort when the variable measured is actually PTP. To prevent further confusion, we suggest defining respiratory effort in a consistent manner, keeping WOB and PTP as the variables for quantifying it physically. We hope that the research community will support this proposal and look forward to reading articles that put it into practice. Paola Papoff, MD Fabio Midulla, MD Francesco Montecchia, PhD References 1) Shetty S, Hickey A, Rafferty GF, et al. Work of breathing during CPAP and heated humidified high-flow nasal cannula. Arch Dis Child Fetal Neonatal Ed 2016; 0:F1-F4. 2) Cabello B, Mancebo J. Work of breathing. Intensive Care Med 2006;32:1311-4. 3) Grinnan DC1, Truwit JD. Clinical review: respiratory mechanics in spontaneous and assisted ventilation. Crit Care 2005;9:472-84.

Conflict of Interest:

None declared

Neonatal mortality in poor countries

We appreciate Dr. Berger's astute observation that most of the babies in the world do not have access to neonatal intensive care. His statistics underestimate the extent of the problem. Around the world, 7 million infants die each year. Most die of diseases that are preventable or treatable. Their deaths are due to lack of access to the most basic medical care. This is not unique to premature babies. Most health outcomes are better in wealthier countries. This is a serious problem of distributice justice.

We would suggest, however, that resource allocation decisions in both poor countries and rich consistently favor adults and older children over neonates. The systematic devaluation of neonates, prevalent in high- income countries, also exists in emerging economies. For example, the Disease Control Priorities Project, an ongoing effort to produce evidence- based analysis and resource materials to inform health policymaking in developing countries, suggests that the death of a 20 year old is worse than the death of a neonate: "An individual life acquires value only as it acquired self-awareness [...] an individual life acquired value as it develop bonds with others." An Institute of Medicine (1985) review of vaccine development priorities judged that the prevention of a death at age 20 should be valued at about two times the value of preventing an infant death. Some studies suggest that the lives of older people are worth three or four times the value of the life of a baby.

Our comment focused on the data from a study of NICU decisions in France. We suspect that we would find a parallel phenomenon at a different point on the cost/age curve in lower income countries. It seems unlikely to us that the solution to infant mortality in poorer countries is to let more babies die in richer countries. Instead, the solution is to insist that, throughout the world, babies' lives should be valued as highly as those of adults and older children.

1. Jamison DT, Shahid-Salles SA, Jamison J, Lawn JE Zupan J. Incorporating deaths near the time of birth into estimates of the global burden of disease. In Jamison DT, et al (Editors) Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): World Bank; 2006.

2. Institute of Medicine. Committee on Issuees PfNVD. Division of Health Promotion and Disease Prevention. New Vaccine Development: Establishing Priorities. The National Academies Press, Washington, DC. 1985.

3. Johannesson M, Johansson PO. Is the valuation of a QALY gained independent of age? Some empirical evidence. J Health Econ. 1997 Oct;16(5):589-99

Conflict of Interest:

None declared

Reply to End of Life Decisions - Do we make them wisely?: End of life decisions: How do we improve process? We thank Dr Cohn for his response to our paper and for voicing the issues it raised for him. Certainly one of the objectives of the study was to explore whether there were differences in approach to similar medical disorders in NICUs across Canada. We hoped that our finding of differences in what appear to be medically similar disorders would cause physicians and teams to reflect on how they come to EOL decisions and why variability exists. We agree that the working environment of an NICU may be a major factor in such decisions and defined the term 'ethical culture' of an NICU as the prevailing ethical consciousness and sensitivity to moral issues in an NICU. This, we believe is understood by the health care professionals as the readiness to engage in ethical discourse, the respect given to diverse views and values, the past experience of the unit and the awareness of the group as to the normative boundaries of deviation in ethical decision making. Although we, together with Dr Cohn, can only speculate that this 'culture' does have a strong influence on individual and team behavior, we were not able to probe this further via the design of our study. Only with very detailed, multidisciplinary (including parental perspectives) description of individual decisions one may be able to uncover how decisions are derived and to what degree they are a manifestation of "this is the way we do things here". As to the concern that consensus may have been achieved in the face of junior members of the team or even parents feeling unable to voice dissent, we specifically asked each responsible neonatologist to comment on the ease of the consensus-building process. We trustingly accepted their description on a spectrum of difficulty. As to the concern of how each individual deals with medical uncertainty, we hope to explore this aspect in a deeper analysis of the study findings. What we cannot agree with is Dr Cohn's "solution" that "ethics panels" judge these matters. It is not clear what is envisaged but a spectrum of bioethics committees and consultation services do exist in North America and elsewhere. Such committees may be decision making or more likely (certainly in Canada) more procedurally oriented in helping teams elucidate values, preferences, and the rightful voices to be heard to ensure fair process and help teams determine the ethical defensibility or vulnerability of different options. There may be other committees in which panels judge decisions but in Ontario this would only come into operation when intractable differences exist between parents and the team as to the best interest of the newborn infant. Here the Consent and Capacity Board can be called into action when the parents' role as substitute decision makers is questioned or the parents seek an alternate pathway to resolution of difference with the team. We firmly believe the safeguards Dr Cohn seeks remain in the integrity of neonatal physicians, parents and teams deriving decisions by open sharing of values, clarification of issues, moral reasoning and negotiation towards consensus (with bioethics consultation when necessary).

Authors: Jonathan Hellmann,1 Prakesh S Shah2 1 Department of Bioethics and Division of Neonatology, Hospital for Sick Children, Toronto 2 Department of pediatrics, Mount Sinai Hospital, Toronto.

Conflict of Interest:

None declared